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.

On April 14, 2021 Adlai Nortye, a global biopharmaceutical company focused on developing innovative oncology drugs, reported that the first patient has been dosed in the global phase III clinical trial (BURAN) at Shanghai Eastern Hospital Medical Center in China (Press release, Adlai Nortye Biopharma, APR 14, 2021, View Source [SID1234578053]). This clinical study evaluates Buparlisib (AN2025), an oral pan-PI3K inhibitor, in combination with paclitaxel for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). This represents the first global multicenter phase III trial for HNSCC in the class of PI3K inhibitors.

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This trial is a randomized, open-label, multicenter phase III study to evaluate the efficacy and safety of Buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with recurrent or metastatic HNSCC. The primary endpoint of this study is overall survival (OS) for the entire population of patients. This study plans to recruit approximately 500 HNSCC patients from around 150 clinical centers across 15 major countries and regions in North America, Europe and Asia-Pacific. Enrollment includes patients who have disease progressed after prior anti–PD–1/anti–PD–L1 monotherapy, prior anti–PD–1/anti–PD–L1 therapy in combination with platinum-based therapy, or after sequential treatment of anti–PD–1/anti–PD–L1 therapy, either prior to or post, platinum-based therapy.

"Results from a previously completed phase II trial have demonstrated that Buparlisib (AN2025) is well tolerated and shows clear clinical benefits," said Professor Denis Soulières, the Primary Investigator of BURAN study." The objective with BURAN is to be able to offer patients with progression after platinum-based and immunotherapy a better option than taxol."

"Although progress has been made in the treatment of patients with HNSCC in recent years, for those with recurrent or metastatic HNSCC, there is still a high unmet medical need. This BURAN study is expected to change the paradigm of second-line treatment for HNSCC, which offers a new treatment option for patients in China and the rest of the world," said Professor Guo Ye, Director of Phase I Clinical Trail Center of Shanghai East Hospital Affiliated to Tongji University and Member of the Head and Neck Cancer Committee of the Chinese Society of Clinical Oncology (CSCO). "As a physician, I am pleased and welcome more and more clinical trials to be carried out in China. This trial will provide us firsthand data in terms of safety and efficacy in Chinese patients with HNSCC and we are looking forward to bringing the best treatment option for them."

"Cooperating with world-class researchers to conduct high-quality clinical trials is an essential part of Adlai Nortye’s global strategy," said Dr. Lars Birgerson, Chief Medical Officer of Adlai Nortye. "We hope to provide safer and more effective treatments to patients in a timely manner to ultimately save lives. With an impressive median overall survival of 10.4 months and the FDA granted Fast-Track designation, Buparlisib (AN2025) has the potential to become the first PI3K inhibitor on the market for patients with HNSCC."

About BURAN study

The BURAN study is a randomized, open-label, multicenter phase III study to assess the treatment effect of once-daily buparlisib in combination with weekly paclitaxel compared to weekly paclitaxel alone in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that have progressed after prior anti–PD–1/anti–PD–L1 monotherapy; prior anti–PD–1/anti–PD–L1 therapy in combination with platinum-based therapy; or after sequential treatment of anti–PD–1/anti–PD–L1 therapy, either prior to or post, platinum-based therapy.

About Buparlisib (AN2025)

Buparlisib (AN2025) is an oral pan-PI3K inhibitor that targets all class I PI3K isoforms and is active in both hematologic malignancies and solid tumors. In the global phase II clinical trial for the treatment of head and neck squamous cell carcinoma (HNSCC), the median overall survival was as high as 10.4 months. It has received Fast-Track designation and an approval for initiating the phase III clinical study from FDA. The BURAN study investigating Buparlisib is also the first global phase III clinical trial conducted by Adlai Nortye.

About HNSCC

HNSCC is the 8th leading cancer by incidence worldwide and constitutes 90% of all head and neck cancers. The overall annual incidence of HNSCC patients globally reached approximately 0.84 million in 2020, and is expected to increase to approximately 1 million in 2030. Most patients are suffering from locally advanced HNSCC present with a high risk of recurrence; approximately 50-60% of HNSCC patients are diagnosed with metastatic disease. Although immune checkpoint inhibitors have significantly benefited patients with HNSCC, the overall response rates are relatively low in general. Treatment option for patients that do not respond to immune checkpoint inhibitors is increasingly becoming a significant unmet medical need.

On April 14, 2021 NantHealth, Inc. (NASDAQ-GS: NH), a provider of enterprise solutions that help transform complex data into actionable insights, reported the signing of a new financing that will include the issuance of $137.5 million aggregate principal amount of new senior unsecured convertible notes due 2026 (the "2026 Notes") in a private transaction, with the common stock that may be issued upon a conversion to be registered under the Securities Act of 1933, as amended (the "Securities Act") (Press release, NantHealth, APR 14, 2021, View Source [SID1234578015]). As part of the transaction, the company will enter into an agreement to extend the maturity of its existing subordinated note to October 2026. The company intends to use the proceeds of the 2026 Notes to retire its existing convertible notes due December 2021 (the "2021 Notes") and further invest in initiatives to grow its business.

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The 2026 Notes will be issued to two existing NantHealth investors: certain funds managed by Highbridge Capital Management, LLC ("Highbridge"), a current holder of the company’s 2021 Notes, and Nant Capital, LLC, an affiliated entity owned by the company’s majority equity investor and holder of the company’s subordinated notes. The investors will purchase $137.5 million in aggregate principal amount of the 2026 Notes. The parties expect the 2026 Notes financing transaction to close on or before April 27, 2021.

In addition, each of Highbridge and Cambridge Equities, LP (also an affiliate owned by the company’s majority shareholder), have agreed to convert $5 million ($10 million in total) of their holdings of the 2021 Notes to shares of NantHealth common stock on April 14, 2021.

"This transaction provides several immediate benefits to NantHealth, including enhancing our financial flexibility and funding our growth initiatives," said Ron Louks, NantHealth’s Chief Operating Officer. "Not only does this financing address the upcoming maturity of our 2021 Notes, but importantly provides us with the resources to invest in our established businesses, NaviNet and Eviti, and accelerate the expansion of our recently acquired OpenNMS business. We thank our financing partners, Highbridge and Nant Capital, for their continued support."

Jonathan Segal, Co-Chief Investment Officer of Highbridge, said, "We are very pleased to increase our investment in NantHealth. Last year, NantHealth made a strategic decision to expand beyond healthcare by providing enterprise solutions to help businesses in other industries. We believe this financing will help NantHealth achieve this goal and continue further product expansion."

The 2026 Notes will bear interest of 4.5% that will be payable semiannually, unless earlier converted to the company’s common stock, redeemed or repurchased in accordance with their terms. The final terms of the 2026 Notes, including the interest rate, initial conversion rate, and other terms, will be disclosed in the company’s filings with the U.S. Securities and Exchange Commission (SEC).

A Special Committee of the NantHealth Board of Directors, consisting of the independent directors, undertook a thorough review of the transaction and unanimously recommended that NantHealth proceed with the transaction.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the 2026 Notes, nor shall there be any sale of the notes in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.