On January 4, 2019 Mersana Therapeutics, Inc., (NASDAQ:MRSN) a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody drug conjugates (ADCs) targeting cancers in areas of high unmet need, reported that after a strategic evaluation the Company will prioritize its resources to focus on the advancement of XMT-1536, a first-in-class ADC candidate targeting NaPi2b. As a result, Mersana and its partner, Takeda, plan to terminate the co-development collaboration for XMT-1522. Mersana will work with investigators to ensure that patients benefitting from XMT-1522 will continue to have access to the therapy as needed.

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"While still in early clinical development, we are encouraged with the safety, tolerability, and activity of XMT-1536 as well as the pace at which the current study is advancing. For this reason, we have decided to focus our resources on advancing XMT-1536, our first-in-class ADC candidate targeting NaPi2b, a clinically validated ADC target broadly expressed in ovarian and non-small cell lung cancer (NSCLC) adenocarcinoma, for which there remains a significant unmet medical need," said Anna Protopapas, President and CEO, Mersana Therapeutics. "We have made the difficult decision to terminate the further development of XMT-1522 despite a favorable emerging profile of efficacy and tolerability due to the competitive environment for HER2-targeted therapies."

"Looking forward, we’re very enthusiastic about our clinical progress with XMT-1536 and the expansion of our clinical pipeline," said Dirk Huebner, M.D., Chief Medical Officer, Mersana Therapeutics. "On behalf of the Company and our partner Takeda we want to thank the patients and their families for their participation in the study, as well as the investigators and our team for their diligent work on the clinical development of XMT-1522. We are committed to leveraging our proprietary ADC platforms to generate a differentiated pipeline of ADCs."

Update on XMT-1536

· XMT-1536 is a first-in-class ADC against a clinically validated target. Ovarian and non-small cell lung cancer (NSCLC) adenocarcinoma express NaPi2b and remain areas of significant unmet need. XMT-1536 has the potential to play a significant role in the treatment of these diseases.

· The data to date from the ongoing XMT-1536 dose escalation study indicate that the trial has reached clinically relevant dose levels but has not yet reached a maximum tolerated dose. The once-every-three-week regimen has been fully explored. The once-every-four-week schedule is currently being evaluated. The 20 mg/m2 dose cohort has been shown to be well tolerated and the 30 mg/m2 is currently being evaluated.

· As of December 31, 2018, the dose escalation study of XMT-1536, in multiple tumor types, includes eight heavily pretreated and evaluable ovarian cancer patients treated at clinically relevant doses. These patients are unselected for NaPi2b expression and had 3 to 11 (median 6) prior regimens in the platinum resistant or refractory setting. Of these eight patients, two achieved a partial response and the remaining six achieved stable disease. The higher dose levels currently being evaluated, as well as additional patient enrollment, provide the opportunity to further define and optimize the profile of XMT-1536.

Mersana Therapeutics 2019 Corporate Goals

XMT-1536

· The Company expects to select a dose for use in its Phase 1 expansion studies and to initiate enrollment of patients in the expansion cohorts in the first half of 2019. The expansion cohorts will focus on platinum-resistant ovarian cancer and NSCLC adenocarcinoma. The Company also plans to utilize its proprietary and validated immunohistochemistry assay to retrospectively determine NaPi2b expression to determine whether a companion diagnostic would facilitate the clinical development of XMT-1536.

· The Company plans to report Phase 1 dose escalation data in the first half of 2019.

Pipeline Expansion

· The Company expects to disclose its next clinical candidate in the second half of 2019 and is targeting the filing of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) in the first half of 2020.

Research and Discovery

· Mersana continues to build a pipeline of promising ADCs across a variety of tumor types with significant unmet need, leveraging its three proprietary ADC platforms (Dolaflexin, Dolasynthen, and Alkymer).

· The Company is applying its expertise in ADCs to optimize and validate Immunosynthen, a new platform designed to allow systemic delivery of a potent immunostimulatory molecule to provide optimal efficacy and tolerability.

