AMENDMENT NUMBER TWO TO THE SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

EXECUTION VERSION

AMENDMENT NUMBER TWO TO

THE SECOND AMENDED AND RESTATED

RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

THIS AMENDMENT NUMBER TWO TO THE SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT (the “Amendment”) is made and effective as of May 10, 2013, by and among AKEBIA THERAPEUTICS, INC., a Delaware corporation (the “Company”), and those Investors executing and delivering a counterpart signature page hereto. Capitalized terms not defined herein have the meanings given them in that certain Second Amended and Restated Right of First Refusal and Co-Sale Agreement, dated as of April 6, 2011, as amended by Amendment No. 1 thereto, by and among the Company, the Investors and the Major Holders (as amended, the “Agreement”).

WHEREAS, the Company and the Investors desire to amend the Agreement to modify the definitions of Appropriate Percentage and Preferred Stock and add a definition for the Series C Preferred Stock of the Company; and

WHEREAS, the Investors hold more than the Appropriate Percentage of the shares of Common Stock required to amend the Agreement pursuant to the provisions of Section 6.8 of the Agreement;

NOW, THEREFORE, in consideration of the foregoing recitals and the mutual promises hereinafter set forth and set forth in the Agreement, the parties hereby agree as follows:

1. Amendment.

(a) The definition of “Appropriate Percentage” shall be deleted in its entirety and replaced with the following: “Appropriate Percentage” means fifty percent (50%).

(b) The definition of “Preferred Stock” shall be deleted in its entirety and replaced with the following: “‘Preferred Stock’ means all shares of Series A Preferred Stock, Series B Preferred Stock, Series C Preferred Stock and Series X Preferred Stock.”

(c) A new definition of “Series C Preferred Stock” shall be added to the Agreement and shall read as follows: “‘Series C Preferred Stock’ shall mean shares of the Series C Preferred Stock of the Company, par value $0.00001 per share.”

(d) Schedule A shall be deleted in its entirety and replaced with the Schedule A attached hereto.

2. Miscellaneous Amendments. The Agreement is amended hereby so that any reference therein to the Agreement shall be deemed to be a reference to the Agreement as amended by this Amendment.

3. Continuance of Agreement. Except as specifically amended by this Amendment, the Agreement shall remain in full force and effect.

4. Governing Law. The laws of the State of Delaware govern all matters arising out of or relating to this Amendment, including, without limitation, its interpretation, construction, performance, and enforcement, without giving effect to such state’s conflicts of law principles or rules of construction concerning the drafter hereof.

5. Counterparts. This Amendment may be executed in two or more counterparts, including by facsimile or PDF signature, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

[Signature Page Follows]

2

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

AKEBIA THERAPEUTICS, INC.
By:		/s/ Xxxxxx X. Xxxxxxx
		Xxxxxx X. Xxxxxxx, Ph.D.
		President and Chief Executive Officer
Address:
Suite 420,
0000 Xxxxxx Xxxx,
Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

AGECHEM VENTURE FUND L.P.
By:		/s/ Xxxxx Xxxxxxx
Name:		Xxxxx Xxxxxxx
Title:		President
Address:
Attn: Xxxxx Xxxxxxx, President
0 Xxxxxxxxx Xxxxxx, Xxxxx 000
Xxxxxxxx, Xxxxxx Xxxxxx X0X 0X0

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

ATHENIAN VENTURE PARTNERS III L.P.
By:		Athenian III, Ltd.
Its:		General Partner
By:		/s/ Xxxx X. Xxxxxxxx
Name:		Xxxx X. Xxxxxxxx
Title:		President
AVP OHIO TECHNOLOGY I L.P.
By:		AVP Ohio I, Ltd.
Its:		General Partner
By:		/s/ Xxxx X. Xxxxxxxx
Name:		Xxxx X. Xxxxxxxx
Title:		President
Address:
000 Xxxx Xxxxx Xxxxxx Xxxx 00/Xxxxx 000X Xxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

