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 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.

On January 4, 2019 Flex Pharma, Inc. (NASDAQ: FLKS), and Salarius Pharmaceuticals, LLC, a clinical-stage oncology company targeting the epigenetic causes of cancers, reported that the companies have entered into a definitive merger agreement under which privately-held Salarius will merge with a wholly-owned subsidiary of Flex Pharma (Press release, Flex Pharma, JAN 4, 2019, View Source [SID1234532463]). Management believes that the proposed transaction will position the combined company to recognize multiple value inflection points based on Salarius’ clinical pipeline, which targets rare, orphan cancers with no targeted treatments and cancers that have a high unmet need.

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Salarius recently completed a $6.4 million private placement, which combined with cash from Flex Pharma is expected to fund the combined company to mid-2020, allowing it to report early cohort data from an ongoing Phase 1 Ewing sarcoma trial. Upon the closing of the transaction, Flex Pharma stockholders will own approximately 19.9% of the combined company and current Salarius investors will own approximately 80.1% of the combined company. Flex Pharma stockholders will also receive a right to receive warrants, six months and one day following the closing date of the transaction, allowing them to purchase additional shares. The total value of these warrants will be calculated such that upon exercise Flex Pharma stockholders would own an additional 2.4%, or a total of 22.3%, of the value of the combined entity, subject to adjustment based on Flex Pharma’s net cash at closing. A live conference call and webcast is scheduled for today at 9:00 a.m. Eastern Time.

Upon closing of the transaction, Flex Pharma is expected to be renamed Salarius Pharmaceuticals, Inc. and be under the leadership of Salarius’ current management team, led by Chief Executive Officer, David Arthur. The Salarius clinical pipeline will become the lead assets of the company following the transaction. Flex Pharma President and Chief Executive Officer, William McVicar, Ph.D., is expected to join the Board of Directors of the combined company following the closing of the transaction.

"After completing a comprehensive and highly competitive selection process, we are confident that the proposed transaction with Salarius offers the best opportunity for significant near- and long-term value creation," stated Dr. McVicar. "We were impressed by the compelling science supporting Salarius’ novel drug, as well as the company’s strong financial position and management team. Based on our diligence, we believe Salarius could be poised to advance multiple potential product opportunities that address significant unmet needs in oncology. I look forward to supporting the company and being a member of the Salarius Board of Directors following the closing of the transaction. Finally, I would like to thank our stockholders for their support and patience during this strategic process and to reiterate that the entire team is fully committed to enhancing stockholder value with this transaction and beyond."

Salarius’ lead compound, Seclidemstat, targets the epigenetic dysregulation underlying Ewing sarcoma, a devastating pediatric, adolescent and young adult bone cancer for which no targeted therapies currently exist. Seclidemstat is a differentiated, reversible inhibitor of the lysine-specific demethylase 1 enzyme, or LSD1, which is a widely studied epigenetic enzyme and a validated drug target for clinical development. The company is currently enrolling patients in an open-label Phase 1 dose escalation/dose expansion study, which is expected to conclude in 2020. Salarius is also preparing to initiate additional studies in advanced solid tumors, including prostate, breast and ovarian cancers.

Salarius’ Chief Executive Officer, David Arthur, commented, "This strategic transaction and Nasdaq listing represent a growth opportunity for both companies. As an emerging public company, we believe that the enhanced visibility and exposure to institutional investors will enable Salarius to showcase the potential of its clinical pipeline, and the progression of its programs should drive increased stockholder value. Our goal is to become a recognized leader in epigenetic cancer therapy."

Mr. Arthur is a seasoned life sciences executive with more than 25 years’ experience in biopharma leadership, building and leading multi-disciplinary teams, as well as launching and managing pharmaceutical and drug delivery device brands. For much of his career, he held executive roles at Eli Lilly and Boehringer-Ingelheim managing product development, business development and global commercialization.

About the Proposed Transaction

The transaction has been approved unanimously by the Board of Director of Flex Pharma and Board of Managers of Salarius. The proposed transaction is expected to close in the first half of 2019, subject to the approval of Flex Pharma stockholders at a special stockholder meeting and other customary conditions, including approval by Salarius’ members.

