On April 14, 2021 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported the publication of a second poster for the GP2 Phase III clinical trial design for recurring breast cancer at the 2021 AACR (Free AACR Whitepaper) Annual Meeting (Press release, Greenwich LifeSciences, APR 14, 2021, View Source [SID1234578013]). The Global Principal Investigator of the GP2 Phase III clinical trial, Dr. Mothaffar F. Rimawi of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, is the lead author of the poster and has recorded an audio track providing an overview.

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Poster Presentation CT256 from 2021 AACR (Free AACR Whitepaper) Annual Meeting Showing GP2 Phase III Clinical Trial Design for Recurring Breast Cancer (Graphic: Business Wire)

Poster Presentation CT256 from 2021 AACR (Free AACR Whitepaper) Annual Meeting Showing GP2 Phase III Clinical Trial Design for Recurring Breast Cancer (Graphic: Business Wire)

The AACR (Free AACR Whitepaper) published the Phase III trial design abstract on April 9, 2021 and the poster on April 10, 2021. The abstract can be viewed at the bottom of this press release and the full poster with audio can be accessed or downloaded on the Company website at View Source

Snehal Patel, CEO of Greenwich LifeSciences, commented, "At present, the Phase III trial is designed to treat up to 500 patients. The data read out for the interim analysis will be event driven and could be completed approximately halfway through the planned 5 year follow-up. The recently reported robust immune response data, which peaked after 6 months in the Phase IIb trial, will help to finalize the Phase III trial design, including the immune response monitoring strategy. We will also assess immune response in an open-label third arm across multiple HLA types to potentially expand the market for GP2. This immune response data could be reported before the interim analysis."

Updated Phase III Clinical Trial Design: The Company and the Baylor College of Medicine presented the updated design of the planned Phase III clinical trial to breast cancer key opinion leaders. The Phase III clinical trial is a prospective, randomized, double-blinded, multi-center trial. The primary efficacy endpoints for the three arms of the Phase III trial are invasive Disease Free Survival (iDFS). The objective is to conservatively reproduce the Phase IIb trial results which demonstrated 100% iDFS with 5 years of follow-up in the HER2/neu 3+ population.

In addition to the trial design updates in the bullet points above, patients meeting all entry criteria will be randomized to receive either GP2 + GM-CSF or placebo. The Phase III trial design includes the use of saline in the placebo arm, instead of GM-CSF, which was used in the placebo arm of the Phase IIb trial. GM-CSF is not the standard of care and may cause immune responses in placebo patients.

Dr. Jaye Thompson, VP of Clinical and Regulatory Affairs, added, "It is critical that the study population and design in the protocol are carefully crafted so that the resulting data provides convincing evidence of safety and efficacy for the BLA submission. We have already engaged a statistician to design the interim analysis and have begun recruiting clinicians and clinical sites for participation in the Phase III trial."

AACR Abstract CT256

Title: A prospective, randomized, multicenter, double-blinded, placebo-controlled phase III trial of the HER2/neu peptide GP2 + GM-CSF versus bacteriostatic saline/WFI placebo as adjuvant therapy after any trastuzumab-based therapy in HER2-positive women with operable breast cancer

Snehal S Patel1, David B McWilliams1, Christine T Fischette1, Jaye Thompson1, F Joseph Daugherty1, C Kent Osborne2 and Mothaffar F Rimawi2.

1Greenwich LifeSciences, Stafford, TX; 2Baylor College of Medicine, Houston, TX

Background: GP2 is a biologic nine amino acid peptide of the HER2/neu protein delivered in combination with an FDA-approved immunoadjuvant Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF, Sargramostim, Leukine) that stimulates an immune response targeting HER2/neu expressing cancers. In a prospective, randomized, single-blinded, placebo-controlled, multicenter Phase IIb clinical trial completed in 2018, no recurrences were observed in the HER2/neu positive adjuvant setting after median 5 years of follow-up, if the HLA 2+ patient received the 6 primary intradermal injections over the first 6 months (p = 0.0338) in a pre-specified subgroup analysis. Furthermore, the GP2 immunotherapy elicited a potent immune response measured by local skin tests and immunological assays. Of the 138 patients that have been treated with GP2 to date over 4 clinical trials, GP2 treatment was well tolerated and no serious adverse events were observed related to the GP2 immunotherapy. This Phase III trial aims to reproduce the Phase IIb study and will explore the use of GP2 + GM-CSF as adjuvant therapy to prevent the recurrence of breast cancer in HER2/neu positive and HLA 2+ patients, post-surgery and following the first year treatment with any trastuzumab-based therapy.

