On September 13, 2022 Akeso, Inc. (9926.HK) ("Akeso"), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, reported that encouraging preclinical results in poster featuring its Fc-mutant anti-TIGIT antibody fused with TGF-βRII protein (AK130) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 (Press release, Akeso Biopharma, SEP 13, 2022, View Source;dual-targeting-antibody-fusion-protein-of-akeso-demonstrated-promise-in-preclinical-results-published-at-esmo-301622658.html [SID1234619522]).

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AK130 is the first and only TIGIT/TGF-β dual-targeting antibody fusion protein and the first novel dual-targeting antibody fusion protein developed in-house by Akeso. The clinical trial application for AK130 was just accepted by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) not long ago, demonstrating Akeso’s ability to develop breakthrough drugs with complete independence and autonomy.

Details of the poster are as follows:

Poster: AK130, a first-in-class Fc-mutant anti-TIGIT antibody fused with TGF-βRII protein, elicits potent anti-tumor efficacy in preclinical studies.
Abstract: #486P
Presenters: Jing Min, Vice President of Akeso
Although TIGIT is considered a promising immune checkpoint molecule, the single-agent efficacy of anti-TIGIT therapy is limited. AK130, a novel anti-TIGIT antibody fused with TGF-βRII protein, was designed to inhibit TIGIT-mediated immunosuppression while decreasing the TGF-β levels in the tumor microenvironment (TME). Mutations were introduced in the Fc region of the antibody with IgG4 backbone to avoid antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to minimize lymphocyte loss.

The encouraging observations from preclinical results of AK130 supports its clinical development for the treatment of human cancers:

AK130 could specifically bind to human TIGIT and TGF-β with high affinity.
In reporter gene assays, AK130 efficiently blocked the interaction between TIGIT and CD155, as well as TGF-β1/TGF-β3 and TGFβ-RII.
As expected, AK130 did not show ADCC or CDC activity compared to tiragolumab.
AK130 shows great anti-tumor efficacy in a mouse tumor model.
About AK130 (TIGIT/TGF-β dual-targeting antibody fusion protein)

AK130 is a bifunctional antibody-fusion protein entirely independently developed by Akeso. It consists of an anti-TIGIT monoclonal antibody fused to the extracellular domain of human transforming growth factor-β receptor II (TGFβ-RII). TIGIT is an emerging immune checkpoint that blocks TIGIT-CD155 interaction, relieves the inhibition of tumor-infiltrating CD8 + T cells and NK cells and promotes their anti-tumor function. TGF-β signaling can lead to immunosuppression, cancer immune escape, and immune checkpoint inhibitor resistance. Dual blockade of TIGIT and TGF-β activates T cell immune responses and reduces TGF-β-mediated immunosuppressive activity of Tregs, thereby achieving better antitumor effects.

On September 13, 2022 GeneCentric Therapeutics, a company making precision medicine more precise through RNA-based diagnostics, reported the poster presentation of further clinical validation data for PurISTSM, a novel RNA-expression test, in collaboration with Tempus (Press release, GeneCentric Therapeutics, SEP 13, 2022, View Source [SID1234619498]). PurIST identifies patients with the classical subtype of pancreatic ductal adenocarcinoma (PDAC) that are likely to experience longer overall survival (OS) with standard of care (SOC) FOLFIRINOX than patients with the basal subtype of PDAC. The presentation will be made at the 8th AACR (Free AACR Whitepaper) Special Conference on Pancreatic Cancer in Boston, Massachusetts, which runs from September 13-16, 2022.

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Title: Purity Independent Subtyping of Tumor (PurIST): Real-world data validation of a pancreatic ductal adenocarcinoma (PDAC) gene expression classifier and its prognostic implications

First Author: Stephane Wenric, PhD, Principal Scientist, Computational Systems Biology, Tempus, Chicago, Illinois

Presenting Author: James M. Davison, PhD, Senior Translational Genomics Scientist, GeneCentric Therapeutics, Durham, NC

PurIST is a laboratory developed test (LDT) validated by Tempus using a real-world dataset of advanced PDAC patients. Over 250 patients with advanced PDAC who were previously treated with SOC FOLFIRINOX or gemcitabine/nab-paclitaxel were identified in Tempus’ multimodal data library. RNA sequencing (RNAseq) was performed on either primary or metastatic tumor tissue using the CAP/CLIA-validated Tempus xT assay platform. Patients were identified as either basal or classical molecular subtype. For FOLFIRINOX-treated patients, those with a classical molecular subtype had extended survival compared to those with basal molecular subtype. Survival was similar for FOLFIRINOX and gemcitabine/nab-paclitaxel treatment regimens in basal patients, but classical patients had extended survival when treated with FOLFIRINOX.

