On June 14, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported positive interim efficacy data from the company’s ongoing Phase 2 clinical trial of tazemetostat, a first-in-class, oral EZH2 inhibitor, as a single-agent treatment for relapsed or refractory patients with follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) grouped by EZH2 mutational status (Press release, Epizyme, JUN 14, 2017, View Source [SID1234519538]). The data were presented today during a plenary session at the International Conference on Malignant Lymphoma (ICML), which is being held June 14-17, 2017 in Lugano, Switzerland. In addition, data from a 62-gene panel biomarker study of tazemetostat in patients with various subtypes of non-Hodgkin lymphoma will be presented during a poster session at the conference.

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Interim data as of June 1, 2017 show that tazemetostat treatment resulted in a clinically meaningful benefit in patients with FL. The subset of FL patients with EZH2 activating mutations have a 92 percent objective response rate (ORR). Patients with FL with EZH2 wild-type have an ORR of 26 percent and 22 percent of patients with stable disease are still on study. Promising activity was also observed in DLBCL patients with EZH2 mutations, which includes recently enrolled patients, with an ORR of 29 percent. As the size of the mutation study groups increase and patients remain on study, Epizyme expects the data will continue to evolve. In addition, tazemetostat continues to demonstrate a favorable safety profile across all patient populations in this study.

"I believe that tazemetostat may play a significant role in disease management for my patients, and am particularly excited by the impact observed in patients with follicular lymphoma," said Franck Morschhauser, M.D., Ph.D., Centre Hospitalier Régional Universitaire de Lille, France, and lead investigator of the Phase 2 study. "I am also encouraged by the level of activity in DLBCL patients with EZH2 mutations, especially in light of the bleak prognosis associated with advanced disease. Tazemetostat has demonstrated a uniquely tolerable safety profile, and I look forward to further exploring its full benefit in patients with relapsed or refractory FL and DLBCL as the data mature."

"These interim data findings represent an important step forward for our tazemetostat program, with anti-tumor activity observed across all groups of the study," said Rob Bazemore, chief executive officer of Epizyme. "The activity we have observed in patients with an EZH2 mutation exceeds what we have seen so far with wild-type EZH2, consistent with our scientific hypothesis, and we are encouraged by both the objective responses and durability of responses in FL and DLBCL. Our focus is on continuing to increase enrollment of patients with an EZH2 mutation, and engaging with FDA in the second half of the year to determine potential registration paths to bring tazemetostat to patients as quickly as we can."

Follicular Lymphoma Efficacy Data
FL, an indolent form of non-Hodgkin lymphoma (NHL), is considered to be incurable with existing treatments and is characterized by cycles of relapse that become increasingly difficult to treat with each disease progression. Approximately 25,000 patients in the U.S. and major European countries are diagnosed with FL every year1, of which an estimated 15 to 20 percent have an EZH2 mutation. There are no approved treatments indicated for patients with FL with an EZH2 mutation. In April 2017, Epizyme was granted Fast Track designation for FL regardless of EZH2 mutational status.

As of June 1, 2017, Epizyme enrolled 19 FL patients with EZH2 activating mutations in the Phase 2 trial, of which 13 are evaluable for efficacy. Enrollment of FL patients with EZH2 wild-type was completed in late 2016 with a total of 54 patients, all of which are evaluable for efficacy. More than 75 percent of evaluable FL patients had three or more prior treatments, and approximately 50 percent of patients in each group were refractory to their last prior therapy.

Key interim efficacy findings are as follows:

FL with EZH2 MT FL with EZH2 WT
Evaluable for efficacy on June 1, 2017 n =13 n =54
Objective Response Rate (CR + PR) 12 (92%) 14 (26%)
Complete Response (CR) 1 (8%) 3 (6%)
Partial Response (PR) 11 (85%) 11 (20%)
Stable Disease (SD) 1 (8%) 23 (43%)
SD study drug ongoing 1 (8%) 12 (22%)
Progressive Disease 0 13 (24%)
No Data, Unknown (UNK) 0 4 (7%)
Time to first Response (weeks)
median (range) 11.9
(6.9 – 35.9) 15.2
(8.1 – 32.1)
The activity of tazemetostat across FL patients is encouraging, and when combined with the well-tolerated safety profile, supports its potential utility as both as monotherapy and a combination agent. Combination treatment has become the evolving standard-of-care for FL, and Epizyme plans to begin investigating tazemetostat as a combination agent in FL this year.

