COLLABORATION, RESEARCH AND LICENSE AGREEMENT

Collaboration Agreement

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WYETH PHARMACEUTICALS DIVISION | CURIS INCORPORATED

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Title: COLLABORATION, RESEARCH AND LICENSE AGREEMENT
Governing Law: New York Date: 3/1/2004
Industry: Biotechnology and Drugs

COLLABORATION, RESEARCH AND LICENSE AGREEMENT, Parties: wyeth pharmaceuticals division , curis incorporated

Exhibit 10.29

Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Asterisks denote omissions.

C OLLABORATION , R ESEARCH AND L ICENSE A GREEMENT

BY AND BETWEEN

W YETH

acting through its

W YETH P HARMACEUTICALS D IVISION

AND

C URIS I NCORPORATED

January 12, 2004

CONFIDENTIAL

TABLE OF CONTENTS


			Page
1.	DEFINITIONS.		1

	1.1	“ ACTIVATOR C OMPOUND ”	1
	1.2	“ AFFECTED P RODUCT ”	1
	1.3	“ AFFILIATE ”	1
	1.4	“ AGREEMENT ”	2
	1.5	“ AGREEMENT C OMPOUND ”	2
	1.6	“ AGREEMENT P RODUCT ”	2
	1.7	“ AGREEMENT P ROTEIN ”	2
	1.8	“ CLINICAL D EVELOPMENT C ANDIDATE ”	2
	1.9	“ COLLABORATION C OMPOUND ”	2
	1.10	“ COLLABORATION T ECHNOLOGY ”	2
	1.11	“ COMMERCIALLY R EASONABLE E FFORTS ”	3
	1.12	“ COMPETING P RODUCT ”	3
	1.13	“ COMPETING P RODUCT M ARKET ”	3
	1.14	“ COMPOUND ”	3
	1.15	“ CONFIDENTIAL I NFORMATION ”	3
	1.16	“ CONTRACT Y EAR ”	4
	1.17	“ CONTROLLED ”	4
	1.18	“ CURIS C OMPOUND ”	4
	1.19	“ CURIS D ATA ”	4
	1.20	“ CURIS F IELD ”	4
	1.21	“ CURIS M ATERIALS ”	5
	1.22	“ CURIS O PTION C OMPOUND ”	4
	1.23	“ CURIS P ATENT R IGHTS ”	4
	1.24	“ CURIS S TAFFING L EVEL ”	5
	1.25	“ CURIS T ECHNOLOGY ”	5
	1.26	“ CURIS T HIRD P ARTY A GREEMENTS ”	5
	1.27	“ DEFAULT ”	5
	1.28	“ DERIVED C OMPOUND ”	5
	1.29	“ DEVELOPMENT C ANDIDATE ”	5
	1.30	“ DEVELOPMENT C OMPOUND ”	6
	1.31	“ DEVELOPMENT T RACK ”	6
	1.32	“ EFFECTIVE D ATE ”	6
	1.33	“ EMEA	6
	1.34	“E UROPE ”	6
	1.35	“ EVALUATION T AIL ”	6
	1.36	“ EXECUTIVE B OARD ”	6
	1.37	“ FDA ”	6
	1.38	“ FIRST C OMMERCIAL S ALE ”	6
	1.39	“ FTE S CIENTIST ”	6
	1.40	“ HATCH -W AXMAN A CT ”	7
	1.41	“ HEDGEHOG P ATHWAY ”	7
	1.42	“ HIT C OMPOUND ”	7
	1.43	“ HSR A CT ”	7

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	1.44	“HSR C LEARANCE D ATE ”	7
	1.45	“HSR F ILING ”	7
	1.46	“IND”	8
	1.47	“ JOINT I NVENTIONS ”	8
	1.48	“ JOINT S TEERING C OMMITTEE ” OR “JSC”	8
	1.49	“ LEAD C OMPOUND ”	8
	1.50	“ LOCAL A DMINISTRATION ”	8
	1.51	“ MAJOR M ARKET C OUNTRY ”	9
	1.52	“ NET S ALES ”	9
	1.53	“ OPTION C OMPOUND ”	10
	1.54	“ OPTION P RODUCT ”	10
	1.55	“ ORPHAN C OMPOUND ”	10
	1.56	“ ORPHAN D EVELOPMENT C OMPOUND ”	10
	1.57	“ ORPHAN I NDICATION ”	11
	1.58	“ ORPHAN P RODUCT ”	11
	1.59	“ PATENT R IGHTS ”	11
	1.60	“ PATHWAY A CTIVATOR A CTIVITY ”	11
	1.61	“ PHASE II T RIAL ”	11
	1.62	“ PIVOTAL T RIAL ”	11
	1.63	“ PRODUCT ”	11
	1.64	“ PROGRAM I NVENTIONS ”	11
	1.65	“ REGULATORY A PPROVAL ”	12
	1.66	“ REGULATORY A PPROVAL A PPLICATION ”	12
	1.67	“ REGULATORY A UTHORITY ”	12
	1.68	“ RESEARCH F IELD ”	12
	1.69	“ RESEARCH M ATERIALS ”	12
	1.70	“ RESEARCH P LAN ”	13
	1.71	“ RESEARCH P ROGRAM ”	13
	1.72	“ RESEARCH P ROGRAM M ATERIALS ”	13
	1.73	“ RESEARCH T ERM ”	13
	1.74	“ REVERTED C OMPOUND ”	13
	1.75	“ ROYALTY T ERM ”	13
	1.76	“ STOCK P URCHASE A GREEMENT ”	13
	1.77	“ TECHNOLOGY ”	13
	1.78	“ TERRITORY ”	14
	1.79	“ THIRD P ARTY ”	14
	1.80	“ VALID P ATENT C LAIM ”	14
	1.81	“ WYETH C OMPOUND ”	14
	1.82	“ WYETH D ATA ”	14
	1.83	“ WYETH F IELD ”	14
	1.84	“ WYETH M ATERIALS ”	14
	1.85	“ WYETH O PTION ”	14
	1.86	“ WYETH T ECHNOLOGY ”	15

2.	LICENSES		15

	2.1	E XCLUSIVE L ICENSES TO W YETH .	15
	2.2	B ACKGROUND R IGHTS .	16
	2.3	L ICENSES TO C URIS .	16
	2.3.1 Research Program License.		16
	2.3.2 Curis Field License.		16
	2.4	C URIS R ETAINED R IGHTS .	16
	2.5	S UBLICENSES .	17

CONFIDENTIAL


	2.6	D IRECT L ICENSES TO A FFILIATES OF W YETH .	17
	2.7	W YETH O PTION .	18
	2.7.1 Option.		18
	2.7.2 Standstill.		18
	2.7.3 Notice.		18
	2.7.4 Exercise of Option; Negotiation of Agreement.		19
	2.7.5 Restrictions.		19
	2.8	C URIS O PTION .	20
	2.9	R IGHT OF R EFERENCE .	20
	2.10	P RESERVATION OF R IGHTS .	21

3.	RESEARCH PROGRAM.		21

	3.1	S COPE AND C ONDUCT OF THE R ESEARCH P ROGRAM .	21
	3.2	E XCLUSIVITY .	23
	3.3	C OLLABORATORS .	24
	3.4	F UNDING OF THE R ESEARCH P ROGRAM .	25
	3.4.1 Wyeth’s Funding Obligation.		25
	3.4.2 Reporting and Reconciliation.		25
	3.4.3 Records and Audits.		26
	3.5	R EPORTING AND D ISCLOSURE .	26
	3.5.1 Reports.		26
	3.5.2 Quarterly Meetings.		27
	3.5.3 Disclosure.		27
	3.6	D ATA .	27
	3.6.1 Storage/Archiving.		27
	3.6.2 Ownership.		27
	3.7	M ATERIALS .	28
	3.7.1 Research Program Materials.		28
	3.7.2 Curis Materials.		29
	3.7.3 Wyeth Materials.		29
	3.7.4 Use of Materials; Disclaimer.		30
	3.8	T ERM OF THE R ESEARCH P ROGRAM .	30
	3.9	E VALUATION T AIL .	30
	3.10	C OMPOUNDS .	31
	3.10.1 Contribution of Curis Compounds.		31
	3.10.2 Wyeth’s Right to Select Compounds.		31
	3.10.3 Reversion of Compounds.		31
	3.11	C OMPOUND I NVENTORY .	31

