On November 13 2019 F1 Oncology, Inc., a biotechnology company discovering and developing adoptive cellular therapies (ACTs) for solid tumors, reported that its international affiliate, EXUMA Biotechnology Hong Kong, has formed Shanghai EXUMA Biotechnology Co., Ltd., a wholly foreign-owned enterprise (WFOE), to acquire all rights to novel chimeric antigen receptor T (CAR-T) cell therapy and manufacturing assets in Shanghai and Shenzhen for the development and commercialization of cellular therapies in Greater China to be used in the treatment of solid tumor malignancies (Press release, EXUMA Biotechnology, NOV 13, 2019, View Source [SID1234551150]).

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Shanghai EXUMA will develop these clinical programs into multicenter trials under a centralized regulatory pathway based on the results of investigator-initiated trials (IITs) of CAR-T therapies for the treatment of metastatic renal cell carcinoma (mRCC) and other solid tumor malignancies. Shanghai EXUMA will be expanding its CAR-T cell processing capabilities at its new facility in the Shanghai International Medical Zone within Zhangjiang Innopark in Shanghai’s Pudong district and its viral manufacturing capabilities at its newly constructed Shenzhen facility.

"The treatment of cancer is advancing at unprecedented speed, and we are pleased to be playing a role in this rapid and positive evolution, of which the formation of Shanghai EXUMA Biotechnology is an important component," said Gregory Frost, Ph.D., Chairman and CEO of F1 Oncology. "The decision to integrate these programs and processes into EXUMA was driven by the favorable early clinical profile, and we are excited to support their advancement toward multicenter trials next year. By turning a hostile tumor microenvironment (TME) into an activating signal for CAR-T cells, this platform could open the therapeutic window of CAR-T to many solid tumors."

EXUMA Biotech integrates BioAtla’s conditionally active biologic (CAB) protein therapeutic technology with F1 Oncology’s proprietary CAR-T technologies to develop and commercialize CAB-CAR-T therapies and other ACTs for the treatment of solid tumor malignancies. CAB-CAR-T cellular therapies are designed to be conditionally active only in the TME and may therefore help reduce potential adverse events associated with on-target, off-tumor effects of CAR-T therapies in solid tumors. While BioAtla’s option to purchase F1 Oncology expired in May 2018, F1 Oncology retains an exclusive global license to discover and develop CAB-based ACTs.

On November 13, 2019 ProMIS Neurosciences, Inc. ("ProMIS" or the "Company") (TSX: PMN; OTCQB:ARFXF), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, reported that it is undertaking a private placement of up to 32.5M Units at a price of CDN$0.20 (or US$0.15) per Unit for gross proceeds of up to CDN$6,500,000 (the "Offering") (Press release, ProMIS Neurosciences, NOV 13, 2019, View Source [SID1234551157]). ProMIS expects to complete a first closing in November 2019 in the amount of approximately CDN$2,055,000.

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"We are pleased to offer this private placement designed to afford a cash runway well into 2020. Proceeds of the offering will support further development of our programs targeting Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease, each of which is the subject of ongoing partnering discussions with large biopharmaceutical companies," stated Dr. Elliot Goldstein, ProMIS President and CEO.

Each Unit will consist of one common share of the Company and one share purchase warrant of the Company (each a "Warrant"). Each Warrant will entitle the holder thereof to purchase one share at an exercise price of $0.35 per share at any time through the fifth anniversary of the offering.

All securities issued in connection with the Offering will be subject to a four-month statutory hold period in accordance with applicable provincial securities laws in Canada. Net proceeds from the Offering are intended to be used to advance the Company’s antibody therapeutic candidates selectively targeting toxic oligomers implicated in neurodegenerative diseases, for working capital and general corporate purposes. Closing of the Offering is subject to TSX approval.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful. The securities issued, or to be issued, under the Offering have not been, and will not be, registered under the United States Securities Act of 1933, as amended, and may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements.

