On November 13, 2019 Turbine, a simulation-based drug discovery company reported the closing of an institutional financing round led by Delin Ventures (Press release, Turbine, NOV 13, 2019, View Source [SID1234551170]). The seed fund will be used to redesign the failure-prone oncology drug discovery process into a series of rational steps facilitated by Turbine’s proprietary human cell model and simulation platform.

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The company’s first institutional financing round of €3m will be used to expand the rational, simulation-based drug discovery workflow into every phase of drug discovery from research to lifecycle management. Leading the round was computational biology venture fund, Delin Ventures with participation from follow-on angel investors such as health-tech veterans Esther Dyson, Vishal Gulati and Atlantic Labs. Newly joining investors include o2h Ventures, who have launched the UK’s first seed and enterprise investment scheme fund backing early stage biotech. Alan Barge, former VP & Head of Oncology Therapy Area at AstraZeneca and Partner at Delin Ventures, now joins the Board of Directors of Turbine.

Turbine was founded on the premise that a computational model of human cell biology would rationalize drug discovery the same way that computer-aided design revolutionized architecture. Based on a decade of research, Turbine’s biologists, bioinformaticians, data scientists, and AI engineers built the Simulated Cell. This platform is comprised of a dynamic computational model of the human cell and the underlying simulation technology to find the smartest route to novel targets, biomarkers, and combination therapies. Unlike other solutions in drug discovery, the Simulated Cell explains the response of cancer cells to drugs on a mechanistic level. The 50-strong team has also recently kicked-off its initial simulation-based drug discovery program centred around DNA Damage Repair (DDR).

Designing life-saving therapies for cancer patients demands a vast amount of financial investment, time and brainpower from pharmaceutical companies, yet 96.6% of new anticancer drugs still fail during clinical trials 1. Many of these failures can be attributed to the incredible complexity of biology. Current lab methodologies provide only a limited understanding of how and why cancer cells respond to drugs. Turbine believes that narrowing down true novelty will be a success rate booster in every step drug discovery can fail today.

Szabolcs Nagy, CEO of Turbine, said: "Over the last couple of years, we have guided the anti-cancer drug discovery process of leading pharmaceutical companies, allowing us to strengthen our simulation-first capabilities. We believe our methods have the potential to transform the current trial-and-error approach to drug discovery into an iterative process, marked by rational decisions, and leading to better drugs faster." Many of the Budapest-based team’s in silico predictions for pharmaceutical partners are now in the clinical validation phase.

Alan Barge, former VP & Head of Oncology Therapy Area at AstraZeneca, Partner at Delin Ventures, and Non-Executive Director at Turbine, commented: "We have been very impressed by Turbine’s capability to model and simulate complex biological problems first, and then decide on the fate of drugs based on a deep understanding of the problem. This resourcefulness is deeply rooted in the DNA of the team. They have come a long way in developing and validating the platform leaning on revenue from industry collaborations, while also arriving at promising in vitro validation of their simulation-first DDR drug discovery program within just a couple of months. We look forward to supporting this talented team during the next stage of its development."

On November 13, 2019 Skyhawk Therapeutics, Inc. (Skyhawk), reported that it has reached a second global strategic collaboration agreement with a subsidiary of Celgene Corporation (NASDAQ: CELG ) (Press release, Skyhawk Therapeutics, NOV 13, 2019, View Source [SID1234551230]). This new agreement is made after the June 2018 collaboration between the two companies and focuses on relevant targets in the field of autoimmune disorders, oncology and immunooncology, thus revalidating the patented SkySTAR TM technology platformfrom Skyhawk. The scope of this collaboration allows the parties to systematically examine a series of targets that have been clinically validated or that are associated at a high level with the genetic basis of the disease, but that have been considered resistant to drugs by conventional based treatments of small molecules.

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Under the collaboration agreement, Skyhawk grants Celgene the option to grant exclusive licenses of intellectual property rights worldwide to pharmacological candidates discovered and developed under the auspices of the collaboration agreement and aimed at the targets of the program. In the event that Celgene decides to make use of this option, Celgene will be responsible for its development and commercialization.