Diffuse Large B-Cell Lymphoma Efficacy Data
DLBCL is an aggressive form of NHL that once diagnosed, typically requires immediate treatment. Approximately 45,000 patients are diagnosed with DLBCL in the U.S. and major European countries every year2. Among patients with germinal center DLBCL, an estimated 15 to 20 percent have an EZH2 mutation. Forty to 50 percent of patients will relapse on their first-line treatment, which is most commonly the chemotherapy regimen R-CHOP, and there are few treatment options for patients who relapse or become refractory to chemotherapy. In November 2016, Epizyme was granted Fast Track designation for DLBCL with EZH2 mutations.

As of June 1, 2017, Epizyme had enrolled 22 DLBCL patients with EZH2 mutations, and efficacy was assessed on 17 patients. Enrollment of DLBCL patients with EZH2 wild-type (germinal center and non-germinal center) was completed in early 2017 with 120 patients, of which 119 were evaluable for efficacy. Patients with DLBCL with EZH2 activating mutations represent the most advanced and severely ill patients in the study, with 82 percent having been previously treated with at least three therapeutic regimens and refractory to their last treatment.

Key interim efficacy findings are as follows:

DLBCL EZH2 MT DLBCL EZH2 WT
Evaluable for efficacy on June 1, 2017 n = 17 n = 119
Objective Response Rate (CR + PR) 5 (29%) 18 (15%)
Complete Response (CR) 0 10 (8%)
Partial Response (PR) 5 (29%) 8 (7%)
Stable Disease (SD) 6 (35%) 22 (18%)
SD study drug ongoing 1 (6%) 4 (3%)
Progressive Disease 6 (35%) 60 (50%)
No Data, Unknown (UNK) 0 19 (16%)
Time to first Response (weeks)
median (range) 8.3
(4.6 – 48.1) 8.5
(5.3 – 24.7)
Epizyme believes that activity is likely to be enhanced for wild-type disease through combination treatment. The company has a robust combination program underway in DLBCL evaluating tazemetostat in an immuno-oncology combination with atezolizumab and a steroid combination with prednisolone. In addition, tazemetostat is being evaluated in the front-line setting in combination with R-CHOP in newly diagnosed, high-risk DLBCL patients.

Tazemetostat Safety Profile
Safety data from patients in this Phase 2 trial (n=210), as of the data cutoff, demonstrate a favorable tolerability profile, consistent with the experience observed in a nearly 400-patient safety database from tazemetostat clinical trials to date. Across all cohorts of this trial, dose reductions and discontinuations due to treatment-related adverse events are low, at only three and two percent, respectively.

The majority of treatment-emergent adverse events are grade 1 or 2, with only 18 percent of grade 3 or higher being considered treatment-related. Treatment-emergent adverse events, regardless of attribution and affecting more than five percent of patients, are nausea (20%); thrombocytopenia (19%); anemia (16%); cough (14%); fatigue (12%); diarrhea (11%); asthenia, neutropenia, pyrexia and vomiting (10% each); bronchitis (7%); and constipation, decreased appetite, upper respiratory infection, abdominal pain, headache and urinary tract infection (6% each).

Poster Presentation Information
Data from a 62-gene panel biomarker study of tazemetostat in patients with various subtypes of NHL will also be presented in a poster by Stephen Blakemore Ph.D., titled "Preliminary evidence of a molecular predictor of tazemetostat response, beyond EZH2 mutation, in NHL patients via characterization of archive tumor and circulating tumor DNA" on June 14, 2017 (Poster Board No.: 154).

The data in the poster detail both potential positive and negative predictors of response to tazemetostat. In the case of positive predictors, both EZH2 and MYD88 are mutations that appear to enhance patients’ sensitivity to tazemetostat. The company has also detected EZH2 mutations by circulating tumor DNA in patient serum, indicating the potential future use of a tube of blood for patient identification of EZH2 mutations rather than testing patient’s archival tumor samples.