Further details surrounding test development and validation will be presented as part of an upcoming publication.

About Pancreatic Cancer

Pancreatic cancer is one of the most common cancers worldwide, and the National Cancer Institute estimates there will be 62,210 new cases and 49,830 deaths in the U.S. in 2022. It is the third-leading cause of cancer-related deaths in the U.S. and has the highest mortality rate of all major cancers. More than 90% of pancreatic cancers are pancreatic ductal adenocarcinoma (PDAC), and the 5-year overall survival for resectable/borderline-resectable and non-resectable PDAC is approximately 20-30% and 1-3%, respectively. The average patient diagnosed with Stage IV PDAC will live for about one year after diagnosis. The three main treatments for PDAC are surgical resection (if diagnosed early), radiation therapy and chemotherapy. For resectable tumors, surgical resection is provided with curative intent, however, for non-resectable tumors, chemotherapy such as FOLFIRINOX or gemcitabine with nab-paclitaxel is often used.

On September 13, 2022 I-Mab (the "Company") ( Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, reported that it has successfully completed an End-of-Phase 2 (EoP2) meeting with the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), and has obtained approval from the CDE to initiate a Phase 3 registrational trial evaluating lemzoparlimab, a novel CD47 antibody, in combination with azacitidine (AZA) for the first-line treatment of patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) (Press release, I-Mab Biopharma, SEP 13, 2022, View Source [SID1234619521]). The outcome of the EoP2 meeting supports the advancement of lemzoparlimab into Phase 3 study for a potential biologic license application (BLA) submission. The Company is on track to initiate the study as planned.

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The EoP2 meeting was supported by encouraging results from the Phase 2 clinical trial evaluating lemzoparlimab in combination with AZA in patients with newly diagnosed HR-MDS (NCT04202003). The top-line efficacy data demonstrated that lemzoparlimab combined with AZA showed encouraging clinical response in HR-MDS patients. Results also showed that lemzoparlimab combined with AZA can be safely administered without the need of a priming dose. The full results were reported in a proffered paper presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 on September 10, 2022.

"We are pleased by the constructive feedback from the CDE, which has given us the greenlight to initiate the Phase 3 trial with lemzoparlimab for HR-MDS, a difficult-to-treat disease with high unmet medical need in this patient population with few treatment options," said Dr. Andrew Zhu, President of I-Mab. "We look forward to initiating our Phase 3 study to support a planned BLA submission in China for lemzoparlimab with the goal of providing a novel therapeutic option for patients suffering from this disease."

About CD47 and Lemzoparlimab

CD47 is a cell surface protein over-expressed in a wide variety of cancers and can act to protect tumors by delivering a "don’t eat me" signal to otherwise tumor-engulfing macrophages. CD47 antibody blocks this signal and enables macrophages to attack tumor cells. However, development of CD47 antibody as a cancer therapy has been hampered by its hematologic side effects, such as severe anemia, caused by natural binding of CD47 antibody to red blood cells. Scientists at I-Mab discovered a novel CD47 antibody, lemzoparlimab, that is designed to target tumor cells while exerting a minimal untoward effect on red blood cells.

Multiple clinical studies of lemzoparlimab are ongoing to explore indications in treating patients with myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), non-Hodgkin’s lymphoma (NHL), and advanced solid tumors in combination with chemotherapy and immune checkpoint inhibitors.

On September 13, 2022 Strata Oncology, Inc. a next-generation precision oncology company enabling smarter and earlier cancer treatment, reported expansion of its clinical collaboration with Pfizer ( NYSE: PFE) in the Strata Precision Indications for Approved THerapies (Strata PATHTM) trial (Press release, Strata Oncology, SEP 13, 2022, View Source [SID1234619520]). Strata PATH is a prospective pan-tumor therapeutic trial designed to evaluate the efficacy and safety of multiple FDA-approved cancer therapies in new, biomarker-guided patient populations. Pfizer will provide Braftovi (encorafenib), Mektovi (binimetinib), and Lorbrena (lorlatinib) for up to six new cohorts of patients with early-stage lung, melanoma, colorectal, and other cancers who have evidence of micrometastatic disease after initial treatment. Pfizer is already providing Strata with Braftovi (encorafenib), Mektovi (binimetinib), Lorbrena (lorlatinib), Talzenna (talazoparib), and Inlyta (axitinib) for evaluation in four late-stage cohorts of the Strata PATH trial.