"Our impressive advances to date in relation to the targets that our collaboration that took place in 2018 includes have led Celgene to sign this new agreement focused on targets that go beyond neurology," said Bill Haney , co-founder and CEO from Skyhawk Therapeutics. "This is further proof of the capacity of our SkySTAR TM technology platformto quickly identify niches where to apply the drugs and the unique chemical matter to correct the incorrect splicing of RNA, and that can lead to new treatment options for patients. We look forward to seeing the progress of the programs in line with this new collaboration and the potential to offer new treatment options to patients with unmet medical needs. "

"The rapid and remarkable progress made by the Skyhawk team shows us the exclusive advantages of the SkySTAR TM platform and has led us to expand our relationship. We see the Skyhawk platform as a revolutionary and key technology that supports the portfolio of disease treatments autoimmune, oncological and immuno-oncology of the company that we are today and that which we have set ourselves to become, "said Rupert Vessey , MA, BM, B.Ch., FRCP, D.Phil., president of Research and Initial Development of Celgene Corporation

On November 13, 2019 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer, autoimmune/inflammatory, and other diseases, reported a corporate update and financial results for the third quarter ended September 30, 2019 (Press release, Alpine Immune Sciences, NOV 13, 2019, View Source [SID1234551138]).

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"The third quarter of 2019 included several significant milestones for Alpine, highlighted by completion of enrollment in our Phase 1 study in healthy volunteers for our lead program, ALPN-101," said Mitchell H. Gold, MD, Executive Chairman and Chief Executive Officer of Alpine. "We believe ALPN-101 has the potential to deliver significantly differentiated efficacy outcomes across a range of inflammatory and autoimmune diseases. We look forward to highlighting our upcoming Phase 1/2 BALANCE study of ALPN-101 during an oral presentation at the ASH (Free ASH Whitepaper) annual meeting next month."

"In addition, we are actively preparing for the initiation of the Phase 1 NEON-1 study of our lead immuno-oncology program, ALPN-202," Dr. Gold said. "At Alpine, we share a deep commitment and drive to deliver the next generation of immunotherapies to patients suffering from debilitating and deadly diseases and I am proud of the work our entire team has done in the transformation of Alpine to an established, clinical-stage company."

Recent Pipeline and Company Highlights

ALPN-101 Clinical Advancement

Completed enrollment of Phase 1 Study of ALPN-101: On October 30, 2019, Alpine announced completion of enrollment of its Phase 1 study of ALPN-101, a first-in-class dual ICOS/CD28 antagonist. Results from this trial will help inform further development of ALPN-101 in serious autoimmune and inflammatory diseases.
Overall, ALPN-101 was generally well-tolerated, without evidence of cytokine storm, cytokine release, or clinical immunogenicity while being dosed as single or multiple doses, intravenously or subcutaneously.
Preliminary analyses indicate well-behaved pharmacokinetics and pharmacodynamics, including on-target inhibition of immune functionality, such as antibody responses to keyhole limpet hemocyanin (KLH) and ex vivo staphylococcal enterotoxin B (SEB)-induced cytokine responses.
These initial findings will be included as part of an oral presentation at ASH (Free ASH Whitepaper) next month, and further details after completion of final analyses are expected to be reported in presentations in the first half of 2020.
New ALPN-101 Data Presented at American College of Rheumatology (ACR) Annual Meeting: Earlier this week, Alpine presented new preclinical data on ALPN-101 in two posters during sessions at ACR. The new data highlighted ALPN-101’s novel dual mechanism of action which modulates unique inflammatory pathways, distinct from the other biologic therapies singly targeting the ICOS or CD28 pathways, and results in potent efficacy in multiple disease models. The full posters from ACR can be viewed here.
Upcoming Oral Presentation at American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting: Alpine will present on its upcoming Phase 1/2 BALANCE study of ALPN-101 in steroid-resistant or steroid-refractory acute Graft-versus-Host Disease (GvHD). Dr. Jan Hillson, Senior Vice President, Clinical Development for Alpine, will present on December 8, 2019 at 11:00 a.m. ET. The full abstract can be viewed here.
ALPN-202 Preparing for Phase I Study

New ALPN-202 Data Presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting: On November 8, 2018, Alpine presented two posters with new preclinical data on its lead oncology program ALPN-202, a conditional CD28 costimulator and dual checkpoint inhibitor. The new preclinical data further highlight ALPN-202’s novel mechanism of action and its superior anti-tumor activity, as well as its potential to be uniquely effective as a monotherapy and in combination with immune checkpoint inhibitors or chemotherapy. The full posters from SITC (Free SITC Whitepaper) can be viewed here.
Data presented at SITC (Free SITC Whitepaper) supports the advancement of ALPN-202 towards its first Phase 1 clinical trial, which Alpine expects to initiate, upon authorization, in the first quarter of 2020.
Financial Results for Third Quarter and Nine Months Ended September 30, 2019

Alpine recorded a net loss of $11.5 million and $12.1 million for the third quarters ended September 30, 2019 and 2018, respectively, and $35.7 million and $25.4 million for the nine months ended September 30, 2019 and 2018, respectively.

