8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of report (Date of earliest event reported): March 9, 2016

EPIZYME, INC.

(Exact Name of Registrant as Specified in Charter)

Delaware	001-35945	26-1349956
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)
400 Technology Square, Cambridge, Massachusetts		02139
(Address of Principal Executive Offices)		(Zip Code)

Registrant’s telephone number, including area code: (617) 229-5872

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions ( see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 2.02 Results of Operations and Financial Condition

On March 9, 2016, Epizyme, Inc., a Delaware corporation (the “Company”) announced its financial results for the year ended December 31, 2015. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

The information provided under Item 2.02 of this Form 8-K (including Exhibit 99.1) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 7.01 Regulation FD Disclosure

On March 9, 2016, the Company issued a press release relating to the Company’s corporate vision and strategy through 2020. The full text of the press release issued in connection with this announcement is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits

(d) Exhibits

99.1	Press release issued by the Company on March 9, 2016*
99.2	Press release issued by the Company on March 9, 2016*

* These exhibits relating to Items 2.02 and 7.01 shall be deemed to be furnished, and not filed.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	EPIZYME, INC.
Date: March 9, 2016	By:	/s/ Robert B. Bazemore
		Robert B. Bazemore
		President and Chief Executive Officer

EXHIBIT INDEX

Exhibit Number	Description of Exhibit
99.1	Press release issued by the Company on March 9, 2016*
99.2	Press release issued by the Company on March 9, 2016*

* These exhibits relating to Items 2.02 and 7.01 shall be deemed to be furnished, and not filed.

EX-99.1

Exhibit 99.1

Epizyme Announces 2015 Financial Results and Financial Guidance

Company reiterates financial runway guidance through at least the end of 2017 and through major research and development milestones

Conference call to be held today at 8:00am E.T.

CAMBRIDGE, Mass. – March 9, 2016 -Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for patients with cancer, today highlighted certain 2015 and recent accomplishments and reported financial results for the fourth quarter of and full year 2015. In addition, earlier today, Epizyme announced a multi-year vision for the company’s growth through 2020.

Key 2015 Accomplishments

• Regained control of key pipeline assets: In 2015, Epizyme reacquired from Eisai the rights to tazemetostat worldwide outside of Japan and assumed leadership of the tazemetostat development strategy. The company also extended and focused its collaboration agreement with Celgene on three specific targets, regaining worldwide rights to the rest of its preclinical pipeline programs excluding the three programs partnered with GlaxoSmithKline (GSK).

• Executed on robust clinical development strategy for tazemetostat: At multiple major medical meetings in 2015, Epizyme presented proof-of-concept data from an ongoing phase 1 trial with tazemetostat that demonstrated clinically meaningful activity and an acceptable safety profile in patients with non-Hodgkin lymphoma (NHL) and in patients with certain genetically defined solid tumors. Based on the findings, Epizyme initiated a global development plan for tazemetostat, which includes a five-arm, phase 2 study in patients with NHL, a three-arm phase 2 study in adult patients with certain genetically defined solid tumors, and a dose-escalation and dose-expansion phase 1 study in pediatric patients with certain genetically defined solid tumors. Epizyme also obtained FDA acceptance of INDs in the U.S. for tazemetostat for the treatment of diffuse-large B-cell lymphoma (DLBCL), the largest subset of NHL, and for certain genetically defined solid tumors.

• Expanded pipeline of preclinical assets: Epizyme made substantial progress in its discovery pipeline, identifying and initiating preclinical work against five new targets, against which the company is developing small molecules wholly owned by Epizyme.

• Strengthened its scientific leadership: Throughout 2015, Epizyme continued to enhance its platform capabilities. The company’s extensive epigenetics expertise with histone methyltransferases (HMTs) led to the expansion of its efforts to encompass other chromatin modifying proteins (CMPs). Epizyme has identified a prioritized set of HMT and CMP targets from which it plans to build a sustainable pipeline of potential new therapies.

Based on these significant advancements throughout 2015, Epizyme has outlined a vision and strategic plan through 2020, focused on quickly bringing tazemetostat to market, maximizing the potential of tazemetostat in a broad range of cancers and treatment settings, continuing the growth of its pipeline and further establishing the company’s scientific leadership in the field of chromatin modifying proteins. More details on the vision and strategy can be found here.

“In 2015, we made substantial progress across all aspects of the organization, which has provided a solid foundation on which to build our future,” said Robert Bazemore, President and Chief Executive officer of Epizyme. “We have a unique lead product candidate, tazemetostat, that is in three registration-supporting clinical trials today, with multiple new clinical trials planned to begin in the near future. In addition, we

are driving forward five new wholly owned programs, and we are continuing to expand our pipeline. We believe that Epizyme has the opportunity for tremendous growth and value creation in the short and long-term, and we look forward to executing on the strategic vision that we have laid out for the company.”

