Common use of During the Study Clause in Contracts

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  Physical exam  The use of proper birth control will be confirmed/reviewed  Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o You will be asked to minimize activity while attached to the monitor  An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  The study investigator may decide to do an alcohol breath test at any time  Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  Urine samples to test for drugs of abuse  Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will be collected to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  You will receive a follow-up phone call about 4 weeks after the last dose of study drug  For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 blood draws. The total amount of blood drawn during the study will be about 485mL. This is equal to about a little more than 16 oz., or a little more than 2 cups. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  • The use of proper birth control will be confirmed/reviewed  (males only) • Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  o Urine samples to test for drugs of abuse  Blood samples for pregnancy testing and cotinine (females able to have children). Pregnancy tests by-product of nicotine) ▪ Cotinine will be done at admission and may be performed done at any time at the discretion of the study investigator in all females o Any leftover blood from the safety lab Blood samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can will also be used to show measure the levels of study drug ▪ As part of understanding how your body works.  Samples to absorbs, distributes, and gets rid of the study drug, the samples may also be used for this purpose will be kept for up the following: ➢ Metabolite identification (by-products or end products of a drug produced as the body processes a drug) ➢ Evaluate safety aspects related to 1 year following completion of this any concerns during or after the study o Banked Biospecimen: ➢ Check the laboratory test which measures the study drug ➢ Other internal exploratory purposes • A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  o This sample will be used to study biological substances in your samplesample(s), including your genes. This will help us learn more about the study drug  o This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples • You will be collected to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples swabbed for study drug levels may also be used for the following:  Metabolite identification and profiling  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  COVID-19 • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, needlesticks or by a cathetercatheter placed in a vein in your arm. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 29 blood drawsdraws for participants with 2 dosing periods and about 43 for participants with 3 dosing periods. The total amount of blood drawn during the study will be about 485mL. up to 205 mL. This is equal to about a little more less than 16 7 oz., . or a little more less than 2 cups1 cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drugs or procedure(s) procedures may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study. Reported side effects include the following: • Sight changes (including double vision, blurred vision, impaired vision, light intolerance, perceived flashes, floaters, or rings of light) • Nausea • Diarrhea • Vomiting • Swelling in the arms, legs, hands, feet, face, or around the eyes • Constipation • Abnormalities in blood tests that may indicate liver damage • Fatigue • Decreased appetite • Decreases in white blood cells that fight infection • Changes in taste • Dizziness • Damage to nerves in arms, legs, feet, or hands, including tingling or numbness in hands or feet • Pain in the abdomen • Slow heartbeat • Inflammation, rash, dryness, redness, or flushing of the skin, including itching • Swelling, inflammation, erosion, infection, or pain in the lining of the mouth, throat, nose, or esophagus (swallowing tube), including difficulty or pain on swallowing • Swelling of the abdomen • Decreases in red blood cells that carry oxygen to the body • Generalized weakness • Headache • Decreased kidney function or abnormalities of blood tests that may indicate kidney damage • Muscle spasms, cramps, or weakness • Indigestion or heartburn • Cough • Low blood phosphate, which can cause confusion or muscle weakness • Difficulty sleeping • Shortness of breath • Low blood calcium, which may increase the risk of seizures or abnormal heart rhythm • Fever • Limb, muscle, bone, back, or chest pain • Decreases in platelets (small particles in the blood that help with clotting) • Weight loss or gain • Low blood protein, which may lead to swelling in the body • Changes in tests of the electrical function of the heart (ECG/EKG) which may lead to a potentially life-threatening or fatal abnormal heart rhythm • Loss of consciousness, fainting, syncope • Dry eyes or mouth • Liver injury • Joint swelling or pain • Inflammation or infection of the lungs • Closed pouches of fluid (cysts) within the kidney that could extend beyond the kidney and require drainage • Low blood pressure • Low blood potassium, which can cause weakness or cramping • Increased blood potassium, which can cause abnormal heart rhythm and muscle weakness • Increased bowel gas • Low blood sodium, which may increase the risk of seizures • High blood sugar which may lead to diabetes • Hair loss • Diminished activity of the testes • Dehydration • Vertigo (feeling dizzy as yourself or things surrounding you are spinning or swaying) • Increases in creatine phosphokinase and lactate dehydrogenase, which may be related to a worsening of a cancer or may indicate damage to your heart or other organs • Ear ringing • Obstruction of the liver • Vision loss including defect in part of vision • Life-threatening or fatal liver failure • Life-threatening or fatal blood clots in the lungs • Fainting • Heart failure There may be side effects that are not known at this time. Until you know how the study drugs will affect you, you should use caution by: • Avoiding stairs • Not driving a car • Not swimming or bathing in a tub • Not working with machinery or at heights Because the study drug is investigational, all of its side effects are not known. There may be rare and unknown side effects. These include reactions that may be life-threatening. All drugs have a potential risk of an allergic reaction. If an allergic reaction is not treated quickly, it could become life-threatening. You should get medical help (by calling 911 or immediately going to an emergency room) right away if you think you have any of the following symptoms: • Trouble breathing • Wheezing • Difficulty swallowing • Swelling of the face, mouth, lips, gums, tongue, or neck Other allergic reactions may include: • Itchiness • Rash • Hives • Blisters • Palpitations (racing heart) • Chest discomfort/tightness • Muscle pains/stiffness At times, the following may also be symptoms of an allergic reaction: • Diarrhea • Nausea • Vomiting • Abdominal pain If a significant side effect occurs, the following may be done: • Tests or treatment may be given as needed for your safety • Depending on how severe your symptoms are, you may be seen by outside medical providers or a hospital. This would be for further evaluation and/or treatment • The study investigator may notify your emergency contact as appropriate in the event of an emergency while you are taking part in the study Genes are pieces of DNA that, through material called RNA, give instructions for building the proteins that make our bodies work. These instructions are stored in the form of a code. This is the code that you inherit from your parents and that you pass on to your children. DNA, RNA, and proteins can be studied as part of genetic research. This study may involve studying your biology and whether a particular biological feature (including genes) is related to the effects or action of the study drug or to a disease. This may include analyzing all of your genetic information. This is called “whole genome sequencing”. Sequencing a gene is like reading a book 1 letter at a time. This is a very thorough way to learn about genes. The genetic analysis is for research purposes only. It is not a medical test. This means that the medical importance of the results may not be known. They may not be related to any medical condition. The results of tests on your sample(s) will not be given to: • You • The study investigator • Any insurance company • Your employer • Your family • Any physician who treats you If you do not want genetic testing to be done on your samples, you should not agree to participate in the research described in this document. Pfizer and researchers will put measures in place to minimize the chance that results from this research could be linked to you. There is always a chance that information from your taking part in the research may be disclosed.