Common use of Division of Cancer Treatment and Diagnosis, NCI Clause in Contracts

Division of Cancer Treatment and Diagnosis, NCI. 1. DCTD will develop and implement its preclinical/pharmacodynamic program for [*]. DCTD also may conduct [*] studies to [*]. DCTD will update Collaborator regarding progress and findings to help ensure optimal experimental designs and avoid duplication. 2. DCTD will conduct [*] studies in [*], and [*] studies using existing supplies of [1MT]. As stated in B(l) above, upon execution of the CRADA, NewLink will be responsible for partial costs associated with such studies. 3. DCTD will provide GMP-grade [*] for [*] clinical studies, initial [*] clinical studies, and [*] clinical trials. As stated in [*], upon execution of the CRADA, [*] will be responsible for the costs associated with the drug production for such clinical studies. 4. The DCTD, as sponsor, will prepare and submit to the FDA an IND for [*] for NCI-sponsored clinical studies. DCTD will permit NewLink to participate in DCTD’s IND preparation process. 5. The DCTD will collaborate solely with NewLink for [*] development, and will assist NewLink in all aspects of the regulatory approval process, so long as NewLink is pursuing clinical development of [*]. 6. To the extent permitted by law, the DCTD will maintain the DCTD-sponsored IND, including protocols and other supporting information relative to [*] as [*] in DCTD’s possession and control, as proprietary and confidential, and make it available exclusively to NewLink. The DCTD will permit NewLink to review, cross-reference and use the IND in conducting clinical trials and in fulfilling all of the requirements necessary for obtaining FDA approval to market [*] as [*]. 7. To the extent permitted by law, the DCTD will maintain the clinical data, results and raw data from all new studies developed under this proposed CRADA in its possession and control, as proprietary and confidential, and make them available exclusively to NewLink for use in obtaining approval for the commercial marketing of [*] as [*], so long as NewLink is pursuing commercial development for [*]. 8. The DCTD will solicit protocol Letters of Intent (LOI) from the investigators in the DCTD’s clinical trials network as appropriate. The Protocol Review Committee (PRC), of the DCTD, will: · Evaluate the rationale of each LOI received at the DCTD; · Review the XXXx for study design, including dose, schedule and comparison groups, if relevant, in order to address any pertinent scientific questions; · Examine the characteristics of the patient population to be studied; · Assess the feasibility of the projected accrual, including the ability of each investigator to accrue the appropriate patient population in a timely manner; · Review competing studies of the investigator in the specified disease(s); · Provide investigator(s) with consensus review(s) of the PRC’s evaluation to be used to revise the protocol; · Provide a copy of the consensus review to NewLink. All CTEP approved clinical XXXx will be sent by NCI to NewLink. NewLink will provide NCI with its approval or disapproval within [*] of receiving the CTEP approved clinical XXXx. Only XXXx that have been approved by both the PRC and NewLink will lead to the submission of full study protocols. The protocols received from investigators in response to the fully approved XXXx will be reviewed and evaluated by the PRC and by NewLink. The PRC will: · Evaluate each protocol from agent, disease, statistical and regulatory perspectives in order to ensure that the study design that was approved by the PRC at the LOI stage is carried out. · Provide each clinical research protocol received by DCTD to NewLink for review and comment approximately [*] before it is reviewed by the PRC of CTEP. Comments from NewLink received by CTEP before the PRC meeting will be discussed by the PRC, will be given due consideration, and will be incorporated into the protocol, absent good cause. Comments from either NewLink or the CTEP staff that are agreed upon in the PRC meeting will be formatted as a consensus review, which is returned to the investigator for necessary and/or suggested changes before the protocol can be given final approval and submitted to the FDA. In addition, the PRC will review any correlative laboratory studies, solicited from investigators, to address cellular pharmacological and/or pharmacokinetics questions as necessary. 9. The DCTD will evaluate each of the active studies as they progress to ensure that the appropriate questions are being addressed and to ensure that the studies are modified as required based on the developing data. The DCTD will utilize its existing procedures and mechanisms to follow the clinical studies to ensure that all studies meet the pertinent FDA regulations.

