On June 28, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that it has expanded its off-the-shelf, iPSC-derived, cell-based cancer immunotherapy collaboration with ONO Pharmaceutical Co., Ltd. (ONO) to include the development of chimeric antigen receptor (CAR) NK cell collaboration candidates (Press release, Fate Therapeutics, JUN 28, 2022, View Source [SID1234616321]). In addition, as part of the collaboration’s expansion, ONO will contribute novel binding domains targeting a second solid tumor antigen. Under the original Collaboration and Option Agreement entered into between Fate and ONO in September 2018, ONO has contributed novel binding domains targeting an initial solid tumor antigen, and Fate is currently conducting preclinical development of a multiplexed-engineered, iPSC-derived CAR T-cell product candidate for solid tumors.

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"Our collaboration with ONO has focused on driving innovation in the field of cell therapy for solid tumors, and we are excited by the preclinical data we have observed with our first iPSC-derived CAR T-cell product candidate," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We are impressed with the differentiated antigen binders that ONO has contributed to the partnership, and we are pleased to expand our collaboration to initiate preclinical development of collaboration products targeting a second solid tumor antigen."

Under the terms of the amended Collaboration and Option Agreement, Fate will advance iPSC-derived CAR NK and CAR T-cell product candidates to a pre-defined preclinical milestone, at which point ONO has an option to assume responsibility for worldwide development and commercialization with Fate retaining the right to jointly develop and commercialize in the United States and Europe. Fate retains all rights of manufacture of collaboration products on a global basis.

"The first multiplexed-engineered, iPSC-derived CAR T-cell product candidate under our collaboration with Fate Therapeutics incorporates multiple mechanisms of action designed to specifically address solid tumors and is successfully advancing toward clinical development," said Toichi Takino, Senior Executive Officer / Executive Director, Discovery & Research of ONO. "Based on the collaboration progress and Fate’s proven ability to develop innovative product candidates, we are excited to expand our collaboration to include a second solid tumor target and to continue our work with Fate in developing first-in-class, off-the-shelf CAR NK and CAR T-cell therapies for cancer patients."

Fate will continue to receive committed research funding from ONO during the preclinical option period, and is eligible to receive a preclinical option exercise fee as well as clinical, regulatory and commercialization milestone payments from ONO in connection with the development and commercialization of each product candidate. In addition, Fate is eligible to receive tiered royalties on net sales by ONO of each product candidate in the ONO territory.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

On June 28, 2022 Palleon Pharmaceuticals Inc., a company pioneering the field of glyco-immunology to treat cancer and inflammatory diseases, reported a strategic collaboration with Shanghai Henlius Biotech, Inc. (2696.HK) to develop and commercialize two bifunctional sialidase programs from Palleon’s EAGLE (Enzyme-Antibody Glyco-Ligand Editing) immuno-oncology platform, including Palleon’s Bifunctional HER2-Sialidase now in preclinical development and a second bifunctional sialidase to be developed with a proprietary target provided by Henlius (Press release, Palleon Pharmaceuticals, JUN 28, 2022, View Source [SID1234616320]).

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Palleon’s EAGLE platform potentiates antitumor immunity by enzymatically removing immunosuppressive sialic acids from tumor and immune cell surfaces. The EAGLE platform is created by genetic fusion of an engineered human sialidase with antibody domains, and includes clinical stage Bi-Sialidase, as well as various bifunctional sialidases comprising a sialidase together with a targeting arm. As one of Palleon’s most advanced bifunctional sialidases, the Bifunctional HER2-Sialidase has shown the potential to treat both HER2-low and HER2-high expressing tumors with modest to high levels of tumor surface sialoglycans, and the candidate is on the verge of entering IND-enabling studies.

Henlius has built a vertically integrated biopharmaceutical platform with core capabilities of high efficiency and innovation embedded throughout the entire product life cycle of R&D, manufacturing, and commercialization, expediting a diversified and robust pipeline covering tumor-associated-antigen (TAA) targets with high market potential. Fully leveraging its experience in biologics development and harnessing the power of innovation, Henlius implements its proprietary antibody and novel conjugating technologies to explore various forms of antibody conjugates to continue building a more diverse innovative pipeline by synergizing its innovation centers in China and the US, as well as its global clinical development teams. Henlius has process development capabilities that span the product lifecycle, starting with cell line development and continuing through commercial manufacturing, effectively supporting the commercialization of its products around the world.