Research and development expenses for the third quarter ended September 30, 2019 were $9.5 million compared to $10.5 million for the third quarter ended September 30, 2018. For the nine months ended September 30, 2019 and 2018, research and development expenses were $30.0 million and $20.0 million, respectively. The company expects a continued increase to research and development activities to support the clinical advancement of its ALPN-101 and ALPN-202 programs.

General and administrative expenses for the third quarter ended September 30, 2019 were $2.5 million compared to $1.9 million for the third quarter ended September 30, 2018. For the nine months ended September 30, 2019 and 2018, general and administration expenses were $7.4 million and $5.8 million, respectively. The increase was primarily attributable to professional and legal services and an increase in facility costs to support the growth and expansion of our business.

Cash Position

As of September 30, 2019, Alpine had cash, cash equivalents, restricted cash, and short-term investments totaling $47.0 million. For the nine months ended September 30, 2019, net cash used in operating activities was $29.7 million compared to $19.0 million for the nine months ended September 30, 2018.

Management will provide updates to cash guidance on the conference call scheduled to discuss third quarter 2019 financial results.

Conference Call and Webcast Details

Alpine will host a conference call to discuss key data, clinical highlights and provide an update on third quarter 2019 results on Wednesday, November 13, 2019 at 4:30 p.m. ET. To access the live call by phone, dial (877) 407-0789 (domestic) or (201) 689-8562 (international). To access a live webcast of the call, please visit the Investor Relations section of the Alpine Immune Sciences website at www.alpineimmunesciences.com. The recorded webcast will be available for replay for approximately 30 days following the call.

About ALPN-101

ALPN-101 is a novel Fc fusion protein of a human inducible T cell costimulator ligand (ICOSL) variant immunoglobulin domain (vIgD), and a first-in-class therapeutic designed to inhibit simultaneously the CD28 and ICOS inflammation pathways. CD28 and ICOS are closely related costimulatory molecules with partially overlapping roles in T cell activation likely connected to multiple autoimmune and inflammatory diseases. In preclinical models of graft versus host disease, inflammatory arthritis, connective tissue disease and multiple sclerosis, ALPN-101 demonstrates efficacy superior to blockade of the CD28 or ICOS pathways alone.

About ALPN-202

ALPN-202 is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor, which has the potential to improve upon the efficacy of combined checkpoint inhibition without significant toxicities. Preclinical studies of ALPN-202 have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. We anticipate initiation, upon authorization, of the first-in-human clinical study of ALPN-202 to begin in the first quarter of 2020.

On November 13, 2019 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a Phase 3 clinical-stage biopharmaceutical company dedicated to developing and commercializing etripamil for the treatment of cardiovascular indications, reported financial results for the third quarter ended September 30, 2019 and provided a clinical and corporate update(Press release, Milestone Pharmaceuticals, NOV 13, 2019, View Source [SID1234551155]).

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"Thanks to the hard work of our study team, a dedicated group of clinical sites, and, importantly, the patients participating in our study, NODE-301 continues to exceed our enrollment and PSVT event rate expectations, with topline data now expected in the middle of the first half of 2020," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "In addition, progress continues with efforts to ramp up our recently initiated global safety study, NODE-303, the largest study ever conducted in PSVT."

Mr. Oliveto added, "I am honored to welcome Dr. Richard Pasternak to our Board of Directors. A cardiologist by training, he brings a wealth of cardiovascular drug development experience that incorporates academia, large pharma and small entrepreneurial companies."