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  You will be asked about any updates to your medical history. This includes prior diseases, medication, drug, alcohol, and tobacco use  Physical exam  The use of proper birth control will be confirmed/reviewed  Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o You will be asked to minimize activity while attached to the monitor asked: “How do you feel?” each day  An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  The study investigator may decide to do an alcohol breath test at any time  You will complete a COVID-19 questionnaire  You will be swabbed for COVID-19  Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  Blood samples for aPTT, PT-INR, and fibrinogen  Urine samples to test for drugs of abuse  Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works. works  Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o  Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling (by-products or end products of a drug produced as the body processes a drug)  Endogenous (within the body) biomarkers  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  Retained Research Samples: Samples of your blood will be collected, stored, and used to learn more about the study drug and safety biomarkers  Biological substances in your samples, including your genes, may be studied  These samples may be kept by Pfizer for as long as the samples are useful for scientific research. This may be for many years (no time limit)  You will receive a follow-up phone call about 4 weeks after the last dose of study drug  For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 76 blood draws. The total amount of blood drawn during the study will be about 485mL. 350 mL. This is equal to about a little more than 16 11 ½ oz., or a little more less than 2 1 ½ cups. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  Physical exam  The use of proper birth control will be confirmed/reviewed  Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o You will be asked “How do you feel?” each day  A DHT device may be placed on one of your wrists o The DHT device is worn like a wristwatch and will be used to minimize activity collect some exploratory vital sign measurements, which may include heart rate, blood pressure, breathing rate, body temperature, o You may be asked to wear it while attached you are confined to the monitor CRU for the study  You must remove the device when showering/bathing  The device must not get wet  You may be required to keep a device with you in addition to the DHT wristband which will capture the DHT measurements  This device is about the size of a smart phone  Both devices will be collected back from you at the end of the study  You will complete a questionnaire about the wearability of the device when you return it to a member of the study staff  An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  The study investigator may decide to do an alcohol breath test at any time  You will complete a COVID-19 questionnaire  You will be tested for COVID-19  Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  Urine samples to test for drugs of abuse  Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females and cotinine o Any leftover blood serum (component of blood) from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works. works  Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o  Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling (by-products or end products of a drug produced as the body processes a drug)  Endogenous (within the body) biomarkers  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  Retained Research Samples: Samples of your blood will be collected, stored, and used to learn more about the study drug and safety biomarkers  Biological substances in your samples, including your genes, may be studied  These samples may be kept by Pfizer for as long as the samples are useful for scientific research. This may be for many years (no time limit)  You will receive a follow-up phone call about 4 weeks after the last dose of study drug  For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 61 blood draws. The total amount of blood drawn during the study will be about 485mL. 270 mL. This is equal to about a little more than 16 9 oz., or a little more than 2 cups1 cup. For comparison, the standard blood donation is about 16 oz. oz (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study. As of March 21, 2022, 35 participants with cancer have been dosed with the study drug across multiple dose levels. Participants in Part 1A of an ongoing study received doses including 75 mg, 150 mg, 225 mg, 300 mg, 375 mg, and 500 mg given twice a day. Six participants have been dosed in Part 1B of this study. These participants received 75 mg of study drug twice a day with 125 mg of Fulvestrant once a day. Fulvestrant is a medication used to treat certain types of breast cancer. Seven additional participants have also been dosed in Part 1B of this study with different dosing strategy. These participants received 150 mg of study drug twice a day and 100 mg of Fulvestrant once a day. Four participants have been dosed in Part 1C of this study. These participants received 75 mg of study drug twice and 125 mg of Letrozole once a day. Letrozole is a medication used to treat certain types of breast cancer. The most common study treatment-related adverse events (side effects), occurring in at least 10% of the participants reporting adverse events were:  Anemia (low red blood cells that carry oxygen in the blood), which may cause tiredness  Blood aspartate aminotransferase increased (an enzyme found in the liver that can help diagnose liver damage or disease)  Decreased appetite  Diarrhea  Fatigue (tiredness)  Hypokalemia (low levels of potassium in the blood), which can cause an abnormal heart rate  Hypercalcemia (high levels of calcium in the blood), which can cause altered mental status, weakness, and/or kidney damage  Hyperuricemia (high levels of uric acid in the blood), which can cause painful joints and/or kidney failure (gout)  Lymphocyte count decreased (lymphocytes are a type of white blood cell that protects against infection), which may increase the risk of infection  Nausea  Neutrophil count decrease (very low amounts of neutrophils which are a type of white blood cells that protect against infection) , which may increase the risk of infection  Platelet count decrease (low levels of platelets in the blood, platelets are cells that help the blood clot), which may increase the risk of bleeding  Vomiting  White blood cell count decreased (cells of the immune system which protect against infections) , which may increase the risk of infection Four serious adverse events considered to be likely related to the study drug have been reported as of the data cut-off of 21 March 2022. These are noted below:  Diarrhea in 1 participant in Part 1A, at a dose of 300 mg of study drug twice a day and another participant in Part 1A, at 500 mg given twice daily.  Acute kidney injury (sudden episode of kidney failure or damage) in 1 participant in Part 1A, at a dose of 500 mg of study drug twice daily.  Pneumonia (lung infection) in 1 participant, based on preliminary data, in Part 1B, at dose level 75 mg of study drug twice daily and 125 mg of Fulvestrant once a day. In animal studies the most common adverse events observed were in the gastrointestinal (GI) tract (stomach, small intestine, and large intestine [colon]) and bone marrow (this is the soft, spongy tissue found in the middle of most bones, which makes blood cells). The GI effects included:  Nausea  Vomiting  Diarrhea  Loss of appetite  Weight loss  Dehydration (lose more fluids than you take in) The bone marrow effects included:  Low white blood cells (could lower the body’s ability to fight infection)  Low hemoglobin also known as anemia), which could result in: o Fatigue (tiredness) o Pallor (paleness) o Shortness of breath  Low platelet counts which could cause you to bleed more easily In animals (rats and dogs), adverse effects were observed on the cells of the reproductive organs in both sexes of the individual animals. It is not known if you will develop any of these symptoms as animal studies do not always predict the side effects that people may experience. The study drug may make your skin more sensitive to light. Because of this, you will be asked to avoid exposure and protect yourself from sunlight throughout the study. You will be asked to use sunscreen after taking the study drug for a certain period of time. Until you know how the study drug will affect you, you should use caution by:  Avoiding stairs  Not driving a car  Not swimming or bathing in a tub  Not working with machinery or at heights Because the study drug is investigational, not all of its side effects are known. There may be rare and unknown side effects. These include reactions that may be life-threatening. All drugs have a potential risk of an allergic reaction. If an allergic reaction is not treated quickly, it could become life-threatening. You should get medical help (by calling 911 or immediately going to an emergency room) right away if you think you have any of the following symptoms:  Trouble breathing  Wheezing  Difficulty swallowing  Swelling of the face, mouth, lips, gums, tongue, or neck Other allergic reactions may include:  Itchiness  Rash  Hives  Blisters  Palpitations (racing heart)  Chest discomfort/tightness  Muscle pains/stiffness At times, the following may also be symptoms of an allergic reaction:  Diarrhea  Nausea  Vomiting  Abdominal pain If a significant side effect occurs, the following may be done:  Tests or treatment(s) may be given as needed for your safety  Depending on how severe your symptoms are, you may be seen by outside medical providers or a hospital for further evaluation and/or treatment  The study investigator may notify your emergency contact as appropriate in the event of an emergency while you are taking part in the study Genes are pieces of DNA that give coded instructions for the