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POSEIDA THERAPEUTICS RECEIVES REGENERATIVE MEDICINE ADVANCED THERAPY (RMAT) DESIGNATION FROM FDA FOR P-BCMA-101

On November 5, 2018 Poseida Therapeutics Inc., a clinical-stage biopharmaceutical company focused on leveraging proprietary next-generation, non-viral gene engineering technologies to create life-saving therapeutics, reported the U.S. Food and Drug Administration (FDA) has granted a Regenerative Medicine Advanced Therapy (RMAT) designation to P-BCMA-101, Poseida’s lead CAR-T therapeutic candidate currently in a Phase 1 clinical trial for the treatment of patients with relapsed/refractory multiple myeloma (Press release, Poseida Therapeutics, NOV 5, 2018, View Source [SID1234565400]). RMAT designation includes all of the benefits of the Fast Track and Breakthrough Therapy designation programs, including early interactions with the FDA.

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"P-BCMA-101 is the first anti-BCMA CAR-T therapy to receive RMAT designation from the FDA and underscores the urgent need for new treatment options for multiple myeloma," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida Therapeutics. "Initial Phase 1 data presented at the CAR-TCR Summit earlier this year included encouraging response rates and safety data, including meaningful responses in a heavily pretreated population, with some patients reaching VGPR and stringent CR. We expect to have an additional data update by the end of the year and look forward to working closely with the FDA to expedite development of P-BCMA-101."

The RMAT designation is a program under the 21st Century Cures Act that is intended to expedite the development and review of regenerative medicines for the treatment of serious or life-threatening diseases and conditions. A regenerative medicine therapy is eligible for the designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the product has the potential to address unmet medical needs for such a disease or condition.

RMAT designation includes all Breakthrough Therapy designation features, including early interactions to discuss any potential surrogate or intermediate endpoints. RMATs may be eligible for accelerated approval based on previously agreed-upon surrogate or intermediate endpoints that are reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites, as appropriate.

About P-BCMA-101
P-BCMA-101 is an autologous CAR-T therapeutic candidate being developed to treat patients with relapsed/refractory multiple myeloma. P-BCMA-101 targets cells that express B cell maturation antigen, or BCMA, which is expressed on essentially all multiple myeloma cells. P-BCMA-101 is engineered with Poseida’s non-viral piggyBac DNA Modification System, resulting in a high percentage of T stem cell memory cells. Preliminary results from the company’s ongoing Phase 1 clinical trial suggest that P-BCMA-101 may have improved response rates with a favorable safety profile compared to published results from clinical trials of other CAR-T therapies at similar doses. Low to no levels of cytokine release syndrome or neurotoxicity have been seen. The Phase 1 study is funded in part by the California Institute for Regenerative Medicine.

SpringWorks Therapeutics Receives FDA Orphan Drug Designation for MEK Inhibitor
(PD-0325901) for the Treatment of Neurofibromatosis Type 1

On November 5, 2018 SpringWorks Therapeutics, a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation for PD-0325901, an investigational, oral, small molecule selective inhibitor of MEK1 and MEK2, for the treatment neurofibromatosis type 1 (Press release, SpringWorks Therapeutics, NOV 5, 2018, View Source [SID1234538852]).

Neurofibromatosis type 1, or NF1, is a rare genetic disorder that is caused by mutations in the NF1 gene, and that affects both children and adults. NF1 mutations can result in a loss of activity in the protein neurofibromin, which can lead to MAPK pathway overactivation, uncontrolled cellular growth, and tumor formation.1 NF1 is a heterogeneous condition that frequently causes plexiform neurofibromas, which are painful, disfiguring tumors of the peripheral nervous system. It is estimated that there are approximately 100,000 patients in the United States living with NF1. 2

"There is an urgent need for an effective treatment for patients with NF1. We are pleased that the FDA has granted Orphan Drug designation for our MEK inhibitor, recognizing its potential to improve the outlook for patients and families facing NF1," said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. "We look forward to working closely with the FDA as we prepare to initiate a Phase 2b study of PD-0325901 in patients with NF1-associated plexiform neurofibromas, a severe form of NF1 that causes tumors to grow on nerves throughout the body, which can cause severe pain, disfigurement, loss of range of motion, and shortened lifespan."

The FDA, through its Office of Orphan Products Development (OOPD), grants orphan drug designation to drugs and biologic products that are intended for treatment of rare diseases or disorders that affect fewer than 200,000 people in the United States. Orphan drug status is intended to facilitate drug development for rare diseases and may provide certain benefits and incentives to drug developers, including seven years of market exclusivity if the drug is approved, FDA assistance in clinical trial design, and tax credits for qualified clinical trial costs. 3

SpringWorks expects to initiate a Phase 2b single-arm, open-label study of PD-0325901 in patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-associated PN) in the first half of 2019.