4.	MANAGEMENT OF THE RESEARCH PROGRAM.		32

	4.1	J OINT S TEERING C OMMITTEE .	32
	4.2	F UNCTION OF J OINT S TEERING C OMMITTEE .	32
	4.3	M EETINGS OF THE JSC.	33
	4.4	D ECISIONS OF THE J OINT S TEERING C OMMITTEE .	34
	4.5	E XECUTIVE B OARD .	34
	4.6	P ROJECT L EADERS .	34
	4.7	A VAILABILITY OF E MPLOYEES .	34
	4.8	V ISIT TO F ACILITIES .	35

5.	DEVELOPMENT AND MARKETING.		35

	5.1	D EVELOPMENT OF A GREEMENT C OMPOUNDS .	35
	5.2	D EVELOPMENT OF O PTION C OMPOUNDS .	35

iii

CONFIDENTIAL


	5.3	W YETH P ERFORMANCE .	35
	5.4	R EPORTS .	36
	5.5	R EGULATORY S UBMISSIONS .	36
	5.6	M ANUFACTURING .	36
	5.7	R EGULATORY R EPORTING .	37

6.	CONSIDERATION.		37

	6.1	I NITIAL P AYMENT .	37
	6.2	C URIS S TOCK .	37
	6.3	D EVELOPMENT P AYMENTS .	38
	6.4	A DDITIONAL D EVELOPMENT P AYMENTS .	38
	6.5	A PPROVAL P AYMENTS .	39
	6.6	R OYALTIES .	39
	6.6.1 Products.		39
	6.6.2 Certain Option Products.		40
	6.7	A DJUSTMENTS TO R OYALTIES .	40
	6.7.1 Wyeth’s Third Party Agreements.		40
	6.7.2 Curis Third Party Agreements.		41
	6.7.3 Competing Products.		41
	6.8	N O P ROJECTIONS .	41
	6.9	R OYALTY R EPORTS ; P AYMENTS .	42
	6.10	W ITHHOLDING T AXES .	42
	6.11	B OOKS AND R ECORDS ; A UDIT R IGHTS .	43

7.	INTELLECTUAL PROPERTY.		44

	7.1	I NVENTIONS .	44
	7.2	P ATENT A PPLICATIONS .	45
	7.2.1 Filing, Prosecution and Maintenance of Patent Rights.		45
	7.2.2 Patent Costs.		48
	7.2.3 Cooperation.		49
	7.3	P ATENT T ERM E XTENSIONS .	49
	7.4	P ATENT C ERTIFICATIONS .	50
	7.4.1 Notice; Actions.		50
	7.4.2 Orange Book Listings.		50
	7.5	E NFORCEMENT OF P ATENT R IGHTS .	50
	7.5.1 Notice.		50
	7.5.2 Course of Action.		51
	7.5.3 Cooperation.		51
	7.5.4 Settlements; Recoveries.		51
	7.6	C OOPERATION .	52
	7.7	R EVOCATION OR I NVALIDITY A CTIONS .	52
	7.8	P ATENT I NFRINGEMENT C LAIMS .	52

8.	CONFIDENTIALITY.		53

	8.1	C ONFIDENTIALITY .	53
	8.2	A UTHORIZED D ISCLOSURE AND U SE .	54
	8.2.1 Disclosure.		54
	8.2.2 Use.		55
	8.3	C ERTAIN R EGULATORY F ILINGS .	55
	8.4	P UBLIC A NNOUNCEMENTS ; P UBLICATIONS .	55
	8.4.1 Announcements.		55
	8.4.2 Initial Press Release.		56

CONFIDENTIAL


	8.5	S CIENTIFIC P UBLICATIONS .	56

9.	REPRESENTATIONS AND WARRANTIES.		56

	9.1	R EPRESENTATIONS AND W ARRANTIES OF E ACH P ARTY .	56
	9.2	A DDITIONAL R EPRESENTATIONS AND W ARRANTIES OF C URIS .	57
	9.3	R EPRESENTATION BY L EGAL C OUNSEL .	58
	9.4	N O I NCONSISTENT A GREEMENTS .	59
	9.5	D ISCLAIMER .	59

10.	GOVERNMENT APPROVALS; TERM; TERMINATION.		59

	10.1	G OVERNMENT A PPROVALS .	59
	10.1.1 HSR Filing.		59
	10.1.2 Other Government Approvals.		59
	10.1.3 Cooperation.		59
	10.2	E XPIRATION .	60
	10.3	T ERMINATION U PON HSR D ENIAL .	60
	10.4	B LOCKING P ATENTS .	60
	10.5	T ERMINATION OF R ESEARCH P ROGRAM U PON AN A CQUISITION .	61
	10.6	T ERMINATION BY W YETH W ITHOUT C AUSE .	62
	10.7	T ERMINATION BY W YETH FOR S AFETY R EASONS .	62
	10.8	D EFAULT .	62
	10.8.1 Notice of Default and Cure Period.		62
	10.8.2 Right to Terminate.		62
	10.8.3 Notice of Termination.		63
	10.9	E FFECTS OF T ERMINATION .	63
	10.9.1 Termination of Research Program.		63
	10.9.2 Termination by Wyeth Under Section 10.6.		64
	10.9.3 Termination by Wyeth under Section 10.7.		64
	10.9.4 Termination by Curis under Section 10.8.2(a).		65
	10.9.5 Termination by Curis under Section 10.8.2(b).		66
	10.9.6 Termination by Wyeth under Section 10.8.2(c).		66
	10.10	B ANKRUPTCY .	66
	10.11	A CCRUED R IGHTS ; S URVIVAL .	67
	10.12	L IABILITIES .	68

11.	INDEMNITY; INSURANCE.		68

	11.1	I NDEMNIFICATION BY W YETH .	68
	11.2	I NDEMNIFICATION BY C URIS .	68
	11.3	P ROCEDURE .	69
	11.4	I NSURANCE .	69

12.	MISCELLANEOUS.		70

	12.1	A SSIGNMENT .	70
	12.2	F ORCE M AJEURE .	70
	12.3	N OTICES .	71
	12.4	A PPLICABLE L AW .	72
	12.5	D ISPUTE R ESOLUTION .	72
	12.5.1 Executive Mediation.		72
	12.5.2 Remedies.		72
	12.5.3 Jurisdiction.		73
	12.5.4 Provisional Remedies.		73
	12.6	N O C ONSEQUENTIAL D AMAGES .	73

CONFIDENTIAL


12.7	E NTIRE A GREEMENT .	73
12.8	H EADINGS .	73
12.9	S EVERABILITY .	73
12.10	I NDEPENDENT C ONTRACTORS .	74
12.11	W AIVER .	74
12.12	I NTERPRETATION .	74
12.13	P ERFORMANCE BY A FFILIATES .	74
12.14	C OUNTERPARTS .	75


Exhibit 1.23				Curis Patent Rights
Exhibit 1.26				Curis Third Party Agreements
Exhibit 9.2				Exceptions to Representations and Warranties

CONFIDENTIAL

COLLABORATION, RESEARCH AND LICENSE AGREEMENT

THIS AGREEMENT, dated as of January 12, 2004 (the “Signature Date”) , between Wyeth , a Delaware corporation, acting through its Wyeth Pharmaceuticals Division, with a place of business at 500 Arcola Road, Collegeville, Pennsylvania 19426 (“Wyeth”), and Curis Incorporated, a Delaware corporation having its principal offices at 61 Moulton Street, Cambridge, Massachusetts 02138. Wyeth and Curis may each be referred to herein individually as a “Party” and collectively as the “Parties”.

W I T N E S S E T H:

WHEREAS, Curis possesses scientific and proprietary technology and data and resources relating to the Hedgehog Pathway (as defined below); and

WHEREAS, Wyeth possesses scientific and technical resources relating to the development and commercialization of pharmaceutical products for the treatment of neurodegenerative and other diseases, and desires to obtain a license to Curis’ proprietary technology to further develop and commercialize pharmaceutical products for the treatment of, among other diseases, neurodegenerative diseases and neuropathies;

NOW, THEREFORE, in consideration of the premises and of the mutual covenants herein contained, the Parties hereto mutually agree as follows:

1.	DEFINITIONS.

1.1

“Activator Compound” shall mean a Compound whose biological activity is achieved in whole or in material part through activation of the Hedgehog Pathway.

1.2

“Affected Product” shall mean with respect to a country in the Territory, an Agreement Product sold in such country by Wyeth, its Affiliates or sublicensees.

