On August 9, 2022 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported financial results for the second quarter ended June 30, 2022 and provided a business update (Press release, Protara Therapeutics, AUG 9, 2022, View Source [SID1234617940]).

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"We are pleased with the continued progress of the ADVANCED-1 study of TARA-002 in non-muscle invasive bladder cancer (NMIBC)," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We remain committed to unlocking the full potential of TARA-002 in this underserved patient population, and look forward to sharing our progress in the coming quarters. In parallel, we are keenly focused on finalizing the design of a clinical trial of TARA-002 in patients with lymphatic malformations (LMs), a rare pediatric indication for which we believe TARA-002 has the potential to serve as a much-needed intervention."

Recent Highlights

TARA-002 in NMIBC

Enrollment is progressing in the Company’s Phase 1 ADVANCED-1 clinical trial evaluating TARA-002, an investigational cell-based immunopotentiator, for the treatment of NMIBC.
In June 2022, a Trials in Progress poster related to the ADVANCED-1 Phase 1 trial was featured at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
TARA-002 in LMs

Protara continues to engage with the Vaccines and Related Products Division of the U.S. Food and Drug Administration (FDA) regarding a development path for TARA-002 in LMs. Following receipt of preliminary guidance from the FDA and in consultation with the Company’s external scientific advisory board, Protara plans to initiate a Phase 2 clinical trial of TARA-002 in LMs, subject to alignment with the agency on a trial protocol.
Protara announced that the European Medicines Agency (EMA) recently granted orphan drug designation (ODD) to TARA-002 for the treatment of LMs.
In May 2022, the Company announced results of a retrospective analysis of OK-432, the originator compound for TARA-002, for the treatment of LMs. Results from the analysis, which were presented during a poster presentation at the International Society for the Study of Vascular Anomalies World Congress 2022, showed that OK-432 met the primary efficacy endpoint of clinical success (defined as complete [90%-100%] or substantial [60%-89%] reduction in LM volume measured radiographically) in treating LMs and demonstrated a favorable safety profile.
IV Choline Chloride in Intestinal Failure Associated Liver Disease (IFALD)

The Company’s prospective study to enhance understanding of the incidence of IFALD in patients dependent on parenteral nutrition remains ongoing. Protara expects to use results from the prospective study, as well as its previously completed retrospective study, to inform next steps for the IV Choline Chloride development program.
In April 2022, the U.S. Patent and Trademark Office issued to the Company a patent claiming a sterile aqueous choline salt composition with a term expiring in 2041.
Second Quarter 2022 Financial Results

As of June 30, 2022, cash, cash equivalents and marketable debt securities were $112.8 million. The Company expects its current cash and cash equivalents will be sufficient to fund its planned operations into mid-2024.
Research and development (R&D) expenses for the second quarter of 2022 decreased to $3.1 million from $5.9 million during the second quarter of 2021. The decreased R&D expenses were primarily due to decreases in manufacturing expenses associated with TARA-002.
General and administrative expenses for the second quarter of 2022 decreased to $5.6 million from $6.9 million for the prior year period. The decrease was primarily due to decreases in stock-based compensation.
For the second quarter of 2022, Protara reported a net loss of $8.5 million, or $0.80 per share, compared with a net loss of $12.8 million, or $1.14 per share, for the same period in 2021. Net loss for the second quarter of 2022 included approximately $3.8 million of stock-based compensation expenses.
About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and LMs for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan and Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully demonstrated manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a strong immune cascade. Neutrophils, monocytes and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor are secreted by immune cells to induce a strong local inflammatory reaction and destroy the abnormal cells.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

About Lymphatic Malformations (LMs)

LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of 3 years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

About IV Choline Chloride and Intestinal Failure-associated Liver Disease (IFALD)

IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN) who have IFALD. Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel/liver transplant. If approved, IV Choline Chloride would be the first approved therapy for IFALD. It has been granted Orphan Drug Designations (ODDs) by the FDA for the treatment of IFALD and the prevention of choline deficiency in PN patients.

On August 9, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported the publication of preclinical study results demonstrating the successful generation, durable anti-tumor response, and functional persistence of TCR-CAR+ iPSC-derived CD8αβ T cells from induced pluripotent stem cells (iPSCs) (Press release, Fate Therapeutics, AUG 9, 2022, View Source [SID1234617939]). The CD8αβ T cells were derived from a single engineered iPSC integrating a novel chimeric antigen receptor (CAR) transgene into the T-cell receptor alpha constant (TRAC) locus, ensuring complete bi-allelic disruption of T-cell receptor (TCR) expression and promoting uniform CAR expression. The discoveries were made under a multi-year research collaboration between the Company and Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, and were published this week in Nature Biomedical Engineering.