On November 13, 2019 Cellectis (Euronext Growth: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported a paper published in Nature Communications that describes a proof-of-concept for rewiring the cell pathway to create highly intelligent T-cells that can recognize cancerous tumors and cause a micro secretion of therapeutic proteins onto these tumors, which ultimately reshapes the tumor microenvironment and improves the T-cells ability to fight cancer (Press release, Cellectis, NOV 13, 2019, View Source [SID1234551149]). By utilizing gene editing techniques to rewire the TCRα, CD25 and PD1 genes, the study enabled CAR T-cells to micro secrete the pro-inflammatory cytokine, IL-12, in a tumor and time-dependent manner, paving the way for a next generation of tightly controlled, highly active and potentially safer CAR T-cell treatments.

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"Discussion around the tumor microenvironment has become a popular topic in the CAR T-cell space, and with recent advancements in gene editing technologies, especially TALEN, it is now possible to manipulate the way a T-cell regulates itself to adapt to its environment," said Dr. Philippe Duchateau, Ph.D., Chief Scientific Officer, Cellectis. "With seamless modification of multiple genes, and subsequently rewiring their natural regulatory processes, this approach causes the T-cells to secrete therapeutic proteins of interest in a tightly controlled and localized manner. We have essentially transformed the current T-cells used today into precise and powerful micro-robots that can spray IL-12 specifically onto cancer cells – potentially avoiding the toxicity of a systemic injection of IL-12, while enhancing CAR-T activity."

"Our extensive knowledge in TALEN-based gene editing and DNA donor template design enabled us to develop this groundbreaking proof-of-concept, a milestone that paves the way to the next generation of CAR T-cells," added Dr. Julien Valton, Ph.D., Innovation Team Leader, Cellectis. "These highly intelligent CAR T-cells can sense and remodel their microenvironment in a tailored, highly regulated, and antigen-specific manner, allowing us to have more control over increasingly potent treatments and less risk of general secretion into healthy tissues. This engineering strategy could bring smarter, safer and more effective treatments to the forefront for patients in need."

Julien Valton, Ph.D., Innovation Team Leader, Cellular Engineering & Adoptive CAR T-Cell Immunotherapy

Dr. Julien Valton obtained his Ph.D. at the University Joseph Fourier in Grenoble, France, where he was trained as an enzymologist. He then joined the Yale School of Medicine to apply his knowledge to therapeutic research by investigating the mechanism of inhibition of receptor tyrosine kinases that are involved in the development of gastrointestinal cancer. In 2009, he moved a step further into the field of applied science by joining the Innovation Department of Cellectis, where he actively participated in using and improving TALEN gene editing technology for targeted gene therapy and genome engineering. He is now using TALEN along with protein engineering techniques to develop the next-generation CAR T-cells to treat different malignancies.

On November 13, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported it has begun preclinical testing of its drug candidate, WP1122, which it believes may present a new approach to treating highly glycolytic tumors like pancreatic cancer and glioblastoma (Press release, Moleculin, NOV 13, 2019, View Source [SID1234551156]).

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Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors. (PRNewsfoto/Moleculin Biotech, Inc.)

"WP1122 represents an opportunity to attack the metabolism of cancer by exploiting the Warburg principle, which explains that some tumors are highly dependent on glycolysis, a specific metabolism of glucose, for growth and survival," commented Walter Klemp, Moleculin’s Chairman and CEO. "What this means in practice is that tumors are vulnerable by being highly dependent on glucose availability. Cancer cells often consume up to 18 times as much glucose as their healthy normal cells’ neighbors, suggesting that we may be able to starve tumors by supplying them with glucose decoys that would inhibit glucose-based energy production. However, until the creation of WP1122, glucose decoys like 2-deoxy-D-glucose (‘2-DG’) lacked the drug-like properties to be effective, primarily because of rapid metabolism and a very short circulation time in the body, which then limits desired organ and tumor uptake."

Dr. Don Picker, Chief Science Officer for Moleculin, added: "WP1122 is a prodrug of 2-DG that has been shown in animal models to significantly increase the half-life of 2-DG and allows for increased uptake to targeted organs and tumors like the brain tumors and pancreatic cancer. Recent discoveries now also suggest that such a glucose decoy could critically impact a process known as glycosylation and glycan formation and that this type of activity can directly impact the function of PD-L1, enabling increased immune system response to cancer cells. We have been working on the clinical formulation of WP1122 for some time, and we are eager to now be taking the next key steps to getting WP1122 into the clinic."

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.