body. Parts of the code are passed down from parents to their children. The genes in your samples may be studied. This may include analyzing all of your genetic information. This is called “whole genome sequencing”. While collection of genetic information does not expose you to physical risk, collection of such information may result in a loss of your privacy if your genetic information is lost or stolen. There is a very small chance that your genetic information could be misused by people not involved with the research, including to discriminate against you. However, steps are in place to prevent a particular result from being linked to you and to prevent unauthorized people from even knowing genetic research was done. U.S. federal law prohibits discrimination in health insurance coverage and employment based on a person’s genetic data. However, U.S. federal law does not protect against discrimination when you are applying for:  Life insurance  Long term care insurance  Disability insurance You should talk to your physician or genetic counselor about the potential for genetic discrimination. The results of tests on your sample(s) will not be given to:  You  The study investigator  Any insurance company  Your employer  Your family  Any physician who treats you Possible side effects of having your blood drawn or an IV catheter inserted include:  Bleeding at the site of the needle puncture  Bruising  Feeling faint  Rarely, infection or blood clot  Redness of the vein  Inflammation of the vein  Swelling  Pain  Nerve damage  Vein irritation from the fluid or medication being given  Local swelling due to IV fluid accidentally entering the tissue rather than the vein  Scarring If you feel faint, tell one of the study staff immediately.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will also be measured  • You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  • Part 1 only: Continuous heart monitoring will be done for at least 12 8 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o You • Part 3 only: A taste questionnaire will be asked to minimize activity while attached to the monitor  An intravenous completed at various times (IV4 times in total) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Urine samples to test for drugs of abuse  ▪ Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood and urine from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  ▪ This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  ▪ This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will be collected to measure the levels of study drug  As part of understanding how in your body absorbs, distributes, and gets rid of the study drug, the blood. These samples for study drug levels may also be used for exploration of metabolites or other internal exploratory purposes. ▪ Part 2: Some of the followingblood samples may be collected using an investigational automated blood draw device ▪ Part 2:  Metabolite identification and profiling  Evaluate safety or efficacy (ability Urine samples will also be used to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the measure study drug  Measure the levels of ritonavir  Other internal exploratory purposes  You will receive a follow-up phone call about 4 weeks after the last dose of study drug  For safety reasons, we levels. These samples may add procedures at any time during the study to check on your health status  You will also be asked “How do you feel?” each day  You will be asked used for metabolite profiling if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 blood draws. The total amount of blood drawn during the study will be about 485mL. This is equal to about a little more than 16 ozneeded., or a little more than 2 cups. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  Physical exam  • Brief physical exam(s) may be done • The use of proper birth control will be confirmed/reviewed  (females able to have children only) • Xxxxx xxxxx will be measured. Your oral temperature will may also be measured  You • Weight will be swabbed for COVID-19  measured • ECGs (triplicate measurements) will be collected done o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Blood tests for amylase, lipase and calcitonin ▪ Urine samples to test for drugs of abuse  ▪ Blood samples or urine pregnancy tests for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood serum or plasma (components of blood) from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. findings ▪ Biomarkers are natural substances present in your body that can be used to show indicate how your body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug  ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  ⮚ Metabolite identification and profiling  (by-products or end products of a drug produced as the body processes a drug) ⮚ Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  ⮚ Check the laboratory test which measures the study drug  Measure the levels of ritonavir  ⮚ Other internal exploratory purposes  ⮚ Genetic testing may also be done on these samples o Biomarkers: Blood samples will also be collected and retained to measure biomarkers (see retained research samples below) o Pharmacogenomics: A blood sample will be taken to determine how your genes affect your response to the study drug. This sample will be used to examine specific genes such as SLCO1B1, SLCO1B3, and SLCO2B1, and potentially other genes, that are responsible for breaking down the study drug in the body ▪ This sample may also be used to back and test other genetic differences associated with the levels of the study drug in your blood, biomarker response, or to explore side effects ▪ This sample will be kept by Pfizer for up to 3 years after the end of the study o Retained Research Samples: Samples of your blood will be collected, stored, and used to learn more about the study drug ▪ Biological substances in your sample, including your genes, may be studied ▪ This may include analyzing all of your genetic information (called “whole gene sequencing”) ▪ These samples may be kept by Pfizer for many years (no time limit) • You will be asked to complete C-SSRS and PHQ-9 • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 113 blood draws. The total amount of blood drawn during this part of the study will be about 485mL. 405 mL. This is equal to about a little more than 16 13½ oz., or a little more than 2 less than1¾ cups. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  exam(s) will be done • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will may also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • You may complete a COVID-19 questionnaire • You may be tested for COVID-19 o COVID-19 testing will be done by collection of a swab sample • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Urine samples to test for drugs of abuse  ▪ Blood samples pregnancy test for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood serum or plasma (components of blood) from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. findings ▪ Biomarkers are natural substances in your body that can be used to show how your body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug. Blood will also be used to measure the blood to plasma ratio of the study drug  (the amount of study drug in the whole blood compared to that in the plasma) ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  ⮚ Metabolite identification and profiling  (by-products or end products of a drug produced as the body processes a drug) ⮚ Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  ⮚ Check the laboratory test which measures the study drug  Measure the levels of ritonavir  ⮚ Other internal exploratory purposes  • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. Some blood samples of about 0.1 mL (about 2 drops) will be taken by the Tasso® microsampling blood draw device. These samples will be used to measure the amount of study drug in your blood. The device will be temporarily attached to your upper arm using an adhesive. When the button is pressed, a vacuum forms and a lancet pricks the surface of the skin. The vacuum draws blood out of the capillaries and into a compatible container attached to the bottom of the Tasso Device. Some people refer to Tasso Devices as a needle-free system since it does not use a hollow venipuncture needle to enter a vein. A separate device will be used for each blood collection timepoint. This will be done 5 times after dosing on Day 2 in Period 1 only. The device collects a single sample and is then removed from the skin. There will be about 69 48 blood draws. The total amount of blood drawn during this part of the study will be about 485mL. 120 mL. This is equal to about 4 oz. or about a little more than 16 oz., or a little more than 2 cups½ cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  Physical exam will be done  The use of proper birth control will be confirmed/reviewed (males only)  Xxxxx xxxxx will be measured. Your oral temperature will may also be measured  You will be swabbed for COVID-19  ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o You will be asked to minimize activity while attached to the monitor asked: “How do you feel?” each day  An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  The study investigator may decide to do an alcohol breath test at any time  You will complete a COVID-19 questionnaire  You will be tested for COVID-19 o COVID-19 testing will be done by collection of a swab sample  Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  Urine samples to test for drugs of abuse  Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood serum (component of blood) from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. findings  Biomarkers are natural substances in your body that can be used to show how your body works. works  Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug and a related substance, and rosuvastatin  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, drug and rosuvastatin the samples for study drug levels may also be used for the following:  Metabolite identification and profiling (by-products or end products of a drug produced as the body processes a drug)  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes o Retained Research Sample: A sample of your blood will be collected, stored, and used to learn more about the study drug and rosuvastatin  Biological substances in your sample, including your genes, may be studied  This sample may be kept by Pfizer for as long as the sample is useful for scientific research. This may be for many years (no time limit)  You will receive a follow-up phone call about 4 weeks after the last dose of study drug  For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 28 blood draws. The total amount of blood drawn during the study will be about 485mL. 170 mL. This is equal to about a little more less than 16 6 oz., or a little more less than 2 cups¾ cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study. We do not know all of the side effects of the study drug. Like all medications, the study drug can cause side effects, although not everybody gets them. Most side effects are mild to moderate. However, some people may experience serious side effects and may require treatment. The study drug is not an approved drug and has only been taken by people in research studies. Therefore, the side effects of the study drug are not well known. Based on the data available as of 6 June 2022, a total of 176 participants have received at least one dose of the study drug, either alone or in combination with another medicine used to treat breast cancer called Palbociclib. One hundred and forty-nine of the participants received study drug alone, and 27 of the participants received it with Palbociclib. The most common possible side effects reported in participants who received the study drug, and are thought to be related or likely to be related to the study drug, as assessed by study investigators treating participants with the study drug include:  Fatigue (tiredness)  Nausea (feeling like you may be sick)  Arthralgia (joint pain)  Hot flush  Increase in blood levels of certain liver enzymes (which may be a sign of liver damage)  Constipation  Vomiting  Decreased appetite  Headache  Insomnia (sleeplessness)  QT prolongation (abnormal electrical conduction within the heart)  Diarrhea  Dry mouth  Hyperhidrosis (increased sweating)  Increase in blood level of a certain liver enzyme (which may be a sign of liver damage)  Myalgia (muscle aches)  Abdominal pain  Alopecia (hair loss)  Increase in blood levels of amylase (enzyme made by the pancreas and salivary gland; this may be a sign of pancreas damage)  Back pain  Bradycardia (slow heartbeat)  Cough  Dry skin  Dyspepsia (heartburn, indigestion)  Hyperglycemia (increase in blood sugar)  Vulvovaginal dryness (involving the vulva and vagina)  Decrease in white blood cells (decrease of the blood cells that fight infection, which increases the risk of infection)  Abdominal distention (pressure and swelling of the abdomen)  Pain in upper abdomen  Increase in certain enzymes produced by various tissues and cells  Dehydration  Hyperphosphatemia (increase in phosphate levels in the blood)  Hypertension (high blood pressure)  Hypokalemia (low blood potassium, which may cause an abnormal rhythm)  Increase in blood levels of lipase (enzyme made by the pancreas, mouth, and stomach; this may be a sign of pancreas damage)  Pain and pain in extremities (limbs)  Neutropenia (low count of a type of white blood cell that fights infection, which increases the risk of infection)  Pruritus (itching)  Rash  Rash maculo-papular (type of rash with both flat and raised parts)  Vision blurred  Venous embolism (blood clotting in a vein)  Abnormal T wave (abnormal heart tracing) The study drug may interact with other drugs, including over the counter or prescription medications, vitamins, and/or herbal supplements. The interaction between the study drug and any other medications may increase the risk of side effects of the study drug, decrease the effectiveness of the study drug, or make the other drugs you are taking less effective. It is important to be honest about your medical conditions and any other medications, both over-the-counter and prescription, that you are taking or plan to take during the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  exams may be done • The use of proper birth control will be confirmed/reviewed  Xxxxx xxxxx will be measured• Vital signs. Your oral temperature will may also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The C-SSRS (Since Last Assessment) will be completed at various times • The study investigator may decide to do an alcohol breath test at any time  • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Urine samples to test for drugs of abuse  ▪ Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood serum (component of blood) from the safety lab samples blood tests taken during the study may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. findings or for other exploratory purposes ▪ Biomarkers are natural substances in your body that can be used to show how your body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug  ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  ⮚ Metabolite identification and profiling  ⮚ Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  ⮚ Check the laboratory test which measures the study drug  Measure the levels of ritonavir  ⮚ Other internal exploratory purposes  • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, reasons we may add procedures at any time during the study to check on your health status  You o Study staff will be asked “How do you feel?” each day  You will be asked provide details of the procedures if you have had a bowel movement each day different from those described above Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 23 blood drawsdraws during the study. The total amount of blood drawn during the study will be is about 485mL. 115 mL. This is equal to about a little more less than 16 4 oz., . or about a little more less than 2 cups½ cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug drugs or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study. To date, the study drug has been given to: • Animals • Healthy human participants • COVID-19 patients. In animal studies, no significant risks or safety events of concern were identified, and the study drug did not cause any harmful effects. As of 24 June 2024, 289 participants have received at least one dose of the study drug. In one study done in COVID-19 patients, the study treatment-related adverse events (side effects) were: • Abdominal pain • Diarrhea • Dyspepsia (indigestion) • Vomiting • Elevation of a liver enzyme called alanine transferase (ALT) Each of these events were seen in no more than 1 participant. During this study, you will be monitored for changes in: • Vital signs • Heart rhythm • Laboratory results You will also be monitored for the occurrence of other symptoms or side effects. Laboratory tests will be done to evaluate any changes in laboratory results. Since the use of the study drug is investigational for the treatment of COVID-19, when taken alone or in combination with other medications, there may be other risks or side effects that are unknown. Human clinical and animal studies do not always predict the side effects of experimental drugs that people may experience. There may be rare and unknown side effects, including reactions that may be life- threatening and could result in sickness or death. There may be rare and unknown side effects, including reactions that may be life-threatening and could result in sickness or death.