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"Scientists have previously differentiated induced pluripotent stem cells to form CAR T cells, however, it was observed that premature αβTCR or constitutive CAR expression resulted in the derivation of innate-like T cells that do not acquire the phenotype nor exhibit the function of conventional CD8αβ T cells," said Dr. Sadelain. "Our published findings are the first to show the generation of iPSC-derived CD8αβ CAR T cells lacking a TCR, where timed and calibrated expression of the CAR in place of the TCR successfully drove T-cell maturation and promoted the acquisition of a transcriptional and functional profile more closely resembling that of natural CD8αβ T cells."

The mass production of TCR-CAR+ CD8αβ T cells from master engineered iPSC lines is a promising approach for development of off-the-shelf, cell-based cancer immunotherapies. Through a systematic assessment of factors that affect T-cell lineage commitment and induce adaptive T-cell formation, the researchers discovered that integrating the CAR construct into the TRAC locus delayed its expression and drove T-cell lineage commitment, and that regulation of CAR signaling strength promoted the generation of CD4+CD8+ double-positive cells mimicking thymic development in the absence of a TCR. Subsequent stimulation of the CAR matured the double-positive population into single-positive CD8αβ T cells with a phenotype highly correlated with peripheral blood CD8αβ effector T cells and distinct from γδ T cells and natural killer cells. Preclinical studies showed that iPSC-derived TCR-CAR+ CD8αβ T cells were able to repeatedly lyse tumor cells in vitro and durably control leukemia in vivo, with persistence in the bone marrow, spleen, and blood, in a systemic NALM6 leukemia model.

"These published findings continue to support our unique ability to generate TCR-CAR+ CD8αβ T cells from master engineered iPSC lines that exhibit a phenotypic profile and anti-tumor activity comparable to healthy donor-derived peripheral blood CAR T cells in preclinical model systems," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We believe our off-the-shelf, iPSC-derived CAR T cell programs overcome the numerous challenges associated with the manufacture, consistency, and reach of autologous and allogeneic CAR T cells, and we look forward to sharing initial clinical data from our landmark Phase 1 study of FT819 later this year."

The Company is conducting a multicenter Phase 1 study of FT819, the first T-cell therapy manufactured from a clonal master iPSC line to undergo clinical investigation. The product candidate’s clonal engineered master iPSC line is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct integrated into the TRAC locus, ensuring complete bi-allelic disruption of TCR expression to prevent graft-versus-host disease and promoting uniform CAR expression for enhanced anti-tumor activity. Dose escalation is currently ongoing in single-dose and multi-dose escalation cohorts for relapsed / refractory B-cell malignancies.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics has licensed intellectual property from MSK on which Dr. Sadelain is an inventor. As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

On August 9, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company focused on developing innovative and affordable oncology medicines to improve treatment outcomes and access for patients worldwide, reported that the global Phase 3 RATIONALE 301 trial with tislelizumab met its primary endpoint of non-inferior Overall Survival (OS) versus sorafenib as a first-line treatment in adult patients with unresectable hepatocellular carcinoma (HCC) (Press release, BeiGene, AUG 9, 2022, View Source [SID1234617938]). The safety profile for tislelizumab was consistent with previous studies and no new safety signals were reported. More than 600 patients in the U.S., Europe, and Asia participated in the study.

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HCC is the sixth most common type of cancer worldwide, accounting for more than 900,000 new cases in 2020i, and despite improvements in screening, surveillance rules, and imaging, more than two-thirds of patients with HCC present with advanced disease at diagnosisii.

"Patients with unresectable HCC face a devastating prognosis, with a median life expectancy of one year. Currently there are few treatment options if patients cannot tolerate TKI therapy or if their condition progresses," said Mark Lanasa M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "We are encouraged by the outcome of the final analysis of RATIONALE 301 and look forward to sharing the full safety and efficacy results at an upcoming medical conference."

