On March 4, 2024 DotBio reported its lead candidate, DB007, has begun animal efficacy studies (Press release, DotBio, MAR 4, 2024, View Source [SID1234646740]). DB007 is a tri-specific antibody designed to reinvigorate exhausted immune cells to fight cancer more effectively. This study was conducted in the Agency for Science, Technology and Research (A*STAR).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On March 4, 2024 A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to A2B530 for the treatment of germline heterozygous HLA-A*02(+) patients with colorectal cancer that expresses carcinoembryonic antigen (CEA) and has lost HLA-A*02 expression (Press release, A2 Biotherapeutics, MAR 4, 2024, View Source [SID1234640748]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A2B530 is the first autologous logic-gated cell therapy developed from A2 Bio’s proprietary TmodTM platform. The Tmod platform utilizes a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. This novel design is aimed at tackling the fundamental challenge in solid tumor cancer medicines – the ability to selectively kill tumor cells and protect normal cells. A2B530 consists of an activator that targets CEA and a blocker that targets HLA-A*02.

Enrollment is ongoing in EVEREST-1 (NCT05736731), a seamless Phase 1/2 study to evaluate safety and efficacy of A2B530 in colorectal, pancreatic and non-small cell lung cancers.

"The FDA granting Orphan Drug Designation validates the tremendous unmet need for improved therapies for patients with colorectal cancer," said William Go, M.D., Ph.D, Chief Medical Officer of A2 Bio. "This designation supports our commitment to use our novel technology platform to develop new treatment options for patients with difficult-to-treat cancers."

FDA Orphan Drug Designation incentivizes the development of innovative drugs and biologics for the safe and effective treatment of rare diseases and conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation qualifies A2 Bio for certain development incentives related to the A2B530 clinical program, including tax credits for clinical trials, prescription drug user fee exemptions and potentially up to seven years of market exclusivity upon regulatory approval.

On March 4, 2024 Biomunex Pharmaceuticals, a French biopharmaceutical company specialized in the development of cutting-edge therapies through the discovery and development of bi- and multi-specific antibodies for the treatment of cancer, reported the signature of an exclusive license and exploitation agreement with Institut Curie (Press release, BIOMUNEX Pharmaceuticals, MAR 4, 2024, View Source [SID1234640747]). This agreement covers the development of a new class of antibodies, capable of specifically targeting and engaging MAIT cells to kill cancer cells. Biomunex, which was already co-inventor and a 50% co-owner of this unique innovative approach, now holds full worldwide rights.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

First identified and described in 1999 by Dr. Olivier Lantz, Director of the Clinical Immunology Laboratory at Institut Curie and scientific advisor to Biomunex, MAIT cells are a subpopulation of non-conventional T cells found throughout the body, particularly in mucosal and barrier tissues. MAIT cells are potent cytotoxic T cells capable of proliferating, migrating and infiltrating solid tumors.

Biomunex’s objective is to use these unique properties to develop MAIT engagers, a new class of antibodies capable of redirecting MAIT lymphocytes to eliminate cancer cells and induce the destruction of tumors, particularly solid tumors, while significantly reducing "dose-limiting" toxicity. This novel approach should also reduce the risk of cytokine release syndrome1, a serious adverse event often observed in immunotherapies based on T cell redirection targeting CD3, which are widely used today in cancer treatment.

In addition, MAIT cells present the MDR-12 protein on their surface, providing them with a natural resistance to some major chemotherapies. This property could enable the combination of MAIT engagers with chemotherapy, or their use directly before or after treatment: a key advantage compared with other T cell engagers.

This new approach has been developed through several collaborations with the Cancer Immunotherapy Center (Institut Curie, Inserm) headed by Dr. Sebastian Amigorena, Biomunex’s scientific advisor, and Dr. Olivier Lantz’s team at Institut Curie.

Building on its collaboration with Institut Curie, France’s first and leading cancer research center, and its advanced work on MAIT cells, Biomunex should soon initiate a Phase 1 clinical trial for the evaluation of its first MAIT engager in the treatment of solid tumors with a high unmet medical need, and in which MAIT cells are particularly present (e.g. colorectal, liver, gastric, lung, esophageal cancers, etc.). Biomunex currently develops two MAIT engager programs in preclinical stage with several others in discovery. Biomunex is currently expanding this approach in several directions (e.g. novel antibodies targeting MAIT cells, trispecific engagers, etc.).

"We are very pleased to announce the signing of this major agreement with Institut Curie, a leading institute in global oncology research and a major historical partner of Biomunex", said Dr. Pierre-Emmanuel Gerard, Founder and CEO of Biomunex. Dr. Simon Plyte, Chief Scientific Officer of Biomunex, added: "This agreement positions Biomunex as the world’s leading player in the disruptive field of MAIT engagers, based on the unique BiXAb best-in-class bi- and multi-specific antibody platform."

"The development of new immunotherapy approaches in oncology has become a key challenge if we are to provide an answer to the millions of cancer patients for whom standard treatments can no longer do anything," continued Dr. Sebastian Amigorena. "The research performed at Institut Curie has led to a major discovery which now opens up promising new therapeutic options. This agreement will enable Biomunex to initiate clinical development to harness the unique properties of MAIT cells and thus bring to life this breakthrough therapies for the benefit of patients", concluded Dr. Olivier Lantz.