· Mersana plans to disclose the progress of these research and discovery efforts at scientific meetings throughout the year.

Corporate Developments

· The Company is proactively evaluating the potential for strategic collaborations that maximize the value of each of its pipeline candidates and platforms.

· Mersana is focused on the continued recruitment and retention of top talent, while maintaining a culture of scientific excellence, focused execution, and patient needs.

Upcoming Events

· The Company will provide further details during its presentation at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco, CA on Wednesday, January 9, 2019 at 3:00 pm PT.

On January 4, 2019 Ribon Therapeutics, a biotechnology company developing first-in-class therapeutics targeting novel enzyme families activated under cellular stress conditions, reported the closing of a $65 million Series B financing (Press release, Ribon Therapeutics, JAN 4, 2019, View Source [SID1234532462]). Proceeds will be used to advance lead programs from the company’s growing pipeline into clinical testing, including small molecule monoPARP inhibitors.

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The financing was led by the Novartis Venture Fund, with participation from new investors JJDC and Celgene Corporation, as well as existing investors, The Column Group, Deerfield Management, U.S. Venture Partners, Osage University Partners, Takeda Ventures and Euclidean Capital.

"We are delighted to have the support of such a distinguished group of investors who share our commitment to bringing novel therapies to cancer patients and excitement for the therapeutic potential of modulating cellular stress responses," said Victoria Richon, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. "Leveraging landmark discoveries made by our scientific founders, which ushered in a better understanding of the molecular action and biological function of novel enzyme classes beginning with monoPARPs, we are applying our expertise in drug discovery to develop novel and effective treatments for defined patient populations with limited therapeutic options."

Targeting MonoPARPs

MonoPARPs are key regulators of stress responses that enable cancer cells to survive and also evade immune detection, and emerging science has linked their activity with disease development. Ribon has built an integrated technology platform to interrogate monoPARPs to develop first-in-class, small molecule therapeutics. The company’s initial focus is in oncology, however, the 12 distinct monoPARPs function across a variety of stress responses relevant to disease development in cancer, inflammatory diseases and neurodegenerative diseases, giving Ribon’s approach broad utility. The focus of Ribon’s lead program is on advancing the science of PARP7 inhibitors for the treatment of cancer, beginning with squamous cell carcinoma of the lung.

"We have been following Victoria and her team for more than a year and are impressed by Ribon’s tremendous progress and ability to execute," said Anja Koenig, Head of the Novartis Venture Fund, who will be joining the Ribon board of directors as part of the Series B financing along with an investor from JJDC. "Ribon has developed a novel platform with the flexibility and rigor to investigate and exploit new targets providing the opportunity to build a diverse and attractive pipeline of first-in-class therapeutics."

On January 4, 2019 Evelo Biosciences, Inc. (NASDAQ:EVLO) ("Evelo") a biotechnology company developing monoclonal microbials, a new modality of oral biologic medicines, reported that it has dosed the first patient in its Phase 1/2 clinical trial of EDP1503 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Evelo Biosciences, JAN 4, 2019, View Source [SID1234532478]). EDP1503 is an orally delivered monoclonal microbial product candidate being developed for the treatment of cancer.

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This open-label clinical trial will evaluate the safety, tolerability, immune response markers, and overall response rates achieved with EDP1503 in combination with KEYTRUDA in up to 120 patients across three groups: microsatellite stable colorectal cancer; triple-negative breast cancer; and patients across multiple tumor types who have relapsed on prior PD-1/L1 inhibitor treatment.

Patients will receive daily EDP1503 monotherapy for two weeks followed by treatment with daily EDP1503 in combination with KEYTRUDA. The study will evaluate biomarkers identified from paired biopsies taken before and after the two-week run-in, as well as clinical outcomes observed over the course of the trial. Evelo expects to report initial clinical data from the trial in the first half of 2020.

