Exhibit 10.22

 

Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Double asterisks denote omissions.

SECOND AMENDMENT

TO

COMPANION DIAGNOSTICS AGREEMENT

This Second Amendment (“Second Amendment”) shall be effective as of this 16th
day of November (“Amendment Effective Date”), by and between Epizyme, Inc.,
having a place of business at 400 Technology Square, 4th Floor, Cambridge,
Massachusetts 02139, U.S.A. (“Epizyme”) and Eisai Co., Ltd., having a place of
business at Koishikawa 4-6-10, Bunkyo-ku, Tokyo 112-8088, Japan (individually,
“Eisai” and collectively with Epizyme, “Pharmaceutical Partners”), on the one
side, and Roche Molecular Systems, Inc., having a place of business at 4300
Hacienda Drive, Pleasanton, California 94588, U.S.A. (“RMS”), on the other side,
as an amendment to the Companion Diagnostics Agreement, dated 18th December 2012
as previously amended on 31 May 2013 (“Agreement”). Capitalized terms used in
this Amendment and not defined in this Amendment shall have the meanings
ascribed to them in the Agreement.

WHEREAS, Epizyme, Eisai and RMS are Parties to the Agreement and desire to amend
the Agreement as set forth in this Second Amendment; and

WHEREAS, the Parties agree to modify the Project Plan and the Payment Plan, as
well as the other provisions specifically set forth herein, in accordance with
Section 4.2 of the Agreement, to reflect the revised timing of the Pivotal
Registrational Trial.

NOW, THEREFORE, in consideration of the agreements contained herein, and other
good and valuable consideration, the receipt and sufficiency of which each Party
hereby acknowledges, the Parties hereby agree as follows:

 

  1. Section 15.7(b) under the Agreement is hereby replaced in its entirety with
the following amended and restated Section 15.7(b):

“(b) If Pharmaceutical Partners terminate this Agreement or a Project Plan
pursuant to Section 15.4, and RMS is not in material breach of this Agreement,
then the Parties shall agree [**] and Pharmaceutical Partners shall pay to RMS
[**]. If the Parties cannot agree [**], the Parties agree that such disputes
shall be resolved by Senior Officers in accordance with Section 4.3, and then,
if applicable, by Arbitration in accordance with Article 16. Without limiting
the foregoing, (i) in the event that such termination occurs prior to initiation
of [**], Pharmaceutical Partners shall pay to RMS [**] dollars ($[**]), and
(ii) in the event that such termination occurs after initiation of [**],
Pharmaceutical Partners shall pay to RMS [**] dollars ($[**]) (either the fees
in (i) or (ii), the “Deferred Fee”); provided that, for clarity, in the event
that Pharmaceutical Partners are obligated to make a payment for Deferred Fee to
RMS pursuant to clause (ii), they shall not also be obligated to make a payment
for Deferred Fee to RMS pursuant to clause (i). Any applicable Deferred Fee in
addition to any applicable [**] that may be due as set forth above in this
Section 15.7(b) shall be collectively the “Termination Fees”. In addition,
Pharmaceutical Partners shall pay to RMS and any additional costs associated
with the agreed upon orderly wind down of any then-ongoing activities under the
Project Plan. For clarity, (1) for purposes of calculating the Termination Fees
(if any) due to RMS pursuant to this Section 15.7(b) only, the milestone
reference amounts set forth on Part I.B of Exhibit E shall apply, (2) for
purposes of any milestones that have been completed prior to termination (which
were not invoiced and/or paid), such milestones shall be

 

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deemed earned and the milestone amounts set forth in Exhibit B shall apply and
be paid in accordance with Article 7; and, unless otherwise expressly agreed by
the Parties in writing, in no event shall Pharmaceutical Partners be obligated
to pay RMS more than an aggregate of fifteen million dollars ($15,000,000)
following the execution of the Second Amendment to this Agreement in milestones
and Termination Fees under this Agreement. For illustrative purposes only, Part
II of Exhibit E provides a sample calculation for a scenario under this
Section 15.7(b).”