1.3

“Affiliate” shall mean any corporation, partnership or other entity that controls, is controlled by, or is under common control with, the Party, person or entity specified. A corporation or other entity shall be regarded as in control of another corporation or entity if it owns, directly or indirectly, at least fifty percent (50%) of the voting or equity rights of the other corporation or entity authorized to cast votes in any election of directors or, in the case of a non-corporate entity, with the power to direct the management and policies of such non-corporate entity. Notwithstanding the foregoing, the term “Affiliate” shall not include subsidiaries in which a Party or its Affiliates owns a majority of the ordinary voting power to elect a majority of the board of directors or other governing body, but is restricted from electing such majority by contract or otherwise, until such time as such restrictions are no longer in effect.

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1.4

“Agreement” shall mean this document, together with all Exhibits hereto.

1.5

“Agreement Compound” shall mean a Curis Compound, Wyeth Compound or Collaboration Compound which has progressed to the level of Lead Compound or beyond. For the sake of clarity, “Agreement Compound” shall not include any Reverted Compound. Notwithstanding the foregoing, any Wyeth Compound that is in Wyeth’s Development Track and, subsequent to entering Wyeth’s Development Track is determined to be an Activator Compound through the use of the Curis Technology hereunder shall nevertheless not be considered to be an Agreement Compound hereunder unless, (i) based on such determination that such Wyeth Compound is also an Activator Compound, Wyeth elects to develop such Compound for therapeutic indications not then included in Wyeth’s development plan for such Wyeth Compound wherein such Wyeth Compound would exert its therapeutic effect for such additional therapeutic indications via activation of the Hedgehog Pathway; or (ii) manufacture, use or sale of such Compound would otherwise require a license under the Curis Patents.

1.6

“Agreement Product” shall mean any Product or Option Product.

1.7

“Agreement Protein” shall mean the Hedgehog protein (as described in [**], included in the [**] which have [**]”Clinical Development Candidate” shall mean a Development Candidate that, according to Wyeth’s then current normal and customary selection criteria for entry into Development Track, is designated by Wyeth or nominated by the JSC and approved by Wyeth as a candidate for further development toward IND filing, which further development may include, without limitation GMP synthesis, pre-IND toxicology studies and pre-IND formulation studies.

1.9

“Collaboration Compound” shall mean any Compound that (i) is not a Wyeth Compound or a Curis Compound and (ii) is screened or first synthesized by either Wyeth or Curis, or by Wyeth and Curis jointly, in the conduct of the Research Program.

1.10

“Collaboration Technology” shall mean that subset of Curis Technology and Wyeth Technology conceived or reduced to practice in the conduct of the Research Program.

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1.11

“Commercially Reasonable Efforts” shall mean, with respect to the efforts to be expended by a Party with respect to any objective, reasonable, diligent, good faith efforts to accomplish such objective as such Party would normally use to accomplish a similar objective under similar circumstances, it being understood and agreed that with respect to the research, development or commercialization of any Agreement Compound or Agreement Product, such efforts shall be substantially equivalent to those efforts and resources commonly used by a Party for a compound or product owned by it or to which it has rights, which compound or product is at a similar stage in its development or product life and is of similar market potential taking into account cost of development, regulatory risk, efficacy, safety, reimbursement factors, pricing, cost of sales and marketing, product life cycle, parallel importation considerations, Regulatory Authority-approved labeling, the competitiveness of alternative products in the marketplace or reasonably anticipated to enter the marketplace, the patent and other proprietary position of the Agreement Compound or Agreement Product, the likelihood of regulatory approval given the regulatory structure involved, the actual or anticipated profitability of the Agreement Compound or Agreement Product taking into account the royalties payable to licensors of patent or other intellectual property rights, alternative products and other relevant commercial factors. Commercially Reasonable Efforts shall be determined on a market-by-market basis for a particular Agreement Compound or Agreement Product, and it is anticipated that the level of effort will change over time (including, to the extent appropriate, the reduction or cessation of active promotional efforts), reflecting changes in the status of the Agreement Compound or Agreement Product and the market(s) involved.

1.12

“Competing Product” shall mean a product (other than a Product sold by a sublicensee of Wyeth) sold under a Regulatory Approval in a country of the Territory by a Third Party that contains as its principal active ingredient the same Activator Compound as is in the Affected Product in such country.

1.13

“Competing Product Market” shall mean, with respect to a country in the Territory, the sum of (i) the units sold of Competing Products in such country and (ii) the units sold of the Affected Product in such country

1.14

“Compound” shall mean a [**] compound (including, without limitation, [**].

1.15

“Confidential Information” shall mean, with respect to a Party, all non-public proprietary data or information Controlled by such Party, including laboratory notebooks, progress reports hereunder and unpublished patent applications, that are disclosed to the other Party in connection with this Agreement or information designated as “Confidential Information” of such Party hereunder, subject, in either case, to the exceptions set forth in Section 8.2.

CONFIDENTIAL

1.16

“Contract Year” shall mean each successive one (1) year period during the Research Term wherein the first such one (1) year period begins on the Effective Date.

1.17

“Controlled” shall mean possession of the ability to grant the other Party access, a license or sublicense (as applicable) as provided for herein without violating the terms of any agreement or other arrangement with any Third Party existing at the time such Party would be first required hereunder to grant the other Party such access, license or sublicense.

1.18

“Curis Compound” shall mean (i) a Compound from a compound library Controlled by Curis or one of its Affiliates as of the Effective Date, which Compound is contributed by Curis hereunder as part of the Research Program in accordance with the terms set forth in Section 3.10.1, (ii) a Compound [**] of the Research Program at any time during the Research Term, which Compound is contributed by Curis hereunder as part of the Research Program in accordance with the terms set forth in Section 3.10.1, or (iii) a Compound [**]. For purposes of this definition, [**] such Compound [**]

1.19

“Curis Data” shall have the meaning set forth in Section 3.6.2 hereof.

1.20

“Curis Field” shall mean [**] Compounds [**] Compounds [**], including but not limited to the [**] Compound [**]

1.21

“Curis Materials” shall mean proprietary Research Materials (other than Research Program Materials) Controlled by Curis as of the Effective Date or coming into Curis’ Control during the Research Term, which Research Materials are used by Curis in the conduct of the Research Program or are provided by Curis to Wyeth for use in the Research Program or in connection with the development by Wyeth of Agreement Compounds or Agreement Products under this Agreement. Curis will own those Curis Materials supplied by Curis to Wyeth hereunder.

1.22

“Curis Option Compound” shall mean a Collaboration Compound (i) which is also an Activator Compound and (ii) for which Curis has exercised the option granted to it under Section 2.8 hereof.

1.23

“Curis Patent Rights” shall mean those Patent Rights (other than Joint Patent Rights) Controlled by Curis as of the Effective Date or coming into the Control of Curis or its Affiliates during the term of this Agreement, which Patent Rights are

CONFIDENTIAL

necessary for the discovery, research, development or commercialization of any Hit Compound, Activator Compound, Agreement Compound, or Agreement Product. All patent applications and patents known to be existing as of the Signature Date and included within the Curis Patent Rights are identified in Exhibit 1.23 attached hereto

1.24

“Curis Staffing Level” shall mean that number of Curis FTE Scientists assigned to work on the Research Program in accordance with Section 3.1(d) hereof, for which Wyeth is obligated to reimburse Curis in accordance with Section 3.4 hereof.

1.25

“Curis Technology” shall mean all Technology Controlled by Curis on the Effective Date or during the term of this Agreement, including Curis Compounds and Curis’ rights in Joint Inventions, that claims or describes, or is necessary for the discovery, characterization, design, development or commercialization of Activator Compounds, Hit Compounds, Agreement Compounds and/or Agreement Products.

1.26

“Curis Third Party Agreements” shall mean those Agreements identified on Exhibit 1.26 attached hereto, which agreements are between Curis or any of its Affiliates and the indicated Third Parties, that relate to the Curis Technology, to any Agreement Compound, to the Hedgehog Pathway or to the Agreement Protein.

1.27

“Default” shall mean a breach of a Party’s obligations, representations or warranties under this Agreement, which breach is of such magnitude that, unless it is cured, it materially and significantly frustrates the benefit of the bargain and the principal purposes reasonably sought to be achieved by the other Party in entering into this Agreement or precludes such Party from performing its material obligations under the terms and conditions of this Agreement.

1.28

“Derived Compound” shall mean a Compound [**] that (i) [**] in the [**] Compound, and (ii) was [**] Compound [**] at least [**] at least [**] In view of the iterative nature of deriving Compounds, for the avoidance of doubt, a “Derived Compound” shall include any [**] Derived Compound [**].

