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BeiGene Announces Acceptance of 12th Regulatory Submission in China for PD-1 Inhibitor Tislelizumab

On December 30, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental biologics license application (sBLA) for tislelizumab in patients with first-line unresectable or metastatic hepatocellular carcinoma (HCC) (Press release, BeiGene, DEC 30, 2022, View Source [SID1234625683]).

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Hepatocellular carcinoma is the most common type of primary liver cancer worldwide and is associated with a very poor prognosis.1 New cases and deaths due to HCC in China account for half of the global numbers and the 5-year survival rate for patients with HCC in China is only 14%.2

"While the incidence of HCC is increasing in China, the treatment landscape has not advanced accordingly; survival benefits with newer treatments are modest and multi-kinase inhibitors have sub-optimal tolerability," said Lai Wang, Ph.D., Global Head of R&D at BeiGene. "We believe the evidence from our rigorously conducted global clinical development program for tislelizumab in HCC support the efficacy and favorable tolerability profile and look forward to working with NMPA on this submission and bringing a new treatment option to patients with HCC in China."

The sBLA is supported by data from the RATIONALE 301 clinical trial (NCT03412773) that enrolled 674 patients from research centers across Asia, Europe, and the United States. RATIONALE 301 results were presented as a late-breaking oral presentation at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Paris.

Tislelizumab was approved by the China NMPA as a treatment for nine indications, including conditional approval ‘for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with at least one systemic therapy’. Additional tislelizumab’s sBLAs under review at CDE include: combination with chemotherapy as a first-line treatment for patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1; combination with chemotherapy as first-line treatment in patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma. Tislelizumab is not approved for use outside of China.

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.

Tislelizumab is the first investigational medicine from BeiGene’s immuno-oncology biologics program and is being evaluated in solid tumor and hematologic malignancies, as monotherapy and in combination.

The global tislelizumab clinical development program includes more than 11,500 subjects enrolled to-date in 21 registration-enabling trials, from more than 30 countries and regions.

About RATIONALE 301

RATIONALE 301 (NCT03412773) is a global, Phase 3, randomized, open-label study of tislelizumab compared with sorafenib as a first-line treatment in adult patients with unresectable HCC. The primary endpoint of the study is non-inferiority of Overall Survival between the two treatment groups. The key secondary endpoint is Overall Response Rate, as assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Other secondary endpoints include other efficacy assessments such as Progression Free Survival, Duration of Response, and Time to Progression per BIRC, as well as measures of health-related quality of life, and safety and tolerability.

AskGene Announces Completion of First Human Dosing of ASKG315, The First IL-15 Prodrug in Clinical Development

On December 30, 2022 AskGene Pharma Inc. reported that the first patient completed their first dose (Cycle 1, Day 1) in the phase I clinical trial of ASKG315 in Shanghai, China (Press release, AskGene Pharmaceuticals, DEC 30, 2022, View Source [SID1234625682]). The study is an open label, multicenter phase I clinical trial evaluating the safety, tolerability, and pharmacokinetics of ASKG315 for injection in patients with locally advanced or metastatic solid tumors. ASKG315 is the first IL-15 prodrug in clinical development in the world.

Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene commented: "ASKG315 is the second cytokine prodrug incubated from our propriety SmartKine cytokine prodrug platform technology. Preclinical data showed that ASKG315 selectively stimulated NK cells and CD8+ T cells. We are looking forward to achieving initial clinical proof of concept of the molecule as well as the platform. With multiple clinical programs, AskGene is establishing its global leading position in the field of cytokine prodrug."

Barbara Hickingbottom, J.D., M.D., Chief Medical Officer of AskGene commented: "Cytokines are natural immune stimulants, which cannot be used widely due to their short half-lives and narrow therapeutic windows. AskGene expects to use its proprietary technology to overcome these challenges. With the recent clearance of the ASKG915 IND by FDA, and an IL-2 prodrug in clinical development through a partnership, AskGene now has three cytokine prodrug programs in clinical development. We are very excited about the progress made in 2022 and look forward to the upcoming POC data from our clinical studies in 2023".