Division of Cancer Treatment and Diagnosis, NCI. 1. DCTD will develop and implement its preclinical/pharmacodynamic program for [*]1MT. DCTD also may conduct [*] studies to [*]] 1MT. DCTD will update Collaborator regarding progress and findings to help ensure optimal experimental designs and avoid duplication. 2. DCTD will conduct [*] studies in [*], and [*] studies using existing supplies of [1MT]. As stated in B(l) above, upon execution of the CRADA, NewLink will be responsible for partial costs associated with such studies. 3. DCTD will provide GMP-grade [*] 1MT for [*] Phase 0 clinical studies, initial [*] Phase 1 clinical studies, and [*] Phase 1 clinical trials. As stated in [*], upon execution of the CRADA, [*] will be responsible for the costs associated with the drug production for such clinical studies. 4. The DCTD, as sponsor, will prepare and submit to the FDA an IND for [*] 1MT for NCI-sponsored clinical studies. DCTD will permit NewLink to participate in DCTD’s IND preparation process. 5. The DCTD will collaborate solely with NewLink for [*] 1MT development, and will assist NewLink in all aspects of the regulatory approval process, so long as NewLink is pursuing clinical development of [*]1MT. 6. To the extent permitted by law, the DCTD will maintain the DCTD-sponsored IND, including protocols and other supporting information relative to [*] 1MT as [*] an anti-cancer agent in DCTD’s possession and control, as proprietary and confidential, and make it available exclusively to NewLink. The DCTD will permit NewLink to review, cross-reference and use the IND in conducting clinical trials and in fulfilling all of the requirements necessary for obtaining FDA approval to market [*] 1MT as [*]an anti-cancer agent. 7. To the extent permitted by law, the DCTD will maintain the clinical data, results and raw data from all new studies developed under this proposed CRADA in its possession and control, as proprietary and confidential, and make them available exclusively to NewLink for use in obtaining approval for the commercial marketing of [*] 1MT as [*]an anti-cancer agent, so long as NewLink is pursuing commercial development for [*]1MT. 8. The DCTD will solicit protocol Letters of Intent (LOI) from the investigators in the DCTD’s clinical trials network as appropriate. The Protocol Review Committee (PRC), of the DCTD, will: · Evaluate the rationale of each LOI received at the DCTD; · Review the XXXx for study design, including dose, schedule and comparison groups, if relevant, in order to address any pertinent scientific questions; · Examine the characteristics of the patient population to be studied; · Assess the feasibility of the projected accrual, including the ability of each investigator to accrue the appropriate patient population in a timely manner; · Review competing studies of the investigator in the specified disease(s); · Provide investigator(s) with consensus review(s) of the PRC’s evaluation to be used to revise the protocol; · Provide a copy of the consensus review to NewLink. All CTEP approved clinical XXXx will be sent by NCI to NewLink. NewLink will provide NCI with its approval or disapproval within [*] of receiving the CTEP approved clinical XXXx. Only XXXx that have been approved by both the PRC and NewLink will lead to the submission of full study protocols. The protocols received from investigators in response to the fully approved XXXx will be reviewed and evaluated by the PRC and by NewLink. The PRC will: · Evaluate each protocol from agent, disease, statistical and regulatory perspectives in order to ensure that the study design that was approved by the PRC at the LOI stage is carried out. · Provide each clinical research protocol received by DCTD to NewLink for review and comment approximately [*] before it is reviewed by the PRC of CTEP. Comments from NewLink received by CTEP before the PRC meeting will be discussed by the PRC, will be given due consideration, and will be incorporated into the protocol, absent good cause. Comments from either NewLink or the CTEP staff that are agreed upon in the PRC meeting will be formatted as a consensus review, which is returned to the investigator for necessary and/or suggested changes before the protocol can be given final approval and submitted to the FDA. In addition, the PRC will review any correlative laboratory studies, solicited from investigators, to address cellular pharmacological and/or pharmacokinetics questions as necessary. 9. The DCTD will evaluate each of the active studies as they progress to ensure that the appropriate questions are being addressed and to ensure that the studies are modified as required based on the developing data. The DCTD will utilize its existing procedures and mechanisms to follow the clinical studies to ensure that all studies meet the pertinent FDA regulations.