On July 21, 2022 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that Sanofi has made the decision to progress IPH6401/SAR’514 into investigational new drug (IND)-enabling studies, triggering a €3 million milestone payment (Press release, Innate Pharma, JUL 21, 2022, View Source [SID1234616816]).

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!

IPH6401/SAR’514 is a BCMA-targeting NK cell engager using Sanofi’s proprietary CROSSODILE multi-functional platform, which comprises the Cross-Over-Dual-Variable-Domain (CODV) format. It induces a dual targeting of the NK activating receptors, NKp46 and CD16, for an optimized NK cell activation, based on Innate’s ANKETTM (Antibody-based NK cell Engager Therapeutics) proprietary platform. NK cell engagers are an alternative for cancer treatment aiming to offer an improved therapeutic window as compared to bispecific T lymphocyte-engaging formats.

IPH6401/SAR’514 has shown anti-tumor activity and promising drug properties in pre-clinical models. Sanofi will be responsible for all future development, manufacturing and commercialization of IPH6401/SAR’514.

"We are pleased that Sanofi has chosen to progress IPH6401/SAR’514 into development, building on our strong partnership which brought the first NKp46-based NK cell engager to the clinic last year," said Pr. Eric Vivier, DVM-PhD, Chief Scientific Officer at Innate Pharma. "Innate/Sanofi’s collaboration integrating Sanofi’s multi-functional CODV format and the dual NK cell targeting based on Innate’s multifunctional ANKET platform is creating an entirely new class of molecules to induce synthetic immunity against cancer, which have been designed to belong to the next wave of impactful medicines in immunotherapy."

This milestone is part of the previously announced research collaboration with Sanofi, under which the companies collaborate on the generation and evaluation of up to two bispecific NK cell engagers, using the ANKET platform from Innate that simultaneously targets two NK activating receptors, NKp46 and CD16, to optimize NK cell activation and Sanofi’s proprietary antibody format as well as anti-tumor target antibodies. In 2021, the companies announced plans to develop IPH6101/SAR’579, which is in Phase 1/2 in relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) and high risk-myelodysplastic syndrome (HR-MDS).

About the Innate-Sanofi agreement:

The Company has a research collaboration and licensing agreement with Sanofi to apply Innate’s proprietary platform to the development of innovative multi-specific antibody formats engaging NK cells through the activating receptors NKp46 and CD16 to kill tumor cells now called the ANKET platform.

Under the terms of the license agreement, Sanofi will be responsible for the development, manufacturing and commercialization of products resulting from the research collaboration. Innate Pharma will be eligible to up to €400m in development and commercial milestone payments as well as royalties on net sales.

About ANKETTM:

ANKETTM (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer.

On July 20, 2022 BioRay Pharmaceutical Co., Ltd. (hereinafter referred to as "BioRay") reported that the first patient with advanced malignant tumors had been dosed in the Phase I Clinical trial of self-developed Category 1 innovative drug BR105 (Press release, Zhejiang Hisun Pharmaceutical, JUL 20, 2022, View Source;a=index&classid=43&id=1 [SID1234634616]). This is an open-label, dose-escalation, and dose-expansion trial to explore the safety, tolerability, and antitumor activity of BR105. The phase Ia part of the trial aims to evaluate the safety and tolerability of BR105 monotherapy (single and multiple doses) in subjects with advanced malignancies and to explore the maximum tolerated dose (MTD). The leading entity of the clinical trial is Beijing Cancer Hospital, and the principal investigators are Prof. Jun Zhu and Prof. Lin Shen.

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!

BR105 is a SIRPα-targeting humanized monoclonal antibody that was independently developed by BioRay, which can recognize the common variants of signal-regulated protein α (SIRPα), blocks the binding of SIRPα to CD47, disengage the "don’t eat me" signal and activate macrophages to promote phagocytosis of tumor cells.