About ASKG315

ASKG315 is a novel and proprietary IL-15 prodrug discovered and developed by AskGene. It is the world’s first IL-15 prodrug moved into clinical development. Preclinical data of ASKG315 showed that this molecule selectively stimulated NK cells and CD8+ T cells in cynomolgus monkeys. Compared to previous generations of cytokine drugs, the prodrug design significantly extended the half-life, effectively improved the safety window, and reduced toxicity. ASKG315 has the longest half-life in cynomolgus monkeys among similar cytokine drugs in development.

AskGene Announces Clearance of IND Application by US FDA for ASKG915, A First-in-Class Anti-PD-1-IL-15 Prodrug Fusion Molecule for the Treatment of Patients with Solid Tumors

On December 30th, 2022 AskGene Pharma Inc. reported that the United States Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for the clinical development of ASKG915, a novel and proprietary anti-PD-1-IL-15 prodrug fusion molecule for the treatment of cancer (Press release, AskGene Pharmaceuticals, DEC 30, 2022, View Source [SID1234625681]). Under this IND, AskGene will soon initiate a phase 1 study in the United States to investigate the safety, tolerability, pharmacokinetics, and efficacy of ASKG915 in patients with advanced solid tumors. ASKG915 will be the first anti-PD-1-IL-15 prodrug fusion molecule moving into clinical development in the world.

Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene commented: "We are pleased that we received IND clearance for ASKG915, which is our third cytokine prodrug program entering clinical development. This important milestone brings us closer to delivering a truly bifunctional molecule with synergistic effect of an IL-15 agonist and PD-1 blockage to treat oncology patients. ASKG915 is expected to benefit patients who do not respond to current immunotherapies."

About ASKG915

ASKG915 is the world’s first PD-1 antibody-IL-15 prodrug fusion molecule to enter clinical development. The molecule can achieve tumor targeting through the anti-PD-1 antibody and be locally activated at the tumor site. It is also designed to allow high enough of a dosage so that the anti-PD-1 antibody has full PD-1 blockage functionality. Preclinical data showed that ASKG915 has extended PK, significantly better efficacy than an anti-PD-1 antibody monotherapy, and an expanded therapeutic window. ASKG915 is expected to benefit patients who are not responding to existing anti-PD-1 antibody therapies. A Phase I clinical trial is expected to start in the first half of 2023.

Chinese Clinical Trials of PSMA-targeted RLT Drug for Metastatic Prostate Cancer Are Approved

On December 28, 2022, Sinotau Pharmaceutical reported the clinical trial application for [177Lu]Lu-XT033 injection, a class I new drug developed by Sinotau, was approved, which means [177Lu]Lu-XT033 is one step closer to commercialization and clinical application (Press release, Sinotau Pharmaceutical, DEC 29, 2022, View Source [SID1234639241]).

The project has already initiated ethical filing and other preparations, and will advance to clinical enrollment as soon as possible.

[177Lu]Lu-XT033 injection, which is another milestone in the innovative development of radionuclide therapeutic drugs in China, will benefit patients with metastatic prostate cancer and is a new option and hope in the field of precision therapy for metastatic prostate cancer.

About [177Lu]Lu-XT033 injection

[177Lu]Lu-XT033 injection is a radioligand therapy (RLT) drug intended for the treatment of adult patients with metastatic prostate cancer whose prostate specific membrane antigen (PSMA) is positive. RLT was introduced in the 1940s and works by combining a targeting compound (ligand) with a therapeutic radioisotope (radioactive particle). When injected into the bloodstream, the radioligand binds to the tumor so that the radiation produced is more locally focused on the tumor tissue, reducing damage to other healthy tissues of peripheral and whole body. The radioisotope, which acts as therapeutic agent, can disrupt tumor cell replication or trigger tumor cell death. Compared with traditional radiotherapy for tumors, RLT therapy has the advantages of precise targeting, powerful killing and limited damage, and plays a crucial role in the treatment of tumors in clinical practice.

