AMENDMENT NO. 6 TO COLLABORATION AND OPTION AGREEMENT

Exhibit 10.46

[ * ] = Certain confidential information contained in this document marked, by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to rule 24b-2 of the Securities Exchange Act of 1934, as amended.

AMENDMENT NO. 6 TO COLLABORATION

AND OPTION AGREEMENT

This Amendment No. 6 to the Agreement (this “Amendment No. 6”) is entered into as of June 11, 2013 (the “Amendment Effective Date”) by and between Cytokinetics, Incorporated (“Cytokinetics”), a Delaware corporation, having its principal place of business at ▇▇▇ ▇▇▇▇ ▇▇▇▇▇ ▇▇▇., ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ and Amgen Inc., a Delaware corporation having its principal place of business at ▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇▇ ▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ (“Amgen”).

WHEREAS, Cytokinetics and Amgen are parties to that certain Collaboration and Option Agreement dated December 29, 2006, as amended (the “Agreement”);

WHEREAS, in May 2009, Amgen exercised its option to obtain an exclusive, worldwide license (excluding Japan) to certain compounds that modulate the contractile elements in cardiac muscle tissue to activate cardiac contractility, including omecamtiv mecarbil (also known as CK-452), as further described in the Agreement;

WHEREAS, Amgen now wishes to extend its license to include Japan and CK is willing to grant such license on the terms and conditions set forth herein;

WHEREAS, Amgen and Cytokinetics have entered into that certain Common Stock Purchase Agreement of even date herewith;

NOW, THEREFORE, in consideration of the mutual promises and covenants set forth herein, and for other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, CK and Amgen, intending to be legally bound, agree to amend the Agreement as set forth below.

1.	Definitions. Capitalized terms used herein and not otherwise defined have the meaning ascribed in the Collaboration Agreement.

2.	Expansion of Territory

(a)

Section 1.35 of the Agreement is replaced in its entirety with the following:

““Global Registration Dossier” shall mean, with respect to a particular Compound being developed under the Collaboration, the collective data package from clinical and other studies specifically applicable to obtaining, maintaining and expanding regulatory approvals for such Compound throughout the United States, the European Union and Japan, excluding country-specific requirements.”

(b)

Section 1.63 of the Agreement is replaced in its entirety with the following:

““Territory” shall mean the world.”

(c)

All references in the Agreement to Cytokinetics’ rights outside of the Territory are deleted from the Agreement, including, without limitation, in Sections 2.6, 2.19, 7.3, 9.2.3, 9.3.1, 13.7 and Article 22, and Cytokinetics will no longer have any right to research, manufacture, develop or commercialize Compounds, including, without limitation, Japan Eligible Compounds, itself or through a Third Party, outside the scope of the Collaboration. The Parties’ rights and obligations under the Agreement will be the same with respect to Japan as they are in the rest of the Territory, subject to the following:

(i)

Amgen will pay Cytokinetics the additional pre-commercial milestone payments described in Exhibit A. [*] under this Amendment No. 6.

(ii)

Amgen will pay Cytokinetics royalties on Net Sales of Compounds in Japan in accordance with Section 13.4 of the Agreement, [*] as set forth in [*] included in the [*] under Sections [*] of the Agreement. [*] for the purpose of the [*] of the Agreement. Section [*] of the Agreement is [*] in Japan.

(d)

In partial consideration for the expansion of the Territory described above, Amgen shall pay Cytokinetics a non-refundable license fee in the amount of $15,000,000 cash on or before June 14, 2013.

3.	Japan PK Bridging Study

(a)

Cytokinetics will conduct a Phase I Trial designed to study the PK of omecamtiv mecarbil in healthy volunteers of Japanese descent (the “PK Bridging Study”) in accordance with a protocol to be approved by the JDC and included in the Development Plan. The PK Bridging Study is expected to be initiated [*].

(b)

[*] to conduct the PK Bridging Study and the [*] the PK Bridging Study [*] to occur in [*] included in the Development Plan.

(c)

Amgen will permit Cytokinetics to cross-reference Amgen’s IND [*] for Cytokinetics’ IND related to the PK Bridging Study.

(d)

Amgen will supply [*] to Cytokinetics’ designee or the designated clinical trial site at Amgen’s option to enable the conduct of the Japanese Ethnic Bridging Study in accordance with the protocol. To the extent necessary, the Parties will [*].

(e)

Notwithstanding Section 17.1 (Indemnity) of the Agreement, Amgen’s indemnification obligations for the PK Bridging Study under the Agreement shall [*] the same as the [*].

(f)

Amgen will [*] for the PK Bridging Study, in accordance with the protocol, using [*] omecamtiv mecarbil.