"This clinical trial of EDP1503 will allow us to explore the potential synergies between EDP1503 and KEYTRUDA and offers the potential to treat multiple cancer types that are otherwise poorly responsive to checkpoint inhibitors," said Humphrey Gardner, M.D., FCAP, chief of medical oncology at Evelo.

In preclinical studies orally delivered EDP1503 shows activation of multiple clinically validated systemic immune pathways which are complementary to and potentially synergistic with checkpoint inhibitors. Effects include increased CXCL9 and CXCL10 production in the tumor microenvironment, augmentation of NK and T cell infiltration to the tumor site as well as upregulation of MHC Class I expression in tumors.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

On January 4, 2019 Recursion, a clinical-stage biotechnology company combining artificial intelligence (AI), experimental biology, and automation to discover and develop drugs at scale, reported it has entered into a licensing agreement with the Ohio State Innovation Foundation (OSIF), the technology transfer function of The Ohio State University, gaining rights to OSU-HDAC42, a clinical-stage compound that will be developed by Recursion as REC-2282 (Press release, Recursion Pharmaceuticals, JAN 4, 2019, View Source [SID1234556193]). Recursion plans to develop the compound in neurofibromatosis type 2 (NF2), a devastating rare tumor syndrome.

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"We leveraged our unique discovery platform to identify potential therapies for NF2 from among known compounds with the potential for accelerated development," said Chris Gibson, Ph.D., co-founder and CEO of Recursion. "We found a strong signal in our data for REC-2282 as a potential treatment for NF2, and upon further diligence, discovered the drug was already being pursued in the treatment of this disease. The universe of experimental treatments is vast, but the data arbitrage generated empirically on our platform gave us the confidence to move forward quickly."

Under the terms of this agreement, Recursion obtains exclusive worldwide rights to develop and commercialize REC-2282. Full financial terms have not been disclosed.

"Adding REC-2282 to our clinical pipeline and driving to a rapid determination of its efficacy and safety for NF2 patients marks another important step in Recursion’s growth and more importantly may offer a better treatment option for this terribly underserved patient population," said Tim Considine, Senior Vice President, Strategic Development at Recursion. "We are excited to build on existing clinical data to advance this program to human proof of concept in NF2 as rapidly as possible."

Last year, Recursion announced that its Investigational New Drug (IND) application for another disease of unmet need, cerebral cavernous malformation (CCM), was cleared by the Food and Drug Administration (FDA), and that program is currently enrolling subjects in Phase 1.

About Neurofibromatosis Type 2

Neurofibromatosis type 2 is a genetic condition most commonly associated with bilateral vestibular schwannomas, also known as acoustic neuromas. These are benign (noncancerous) tumors that occur on the nerves responsible for balance and hearing in the inner ear. Patients can also have meningiomas, a slow-growing tumor that usually develops on the surface of the brain. Although these tumors are benign, they can cause loss of hearing and balance problems, and in severe cases can be life threatening. It is estimated that about one in 40,000 people has NF2. Approximately 50% of people with NF2 do not have a family history of the condition. Current treatment involves surgical removal of the tumors, which provides temporary relief of symptoms but bears a significant risk of hearing loss and other complications.

About REC-2282 (OSU-HDAC42)

REC-2282 is a pan-histone deacetylase (HDAC) inhibitor. There are multiple lines of evidence that REC-2282 exhibits both histone-independent and acetylation-independent mechanisms, at both epigenetic and cellular levels. The compound was previously in clinical development by Arno Therapeutics (as AR-42) for various solid and liquid tumors. Exploratory investigator-initiated studies have been conducted in patients with vestibular schwannomas and meningiomas. Rights to the compound were returned to OSIF in November 2017.