About Neurofibromatosis Type 1
Neurofibromatosis type 1, or NF1, is a rare genetic disorder that is caused by mutations in the NF1 gene, and that affects both children and adults. Throughout their lifetime, about 30 to 50 percent of NF1 patients progress to a more severe form of the disease that results in the development of plexiform neurofibromas (PN), which are progressive peripheral nerve sheath tumors that cause severe pain, morbidity, and can significantly shorten lifespan.4-6 The clinical course of NF1-associated PN is heterogeneous with varying manifestations and severity across patients.

It is estimated that NF1 affects 1 in 3,000 individuals worldwide, and that there are approximately 100,000 patients in the United States living with this disease.2 Most patients with NF1-associated PN are treated with surgical removal of the tumors, sometimes requiring amputation; however, surgery has variable success rates and a high rate of recurrence has been observed because of the aggressive nature of these tumors.7 There are no therapies currently approved for the treatment of NF1-associated PN.

About PD-0325901
PD-0325901 is an investigational, oral, small molecule, selective inhibitor of MEK1 and MEK2, proteins that play key roles in the MAPK pathway. The MAPK pathway is critical for cell survival and proliferation, and overactivation of this pathway has been shown to help enable tumor growth. By blocking activity of the MAPK pathway, PD-0325901 may help arrest uncontrolled cellular growth associated with many types of tumors.

PD-0325901 has been tested in several Phase 1 and Phase 2 clinical trials, and approximately 260 subjects have been exposed to treatment. SpringWorks is evaluating PD-0325901 as a monotherapy for the treatment of patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-associated PN). In addition, given the critical role that the MAPK pathway plays in the growth and proliferation of a large number of tumor types, SpringWorks is also pursuing PD-0325901 in combination with other rational anticancer agents across a range of solid tumors.

Cotinga Pharmaceuticals Announces Research Partnership with St. Vincent’s University Hospital to Evaluate COTI-2

On November 5, 2019 Cotinga Pharmaceuticals Inc. (TSX Venture: COT; OTCQB: COTQF) ("Cotinga" or the "Company"), a clinical-stage pharmaceutical company advancing a pipeline of targeted therapies for the treatment of cancer, reported that it has entered into a research collaboration with St. Vincent’s University Hospital in Dublin, Ireland to evaluate COTI-2 in combination with eribulin in patients with triple negative metastatic breast cancer (Press release, Cotinga, NOV 5, 2018, View Source [SID1234533149]).

"Cotinga is committed to the development of therapies for a wide range of cancers, and our collaboration with St. Vincent’s University Hospital represents an important step towards realizing the full potential of our lead compound, COTI-2," said Dr. Richard Ho, M.D., Ph.D., Chief Scientific Officer. "Throughout this year we presented preclinical and early clinical results that support COTI-2 as a possible combination therapy, and this partnership with St. Vincent’s will allow us to further explore how COTI-2 may work alongside the standard of care in cancers with severe unmet medical need."

The Phase 1 study will aim to evaluate COTI-2 in combination with eribulin in the second or subsequent line therapy of patients with triple negative metastatic breast cancer. The primary objectives of the study will be to determine the optimal tolerated dose of COTI-2 that can be added to standard dose eribulin in the second or subsequent line treatment of metastatic breast cancer, and to assess the safety and tolerability of COTI-2 when administered with eribulin.

"Triple-negative metastatic breast cancer is a serious and difficult-to-treat disease that tends to be more aggressive than other types of breast cancer," said Professor John Crown, M.D., M.B.A., consultant medical oncologist at St. Vincent’s University Hospital. "Our research demonstrates that the p53 gene is mutated in approximately 80% of triple-negative tumors, and suggests that mutant p53 has potential as a therapeutic target. We are encouraged by early data from COTI-2, which targets mutant p53, and having seen synergy in our own preclinical testing of COTI-2 and eribulin, we look forward to evaluating the compound in combination with standard of care for patients with triple negative metastatic breast cancer."

Flex Pharma Reports Third Quarter 2018 Financial Results

On November 5, 2018 Flex Pharma, Inc. (NASDAQ: FLKS), reported its financial results for the three months ended September 30, 2018 (Press release, Flex Pharma, NOV 5, 2018, View Source [SID1234532475]).

On June 13, 2018, the Company announced that it was ending its ongoing Phase 2 clinical trial investigations of FLX-787 in Motor Neuron Disease (MND), which primarily included patients with amyotrophic lateral sclerosis (ALS), and in Charcot-Marie-Tooth disease (CMT), was reducing its workforce and engaged Wedbush PacGrow to help the Company assess its strategic alternatives.

"During the third quarter, we continued our assessment of strategic alternatives for the Company. While that assessment is underway, we are working diligently to conserve working capital and enhance stockholder value. We plan to announce additional information once our assessment is complete," stated Bill McVicar, Ph.D., President and CEO of Flex Pharma.

Corporate Activities:

The Company has stopped its clinical trials in MND and CMT and the wind-down of the associated activities was completed in the third quarter of 2018.

