On June 15, 2018 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage company developing novel epigenetic therapies, announced positive interim data from an ongoing Phase 2 study of its lead candidate tazemetostat, a potent, selective, orally available EZH2 inhibitor, as a monotherapy for patients with relapsed or refractory follicular lymphoma (FL) (Press release, Epizyme, JUN 15, 2018, View Source [SID1234527346]). The data, presented today at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, show that tazemetostat demonstrated meaningful clinical activity and was generally well tolerated in these heavily pre-treated patients.

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Interim data as of May 1, 2018 included 82 evaluable patients across two cohorts, prospectively assigned by EZH2 status. In the EZH2 activating mutation cohort (n=28), an objective response rate (ORR) of 71 percent was observed; 11 percent of patients achieved a complete response (CR), and 61 percent achieved a partial response (PR). Twenty-nine percent achieved stable disease (SD) as best response; of those, 21 percent are still on study with the potential to respond. All patients in this cohort experienced reduction in tumor burden, and no patients experienced progressive disease (PD) as best response. At the time of this analysis, the median progression-free survival (PFS) was 49 weeks and the median duration of response (DOR) was 32 weeks, and both endpoints continue to mature.

In the fully-enrolled cohort of FL patients with wild-type (WT) EZH2 (n=54), the ORR was 33 percent; six percent achieved a CR, and 28 percent achieved a PR. An additional 31 percent of patients achieved SD as best response, including one patient who is still receiving treatment. At the time of this analysis, the median PFS was 30 weeks and median DOR was 76 weeks. The median DOR figure continues to mature, with more than half of the responders still on therapy.

"I am impressed by the sustained clinical activity and the good tolerability of tazemetostat in this heavily pre-treated patient population. This is important for patients with relapsed or refractory follicular lymphoma, as both the response rates and durations of response usually tend to decrease with each successive line of treatment," said Gilles Salles, M.D., Ph.D., at the University Hospital of Lyon France, and president of the Lymphoma Study Association (LYSA) cooperative group. "I believe tazemetostat has the potential to fill a significant unmet need for these patients and continued investigation of tazemetostat as single agent or in combination with other agents is warranted."

*median not yet reached; data continue to mature
†includes discontinued patients with response ongoing at time of discontinuation
This ongoing global, multi-center Phase 2 study is assessing the safety and efficacy of 800 mg of tazemetostat, administered orally twice daily, in adult patients who had received at least two prior therapies. The two cohorts represented in the interim assessment included patients with an EZH2 activating mutation or those with WT EZH2. The primary endpoint is ORR, defined as CR and PR. Secondary endpoints include PFS, DOR and safety/tolerability.

Tazemetostat was generally well tolerated in this study. Interim safety results at the time of this analysis show only six percent of FL patients discontinued treatment due to treatment-related adverse events (AEs). AEs of Grade 3 or higher were reported across 17 percent of patients, the most frequent of which included thrombocytopenia, anemia, asthenia and fatigue.

"Today’s interim update underscores our belief that tazemetostat may be an important therapeutic candidate in relapsed or refractory follicular lymphoma and may play a key role in the treatment landscape, regardless of mutational status," said Robert Bazemore, president and chief executive officer of Epizyme. "The patients who are participating in this study deserve our gratitude. At Epizyme, we are dedicated to continuing our work with the global investigator community to resolve the partial clinical hold and complete enrollment in this study, in an effort to bring tazemetostat to people living with follicular lymphoma."

Investor Conference Call Reminder
Epizyme will host an investor conference call and webcast today at 8:30 a.m. EDT to discuss interim clinical activity and tolerability data from adult patients with relapsed or refractory FL who are receiving tazemetostat in the company’s ongoing Phase 2 study. To participate in the call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 4869637. A live webcast will be available in the investor section of the company’s website at www.epizyme.com. The webcast will be archived on the website for 60 days.

About Follicular Lymphoma (FL)
An estimated 40,000 people in the U.S. and EU5 are treated for FL each year. FL is an incurable and deadly form of cancer that is most frequently treated with multiple lines of systemic chemotherapy. As a result, there remains a significant need for an effective, convenient and tolerable medicine that patients can take for long durations.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing Phase 1 and 2 programs in certain molecularly defined solid tumors, including epithelioid sarcoma (ES) and other INI1-negative tumors; both follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma (NHL); mesothelioma and combination studies in DLBCL

On June 15, 2018 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported positive long-term outcomes including durable remissions and encouraging safety findings from two Phase 2 studies of tab-cel (tabelecleucel), Atara’s most advanced off-the-shelf T-cell immunotherapy (Press release, Atara Biotherapeutics, JUN 15, 2018, View Source [SID1234527345]). These single center, open-label studies enrolled patients with Epstein-Barr virus associated post-transplant lymphoproliferative disorder (EBV+ PTLD) following allogeneic hematopoietic cell transplant (HCT) or solid organ transplant (SOT) who failed first-line therapy. Atara and its collaborating investigators at Memorial Sloan Kettering Cancer Center (MSK) reported the Phase 2 results in a poster presentation at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), being held in Stockholm, Sweden, June 14-17, 2018.