On January 4, 2019 Epizyme, Inc. (Nasdaq: EPZM), a clinical-stage company developing novel epigenetic therapies, reported a comprehensive set of pipeline updates, including that the company has identified a path to submission for accelerated approval of tazemetostat for patients with relapsed and/or refractory follicular lymphoma (FL), both with and without EZH2 activating mutations (Press release, Epizyme, JAN 4, 2019, View Source [SID1234532444]). The company recently conducted a productive meeting with the U.S. Food and Drug Administration (FDA) to discuss the FL registration strategy based on the current patient population in its ongoing Phase 2 clinical trial. Following the discussion, Epizyme has defined a registration strategy for tazemetostat in both EZH2 mutant and wild type FL patient populations, where patients’ disease has progressed following two or more lines of therapy. Based on this, the company anticipates submitting a New Drug Application (NDA) for this indication in the fourth quarter of 2019. In addition, the company provided an update on its clinical and preclinical pipeline and anticipated milestones for 2019.

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"Follicular lymphoma is an incurable cancer today, and in the third line and later settings, there are limited effective treatment options. Defining a clear path to a regulatory submission for tazemetostat for this patient population marks a huge step forward for patients and an opportunity to change the course of FL treatment," said Shefali Agarwal, M.D., chief medical officer of Epizyme. "This FL NDA submission would mark the second for tazemetostat in one year, following our first submission for epithelioid sarcoma, which is on track for the second quarter of 2019. If successful, tazemetostat is poised to be the first commercially available EZH2 inhibitor. We look forward to advancing our submission preparations and further engaging with FDA, as we work expeditiously to bring tazemetostat to the patients who need it."

Tazemetostat Registration Update for Follicular Lymphoma

Phase 2 Study Fully Enrolled: The ongoing Phase 2 study has been fully enrolled and based on discussions with FDA, is expected to provide the necessary relapsed and/or refractory FL patients needed for an NDA submission, with 45 patients with EZH2 activating mutations and 54 patients with wild-type EZH2.

Registration Path Identified for NDA Submission in Follicular Lymphoma: Epizyme recently met with FDA to review its planned registration strategy for tazemetostat for patients with FL who have been previously treated with two or more systemic therapies, which represents a population of unmet medical need. The company has identified a path to a submission for accelerated approval for patients with both mutant and wildtype EZH2, based on the ongoing Phase 2 study. Epizyme will further advance the Phase 2 study, with updated data to be reported at a medical meeting in mid-2019 and an NDA submission targeted for the fourth quarter of 2019.

Confirmatory Program Could Support Expansion into Earlier Treatment Lines of Follicular Lymphoma: As part of an accelerated approval strategy, Epizyme plans to conduct a confirmatory program to support full approval of tazemetostat in FL, while also supporting its potential expansion into the second-line treatment of FL. Under its Fast Track designation, the company intends to engage with FDA in the first half of 2019 to discuss the confirmatory program and will share details upon initiation.

Tazemetostat Registration Update for Epithelioid Sarcoma

NDA Submission for Epithelioid Sarcoma on Track for Second Quarter of 2019: Epizyme is advancing preparations for its first NDA submission for tazemetostat in the second quarter of 2019 using the accelerated approval pathway for the treatment of patients with epithelioid sarcoma (ES). ES is an ultra-rare and difficult-to-treat sarcoma with no specifically indicated FDA-approved therapies today. If approved, tazemetostat could be the first treatment specifically indicated for patients with ES. The company has begun pre-commercial activities, with plans to commercialize tazemetostat on its own in the U.S.

Tazemetostat Program Expansion Updates

Combination Study to Begin in Follicular Lymphoma in 2019: Based on the monotherapy efficacy and safety data generated to-date, Epizyme plans to explore the potential of tazemetostat in earlier lines of FL as combination therapy. The company is assessing the opportunity to conduct a combination study that would compare the chemo-free combination of rituximab and Revlimid (R2) with tazemetostat versus R2 with placebo in patients with relapsed or refractory FL. Epizyme plans to provide an update on its combination study plans once they have been finalized.