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes prior diseases, medication, drug, alcohol, and tobacco use  • Physical exam  • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will may also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • You will complete a COVID-19 questionnaire • You will be swabbed for COVID-19 • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Blood samples for aPTT, PT-INR, and fibrinogen ▪ Urine samples to test for drugs of abuse  ▪ Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug  and ritonavir ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drugdrug and ritonavir, the samples for study drug levels may also be used for the following:  ⮚ Metabolite identification and profiling  (by-products or end products of a drug produced as the body processes a drug) ⮚ Endogenous (within the body) biomarkers ⮚ Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  ⮚ Check the laboratory test which measures the study drug  Measure the levels of and ritonavir  ⮚ Other internal exploratory purposes  You o Blood/Plasma (a component of blood) Ratio: Blood samples will receive a follow-up phone call about 4 weeks after the last dose also be used for blood/plasma analysis of study drug  For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. and ritonavir (Study Treatments A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 blood draws. The total amount of blood drawn during the study will be about 485mL. This is equal to about a little more than 16 oz., or a little more than 2 cups. For comparison, the standard blood donation is about 16 oz. (2 cupsand B only), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  exam(s), will be done • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will may also be measured  • You will be swabbed for COVID-19  ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with asked: “How do you during the monitoring period o You will be asked to minimize activity while attached to the monitor  feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the followingincluding:  Urine samples to test for drugs of abuse  ▪ Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed done at the discretion of the study investigator in all females o Any leftover blood serum or plasma (components of blood) from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. findings ▪ Biomarkers are natural substances in your body that can be used to show how your the body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this the study o Banked BiospecimenStudy Drug Levels: Blood and urine samples (Dosing Groups 1 – 4 only) will also be used to measure the levels of study drug ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the blood samples may also be used for the following: ⮚ Metabolite identification (by-products or end products of a drug produced as the body processes a drug) ⮚ Endogenous (within the body) biomarkers ⮚ Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study ⮚ Check the laboratory test which measures the study drug ⮚ Other internal exploratory purposes ▪ All of your urine will be collected for 72 hours after study drug dosing (Dosing Groups 1 – 4 only) ⮚ As part of understanding how your body gets rids of the study drug in the urine, samples may also be used to check the laboratory test which measures the study drug as well as other exploratory purposes o Pharmacogenomics: A blood sample will be taken to determine how your genes affect your response to the study drug. This sample will be used to examine specific genes, including, but not limited to CYP3A and UGT2B7, and potentially other genes, that are responsible for breaking down the study drug in your body ▪ This sample may also be used to go back and test other genetic differences associated with the levels of the study drug in the blood, biomarker response, or to explore side effects ▪ This sample will be kept by Pfizer for up to 3 years after the Clinical Study Report (CSR) has been finalized ▪ A replacement blood sample may be requested if there are problems with this testing o Retained Research Sample: A sample of your blood will be collected collected, stored, and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to learn more about the study biological drug ⮚ Biological substances in your sample, including your genes. This will help us learn more about the study drug  , may be studied ⮚ This sample may be kept by Pfizer in a facility approved by Pfizer for as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples • You will be collected return to measure the levels of CRU for a follow-up visit about 4 weeks after study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling  Evaluate safety or efficacy dosing (ability female participants able to produce a desired effecthave children only) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  dosing (male participants and female participants unable to have children) • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be up to about 69 18 blood drawsdraws (needle stick or catheter). The total amount of blood drawn during the this study will be up to about 485mL. 100 mL. This is equal to about a little more than 16 3 oz., . or about a little more less than 2 cups½ cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study. Like all drugs, the study drug can cause side effects, although not everybody may experience them. The percentages listed below do not predict what could happen during this study. Please be aware that the side effects mentioned below could occur more or less often than indicated, and side effects not listed could occur. As of September 2, 2022, there are data available for 66 study participants who have been treated with multiple doses of study drug PF-07220060 alone for various types of late stage cancer or in combination with a hormone therapy drug for late stage breast cancer in the C4391001 study. There have been no deaths reported in the study considered related to the study drug. The following side effects were seen in C4391001 study participants who received PF-07220060 alone, or in combination with endocrine (hormone) therapy: Very Common (seen in 10% of participants or more) • Neutropenia (low neutrophil [type of white blood cell] counts), which may lead to infection • Anemia (low red blood cell count), which may lead to fatigue and shortness of breath • Thrombocytopenia (low platelet [helps the blood to clot] counts, which may lead to bleeding) • Leukopenia (low white blood cell counts) • Nausea • Vomiting • Diarrhea • Fatigue (tiredness) Common (seen in more than 5% but less than 10% of participants) • Gastroesophageal reflux disease (acid reflux or heartburn) • Hot flush • Arthralgia (aching or pain in joints) Less Common (seen in more than 2% but less than 5% of participants) • Dry mouth • Peripheral edema (swelling of the arms and/or legs) • Cough • Increase in a liver enzyme (may indicate liver problems) • Increase in lipase (enzyme produced by the pancreas, may indicate pancreatic problems) • Pyrexia (fever) • Hyperglycemia (high blood sugar) • Pruritus (itching) • Increase in blood creatinine, may indicate kidney problems) The study drug was tolerated in animal studies in rats and dogs. The following side effects were seen in animals: • Low white blood cell counts (neutropenia and leukopenia) • Thrombocytopenia • Anemia • Inflammation of the digestive tract including the mouth, stomach, and small and large bowels • Photosensitivity (sensitivity to the sun) Studies to determine the effect of the study drug on fertility and unborn children have not yet occurred, but toxicity to reproductive organs was observed in animal studies conducted with the study drug in rats and dogs. Therefore, you should speak to your study investigator regarding egg donation if you are a woman and can get pregnant or sperm donation if you are a male. Animal studies do not always predict the side effects that people may experience. Animal studies cannot completely predict symptoms that you may have after taking the study drug. The study drug may make your skin more sensitive to light. Because of this, you will be asked to avoid exposure and protect yourself from sunlight throughout the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • You will be swabbed for COVID-19 • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Urine samples to test for drugs of abuse  ▪ Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked BiospecimenStudy Drug Levels: Blood samples will also be used to measure the levels of study drug and ritonavir in each sample ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples may also be used for the following: ➢ Metabolite identification (by-products or end products of a drug produced as the body processes a drug) ➢ Evaluate safety or efficacy (ability to produce a desired effect) aspect related to any concerns during or after the study ➢ Check the laboratory test which measures the study drug ➢ Other internal exploratory purposes o Retained Research Sample: A sample of your blood will be collected collected, stored, and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to learn more about the study biological drug ▪ Biological substances in your sample, including your genes. This will help us learn more about the study drug  , may be studied ▪ This sample may be kept by Pfizer in a facility approved by Pfizer for as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples • C-SSRS (Since Last Assessment) will be collected to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  completed at various times • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 24 blood draws. The total amount of blood drawn during the study will be about 485mL. 185 mLs. This is equal to about a little more than 16 6 oz., or a little more than 2 cups¾ cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes prior diseases, medication, drug, alcohol, and tobacco use  • Physical exam, including eye exam  • Weight will be measured • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o • It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o • Your chest may be marked with a pen to identify the correct areas for ECG patch placement  • Continuous heart monitoring will be done for at least 12 6 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o dosing • This involves the attachment of a small box like unit (transmitter) to your chest o • The box is attached by a few wires (similar to those of an ECG) o • The monitor sends information about your heart’s activity by a radio signal to a monitor o • You may not sleep during the 2 hours of continuous monitoring done before dosing o • You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o • You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  • You will be asked: “How do you feel?” each day • An intravenous (IV) IV catheter may will be placed in a vein in one of your arms for study drug or placebo administration. A second IV may be placed in the opposite arm for blood collection  or