On February 24, 2023 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that the China National Medical Products Administration (NMPA) granted approval for the company’s PD-1 inhibitor, tislelizumab, in combination with fluoropyrimidine and platinum chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma with high PD-L1 expression (Press release, BeiGene, FEB 24, 2023, View Source [SID1234627675]).

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In China, gastric cancer (GC) has become the third most common canceri and adenocarcinoma represents the major histologic subtype, comprising over 90% of reported GC cases across the worldii. More than 70% of patients in China are in advanced or late stage when diagnosediii and the previous standard first-line treatment in China for advanced GC, chemotherapy, provided median overall survival (OS) around one yeariv. Newer treatments, including immunotherapy, have improved survival in this treatment settingv.

"Advanced gastric cancer remains a significant cause of cancer-related mortality in China and we are pleased that tislelizumab plus chemotherapy demonstrated a meaningful survival benefit for patients whose tumors express PD-L1 in the RATIONALE 305 study," said Lai Wang, Ph.D., Global Head of R&D at BeiGene. "We are grateful to the patients, investigators, and experts from across the world who took part in the RATIONALE 305 trial and look forward to bringing another immunotherapy-based treatment option to patients in China."

The approval was based on data from an interim analysis of the global, randomized, double-blind, placebo-controlled RATIONALE 305 trial (NCT03777657) of tislelizumab in combination with chemotherapy in the first-line treatment setting. A total of 997 patients with locally advanced, unresectable or metastatic G/GEJ from 13 countries and regions across the world were enrolled and randomized 1:1 to receive either tislelizumab and chemotherapy or placebo and chemotherapy, including 546 patients with locally advanced unresectable or metastatic G/GEJ adenocarcinoma with high PD-L1 expression.

Xu Ruihua, M.D., Ph.D., Director of Cancer Control Center of Sun Yat-sen University, and the global principal investigator for RATIONALE 305 noted, "The prognosis for patients with advanced G/GEJ adenocarcinoma was poor with traditional chemotherapy treatment and we undertook the global Phase 3 RATIONALE 305 trial with the aim to improve outcomes. With approval from the NMPA, we now have another option for our patients and I expect tislelizumab plus chemotherapy will soon become the new standard of care in this treatment setting in China."

Results of the RATIONALE 305 interim analysis were shared in an oral presentation at the 2023 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium. In patients with G/GEJ adenocarcinoma with high PD-L1 expression, tislelizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvement in OS versus placebo plus chemotherapy [median OS: 17.2 vs 12.6 months; HR 0.74 (95% CI 0.59, 0.94); P=0.0056] with a manageable safety profile, and no new safety signals were identifiedvi. The study is continuing as double-blind towards the final OS analysis in the ITT population.

Tislelizumab is currently under review by the U.S. Food and Drug Administration and the European Medicines Agency (EMA) for advanced or metastatic esophageal squamous cell carcinoma after prior chemotherapy. The EMA is also reviewing tislelizumab for advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated advanced or metastatic NSCLC. Tislelizumab is not approved for use outside of China.

About RATIONALE 305 (NCT03777657)

RATIONALE 305 is a randomized, double-blind, placebo-controlled, global Phase 3 trial comparing the efficacy and safety of tislelizumab combined with platinum and fluoropyrimidine chemotherapy and placebo combined with platinum and fluoropyrimidine chemotherapy as a first-line treatment for patients with locally advanced, unresectable or metastatic G/GEJ adenocarcinoma. The primary endpoint of the trial is OS in patients with PD-L1 high population and in ITT population. Secondary endpoints include progression-free survival, overall response rate, duration of response, and safety.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

BeiGene has initiated or completed more than 20 potentially registration-enabling clinical trials in 35 countries and regions, including 17 Phase 3 trials and four pivotal Phase 2 trials. More information on the clinical trial program for tislelizumab can be found at: View Source

On February 24, 2023 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the Company) reported that Peter Greenleaf, President and Chief Executive Officer, will give a corporate presentation at the upcoming investor healthcare conference (Press release, Aurinia Pharmaceuticals, FEB 24, 2023, View Source [SID1234627674]).