BLUE CHIP VALIDATION FUND, LTD
By:		Blue Chip Venture Company, LTD
Its:		Manager
/s/ Xxxx XxXxxxxxxx
Xxxx XxXxxxxxxx Managing Director
Address:
000 Xxxxxx Xxxxxx Xxxxx 0000 Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

CINCINNATI CORNERSTONE INVESTORS AKB, LLC
By:		/s/ Xxxxxx X. Xxx
		Xxxxxx X. Xxx, Xx.
		President
Address:
00 Xxxx 0xx Xxxxxx, 0xx Xxxxx Xxxxxxxxxx, XX 00000-0000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXXXX XXXX

/s/ Xxxxxxx Xxxx

Xxxxxxx Xxxx

Address:

00 Xxx Xxxxxxx

Xxx Xxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXX X. XXXXXX TRUST
By:		/s/ Xxxx Xxxxxx
Name:		Xxxx Xxxxxx
Title:		Trustee
XXXX XXXXXX
/s/ Xxxx Xxxxxx
Xxxx Xxxxxx
Address:
0000 Xxxxxx Xxxxxx Xxxxx Xxxx Xxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

FAMILY AKEBIA INVESTMENTS LLC
By:		/s/ Xxxxxx Xxxxxxxxx
Name:		Xxxxxx Xxxxxxxxx
Title:		Managing Member
Address:
0000 Xxxx Xxxxxx #00X
Xxx Xxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXX XXXXXXX

/s/ Xxxx Xxxxxxx

Xxxx Xxxxxxx

Address:

0000 Xxxxxxxxxx Xx.

Xxxxxxxxxx, XX 00000-0000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXX XXXXXXXX TRUST, XXXXXX XXXXXXXX, TRUSTEE
By:		/s/ Xxxxxx Xxxxxxxx
		Name:		Xxxxxx Xxxxxxxx
		Title:		Trustee
Address:
0000 Xxxxxx Xxxx Xxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXXX X. XXXXXXX
By:		/s/ Xxxxxx X. Xxxxxxx
Address:
0000 Xxxxxx Xxxx Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXXXX FAMILY TRUST, XXXX X. XXXXXXX TRUSTEE
By:		/s/ Xxxx X. Xxxxxxx
		Xxxx X. Xxxxxxx
		Trustee
Address:
000 Xxxx Xxxxx Xxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

GITANA FAMILY TRUST, XXXXXXXXX X. XXXXXXXX TRUSTEE
By:		/s/ Xxxxxxxxx X. Xxxxxxxx
		Xxxxxxxxx X. Xxxxxxxx
		Trustee
Address:
0000 Xxxxxx Xxxxx Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

IAN X.X. XXXXX, XXX, STERLING TRUST CUSTODIAN
By:		/s/ Ian X. X. Xxxxx
Name:		Ian X. X. Xxxxx
Title:		Trustee
IAN X. X. XXXXX
/s/ Xxx X. X. Xxxxx
Xxx X. X. Xxxxx
Address:
000 Xxxxxxxxx Xxxxx Xxxxxx Xxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

KEARNY VENTURE PARTNERS, L.P.
By:		/s/ Xxxxxx Xxxxx
Name:		Kearny Venture Associates, LLC
Title:		its General Partner
Address:
Attn: Xxxxxx Xxxxx Kearny Venture Associates LLC 00 Xxxxxx Xxxxxx, Xxxxx 000 Xxx Xxxxxxxxx, XX 00000-0000
KEARNY VENTURE PARTNERS, ENTREPRENEURS FUND, L.P.
By:		/s/ Xxxxxx Xxxxx
Name:		Kearny Venture Associates, LLC
Title:		its General Partner
Address:
Attn: Xxxxxx Xxxxx Kearny Venture Associates LLC 00 Xxxxxx Xxxxxx, Xxxxx 000 Xxx Xxxxxxxxx, XX 00000-0000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

MCILWRAITH INVESTMENTS, LLC
By:		/s/ Xxxx XxXxxxxxxx
Name:		Xxxx XxXxxxxxxx
Title:		Manager
Address:
Attn: Xxxx XxXxxxxxxx 0000 Xxxxxxx Xxxx Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