safety reasons • The study investigator may decide to do an alcohol breath test at any time  • You will complete a COVID-19 questionnaire • You will be swabbed for COVID-19 • Blood and urine samples will be collected at various times throughout the study o • Safety Labs: The blood and urine samples will be used for safety labs including the following:  • Blood samples for aPTT and PT-INR • Urine samples to test for drugs of abuse  Blood • blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood serum (component of blood) from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  findings ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o • Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug  • As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  • Metabolite identification and profiling  (by-products or end products of a drug produced as the body processes a drug) • Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  • Check the laboratory test which measures the study drug  Measure the levels of ritonavir  • Other internal exploratory purposes  • Biomarkers: Blood samples will also be used to measure a number of specific biomarkers related to the body’s immune system and AD or other inflammatory skin conditions for exploratory purposes • Retained Research Samples: Samples of your blood will be collected, stored, and used to learn more about the study drug and AD or other inflammatory skin conditions • Biological substances in your samples, including your genes, may be studied • These samples may be kept by Pfizer for as long as the samples are useful for scientific research. This may be for many years (no time limit) • Immunogenicity: Blood samples will also be used to measure your immune system response to the study drug: • Anti-drug antibody (ADA) • Neutralizing antibody (NAb) • Samples may also be used for the following: • Additional evaluation of the immune response • Check the laboratory tests which measure the immune response • Other exploratory purposes • Your infusion site will be checked for any reactions You will receive a return to the CRU for follow-up phone call about 4 weeks visits after the last dose of study drug  or placebo as follows: • Days 8, 15, 32, 46, 61, 91, 181, and 271 - Groups 1 and 2 • Days 8, 15, 32, 46, 61, 91, 181, 271, 361, 451, and 541 – Groups 3 – 8 and 12 For safety reasons, we may add procedures at any time during the study to check on your health status  You will status, or additional follow-up visits beyond those scheduled (as detailed above) Follow-ups may be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day done using telehealth visits (by phone or zoom) and/or home health visits (health care provider comes to you) Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be up to about 69 22 blood draws. The total amount of blood drawn during the study will be about 485mL. 770 mL. This is equal to about a little more than 16 oz., or a little more than 2 26 oz (about 3 ¼ cups). For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-the- counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  • The use of proper birth control will be confirmed/reviewed  (males only) • Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements3 measurements ) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring • The application areas of your skin will be done for at least 12 hours after dosing. There will also be marked with a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o pen • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • You will complete a COVID-19 questionnaire • You will be swabbed for COVID-19 • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Urine samples to test for drugs of abuse  Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  findings ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked BiospecimenStudy Drug Levels: A sample Blood samples will also be used to measure the levels of study drug ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drugs, the samples may also be used for the following: ⮚ Metabolite identification (by-products or end products of a drug produced as the body processes a drug) ⮚ Check the laboratory test which measures the study drugs ⮚ Other internal exploratory purposes o Retained Research Samples: Samples of your blood will be collected collected, stored, and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample drugs ▪ Biological substances in your samples, including your genes, may be studied ▪ These samples may be kept by Pfizer in a facility approved by Pfizer for as long as the sample is samples are useful for scientific research. This may be for many years (no time limit) o Study Drug LevelsBiomarkers: Blood samples will also be collected used to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid following proteins ▪ High-sensitivity C-reactive protein (hsCRP) ▪ Interferon gamma-inducible protein 10 (IP-10) • Assessments of the study drugdrug application site(s) o Photographs of the application site(s) may be taken. Photographs are photographic images of the application site(s) that the study team may take of you during the study. You will not be identified in these photographs. However, if you have any markings on the area of your skin photographed, like a tattoo, those markings may appear in the photographs. Pfizer will own these photographs. The photographs will be used and shared along with your study records, as described in this consent document. In addition, the samples for study drug levels photographs may also be used in publications, presentations, brochures, or other ways. The photographs may be used along with text, graphics, or audio materials. You will not be identified by name in any use of the photographs. By signing and dating this consent document, you are giving permission for the following:  Metabolite identification study staff to take these types of photographic images and profiling  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after for the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  uses described above. • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 21 blood draws. The total amount of blood drawn during the study will be about 485mL. 165 mL. This is equal to about a little more than 16 5½ oz., or a little more less than 2 cups¾ of a cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes prior diseases, medication, drug, alcohol, and tobacco use  • Physical exam  • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will may also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • You will complete a COVID-19 questionnaire • You will be tested for COVID-19 • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Blood samples for aPTT, PT-INR, and fibrinogen ▪ Urine samples to test for drugs of abuse  ▪ Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will also be collected used to measure the levels of study drug  and ritonavir ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drugdrug and ritonavir, the samples for study drug levels may also be used for the following:  ⮚ Metabolite identification and profiling  (by-products or end products of a drug produced as the body processes a drug) ⮚ Endogenous (within the body) biomarkers ⮚ Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  ⮚ Check the laboratory test which measures the study drug  Measure the levels of and ritonavir  ⮚ Other internal exploratory purposes  You o Blood/Plasma (a component of blood) Ratio: Blood samples will receive a follow-up phone call about 4 weeks after the last dose also be used for blood/plasma analysis of study drug  For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. and ritonavir (Study Treatments A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 blood draws. The total amount of blood drawn during the study will be about 485mL. This is equal to about a little more than 16 oz., or a little more than 2 cups. For comparison, the standard blood donation is about 16 oz. (2 cupsand B only), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, vaccines, alcohol, and tobacco use  • Physical exam  exams may be done • The use of proper birth control will be confirmed/reviewed  Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  • Vital signs • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o You will be asked to minimize activity while attached to the monitor  An intravenous (IV) catheter may • You will be placed in a vein in one of your arms for blood collection  asked: “How do you feel?” at each visit • The study investigator may decide to do an alcohol breath test at any time  • Rapid antigen tests for flu will be conducted • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Urine samples to test for drugs of abuse  Blood ▪ Urine or blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood from the safety lab ) ▪ Blood samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can will also be used to show how measure your body works.  Samples to be used for this purpose immune response and peripheral blood mononuclear cells (PBMCs) isolation ⮚ PBMCs are a certain type of white blood cells • You will be kept observed for about 30 minutes after each study vaccination • You will return to the CRU for follow-up to 1 year following completion of this visits and your second study vaccination o Banked Biospecimen: A sample of your blood There will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will be collected to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  You will receive a follow-up phone call visit about 1 week after your first study vaccination o You will receive your second study vaccination at least 18 days after your first vaccination o There will be follow-up visits after your second study vaccination at 1 week, 4 weeks after the last dose of study drug  weeks, 3 months, and 6 months • For safety reasons, reasons we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day must provide biological samples in order to take part in this study. Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in needlesticks from a vein in your arm to take blood when requiredarm. Catheters are used when ordered by Additional samples may be collected depending on the study investigator results of your laboratory tests or when required by the study plan. They are not used at the request of the participantif a replacement sample is needed. There will be about 69 up to 8 blood drawsdraws during the entire course of the study. The total amount of blood drawn during the study will be about 485mL. is up to 572 mL. This is equal to about a little more than 16 19 oz., or about a little more less than 2 2½ cups. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. These samples will be used to measure your level of antibodies, and to isolate PBMCs to understand your response to the study vaccine. As with all studies with blood draws, rest rest, hydration, and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  Physical exam  The use of proper birth control will be confirmed/reviewed  Xxxxx xxxxx will be measured. Your oral temperature will also be measured  You will be swabbed for COVID-19  ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o You will be asked to minimize activity while attached to the monitor  An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  The study investigator may decide to do an alcohol breath test at any time  Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  Urine samples to test for drugs of abuse  Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood and urine from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can be used to show how your body works.  Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked Biospecimen: A sample of your blood will be collected and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to study biological substances in your sample, including your genes. This will help us learn more about the study drug  This sample may be kept by Pfizer in a facility approved by Pfizer as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood Blood, urine, and feces samples will be collected to measure the levels of study drug in each sample  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:   Metabolite identification and profiling   Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study   Check the laboratory test which measures the study drug  Measure the levels of ritonavir   Other internal exploratory purposes  Prior to dosing on Day 1, a urine and fecal sample will be collected. During your in- house stay, all of your urine and feces will be collected from the time of dosing on Day 1 through 240h post dose on Day 11.  You will receive a follow-up phone call about 4 weeks after the last dose of study drug  For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 17 blood draws. The total amount of blood drawn during the study will be about 485mL. up to 160 mL. This is equal to about a little more than 16 5 oz., or a little more than 2 cups½ cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. history o This includes medication, drug, alcohol, and tobacco use  • Physical exam  exam(s) will be done • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. measured o Your oral temperature will may also be measured  You will be swabbed for COVID-19  • ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with you during the monitoring period o • You will be asked to minimize activity while attached to the monitor  asked: “How do you feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • The study investigator may decide to do an alcohol breath test at any time  • You will complete a COVID-19 questionnaire • You will be tested for COVID-19 o COVID-19 testing will be done by collection of a swab sample • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the following:  ▪ Urine samples to test for drugs of abuse  ▪ Blood samples pregnancy test for pregnancy testing (females able to have children). children ⮚ Pregnancy tests may be performed at the discretion of the study investigator in all females o Any leftover blood serum or plasma (components of blood) from the safety lab samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. findings ▪ Biomarkers are natural substances in your body that can be used to show how your the body works.  works ▪ Samples to be used for this purpose will be kept for up to 1 year following completion of this study o Banked BiospecimenStudy Drug Levels: Blood and urine will also be used to measure the levels of study drug. Blood will also be used to measure the blood to plasma ratio of the study drug (the amount of study drug in the whole blood relative to that in the plasma) ▪ As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples may also be used for the following: ⮚ Metabolites identification (by-products or end products of a drug produced as the body processes a drug) ⮚ Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study (blood only) ⮚ Check the laboratory test which measures the study drug ⮚ Other internal exploratory purposes o Retained Research Sample: A sample of your blood will be collected collected, stored, and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to learn more about the study biological drug ▪ Biological substances in your sample, including your genes. This will help us learn more about the study drug  , may be studied ▪ This sample may be kept by Pfizer in a facility approved by Pfizer for as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples will be collected to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. On Day 1, at the 1-hour timepoint only, a 0.1 mL (about 2 drops) portion of the blood collected to measure the study drug in your blood will be used to determine the blood to plasma (B/P) concentration ratio of the study drug. Additionally, some blood samples of about 0.1 mL (about 2 drops) will be taken by the Tasso® microsampling automated blood draw device. These samples will be used to measure the amount of study drug in your blood. The device will be temporarily attached to your upper arm using an adhesive. A separate device will be used for each blood collection timepoint. This will be done 5 times after dosing with the study drug in Period 1 only. The device collects a single sample and is then removed from the skin. There will be about 69 28 blood draws. The total amount of blood drawn during the study will be up to about 485mL. 255 mL. This is equal to about a little more than 16 8 ½ oz., or a little more than 2 cups1 cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drugs or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study. To date, the study drug has been given to healthy participants and animals. In the animal studies, no significant risks or safety events of concern were identified. The study drug did not cause adverse effects at any of the dose levels that will be used in clinical studies. Based on the studies done in animals dosed with the study drug, the potential risks include: • Increased breathing rate • Small decreases in heart rate • Small increases in blood pressure • Vomiting • Decreased limb strength (or weakness) As of 06 February 2023, the study drug has been given as a single dose and multiple doses (twice daily for 10 days) to a limited number of healthy volunteer participants. Although only preliminary data are available, the early data in the healthy participant study did not show significant safety concerns when participants were given doses up to 1,500 mg twice daily for 10 days. However, the clinical data from the administration of study drug in humans is limited. During this study you will be monitored for changes in: • Breathing rate, heart rate and blood pressure • Laboratory results, as well as for the occurrence of other symptoms or side effects o Laboratory assessments will be taken to check for any changes in laboratory test results The effects of the study drug on reproduction are unknown. At this time, it is not known whether the study drug can cause harm to an unborn child or whether it is secreted in human milk. Therefore, the study drug should not be given to pregnant women or women who are breastfeeding. An appropriate method of birth control is required. Since the use of the study drug is investigational for the treatment of COVID-19 when taken alone or in combination with other medications, there may be other risks or side effects that are unknown. Human clinical and animal studies do not always predict the side effects of investigational drugs that people may experience. There may be rare and unknown side effects, including reactions that may be life-threatening and could result in sickness or death.

