Portions of this exhibit have been omitted pursuant to a request for confidential treatment by BioMimetic Therapeutics, Inc. The omitted portions, marked by [**], have been separately filed with the Securities and Exchange Commission. FOURTH AMENDMENT TO DEVELOPMENT, MANUFACTURING AND SUPPLY AGREEMENT

This Fourth Amendment (the “Amendment”) to the Development, Manufacturing and Supply Agreement (the “Agreement”) dated as of September 30, 2010 between Kensey Nash Corporation, a Delaware corporation, having its principal place of business at 735 Pennsylvania Drive, Exton, PA 19341 (hereinafter referred to as “KNC”) and BioMimetic Therapeutics, Inc. (formerly, BioMimetic Pharmaceuticals Inc.), a Delaware corporation, having its principal place of business at 389-A Nichol Mill Lane, Franklin, TN 37067 (hereinafter referred to as “BMTI”).

WHEREAS, KNC and BMTI previously entered the Agreement dated June 28, 2005, as amended; and

WHEREAS, KNC and BMTI desire to amend the Agreement as set forth herein.

NOW, THEREFORE, in consideration of the mutual agreements contained herein, and pursuant to Section 16.2 of the Agreement, the parties agree as follows:

1.

Capitalized terms not otherwise defined herein shall have the meaning ascribed to such terms in the Agreement.

2.

Section 6.1 of the Agreement is hereby deleted in its entirety, including all amendments to Paragraph 6., and restated in its entirety as follows:

“6.1    Milestone Payments.  BMTI agrees to make Milestone Payments to KNC according to Schedule G, which is attached hereto and made part of the Agreement.  If BMTI (i) fails to make any Milestone Payment within forty-five (45) days of the occurrence of the specified event, and (ii) does not cure such failure to pay within thirty (30) days of receiving notice of such failure from KNC, KNC will have the option but not the obligation to terminate this Agreement.  Upon such termination, KNC shall be relieved of all obligations to BMTI under this Agreement.”

3.

Schedule A to the Agreement, “Development Plan”, is hereby amended and restated in its entirety to read as indicated in the Amended Schedule A, attached hereto.

4.

Schedule B to the Agreement, “Material Specifications”, is hereby amended and restated in its entirety to read as indicated in the Amended Schedule B, attached hereto.

5.

Schedule C to the Agreement, “Product Specifications”, is hereby amended and restated in its entirety to read as indicated in the Amended Schedule C, attached hereto.

6.

Schedule D to the Agreement, “Transfer Price”, as amended, is hereby amended and restated in its entirety to read as indicated in the Amended Schedule D, attached hereto.

7.

Schedule F to the Agreement, “Certificate of Conformance and Certificate of Analysis”, is hereby amended and restated in its entirety to read as indicated in the Amended Schedule F, attached hereto.

9.

The parties will negotiate in good faith a Quality Agreement.

10.

This Amendment is meant to amend, modify or supersede only those specific sections, rights, responsibilities, liabilities and/or covenants expressly referred to in this Amendment, and only to the extent so referred to; and accordingly all other sections and covenants of the Agreement shall remain unaffected and shall continue to have full force and effect.

IN WITNESS WHEREOF, the parties have executed this Amendment through their duly authorized representatives as of the date first written above.

BIOMIMETIC THERAPEUTICS, INC.			KENSEY NASH CORPORATION
By:	/s/ Earl Douglas		By:	/s/ Joseph W. Kaufman
	Earl Douglas			Joseph W. Kaufmann
	General Counsel			President & CEO

Kensey Nash Corporation and BioMimetic Therapeutics, Inc.

Amended Schedule A: Development Plan

Dated: August 30, 2010

 

To design a new methodology/system for supplying the matrix component and mixing the matrix component with PDGF that improves the speed and ease of product mixing and reduces waste as compared to the existing manual kneading of the ** matrix and PDGF in a bowl.

 

·

Initially: Open surgical applications.

·

Future: Percutaneous delivery/injection.