Conference Call Information
Epizyme will host a conference call and audio webcast today at 10:30 a.m. ET. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 15855261. The webcast, and accompanying slides for the call, will be accessible under "Events and Presentations" in the Investor Relations section of the Company’s website at View Source

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing Phase 2 programs in both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors; and mesothelioma, as well as in combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for both relapsed/refractory follicular lymphoma and DLBCL with EZH2 activating mutations, as well as Orphan Drug designation for malignant rhabdoid tumors.

On June 13, 2017 Threshold Pharmaceuticals, Inc. (NASDAQ:THLD) a clinical-stage biopharmaceutical company developing novel therapies for cancer, reported that the University of Texas MD Anderson Cancer Center has dosed the first patient in a Phase 1 immunotherapy clinical trial investigating ipilimumab and evofosfamide for the treatment of patients with metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma or human papillomavirus (HPV) negative squamous cell carcinoma of head and neck for which standard therapy does not offer the potential for increased survival (Press release, Threshold Pharmaceuticals, JUN 13, 2017, View Source [SID1234519545]).

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“We believe that adding evofosfamide to certain immunotherapies has the potential to render some of the most therapeutically resistant cancers more sensitive to the immunotherapy and we are excited to have dosed the first patient in this study,” said Tillman Pearce, M.D., Chief Medical Officer at Threshold Pharmaceuticals. “Thanks to preclinical research conducted by Dr. Curran at MD Anderson Cancer Center, it is well-understood that certain tumors have hypoxic zones that resist infiltration by T cells, which are capable of attacking and killing tumor cells, and that combination therapy with evofosfamide and anti-CTLA-4/anti-PD-1 treatment opens up the hypoxic zones to T cell infiltration.”

Evofosfamide (also known as TH-302) is Threshold’s proprietary, hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. In preclinical research conducted by Michael Curran, Ph.D., Assistant Professor at the University of Texas MD Anderson Cancer Center, evofosfamide has sensitized highly resistant solid tumor models to treatment with certain immune checkpoint inhibitors through evofosfamide-driven disruption of hypoxic zones. Specifically, hypoxia in the tumor microenvironment forms a barrier to T cell infiltration and fosters immunotherapy resistance in prostate cancer and other solid tumors.

The Phase 1 clinical trial is a single-arm, open label study that will enroll up to 69 patients with metastatic or locally advanced prostate cancer, metastatic pancreatic cancer, melanoma or HPV-negative squamous cell carcinoma of head and neck. Eligible patients will receive evofosfamide on Days one and eight of the first two cycles and ipilimumab on Day eight of a 28-day cycle. Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) response rate is the primary endpoint. Secondary endpoints include duration of response, progression-free survival, overall survival, safety, tolerability and pharmacokinetics. The study is open at MD Anderson Cancer Center in Houston, Texas. More details can be found here.

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. Discussions remain ongoing with the Japanese PMDA regulatory agency on what additional clinical trials may be required to support submission of evofosfamide for the treatment of pancreatic cancer patients in Japan.

On June 13, 2017 (GLOBE NWarp* TG Therapeutics, Inc. (NASDAQ:TGTX), reported the schedule of presentations featuring TG-1101 and TGR-1202 at the upcoming 14th International Conference on Malignant Lymphoma (ICML), being held June 14 – 17, 2017, in Lugano, Switzerland and the upcoming 22nd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress (EHA) (Free EHA Whitepaper), being held June 22 – 25, 2017, in Madrid, Spain (Press release, TG Therapeutics, JUN 13, 2017, View Source [SID1234519524]).