1.29

“Development Candidate” shall mean a Lead Compound that, according to the criteria established by the JSC, is sufficiently active and specific to warrant further exploration as a potential Clinical Development Candidate (lead/series optimization; identification of a backup; pharmacology, acute tox, etc.).

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1.30

“Development Compound” shall mean a Clinical Development Candidate for which Wyeth has filed an IND with a Regulatory Authority in a Major Market Country seeking approval to initiate clinical trials in humans.

1.31

“Development Track” shall mean the research and development program for a Compound initiated upon designation by Wyeth’s Discovery Board (or any successor or substitute entity) in its sole discretion, of such Compound for advancement to pre-development stage (“Phase 0” or any successor or substitute designation) pursuant to Wyeth’s internal criteria and procedures.

1.32

“Effective Date” shall mean the later of (a) the date first set forth above as the Signature Date, (b) the date on which a determination is made by Wyeth that a notification of this Agreement is not required to be made under the HSR Act or (c) if Wyeth determines that a notification of this Agreement is required to be made under the HSR Act, the HSR Clearance Date.

1.33

“EMEA shall mean the European Medicines Evaluation Agency or any successor agency thereof.

1.34

“Europe” shall mean the member countries of the European Union and the member countries of the European Economic Area.

1.35

“Evaluation Tail” shall mean the one (1) year period following the expiration of the Research Term.

1.36

“Executive Board” shall mean a committee comprised of Wyeth’s Senior Vice President for Discovery Research and Curis’ Chief Scientific Officer, or their respective designees, which committee would be responsible for (i) approving the Annual Budget or any modifications thereto and (ii) approving the Staffing Level or any modifications thereto.

1.37

“FDA” shall mean the Food and Drug Administration of the United States Department of Health and Human Services or any successor agency thereof.

1.38

“First Commercial Sale” shall mean, with respect to any Agreement Product, the first sale by Wyeth, its Affiliates or sublicensees (other than Curis) to a Third Party of such Agreement Product in a country after all required marketing and pricing or reimbursement approvals have been granted by the applicable Regulatory Authority for such country.

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1.39

“FTE Scientist” shall mean a full time equivalent scientific person year, consisting of a total of [**] ([**]) hours per year of scientific work on or directly related to the Research Program. Such output must come from a scientific person holding a Bachelor of Science or graduate-level scientific degree (or such other person who regularly performs duties for a Party similar to those performed by persons holding such degrees) whose work is dedicated entirely to the Research Program. Scientific work on or directly related to the Research Program can include, but is not limited to, experimental laboratory work, recording and writing up results, reviewing literature and references, holding scientific discussions, managing and leading scientific staff, carrying out management duties related to the Research Program, writing up results for publications or presentation and attending or presenting appropriate education programs, seminars and symposia.

1.40

“Hatch-Waxman Act” shall mean the United States Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. Law 98-471), and the rules and regulations promulgated thereunder (or any successor thereto) and any equivalent legal requirements in other countries, as in effect from time to time during the term of this Agreement.

1.41

“Hedgehog Pathway” shall mean the [**] Hedgehog[**] as evidenced by the [**]

1.42

“Hit Compound” shall mean any Activator Compound that is demonstrated by initial screening (x) in the Research Program or (y) by Curis (with respect to Compounds Controlled by Curis) prior to the Effective Date, to have Pathway Activator Activity at a minimum level specified by the JSC.

1.43

“HSR Act” shall mean the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, and the rules and regulations promulgated thereunder.

1.44

“HSR Clearance Date” shall mean the earliest date on which the Parties have actual knowledge that all applicable waiting periods under the HSR Act with respect to the transactions contemplated hereunder have expired or have been terminated.

1.45

“HSR Filing” shall mean filings by Wyeth and Curis with the United States Federal Trade Commission and the Antitrust Division of the United States Department of Justice of a Notification and Report Form for Certain Mergers and Acquisitions (as that term is defined in the HSR Act) with respect to the matters set forth in this Agreement, together with all required documentary attachments thereto.

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1.46

“IND” shall mean an Investigational New Drug Application covering a Product filed with the FDA pursuant to 21 CFR 312.20 or an equivalent filing in any other Major Market Country required for the clinical testing in humans of a pharmaceutical product.

1.47

“Joint Inventions” shall mean all Program Inventions for which it is determined, in accordance with United States patent law, that both: (i) one or more employees, consultants or agents of Curis or any other persons obliged to assign such Program Invention to Curis; and (ii) one or more employees, consultants or agents of Wyeth or any other persons obliged to assign such Program Invention to Wyeth, are joint inventors of such Program Invention.

1.48

“Joint Steering Committee” or “JSC” shall mean a committee comprised of up to four (4) representatives of each of Curis and Wyeth (or such lesser number as the JSC may determine) responsible for the supervision and coordination of the Research Program as set forth in Article 3 below.

1.49

“Lead Compound” shall mean (i) a Curis Compound, a Wyeth Compound or a Collaboration Compound that is identified during the conduct of the Research Program as being an Activator Compound, that is identified by Curis (with respect to Compounds Controlled by Curis) prior to the Effective Date as having Pathway Activator Activity at or above a minimum level specified by the JSC, or that is identified by or for Wyeth during the Evaluation Tail as having Pathway Activator Activity at or above a minimum level specified by the JSC; and (ii) any Derived Compound of the foregoing or any Derived Compound of a Hit Compound that is identified by or for either Party after the Research Term as being an Activator Compound. Notwithstanding the foregoing, (A) any Wyeth Compound for which development efforts are conducted by Wyeth after the Research Term without the use of any Curis Technology and (B) any Curis Compound that was not designated as a Lead Compound prior to the end of the Evaluation Tail and where development efforts are conducted by Curis after the Research Term, which Wyeth Compound or Curis Compound is developed or commercialized solely for the treatment or prevention of diseases in humans whose therapeutic, prophylactic or other beneficial effects are not mediated, in whole or in material part, through activation of the Hedgehog Pathway, shall not be deemed a Lead Compound, even if such Compound tested positive as a Activator Compound during the Research Term.

1.50

“Local Administration” shall mean the administration of a Compound at or near the target site desired to be affected by the Compound ( e.g., within the lumen of a vessel where it is desired to prevent restenosis after implantation of a cardiovascular stent coated with the Compound) in order to achieve a high local

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concentration (as opposed to a diffused systemic concentration) of such Compound at or near such target site. For the sake of clarity “Local Administration” shall not include any administration of a Compound at a site distally located to the target site, including, without limitation, oral administration or administration via intravenous catheter or other parenteral methods.

1.51

“Major Market Country” shall mean [**].

1.52

“Net Sales” with respect to any Agreement Product shall mean the gross amount invoiced by Wyeth, its Affiliates, licensees or sublicensees (including any co-marketing partners), to unrelated third persons less, to the extent included in the gross invoice amount, the reasonable and customary deductions for: (i) trade, quantity and cash discounts and allowances actually allowed or given; (ii) freight, shipping insurance and other transportation expenses incurred in transporting such Agreement Product in final form to such customers; (iii) credits or refunds actually allowed for rejections, defects or recalls of such Agreement Products, outdated or returned Agreement Products, or retroactive price reductions; (iv) sales, value-added, excise taxes, tariffs and duties, and other taxes directly related to the sale (but not including taxes assessed against the income derived from such sale); (v) chargebacks granted to wholesalers; (vi) rebates, including managed care, Medicaid and other governmental rebates, in respect of the sales of the Agreement Products; and (vii) management fees paid during the relevant time period to group purchasing organizations and relating specifically to the sale of the Agreement Product to its members. All such discounts, allowances, credits, rebates and other deductions shall be fairly and equitably allocated to the Agreement Products and other products or services of Wyeth, its Affiliates, licensees or sublicensees such that the Agreement Products do not bear a disproportionate portion of such deductions. The transfer of Agreement Products by Wyeth or one of its Affiliates to either (i) another Affiliate of Wyeth or (ii) a licensee or sublicensee of Wyeth, shall not be considered a sale; in such cases, Net Sales shall be determined based on the invoiced sales price by the Affiliate, licensee or sublicensee to an unrelated third person, less the deductions allowed under this Section 1.52. Every other commercial use or disposition of a Agreement Product by Wyeth or its Affiliates, licensees or sublicensees in barter or other transactions (other than dispensing of reasonable and customary quantities of promotional samples) shall be considered a sale of such Agreement Product at the weighted average Net Sales price for such Agreement Product during the preceding quarter.