NODE-301 Update

Milestone reported that it now expects to report topline data for the NODE-301 trial in the middle of the first half of 2020. The NODE-301 trial is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial of etripamil, the Company’s novel short-acting calcium channel blocker, for terminating paroxysmal supraventricular tachycardia (PSVT) episodes in the outpatient setting. The study is designed to treat an enriched population of those PSVT patients who historically experience 20 minutes or longer PSVT episodes or episodes requiring termination in the emergency department. The primary endpoint of the NODE-301 study is time to conversion of PSVT to sinus rhythm after the administration of study drug, as confirmed by a central independent adjudication committee. Secondary study endpoints include relief of symptoms commonly associated with an episode of PSVT such as heart palpitations, chest pain, anxiety, shortness of breath, dizziness, or fainting, and rating of treatment satisfaction questionnaire for medication (TSQM).

As previously announced, after the NODE-301 trial reaches its target number of adjudicated PSVT events, collection of blinded data from randomized patients who have not yet experienced an event will continue. These data will be analyzed separately as a secondary data set, referred to as NODE-301B, and may contribute further to sub-population analyses and pharmacoeconomic assessments.

Recent Updates

· Richard C. Pasternak, M.D. Appointed to Board of Directors. The Company also reported that Richard C. Pasternak, M.D. has been appointed to its Board of Directors. He brings to Milestone over 40 years of clinical, academic, and biopharmaceutical industry experience in the area of cardiology. He will serve as a member of the Company’s compensation committee.

Dr. Pasternak recently retired from Cerenis Therapeutics (now ABIONYX Pharma), a French publicly-traded company focused on developing treatments for cardiovascular diseases, where he served as Chief Executive Officer and Chair of the Board of Directors. He previously served as Vice President, Head of Cardiovascular Clinical Research, and Head of Global Scientific Affairs and Scientific Leadership, at Merck & Co. from 2004 to 2010. Prior to joining Merck, he was the Director of Preventive Cardiology and Cardiac Rehabilitation at Massachusetts General Hospital, and an Associate Professor of Medicine at Harvard Medical School.

Dr. Pasternak is currently a Clinical Professor at the Weill Cornell Medical College, and serves on the Boards of Anthos Therapeutics and Magenta Medical Ltd. He previously served on the Boards of Essentialis Therapeutics and Haptocure Ltd., as well as several nonprofit organizations. He was also previously a senior advisor to Bay City Capital and Bridge Medicines. Dr. Pasternak has authored more than 100 publications and has lectured internationally on cardiovascular disease drug development. He received his B.A. and M.D. from Yale University, and completed his medical and cardiology training at Massachusetts General Hospital.

·Company to Commence Clinical Evaluation of Etripamil in Atrial Fibrillation with Rapid Ventricular Rate (RVR). In 2020, Milestone plans to initiate a proof-of-concept clinical trial of etripamil for the treatment of patients with atrial fibrillation with RVR, another type of supraventricular tachycardia, in which most patients experience episodes of elevated heart rates and for which L-type calcium channel blockers are approved for rate control.

· Enrolled First Patient in NODE-303 Study. In October 2019, Milestone announced enrollment of the first patient in the Company’s Phase 3 open-label, global safety study of etripamil in patients with PSVT. The study will primarily evaluate the safety of etripamil when self-administered without medical supervision during single or multiple PSVT episodes. Important secondary measures include efficacy, patient quality of life and pharmacoeconomic assessments. The study represents the largest study ever conducted in PSVT, assessing up to 1,500 patient episodes from patients who did not participate in NODE-301 or its open-label safety extension study, NODE-302.

Announced Appointment of Amit Hasija as Chief Financial Officer and Executive Vice President of Corporate Development. In September 2019, the Company announced the appointment of Amit Hasija as Chief Financial Officer and Executive Vice President of Corporate Development. Mr. Hasija brings to Milestone two decades of experience in corporate finance and business development within the healthcare industry.

Third Quarter 2019 Financial Results

· As of September 30, 2019, Milestone had cash, cash equivalents, and short-term investments of $136.5 million and 24.5 million shares outstanding.

·Research and development expense for the third quarter of 2019 was $9.5 million compared with $3.9 million for the prior year period. For the nine months ended September

30, 2019, research and development expense was $27.8 million compared with $9.6 million for the prior year period. The increase in 2019 amounts reflects spending on Milestone’s full Phase 3 clinical program evaluating etripamil for the treatment of PSVT.