(Press release, TG Therapeutics, JUN 13, 2017, View Source [SID1234519524])

ICML PRESENTATION SCHEDULE:

Oral Presentations:

Title: Updated results of a multicenter phase I/Ib study of TGR-1202 in combination with ibrutinib in patients with relapsed or refractory MCL or CL
• Abstract Number: 040
• Presentation Date & Time: Wednesday, June 14, 2017 17:50 CEST
• Session Title: Chemotherapy-Free Combinations
• Presenter: Matthew S. Davids, MD, Dana-Farber Cancer Institute
Title: Ublituximab and ibrutinib for previously treated genetically high-risk chronic lymphocytic leukemia: Results of the GENUINE Phase 3 study
• Abstract Number: 101
• Presentation Date & Time: Friday, June 16, 2017 11:20 CEST
• Session Title: Session 7 – Advances in CLL
• Presenter: Anthony R. Mato, MD, University of Pennsylvania, Abramson Cancer Center
Title: Chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib is well tolerated and highly active in patients with advanced CLL and NHL
• Abstract Number: 102
• Presentation Date & Time: Friday, June 16, 2017 11:35 CEST
• Session Title: Session 7 – Advances in CLL
• Presenter: Loretta J. Nastoupil, MD, MD Anderson Cancer Center
Poster Presentation:

Title: Combination of TGR-1202, Ublituximab, and Bendamustine is safe and highly active in patients with advanced DLBCL and Follicular Lymphoma
• Abstract Number: 277
• Presentation Date: Friday, June 16, 2017 (Poster Session)
• Presenter: Mathew Lunning, DO, University of Nebraska, Omaha, NE
EHA PRESENTATION SCHEDULE:

Oral Presentation:

Title: Chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib is well tolerated and highly active in patients with advanced CLL and NHL
• Abstract Number: S772
• Presentation Date & Time: Sunday, June 25, 2017 8:45 – 9:00 CEST
• Session Title: Targeted therapies in relapsed chronic lymphocytic leukemia
• Location: Hall A
• Presenter: Loretta J. Nastoupil, MD, MD Anderson Cancer Center
Poster Presentation:

Title: Combination of TGR-1202, Ublituximab, and bendamustine is safe and highly active in patients with advanced DLBCL and follicular lymphoma
• Abstract Number: P563
• Presentation Date & Time: Saturday, June 24, 2017 17:30 – 19:00 CEST
• Session Title: Aggressive Non-Hodgkin Lymphoma- Relapsed/Refractory
• Location: Poster Area Hall 7
• Presenter: Matthew Lunning, DO, University of Nebraska Medical Center
Abstracts are available online, respectively through the ICML meeting website at www.lymphcon.ch, or through the EHA (Free EHA Whitepaper) meeting website at www.ehaweb.org. Following each presentation, the data presented will be available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 13, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a preclinical pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported it has begun taking steps to file an IND with the FDA for its molecule WP1220 for the treatment of Cutaneous T-Cell Lymphoma (CTCL), a rare form of skin cancer (Press release, Moleculin, JUN 13, 2017, View Source [SID1234519500]).

Moleculin’s WP1220 (aka MOL4239) has data demonstrating significant activity in preclinical studies and is being studied as a possible topical treatment for CTCL. The FDA previously granted an IND to WP1220 for development as a topical treatment of psoriasis, and although the molecule completed a Phase I clinical trial, providing initial data suggesting safety in humans, Phase II clinical trials did not demonstrate sufficient activity to warrant further development for that indication. To pursue further development of WP1220, the Company believes the data used to support the prior IND may allow for a quicker pathway to an IND for CTCL.

"Our primary focus has been further developing our most advanced and promising drug, Annamycin, for the treatment of acute myeloid leukemia," commented Walter Klemp, Chairman and CEO of Moleculin. "Nevertheless, we believe some of the less advanced technologies in our portfolio have significant potential in other cancer indications. WP1220 is a great example of such potentially useful technology, and because the FDA previously found the data package supporting an IND for WP1220 to be adequate in another context, we are hopeful that we can expeditiously move forward to studying the molecule in humans for the topical treatment of this potentially deadly skin disease."

Mr. Klemp added: "Developing WP1220 for indications like CTCL may provide opportunities for strategic collaboration and out-licensing while maintaining our ability to develop other molecules to their highest and best potential. We will be actively looking for such opportunities to help fund the projects we believe hold the most potential for Moleculin stakeholders."