SIRPα is a transmembrane protein expressed on the surface of myeloid cells such as macrophages, monocytes, dendritic cells, and granulocytes. The binding of SIRPα to CD47 activates phagocytosis-inhibitory signals in multiple cancer types, and tumor cells are able to evade phagocytosis by macrophages. Blocking CD47/SIRPα signaling potentiates phagocytosis of tumor cells by macrophages, and suppresses tumor growth. CD47/SIRPα can be a viable immune target for antitumor therapy.

Multiple tumor models have demonstrated the effectiveness of targeting CD47/SIRPα. Clinical studies suggest that blockage of CD47–SIRPα signaling pathway may generate antitumor activity in broad-spectrumof malignancies, including various hematologic and solid tumors. CD47/SIRPα-targeted therapy has shown positive efficacy results in acute myeloid leukemia, lymphoma, head, and neck squamous cell carcinoma, gastric cancer, and other tumors.

Unlike CD47, SIRPα has a limited tissue expression pattern. BR105 blocks CD47/SIRPα signaling pathway by targeting SIRPα, which is superior in safety. In addition, CD47 can interact with other proteins such as TSP-1 and SIRPγ, which are involved in more complex signaling pathways, and the corresponding targeted therapeutic regimens have more risk considerations to balance; therefore, developing SIRPα antibodies to block the CD47/SIRPα signaling pathway may be a more effective strategy for oncology drug development.

"CD47/SIRPα is considered one of the most prospective targets for tumor immunotherapy after PD-1/PD-L1," said Dr. Wei Zhu, Chief Medical Officer of BioRay, "BR105 is an important candidate of our tumor immunization pipeline. We are pleased that the first patient’s dosing of BR105 has been completed, and this marks important progress in the innovation and R&D of BioRay. We will next push forward with our research and development projects in the field of popular targets for tumor immunity and autoimmunity to benefit patients."

On July 20, 2022, Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics" hereafter) reported that its CSF-1R inhibitor ABSK021 had been granted the breakthrough therapy designation from Center for Drug Evaluation, NMPA for the treatment of tenosynovial giant cell tumor (TGCT) that not amenable to surgery (Press release, Abbisko Therapeutics, JUL 20, 2022, View Source [SID1234633494]).

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!

The Breakthrough Therapy Designation is a CDE program for innovations during clinical trials that are used for the prevention and treatment of serious life-threatening diseases or seriously affect the quality of life, and there are no effective prevention and treatment methods or there is sufficient evidence to show that they have obvious clinical advantages compared with existing treatment methods.

This breakthrough therapy designation approval is based on results from the phase Ib clinical trial of TGCT cohort in China for CSF-1R inhibitor ABSK021.

TGCT, also known as pigmented villonodular synovitis, is a locally aggressive neoplasm that affects synovial joints, mucous sacs, and tendon membranes, resulting in swelling, pain, stiffness, and decreased activity of the affected joints which seriously affect the patient’s quality of life.

According to the 2013 World Health Organization classification, TGCTs were classified as localized TGCT and diffuse TGCT. Compared with localized TGCT (80%-90%), the incidence rate of diffuse TGCT is lower (10-20%).

Overexpression of colony-stimulating factor 1(CSF1) occurs in most TGCTs. Surgical resection is the standard treatment for TGCT. However, not all patients are suitable for surgical treatment. It is difficult to remove tumors of diffuse patients by surgery, which may possibly lead to severe joint damage, total synovectomy, joint replacement, or even amputation, and the risk of surgical complications can be high. It has been reported that more than 50% of patients with diffuse TGCT will undergo recurrence after surgical resection. For those TGCT patients not amenable to surgery, there is currently no approved drug available in China.

ABSK021 is a novel, orally available, highly selective, and highly potent small molecule inhibitor of CSF-1R, independently developed by Abbisko Therapeutics. It is also the first selective CSF-1R inhibitor discovered by a Chinese company that has advanced into human clinical trial. A number of studies have shown that blocking the CSF-1R signaling pathway could effectively modulate and change macrophage functions, and potentially treat many macrophage-dependent human diseases. Abbisko has completed a phase Ia dose escalation study for ABSK021 in the U.S., with phase Ib expansion ongoing in both U.S. and China. In addition to TGCT, Abbisko is actively exploring the potential of ABSK021 in treating other indications including many types of solid tumors in clinic, and has collaborated with Sperogenix in exploring its potential for treating ALS and other CNS diseases. As of the date of this press release, no high-selective CSF-1R inhibitor has been approved in China.