"We’re very pleased to partner with Henlius to develop and expand Palleon’s pipeline to realize the potential of bifunctional sialidases as a treatment option for a wide range of cancer types," said Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon. "Henlius has a strong track record of providing groundbreaking and cost-effective medicines for patients in China, and the development of these two therapeutic candidates will benefit from their expertise and capabilities."

Under the terms of the agreement, Palleon will perform research and the parties will then share preclinical and global clinical development responsibilities and costs for the Bifunctional HER2-Sialidase and a second bifunctional sialidase. Henlius has an exclusive license to the two investigational therapies in China (including Hong Kong, Macau, and Taiwan), while Palleon retains all other global rights and, for the second product, receives a royalty-bearing exclusive license to Henlius’ antibody technology outside China. Palleon received an upfront payment and is further eligible to receive up to $196.5 million in certain predetermined R&D and commercial milestones, in addition to royalties upon Henlius commercialization in China.

"We strive to offer innovative and affordable biologics to all patients," said Wenjie Zhang, Chairman, Executive Director, and CEO of Henlius. "Henlius is currently exploring various forms of antibody conjugates utilizing our proprietary antibody expertise and novel conjugating technologies. Together with Palleon’s cutting-edge EAGLE immuno-oncology platform, we believe that this collaboration will complement Henlius’ innovative early-stage pipeline and accelerate our progress of providing breakthrough treatments for patients with unmet medical needs."

On June 28, 2022 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a late clinical-stage biopharmaceutical company focused on oncology, reported that the Company has entered into a collaboration agreement with GenFleet Therapeutics, an immuno-oncology focused biopharmaceutical company based in China, to advance Motixafortide through a randomized Phase 2b clinical trial in pancreatic ductal adenocarcinoma, or PDAC (Press release, BioLineRx, JUN 28, 2022, View Source [SID1234616319]).

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Under the terms of the agreement, GenFleet will fully fund, design and execute a randomized Phase 2b clinical trial that will enroll approximately 200 first-line metastatic PDAC patients in China. This randomized controlled study will aim to evaluate the superiority of Motixafortide in combination with an anti-PD-1 and chemotherapy compared to chemotherapy alone, the current standard of care. As part of the collaboration, BioLineRx will supply Motixafortide, while GenFleet will supply the other study drugs for the trial. Trial oversight will be administered by a Joint Development Committee. GenFleet will be eligible to receive low-to-mid-single digit tiered percentage royalties on future Motixafortide sales, if approved.

"This collaboration is based on the highly encouraging results from our Phase 2a COMBAT/KEYNOTE-202 study of Motixafortide in combination with an anti-PD-1 and chemotherapy, which provide strong support for continued development in this very challenging disease," stated Philip Serlin, Chief Executive Officer of BioLineRx. "With its broad solid tumor oncology pipeline and highly experienced development team, we believe we have found an outstanding partner in GenFleet to execute a rigorously designed randomized Phase 2b trial."

"At the same time, we remain on track to submit our New Drug Application (NDA) for Motixafortide in stem cell mobilization in the U.S. in the next few months, and we are continuing our pre-launch activities in anticipation of potential FDA approval in 2023."

"Together, these programs demonstrate the potential versatility of Motixafortide and its promise of new combination therapies targeting both hematological and solid tumor cancers," Mr. Serlin concluded.

"The results of the COMBAT/KEYNOTE-202 Phase 2a study demonstrate the benefit of combining the CXCR4 inhibitor Motixafortide with an anti-PD-1 and chemotherapy in a second-line setting," said Qiang Lu, Chairman of GenFleet. "We believe that this combination could be beneficial to patients in a first-line setting as well, and we hope to confirm this in a randomized trial. We are thrilled to be partners with BioLineRx in the development of this late-stage clinical asset, and look forward to initiating this important trial as quickly as possible."

In parallel, BioLineRx is continuing its collaboration with Colombia University in an on-going Phase 2 investigator-initiated study (NCT04543071) to evaluate Motixafortide in combination with the anti-PD-1 LIBTAYO (cemiplimab) and standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) in first-line PDAC patients.

MSQ Ventures served as advisor to BioLineRx on this transaction.