Full Year 2015 Results and Financial Guidance

• Collaboration revenue was $2.6 million for the year ended December 31, 2015, compared to $41.4 million for the prior year. The decrease in collaboration revenue primarily reflects the completion of a significant portion of the Company’s performance obligations under its collaborations during 2014 and achievement of a $3.0 million milestone under its agreement with GSK during 2014. The company expects to recognize an additional $1.9 million of deferred revenue related to the Celgene agreement through December 31, 2016 as the company completes its pinometostat phase 1 clinical trials.

• Research and development (R&D) expenses were $111.2 million for the year ended December 31, 2015 compared to $75.6 million for the year ended December 31, 2014. The increase in costs were primarily driven by the expansion of tazemetostat clinical trials and related EZH2 activities and the $40.0 million upfront payment to Eisai in the first quarter of 2015 to reacquire rights to tazemetostat worldwide outside of Japan, partially offset by reductions in external spending on pinometostat and discovery and preclinical programs during 2015 compared to the prior year. After adjusting for the 2015 in-process research and development payment made to Eisai of $40.0 million, Epizyme expects that R&D expenses will increase in 2016, when compared to 2015. The planned increase is primarily driven by the costs of its ongoing and planned clinical trials with tazemetostat, including its registration-supporting trials in patients with non-Hodgkin lymphoma and adult and pediatric patients with certain genetically defined solid tumors, as well as planned combination studies in patients with DLBCL and the planned study in patients with BAP1 loss-of-function mesothelioma. In addition, discovery and preclinical research costs are expected to increase as the company advances its wholly owned small molecule programs against five novel targets, continues the research efforts for its Celgene partnered programs, and expands its target identification and discovery activities. Epizyme plans to offset a portion of the increased cost of its research and development programs through strategic collaborations that it will be evaluating later this year.

• General and administrative (G&A) expenses increased to $23.9 million for the year ended December 31, 2015, compared to $20.9 million for the year ended December 31, 2014. The increase in G&A expense was largely due to increased intellectual property-related legal costs and personnel-related expenses associated with scaling up Epizyme’s business operations.

• Net loss was $132.4 million for the year ended December 31, 2015, compared to a net loss of $55.0 million for the year ended December 31, 2014. The year-over-year decline was driven by a decrease in collaboration revenue, as well as by the costs associated with reacquiring tazemetostat rights from Eisai.

• Cash and cash equivalents as of December 31, 2015 were $208.3 million, compared with $190.1 million as of December 31, 2014. Epizyme’s follow-on public offering in January 2016 raised $130.1 million in net proceeds, after underwriting discounts and commissions, upon the sale of 15.3 million common shares. As this event occurred in fiscal 2016, it is not reflected in the December 31, 2015 cash and cash equivalent balances.

• Financial Guidance from Epizyme states that the Company believes its cash and cash equivalents of $208.3 million as of December 31, 2015, together with the net proceeds of $130.1 million from the January 2016 follow-on offering, will be sufficient to fund the Company’s operations through at least the end of 2017, and importantly through many key milestones.

Conference Call Information

Epizyme will host a conference call and live audio webcast today at 8:00 a.m. ET to discuss its 2015 financial results and provide business updates. To participate in the conference call, please dial 1-877-497-1428 (domestic) or 1-929-387-3949 (international). The live and archived versions of webcast can be accessed under Events in the Investor Center section of the company’s website at http://www.epizyme.com.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with non-Hodgkin lymphoma and for patients with certain genetically defined solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in dysregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-6438.

Additional information about tazemetostat, including clinical trial information, can be found here.

About Epizyme, Inc.

Epizyme, Inc. is a clinical-stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients. Epizyme has built a proprietary product platform that the Company uses to create small molecule inhibitors of chromatin modifying proteins (CMPs), such as histone methyltransferases or HMTs. CMPs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of CMPs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme’s targeted science seeks to match the right medicines with the right patients.

For more information, visit www.epizyme.com and connect with us on Twitter at @EpizymeRx.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for Epizyme, Inc. and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the initiation of future clinical studies or expansion of ongoing clinical studies, availability and timing of data from ongoing clinical studies, whether interim results from a clinical trial such as the results described in this release will be predictive of the final results of the trial or the results of future trials, expectations for regulatory approvals to conduct trials or to market products, development progress of the Company’s companion diagnostics, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements, ability to enter into third party collaborations on favorable terms or at all, other matters that could affect the availability or commercial potential of the Company’s therapeutic candidates or companion diagnostics and other factors discussed in

the “Risk Factors” section of the Company’s Form 10-K filed with the SEC on March 9, 2016 and in the Company’s other filings from time to time with the SEC. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof.