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Oppenheimer 33rd Annual Virtual Healthcare Conference being held March 13 – 15, 2023. Presentation time Tuesday, March 14, from 9:20 – 9:50 AM ET.
To participate in the audio webcast, interested parties can access the live webcast under "News/Events" through the "Investors" section of the Aurinia corporate website at www.auriniapharma.com.

On February 24, 2023 Apellis Pharmaceuticals, Inc., (Nasdaq:APLS), a global biopharmaceutical company and leader in complement, reported the pricing of its underwritten public offering of 3,174,603 shares of its common stock at a public offering price of $63.00 per share and, in lieu of common stock to investors who so choose, pre-funded warrants to purchase 2,380,956 shares of its common stock at a public offering price of $62.9999 per pre-funded warrant, for total gross proceeds of approximately $350 million, before deducting underwriting discounts and commissions and offering expenses payable by Apellis (Press release, Apellis Pharmaceuticals, FEB 24, 2023, View Source [SID1234627673]). The purchase price of each pre-funded warrant equals the price per share at which the shares of common stock are being sold in the offering, minus $0.0001. All of the shares and pre-funded warrants in the offering are being sold by Apellis. The offering is expected to close on February 27, 2023, subject to customary closing conditions. In addition, Apellis has granted the underwriters a 30-day option to purchase up to 833,333 additional shares of its common stock at the public offering price, less the underwriting discounts and commissions.

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J.P. Morgan Securities LLC, Goldman Sachs & Co. LLC and Evercore Group L.L.C. are acting as joint book-running managers for the offering. Robert W. Baird & Co. Incorporated and Raymond James & Associates, Inc. are acting as co-managers for the offering.

The securities are being offered by Apellis pursuant to an automatically effective shelf registration statement that was filed with the Securities and Exchange Commission ("SEC") on February 22, 2023. This offering is being made only by means of a prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement relating to and describing the terms of the offering has been filed with the SEC and may be obtained for free by visiting the SEC’s website at www.sec.gov. A final prospectus supplement relating to the offering will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus may also be obtained by contacting: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at 866-803-9204, or by email at [email protected]; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, or by telephone at (866) 471-2526, or by email at [email protected]; or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, New York 10055, by telephone at (888) 474-0200, or by email at [email protected].

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

On February 23, 2023 Neuren Pharmaceuticals (ASX: NEU) reported its full-year financial results for 2022 (Press release, Neuren, FEB 24, 2023, View Source;[email protected] [SID1234627651]).

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Neuren CEO Jon Pilcher commented: "The substantial progress that was made in 2022 across the whole business leaves Neuren very well placed for the transforming catalysts that have been anticipated to crystallise in 2023. We are now approximately two weeks away from the first of those – the FDA PDUFA action date for trofinetide in Rett syndrome. The Neuren team is excited about the year ahead and the prospects for both trofinetide and NNZ-2591."

Commentary on events and outlook

Trofinetide for Rett syndrome

In December 2021 Neuren’s partner for trofinetide in North America, Acadia Pharmaceuticals (Nasdaq: ACAD), announced positive top-line results from the pivotal, Phase 3 Lavender study evaluating the efficacy and safety of trofinetide in 187 girls and young women aged 5-20 years with Rett syndrome. The 12-week placebo-controlled study demonstrated a statistically significant improvement over placebo for both co-primary endpoints. In September 2022 the US Food and Drug Administration (FDA) accepted for review the New Drug Application (NDA) for trofinetide to treat Rett syndrome in adults and pediatric patients two years of age or older, that was submitted in July by Acadia. The FDA granted a Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) action date of 12 March 2023. The FDA also informed Acadia that they were not planning to hold an Advisory Committee meeting. If approved, trofinetide will be the first drug for the treatment of Rett syndrome. The trofinetide program has Orphan Drug, Fast Track and Rare Pediatric Disease designations from the FDA.