MRK INTERNATIONAL, LLC
By:		/s/ Xxxxxxx X. Xxxxx
Name:		Xxxxxxx X. Xxxxx
Title:		Principal Member
Address:
0000 Xxxxxxxx Xxxxx Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

NOVARTIS BIOVENTURES LTD.
By:		/s/ X. X. Xxxx
Name:		X. X. Xxxx
Title:		Deputy Chairman
By:		/s/ Xxxxxxx Xxxxx
Name:		Xxxxxxx Xxxxx
Title:		Authorized Signatory
Address:
NOVARTIS BIOVENTURES LTD. Attn: Xxxxx Xxxxx Zivi 000 Xxxxx Xxxxxx Xxxxxxxx XX 12 Bermuda
But for mail, to: Novartis BioVentures Ltd. Attn: Xxxxx Xxxxx Zivi PO Box HM 2899 Xxxxxxxx XX LX Bermuda
And, also send a copy to: Novartis Venture Fund Attn: Xxxxxxxx Xxxxxx Five Xxxxxxxxx Xxxxxx, Xxxxx 000 Xxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXX XXXXXX

/s/ Xxxxx Xxxxxx

Xxxxx Xxxxxx

Address:

0000 Xxxxx Xxxx

Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

QCA FIRST FUND II
By:		/s/ Xxxx Xxxxxxx
Name:		Xxxx Xxxxxxx
Title:		Manager
Address:
000 Xxxxxxxx Xx. Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXXX X. XXXXXX REVOCABLE TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Trustee
THE XXXXXX FOUNDATION
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Trustee
XXXXXX FAMILY TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Investment Advisor
XXXXXX CHILDREN’S TRUST I
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Investment Advisor
Address:
c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXXXX XXXXXX XXXXXX REVOCABLE TRUST
By:		/s/ Xxxxxxx Xxxxxx Xxxxxx
Name:		Xxxxxxx Xxxxxx Xxxxxx
Title:		Trustee
Address:
c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXX-XXXXXX XXXXXX INSURANCE TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Trustee
ROSE XXXXXXX XXXXX INSURANCE TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Investment Advisor
XXXX X. XXXXXX INSURANCE TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Investment Advisor
XXXX XXXX TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Investment Advisor
Address:
c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

ADBUS XXXXXX INSURANCE TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Trustee
XXXXXX AND XXXXXXX XXXX XXXXXX INSURANCE TRUST
By:		/s/ Xxxxxx X. Xxxxxx
Name:		Xxxxxx X. Xxxxxx
Title:		Trustee
Address:
c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXXX XXXXXXXX
By:		/s/ Xxxxxx Xxxxxxxx
Address:
0000 Xxxxxx Xxxx Xxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

SIGVION FUND I, LP
By:		/s/ X. X. Xxxxxxxx
		X. X. Xxxxxxxx
		Founding Partner
Address:
000 Xxxx Xxxxxxxxxx Xxxxxx, Xxxxx 000 Xxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXXXX XXXXXX HEALTHCARE VENTURE PARTNERS, L.P.
By:		Xxxxxx Xxxxxx Capital Management LLC
Title:		its Managing Member
By:		/s/ Xxxxxx Xxxxx
Name:		Xxxxxx Xxxxx
Title:		Managing Director
Address:
00 Xxxxxx Xxxxxx, 0xx Xxxxx Xxx Xxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

TRIATHLON MEDICAL VENTURES FUND, L.P.
By:		Triathlon Medical Ventures, LLC
Its:		General Partner
By:		/s/ Xxxx X. Xxxx
		Xxxx X. Xxxx
		Managing Partner
Address:
000 X-Xxxxxxxx Xxx Xxxxx 000 Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