 

Proposed final packaged kit containing:

·

Matrix tray: the following components to be held in an open tray inside an Aclar-coated outer tray, sealed with a foil lid to act as a moisture barrier, terminally sterilized via gamma radiation (provided by KNC).

o

Matrix component packaged inside a suitably sized, capped ** syringe,

o

a second identical empty syringe,

o

one female-female luer lock connector,

o

one ** Blunt Fill Needle,

o

one ** Blunt Needle.

·

PDGF component, packaged and terminally sterilized via EtO (This component and the final kit packaging to be performed by BMTI).

 

·

System will utilize current formulation of the collagen/β-TCP ceramic material (**: β-TCP: ** bovine type I collagen, ** format).

·

System design will need to accommodate **, **, and ** (PDGF) configurations. This corresponds to **, **, and ** of ** collagen/ceramic matrix, respectively.

·

System will be designed to release approximately **% of the rhPDGF from the implant within ** of application (exact number to be further defined by BMTI).

·

System should allow product materials to be hydrated for **.  Product should form a homogeneous paste following mixing for ** (approximately ** mixing cycles).

·

System components that may contact product must be made from biocompatible polymer.

·

PDGF should be extracted from the vial directly into the mixing system.

·

System should allow clinician to present mixed material to a clinical site of no less than ** inches in diameter directly from mixing device.

·

Mixed material shall be able to pass through a cannula of ** gauge and ** in length.

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

Amended Schedule A: Development Plan (continued)

Dated: August 30, 2010

 

 

Item		Description		Responsibility		Target Completion Date
1.		Conduct design review (matrix and KNC-provided accessories)		KNC/BMTI		**
2.		Receive packaging materials		KNC		**
3.		Initiate commercial stability program (product/packaging)		KNC		**
4.		Complete validations (sterilization, LAL, product, packaging)		KNC		**
5.		Submit PMA		BMTI		**
6.		Launch product (est.)		BMTI		**

 

Note:

Estimated kit sales figures represent the aggregate sales of all product sizes.  All product sizes are not necessarily required to begin commercial launch.

 

 

·

Internal meetings as needed

·

Joint conference calls/meetings no less frequent than monthly

 

 

Kensey Nash Corporation and BioMimetic Therapeutics, Inc.

Amended Schedule B: Material Specifications

Dated: August 30, 2010

KNC Design Spec – Specification tested/confirmed during KNC validations only.

KNC Final Product Spec – Specification tested on every lot during KNC lot release testing (i.e., recorded on KNC Inspection History Record [IHR]).  “CoA” is included if the attribute will be reported to BMTI on the Certificate of Analysis.

BMTI AIBG Design Spec – Specification included as part of AIBG overall design features but not tested by either KNC or BMTI on every lot.

BMTI Incoming Spec – Specification tested on every lot during BMTI incoming receipt testing.

For all Tables: All specifications apply to non-sterile material unless otherwise noted.

Attribute

Specification

Test Method

KNC Design Spec

KNC Final Product Spec

BMTI AIBG Design Spec

BMTI Incoming Spec

Tested in Stability

Purpose

Animal Age

**

Verify cert from vendor

ü

Ensures material is suitable for creating ** collagen component

Regulatory Requirements

Must meet definition of closed herd as specified in ISO 22442-2

Verify cert from vendor

ü CoA

Ensures safety of starting material with regard to TSE/BSE

Attribute

Specification

Test Method

KNC Design Spec

KNC Final Product Spec

BMTI Design Spec

BMTI Incoming Spec

Tested in Stability

Purpose

Total Bacterial Count

**/gm (Average of 2 plate counts)

KNC SOP **, Bioburden Determination by Pour Plate

ü

n/a

n/a

Intermediate check at KNC verifies bioburden is adequately low before continuing with downstream processing

Attribute

Specification

Test Method

KNC Design Spec

KNC Final Product Spec

BMTI Design Spec

BMTI Incoming Spec

Tested in Stability

Purpose

Nitrogen Content

**% -**%

KNC SOP **, Nitrogen Determination (Kjeldahl Method)

ü

Verifies that manufacturing process has adequately removed non-protein materials

Hydroxyproline Content

**%-**%

KNC SOP **, Determination of  Hydroxyproline

ü

Used to indirectly estimate collagen content in tissue preparations

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

 