·General and administrative expenses for the third quarter of 2019 were $2.1 million compared with $0.6 million for the prior year period. For the nine months ended September 30, 2019, general and administrative expense was $4.7 million compared with $1.8 million for the prior year period. During 2019, Milestone increased its managerial headcount and, as a result, the related personnel costs. In addition, Milestone incurred increased spending for consulting fees, recruiting fees and professional fees, including legal and accounting services incurred to support its IPO.

· Commercial expense for the third quarter of 2019 was $2.1 million compared with $1.2 million for the prior year period. For the nine months ended September 30, 2019, commercial expense was $6.4 million compared with $2.3 million for the prior year period. These increases reflect increased commercial headcount and related costs, continued commercial and market research, increases in Milestone’s patient advocacy activities and costs for its medical affairs team focused on key opinion leaders’ engagement and disease awareness.

·For the third quarter of 2019, operating loss was $12.9 million compared to $5.7 million in 2018. For the nine months ended September 30, 2019, Milestone’s operating loss was $37.0 million compared to $13.5 million in the prior year period.

About Etripamil in Paroxysmal Supraventricular Tachycardia

Paroxysmal Supraventricular Tachycardia (PSVT) is a rapid heart rate condition that starts and stops without warning, often experienced by patients with symptoms including palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting and anxiety. Calcium channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions, however, for episodes of PSVT calcium channel blockers are currently administered intravenously under medical supervision, usually in the emergency department. By contrast, etripamil is designed to serve as a self-administered therapy for the rapid termination of episodes of PSVT. With its combination of convenient delivery, rapid onset and short duration of action, etripamil has the potential to shift the current treatment paradigm for PSVT away from the burdensome and costly emergency department settings by treating episodes of PSVT wherever and whenever they occur.

On November 13, 2019 Verastem, Inc. (Nasdaq: VSTM), (Verastem Oncology or the Company), a biopharmaceutical company focused on developing and commercializing medicines seeking to improve the survival and quality of life of cancer patients, reported that Andrei Shustov, M.D., Professor of Medicine and Hematology, University of Washington, Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center and President and Founder of the T-Cell Leukemia and Lymphoma Foundation (TCLLF) has been selected to receive the Company’s Innovation in Care Award (Press release, Verastem, NOV 13, 2019, View Source [SID1234551171]).

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The Verastem Oncology Innovation in Care Award recognizes individuals, organizations or teams who are leading the way in advancing the principles of patient-focused care, including coordination and integration of care, engaging patients, families, and caregivers in providing comprehensive support as well as collaborating with others in the cancer care system for ongoing quality improvement.

"Recognizing a critical lack of resources available to those affected by T-cell leukemias and lymphomas, Dr. Shustov has dedicated his career to breaking new ground to expand support and research efforts to those affected by these diseases," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "As a company, we aim to follow the example of leaders like Dr. Shustov as we not only seek to deliver therapies that keep cancer at bay, but also continually look to innovate to improve the lives of those diagnosed with cancer."

The TCLLF is committed to providing reliable, accurate and quality resources to patients, family members, caregivers and medical professionals looking to learn more about T-cell leukemias and lymphomas. Its patient education forums give direct access to T-cell leukemia/lymphoma specialists, which allows them the opportunity to learn more about their specific disease and ask personalized questions. The Foundation has also recently started sponsoring an annual T-Cell Leukemia/Lymphoma Young Investigator Grant with the goal of producing valuable research efforts and encouraging new oncologists/hematologists to specialize in the treatment of these diseases.

"Patients and their families affected by rare lymphoid malignancies like T-cell lymphomas have very limited resources available to them to learn about their disease and its management. With knowledge comes hope and power to take charge in making important decisions regarding one’s life, and all patients deserve that," said Dr. Shustov. "The fight with cancer, like lymphomas, only begins in the doctor’s offices and treatment centers; the real challenge faces patients and families at home. This aspect of patient care always felt missing. Filling this gap and providing patients with education, access to expert opinions, and opportunity to connect with other patients and families, were the inspirations behind the founding of TCLLF."

The Verastem Oncology Innovation in Care Award will be presented to Dr. Shustov at a Verastem Oncology reception on December 6, 2019 during the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in Orlando, FL. Last year, the inaugural award recipient was Brian Koffman, M.D., founder and volunteer Medical Director of the nonprofit CLL Society (CLLS). Since his own CLL diagnosis in 2005, Dr. Koffman has dedicated himself to teaching and advocating on behalf of the CLL community.