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With respect to a Agreement Product that contains one or more Agreement Compounds combined as a single pharmaceutical product with one or more other therapeutically active ingredients (other than any drug delivery vehicles, adjuvants, or excipients)(a “Combination Product” ), the Net Sales of such Combination Product shall first be calculated in accordance with the definition of Net Sales set forth above, and then the Net Sales of such Combination Product shall be determined on a country-by-country basis as follows:

(i)

multiply the Net Sales of such Combination Product by the fraction A/(A+B), where A is the total of the average selling prices of such Agreement Compound(s) when sold separately as a pharmaceutical product in such country and B is the total of the average selling prices of each other active ingredient when sold alone as a pharmaceutical product in such country; or

(ii)

if either the average selling price of all Agreement Products containing as their sole active ingredient an Agreement Compound in such Combination Product or the average selling price of all other active ingredients in such Combination Product is not available, multiply the Net Sales of such Combination Product by a percentage, determined by mutual agreement of the Parties, which represents the proportionate economic value contributed by the Agreement Compound(s) in such Combination Product.

Notwithstanding the foregoing, Net Sales shall not include any consideration received by Wyeth, its Affiliates, licensees or sublicensees in respect of the sale, use or other disposition of a Agreement Product in a country as part of a clinical trial prior to the receipt of all marketing and pricing or reimbursement approvals by Regulatory Authorities in such country required to commence full commercial sales of such Agreement Product in such country.

Additionally, for the sake of clarity, sales of a Agreement Product in any country of the Territory after the expiration of the Royalty Term for such Agreement Product in such country shall not be included in the calculation of Net Sales for such Agreement Product.

1.53

“Option Compound” shall have the meaning set forth in Section 2.7.1 hereof.

1.54

“Option Product” shall mean any product for commercial sale containing an Option Compound.

1.55

“Orphan Compound” shall mean a Reverted Compound or Curis Option Compound being developed by Curis for use in an Orphan Indication.

1.56

“Orphan Development Compound” shall mean an Orphan Compound for which Wyeth has exercised the Wyeth Option.

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1.57

“Orphan Indication” shall mean a therapeutic indication wherein a Compound being developed for the treatment thereof would qualify for designation as an Orphan Drug according to the criteria specified by the U.S. FDA and as set forth in the U.S. Orphan Drug Act (21 USC 360aa, et seq .).

1.58

“Orphan Product” shall mean a product for commercial sale containing an Orphan Development Compound.

1.59

“Patent Rights” shall mean all rights and interests in and to all issued patents and pending patent applications in any country, including all provisional applications, substitutions, continuations, continuations-in-part, divisions, and renewals, all letters patent granted thereon, and all patents-of-addition, reissues, reexaminations and extensions or restorations by existing or future extension or restoration mechanisms, including Supplementary Protection Certificates or the equivalent thereof.

1.60

“Pathway Activator Activity” shall mean the activation of the Hedgehog Pathway as evidenced by [**].

1.61

“Phase II Trial” shall mean a study of an Agreement Compound in human patients to determine initial efficacy or dose range finding before initiating a Pivotal Trial, which study is initiated after the completion of all phase I clinical trials of such Agreement Compound.

1.62

“Pivotal Trial” shall mean a phase III clinical trial which, if the pre-defined endpoints are met, is intended to be submitted as the primary part of a Regulatory Approval Application as statistically significant data in support of a Product’s safety and efficacy for the intended indication.

1.63

“Product” shall mean any final dosage form of a pharmaceutical product containing a Development Compound, independent of indication, route of administration, or dosage strength or form.

1.64

“Program Inventions” shall mean all inventions, discoveries and improvements (whether or not patentable), necessary or useful to discover, develop, make, use, or sell pharmaceutical products for clinical use in the Wyeth Field or Curis Field, including Derived Compounds, Collaboration Compounds, and inventions, discoveries and improvements relating to the Hedgehog Pathway or the discovery or use of Activator Compounds, that, in all cases, are conceived or first reduced to practice in the conduct of the Research Program by one or more individuals who are employees, agents, consultants or subcontractors of one of the Parties and who is working on the Research Program at the time of their inventive contribution.

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1.65

“Regulatory Approval” shall mean shall mean the technical, medical and scientific licenses, registrations, authorizations and approvals (including, without limitation, approvals of Regulatory Approval Applications, supplements and amendments, pre- and post- approvals, pricing and third party reimbursement approvals, and labeling approvals) of any national, supra-national, regional, state or local regulatory agency, department, bureau, commission, council or other governmental entity, necessary for the commercial manufacture, distribution, marketing, promotion, offer for sale, use, import, export or sale of Agreement Products in a regulatory jurisdiction. For the sake of clarity, Regulatory Approval shall not be deemed to have been obtained for an Agreement Product in a country until all applicable pricing and reimbursement approvals have also been obtained for such Agreement Product in such country.

1.66

“Regulatory Approval Application” shall mean an application submitted to the appropriate Regulatory Authority seeking Regulatory Approval of an Agreement Product for use in one or more indications in a regulatory jurisdiction within the Territory.

1.67

“Regulatory Authority” shall mean any national ( e.g., the FDA), supra-national ( e.g., the European Commission, the Council of the European Union, or the European Agency for the Evaluation of Medicinal Products), regional, state or local regulatory agency, department, bureau, commission, council or other governmental entity in each country of the Territory involved in the granting of Regulatory Approval for a Product or whose approval is required for the conduct of clinical trials of an Agreement Compound in such country(ies).

1.68

“Research Field” shall mean the discovery, characterization, design, development and commercialization of Compounds for the treatment or prevention of neurodegenerative diseases or conditions and/or neuropathies wherein such Compounds exert such therapeutic, prophylactic or other beneficial effects are achieved, in whole or in material part, through Pathway Activator Activity.

1.69

“Research Materials” shall mean all knockout and transgenic mice and other animal models, cell lines, tissue samples, cDNA, genes, plasmids, constructs, vectors, receptors and other proteins, crystals, and other biological and chemical materials that are necessary or may be useful as research tools to conduct the Research Program (other than any Compounds).

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1.70

“Research Plan” shall mean the plan agreed to by the Parties for the collaborative conduct of a research and development program to discover and develop Activator Compounds in the Research Field, as amended from time to time as agreed by the JSC.

1.71

“Research Program” shall mean the synthesizing of Compounds, screening, testing, evaluation, optimization, and other activities to be conducted by or on behalf of the Parties during the Research Term, in accordance with the Research Plan.

1.72

“Research Program Materials” shall mean Research Materials developed by Curis and/or Wyeth in the course of conduct of the Research Program. Research Program Materials also will include the Agreement Protein and clones, cell lines and other materials encompassing, expressing, and/or containing the Agreement Protein or any component of the Hedgehog Pathway.

1.73

“Research Term” shall mean the period of time inclusive of the Initial Term and, to the extent applicable if entered into in accordance with Section 3.8, the First Extension and each Additional Extension.

1.74

“Reverted Compound” shall mean a Compound that reverts to Curis in accordance with Section 3.10.3 hereof.

1.75

“Royalty Term” shall mean, with respect to each Agreement Product in each country in the Territory, the period of time ending on the later of: (i) ten (10) years from the date of the First Commercial Sale of such Agreement Product in such country; and (ii) the latest date on which the manufacture, use or sale of such Agreement Product in such country is covered by a Valid Patent Claim.

1.76

“Stock Purchase Agreement” shall mean that certain common stock purchase and registration rights agreement entered into by and between Wyeth and Curis on even date herewith.

1.77

“Technology” shall mean Patent Rights, Research Materials, Compounds, proprietary data, information and all intellectual property, including trade secrets, know-how, electronic and physical databases of chemical structures and Compounds, practices, knowledge, skill, experience, test data, and marketing, sales and manufacturing data, inventions and technology, whether patentable or not, pertaining to the Hedgehog Pathway and/or activation thereof.

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1.78

“Territory” shall mean the entire world.

1.79

“Third Party” shall mean any entity other than Curis or Wyeth and their respective Affiliates.

1.80

“Valid Patent Claim” shall mean any of: (a) a claim of an issued and unexpired patent included with the Curis Technology, which claim has not lapsed, been canceled or become abandoned and has not been declared invalid by a decision or judgment of a court or other appropriate body of competent jurisdiction, and which has not been admitted to be invalid or unenforceable through reissue or disclaimer, or (b) a claim of a pending application included with the Curis Technology for a patent to the extent the invention described in such claim has not been abandoned without being refiled in another application or finally rejected by an administrative agency action from which no appeal can be taken, or shall not have been pending for more than seven (7) years. For purposes of this definition, time periods shall be measured cumulatively for claims in a later filed application in a country which are substantially the same as claims in an earlier filed application in that country (other than a provisional patent application). If a claim of a patent application that ceased to be a Valid Patent Claim under clause (b) above due to the passage of time later issues as part of a patent described within clause (a) above then it shall again be considered to be a Valid Patent Claim effective as of the issuance of such patent.