The reduction in the Company’s workforce announced on June 13, 2018 was completed by September 30, 2018.
Third Quarter 2018 Financial Results

Cash Position: As of September 30, 2018, Flex Pharma had cash and cash equivalents of $13.0 million. The Company held no marketable securities at September 30, 2018. During the three months ended September 30, 2018, cash and cash equivalents decreased by $2.8 million.

Total Revenue: Total HOTSHOT revenue for the three months ended September 30, 2018 was approximately $251,000.

Cost of Product Revenue: Cost of product revenue for the three months ended September 30, 2018 was approximately $92,000. There were no inventory write-offs during the three months ended September 30, 2018.
R&D Expense: Research and development expense for the three months ended September 30, 2018 was $0.9 million. Research and development expense for this period primarily included costs associated with the Company’s clinical operations and wind-down of FLX-787 Phase 2 clinical studies, personnel costs (including salaries, termination-related costs, retention-related costs and stock-based compensation costs) and external consultant costs.
SG&A Expense: Selling, general and administrative expense for the three months ended September 30, 2018 was $2.0 million. Selling, general and administrative expense for this period primarily included personnel costs (including salaries, retention-related costs and stock-based compensation costs), fulfillment costs related to HOTSHOT, legal and professional costs, and external consultant costs.

Net Loss and Cash Flow: Net loss for the three months ended September 30, 2018 was ($2.6) million, or ($0.15) per share and included $0.3 million of stock-based compensation expense. As of September 30, 2018, Flex Pharma had 18,066,767 shares of common stock outstanding. The net loss for the third quarter of 2018 was primarily driven by the Company’s operating expenses related to its research and development efforts, costs associated with HOTSHOT, and general and administrative costs.

BioXcel Therapeutics Announces FDA Acceptance of IND for Lead Immuno-oncology Candidate, BXCL701, in Treatment Emergent Neuroendocrine Prostate Cancer

On November 5, 2018 BioXcel Therapeutics, Inc. ("BTI" or "Company") (BTAI), reported that the U.S. Food and Drug Administration ("FDA"), has accepted its Investigational New Drug ("IND") application for its lead immuno-oncology candidate, BXCL701 (Press release, BioXcel Therapeutics, NOV 5, 2018, View Source [SID1234530886]). BTI plans to evaluate BXCL701 in combination with pembrolizumab (Keytruda) as a potential therapy for treatment-emergent neuroendocrine prostate cancer ("tNEPC"), with the trial expected to initiate in the fourth quarter of 2018. BTI is a clinical stage biopharmaceutical development company that utilizes novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology.

Dr. Vincent J. O’Neill, Senior Vice President and Chief Medical Officer of BTI, commented, "FDA approval of this IND is a significant milestone for our BXCL701 program, as we are now able to commence the Phase 1b/2 combination study in tNEPC patients. We believe that the combination of BXCL701 and pembrolizumab has the potential to meaningfully improve the lives of patients with this highly aggressive, rare form of prostate cancer, and to succeed where current checkpoint inhibitor monotherapies have demonstrated limited clinical benefit. We have an obligation to tNEPC patients to find a viable treatment and look forward to evaluating the combination in this trial."

Dr. Vimal Mehta, Chief Executive Officer of BTI added, "The FDA approval of this IND and initiation of this trial provides an important validation of our AI-powered approach to drug development, which enables us to develop therapeutic candidates more quickly, at a lower cost and with a higher probability of success than with traditional drug development approaches."

The Phase 1b/2 study is expected to enroll up to 40 subjects at multiple trial sites. The goal of this single arm, Simon 2-stage open label study is to examine the safety, pharmacokinetics and anti-tumor activity of the combination of BXCL701 and pembrolizumab in tNEPC patients with the efficacy endpoint of objective response rate. Data readouts are expected throughout 2019.

About BXCL701

BXCL701 is an orally-available systemic innate-immune activator with dual mechanisms of action. It has demonstrated single agent activity in melanoma, with an established

safety profile from 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 works by inhibiting dipeptidyl peptidase (DPP) 8/9 and blocking immune evasion by targeting Fibroblast Activation Protein (FAP). Preclinical combination data evaluating BXCL701, a checkpoint inhibitor and other immuno-oncology agents has demonstrated encouraging anti-tumor activity in multiple tumor types and formation of functional immunological memory. BXCL701’s primary mechanism of action has recently been highlighted in multiple peer reviewed journals, providing an important validation of the scientific rationale behind BXCL701.

About Treatment-emergent neuroendocrine prostate cancer (tNEPC)

tNEPC is a rare hormone-refractory manifestation of prostate cancer occurring secondary to treatment with androgen deprivation therapies such as Zytiga (Johnson & Johnson) and Xtandi (Pfizer). This form of highly aggressive tumor, with no current treatment, is observed in approximately 20-30% of patients treated with androgen inhibitors and has a median survival time of less than one year. Single agent checkpoint inhibitor therapy produces very low response rates in hormone refractory prostate cancer, creating a major unmet medical need for tNEPC patients.