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"Tab-cel demonstrated durable remissions and an encouraging safety profile after substantial follow-up time for patients with EBV-associated lymphomas who have limited treatment options and often experience poor outcomes," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "No patient who responded to tab‑cel in these studies died of EBV+ PTLD after treatment with this off-the-shelf, allogeneic T-cell immunotherapy. We are progressing two tab-cel Phase 3 clinical studies to confirm the Phase 2 findings in patients with EBV+ PTLD following HCT and SOT who have failed first line therapy."

Overall Survival (OS)

One- and three-year OS for tab-cel treated patients with EBV+ PTLD following HCT who failed rituximab (n=35) was 68% and 55%, respectively. Median OS was not reached after 23.3 months of follow-up in this patient group. The expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16 to 56 days.1,2
In patients with EBV+ PTLD following SOT who failed rituximab, the one- and three-year OS after treatment with tab-cel (n=14) was 64% and 43%, respectively. Median survival in this patient group was 21.3 months, which compares favorably to the expected 12- to 13-month median survival in patients with EBV+ PTLD following SOT who fail to achieve a complete response to first-line therapy with single-agent rituximab.3
None of the EBV+ PTLD patients who had complete or partial responses (CR or PR) after treatment with tab-cel died of EBV+ PTLD. Two-year OS for these responding patients was 83% and 86% following HCT (n=24) and SOT (n=7), respectively.
Overall response rates (ORR)

Tab-cel was associated with durable ORR (CR plus PR) of 69% and 50% in patients with EBV+ PTLD following HCT and SOT, respectively, who have failed rituximab.
Safety

Tab-cel was generally well-tolerated. Safety findings were consistent with previous reports of these studies with no new signals noted with additional follow up.
Atara anticipates results from the first tab-cel Phase 3 study and submission of an EU conditional marketing authorization application in the first half of 2019.

Details for the poster presentation at the EHA (Free EHA Whitepaper) Congress are as follows:

Abstract PF401: Long Term Outcomes of Tabelecleucel (Allogeneic Third-Party EBV-Targeted Cytotoxic T Lymphocytes) for Rituximab-Refractory Post-Transplant EBV+ Lymphomas: A Single Center Experience
Session Title: Gene therapy, cellular immunotherapy and vaccination – Clinical
Presentation Date & Time: Friday, June 15; 5:30 p.m. to 7:00 p.m. CEST
Authors:Susan Prockop, Ekaterina Doubrovina, Amy Feng, Guenther Koehne, Parastoo Dahi, Esperanza Papadopoulos, Craig Sauter, Stephanie Suser, Willis Navarro, Akshay Sudhindra, Richard O’Reilly
Location: Poster area, Älvsjö building, Stockholm International Fairs and Congress Centre (Stockholmsmässan)

About EBV+ PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas, and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) represents a life-threatening condition. Median overall survival in patients with EBV+ PTLD following HCT who have failed rituximab-based first line therapy is 16-56 days. In EBV+ PTLD following SOT, patients failing rituximab experience increased chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+ PTLD following SOT is 36% and 0%, respectively.

About tab-cel (tabelecleucel; formerly known as ATA129)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. Atara also received positive regulatory feedback from Health Canada in September 2017 supporting the submission of tab-cel for an expedited approval pathway. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara is planning a Phase 1/2 study in NPC. Tab-cel is also available to eligible patients with EBV-associated hematologic and solid tumors through an ongoing multicenter expanded access protocol clinical study, positive interim results of which were presented in December 2017 at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

On June 15, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG-806, a highly potent pan-FLT3/pan-BTK inhibitor, exhibits a distinct mechanism of action and greater potency on patient-derived hematologic cancer cells than ibrutinib, a BTK inhibitor approved for the treatment of certain hematologic malignancies (Press release, Aptose Biosciences, JUN 15, 2018, View Source;p=RssLanding&cat=news&id=2354764 [SID1234527344]). The data were presented in a poster on Friday, June 15, at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), taking place June 14-17, 2018 in Stockholm, Sweden.