RATIONALE 301 (NCT03412773) is a global, Phase 3, randomized, open-label study of tislelizumab compared with sorafenib as a first-line treatment in adult patients with unresectable HCC. The primary endpoint of the study is non-inferiority of OS between the two treatment groups. The key secondary endpoint is Overall Response Rate, as assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Other secondary endpoints include other efficacy assessments such as Progression-Free Survival, Durability of Response, and Time to Progression per BIRC, as well as measures of health-related quality of life, and safety and tolerability.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The global tislelizumab clinical development program includes more than 11,000 subjects enrolled to-date in 30 countries and regions. BeiGene has initiated or completed 22 registration-enabling clinical trials. More information on the clinical trial program for tislelizumab can be found here.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 3,300 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the U.S., China, the European Union, Great Britain, Canada, Australia, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody, tislelizumab, as well as the PARP inhibitor, pamiparib, in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021, BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody, tislelizumab, in North America, Europe, and Japan. Building upon this productive collaboration, BeiGene and Novartis announced an option, collaboration, and license agreement in December 2021 for BeiGene’s TIGIT inhibitor, ociperlimab, that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China.

On August 9, 2022 Sensei Biotherapeutics, Inc. (NASDAQ: SNSE), an immuno-oncology company focused on the discovery and development of next generation therapeutics for cancer, reported financial results for the second quarter ended June 30, 2022 and provided recent business updates (Press release, Sensei Biotherapeutics, AUG 9, 2022, View Source [SID1234617937]).

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"This has been a productive and rewarding time as we progress our TMAb platform in pursuit of potentially revolutionary therapies for cancer patients that address the challenge of resistance to checkpoint blockade. Our TMAb platform is designed to generate conditionally active antibodies with enhanced tumor specificity. Notably, we have been pleased with the breakthrough preclinical data on SNS-101, our anti-VISTA antibody, which we believe support our hypothesis that an antibody binding selectively in low-pH environments has the potential to effectively inhibit tumor growth across a range of indications without on-target, off-tumor effects," said John Celebi, president and chief executive officer of Sensei Biotherapeutics. "We have also achieved a milestone with the generation of pH-sensitive antibodies for a second program targeting VSIG4. With cash runway into 2025, we believe we are well positioned to achieve near-term milestones, including the anticipated submission of an Investigational New Drug application for SNS-101 in the first half of 2023."

Highlights and Milestones

SNS-101

Sensei continues preclinical studies to evaluate SNS-101, a monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation), which is implicated in resistance to PD-1/PD-L1 therapy and correlates with poor survival across numerous cancers. Recent updates for SNS-101 include:

Sensei has received pre-IND meeting feedback from the U.S. Food and Drug Administration and expects to submit an IND in the first half of 2023.
The Company plans to present new data from a single dose pharmacokinetic (PK) and toxicology model in non-human primates in the third quarter of 2022.
Sensei will present new preclinical cytokine release data comparing SNS-101 to a non-pH-selective anti-VISTA antibody at the Sixth CRI-ENCI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science Into Survival, being held September 28 – October 1, 2022 in New York City.
In April 2022, Sensei presented preclinical data demonstrating that SNS-101 had a favorable pharmacokinetic profile in a single-dose mouse model. Notably, SNS-101 demonstrated a long mean residence time in the blood, indicating a lack of significant target-mediated drug disposition and clearance in non-malignant tissues.
Also in April 2022, preclinical data in an MC38 syngeneic tumor model in human VISTA knock-in mice demonstrated synergistic anti-tumor activity in combination with anti-PD-1 therapy.
SNS-101 has demonstrated excellent manufacturing productivity to date and GMP manufacturing timelines remain on track.
SNS-102

Sensei is advancing several pH-sensitive antibodies targeting VSIG4 (V-Set and Immunoglobulin Domain Containing 4). VSIG4 is a B7-family related protein that is a potent inhibitor of T cell activity and is frequently overexpressed on tumor-associated macrophages.

Sensei remains on track to select a product candidate and initiate IND-enabling studies in 2023.
Sensei has identified eight parental pH-sensitive antibodies targeting VSIG4 for further optimization.
The Company aims to develop a pH-dependent, high-affinity inhibitory antibody which selectively binds VSIG4 in the tumor microenvironment versus normal tissue.
SNS-103

Sensei remains on track to select a product candidate in 2023 for SNS-103, a monoclonal antibody targeting ENTPDase1 (ecto-nucleoside triphosphate diphosphohydrolase-1, also known as CD39), the upstream, rate-limiting enzyme that leads to the breakdown of extracellular ATP.
Second Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $123.7 million as of June 30, 2022, as compared to $147.6 million as of December 31, 2021. Sensei expects its current cash balance to fund operations into the first quarter of 2025.

Research and Development (R&D) Expenses: R&D expenses were $6.4 million for the quarter ended June 30, 2022, compared to $5.9 million for the quarter ended June 30, 2021. The increase in R&D expenses was primarily attributable to increased headcount and inflation on supplies to support Sensei’s research, development, and manufacturing activities.

