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 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 Arvinas, Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s investigational new drug application (IND) for ARV-110, an oral androgen receptor (AR) PROTAC protein degrader, for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Arvinas, JAN 4, 2019, View Source [SID1234532476]). Arvinas expects to begin enrollment of a Phase 1 clinical trial for ARV-110 in the first quarter of this year.

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"This IND clearance is a key step forward for Arvinas and for the field of protein degradation," said John Houston, Ph.D., President and CEO of Arvinas. "Our PROTAC platform has demonstrated exciting promise in preclinical studies and represents an entirely new approach to treating patients with mCRPC and many other diseases. We hope ARV-110 will deliver a much-needed new therapeutic option for patients, and we expect to dose our first patient in the first quarter of 2019."

ARV-110 was developed using Arvinas’ proprietary technology platform – PROTAC (proteolysis-targeting chimera) protein degraders – that uses small molecules to harness the body’s own natural protein recycling system (the ubiquitin proteasome system) to selectively and efficiently remove disease-causing proteins. ARV-110 is a PROTAC protein degrader specifically designed to target and degrade AR, and has demonstrated activity in preclinical models of AR overexpression and AR mutations, which are both common resistance mechanisms to current standard-of-care agents in men with prostate cancer. The Phase 1 study will investigate the safety and tolerability of ARV-110 in patients with mCRPC who have progressed on at least two standard of care treatment regimens and includes exploratory measures of efficacy.

On January 4, 2019 ViewRay, Inc. (Nasdaq: VRAY) reported the enrollment of the first patient in the Stereotactic MRI-guided On-table Adaptive Radiation Therapy (SMART) Trial, a multi-center, prospective clinical trial for locally advanced or borderline pancreatic cancer (Press release, ViewRay, JAN 4, 2019, View Source [SID1234532472]). The trial will explore the clinical benefits of precise, high dose radiation therapy enabled by MR-guidance combined with daily on-table adaptation in the treatment of pancreatic cancer.

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Retrospective analysis of precise, high-dose MR-guided radiation therapy delivered using adaptive dose planning has shown promising results with locally advanced pancreatic cancer, suggesting the potential for improving overall survival relative to patients receiving lower radiation doses, without increasing the rate of serious gastrointestinal toxicity. The compelling nature of the retrospective data prompted the SMART trial, aimed at investigating in a controlled, prospective manner, the robustness of this outcome and tracking quality of life over a 5-year trial period.

"High-definition MR and daily treatment plan adaptation allow us to deliver ablative radiation doses safely to pancreatic cancer patients for the first time ever," said Parag Parikh, M.D., co-PI of the study and Director of GI Radiation Oncology and MR-Guided Radiation Therapy at the Henry Ford Cancer Institute in Detroit. "Through the SMART trial, we will build upon the promising experience from UCLA, Washington University, Amsterdam UMC, University of Miami and University of Wisconsin by further exploring MRIdian’s impact on associated toxicity, local control and patient outcomes in pancreatic cancer at multiple institutions around the world."

The SMART trial is the first prospective, multi-institutional study to deliver ablative doses of radiation to pancreatic cancer patients. It aims to enroll 133 participants with borderline resectable or inoperable locally advanced pancreatic cancer. In the single-arm study, participants will receive radiation therapy at a dose of 50 Gray in 5 fractions (treatment sessions) using ViewRay’s MRIdian. On-table adaptive re-planning will be used when clinically indicated. In all patients, real-time MRI imaging will be used throughout treatment delivery to monitor the target location and control the radiation beam as necessary.

The trial’s primary outcome measure is grade 3 or higher gastrointestinal toxicity in the first 90 days after treatment, with secondary measures including overall survival at two years, distant progression-free survival at six months, and changes in patient-reported quality of life.

"Early evidence on the use of MRIdian to treat locally advanced pancreatic cancer suggests the potential for significantly prolonged survival and lower toxicity rates. Through this rigorously designed study, we hope to further validate the long-term benefits of treatment on the MRIdian," said Scott Drake, President and Chief Executive Officer of ViewRay. "We believe MRIdian’s unique combination of real-time visualization, automated beam control, and daily on-table treatment adaptation has the potential to become the standard of care in radiation oncology."

Along with Parag Parikh, M.D. from Henry Ford Cancer Institute, the trial is led by Percy Lee, M.D. from the University of California Los Angeles.

For more information on the SMART trial, please visit View Source

About the SMART Trial

The SMART trial is designed to enroll 133 participants with borderline resectable or inoperable locally advanced pancreatic cancer. Patients must be 18 years and older and have documented non-metastatic disease after 3 months of systemic therapy. Radiation therapy will be delivered using ViewRay’s MRIdian at a prescribed dose of 50 Gray (Gy) in 5 fractions. Each participant will be aligned in the treatment system with MRI image-guidance. On-table adaptive re-planning will be used when clinically indicated. In all patients, real-time MRI imaging will be used throughout treatment delivery to monitor the target location and control the radiation beam as necessary. The primary outcome measure of the study is grade 3 or higher gastrointestinal toxicity in the first 90 days after treatment. Secondary measures include overall survival at two years, distant progression-free survival at six months and changes in patient reported quality of life (pre-treatment to 12 months post-treatment and for longer periods up to five years).

On January 4, 2019 Sangamo Therapeutics, Inc. (NASDAQ: SGMO) reported that Sandy Macrae, CEO of Sangamo, will present a corporate overview at the 37th Annual J.P. Morgan Healthcare Conference on Wednesday, January 9th at 11:30 a.m. PT in San Francisco (Press release, Sangamo Therapeutics, JAN 4, 2019, View Source [SID1234532471]). Dr. Macrae’s presentation will be followed by a separate Q&A session starting at 12:00 p.m. PT.

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The presentation and Q&A session will be webcast live and may be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. The presentation will be archived on the Sangamo website for two weeks after the event.