In October 2022, Neuren received from Acadia a milestone payment of US$10 million following the acceptance of the NDA for review by the FDA. If the NDA is approved by the FDA, Neuren expects to earn revenue in 2023 for Rett syndrome in the US alone of A$104 million plus royalties. The next potential milestone payment to Neuren would be US$40 million (A$57 million at an assumed exchange rate of 0.70), payable following the first commercial sale of trofinetide in the United States. Subsequently, Neuren is eligible to receive ongoing doubledigit percentage royalties on net sales of trofinetide in North America, plus milestone payments of up to US$350 million (A$500 million) on achievement of a series of four thresholds of total annual net sales, plus one third of the market value of a Rare Pediatric Disease Priority Review Voucher if awarded by the FDA upon approval of the NDA, with the one third share estimated by Neuren as US$33 million (A$47 million). No royalties or similar costs are payable by Neuren to third parties, which means that Neuren’s revenue from Acadia will flow through to pre-tax profit.

Acadia has exclusive rights to develop and commercialize trofinetide in North America, which is fully funded by Acadia. Neuren retains all rights to trofinetide for all countries outside North America and has a fully paid-up, irrevocable licence for use in those countries to all data generated by Acadia. Neuren has received strong interest for potential commercial partnerships and discussions are advancing under a process to secure the optimum outcome.

NNZ-2591 for multiple neurodevelopmental disorders

Neuren is developing NNZ-2591 for four serious neurological disorders that emerge in early childhood and have no or limited approved treatment options. Phase 2 clinical trials are currently ongoing in children with each of Angelman, Phelan-McDermid and Pitt Hopkins syndromes and in preparation for Prader-Willi syndrome. All four programs have been granted Orphan Drug designation by the FDA. The estimated number of potential patients being targeted across these four disorders is more than five times larger than Rett syndrome. Neuren retains all global rights to NNZ-2591.

In July and August 2022, Neuren announced the commencement of Phase 2 clinical trials of NNZ-2591 for Phelan-McDermid syndrome, Angelman syndrome and Pitt Hopkins syndrome, after receiving in March 2022 approval from the FDA for Investigational New Drug (IND) applications to conduct the trials. In December 2022, Neuren submitted an IND application to the FDA for approval to proceed with a Phase 2 trial in Prader-Willi syndrome and received approval from the FDA in January 2023.

The open label Phase 2 trials are each enrolling up to 20 children to examine safety, tolerability, pharmacokinetics and efficacy over 13 weeks of treatment with NNZ-2591.  All subjects receive NNZ-2591 as an oral liquid dose twice daily, with escalation in two stages up to the target dose during the first 6 weeks of treatment, subject to independent review of safety and tolerability data.

The current trials are enrolling subjects in three age groups.  Safety and tolerability data in the oldest age group must be independently reviewed before proceeding with dosing in the second age group and then safety and tolerability data in the second age group must be independently reviewed before proceeding with dosing in the youngest age group.

The study begins with 4 weeks of observation to thoroughly examine baseline characteristics prior to treatment, against which safety and efficacy are assessed for each child. This is followed by the treatment period of 13 weeks.  A follow-up assessment is made 2 weeks after the end of treatment. 

Phelan-McDermid Pitt Hopkins Angelman Subjects Up to 20, aged 3 to 12 Up to 20, aged 3 to 17 Up to 20, aged 3 to 17 Number of sites 4 (US) 5 (US) 3 (Australia) www.clinicaltrials.gov NCT05025241 NCT05025332 NCT05011851

In December 2022, Neuren announced that in the Phelan-McDermid syndrome trial and in the Angelman syndrome trial, the first subject in the oldest age group had completed the treatment period of 13 weeks, with a good safety and tolerability profile. Each subject was successfully escalated up to the target dose following safety and tolerability reviews by an independent data and safety monitoring committee (DSMC). No serious adverse events were reported and no dose modifications were required. Most of the adverse events reported were mild and not considered to be related to study drug. There were no clinically relevant observations in safety laboratory measurements or cardiac tests.