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CONTACTS

Investors:

Epizyme, Inc., Investor Relations and Corporate Communications

Rebecca Cohen, 617-401-0722

rcohen@epizyme.com

Media:

Scient Public Relations

Michael Lampe, 484-575-5040

michael@scientpr.com

EPIZYME, INC.

CONSOLIDATED BALANCE SHEET DATA (UNAUDITED)

(Amounts in thousands)

	As of December 31,
	2015		2014
	(In thousands)
Consolidated Balance Sheets Data :
Cash and cash equivalents	$	208,323	$	190,095
Total assets		217,903		199,203
Deferred revenue		30,709		23,151
Total stockholders’ equity		169,532		160,282

EPIZYME, INC.

CONSOLIDATED STATEMENTS OF OPERATIONS (UNAUDITED)

(Amounts in thousands except per share data)

	Three Months Ended December 31,						Year Ended December 31,
	2015			2014			2015			2014
Collaboration revenue	$	555		$	10,349		$	2,560		$	41,411
Operating expenses:
Research and development		16,819			20,505			111,209			75,595
General and administrative		6,017			4,935			23,900			20,866
Total operating expenses		22,836			25,440			135,109			96,461
Loss from operations		(22,281	)		(15,091	)		(132,549	)		(55,050	)
Other income, net		55			47			173			154
Loss before income taxes		(22,226	)		(15,044	)		(132,376	)		(54,896	)
Income tax (benefit) expense		—			(9	)		—			109
Net loss	$	(22,226	)	$	(15,035	)	$	(132,376	)	$	(55,005	)
Loss per share allocable to common stockholders:
Basic	$	(0.53	)	$	(0.44	)	$	(3.32	)	$	(1.67	)
Diluted	$	(0.53	)	$	(0.44	)	$	(3.32	)	$	(1.67	)
Weighted average shares outstanding:
Basic		41,725			34,273			39,839			33,027
Diluted		41,725			34,273			39,839			33,027

EX-99.2

Exhibit 99.2

Epizyme Unveils Corporate Strategy to Guide Efforts over Next Five Years

CAMBRIDGE, Mass. - March 9, 2016 - Epizyme, Inc., (NASDAQ:EPZM) a clinical stage biopharmaceutical company creating novel epigenetic therapies for patients with cancer, today announced its corporate vision and strategy through 2020. During the next five years, Epizyme will focus on four transformative activities:

• Transitioning to a commercial-stage organization through the global launch of tazemetostat in patients with non-Hodgkin lymphoma (NHL) and in patients with certain genetically defined solid tumors;

• Expanding the clinical program for tazemetostat to support its utilization in earlier lines of therapy, in combination regimens, and in at least five new tumor types;

• Growing the pipeline, with at least three new oncology product candidates in clinical development and a robust set of preclinical assets behind those; and,

• Further establishing the company’s leadership in the field of epigenetics and chromatin remodeling in oncology and beyond to enable long-term, sustainable business growth.

“Our entire company is driven by our vision of rewriting cancer therapy through targeted medicines for patients with unsolved diseases,” said Robert Bazemore, President & Chief Executive Officer. “Epizyme is committed to scientific excellence and pipeline innovation, which has allowed us to become the leading company in the discovery and development of epigenetic therapies in oncology. We have a clear set of priorities for 2016 designed to position us to deliver for patients and our stakeholders over the short, intermediate, and long term.”

Accelerating Tazemetostat Registration

Epizyme is focused on a number of critical activities intended to accelerate the development of tazemetostat, aiming to bring it patients who may benefit as quickly as possible. Tazemetostat has demonstrated the potential to treat both hematologic malignancies and solid tumors, which laid the foundation for its aggressive development plan. Epizyme is currently evaluating tazemetostat in multiple global registration-supporting clinical trials, including a phase 2 five-arm study in patients with NHL, a phase 2 three-arm study in adult patients with certain genetically defined solid tumors, and a phase 1 dose-escalation and expansion study in pediatric patients with genetically defined solid tumors. Planned activities include:

• Accelerating enrollment in the ongoing tazemetostat clinical trials through expansion into the U.S. and other countries, doubling the number of trial sites for the NHL study, and opening up to 45 trial sites for the genetically defined solid tumor studies.

• Assessing expedited paths to market, including opportunities to proceed without randomized clinical trials prior to market entry.

• Advancing clinical pharmacology studies to support registration and making manufacturing investments to prepare for approval.

• Strengthening company functions needed to support an expedited development and launch plan.

“We have a number of important clinical and data milestones on the horizon in 2016, including reporting interim findings from our five-arm phase 2 study of tazemetostat in patients with NHL in the middle of this year,” said Peter Ho, M.D., Ph.D., Chief Medical Officer. “The study is enrolling patients ahead of our expectations, and we look forward to assessing the data mid-year and with sufficient evidence of activity, we intend to move quickly into discussions with regulatory authorities to establish the path forward in each subtype of NHL.”