 

  2. The current Project Plan under the Agreement is hereby replaced in its
entirety with the amended and restated Project Plan set forth in Attachment 1 to
this Amendment.

 

  3. The current Exhibit B of the Agreement is hereby replaced in its entirety
with the amended and restated Exhibit B set forth in Attachment 2 to this
Amendment.

 

  4. The current Exhibit C of the Agreement is hereby replaced in its entirety
with the amended and restated Exhibit C set forth in Attachment 3 to this
Amendment.

 

  5. The current Exhibit E of the Agreement is hereby replaced in its entirety
with the amended and restated Exhibit E set forth in Attachment 4 to this
Amendment.

 

  6. This Amendment is effective and shall become part of the Agreement as of
the Amendment Effective Date.

 

  7. Except as provided herein, all other terms and conditions of the Agreement
remain unchanged and are in full force and effect.

 

  8. This Amendment may be signed in any number of counterparts (facsimile and
electronic transmission included), each of which shall be deemed an original,
but all of which shall constitute one and the same instrument. After facsimile
or electronic transmission, the Parties agree to execute and exchange documents
with original signature.

 

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The Parties have executed this Amendment, by their duly authorized
representatives.

 

ROCHE MOLECULAR SYSTEMS, INC.      EPIZYME, INC. By:  

/s/ Paul Brown

     By:  

/s/ Robert Bazemore

  (signature)        (signature) Name:  

Paul Brown

     Name:  

Robert Bazemore

  (printed name)        (printed name) Title:   President & CEO      Title:  
President & CEO Date:   8 December 2015      Date:   11-16-15        EISAI CO.,
LTD.        By:  

/s/ Terushige Iike

         (signature)        Name:  

Terushige Iike

         (printed name)        Title:   Chief Product Creation Officer       
Date:   December 15, 2015

 

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ATTACHMENT 1

PROJECT PLAN (updated October 2015)

To Develop a Companion Diagnostic (CoDx) Test for EZH2 Mutation Detection to
Select Patients for Treatment with E7438 (tazemetostat)

This Project Plan describes the activities and deliverables planned for a joint
collaboration between Epizyme and Eisai (collectively and applicably the
Pharmaceutical Partners) and RMS to develop a companion diagnostic (CoDx)
testing kit against EZH2 change of function mutations in the catalytic domain
for the selection of Non-Hodgkin Lymphoma (NHL) patients for treatment with
tazemetostat.

Background – Diagnostic Test:

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 3 pages were omitted. [**].

Scope of this Project Plan:

The Pharmaceutical Partners and RMS would like to engage in a collaboration to
develop and commercialize a companion diagnostic test (RMS Product) for the
prospective selection of EZH2 mutation positive Non-Hodgkin’s Lymphoma (NHL)
patients for treatment with tazemetostat. This Project Plan describes the
activities, deliverables, and estimated budget anticipated for a collaboration
between the Pharmaceutical Partners and RMS for Stage 1 – Specimen access,
pre-IDE development activities with minimal set of verification studies required
for IND supplement/IDE submission, Stage 2 – IVD development/core TPV studies
required for Device Authorization Application submission and start of Proof of
Concept (PoC) Phase 2 studies, Stage 3 –first pivotal registrational
(open-label, single-arm) clinical trials to establish clinical utility, Stage 4
– Clinical reproducibility studies required for Device Authorization Application
submission, and Stage 5 – CE-IVD marking and Device Authorization Application
submission to FDA.

Note: This updated project plan and updated payment plan are based on the Key
Assumptions (updated October 2015) set forth in Attachment 2. Any changes to the
updated Key Assumptions may lead to a change in the project plan and payment
plan.

[**].

In addition, high level budget estimates of activities that are planned in the
long term for support of a [**] will be provided to the Pharmaceutical Partners.
These “ball park” estimates are based on the assumptions listed below and may be
modified in the future as the scope of the project becomes more fully defined.
Modification of the scope and budget of long term activities will be agreed upon
by the Pharmaceutical Partners and RMS.