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"The new cohorts of Strata PATH, supported by Pfizer, afford us a very exciting opportunity to move the advances we’ve seen in late-stage cancer into earlier stages of the disease," said Dan Rhodes, Ph.D., co-founder and Chief Executive Officer, Strata Oncology. "Our goal is to deliver smarter and earlier treatment to every patient and having the support of Pfizer is a testament to the potential of the clinical trials that we are using to accelerate the impact of precision oncology."

Many of the patients for the new micrometastatic cohorts of Strata PATH will be identified through the Strata SentinelTM trial, a 100,000-patient, prospective, observational, pan-solid tumor study of Strata Oncology’s highly sensitive, tumor-informed circulating tumor DNA (ctDNA)-based MRD test. An advanced molecular therapy selection profile is created simultaneously for every patient assessed with the MRD test. This enables rapid identification of clinical trial opportunities, including Strata PATH, for patients who are positive for ctDNA.

About Strata PATH
The Strata Precision Indications for Approved THerapies (Strata PATH) trial, is a 700-patient prospective pan-tumor therapeutic trial designed to evaluate the efficacy and safety of multiple FDA-approved cancer therapies in new, biomarker-guided patient populations. Strata PATH will enroll patients with advanced cancer, as well as patients with early-stage cancer who have evidence of micrometastatic disease after initial treatment. All therapies being evaluated in Strata PATH are FDA-approved in oncology with demonstrated safety profiles in the advanced setting. Enrollment for multiple arms in Stata PATH is based on novel quantitative RNA and multivariate algorithms Strata Oncology developed using its clinical molecular database comprising DNA mutation profiles and quantitative RNA expression data from tens of thousands of patients coupled with detailed treatment history and outcomes data. A range of therapeutic classes will be evaluated in Strata PATH including targeted therapies, antibody-drug conjugates, immunotherapies, and angiogenesis inhibitors.

On September 13, 2022 TC Biopharm (Holdings) PLC ("TC Biopharm" or the "Company") (NASDAQ: TCBP) (NASDAQ: TCBPW), a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer reported that it has received approval from the UK regulatory body MHRA to apply an 18-month extrapolated shelf life to its current allogeneic cell therapy product, OmnImmune (Press release, TC Biopharm, SEP 13, 2022, View Source [SID1234619519]).

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This award enables TC BioPharm to ship and store sufficient product which can then be held cryopreserved at clinical sites to fulfill the requirements not only for its current Advanced Myeloid Leukemia trial ACHIEVE, but also for future clinical trials and eventually commercial treatment of patients. Additionally, TC BioPharm’s in-house quality control department will continue to gather data in order to extend the shelf-life of OmnImmune.

"The approval received from the MHRA for our frozen product is another very important piece of a complex jigsaw. It is indeed a further step towards the achievement of a platform to deliver truly off-the-shelf products in the cell therapy space. This milestone is a result of an incredible concerted effort from all the departments within TCB, including Product Development, Quality Control and Assurance, Production and Clinical. It is an exciting time to be working in this sector and I feel incredibly privileged and proud to be part of this amazing team at TC Biopharm."

Bryan Kobel, CEO, commented, "This MHRA approval of our freeze/thawed protocol for an 18-month shelf life is an encouraging step forward in TC BioPharm’s developmental trajectory and further validation of the continuous effort and forward thinking of our development team. We are extremely pleased to receive MHRA approval for our Freeze/Thawed product, OmnImmune, the first freeze/thawed gamma delta product in clinical trials. Being able to ship frozen gamma-delta T cells and deliver them clinics all around the world for storage and use in clinical trials as well as commercial treatment increases our economies of scale and our efficiency."

"The approval received from the MHRA for our frozen product is another very important piece of a complex jigsaw," said Emilio Cosimo, Director of Product Development at TC BioPharm. "It is indeed a further step towards the achievement of a platform to deliver truly off-the-shelf products in the cell therapy space. This milestone is a result of an incredible concerted effort from all the departments within TCB, including Product Development, Quality Control and Assurance, Production and Clinical. It is an exciting time to be working in this sector and I feel incredibly privileged and proud to be part of this amazing team at TC Biopharm. "

Kobel continued, "This approval brings OmnImmune truly to the forefront as an "off the shelf" cell therapy, with the clinician’s ability to bring product from the storage facility to the specialty pharmacy for thawing and deliver the therapeutic to the patient in a short window of time. We look forward to progressing our clinical trials in AML as well as other blood cancers and continue to evaluate partnering opportunities for our allogeneic gamma delta platform and advance our modified CAR gamma delta program."