About Pancreatic Cancer

Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. Its incidence rate in the US is estimated at 3.2% of new cancer cases. In 2022, approximately 495,000 individuals globally are expected to be diagnosed with this condition, 62,000 of them in the US; and the incidence of pancreatic cancer is expected to continue to increase. Symptoms are usually non-specific and as a result, pancreatic cancer is often not diagnosed until it reaches an advanced stage. Surgical resection does not offer adequate treatment since only 20% of patients have resectable tumors at the time of diagnosis. Even among patients who undergo resection for pancreatic cancer and have tumor-free margins, the five-year survival rate is only 10-25%. The overall five-year survival rate among pancreatic cancer patients is 8%, which constitutes the highest mortality rate among solid tumor malignancies. The overall median survival is less than one year from diagnosis, highlighting the need for the development of new therapeutic options.

Despite advances in chemotherapeutics and immunotherapy, increases in median and overall survival rates in pancreatic cancer have been modest. Pancreatic cancer remains an area of unmet medical need, with very limited new approved therapies for the majority of PDAC patients since the approval of nab-paclitaxel (Abraxane) in combination with gemcitabine for first-line treatment in 2013 and Onivyde in combination with fluorouracil and leucovorin for second-line treatment in 2015. The limited clinical benefits demonstrated by these existing standard treatment options reinforce the need for additional approaches.

About COMBAT/KEYNOTE-202

In December 2020, BioLineRx announced final positive results from its Phase 2a COMBAT/KEYNOTE-202 triple combination study of Motixafortide in second line PDAC. The highly encouraging results demonstrated improvement across all study endpoints, including overall survival, progression free survival and overall response rate, in the most challenging PDAC patients, as compared to historical data. All patients were diagnosed at Stage IV, and greater than 70% had liver metastases, a key determinant of poor prognoses in this patient population.

On June 28, 2022 Akoya Biosciences, Inc., (Nasdaq: AKYA), The Spatial Biology Company, and Acrivon Therapeutics, Inc., a clinical-stage oncology therapeutics company with proprietary technologies driving a new era of precision-based medicine, reported an agreement to co-develop, validate, and commercialize Acrivon’s OncoSignature test, a first-of-its-kind companion diagnostic (Press release, Akoya Biosciences, JUN 28, 2022, View Source [SID1234616318]). The test will be used to identify cancer patients most likely to respond to treatment with ACR-368, a targeted DNA damage response inhibitor therapy being developed by Acrivon. ACR-368 has been cleared by the FDA to be advanced in a Phase 2 master protocol trial to treat patients with ovarian, endometrial, and urothelial cancer based on predicted sensitivity to ACR-368.

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ACR-368 has been evaluated in over 1,000 patients and has demonstrated durable monotherapy activity, including complete responses, in a proportion of patients with platinum-resistant ovarian cancer. These patients currently have no effective treatment options, and the median survival time with this disease is less than one year. In addition to ovarian cancer, ACR-368 is being evaluated as a treatment for endometrial and urothelial cancers — two other high unmet need solid tumor types predicted by OncoSignature to be highly sensitive to the drug. The OncoSignature test, developed by Acrivon, will be run on Akoya’s PhenoImager solution during clinical development and, pending ACR-368 approval and commercialization, will enable physicians to identify and treat the patients most likely to respond to the therapy.

Akoya, in partnership with Acrivon, will develop, clinically validate, and seek regulatory co-approval for the OncoSignature test, and, pending ACR-368 approval, commercialize the test as the exclusive provider of the companion diagnostic required for prescribing ACR-368. The test will leverage the spatial phenotyping capabilities of the PhenoImager solution to localize and quantify the expression of a signature of clinically relevant protein biomarkers within the tumor.

"The ability to select patients for ACR-368 is a foundational part of our efficient clinical development strategy and is a critical part of our mission to bring our targeted therapies to the patients most likely to benefit from treatment," said Peter Blume-Jensen, M.D., Ph.D., chief executive officer and president of Acrivon. "We believe that Akoya is an ideal partner to develop and commercialize this next-generation companion diagnostic with their technically advanced, quantitative PhenoImager solution. We look forward to working with Akoya towards bringing this companion diagnostic to patients and clinicians around the world."

In the initial phase of this co-development agreement, studies were conducted in collaboration with Acrivon at Akoya’s CLIA-certified Advanced Biopharma Solutions (ABS) lab to complete the analytical validation of the clinical trial assay version of the OncoSignature test on the PhenoImager platform. ABS is a premium high-value partner for biopharmaceutical companies enabling the use of Akoya’s platform in clinical trials. In the next phase of the agreement, the companion diagnostic for ACR-368 will be developed and clinically validated.