PSMA is an ideal target for prostate cancer precision therapy. The world’s first PSMA-targeted prostate cancer RLT drug, 177Lu-PSMA-617 (trade: Pluvicto) developed by Novartis, was approved for marketing in the U.S. on March 23, 2022. In 2018, Novartis acquired Endocyte for $2.1 billion and acquired this product. Results from a subsequent global phase III clinical trial showed that 177Lu-PSMA-617 significantly improved overall survival (OS) and radiologic progression-free survival (rPFS) in patients with PSMA-positive mCRPC and reduced the risk of death for patients by 38% compared to the best standard of care.

177Lu-labeled PSMA-targeted RLT drugs can specifically bind prostate-specific membrane antigen (PSMA) to achieve enrichment of the active ingredient at the prostate tumor site and kill tumor cells using beta-rays emitted by [177Lu] lutetium decay, causing DNA damage, disrupting the replication ability of tumor cells and/or triggering cell death, thus achieving precise treatment of metastatic prostate cancer adult patients. [177Lu]Lu-XT033 injection innovates on the basis of 177Lu-PSMA-617 by introducing an albumin affinity group-Evans blue (EB), with a view to achieving increased drug uptake in the target tumor and enhancing its anti-tumor activity.

Prostate cancer is the second most common cancer in men, and the fifth most common cause of cancer death in men. In recent years, the incidence of prostate cancer in China has been on a significant rise, with an incidence rate of 9.92/100,000, which means that there are nearly 9.8 prostate cancer patients among 100,000 people. Although the incidence of prostate cancer in China is lower than that in Western countries, the proportion of patients with advanced stages at diagnosis is higher than that in Western countries.

Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing.

On December 22, 2022, Athersys, Inc. (the "Company") received a written notice (the "Notice") from the Listing Qualifications Department of The Nasdaq Stock Market LLC ("Nasdaq") that the Company is not in compliance with the requirement to maintain a minimum closing bid price of $1.00 per share, as set forth in Nasdaq Listing Rule 5550(a)(2) (the "Bid Price Requirement"), because the closing bid price of the Company’s common stock (the "Common Stock") was below $1.00 per share for 30 consecutive business days. The Notice does not impact the listing of the Common Stock on the Nasdaq Capital Market at this time (Filing, 8-K, Athersys, DEC 29, 2022, View Source [SID1234625672]).

The Notice provided that, in accordance with Nasdaq Listing Rule 5810(c)(3)(A), the Company has a period of 180 calendar days from the date of the Notice, or until June 20, 2023, to regain compliance with the Bid Price Requirement. During this period, the Common Stock will continue to trade on the Nasdaq Capital Market. If at any time before June 20, 2023 the bid price of the Common Stock closes at or above $1.00 per share for a minimum of ten consecutive trading days, Nasdaq will provide written notification that the Company has achieved compliance with the Bid Price Requirement and the matter will be closed.

The Company is considering all available options to regain compliance with the Bid Price Requirement. However, there can be no assurance that the Company will be able to regain compliance with the rule or will otherwise be in compliance with other Nasdaq listing criteria. In the event the Company does not regain compliance by June 20, 2023, the Company may be eligible for an additional 180 calendar day compliance period to demonstrate compliance with the Bid Price Requirement. To qualify for the additional 180-day period, the Company will be required to meet the continued listing requirements for market value of publicly held shares and all other initial listing standards (with the exception of the Bid Price Requirement). In addition, the Company will need to provide written notice to Nasdaq of its intention to cure the deficiency during the second compliance period by effecting a reverse stock split, if necessary. If the Company does not qualify for the second compliance period or fails to regain compliance during the second 180-day period, then Nasdaq will notify the Company that its Common Stock is subject to delisting. At that time, the Company may appeal the delisting determination to a Nasdaq Hearings Panel.