General and Administrative (G&A) Expenses: G&A expenses were $4.3 million for the quarter ended June 30, 2022, compared to $3.9 million for the quarter ended June 30, 2021, with the increase mainly driven by franchise tax increases.

Net Loss: Net loss was $10.5 million for the quarter ended June 30, 2022, compared to $9.8 million for the quarter ended June 30, 2021.

On August 9, 2022 Epizyme (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering transformative therapies for cancer patients against novel epigenetic targets, reported second quarter 2022 financial results and provided a business update (Press release, Epizyme, AUG 9, 2022, View Source [SID1234617936]).

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"I am pleased with the progress we made as an organization in the second quarter. In addition to the growth of TAZVERIK net product revenue, we are continuing to advance several of our tazemetostat clinical studies, and we also dosed the first patient in the Phase 1 portion of our SET-101 study with our SETD2 inhibitor candidate. For TAZVERIK, we saw double-digit quarter-over-quarter growth in total end user demand and continued improvement in key metrics suggesting greater prescriber understanding and adoption of TAZVERIK, consistent with our label," said Grant Bogle, President and Chief Executive Officer. "Most importantly, the quarter brought with it news of Epizyme’s decision to enter into a definitive merger agreement with Ipsen. Through this merger, we expect continued investment in our epigenetic pipeline for the benefit of patients."

Recent Progress

TAZVERIK commercial progress:
TAZVERIK generated net product revenue of $11.0 million for the second quarter of 2022, including $8.9 million related to TAZVERIK commercial net sales, representing an increase of approximately 10% when compared to $8.1 million in the first quarter of 2022. Sales of TAZVERIK commercial product for third-party pharmaceutical company use in clinical trials was $2.1 million in the second quarter of 2022.
Total end user demand grew 17% in the second quarter of 2022 when compared to the first quarter of 2022, which includes commercial demand and free goods supplied through Epizyme’s patient assistance program. Commercial demand grew 8% when compared to the first quarter of 2022.
The amount of free goods supplied to patients through the patient assistance program was approximately 22% of total end user demand for the second quarter of 2022 as compared to approximately 15% in the first quarter of 2022. The free goods level in the second quarter of 2022 was consistent with the second quarter of 2021.
First patient dosed in the Phase 1 portion of the SET-101 Phase 1/1b study of EZM0414 in multiple myeloma (MM): Dosing of the first patient was recently completed in SET-101, the Phase 1/1b study of EZM0414, Epizyme’s novel, first-in-class, oral SETD2 inhibitor candidate, which is being developed for the treatment of adult patients with relapsed/refractory (R/R) MM and R/R diffuse large B-Cell lymphoma (DLBCL).
Merger with Ipsen: In June, Ipsen and Epizyme executed a definitive merger agreement under which Ipsen has initiated a tender offer to acquire all outstanding shares of Epizyme for $1.45 per share, plus a contingent value right (CVR) of $1.00 per share. The merger is expected to close by the end of the third quarter of 2022 (subject to the satisfaction of all closing conditions). Additional details can be found in the announcement press release as well as in Epizyme’s recent SEC filings.
Tazemetostat Clinical Updates