TRI-STATE GROWTH CAPITAL FUND II, L.P.
By:		Tri-State Ventures II, LLC
Its:		General Partner
By:		Fort Washington Investment Advisors, Inc.
Its:		Managing Member
By:		/s/ Xxxxx Xxxxx
Name:		Xxxxx Xxxxx
Title:		Managing Director
By:		/s/ Xxxxxxxx X. Xxxx
Name:		Xxxxxxxx X. Xxxx
Title:		President and Chief Executive Officer
Address:
000 Xxxxxxxx, Xxxxx 0000 Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

VENTURE INVESTORS EARLY STAGE FUND IV LIMITED PARTNERSHIP
By:		VIESF IV GP, LLC, its General Partner
By:		/s/ Xxxx X. Xxxxx
Name:		Xxxx X. Xxxxx, PhD
Title:		Managing Director
Address:
000 Xxxxx Xxxx Xxxx Xxxxxxx, XX 53719·1262 Attn: Xxxx Xxxxx, Managing Director Phone: (608) 441·2700 Fax: (000) 000-0000 Email: xxxx@xxxxxxxxxxxxxxxx.xxx

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be executed as of the date first written above.

XXXX X. XXXXX

/s/ Xxxx X. Xxxxx

Xxxx X. Xxxxx

Address:

Blue Chip Venture Company

1120 Scripps Center

000 Xxxxxx Xxxxxx

Xxxxxxxxxx, XX 00000

SIGNATURE PAGE TO AMENDMENT NUMBER TWO TO SECOND AMENDED AND RESTATED RIGHT OF FIRST REFUSAL AND CO-SALE AGREEMENT

Exhibit 4.8

SCHEDULE A

INVESTORS

Name and Address		Number of Shares of Common Stock				Number of Shares of Series A Preferred Stock				Number of Shares of Series B Preferred Stock				Number of Shares of Series C Preferred Stock
Triathlon Medical Ventures Fund, L.P. Attn: Xxxx X. Xxxx Managing Partner 000 X-Xxxxxxxx Xxx, Xxxxx 000 Xxxxxxxxxx, XX 00000			20,000.00				128,095.46				124,501.72				118,397.71
Novartis BioVentures Ltd. Attn: Xxxxx Xxxxx Zivi 000 Xxxxx Xxxxxx Xxxxxxxx XX 12 Bermuda But for mail, to: Novartis BioVentures Ltd. Attn: Xxxxx Xxxxx Zivi PO Box HM 2899 Xxxxxxxx XX LX Bermuda And, also send a copy to: Novartis Venture Fund Attn: Xxxxxxxx Xxxxxx Five Xxxxxxxxx Xxxxxx, Xxxxx 000 Xxxxxxxxx, XX 00000 and Xxxxxxx Xxxxxx Xxxxxx & Dodge LLP Attn: Xx Xxxxx 000 Xxxxxxxxxx Xxxxxx Xxxxxx, XX 00000 xxxxxx@xxxxxxx.xxx			0				257,031.16				347,830.73				708,647.43
Venture Investors Early Stage Fund IV Limited Partnership Attn: Xxxx Xxxxx Managing Director 000 Xxxxx Xxxx Xxxx Xxxxxxx, XX 00000-0000			0				153,434.52				173,915.36				201,811.43
Kearny Venture Partners, L.P. Attn: Xxxxxx Xxxxx Kearny Venture Associates, LLC 00 Xxxxxx Xxxxxx, Xxxxx 000 Xxx Xxxxxxxxx, XX 00000-0000			0				44,606.15				43,354.71				308,448.29