On July 20, 2022 Manhattan BioSolutions, Inc. reported it has entered into two commercial evaluation license agreements with the National Cancer Institute (NCI), part of the US National Institutes of Health (NIH), to generate and validate novel antibody-drug conjugate (ADC) therapies using monoclonal antibodies developed by NCI (Press release, Manhattan BioSolutions, JUL 20, 2022, View Source [SID1234618289]). ADCs harness the targeting ability of antibodies to deliver drugs to the tumor microenvironment or directly to cancer cells.

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!

Under the first agreement, Manhattan BioSolutions obtained the proprietary monoclonal antibody discovered and validated by Drs. Ira Pastan, MD, Distinguished Investigator, Chief Emeritus of the Laboratory of Molecular Biology and Mitchell Ho, PhD, Director of the Antibody Engineering Program and Deputy Chief of the Laboratory of Molecular Biology at the NCI Center for Cancer Research. This antibody targets a cell surface glycoprotein overexpressed in multiple cancers including mesothelioma, lung, ovarian and pancreatic cancer. Dr. Ira Pastan is recognized for his pioneering contributions to the fields of receptor biology, which led to the discovery of the new class of antibody drugs called recombinant immunotoxins. The targeted immunotoxin he developed to treat a deadly form of leukemia is now an approved medication marketed by Astra Zeneca under the name Lumoxiti.

The second license agreement provides access rights toa new monoclonal antibody directed to a cell surface receptor tyrosine kinase overexpressed and mutationally activated in a rare pediatric cancer as well as in other solid tumors. This antibody was discovered by the team of Dr. Javed Khan, MD, Senior Investigator and Deputy Chief at the Genetics Branch at the NCI Center for Cancer Research.

The partnerships allow Manhattan BioSolutions to further expand its preclinical pipeline of innovative biologic agents for oncology applications. The antibodies discovered at NCI will be combined with the proprietary immune-stimulating linker-payloads invented by Dr. L. Nathan Tumey, an ex-Pfizer medicinal chemist, who is currently an Associate Professor in the School of Pharmacy and Pharmaceutical Sciences at Binghamton University. The current collaboration follows the previously announced grant award and collaborative research agreement with the laboratory of Dr. Dhaval Shah, a former Pfizer scientist, now an Associate Professor at the Department of Pharmaceutical Sciences, University at Buffalo.

"The synergistic combination of assets and platforms enables the discovery of novel classes of medicines designed to activate innate, microbial host-defense immunity in tumor microenvironment," said Dr. Borys Shor, CEO of Manhattan BioSolutions. "We have assembled a world-class team of drug discovery experts to develop next-generation ADCs: a trio of ex-Pfizer scientific leaders, including Drs. Dhaval Shah and Nathan Tumey, all with a proven track record of bringing transformative oncology medicines to clinical development."

On July 20, 2022 Singapore-based biotech start-up, Tetris Therapeutics Pte. Ltd. reported that it has changed its name to Axcynsis Therapeutics Pte. Ltd (Press release, Axcynsis Therapeutics, JUL 20, 2022, View Source [SID1234618243]).. The new name will better reflect the company’s core business and platform technology – AXC (Antibody-X Conjugate) Synthesis.

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!

"Antibody Drug Conjugates (ADCs) are a class of anticancer agents designed by conjugating cytotoxic drugs to monoclonal antibodies." said Dr. Zou Bin, founder and CEO of Axcynsis Therapeutics. "In fact, this concept can be extended beyond cytotoxic drugs. Hence we are developing our platform technologies to synthesize Antibody-X Conjugates, where "X" could be any molecules that disrupt the abnormal cells."

Axcynsis Therapeutics will continue to strengthen the company’s pipeline and provide new treatment options to address unmet medical needs.