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CG-806 is an oral small molecule pan-FLT3/pan-BTK inhibitor being developed by Aptose for acute myeloid leukemia (AML) and B-cell malignancies. It is a highly potent, reversible (non-covalent) inhibitor of the wild type and mutant forms of the Bruton’s tyrosine kinase (BTK) enzymes. Ibrutinib, a covalent BTK inhibitor approved for chronic lymphocytic leukemia (CLL) and certain B-cell malignancies, is limited by acquired resistance, as well as refractory disease and tolerance challenges.

The poster, entitled CG’806, A NON-COVALENT PAN-FLT3/PAN-BTK INHIBITOR, EXHIBITS UNIQUE BINDING TO WILD TYPE AND C481S MUTANT BTK AND GREATER POTENCY THAN IBRUTINIB AGAINST MALIGNANT B CELLS, compared CG-806 and ibrutinib with respect to BTK binding mode, kinase inhibition profiles and cytotoxic activity against patient-derived and cultured malignant B-cells. Kinase profiling revealed that CG-806 most potently inhibits kinases from the BTK, FLT3, TRK, and AURK clusters and had similar potency against BTK-WT (IC50 = 8.4 nM) and C481S mutant (IC50 = 2.5 nM), as opposed to ibrutinib that was >60-fold less potent against the C481S mutant. CG-806 did not inhibit TEC, EGFR or ERBB2/4, which are related to ibrutinib’s side effects; CG-806 also demonstrated a favorable safety profile. CG-806 inhibited cell proliferation 2-6,000 times more potently than ibrutinib in 14 tested malignant B-cell lines; it also had greater activity on primary CLL samples than ibrutinib.

"A safe and potent agent that inhibits all forms of BTK and other key rescue pathways (including AKT/PI3K, ERK and NFƙB) is needed for patients intolerant, refractory and resistant to ibrutinib," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "These data strongly support the clinical development of CG-806 to address the limitations and challenges of ibrutinib. CG-806 is being readied for the clinic and we look forward to reporting on its development."

The EHA (Free EHA Whitepaper) poster can be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.

About CG-806

CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors.

On June 15, 2018 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, reported that new interim data from the Phase 1b dose escalation study evaluating AFM13, its lead NK cell engager candidate, at the European Hematology Association (EHA) (Free EHA Whitepaper) 23rd Congress in Stockholm (Press release, Affimed, JUN 15, 2018, View Source [SID1234527342]). Dr. Eva Domingo of the Instituto Catalán de Oncología L’Hospitalet, Barcelona, Spain, presented the poster, titled A Phase 1 Study Investigating the Combination of AFM13 and the Monoclonal Anti-PD-1 Antibody Pembrolizumab in Patients with Relapsed/Refractory Hodgkin Lymphoma after Brentuximab Vedotin Failure: Updated Safety and Efficacy Data. The poster is available on the Affimed website at: View Source

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Assessment of 18 patients treated at the highest AFM13 dose showed best overall response rate (ORR) of 89% (16/18 patients) and complete metabolic response rate (CmR) of 28% (5/18 patients). The ORR and CmR for these 18 patients compare favorably to those of anti-PD-1 monotherapy in similar patient populations.

Responders included three patients who were either primary refractory to or had relapsed during front-line therapy and were refractory to all subsequent lines of therapy. The combination of AFM13 and pembrolizumab was well tolerated, with most adverse events mild to moderate in nature and manageable with standard of care measures.

"The high response rates in this study, in terms of both partial and complete responses, continue to compare favorably to the historical data of anti-PD-1 monotherapy, and would be expected to translate into meaningful progression free and overall survival over time," said Dr. Stephen Ansell, Principal Investigator of the study. "Importantly, these data have shown that AFM13 can be safely administered in combination with Keytruda and has the potential to improve patient outcomes."

A total of 30 patients were recruited into the Phase 1b study with enrollment completed in February 2018. The interim analysis included 24 of the 30 patients (6 from cohorts 1 and 2, and 18 from cohort 3 and the extension cohort) who had undergone at least one post-baseline disease assessment as of the data cut-off date.

"We are very excited about the potential opportunities for AFM13 to benefit patients with CD30-positive malignancies," said Dr. Leila Alland, Affimed’s Chief Medical Officer. "We are planning additional studies of AFM13 in patients with CD30-positive malignancies and are actively seeking guidance from experts on our development plans including potential accelerated approval paths."

Conference Call and Webcast Information

Affimed’s management will host a conference call today, June 15, 2018, at 8:30 a.m. ET. For both "listen-only" participants and those participants who wish to take part in the question-and-answer session, the call can be accessed by dialing +1 929-477-0448 (international numbers are available on Affimed’s homepage) five minutes prior to the start of the call and providing the Conference ID 6246081. A webcast of the conference call can be accessed in the "Events" section on the "Investors & Media" page of the Affimed website at View Source A replay of the webcast will be available on Affimed’s website shortly after the conclusion of the call and will be archived on the Affimed website for 30 days following the call.