Presented updates from SYMPHONY-1 tazemetostat + R2 combination study in R/R follicular lymphoma (FL) at ASCO (Free ASCO Whitepaper) 2022: In June, Epizyme presented updated safety and activity data from the Phase 1b portion of the SYMPHONY-1 study at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The Phase 1b portion of the study showed continued improvement in both objective and complete response rates, as well as response data for a subgroup of patients who are rituximab-refractory and/or relapsed within 24 months (POD24). The study is open for enrollment globally, and Epizyme anticipates providing longer term follow-up data from the Phase 1b portion of the study at a medical conference later this year.
CELLO-1 Phase 1b/2 study has completed enrollment; updated safety run-in data expected later in 2022: The Phase 2 randomized portion of the CELLO-1 study (EZH-1101), which is evaluating tazemetostat plus enzalutamide compared to enzalutamide monotherapy in metastatic castration-resistant prostate cancer patients, has completed enrollment with a total of 80 patients. Epizyme expects to present updated data from the safety run-in portion later in 2022.
LYSA Phase 1/2 combination study has completed enrollment; top-line results expected later in 2022: Enrollment in both the DLBCL and FL arms of this study is complete. The Lymphoma Study Association (LYSA) study is a Phase 1/2 combination study of tazemetostat with R-CHOP in high-risk, front-line FL and DLBCL patients. Epizyme, in collaboration with LYSA, anticipates sharing top-line results from the Phase 2 portion of the study later in 2022.
ARIA hematological basket study (EZH-1501) open for enrollment: The Company continues to screen patients for ARIA, the Phase 1b/2 basket study evaluating tazemetostat combinations in patients with hematological malignancies.
Updates on tazemetostat development in China: On August 1, Epizyme’s collaboration partner, HUTCHMED, announced the initiation of a bridging study of tazemetostat in China with the first patient dosed on July 29, 2022. This multicenter, open-label, Phase 2 study will evaluate the efficacy, safety, and pharmacokinetics of tazemetostat for the treatment of patients with R/R FL.
Second Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $144.4 million as of June 30, 2022, compared to $199.7 million as of March 31, 2022.
Revenue: Total revenue was $27.5 million for the second quarter of 2022, an increase of 112% vs. $13.0 million for the second quarter of 2021. Total revenue for the second quarter of 2022 consisted of $11.0 million of net product revenue and $16.5 million of collaboration and other revenue. The net product revenue was comprised of $8.9 million in commercial net sales of TAZVERIK and $2.1 million of TAZVERIK related to the sale of commercial product by one of the Company’s customers to a third-party pharmaceutical company for use in its clinical trials. Net product revenue of TAZVERIK in the U.S. in the second quarter of 2022 increased 38% vs. $8.0 million for the second quarter of 2021. The $16.5 million of collaboration and other revenue was recognized under our license agreement with HUTCHMED, $11.8 million of which related to the recognition of revenue that had previously been deferred.
Operating Expenses: Total GAAP operating expenses were $57.3 million for the second quarter of 2022, a decrease of 20% vs. $71.2 million for the second quarter of 2021, reflecting focused efforts on streamlining operations. Total non-GAAP adjusted operating expenses were $51.6 million for the second quarter of 2022, compared to $63.2 million for the second quarter of 2021.
R&D expenses: GAAP R&D expenses were $28.1 million for the second quarter of 2022, a 19% decrease compared to $34.9 million for the second quarter of 2021. Non-GAAP adjusted R&D expenses were $26.5 million for the second quarter of 2022, compared to $32.7 million for the second quarter of 2021.
SG&A expenses: GAAP SG&A expenses were $24.1 million for the second quarter of 2022, compared to $33.9 million for the second quarter of 2021, representing a 29% decrease following the previously announced operating expense and workforce reductions. Non-GAAP adjusted SG&A expenses were $21.0 million for the second quarter of 2022, compared to $29.1 million for the second quarter of 2021.
Net Loss (GAAP): Net loss attributable to common stockholders was $35.7 million, or $0.21 per share, for the second quarter of 2022, compared to $64.4 million, or $0.63 per share, for the second quarter of 2021.
A reconciliation of non-GAAP adjusted financial measures directly comparable to GAAP financial measures is presented in the table attached to this press release.
About Non-GAAP Financial Measures

In addition to financial information prepared in accordance with the U.S. generally accepted accounting principles (GAAP), this press release includes the following non-GAAP financial measures: total non-GAAP adjusted operating expenses on a historical basis, non-GAAP adjusted R&D expenses on a historical basis and non-GAAP adjusted SG&A expenses on a historical basis. Epizyme derives these non-GAAP financial measures by excluding certain expenses and other items from the respective GAAP financial measure that is most directly comparable to each non-GAAP financial measure. Specifically, the non-GAAP financial measures exclude stock-based compensation expense and depreciation and amortization of intangibles. The Company’s management believes that these non-GAAP financial measures are useful to both management and investors in analyzing its ongoing business and operating performance. Management does not intend the presentation of these non-GAAP financial measures to be considered in isolation or as a substitute for results prepared in accordance with GAAP, but as a complement to provide greater transparency. In addition, these non-GAAP financial measures may differ from similarly named measures used by other companies.

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 is contingent upon verification and description of clinical benefit in confirmatory studies.

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 EZM0414

EZM0414 is a potent selective, oral, small molecule, investigational drug agent that inhibits the histone methyltransferase, SETD2, which plays a role in oncogenesis. SETD2 methylates histone as well as non-histone proteins, and this activity is involved in several key biological processes including transcriptional regulation, RNA splicing, and DNA damage repair. Based on the preclinical data on SETD2 inhibition by EZM0414 in multiple settings, including high risk t(4;14) multiple myeloma (MM) and in other B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL), the Company is conducting SET-101, a Phase 1/1b study of EZM0414, for the treatment of adult patients with relapsed or refractory MM and DLBCL.