On March 4, 2024 AnHeart Therapeutics ("AnHeart"), a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer, and Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has accepted a second New Drug Application (NDA) for taletrectinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI) (Press release, AnHeart Therapeutics, MAR 4, 2024, View Source [SID1234640746]). This NDA is for taletrectinib as a first-line treatment for adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have not previously been treated with ROS1 TKIs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In 2023, China’s NMPA accepted taletrectinib’s first NDA and granted Priority Review Designation for adult patients with locally advanced or metastatic ROS1-positive NSCLC who have been previously treated with ROS1 TKIs. Both NDAs in China are based on positive results from the Phase 2 TRUST-I (NCT04395677) trial. Data from an interim analysis of TRUST-I were presented at the European Lung Cancer Congress (ELCC) 2023 and additional data from TRUST-I is planned to be presented at an upcoming medical meeting in 2024.

"I am pleased this second NDA for taletrectinib has been accepted in China. We need additional options for our patients who are newly diagnosed with advanced or metastatic ROS1-positive NSCLC that may improve upon the first-generation medicines," said Professor Caicun Zhou, Principal Investigator and Oncologist at Shanghai Pulmonary Hospital.

"The acceptance of this NDA in China supports our belief in taletrectinib as a first-line treatment for people with advanced or metastatic ROS1-positive NSCLC, and we are excited by the opportunity to bring a potentially transformative medicine to people earlier in their treatment journey," said Bing Yan, MD, President, AnHeart China. "We plan to work closely with our partners at Innovent and regulatory authorities in China to continue progressing taletrectinib as part of our mission to improve the lives of people with cancer."

"Given the clinically demonstrated benefits of taletrectinib in the TRUST-I trial, we are pleased to see the second NDA accepted by the NMPA of China," said Dr. Hui Zhou, Senior Vice President of Innovent. "We will continue close communications with our partner AnHeart Therapeutics and regulatory authorities in China, hoping to bring this new generation of targeted therapy to all appropriate patients with ROS1-positive NSCLC as a standard initial treatment option."

About Taletrectinib

Taletrectinib is an oral, potent, brain penetrant, selective, next-generation potential best-in-class ROS1 inhibitor.

Taletrectinib is being evaluated for the treatment of ROS1-positive NSCLC patients in two Phase 2 trials, TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global pivotal trial.

In 2022, taletrectinib was granted Breakthrough Therapy Designation by the CDE of China’s NMPA for the treatment of adult patients with advanced or metastatic ROS1-positive NSCLC who are ROS1 TKI naïve as well as those who have previously been treated with ROS1 TKIs.

Taletrectinib has also been granted Breakthrough Therapy Designation in the United States for the treatment of ROS1-positive NSCLC by the U.S. Food and Drug Administration (FDA).

In 2021, AnHeart and Innovent entered into an exclusive license agreement for the co-development and commercialization of taletrectinib in Greater China, including mainland China, Hong Kong, Macau and Taiwan.

About ROS1-Positive NSCLC in China

More than one million people globally are diagnosed with NSCLC annually, the most common form of lung cancer. It is estimated that approximately 3% of people with NSCLC in China are ROS1-positive. There are two approved first-generation TKIs for people with newly diagnosed advanced or metastatic ROS1-positive NSCLC in China and no approved therapies for people whose ROS1-positive NSCLC has progressed following treatment with these medicines. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to the brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment.

On March 4, 2024 The European Society of Gynecological Oncology (ESGO) 2024 Conference reported that it has recently made selected abstracts available online (Press release, Qilu Pharmaceutical, MAR 4, 2024, View Source [SID1234640745]). The abstract (abstract # 251) that details results from the Phase II clinical trial (DUBHE-C-206) evaluating the efficacy and safety of Qilu Pharmaceuticals’ iparomlimab and tuvonralimab (QL1706) in cervical cancer was selected for oral presentation on 8 March, local time.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Access the abstract here: View Source;trackid=548#!

This study was led by Professor Jihong Liu from the Sun Yat-sen University Cancer Center and Professor Hanmei Lou from the Zhejiang Cancer Hospital. This was a multi-center, single-arm, phase II study which recruited patients with recurrent or metastatic cervical cancer unresponsive to first-line platinum-based chemotherapy (with or without bevacizumab) and without prior immunotherapy. Participants received QL1706 at a dose of 5.0 mg/kg once every three weeks (Q3W). The study involved 38 medical centers across China and enrolled 148 patients, with a median follow-up of 11.0 months at the data cut-off. The primary endpoint, the objective response rate (ORR), as assessed by an Independent Evaluation Committee (IRC), was 33.8%, meeting the prespecified criteria. The disease control rate (DCR) was 64.9% and median progression-free survival (PFS) was 5.4 months. Overall survival (OS) was not reached. Treatment-related adverse events (TRAEs) occurred in 104 (70.3%) subjects, with 36 (24.3%) experiencing grade ≥3 TRAEs. Anemia (4.1%) was the most common TRAE. Treatment discontinuation due to TRAEs occurred in three patients (2.0%). TRAE leading to death didn’t occur.

The trial indicates that QL1706 is an effective and safe therapy for patients with recurrent or metastatic cervical cancer whose disease progressed after first-line standard of care. In August 2023, the China NMPA, Center for Drug Evaluation (CDE) accepted the new drug application for QL1706, making it the first MabPair product targeting PD-1 and CTLA-4 worldwide and a potential new treatment option for patients with cervical cancer.