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Maximizing Tazemetostat Potential

In parallel to the accelerated development efforts for tazemetostat, Epizyme is working to expand the future utility of tazemetostat for a broad range of patients and physicians. Company activities to enable this include:

• Exploring the potential of tazemetostat in front-line NHL by initiating a phase 1b/2 clinical trial of tazemetostat in combination with the current standard of care, R-CHOP. This study is expected to initiate in the second quarter of 2016.

• Evaluating the additional potential of tazemetostat to enhance the clinical activity of immuno-oncology therapies by combining with an anti-PD1 or PDL-1 agent. Preclinical studies in the field show that EZH2 inhibitors, including tazemetostat, may potentially prime tumor cells and the microenvironment for synergy with immune checkpoint inhibitors. We plan to enter into a collaboration with a partner for this phase 1b combination study in the second quarter of 2016, and initiate the study in mid-year.

• Identifying new indications where tazemetostat may provide benefit and initiating clinical development in five new indications over the next five years. The first of these is BAP1 loss-of-function mesothelioma, which will enter clinical development in the third quarter of 2016.

• Acting rapidly to initiate proof-of-concept studies where there is strong preclinical evidence of tumor sensitivity to EZH2 inhibition in a clearly defined patient population.

• Continuing to invest in academic collaborations to evaluate the role of tazemetostat in new preclinical models.

Pipeline Growth and Scientific Leadership

Epizyme’s scientific expertise has led the company to expand its efforts to encompass histone methyltransferases (HMTs), as well as other chromatin modifying proteins (CMPs), which are implicated in multiple forms of hematological malignancies, solid tumors and other serious illnesses.

“Epizyme’s leadership in the areas of epigenetics and chromatin modification is the foundation of our long-term growth,” said Robert Copeland, Ph.D., President of Research and Chief Scientific Officer. “We have demonstrated that our discovery platform can rapidly identify important therapeutic targets and effectively create small molecule drug candidates against those targets. We believe we have many opportunities to replicate the success we’ve seen with tazemetostat as we go forward.”

To enable Epizyme’s long-term growth, the company plans to:

• Build on the significant anti-tumor potential of histone methyltransferase inhibition and chromatin modifying protein inhibition by investing in the continued expansion and utilization of its proprietary platform to develop a pipeline of HMT and other CMP inhibitors.

• Identify the most attractive targets for program development by utilizing CRISPR-based screening methodology to pinpoint targets where there is a clear signal for activity in specific tumor types.

• Develop small molecule inhibitors against five novel targets identified by Epizyme that the company has designated as priority programs. These efforts are underway along with preclinical drug discovery to evaluate their viability as future clinical programs.

• Initiate clinical development of at least three new small molecule oncology programs by 2020.

• Retain rights to its wholly owned programs in the U.S., as well in certain foreign areas as part of potential future partnerships.

• Evaluate potential new platform and program partnering opportunities both within and outside of oncology that might benefit from having a strategic partner, and provide additional downstream value-creation.

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Summary

Bazemore concluded: “We are confident that we will continue to achieve great things to bring value for patients and our stakeholders. We have significant assets in tazemetostat, our early-stage pipeline, and our scientific platform, and following our financing in January, we have the resources to maximize their value through key milestones. In short, we have a clear strategy and are in a strong position to accomplish our goal.”

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with non-Hodgkin lymphoma and for patients with certain genetically defined solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in dysregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-6438.

Additional information about tazemetostat, including clinical trial information, can be found here.

About Epizyme, Inc.

Epizyme, Inc. is a clinical-stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients. Epizyme has built a proprietary product platform that the Company uses to create small molecule inhibitors of chromatin modifying proteins (CMPs), such as histone methyltransferases or HMTs. CMPs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of CMPs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme’s targeted science seeks to match the right medicines with the right patients.

For more information, visit www.epizyme.com and connect with us on Twitter at @EpizymeRx.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for Epizyme, Inc. and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in drug discovery and the initiation of future clinical studies or expansion of ongoing clinical studies; availability and timing of data from ongoing clinical studies; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; development progress of the Company’s companion diagnostics, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and to achieve the goals set forth in this release; whether orphan drug designation will lead to orphan drug exclusivity or the other potential benefits of orphan drug designation for which we are eligible; other matters that could affect the availability or commercial

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potential of the Company’s therapeutic candidates or companion diagnostics or our ability to transition to a commercial-stage enterprise; and other factors discussed in the “Risk Factors” sections of the Company’s Form 10-K filed with the SEC on March 9, 2016 and in the Company’s other filings from time to time with the SEC. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof.

Investors:

Epizyme, Inc., Investor Relations and Corporate Communications

Rebecca Cohen, 617-401-0722

rcohen@epizyme.com

Media:

Scient Public Relations

Michael Lampe, 484-575-5040

michael@scientpr.com

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