"We are honored to partner with Acrivon in the advancement of their promising therapy ACR-368, which has the potential to substantially impact the well-being of these patients," said Brian McKelligon, chief executive officer of Akoya. "We believe that the next generation of personalized medicines will go beyond the genetic markers currently being used today. Our spatial phenotyping technology and complete workflow solution with the PhenoImager platform can enable the sophisticated analyses necessary to achieve diagnostic capabilities required for patient selection, and we are excited to have Acrivon’s leading-edge OncoSignature test run on our solution."

About Acrivon’s Precision Predictive Proteomics (AP3) and OncoSignature Tests
Acrivon Predictive Precision Proteomics, AP3, is a proprietary, streamlined approach to develop patient selection tumor biopsy tests, called OncoSignature tests. The technology is engineered to be agnostic to underlying genetic alterations and designed to enable identification and treatment of the patients whose tumors are regulated by and sensitive to the drug based on direct protein measurement of the critical tumor-driving mechanisms. The AP3 approach leverages unbiased differential global phosphoproteomic drug profiling using mass spectrometry, biased tumor model analyses, and quantitative multispectral in situ imaging of patient derived xenograft (PDX) in vivo models and intended-use tumor samples and clinical trial biopsies, to identify and evaluate biomarkers. The output of AP3 is clinically actionable, drug-tailored, proprietary OncoSignature tests. These are automated, quantitative protein multiplex imaging tests applied to pretreatment tumor biopsies as a companion diagnostic (CDx) to select and treat the patients predicted to benefit from the drug candidate. The AP3 method is broadly applicable across drugs and drug candidates and is a transformative, efficient method to accurately match the right therapy to the right patient.

On June 28, 2022 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported the first patient was dosed in its Phase 1/1b monotherapy clinical trial of RMC-6236, the company’s oral, potent, tri-complex RAS(ON) Inhibitor designed to treat patients with cancers driven by a variety of RAS mutations (Press release, Revolution Medicines, JUN 28, 2022, View Source [SID1234616317]). RMC-6236, which the company refers to as a RASMULTI (ON) Inhibitor, is the first development candidate from Revolution Medicines’ portfolio of novel RAS(ON) Inhibitors to enter clinical development.

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The Phase 1/1b trial (NCT05379985) is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6236 in patients with advanced solid tumors harboring selected KRASG12 mutations, including KRASG12D, KRASG12V and KRASG12R. The primary objectives of the study are to evaluate safety and tolerability and to inform the recommended Phase 2 dose and schedule (RP2DS) for the compound. The study’s first patient has pancreatic cancer with a KRASG12D mutation, the most common genetic variant of RAS proteins causing cancer.

"Beginning clinical evaluation of the first compound from our broad portfolio of RAS(ON) Inhibitors marks a significant milestone in our efforts to serve unmet needs of patients with RAS-addicted cancers," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "To our knowledge, RMC-6236 is the first oral, direct RAS inhibitor to be deployed against a tumor harboring the KRASG12D variant, and it ushers in a wave of groundbreaking RAS(ON) Inhibitors we expect to advance."

Steve Kelsey, M.D., president, research and development at Revolution Medicines said, "RMC-6236 is a compelling drug candidate with the potential to demonstrate broad utility across many RAS cancer variants, particularly those harboring KRASG12 mutations. We are enthusiastic about its potential both to display first-in-class single agent activity as an inhibitor of mutant RAS and to be deployed as a RAS Companion Inhibitor in combination with mutant-selective RAS(ON) Inhibitors we have in development."

The company also highlights the election of Sushil Patel, Ph.D., to its board of directors at its recent annual meeting of stockholders. Dr. Patel has more than twenty years of experience in the biotech industry, focused on commercialization strategy and execution in U.S. and global oncology markets. He currently serves as chief commercial officer of Replimune Group, a clinical-stage biotechnology company developing novel tumor-directed oncolytic immunotherapies. Previously, Dr. Patel held various positions at Genentech, Inc., where he served as franchise head for lung, skin, and rare cancers that included several blockbuster products in both targeted therapies and immuno-oncology. Notably, he led lifecycle management of Tecentriq (atezolizumab) in lung cancer and helped lead more than eight product launches across more than twenty different indications. Dr. Patel holds a Ph.D. in molecular biology from the University of London and a Master’s degree in biotechnology from the Imperial College London.

Dr. Goldsmith added, "We are very fortunate to have Sushil join our board of directors. His commercial expertise in bringing innovative cancer drugs to patients will provide a valuable perspective as we advance our deep product pipeline."