1.81

“Wyeth Compound” shall mean (i) a Compound [**] Wyeth as of the Effective Date, which Compound is contributed by Wyeth hereunder as part of the Research Program[**] (ii) a Compound [**] Wyeth [**] Wyeth [**] Wyeth hereunder as part of the Research Program, or (iii) a Compound [**] Wyeth in accordance with [**]. For purposes of this definition, [**].

1.82

“Wyeth Data” shall have the meaning set forth in Section 3.6.2 hereof.

1.83

“Wyeth Field” shall mean the treatment or prevention of diseases and/or disorders in humans.

1.84

“Wyeth Materials” shall mean proprietary Research Materials (other than Research Program Materials) Controlled by Wyeth as of the Effective Date or coming into Wyeth’s Control during the Research Term, which Research Materials are used by Wyeth in the conduct of the Research Program or are provided by Wyeth to Curis for use in the Research Program. Wyeth will own those Wyeth Materials supplied by Wyeth to Curis hereunder.

1.85

“Wyeth Option” shall mean the right of first negotiation granted to and exercisable by Wyeth under Section 2.7 hereof.

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1.86

“Wyeth Technology” shall mean all Technology Controlled by Wyeth, including Wyeth Compounds and Wyeth’s rights in Joint Inventions, on the Effective Date or during the term of this Agreement that relates specifically to, claims or describes, or is necessary for the discovery, characterization, design, development or commercialization of Hit Compounds, Agreement Compounds, Agreement Products, and/or the Agreement Protein.

2.	LICENSES

2.1

Exclusive Licenses to Wyeth. Curis hereby grants to Wyeth:

(a)

during the Research Term, the exclusive worldwide right and license to use the Curis Technology to the extent necessary to conduct the Research Program;

(b)

during the Evaluation Tail, the exclusive worldwide right and license to use the Curis Technology to the extent necessary to determine whether any of the then identified Hit Compounds or Activator Compounds can become Lead Compounds and to further screen and conduct selectivity testing of any Lead Compounds identified in the Research Term for the purpose of determining whether Wyeth will select any such Lead Compounds as Development Candidates;

(c)

the exclusive royalty-bearing right and license to use the Curis Technology to develop and have developed Agreement Compounds and Products and to make, have made, use, import, export, market, offer for sale, sell and have sold Products in the Territory for use in the Wyeth Field; and

(d)

if Wyeth exercises the Wyeth Option with respect to any Option Compound, the exclusive royalty-bearing right and license to use the Curis Technology to develop and have developed such Option Compound and any Option Product containing such Option Compound and to make, have made, use, import, export, market, offer for sale, sell and have sold such Option Products in the Territory for use in the Wyeth Field.

The licenses granted under paragraphs (c) and (d) of this Section 2.1 shall continue on an Agreement Product-by-Agreement Product and country-by-country basis for the duration of the applicable Royalty Term. Upon expiration of each Royalty Term in each country for each Agreement Product, the license granted to Wyeth under Section 2.1(c) or Section 2.1(d), as applicable, for such Agreement Product in such country shall thereafter be a fully paid-up, perpetual, irrevocable, royalty-free license.

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2.2

Background Rights. If the development, manufacture, use, importation, exportation or sale by Wyeth, its Affiliates or sublicensees of any Agreement Compound or Agreement Product within the scope of the licenses granted under this Article 2 would infringe during the term of this Agreement any rights under Curis Technology or other Technology Controlled by Curis (“Background Rights”) and which Background Rights are not covered by the applicable grant in this Article 2, Curis agrees that it will not assert such Background Rights against Wyeth, its sublicensees, successors or assignees, so as to prevent Wyeth, its sublicensees, successors or assignees from exercising such license rights to develop, make, have made, use, import, export, sell and have sold such Agreement Compound and Agreement Product or to so practice the Collaboration Technology in the Territory or so as to obtain any payment or consideration, in excess of that expressly provided for in this Agreement, from Wyeth, its sublicensees, successors and/or assignees.

2.3

Licenses to Curis.

2.3.1

Research Program License. Wyeth hereby grants to Curis during the Research Term (i) a non-transferable, non-exclusive right and license, with no right to sublicense, under the Wyeth Technology to the extent that such right and license shall be necessary for Curis to perform its obligations under the Research Program, and (ii) a non-transferable, non-exclusive right and license to use all data and information generated in the conduct of the Research Program, but only as shall be reasonably necessary for Curis to perform its obligations under the Research Program.

2.3.2

Curis Field License. Subject to Section 2.7 below, Wyeth hereby grants to Curis an irrevocable, exclusive sublicense under that Curis Technology licensed to Wyeth under Section 2.1 above for Curis to develop, make, have made, offer for sale, sell and have sold Reverted Compounds for use in the Curis Field. For the sake of clarity, the license granted to Curis under this Section 2.3.2 shall include no right to any Wyeth Compound.

2.4

Curis Retained Rights. The exclusive licenses granted to Wyeth in Section 2.1 above shall be subject to the retention by Curis of a non-exclusive right and license (with no right to sublicense, except to its Affiliates), to the extent necessary for Curis to perform its obligations under the Research Program hereunder and for [**] . For the avoidance of doubt, Curis retains a non-exclusive right and license, with rights to sublicense, consistent with those obligations contained in the Curis Third Party Agreements, to the Curis Technology, including the Research Materials and Agreement Protein, and the Curis Patents associated with the Agreement Protein, to the limited extent necessary for Curis to perform

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its obligations under such Curis Third Party Agreements, provided, however , that in no event shall Curis grant to any Third Party and right to make, use or commercialize any Agreement Compound except to the extent permitted under Section 2.7 hereof. In addition, for clarification purposes, Curis expressly reserves the right to practice and to grant licenses under the Curis Technology [**] that are [**] and no explicit or implied license is granted to Wyeth [**] under the Curis Technology.

2.5

Sublicenses. Neither Party may grant any sublicenses to the rights granted to it under this Article 2 without the prior written consent of the other Party, which consent shall not be unreasonably withheld. Notwithstanding the foregoing: (a) each Party may grant sublicenses to any of its Affiliates to conduct portions of the Research Program and, to the extent that such sublicense is approved by the JSC, either Party may grant sublicenses to Third Parties to conduct portions of the Research Program, (b) Wyeth may grant sublicenses to Affiliates, Third Parties which resell or otherwise distribute Products, and Third Parties which manufacture such Products for sale by such parties, (c) Wyeth may appoint co-marketing partners, and (d) Wyeth may grant sublicenses to one or more Third Parties to conduct the clinical development of Products. All sales of Agreement Products by any such sublicensees (other than Curis or any of Curis’ Affiliates) or co-marketing partners (other than Curis or any of Curis’ Affiliates) of Wyeth shall be included in Net Sales. In the event that any sublicenses are granted under this Section 2.5, such sublicenses shall be set forth in a written agreement containing confidentiality, indemnity, reporting and access to data and information obligations comparable to those set forth herein, and such other terms as are required under existing Curis Third Party Agreements, and no sublicense shall relieve such Party of any of its obligations under this Agreement. Wyeth’s right to sublicense is limited to the extent the existing Curis Third Party Agreements permit Wyeth, as Curis’ sublicensee under such existing Curis Third Party Agreements, to grant further sublicenses Wyeth and its permitted sublicensees agree to be bound by the applicable terms and provisions of those Curis Third Party Agreements existing as of the Signature Date. Wyeth agrees that, to the extent Wyeth is a sublicensee of Curis’ rights [**] Wyeth shall be subject to the provisions set forth [**] that apply to Curis, and that to the extent Wyeth is a sublicensee of Curis’ rights [**] Wyeth shall be subject to the provisions set forth [**].

2.6

Direct Licenses to Affiliates of Wyeth. Wyeth may at any time request and authorize Curis to grant licenses directly to Affiliates of Wyeth by giving written notice designating to whom a direct license is to be granted. Upon receipt of any such notice, Curis shall enter into and sign a separate direct license agreement with such designated Affiliate of Wyeth. All such direct license agreements shall

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be consistent with the terms and conditions of this Agreement, except for such modifications as may be required by the laws and regulations in the country in which the direct license will be exercised. In countries where validity of the direct license agreement requires prior government approval or registration, such direct license agreement shall not become binding between the parties thereto until such approval or registration is granted, which approval or registration shall be obtained by Wyeth.

