Epizyme, Inc. (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering transformative therapies against novel epigenetic targets, today presented updated safety and activity data from the Phase 1b portion of its Phase 1b/3 confirmatory study evaluating the investigational use of TAZVERIK^® (tazemetostat), a first-in-class, oral, selective inhibitor of EZH2, in combination with rituximab + lenalidomide (R²) in patients with relapsed/refractory follicular lymphoma (FL) who have been treated with at least one prior systemic therapy, including patients who are rituximab-refractory and/or POD24, at the 2021 American Society of Hematology (ASH) Annual Meeting.

Updated data from the Phase 1b portion of the study reported today included 40 FL patients who had received treatment with tazemetostat and R² (400 mg [n=4], 600 mg [n=18], or 800 mg [n=18]) as of the September 29, 2021 data cut-off. The findings demonstrated that the safety profile of the tazemetostat and R² combination was consistent with the previously reported safety information in the prescribing information for both tazemetostat and R², respectively. Additionally, there was no clear dose response for treatment-emergent adverse events (TEAEs) or dose modifications. Thirty-five of the 40 patients were evaluable for tumor assessments as of the data cut off, with 32 patients responding to treatment. The activity findings showed an objective response rate of 91.4 percent (37.1 percent complete response rate and 54.3 percent partial response rate). The duration of response data continue to mature as the study is ongoing.

“The data presented today on the combination of rituximab, lenalidomide and tazemetostat, known as R² + tazemetostat, have shown promising responses in the second-line FL setting and the side effects observed to date have been consistent with lenalidomide-based combinations,” said Connie Lee Batlevi, MD PhD, medical oncologist with Memorial Sloan Kettering Cancer Center. “We are excited to start the randomized Phase 3 portion of the study, with the hope of developing a chemotherapy-free combination regimen for patients with follicular lymphoma.”

SYMPHONY-1 (EZH-302) is an international, multicenter, randomized, double-blind, active-controlled, 3-stage, biomarker-enriched, confirmatory Phase 1b/3 study, which is designed to evaluate the safety and efficacy of tazemetostat in combination with R² in patients with relapsed or refractory FL after at least one prior line of therapy. The Phase 1b portion of the study is designed to determine the recommended Phase 3 dose, activity, and safety of tazemetostat and R². In addition to the safety run-in analysis, the study also assessed the pharmacokinetics and continues to assess clinical activity of tazemetostat when administered in combination with R².

The Phase 1b safety run-in component evaluated tazemetostat at three dose levels (400 mg, 600 mg, and 800 mg orally twice daily) in 28-day cycles with standard-dose R² using a 3 + 3 design. Rituximab was administered at 375 mg/m² intravenously on days 1, 8, 15 and 22 of cycle 1, then on day 1 of cycles 2 to 5. Lenalidomide was administered at 20 mg (creatinine clearance ≥60 mL/min) or 10 mg (if creatinine clearance <60 mL/min) orally once daily on days 1 to 21 every 28 days for 12 cycles. In the Phase 3 component, approximately 500 patients will be randomly assigned to receive the RP3D of tazemetostat + R² or placebo + R². The study will also include a maintenance arm with tazemetostat or placebo following the first year of treatment with tazemetostat + R² or placebo + R².

Treatment with tazemetostat and R² was generally well tolerated. Grade 3/4 TEAEs were observed in 17 (42.5%) patients; the most common grade 3/4 TEAE (≥10%) was neutrophil count decrease/neutropenia (15.0.%) Ten patients (25.0%) reported a total of 16 SAEs (serious adverse events). The only SAE reported in >1 patient was COVID-19, reported in 2 patients; all other SAEs were reported in 1 patient each.

A table of the activity findings as of the data cut off are below:

“We are encouraged to share progress of our tazemetostat program in follicular lymphoma with the cancer community, as we believe these data support the potential tazemetostat may play as a backbone of therapy in combination with current standards of care for patients living with the disease. We will continue to monitor these patients and we look forward to sharing follow-up data as they mature over time,” said Dr. Shefali Agarwal, Executive Vice President and Chief Medical and Development Officer at Epizyme. “At Epizyme, we are committed to advancing the follicular lymphoma treatment landscape for patients, the healthcare teams who treat them, and the families who support them.”

In addition to the SYMPHONY-1 presentation (Abstract #2207), two additional tazemetostat studies are being presented during the ASH Annual Meeting. The first is a trial-in-progress/study design presentation for SYMPHONY-2 (Abstract #3541), a multi-center, open-label, single-arm, Phase 2 study of tazemetostat in combination with rituximab for the treatment of relapsed or refractory FL. The trial is actively enrolling patients across 18 sites in the United States. The second presentation (Abstract #1183) focuses on the analysis of the molecular and genetic characterization of patients treated with tazemetostat to better understand the drivers of response to treatment.

About TAZVERIK^® (tazemetostat)

TAZVERIK is a methyltransferase inhibitor indicated for the treatment of:

• Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
• Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
• Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

View the U.S. Full Prescribing Information here: Epizyme.com

About Epizyme, Inc.

Epizyme, Inc. is a fully integrated, commercial-stage biopharmaceutical company committed to its mission of rewriting treatment for cancer through novel epigenetic medicines. The Company is focused on creating medicines that are targeted at specific causes of diseases, that are orally administered, tolerable, easy to take and based on a deep understanding of the patients that may benefit from them. The Company aspires to change the standard-of-care for patients and physicians by developing medicines with fundamentally new mechanisms of action. For more information, visit www.epizyme.com.

Revlimid + Rituximab (R²) is a registered trademark of Celgene Corporation, a Bristol Myers Squibb company.

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: whether commercial sales of TAZVERIK for epithelioid sarcoma and follicular lymphoma in the approved indications will be successful; whether tazemetostat will receive marketing approval for epithelioid sarcoma or follicular lymphoma in other jurisdictions, full approval in the United States or approval in any other indication; whether results from preclinical studies or earlier clinical studies will be predictive of the results of future trials, such as the ongoing confirmatory trials of TAZVERIK; whether interim results of clinical studies will be predictive of the final results of the studies; whether results from clinical studies will warrant meetings with regulatory authorities, submissions for regulatory approval or review by governmental authorities under the accelerated approval process; whether the company will receive regulatory approvals, including accelerated approval, to conduct trials or to market products; the impact of the COVID-19 pandemic on the company’s business, results of operations and financial condition; whether the company's cash resources will be sufficient to fund the company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availability or commercial success of tazemetostat; and other factors discussed in the “Risk Factors” section of the company’s most recent Form 10-K or Form 10-Q filed with the SEC 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 and should not be relied upon as representing the company’s views as of any date subsequent to 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.

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