R-CHOP Combination Data Further Support Tazemetostat Combination Potential: Under its collaboration agreement with Epizyme, the Lymphoma Study Association (LYSA) reported data at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on the combination of tazemetostat with R-CHOP as a front-line treatment for patients with diffuse large B-cell lymphoma. The data showed that the combination of the two agents was generally well-tolerated, confirmed the recommended tazemetostat dose for the combination to be 800mg twice-daily and demonstrated clinical activity, with 87 percent of patients experiencing a metabolic complete response. Based on these data, Epizyme is considering opportunities to expand the evaluation of this combination into patients with FL.

Plans in Place to Expand Tazemetostat into New Indications and Combinations: Based on its mechanism of action, favorable safety reported and demonstrated activity in multiple tumor types and treatment settings, Epizyme plans to expand tazemetostat’s potential utility into additional combinations and indications. The company has identified the next set of clinical assessments for tazemetostat, including a combination study in castration-resistant prostate cancer that is slated to begin in mid-2019, and assessment in platinum-resistant tumors, such as small-cell lung cancer, triple-negative breast cancer and ovarian cancer, slated to begin in the second half of 2019.

Genentech and Epizyme to Close Tecentriq Combination Assessment in NSCLC: As part of a collaboration agreement, Genentech/Roche initiated assessment of tazemetostat in combination with Tecentriq for the treatment of non-small cell lung cancer (NSCLC) in an arm of its MORPHEUS NSCLC Trial. Before patients had been enrolled in the study, recruitment was halted due to the partial hold placed on tazemetostat studies. Epizyme has since reopened enrollment in the United States and Germany for studies for which it is the sponsor. Due to the hold and strategic reprioritizations, the companies have jointly opted not to move forward with the NSCLC combination study.

Preclinical and Discovery Pipeline Update

EZM8266 on Track to Begin Clinical Development: Throughout 2018, Epizyme conducted IND-enabling studies on its next development candidate, EZM8266, a novel G9a inhibitor for the treatment of sickle cell disease. The company is on track to begin clinical development of EZM8266 in the second half of 2019 with a dose-finding and safety study.

Two Research Programs to Be Advanced under Boehringer Ingelheim Collaboration: In November 2018, Epizyme entered a strategic collaboration with Boehringer Ingelheim focused on the research, development and commercialization of novel small molecule inhibitors directed toward two previously unaddressed epigenetic targets as potential therapies for people with cancer. Specifically, these targets are enzymes within the helicase and histone acetyltransferase (HAT) families that when dysregulated have been linked to the development of cancers that currently lack therapeutic options.

Updated Financial Guidance

Based on enhanced operating efficiencies, partner revenues and proceeds from the company’s underwritten public offering completed in October 2018, Epizyme has extended its expected capital runway into the second quarter of 2020 based on current operating plans.

"We are at a point in our company’s evolution where we are beginning to realize the true value of all of the hard work to which we have dedicated ourselves over the past several years. 2019 is set to be a year of pivotal milestones for Epizyme, providing validation of our expertise in drug development and bringing us closer to achieving our mission of helping patients," said Robert Bazemore, president and chief executive officer of Epizyme. "With defined registration paths for tazemetostat in two indications and plans to expand into other combinations and indications, tazemetostat has the potential to generate significant value for the patients and physicians who need new treatment options, and for Epizyme. Outside of tazemetostat, our research capabilities provide additional advantages to our company, and we are excited to be moving EZM8266 into the clinic and working with our partners to advance earlier programs. I am proud of what we have accomplished, and look forward to what is ahead as we transition to a commercial-stage company that can truly have an impact on patients."

Conference Call Information

Epizyme will host a conference call today, Jan. 4, at 8:30 a.m. ET to review this corporate update. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 7289720. A live webcast and slides will be available in the investor section of the company’s website at www.epizyme.com. The webcast and slides will be archived for 60 days following the call and presentation.