On September 13, 2022 The Swedish scale-up company Genagon Therapeutics, together with Mosaique Diagnostics, reported that it receive 7 MSEK in funding from Eurostars for the continued development of biological treatment for triple negative breast cancer (Press release, Genagon Therapeutics, SEP 13, 2022, View Source;utm_medium=rss&utm_campaign=genagon-receive-eurostars-grant-funding [SID1234619530]).

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The consortium partners aim to jointly undertake major steps towards the transition from the preclinical to clinical development of GEN209 – a drug candidate for triple-negative breast cancer (TNBC). This will be a first-in-class monoclonal antibody-drug conjugate (ADC) targeting Clptm1, a novel molecular target expressed in solid tumors.

"This is very positive, and we are happy for this. This will help us secure in vivo efficacy data, identify biomarkers for patient selection and treatment outcome follow-up. We will also design regulatory and toxicology programs allowing for a successful transition to clinical trials", says Moa Fransson, CEO at Genagon Therapeutics.

On September 13, 2022 GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with severe chronic liver diseases, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to GNS5611 (ezurpimtrostat), a novel clinical-stage autophagy/PPT1 inhibitor, for the treatment of cholangiocarcinoma (Press release, Genfit, SEP 13, 2022, https://ir.genfit.com/news-releases/news-release-details/fda-grants-genfits-gns561-orphan-drug-designation-treatment [SID1234619526]).

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Cholangiocarcinoma is a rare liver malignancy with high mortality and limited treatment options. It occurs mostly in people over the age of 50.

GNS561 (ezurpimtrostat) is a PPT-1 (Palmitoyl Protein Thioesterase-1) inhibitor that blocks autophagy. Autophagy is activated in tumor cells in response to certain conditions, due to a tumor cell growth in advanced cancers. GNS561 has completed pre-clinical studies and a Phase 1b trial confirming the rationale for targeting cholangiocarcinoma. A Phase 2 trial is expected to start in the fourth quarter 2022, with a first patient visit expected in the first quarter 2023.

Dr Mark Yarchoan, Associate Professor of Oncology at John Hopkins Medicine (Baltimore, MD) commented: "Cholangiocarcinoma is a rare cancer with a high mortality rate. Patients have limited treatment options, particularly following first line therapy. This is why new therapies are urgently needed and is one of the reasons that GNS561 was granted Orphan Drug Designation by the FDA. There is a real path forward for new options for second line treatment in cholangiocarcinoma, and GNS561 represents a strong second-line therapy candidate and hope to patients."

ABOUT GNS561

GNS561 is a PPT-1 (Palmitoyl Protein Thioesterase-1) inhibitor that blocks autophagy. Autophagy is activated in tumor cells in response to certain conditions, due to a tumor cell growth in advanced cancers. One of the key cellular organs implicated in the autophagy process is the lysosome. By entering the lysosomes and binding to its target, GNS561 has an important inhibiting activity on late-stage autophagy, which leads to tumor cell death.

ABOUT CHOLANGIOCARCINOMA

Cholangiocarcinoma is a type of cancer that forms in the slender tubes (bile ducts) that carry the digestive fluid bile. Cholangiocarcinoma occurs mostly in people over the age of 50. Cholangiocarcinoma is divided into intrahepatic and extrahepatic types based on where the disease occurs in the bile ducts. Cholangiocarcinoma is often diagnosed when it is advanced, making successful treatment difficult to achieve. Several risk factors of chronic inflammatory damage and increased cellular turnover have been established, such as primary sclerosing cholangitis (a cholestatic liver disease), liver flukes, biliary tract cysts, hepatolithiasis and toxins. Treatment options for cholangiocarcinoma are limited and associated with high rates of tumor recurrence, and short survival times.

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.