Trial Design: This Phase III trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy or an approved biosimilar, treatment with GP2 + GM-CSF or placebo (Bacteriostatic Saline/WFI) will be administered intradermally for the 6 primary immunization series over the first 6 months and 5 subsequent boosters over the next 2.5 years for a total of 11 injections over 3 years of treatment. The participant duration of the trial will be 3 years treatment plus 2 years follow-up for a total of 5 years following the first year treatment with trastuzumab-based therapy or approved biosimilar. An interim analysis is planned and patients will be stratified based on prior and current treatments, among other factors.

Eligibility Criteria: The majority of breast cancer patients will be HER2/neu positive and HLA 2+, disease-free, conventionally treated node-positive, post breast tumor removal surgery and following the first year treatment with trastuzumab-based therapy.

Trial Objectives:

To determine if GP2 therapy reduces recurrence in HER2/neu positive breast cancer patients.
To monitor the in vitro and in vivo immunologic responses to GP2 therapy and correlate these responses with the clinical outcomes.
To monitor for any unexpected adverse events and toxicities related to GP2 therapy.
Accrual: The target enrollment is up to approximately 500 patients.

Funding: This trial is supported by Greenwich LifeSciences.

About the AACR (Free AACR Whitepaper) Annual Meeting 2021

The AACR (Free AACR Whitepaper) is the first and largest cancer research organization dedicated to accelerating the conquest of cancer and has more than 48,000 members residing in 127 countries and territories. The AACR (Free AACR Whitepaper) Annual Meeting program covers the latest discoveries across the spectrum of cancer research — from population science and prevention; to cancer biology, translational, and clinical studies; to survivorship and advocacy — and highlights the work of the best minds in research and medicine from institutions all over the world.

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 266,000 new breast cancer patients and 3.1 million breast cancer survivors in 2018. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On April 14, 2021 GlaxoSmithKline plc reported, following a recommendation by the Independent Data Monitoring Committee, that it has taken the decision to stop enrolling patients in the phase II INDUCE-3 trial, including discontinuing treatment with feladilimab (Press release, GlaxoSmithKline, APR 14, 2021, View Source [SID1234578032]).

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The INDUCE-3 study is investigating feladilimab in combination with pembrolizumab versus placebo in combination with pembrolizumab in patients with PD-L1 positive recurrent locally advanced or metastatic head and neck squamous cell carcinoma.

GSK has also made the decision to stop the INDUCE-4 phase II trial, a study investigating feladilimab versus placebo in combination with pembrolizumab and chemotherapy.

The totality of the data will be evaluated to assess the impact on the overall clinical development programme for feladilimab.

The INDUCE-3 and INDUCE-4 studies are conducted pursuant to an agreement between GSK and Merck & Co, Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the US and Canada).

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline of oncology assets in development is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On April 14, 2021 StemSynergy Therapeutics reported that A major scientific breakthrough in the development of novel cancer therapeutics targeting the Notch pathway has been published online ahead of print in the journal Cancer Research (Press release, StemSynergy, APR 14, 2021, View Source [SID1234578051]). In this report scientists describe a small-molecule inhibitor of the Notch pathway that is selective against Notch1, which contributes to many stages of cancer including in the maintenance of cancer stem cells, a main cause of resistance to chemotherapy and metastatic disease. StemSynergy Therapeutics, Inc., who collaborated on this study holds worldwide exclusivity to develop these molecules for the clinic.

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"The Notch pathway is an extremely attractive target for cancer therapeutics, as it is a critical driver of many human cancers. However, several approaches have failed to inhibit Notch safely in clinical trials and progress has nearly stagnated over the last few decades," said Anthony J. Capobianco, Ph.D., corresponding author of the study. "To date, there are no inhibitors that directly target the intracellular Notch pathway with any significant specificity, which is central to safety in humans. Pharma has been trying to target this pathway for more than 20 years and this is the first example of a targeted therapeutic specific for Notch1 that has robust efficacy and minimal toxicity in human-derived malignant tumors models."