The overall aim of these first clinical trials in patients is to expedite the generation of data that will enable the subsequent trials to be designed as registration trials. The four trials will likely complete at different times, with a series of top-line results announcements anticipated, commencing with Phelan-McDermid syndrome in H2 2023.

In order to accelerate the overall development plan, in parallel with conducting the Phase 2 trials Neuren is executing additional development work required for Phase 3 development. This includes non-clinical toxicity studies to support longer clinical trials and commercial use of the product, as well as optimisation of the drug product and drug substance manufacturing arrangements.

Neuren is well funded from current cash reserves to execute the Phase 2 trials and Phase 3 preparation, notwithstanding the anticipated material cash flows from trofinetide.

Financials

Profit after tax for the year ended 31 December 2022 was A$0.2 million compared with a loss of A$7.8 million in 2021. Revenue of A$14.6 million was received under the licence agreement with Acadia (2021: nil) and foreign exchange gains were A$1.2 million (2021: A$0.4 million). These were offset by an increase of A$3.2 million in research and development costs, due to higher expenditures in 2022 for the NNZ-2591 Phase 2 clinical trials and the foundational work to prepare for Phase 3 development of NNZ-2591 across multiple indications. There was also an increase in corporate and administrative costs of A$1.5 million, mainly due to share-based payments and higher employee benefits expense, reflecting some expansion for the NNZ-2591 program. In addition, a loss of A$0.7 million on the fair value of outstanding forward contracts to sell Australian dollars and buy US dollars was recognised at 31 December 2022. Prudent control of expenditure continues to be an important principle in the Group’s operations and financing.

Cash reserves at 31 December 2022 were $40.2 million (2021: $36.8 million). Net cash received from operating activities was $3.6 million, compared with net cash used in operating activities of $10.0 million in 2021. The increase of $13.6 million was due to the receipt of the first milestone payment from Acadia of $15.9 million (2021: nil), offset by higher payments for employees and directors of $2.8 million (2021: $1.8 million) and a lower receipt under the R&D Tax Incentive program of $1.4 million (2021: $2.5 million). Net cash from financing activities for 31 December 2022 was nil, compared with $22.2 million in 2021 from the issue of new ordinary shares in a share placement and share purchase plan.

The large increase in market capitalization during the year resulted in Neuren being promoted in September into the S&P/ASX 300 index.

On February 23, 2023 BullFrog AI Holdings, Inc. (NASDAQ:BFRG; BFRGW) ("Bullfrog AI" or the "Company"), a digital technology company using machine learning to usher in a new era of precision medicine reported a co-development arrangement with the J. Craig Venter Institute (JCVI), a world-leading institution in genomics research and innovation, for the design and validation of a synthetic HSV-1 (herpes simplex type 1) virus particle targeting colorectal cancer (Press release, Bullfrog AI, FEB 23, 2023, View Source [SID1234635367]).

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"This project leverages our bfLEAP artificial intelligence and machine learning platform to optimize oncolytic HSV-1 particle design for cancer-cell-specific targeting, reduced toxicity, and therapeutic payload," said BullFrog AI’s founder and CEO, Vin Singh. "Our objective with this collaboration is to generate a novel class of targeted colorectal cancer therapeutics with potential for a best-in-class toxicity profile, while providing a clear demonstration of our ability to advance development of new medicines using artificial intelligence."

"The JCVI has been at the forefront of synthetic biology for more than 25 years, and we’ve long stated that the knowledge, tools, and techniques developed have broad use. It is gratifying seeing their application in such an impactful area of human health, and we look forward to working with BullFrog AI," remarked J. Craig Venter, Ph.D., chairman, CEO, and founder of JCVI.

"We are excited to partner with Bullfrog AI. The combination of artificial intelligence and engineered biology approaches has the potential to rapidly develop safer precision cancer therapeutics," added Sanjay Vashee, Ph.D., professor and director of the JCVI, Rockville, Maryland campus.

According to the American Cancer Society, colorectal cancer is the third most common cancer diagnosed in both men and women in the U.S., excluding skin cancers, and is the third leading cause of cancer-related deaths in the U.S.