During the Study. The events below will take place throughout the study. If you would like to know when exactly these will take place, please ask the study staff.  • You will be asked about any updates to your medical history. This includes medication, drug, alcohol, and tobacco use  • Physical exam  exam(s), will be done • Nasal inspections will be done • The use of proper birth control will be confirmed/reviewed  • Xxxxx xxxxx will be measured. Your oral temperature will may also be measured  • You will be swabbed for COVID-19  ECGs (triplicate measurements) will be collected o It may be necessary to shave or trim hair on your chest so that the patches for the ECGs will stick to your skin o Your chest may be marked with a pen to identify the correct areas for ECG patch placement  Continuous heart monitoring will be done for at least 12 hours after dosing. There will also be a period of at least 2 hours where monitoring will be done before the first dosing. o This involves the attachment of a small box like unit (transmitter) to your chest o The box is attached by a few wires (similar to those of an ECG) o The monitor sends information about your heart’s activity by a radio signal to a monitor o You may not sleep during the 2 hours of continuous monitoring done before dosing o You will need to stay in the procedure room for at least 4 hours after the last dosing on Day 1 while attached to the monitor o You will need to keep the box with asked: “How do you during the monitoring period o You will be asked to minimize activity while attached to the monitor  feel?” each day • An intravenous (IV) catheter may be placed in a vein in one of your arms for blood collection  • Microsampling devices will be placed on your arm(s) for blood collection • The study investigator may decide to do an alcohol breath test at any time  • Blood and urine samples will be collected at various times throughout the study o Safety Labs: The blood and urine samples will be used for safety labs including the followingincluding:  Urine samples to test for drugs of abuse  ▪ Blood samples for pregnancy testing (females able to have children). Pregnancy tests may be performed done at the discretion of the study investigator in all females o Any leftover blood from the safety lab Study Drug Levels: Blood samples may be stored and used to assess exploratory safety biomarkers or unexpected safety findings. Biomarkers are natural substances in your body that can will also be used to show measure the levels of study drug. Blood will also be used to measure the blood to plasma ratio of the study drug (the amount of study drug in the whole blood relative to that in the plasma [a component of blood]) ▪ As part of understanding how your body works.  Samples to absorbs, distributes, and gets rid of the study drug, the samples may also be used for this purpose will be kept for up the following: ⮚ Metabolite identification (by-products or end products of a drug produced as the body processes a drug) ⮚ Evaluate safety or efficacy (ability to 1 year following completion of this produce a desired effect) aspects related to any concerns during or after the study ⮚ Check the laboratory test which measures the study drug ⮚ Other internal exploratory purposes o Banked BiospecimenRetained Research Sample: A sample of your blood will be collected collected, stored, and sent to Pfizer’s biobank. Pfizer calls this sample a “Banked Biospecimen”  This sample will be used to learn more about the study biological drug ▪ Biological substances in your sample, including your genes. This will help us learn more about the study drug  , may be studied ▪ This sample may be kept by Pfizer in a facility approved by Pfizer for as long as the sample is useful for scientific research. This may be for many years (no time limit) o Study Drug Levels: Blood samples • You will be collected to measure the levels of study drug  As part of understanding how your body absorbs, distributes, and gets rid of the study drug, the samples for study drug levels may also be used for the following:  Metabolite identification and profiling  Evaluate safety or efficacy (ability to produce a desired effect) aspects related to any concerns during or after the study  Check the laboratory test which measures the study drug  Measure the levels of ritonavir  Other internal exploratory purposes  complete Taste Assessment Questionnaires • You will receive a follow-up phone call about 4 weeks after the last dose of study drug  • For safety reasons, we may add procedures at any time during the study to check on your health status  You will be asked “How do you feel?” each day  You will be asked if you have had a bowel movement each day Blood samples will be taken by individual needlesticks, or by a catheter. A catheter is a small tube that is placed in a vein in your arm to take blood when required. Catheters are used when ordered by the study investigator or when required by the study plan. They are not used at the request of the participant. There will be about 69 9 blood drawsdraws (needle stick or catheter) for non-Japanese participants and 14 for Japanese participants. The total amount of blood drawn during the this study will be about 485mL. up to 85 mL. This is equal to about a little more than 16 2½ oz., . or about a little more than 2 cups¼ cup. For comparison, the standard blood donation is about 16 oz. (2 cups), once in any 56-day period. Some blood samples of about 0.1 mL (about 2 drops) up to 0.6 mL (about 12 drops) will be taken by the Tasso microsampling automated blood draw devices. This will be done in period 1 only. These samples will be used to measure the amount of study drug in your blood. The device will be temporarily attached to your upper arm using an adhesive. A separate device will be used for each blood collection timepoint. This will be done 6 times after dosing with the study drug, 3 from each arm. The device collects a single sample and is then removed from the skin. As with all studies with blood draws, rest and good eating habits are recommended. Blood loss in this amount may lead to a low red blood cell count (anemia). Anemia can make you feel more tired than usual. Once you finish the study, the study investigator may recommend that you take an over-the-counter iron pill or vitamins with iron. This is meant to help you build up your red blood cell count. Taking part in this study has some risks. The study drug(s) drug or procedure(s) may make you feel unwell or uncomfortable or could harm you. If you do not understand what any of the side effects described below mean, please let us know. The study investigator or study staff will explain them to you. It is important that you report all side effects that you have as soon as they occur. This is regardless of whether or not you believe they are caused by the study drug or your participation in this study. If you are not honest about any side effects that you have during the study, you may be harmed by staying in the study. Like all drugs, the study drug can cause side effects, although not everybody may experience them. The percentages listed below do not predict what could happen during this study. Please be aware that the side effects mentioned below could occur more or less often than indicated, and side effects not listed could occur. The safety of the study drug for the treatment of migraine in adults has been evaluated in 2 clinical trials. In these studies, 1,023 participants with a migraine received one 10 mg dose of the study drug as a nasal spray. Side effects included the following: • Taste disorders (18%) including: o Distortion of the sense of taste o Loss of sense of taste • Nausea (4 %) • Nasal discomfort (3%) • Vomiting (2%) Hypersensitivity, including facial swelling and hives, happened in less than 1% of participants treated with the study drug. Long-term safety was evaluated in a study with 603 participants dosed occasionally for up to 1 year. This included 360 participants dosed occasionally for at least 6 months and 298 for at least 1 year. These participants were treated with the study drug for a migraine an average of at least twice a month. Until you know how the study drug will affect you, you should use caution by: • Avoiding stairs • Not driving a car • Not swimming or bathing in a tub • Not working with machinery or at heights There may be rare and unknown side effects. These include reactions that may be life-threatening. All drugs have a potential risk of an allergic reaction. If an allergic reaction is not treated quickly, it could become life-threatening. You should get medical help right away (by calling 911 or immediately going to an emergency room) if you think you have any of the following symptoms: • Trouble breathing • Wheezing • Difficulty swallowing • Swelling of the face, mouth, lips, gums, tongue, or neck Other allergic reactions may include: • Itchiness • Rash • Hives • Blisters • Palpitations (racing heart) • Chest discomfort/tightness • Muscle pains/stiffness At times, the following may also be symptoms of an allergic reaction: • Diarrhea • Nausea • Vomiting • Abdominal pain If a significant side effect occurs, the following may be done: • Tests or treatment may be given as needed for your safety • Depending on how severe your symptoms are, you may be seen by outside medical providers or a hospital. This would be for further evaluation and/or treatment • The study investigator may notify your emergency contact as appropriate in the event of an emergency while you are taking part in the study Possible side effects of having your blood drawn or an IV catheter inserted include: • Bleeding at the site of the needle puncture • Bruising • Feeling faint • Rarely, infection or blood clot • Redness of the vein • Inflammation of the vein • Swelling • Pain • Nerve damage • Vein irritation from the fluid or medication being given • Local swelling due to IV fluid accidentally entering the tissue rather than the vein • Scarring If you feel faint, tell one of the study staff immediately.