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(g)

Amgen will bear the costs for the PK Bridging Study [*] in accordance with Section 4.7.1.2 of the Agreement (it being understood that [*] of the Agreement), provided that [*] the PK Bridging Study [*] the PK Bridging Study on [*] (the “[*] Cost”). Following [*] Cytokinetics will [*] the PK Bridging Study for [*] will be [*] Cost. Amgen will [*]. If [*], then [*] will promptly provide [*] Cost, along with a [*], including all [*]. Amgen will [*] as reasonably requested by Cytokinetics and will [*] regarding such [*]. The Parties intend to [*] the PK Bridging Study [*]. If the [*] the PK Bridging Study [*] in accordance with [*] set forth above.

4.	Joint Press Release. Within four business days of the execution of this Amendment No. 6, the Parties shall issue a joint press release announcing such Amendment in the form attached as Exhibit C.

Except as expressly set forth herein, all of the terms and conditions of the Agreement will remain in full force and effect. This Amendment No. 6 and the Common Stock Purchase Agreement of even date herewith constitute the entire agreement between the Parties as to their subject matter, and supersedes and merges all prior negotiations, representations, agreements and understandings regarding the same.

IN WITNESS WHEREOF, the Parties have executed this Amendment No. 6 as of the Amendment Effective Date.


Cytokinetics, Inc.		Amgen Inc.

By:	/s/ ▇▇▇▇▇▇ ▇. ▇▇▇▇	By:	/s/ ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇

Name:	▇▇▇▇▇▇ ▇. ▇▇▇▇	Name:	▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇

Title:	President and CEO	Title:	Chairman and Chief Executive Officer

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EXHIBIT A

Japan Milestones

Event

[*]

[*]

]

[*]

]

[*]

]

Total (Max)

]

^† This [*] milestone is payable if [*] of the [*] such that [*] at any time [*] Japan.

[*] means achievement of [*] as defined by the [*].

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EXHIBIT B

[*]

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EXHIBIT C

Joint Press Release

[attached]

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AMGEN AND CYTOKINETICS ANNOUNCE

EXPANSION OF LICENSE FOR OMECAMTIV MECARBIL

Cytokinetics Will Receive $25 Million

Plus Potential Milestone Payments and Royalties

THOUSAND OAKS, Calif. AND SOUTH SAN FRANCISCO, Calif, (June 12, 2013) – Amgen (NASDAQ:AMGN) and Cytokinetics Incorporated (NASDAQ:CYTK) today announced an expansion of their strategic collaboration to include Japan. In 2006, Cytokinetics and Amgen entered into a collaboration to discover, develop and commercialize novel small-molecule therapeutics that activate cardiac muscle contractility for potential applications in the treatment of heart failure. Omecamtiv mecarbil is the most advanced drug candidate in this collaboration. Initially, Cytokinetics’ license to Amgen for omecamtiv mecarbil excluded Japan. Under the amendment to the collaboration announced today, the companies have agreed on terms expanding Amgen’s license for omecamtiv mecarbil and related compounds to include Japan.

In consideration of the expanded license, Cytokinetics will receive $25 million from Amgen comprised of a non-refundable license fee of $15 million and $10 million for Amgen’s purchase of Cytokinetics’ common stock. The companies have executed a stock purchase agreement providing for the sale of Cytokinetics’ common stock to Amgen at a price per share equal to the 10-day trailing average of the closing price of Cytokinetics’ stock on the last trading day prior to execution of the stock purchase agreement. In addition, Cytokinetics is eligible to receive additional pre-commercialization milestone payments for the development of omecamtiv mecarbil in Japan of up to $50 million as well as royalties on sales of omecamtiv mecarbil in Japan. Under the terms of the amended collaboration agreement, Cytokinetics plans to conduct a Phase I pharmacokinetic study, the costs of which will be reimbursed by Amgen, intended to support the inclusion of Japanese patients in a potential Phase III clinical development program for omecamtiv mecarbil.

“We are pleased to expand our collaboration with Amgen to include Japan,” stated ▇▇▇▇▇▇ ▇. ▇▇▇▇, Cytokinetics’ President and Chief Executive Officer. “Our decision to amend the agreement at this time is based on our confidence in the progress of our collaborative development program for omecamtiv mecarbil and on Amgen’s recent commitment to expand its business activities in Japan. We look forward to the integration of Japan into our collaboration’s global development plan for this promising drug candidate.”

“This expanded collaboration furthers Amgen’s hopes to address the needs of patients with heart failure in Japan,” said ▇▇▇▇ ▇. ▇▇▇▇▇▇, M.D., Amgen’s Executive Vice President of Research and Development.

About Omecamtiv Mecarbil

Omecamtiv mecarbil is a small molecule cardiac myosin activator which was discovered by Cytokinetics’ scientists and is the subject of a collaboration between Cytokinetics and Amgen. It is being investigated for the treatment of heart failure.

About Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe, effective medicines from lab to manufacturing plant to patient. Amgen therapeutics have changed the practice of medicine, helping people around the world in the fight against serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. For more information, visit ▇▇▇.▇▇▇▇▇.▇▇▇ and follow us on ▇▇▇.▇▇▇▇▇▇▇.▇▇▇/▇▇▇▇▇.

About Cytokinetics

Cytokinetics is a clinical-stage biopharmaceutical company focused on the discovery and development of novel small molecule therapeutics that modulate muscle function for the potential treatment of serious diseases and other medical conditions. Cytokinetics currently has three compounds in clinical development: omecamtiv mecarbil in Phase II for acute and chronic heart failure, tirasemtiv in Phase II for amyotrophic lateral sclerosis and CK-212107 in a Phase I study in healthy volunteers. All of the company’s drug candidates have arisen from Cytokinetics’ muscle biology focused research activities and are directed towards the cytoskeleton. The cytoskeleton is a complex biological infrastructure that plays a fundamental role within every human cell. Additional information about Cytokinetics can be obtained at ▇▇▇▇://▇▇▇.▇▇▇▇▇▇▇▇▇▇▇▇.▇▇▇.

Forward-Looking Statements: Amgen

This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in Amgen’s Form 10-K for the year ended December 31, 2012, and in any subsequent periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

No forward-looking statement can be guaranteed and actual results may differ materially from those Amgen projects. Amgen’s results may be affected by Amgen’s ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments (domestic or foreign) involving current and future products, sales growth of recently launched products, competition from other products (domestic or foreign) and difficulties or delays in manufacturing its products. In addition, sales of Amgen products are affected by reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others’ regulations and reimbursement policies may affect the development, usage and pricing of Amgen products. Furthermore, Amgen’s research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and

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foreign government regulatory authorities. Amgen or others could identify safety, side effects or manufacturing problems with Amgen products after they are on the market. Amgen’s business may be impacted by government investigations, litigation and product liability claims. If Amgen fails to meet the compliance obligations in the corporate integrity agreement between Amgen and the U.S. government, Amgen could become subject to significant sanctions. Further, while Amgen routinely obtains patents for its products and technology, the protection offered by its patents and patent applications may be challenged, invalidated or circumvented by its competitors. Amgen depends on third parties for a significant portion of its manufacturing capacity for the supply of certain of its current and future products and limits on supply may constrain sales of certain of its current products and product candidate development. In addition, Amgen competes with other companies with respect to some of its marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for Amgen products are supplied by sole third-party suppliers. Amgen’s business performance could affect or limit the ability of its Board of Directors to declare a dividend or its ability to pay a dividend or repurchase its common stock.

Forward-Looking Statements: Cytokinetics

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements relating to Cytokinetics’ and Amgen’s research and development activities, including the planned conduct of clinical trials; the potential receipt of milestones, royalties and other payments; and the properties and potential benefits of omecamtiv mecarbil and Cytokinetics’ other drug candidates. Such statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to: Cytokinetics anticipates that it will be required to conduct at least one confirmatory Phase III clinical trial of tirasemtiv in ALS patients which will require significant additional funding, and it may be unable to obtain such additional funding on acceptable terms, if at all; potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics’ drug candidates that could slow or prevent clinical development or product approval, including risks that current and past results of clinical trials or preclinical studies may not be indicative of future clinical trials results, patient enrollment for or conduct of clinical trials may be difficult or delayed, Cytokinetics’ drug candidates may have adverse side effects or inadequate therapeutic efficacy, the U.S. Food and Drug Administration or foreign regulatory agencies may delay or limit Cytokinetics’ or its partners’ ability to conduct clinical trials, and Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; Amgen’s decisions with respect to the design, initiation, conduct, timing and continuation of development activities for omecamtiv mecarbil; Cytokinetics may incur unanticipated research and development and other costs or be unable to obtain additional financing necessary to conduct development of its products; Cytokinetics may be unable to enter into future collaboration agreements for its drug candidates and programs on acceptable terms, if at all; standards of care may change, rendering Cytokinetics’ drug candidates obsolete; competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics’ drug candidates and potential drug candidates may target; and risks and uncertainties relating to the timing and receipt of payments from its partners, including milestones and royalties on

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future potential product sales under Cytokinetics’ collaboration agreements with such partners. For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission.

Contacts:

▇▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇-▇▇▇-▇▇▇▇ (Amgen media)

▇▇▇▇▇▇ ▇▇▇▇, 805-447-1060 (Amgen investors)

▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇, 650-624-3000 (Cytokinetics investors & media)

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AMENDMENT NO. 6 TO COLLABORATION AND OPTION AGREEMENT

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