About AFM13

AFM13 is a first-in-class tetravalent, bispecific NK cell engager that specifically binds to CD30 on tumor cells and to CD16A on NK cells. AFM13 is being developed in Hodgkin lymphoma (HL) and

in other CD30-positive lymphomas. AFM13 has shown a favorable safety profile and signs of therapeutic efficacy in a monotherapy setting in studies in Hodgkin Lymphoma and CD30+ lymphoma with cutaneous manifestation. In addition, data from a combination study of AFM13 with Merck’s anti-PD1 antibody Keytruda (pembrolizumab) supports proof of principle for the combination of NK cell engagement with checkpoint inhibition. AFM13 has been granted orphan drug designation by the U.S. Food and Drug Administration.

About Affimed’s Phase 1b study of AFM13 in combination with Keytruda (pembrolizumab) (NCT02665650)

Ongoing Phase 1b study to evaluate the safety and tolerability of the combination of the Affimed’s lead product candidate AFM13 with pembrolizumab (Keytruda) as salvage therapy after failure of standard therapies including brentuximab vedotin (BV) in relapsed or refractory (R/R) Hodgkin lymphoma (HL). Patients received escalating doses of AFM13 in combination with pembrolizumab at a flat dose of 200 mg administered every 3 weeks following the classical 3+3 design. Response assessment is performed every 12 weeks by PET/CT according to the Lugano Classification Revised Staging System for malignant lymphoma.

On June 15, 2018 Aclaris Therapeutics, Inc. (NASDAQ:ACRS), a dermatologist-led biopharmaceutical company committed to identifying, developing, and commercializing innovative therapies to address significant unmet needs in dermatology and immunology, reported the expansion of its executive leadership team with the appointment of David Gordon, MB ChB, as Chief Medical Officer (Press release, Aclaris Therapeutics, JUN 15, 2018, View Source [SID1234527341]). Dr. Gordon will report to President and Chief Executive Officer, Dr. Neal Walker, and will lead Aclaris’ clinical research and medical affairs functions. Christopher Powala, Chief Regulatory and Development Officer, has added Elaine Morefield, Ph.D to his team as Director, Product Quality. Product Quality was Dr. Morefield’s area of focus for more than eight years at the U.S. Food and Drug Administration (FDA).

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"We are excited to have David join the leadership team at this critical time when we are expanding the number of clinical programs for our pipeline of JAK inhibitors and preparing to initiate a Phase 3 program for common warts," said Dr. Walker. "David has a wealth of experience developing first-in-class treatments and drugs with stand-out clinical profiles," he added.

Prior to joining Aclaris, Dr. Gordon was Senior Vice President and Head of Dermatology Research and Development at GlaxoSmithKline plc (GSK). Over eighteen years at GSK, he led teams responsible for all stages of research from drug discovery through development and post-approval. He served as Clinical Vice President and Medicine Development Leader in the Immuno-Inflammation and Biopharmaceutical groups at GSK. His experience includes successfully developing and obtaining regulatory approval for drugs in a range of therapeutic areas, including NUCALA (mepolizumab)‎ and BENLYSTA (belimumab). His British medical degree (MB ChB) was awarded from Aberdeen University. He is accredited as a specialist in Pharmaceutical Medicine by the Faculty of Pharmaceutical Medicine in London.

"The time I have spent in immuno-inflammation and dermatology has taught me about both the impact of dermatological diseases and how we can apply our knowledge of science to address the needs of these patients," said Dr. Gordon. "I am pleased to be joining Aclaris, a company that is passionate about finding solutions for these patients by developing and commercializing new therapies for dermatologic conditions, including diseases for which no FDA-approved medications exist."

Aclaris also welcomes the addition of Dr. Elaine Morefield. While at the FDA, Dr. Morefield managed the New Drug Application CMC review process and implementation of FDA’s quality by design (QbD) effort. Dr. Morefield’s 30 years of pharmaceutical product development experience also includes positions at Wyeth, Schering-Plough, DSM, and Vertex Pharmaceuticals. Dr. Morefield has had an instrumental role in the development of over one hundred pharmaceutical products.

"I share Dr. Gordon’s enthusiasm for contributing to the efforts of Aclaris to develop new treatments for underserved dermatologic diseases," said Dr. Morefield.

"We are thrilled that Dr. Morefield has joined Aclaris and is contributing her considerable expertise in regulatory strategy and unique insight into FDA," adds Christopher Powala.