2.7

Wyeth Option.

2.7.1

Option. Curis hereby grants to Wyeth the exclusive option to obtain a worldwide, exclusive license under the Curis Technology to develop, have developed, make, have made, use, import, offer for sale, sell and have sold any (i) Orphan Compound and (ii) any Reverted Compound or Curis Option Compound which has been or is being developed for the treatment of cardiovascular disease by local administration ( e.g., in a coronary artery stent) each of which by the JSC’s determination would otherwise meet the requirements for a Clinical Development Candidate (each, an “Option Compound”).

2.7.2

Standstill. Except and until such time as expressly permitted under Section 2.7.4, Curis shall not, directly or indirectly, expressly or implicitly,

(i)

grant to any Third Party any license or other right under any of the Curis Technology with respect to any Option Compound; or

(ii)

enter into negotiations with any Third Party, make any offer to any Third Party, solicit any offer from any Third Party, or otherwise engage in any discussions with any Third Party with respect to or in contemplation of the actual or potential grant to any such Third Party of a license or other rights under any of the Curis Technology with respect to any Option Compound.

2.7.3

Notice. On an Option Compound by Option Compound basis, promptly after Curis has completed all studies on such Option Compound and collected that data with respect to such Option Compound which would be necessary for the JSC to determine that such Option Compound would meet the requirements for designation as a Clinical Development Candidate if such Option Compound were otherwise an Agreement Compound, Curis shall provide written notice to Wyeth offering Wyeth the opportunity to obtain an exclusive worldwide license for the development, manufacture and commercialization of such Option

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Compound. Any such notice provided to Wyeth shall be accompanied by complete and accurate copies, certified by an officer of Curis, of all available data and summaries thereof and all other information that Curis has in its possession or control with respect to such Option Compound.

2.7.4

Exercise of Option; Negotiation of Agreement. Within [**] ([**]) days of Wyeth’s receipt of the written notice and all accompanying information as required under Section 2.7.3, Wyeth shall notify Curis, in writing, as to whether Wyeth desires to obtain a license to develop, manufacture and commercialize such Option Compound. In the event that Wyeth exercises its option for such Option Compound within such [**] ([**]) day period, the license granted under Section 2.1(d) with respect to such Option Compound for Orphan Compounds shall automatically become effective For Option Compounds other than Orphan Compounds, Wyeth and Curis shall negotiate mutually acceptable license terms and, in the event that the Parties are able to reach agreement on such terms, shall amend this Agreement accordingly. This negotiation shall occur within [**] ([**]) days of Wyeth’s original notice to Curis. In the event that Wyeth, within the [**] ([**]) day period set forth above in this Section 2.7.4 either notifies Curis that it does not desire to obtain a license for such Option Compound that are Orphan Compounds, or fails to notify Curis that it desires to obtain a license for such Option Compound, that are Orphan Compounds, Curis, notwithstanding Section 2.7.2, but subject to Section 2.7.5, shall be free to enter into discussions or negotiations with any Third Party for the grant to such Third Party of a license to develop, manufacture and/or commercialize such Option Compound. In the event that the Parties, following the [**] ([**]) day period set forth above in this Section 2.7.4 for negotiation of a license to Option Compounds that are not Orphan Compounds, are unsuccessful in reaching an agreement on terms, Curis, notwithstanding Section 2.7.2, but subject to Section 2.7.5, shall be free to enter into discussions or negotiations with any Third Party for the grant to such Third Party of a license to develop, manufacture and/or commercialize such Option Compound.

2.7.5

Restrictions. During the [**] period following the expiration of the relevant [**] ([**]) day [**] ([**]) day period (as may be[**]extended by mutual agreement described above, Curis shall [**] which,[**] terms and conditions contained in this Agreement with respect to [**] such terms and conditions [**] such terms and conditions. [**] such terms and conditions, the Parties shall promptly [**] such terms and conditions. [**] such terms and conditions, Curis shall thereafter [**] such terms and conditions.

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2.8

Curis Option. Wyeth hereby grants to Curis an option for Curis to obtain a worldwide, exclusive license under the Wyeth Technology and a worldwide, exclusive sublicense under the Curis Technology licensed to Wyeth hereunder, each subject to the Wyeth Option, to develop, have developed, make, have made, use, import, offer for sale, sell and have sold, for use in the Curis Field or as an Orphan Product, any Collaboration Compound which (i) is also an Activator Compound, (ii) has reverted to Wyeth in accordance with Section 3.10.3 hereof, and (iii) has not been designated by Wyeth as a lead compound or is not the member of a series of compounds including a compound that has been designated by Wyeth as a lead compound in a Wyeth discovery program for the treatment of a disease or disorder other than through activation of the Hedgehog Pathway. On a Collaboration Compound by Collaboration Compound basis, within [**] ([**]) days after such Collaboration Compound reverts to Wyeth in accordance with Section 3.10.3 hereof, Curis may exercise the option granted to it under this Section 2.8 by providing Wyeth with written notice so exercising such option, such notice specifying the Collaboration Compound for which the option is being exercised and whether Curis intends to develop such Collaboration Compound in the Curis Field and/or as an Orphan Product. If Curis so exercises such option with respect to such Collaboration Compound, Wyeth and Curis, shall negotiate and sign an agreement pursuant to which Wyeth grants to Curis an exclusive license under the Wyeth Technology and an exclusive sublicense under the Curis Technology, to develop, have developed, make, have made, use, import, offer for sale, sell and have sold such Compound for use in the Curis Field and/or as an Orphan Product, consistent with the notice so provided by Curis. Such license agreement shall (i) include payment provisions to be mutually agreed upon by the Parties in good faith, (ii) include diligence obligations with respect to Curis’ development and commercialization of such Collaboration Compound similar to those imposed upon Wyeth for Agreement Compounds and Agreement Products in Article 5 hereof, (iii) include provisions for reimbursement by Curis of patent prosecution and maintenance expenses incurred in connection with such Collaboration Compound and (iv) other reasonable, non-financial terms and conditions customary for an agreement of such type. If Curis fails to exercise such option within the [**] ([**]) day period provided for in this Section 2.8 Curis shall have no further right, title or interest in or to such Collaboration Compound.

2.9

Right of Reference. Curis hereby grants to Wyeth a “Right of Reference,” as that term is defined in 21 C.F.R. § 314.3(b), to any data Controlled by Curis or its Affiliates that relates to the Curis Technology, any Agreement Compound or any Product, and, if requested by Wyeth, Curis shall provide a signed statement to this effect in accordance with 21 C.F.R. § 314.50(g)(3).

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2.10

Preservation of Rights. During the term of this Agreement, Curis will use diligent efforts not to diminish the rights under the Curis Technology granted to Wyeth hereunder, including, without limitation, (i) not amending any Curis Third Party Agreement under which Curis Controls any such Curis Technology in any manner which may be detrimental to Wyeth, without Wyeth’s prior written consent, and (ii) using diligent efforts not to take or omit to take any actions that would breach any agreements between itself and Third Parties that provide for intellectual property rights applicable to the research, development, manufacture or commercialization of any Agreement Compound or Agreement Product, the breach of which would be reasonably likely to have a material adverse effect on the discovery, research, development, manufacture or commercialization of any Agreement Compound or Agreement Product. Curis will provide Wyeth promptly with notice of any such alleged breach. In order for Curis to comply with (ii) above, Wyeth agrees to use its Commercially Reasonable Efforts to assist Curis in complying with Curis’ obligations (including diligence obligations) under the Curis Third Party Agreements, to the extent such obligations relate to Agreement Compounds, Agreement Products or otherwise to the rights arising under such Third Party Agreements and sublicensed by Curis to Wyeth hereunder.

3.	RESEARCH PROGRAM.

3.1

Scope and Conduct of the Research Program.

(a)

Promptly after the Signature Date, the Parties will meet to prepare and approve the initial Research Plan, which Research Plan will not become effective prior to the Effective Date.

(b)

Curis and Wyeth will conduct research and development on a collaborative basis with the goal of the discovery, development and commercialization of Activator Compounds for the treatment of diseases in humans in the Research Field, as more specifically provided in the Research Plan.