Amended Schedule B: Material Specifications (continued)

Dated: August 30, 2010

Table B.4: b-TCP Component (KNC PN **)

Attribute

Specification

Test Method

KNC Design Spec

KNC Final Product Spec

BMTI AIBG Design Spec

BMTI Incoming Spec

Tested in Stability

Purpose

Chemical Formula

b-Ca3(PO4)2

Verify cert from vendor

ü

Ensures proper ceramic is used

Composition

Meets ASTM 1088-04A for b-TCP

Verify cert from vendor

ü

ü

Ensures proper ceramic is used

Particle Size

**µm-**µm

Verify cert from vendor

ü

ü

Ensures ceramic range needed for clinical efficacy

Trace Elements

As: < 3ppm Cd: < 5ppm Hg: < 5ppm Pb: < 30ppm Total Heavy Metal as Lead: less than 50ppm

Verify cert from vendor

ü

Ensures purity of raw ceramic

X-Ray Diffraction (XRD)

The XRD pattern results are required from the vendor and must conform to JCPDS 9-169

Verify cert from vendor

ü

Ensures purity of raw ceramic

Wetability

**%

KNC SOP **, Beta Tricalcium Phosphate Wetability Testing Procedure

ü

Confirms adequate b-TCP wetting properties prior to downstream processing

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

 

Kensey Nash Corporation and BioMimetic Therapeutics, Inc.

Amended Schedule C: Proposed Product Specifications

Dated: August 30, 2010

Specification		Requirement
Implant Level: KNC PN **
Physical Appearance		White to light yellow, light yellow and/or yellow speckling is acceptable when tested in accordance with KNC SOP **
Mass		** device: ** when tested in accordance with KNC SOP **
Allowable Particulate		Maximum of ** (**) particle that has an area less than or equal to ** per individual matrix sub-component when tested in accordance with KNC SOP **; Multiple sub-components may make up a matrix component
Dry Weight Ratio (ash testing)		**% b-TCP by mass, average of 3 measurements when tested in accordance with KNC SOP **
Porosity		**% minimum, average of 3 measurements when tested in accordance with KNC SOP **
Loss on Drying (% Solids)		**% solids minimum, average of 3 measurements when tested in accordance with KNC SOP **
Hydration/Kneading Test		Homogenous construct devoid of nodules/hard spots when tested in accordance with KNC SOP **
Packaged Level: KNC PN **
Configuration		“**” implant sealed within an inner pouch, sealed within a labeled outer pouch
Allowable Particulate		Inner Pouch - Maximum of ** (**) observed particle that has an area less than or equal to ** (per TAPPI Dirt Estimation Chart) is allowed. Outer Pouch - Maximum of ** (**) observed particle that has an area less than or equal to ** (per TAPPI Dirt Estimation Chart), or ** (**) observed particles that each have areas less than or equal to ** (per TAPPI Dirt Estimation Chart).
LAL Endotoxin Level		** EU/device maximum, post sterilization
Sterility		Gamma sterilized at a range of **; validated method
Package Integrity – Peel Strength		**./linear in. minimum for both inner and outer pouch

Standard Lead Time: 8 weeks

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

 

Amended Schedule C: Proposed Product Specifications (continued)

Dated: August 30, 2010

Attribute

Specification

Test Method

KNC Design Spec

KNC Final Product Spec

BMTI AIBG Design Spec

BMTI Incoming Spec

Tested in Stability

Purpose

Material

Manufactured from collagen raw material that meets ASTM F2212-02 and ceramic that meets ASTM F1088-04

Component material certificates of conformance, lot release results

ü CoA

ü CoA

Ensures medical grade components are used

Physical Appearance

White to off-white non-sterile ** material

Visual examination per 6453-01.xls Inspection History Record (IHR)

ü

n/a

n/a

Verifies visual quality of intermediate material at KNC

Contamination

No foreign or denatured collagen material

Visual examination per KNC SOP**, Particulate Inspection for Ground Collagen Powders