In this study, the team of scientists refined their previous proof-of-concept inhibitor using computer modeling and experimental validation to identify chemical compounds that are selective for the Notch1 transcriptional complex. The lead compound, NADI-351, potently disrupts the formation of the Notch1 transcriptional complex which prevents transcription of oncogenic target genes and inhibits the growth of Notch1-dependent cancer cells and tumors.

Further validation confirmed NADI-351 is selective against Notch1 and against cancer stem cells, which require Notch1 activity. This mechanism was observed in multiple in vitro cancer models and replicated in NADI-351-treated human tumors in mice. "Our analysis confirms NADI-351 selectively disrupts Notch1-dependent transcription and that this mechanism has powerful downstream effects on cancer," said Annamil Alvarez-Trotta, Ph.D., first author on the study. "Specifically, NADI-351 clears cancer stem cells by starving them of Notch signaling and causes cell death in tumors, including esophageal and triple-negative breast cancer. "

Most importantly, NADI-351 does not induce the gastrointestinal toxicity which has long hampered development of Notch pathway inhibitors. The key to this therapeutic window is in the selective inhibition of the Notch1 transcriptional complex, while sparing those of other Notch proteins. "It’s likely that this selectivity, along with the short ‘pulse’ of inhibition that small molecules achieve, allows us to preferentially inhibit tumors addicted to Notch1 signaling without causing toxicity in tissues dependent on Notch signaling more generally," noted William Guerrant, Ph.D., Senior Scientist at StemSynergy Therapeutics.

"We feel this new class of Notch1 inhibitors could be a game-changer for patients with Notch-dependent tumors and those that are highly resistant due to cancer stem cell activity," said Capobianco, who is also a co-founder and President of StemSynergy Therapeutics. At the same time this breakthrough science is being published, StemSynergy Therapeutics is developing this class of compound for clinical evaluation. "We plan on aggressively pushing this through preclinical development and into cancer patients as a high priority and hope to be in clinical trials in the near term."

On April 14, 2021 Vascular Biogenics Ltd. ("VBL Therapeutics" or the "Company") (NASDAQ: VBLT), reported the closing of its underwritten public offering of 6,901,790 ordinary shares, and, to certain investors in lieu thereof, pre-funded warrants to purchase 8,050,000 ordinary shares in an underwritten public offering, at a price to the public of $1.90 per ordinary share and $1.89 per pre-funded warrant (Press release, VBL Therapeutics, APR 14, 2021, View Source [SID1234578014]). The pre-funded warrants allow investors that have restrictions on their ability to own Company stock above a designated ownership threshold (such as 4.99% or 19.99%) to invest additional capital. In practice, the pre-funded warrants are the equivalent to ordinary shares without voting rights. All of the securities in the offering were sold by VBL Therapeutics.

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The gross proceeds to the Company from the public offering, before deducting underwriting discounts and commissions and offering expenses payable by VBL Therapeutics, were approximately $28.3 million. VBL Therapeutics intends to use the net proceeds from the offering for working capital and other general corporate purposes.

Guggenheim Securities, LLC acted as bookrunning manager for the offering. Oppenheimer & Co. Inc. also acted as a joint bookrunner. Roth Capital Partners and JonesTrading Institutional Services LLC acted as co-managers.

The securities described were offered by VBL Therapeutics pursuant to a shelf registration statement on Form F-3 (No. 333-251821), including a base prospectus, previously filed with and declared effective by the Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement and a final prospectus supplement relating to and describing the terms of the offering has been filed with the SEC. The final prospectus supplement is available on the SEC’s website located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the securities being offered may also be obtained by contacting Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, New York 10017, by telephone at (212) 518-9544, or by email at [email protected].

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

On April 14, 2021 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported that it will report first quarter 2021 financial results after the Nasdaq market closes on Wednesday, May 5, 2021 (Press release, Neurocrine Biosciences, APR 14, 2021, View Source [SID1234578033]). Neurocrine will then host a conference call and webcast to discuss its financial results and provide a company update that day at 1:30 p.m. Pacific Time (4:30 p.m. Eastern Time).

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Participants can access the live conference call by dialing 800-895-3361 (US) or 785-424-1062 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine’s website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.