(c)

The Research Program shall be conducted by the Parties in compliance with all applicable good laboratory practices and other applicable legal requirements and in good scientific manner to attempt to achieve its objectives efficiently and expeditiously.

(d)

Each Party shall use Commercially Reasonable Efforts to perform its obligations under the Research Program according to the priorities established by the Research Plan and the JSC. Scientists at Curis and Wyeth shall cooperate to facilitate achievement of the goals of the Research Program. Each Party shall commit to the Research Program such

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personnel, facilities, equipment, materials, Technology and other scientific resources as may be required consistent with its obligation to use Commercially Reasonable Efforts to attempt to achieve the objectives set forth in the Research Plan or otherwise established by the JSC from time to time.

(e)

Without limiting the foregoing, Curis initially will devote to the Research Program at least [**] ([**]) FTE Scientists during each Contract Year. At six (6) month intervals during the Research Term, the JSC shall review the staffing needs to accomplish the objectives of the Research Program during the following six (6) months and recommend to the Executive Board an increase or decrease to the then current Curis Staffing Level. The Executive Board, after considering in good faith the recommendation of the JSC, shall determine the Curis Staffing Level for such six (6) month period, provided, however , that in no event shall the Curis Staffing Level be greater than [**] ([**]) FTE Scientists or less than [**] ([**]) FTE Scientists during the Research Program and, provided further , that the JSC shall not require Curis to utilize Third Party subcontractors to provide more than [**] ([**]) such FTE scientists to fulfill Curis’ commitments hereunder without Curis’ consent. All of the Curis scientists that are identified as FTE Scientists assigned to the Research Program shall be required to devote substantially all of the total time actually worked by such scientists to scientific work directly in support of the Research Program. If any such full time scientist ceases to be employed by Curis (or is placed on medical or other leave), Curis shall replace such scientist with another scientist and such replacement scientist’s time working on the Research Program shall be “tacked” on to the time worked on the Research Program by such replaced scientist.

(f)

No later than ninety (90) days prior to the commencement of each Contract Year after the first Contract Year, the JSC shall review the Research Plan and confirm or amend its applicability for the following Contract Year. Each annual Research Plan shall be in writing and, to the extent the JSC determines appropriate, shall set forth with reasonable specificity the research objectives, priorities, research milestones, budgets (which shall be subject to the approval of the Executive Board), and Curis Staffing Level (subject to adjustment as provided in Section 3.1(d) above) requirements for the period covered by such annual Research Plan to the extent not addressed by this Agreement and the Exhibits attached hereto. The JSC may make adjustments to the Research Plan at its quarterly meetings or as it may otherwise determine.

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3.2

Exclusivity.

(a)

Unless specifically permitted under this Agreement and except to the extent research has been undertaken by Third Parties pursuant to Curis Material Transfer Agreements and Sponsored Research Agreements in existence as of the Signature Date: (i) until the expiration or termination of the Evaluation Tail, Curis and its Affiliates shall not, either directly or indirectly, enter into any new agreement with any Third Party with respect to the Curis Technology for use in the Research Field, other than Material Transfer Agreements or Sponsored Research Agreements that are approved by the JSC and (ii) until the expiration or termination of the Research Term, neither Curis nor Wyeth shall, either directly or indirectly, otherwise knowingly engage in any research, development or commercialization in the Research Field. Notwithstanding the forgoing, ifnew Activator Compoundscome into the Control of Curis or its Affiliates or are synthesized or acquired by Curis during the Research Term but outside the conduct of the Research Program and are not synthesized or acquired primarily for use in other discovery programs (whether conducted internally or with Third Parties),Curis will promptly notify Wyeth and the new Activator Compounds will be included in the Research Program.

(b)

Notwithstanding the foregoing, each Party may collaborate in the Research Field with universities and other non-profit organizations so long as: (i) such entities shall be subject to confidentiality undertakings in respect to the Confidential Information of both Parties; (ii) all rights acquired by the collaborating Party to use in the Wyeth Field or Curis Field any Patent Rights and data resulting from such collaboration shall be licensed to the other Party in accordance with the terms of this Agreement, however, no independent obligation is imposed upon either Party to acquire such new license rights if they are not otherwise required in order for Wyeth to practice the rights granted to it under Article 2 of this Agreement.; and (iii) such collaboration is approved by the JSC, to the extent it involves the discovery or development of any Activator Compound, Hit Compound or Agreement Compound or the determination of the physical or biological properties of any Activator Compound, Hit Compound or Agreement Compound.

(c)

Notwithstanding Section 3.2(a), in the event that Wyeth acquires, is acquired by or merges with a Third Party, which Third Party, at the time of such acquisition or merger, is engaged in research, development or commercialization in the Research Field (the “Acquired Research Program”), such acquisition and Wyeth’s participation in such Acquired Research Program shall not be deemed a breach of this Section 3.2 by Wyeth provided, however , that is such event, (i) Wyeth shall not be relieved of its other obligations under this Agreement, (ii) Curis shall have

no right, title or interest in or to any compounds or products developed under the Acquired Research Program, and (iii) during the Research Term, Wyeth shall not use any Curis Technology licensed hereunder in connection with such Acquired Research Program without the prior written consent of Curis.

(d)

Notwithstanding Section 3.2(a), in the event that Curis is acquired by or merges with a Third Party, which Third Party, at the time of such acquisition or merger, is engaged in research, development or commercialization in the Research Field (the “Curis Acquired Research Program”) such acquisition and such Third Party’s continued conduct of such Curis Acquired Research Program shall not be deemed a breach of this Section 3.2 by Curis provided, however , that in such event, (i) Curis shall not be relieved of its other obligations under this Agreement, (ii) Wyeth shall have no right, title or interest in or to any compounds or products developed under the Curis Acquired Research Program, (iii) during the Research Term, Curis and such Third Party shall not use any Curis Technology licensed to Wyeth hereunder in connection with such Curis Acquired Research Program, and (iv) except as otherwise provided in (ii) above, all Technology Controlled by Curis or such Third Party shall be included in the Curis Technology licensed to Wyeth hereunder to the extent necessary to provide the licenses granted to Wyeth under Article 2 hereof.

3.3

Collaborators. Curis may use its Affiliates or other Third Parties to perform portions of the work assigned to Curis in the Research Plan to the extent provided for in the Research Plan or to the extent that the JSC otherwise determines the use of such external resources is desired. Wyeth may in its discretion use its Affiliates or, to the extent provided for in the Research Plan or to the extent that the JSC otherwise determines the use of such resources is desired, Third Parties, to perform portions of the work assigned to Wyeth in the Research Plan. The use of such other entities or Third Parties shall be subject to the following conditions: (i) each Party shall pay the costs of the Third Party engaged by it, unless otherwise approved by the JSC, (ii) all Program Inventions and other results of such work performed by such entities and Third Parties shall be assigned by such Third Party to Curis or Wyeth, as the case may be, and such Program Inventions and other results of such work shall be treated as if they occurred under this Agreement, and (iii) the use of such entities and Third Parties shall not count toward the Curis Staffing Level obligations under Section 3.1 unless otherwise approved in advance by the JSC or in accordance with Section 3.1(e) hereof. Except as set forth in this Section 3.3, unless otherwise approved by the JSC, or otherwise set forth in the Research Plan, neither Party may subcontract or outsource to Third Parties any portion of the Research Program assigned to it under the Research

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Plan without the consent of the JSC. Neither Party may disclose or grant rights to the other Party’s Technology to any such Third Party without the written consent of the other Party. Any such subcontractor shall be subject to appropriate confidentiality undertakings and shall comply with all applicable laws and regulations, including good laboratory practices.

3.4

Funding of the Research Program.

3.4.1

Wyeth’s Funding Obligation. During the Research Term, Wyeth shall reimburse Curis for those Curis FTE Scientists working on the Research Program at the rate of [**] dollars ($[**]) per FTE per year (the “FTE Rate”). Wyeth shall have no obligation to reimburse Curis for any Curis FTE Scientist working on the Research Program in excess of the then current Curis Staffing Level. Subject to reconciliation in accordance with Section 3.4.2 below, Wyeth will provide the funding (prorated by calendar quarter or partial calendar quarter, as applicable) set forth in this Section 3.4.1 to Curis in advance [**] during the term of the Research Program, provided, however , that the first payment will be due on the fifth (5 ^th ) business day following the Effective Date. For example, [**] in which the Curis Staffing Level is expected to be [**] ([**]) FTE Scientists, Wyeth would pay to Curis the sum of [**] dollars ($[**]) ( i.e., ([**] x $[**])/[**]).