Schedule A-1

Name and Address		Number of Shares of Common Stock				Number of Shares of Series A Preferred Stock				Number of Shares of Series B Preferred Stock				Number of Shares of Series C Preferred Stock
Kearny Venture Partners Entrepreneurs Fund, L.P. Attn: Xxxxxx Xxxxx Kearny Venture Associates, LLC 00 Xxxxxx Xxxxxx, Xxxxx 000 Xxx Xxxxxxxxx, XX 00000-0000			0				909.78				884.26				6,290.57
Xxxxxx Xxxxxx Healthcare Venture Partners, L.P. 00 Xxxxxx Xxxxxx, 0xx Xxxxx Xxx Xxxxxxxxx, XX 00000			0				45,515.99				44,239.03				74,475.86
The Procter & Xxxxxx Company Attn: Xxxxx Xx Xxxxx Director, Corporate Acquisitions, Divestitures and Equity Ventures 0 Xxxxxxx & Xxxxxx Xxxxx Xxxxxxxxxx, XX 00000			72,047.44				0				8,475.71				0
Athenian Venture Partners III L.P. Attn: Xxxx X. Xxxxxxxx President Athenian III, Ltd. 000 Xxxx Xxxxx Xxxxxx Xxxx 00/Xxxxx 000X Xxxxxx, XX 00000			0				22,964.77				31,575.85				124,832.79
AVP Ohio Technology I L.P. Attn: Xxxx X. Xxxxxxxx President AVP Ohio I, Ltd. 000 Xxxx Xxxxx Xxxxxx Xxxx 00/Xxxxx 000X Xxxxxx, XX 00000			0				7,654.92				9,004.41				24,194.21
Sigvion Fund I, LP Attn: X. X. Xxxxxxxx Founding Partner 000 X. Xxxxxx Xxxxxx Xxxxxxx, XX 00000			8,000.00				13,660.69				13,277.43				21,402.57
Cincinnati Cornerstone Investors AKB, LLC Attn: Xxxxxx X. Xxx, Xx. President 00 Xxxx 0xx Xxxxxx, 0xx Xxxxx Xxxxxxxxxx, XX 00000-0000			0				13,122.75				12,754.59				118,391.79

Schedule A-2

Name and Address		Number of Shares of Common Stock				Number of Shares of Series A Preferred Stock				Number of Shares of Series B Preferred Stock				Number of Shares of Series C Preferred Stock
Tri-State Growth Capital Fund II, L.P. Attn: Xxxxx Xxxxx 000 Xxxxxxxx, Xxxxx 0000 Xxxxxxxxxx, XX 00000			0				12,804.65				12,445.41				21,488.36
Blue Chip Validation Fund, Ltd. Attn: Xxxx XxXxxxxxxx Managing Director 1100 Xxxxxxxx Center 000 Xxxx Xxxxx Xxxxxx Xxxxxxxxxx, XX 00000			0				3,402.09				0				0
QCA First Fund II Attn: Xxxx Xxxxxxx 0000 Xxxxxx Xxxxxx, XX #000 Xxxxxxxxxx, XX 00000			0				3,375.00				0				0
Gitana Family Trust, Xxxxxxxxx X. Xxxxxxxx Trustee Attn: Xxxxxxxxx X. Xxxxxxxx Trustee 0000 Xxxxxx Xxxxx Xxxxxxxxxx, XX 00000			0				2,765.57				828.17				1,551.57
Xxxxxx Xxxxxxxx 0000 Xxxxxx Xxxx Xxxxxx, XX 00000			127,637.41				849.53				2,070.42				2,500.00
Xxxx Xxxxxxxx Trust, Xxxxxx Xxxxxxxx, Trustee Attn: Xxxxxx Xxxxxxxx Trustee 0000 Xxxxxx Xxxx Xxxxxx, XX 00000			0				3,403.13				0				0
Xxxxxx X. Xxxxxxx 0000 Xxxxxx Xxxx Xxxxxxxxxx, XX 00000			161,423.79				9,038.87				11,594.35				26,383.21
Xxxxxxx Family Trust, Xxxx X. Xxxxxxx Trustee Attn: Xxxx X. Xxxxxxx Trustee 000 Xxxx Xxxxx Xxxxxx, XX 00000			0				6,901.99				7,288.07				2,485.00