ü

n/a

n/a

Intermediate check at KNC ensures no foreign particulates contaminate the ** material

Dry Weight Ratio

** b-TCP by mass, average of 3 measurements

KNC SOP **, Low Temperature Microwave Ash Content Determination

ü CoA

ü CoA

Verifies components were mixed in proper ratio for clinical efficacy

Loss on Drying (% Solids)

** average of 3 measurements

KNC SOP **, Total Dry Solids Determination

ü CoA

ü CoA

ü

Verifies matrix does not contain excessive moisture [potential impact on product preparation/handling characteristics]

Bulk Density

** grams/cc (to be finalized)

KNC SOP TBD (based on ASTM standard)

ü

n/a

n/a

Possible indicator at KNC of particle size distribution and/or hydration properties

Hydration/Extrusion

Material must be able to be hydrated

KNC SOP TBD

ü

n/a

n/a

Intermediate check at KNC verifies acceptable product handling prior to release for matrix loading/packaging

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

 

Attribute

Specification

Test Method

KNC Design Spec

KNC Final Product Spec

BMTI AIBG Design Spec

BMTI Incoming Spec

Tested in Stability

Purpose

Mass

KNC PN 2080X-02 (3cc product): **

Balance Scale

ü CoA

ü

Ensures appropriate amount of dry material to generate desired post-hydration volume

Physical Appearance [** Material, post sterilization]

White to light yellow; light yellow and/or yellow speckling is acceptable

Visual examination per 20801-01.xls IHR

ü (for PN **)

ü CoA (for PN **)

ü

Verifies visual integrity of the matrix material

Allowable Particulate

Maximum of ** (**) observed particle that has an area ** (per TAPPI Dirt Estimation Chart) is allowed on or in each component

Visual examination per ** or **

ü CoA

ü CoA

Verifies visual integrity of the packaged components

** Content [post sterilization]

** ppm maximum

BMTI SOP TBD

ü

Ensures ** level does not adversely affect clinical efficacy

Configuration

One ** syringe filled with ** collagen/ceramic matrix, one empty ** syringe, one female luer style coupler, one female luer style cap, one ** cannula, and one ** cannula

Visual examination per ** or **

ü

ü

Verifies all required matrix sub-kit components are included

Hydration/Extrusion [post sterilization]

Material must be able to be mixed and produce a homogenous paste after ** mixing cycles with minimal material left unmixed; material must be able to extrude through ** cannula, ** long

KNC SOP **, BioMimetic Collagen Beta TCP Component Physical Testing Procedure

ü CoA

ü CoA

ü

Verifies acceptable product handling

Package Integrity – Peel Strength

Foil pouch seals: ** lb/linear inch PETG tray with foil lid: **/linear inch

KNC SOP **, Peel Test Procedure

ü CoA

ü CoA

ü (Separate packaging stability study)

Verifies product package can maintain product sterility

Sterility

Sterile per ISO 11137-2 requirements (SAL 10-6)

Verify cert from contract sterilizer

ü CoA

ü CoA

Verifies final product meets safety requirements

LAL Endotoxin Level [post sterilization]

**/device

Verify CoA from contract test laboratory

ü CoA

ü CoA

Verifies final product meets safety requirements

Standard Lead Time: 8 weeks

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

 

Amended Schedule C: Proposed Product Specifications (continued)

Dated: August 30, 2010

Table C.4: ** Product

**.

 

Table C.5: ** Product

**.

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

 

Kensey Nash Corporation and BioMimetic Therapeutics, Inc.

Amended Schedule D: Transfer Price

Revision Dated: August 30, 2010

Effective as of: January 1, 2011

KNC Part Number

Product Size and Configuration

1 – ** Units*

** – ** Units*

** – ** Units*

>** Units*

**

**** **

$

**

$

**

$

**

$

**

**

**** **/Syringe

$

**

$

**

$

**

$

**

* Any combination of product configurations purchased annually.

** Volume after hydration with PDGF.

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

Kensey Nash Corporation and BioMimetic Therapeutics, Inc.

Amended Schedule F: Certificate of Conformance and Certificate of Analysis

Dated: August 30, 2010

An example of a Certificate of Conformance/Certificate of Analysis is included below.

