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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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."

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On November 5, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the European Medicines Agency (EMA) validated for review and granted accelerated assessment to the Marketing Authorization Application (MAA) for quizartinib for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) which is FLT3-ITD positive (Press release, Daiichi Sankyo, NOV 5, 2018, View Source [SID1234530874]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). Accelerated assessment is given to products expected to be of major interest for public health and therapeutic innovation and can significantly reduce the review timelines.

The EU MAA is based on results of the pivotal phase 3 QuANTUM-R study of quizartinib, which was the first randomized phase 3 study to show that a FLT3 inhibitor prolonged overall survival as an oral, single agent compared to chemotherapy in patients with relapsed/refractory FLT3-ITD AML. Topline results of the phase 3 QuANTUM-R study were presented during the plenary program at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June 2018.

"The accelerated assessment of the quizartinib MAA underscores the significant unmet need for patients with relapsed/refractory FLT3-ITD AML, a very aggressive form of the disease with no approved targeted treatment options in Europe," said Arnaud Lesegretain, Vice President, Oncology Research and Development and Head, AML Franchise, Daiichi Sankyo. "Achieving both these milestones are significant next steps and we look forward to working with the EMA to bring this important potential new targeted treatment option to patients in the EU."

Quizartinib is currently under accelerated regulatory review with the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of adult patients with relapsed/refractory FLT3-ITD AML. Submission in the U.S. remains on track for the second half of fiscal year 2018.

In the QuANTUM-R study, the median treatment duration with quizartinib was 4 cycles of 28 days each versus 1 cycle in the salvage chemotherapy arm. Incidence of treatment-emergent adverse events was comparable between patients who received single agent quizartinib and those who received salvage chemotherapy. The most common adverse drug reactions (>30 percent, any Grade) in patients treated with quizartinib included infections, bleeding, nausea, asthenic conditions, pyrexia, febrile neutropenia and vomiting, and the most common Grade ≥ 3 adverse drug reactions (>20 percent) were infection and febrile neutropenia. The most common laboratory adverse reactions (incidence >50 percent) were decreased white blood cell count, decreased lymphocyte count, decreased hemoglobin, decreased neutrophil count and decreased platelet count. The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program.

About FLT3-ITD Acute Myeloid Leukemia
AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells.1FLT3 gene mutations are one of the most common genetic abnormalities in AML.2 FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML.3,4,5,6 FLT3-ITD is a driver mutation that presents with high leukemic burden and has poor prognosis and a significant impact on disease management for patients with AML.4,7

Patients with FLT3-ITD AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapse and a higher likelihood of relapse following hematopoietic stem cell transplantation as compared to those without this mutation.8,9

About Quizartinib

Quizartinib, the lead investigational agent in the AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective FLT3 inhibitor currently in phase 3 development for relapsed/refractory FLT3-ITD AML (QuANTUM-R) in the U.S. and EU; phase 3 development for newly-diagnosed FLT3-ITD AML (QuANTUM-First) in the U.S., EU and Japan; and, phase 2 development for relapsed/refractory FLT3-ITD AML in Japan.

Quizartinib has been granted Breakthrough Therapy designation for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, and Fast Track designation for the treatment of relapsed/refractory AML by the U.S. Food and Drug Administration (FDA). Quizartinib also has been granted Orphan Drug designation by both the FDA and the European Commission (EC) for the treatment of AML and by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of FLT3-mutated AML.

Quizartinib is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.