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission. A total of 7 pages were omitted. [**].

 

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ATTACHMENT #2

EXHIBIT B

PAYMENT PLAN

Milestones: Epizyme, on behalf of Epizyme and Eisai, will pay RMS the following
milestone payments upon completion of activities associated with the milestone:

I. Milestone payments made prior to the execution of the Second Amendment to
this Agreement:

 

Milestone    Payment [**]    [**] [**]    [**] [**]    [**] [**]    [**]

II. Milestone payment to be paid by Epizyme, on behalf of Epizyme and Eisai, to
RMS within [**] days after the execution of the Second Amendment to this
Agreement:

 

[**]    [**]  

III. Remaining milestone payments that may become payable after the execution of
the Second Amendment to this Agreement:

 

[**]    [**]               [**]    [**]   [**]    [**]               [**]   
[**]   [**]    [**]   [**]    [**]  

 

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[**]    [**]   [**]    [**]   [**]    [**]   [**]    [**]   [**]    [**]   [**]
   [**]  

In the event that RMS has completed [**] Project Plan and thereafter any
excessive delay or failure of performance by Pharmaceutical Partners prevents
RMS from filing and therefore obtaining Regulatory Approval thereof in the
United States, where RMS would otherwise have earned such subsequent
milestone(s) but for such excessive delay or failure of performance by
Pharmaceutical Partners, then RMS may send a notice to Pharmaceutical Partners
asserting that such circumstances exist. If Pharmaceutical Partners do not
either send RMS a notice of termination pursuant to Article 15 or a notice
disputing the existence of such circumstances within [**] days after the notice
from RMS asserting such circumstances, and if RMS is not in material breach of
the Agreement, RMS shall be deemed to have earned [**] dollars ($[**]), which
amount shall be creditable against all unearned milestones and Termination Fees,
if any. Any dispute as to the applicability of this paragraph shall be resolved
in accordance with the terms of Article 16. For clarity, unless otherwise
expressly agreed by the Parties in writing, in no event shall Pharmaceutical
Partners be obligated to pay RMS more than an aggregate of fifteen million
dollars ($15,000,000) ) following the execution of the Second Amendment to this
Agreement in milestones (including any amount that may become payable pursuant
to this paragraph) and Termination Fees under this Agreement.

 

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ATTACHMENT #3

KEY ASSUMPTIONS (updated October 2015 )

As of the Amendment Effective Date, the following items shall be deemed Key
Assumptions which were used to prepare the updated Project Plan (updated May
2013) and updated Payment Plan agreed upon by the Parties:

Note: The updated project plan ( October 2015) and updated payment plan are
based on the assumptions stated below. Any changes to the assumptions may lead
to a change in the project plan and payment plan.

[**].

In addition, high level budget estimates of activities that are planned in the
long term for support of a [**] will be provided to the Pharmaceutical Partners.
These “ball park” estimates are based on the assumptions listed below and may be
modified in the future as the scope of the project becomes more fully defined.
Modification of the scope and budget of long term activities will be agreed upon
by the Pharmaceutical Partners and RMS.

Key Assumptions:

Key Assumptions for: [**]

[**]

 

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ATTACHMENT #4

EXHIBIT E

MILESTONES AND EXAMPLES FOR SECTION 15.7(b)

Part I.A: Milestone Reference Amounts No Longer Applicable for Purposes of
Section 15.7(b) After the Execution of the Second Amendment to the Agreement

 

Milestone    Payment [**]    [**] [**]    [**] [**]    [**]

Part I.B: Milestone Reference Amounts Applicable for Purposes of Section 15.7(b)
After the Execution of the Second Amendment to the Agreement

 

[**]    [**] [**]    [**] [**]    [**] [**]    [**] [**]    [**] [**]    [**]
[**]    [**] [**]    [**]

Part II: Sample Calculation under Section 15.7(b) (for illustrative purposes
only)

[**]

 

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