 

[logo]

 

Supplier:	Kensey Nash Corporation
Address:	735 Pennsylvania Drive
	Exton, PA 19341
Customer:	BioMimetic Therapeutics, Inc.

 

	Reference:
	Description	BioMimetic Augmentä Injectable Bone Graft
	KNC Part Number	**
	KNC Lot Number	**
	Quantity Shipped	330
	Manufacture Date	March 2009

We hereby certify that the products shipped on the above purchase order conform to all dimensions and specifications referenced or required on the specification sheet or the purchase order. Exceptions, if any, will be noted.

We hereby confirm that materials of animal origin used in the products specified above meet current regulatory and BioMimetic requirements for TSE/BSE minimization, including:

·

The materials were sourced from animals considered to be low risk for TSE/BSE using a documented Quality Management System.

·

Materials were sourced, collected and handled per ISO 22442-2 (2007) and applicable regulatory requirements from the source and destination countries, including feeding, veterinary care and slaughtering methods.

·

Identification and traceability of the material to the animal origin was maintained and documented with means for controlling cross contamination.

 

Certifications and/or chemical/physical test reports for the materials used are on file and will be available to your company or to the government on request.

Manufactured in the USA.

Attribute		Analytical Method		Specification		Result
Physical Appearance		Visual examination (KNSY **)		White to light yellow, light yellow and/or yellow speckling is acceptable		PASS
Mass		Gravimetric (KNSY **)		** g		PASS Avg. = **
Particulate		Visual examination (KNSY **)		Maximum of one (1) particle that has an area less than or equal to **		PASS
Dry Weight Ratio (Ash Test)		Gravimetric (KNSY **)		**-**% b-TCP by mass		PASS Avg. = **%
Porosity		He-Pycnometry (KNSY **)		**% minimum		PASS Avg. = **%

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

Attribute		Analytical Method		Specification		Result
Loss on Drying (Solids Test)		Gravimetric (KNSY **)		**% solids minimum		PASS Avg. = **%
Hydration/Kneading Test		Manual Mix (KNSY **)		Homogenous construct devoid of nodules/hard spots		PASS
Endotoxin Level		USP <85>		** EU per matrix component		PASS
Sterility		Review Certificate of Processing		Irradiated with **-** kGy		PASS (** - ** kGy)
Min. Peel Strength, Inner Pouch		Peel Strength (KNSY **)		** lb / linear inch minimum, 3 measurements		PASS Avg. = ** lbs.
Min. Peel Strength, Outer Pouch		Peel Strength (KNSY **)		** lb / linear inch minimum, 3 measurements		PASS Avg. = ** lbs.

 

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.

Kensey Nash Corporation and BioMimetic Therapeutics, Inc.

Schedule G: Milestone Payments

Dated: August 30, 2010

Subsection			Amount			Description		Forecasted Completion Date
G.1			$	**		Upon the filing of the first PMA for US Approval of the first Commercial Product			**
G.2			$	**		Upon receipt of Approval for marketing of the first Commercial Product in the United States from the FDA (generally "Approved Commercial Product") for open and/or closed fractures via an open approach			**
G.3			$	**		Upon receipt of Approval for marketing of the first Approved Commercial Product for percutaneous applications of such Approved Commercial Product for closed fractures			**
G.4			$	**		Upon the First Commercial Sale of the first Approved Commercial Product as noted in G.2, above			**
G.5			$	**		Upon the one-year anniversary of the First Commercial Sale of the first Approved Commercial Product for use in procedures as noted in G.2, above			**
G.6			$	**		Upon the First Commercial Sale of the first Approved Commercial Product as noted in G.3, above			**
G.7			$	**		Upon the one-year anniversary of the First Commercial Sale of the first Approved Commercial Product, as noted in G.3, above			**

*BMTI makes no representations or warranties regarding the forecasted dates.  Failure to meet any of the dates shall not effect either party’s rights or obligations under this Agreement.

 

[**]  Redacted pursuant to confidential treatment request by BioMimetic Therapeutics, Inc.