Schedule A-3

Name and Address		Number of Shares of Common Stock				Number of Shares of Series A Preferred Stock				Number of Shares of Series B Preferred Stock				Number of Shares of Series C Preferred Stock
Ian X. X. Xxxxx, XXX, Sterling Trust Custodian Attn: Ian X. X. Xxxxx Trustee 000 Xxxxxxxxx Xxxxx Xxxxxx Xxxx, XX 00000			0				5,000.00				5,797.18				7,142.00
Ian X. X. Xxxxx 000 Xxxxxxxxx Xxxxx Xxxxxx Xxxx, XX 00000			46,925.51				0				0				2,902.21
Xxxxx Xxxxxx 0000 Xxxxx Xxxx Xxxxxxxxxx, XX 00000			46,925.51				0				1,449.29				3,473.00
Xxxxxxx Xxxx 00 Xxx Xxxxxxx Xxx Xxxxxxxx, XX 00000			60,810.00				0				0				13,488.86
Xxxxxx X. Xxxxxx Revocable Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				115,943.58				182,551.50
Xxxx Xxxx Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				0				3,571.00
The Xxxxxx Foundation c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				57,971.78				191,275.86
Xxxxxx X Xxxxxx XXX, Millennium Trust Company, Custodian			0				0				0				14,285.00
Xxxxxx Children’s Trust I c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				57,971.78				66,275.86

Schedule A-4

Name and Address		Number of Shares of Common Stock				Number of Shares of Series A Preferred Stock				Number of Shares of Series B Preferred Stock				Number of Shares of Series C Preferred Stock
Xxxxxxx Xxxxxx Xxxxxx Revocable Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				0				7,142.00
Xxxx-Xxxxxx Xxxxxx Insurance Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				0				7,142.00
Rose Xxxxxxx Xxxxx Insurance Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				0				7,142.00
Xxxx X. Xxxxxx Insurance Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				0				7,142.00
Xxxxx Xxxxxx Insurance Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				0				3,571.00
Xxxxxx and Xxxxxxx Xxxx Xxxxxx Insurance Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				0				3,571.00
Xxxxxx Family Trust c/x Xxxxxx Investment Management, LLC 000 X. Xxxxxxxx Xxxxxx, Xxxxx 0000 Xxxxxxx, XX 00000 Attn: Xxxxxx X. Xxxxxx			0				0				28,985.89				31,351.93
AgeChem Venture Fund L.P. Attn: Xxxxx Xxxxxxx President 0 Xxxxxxxxx Xxxxxx, Xxxxx 000 Xxxxxxxx, Xxxxxx, Xxxxxx X0X 0X0			0				0				173,915.35				123,143.86

Schedule A-5

Name and Address		Number of Shares of Common Stock				Number of Shares of Series A Preferred Stock				Number of Shares of Series B Preferred Stock				Number of Shares of Series C Preferred Stock
Xxxxx X. Xxxxxx Trust Attn: Xxxx Xxxxxx Trustee 0000 Xxxxxx Xxxxxx Xxxxx Xxxx Xxxxxxx, XX 00000			0				0				1,449.29				139.00
Xxxx Xxxxxx 0000 Xxxxxx Xxxxxx Xxxxx Xxxx Xxxxxxx, XX 00000			0				0				0				1,670.79
MRK International, LLC Attn: Xxxxxxx X. Xxxxx Principal Member 0000 Xxxxxxxx Xxxxx Xxxxxxxxxx, XX 00000			0				0				0				396.00
McIlwraith Investments, LLC Attn: Xxxx XxXxxxxxxx Manager 0000 Xxxxxxx Xxxx Xxxxxxxxxx, XX 00000			0				0				0				4,597.00
Xxxx X. Xxxxx 0000 Xxxxxxx Xxxx Xxxxxxxxxx, XX 00000			0				0				0				1,039.36
Xxxx Xxxxxxx 0000 Xxxxxxxxxx Xxxxx Xxxxxxxxxx, XX 00000-0000			0				0				0				1,428.00
Family Akebia Investments LLC Attn: Xxxxxx Xxxxxxxxx 0000 Xxxx Xxxxxx #00X Xxx Xxxx, XX 00000			0				0				0				142,858.00
Xxxx X/X Xxxx Xxxxxxxx Xxxxxx Xxxxxxxx 00 DK – 2900 – Hellerup			0				0				0				714,285.00

Schedule A-6