Flex Pharma’s strategic advisor in the transaction is Wedbush PacGrow. Healthios Capital Markets is serving as financial advisor to Salarius Pharmaceuticals. Dentons Canada LLP and Duane Morris LLP are serving as legal counsel to Flex Pharma and Pillsbury Winthrop Shaw Pittman LLP is serving as legal counsel to Salarius Pharmaceuticals.

Conference Call and Webcast

Flex Pharma and Salarius will host a joint conference call and simultaneous live audio webcast today at 9:00 a.m. Eastern Time to discuss the proposed transaction. The live call may be accessed by dialing:

(855) 780-7202 (U.S.)
(631) 485-4874 (international)
Conference ID: 4498626
A live audio webcast of the call will be available online from the investor relations section of the Flex Pharma website at www.flex-pharma.com and will be archived there for 30 days.

On January 4, 2019 Heat Biologics, Inc. ("Heat") (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported that it will be presenting at the Biotech Showcase 2019 conference on Tuesday, January 8, 2019, at 11:30 a.m. PST in the Yosemite C ballroom at the Hilton San Francisco Union Square. Jeff Wolf, CEO of Heat Biologics, will be presenting (Press release, Heat Biologics, JAN 4, 2019, View Source [SID1234532578]).

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On January 4, 2019 Alder BioPharmaceuticals, Inc. reported that it has entered into a Distribution Agreement (the "Distribution Agreement") with J.P. Morgan Securities LLC, as our sales agent (the "Sales Agent"), pursuant to which we may offer and sell from time to time through the Sales Agent up to $100,000,000 maximum aggregate offering price of our common stock, par value $0.0001 per share ("Common Stock"), in such amounts as we may specify by notice to the Sales Agent, in accordance with the terms and conditions set forth in the Distribution Agreement (Filing, 8-K, Alder Biopharmaceuticals, JAN 4, 2019, View Source [SID1234532445]).

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Sales, if any, of the Common Stock pursuant to the Distribution Agreement may be made in negotiated transactions or transactions that are deemed to be "at-the-market" offerings as defined in Rule 415 under the Securities Act, including sales made directly on the Nasdaq Stock Market, or sales made to or through a market maker other than on an exchange. Under the Distribution Agreement, we will set the parameters for the sale of shares, including the number of shares to be issued, the time period during which sales are requested to be made, limitation on the number of shares that may be sold in any one trading day and any minimum price below which sales may not be made. We are not obligated to sell any Common Stock under the Distribution Agreement. The Common Stock will be offered and sold pursuant to our shelf registration statement on Form S-3 (File No. 333-216199) which was automatically effective upon filing with the Securities and Exchange Commission on February 23, 2017. We may terminate the Distribution Agreement upon written notice to the Sales Agent for any reason or by the Sales Agent upon written notice to us for any reason or at any time under certain circumstances, including but not limited to the occurrence of a material adverse change in our company.

The Distribution Agreement contains customary representations, warranties and agreements by us, and indemnification rights and obligations of the parties. The Distribution Agreement provides that the Sales Agent will be entitled to compensation for its services equal up to 3.0% of the gross sales price per share of all shares sold through the Sales Agent under the Distribution Agreement. Under the terms of the Distribution Agreement, we have agreed to indemnify the Sales Agent against certain specified types of liabilities, including liabilities under the Securities Act of 1933, as amended, to contribute to payments the Sales Agent may be required to make in respect of these liabilities, and to reimburse the Sales Agent for certain expenses. In the ordinary course of business, the Sales Agent or their respective affiliates from time to time have provided and may in the future provide various investment banking, commercial banking and financial advisory services to the company and/or its affiliates, for which they have received or may receive customary compensation.

We intend to use the net proceeds from the sale, if any, of the securities offered in the offering for the commercialization of eptinezumab up to and through launch and the manufacture of commercial supply for eptinezumab, and may also use net proceeds for future eptinezumab clinical trials, the development of ALD1910 and for working capital and general corporate purposes.

The above summary of the Distribution Agreement does not purport to be complete and is qualified in its entirety by reference to the Distribution Agreement, a copy which is attached as Exhibit 1.1 to this Current Report on Form 8-K and incorporated herein by reference. The legal opinion of Cooley LLP relating to the shares of Common Stock being offered pursuant to the Distribution Agreement is filed as Exhibit 5.1 to this Current Report on Form 8-K.

This Current Report shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any sale of such securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.