Merck to Participate in the Guggenheim Biopharma Strategy Series

On June 17, 2021 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that Dr. Dean Li, executive vice president and president, Merck Research Laboratories, is scheduled to participate in a virtual fireside chat at the Guggenheim Biopharma Strategy Series with Senior Management to discuss Biopharma’s Next Decade: Views from the Top on Global Strategy and Innovation on June 22, 2021, at 9:00 a.m. EDT(Press release, Merck & Co, JUN 17, 2021, View Source [SID1234584095]).

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Investors, analysts, members of the media and the general public are invited to listen to a live audio webcast of the presentation at View Source

Entry into a Material Definitive Agreement

On June 14, 2021 Intellia Therapeutics, Inc. ("Intellia") entered into Amendment #3 (the "Amendment") to its License and Collaborative Research Agreement (the "Collaboration Agreement"), dated as of December 18, 2014, with Novartis Institutes for Biomedical Research, Inc. ("Novartis")(Press release, Intellia Therapeutics, JUN 17, 2021, View Source [SID1234584115]). The Amendment amends Novartis’ rights with respect to all the CAR-T Therapeutic Targets (as defined in the Collaboration Agreement) that Novartis selected under the Collaboration Agreement, including (a) making Novartis’ license non-exclusive for such CAR-T Therapeutic Targets, (b) removing Novartis’ diligence and related reporting obligations for such CAR-T Therapeutic Targets, and (c) refining the scope of Novartis’ sublicense rights for such CAR-T Therapeutic Targets. Intellia agreed to pay to Novartis a one-time payment of $10.0 million within 30 days after the effective date of the Amendment.

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The foregoing summary is qualified in its entirety by reference to the Amendment filed as an exhibit to this Form 8-K. The Company has sought confidential treatment for certain portions of the Amendment.

Onconova Therapeutics Announces The Peer-Reviewed Publication Of Preclinical Data Demonstrating The Synergistic Anti-Cancer Activity Of Rigosertib Combined With Immune Checkpoint Blockade

On June 17, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported the publication of a preclinical study in the journal Molecular Cancer (Press release, Onconova, JUN 17, 2021, View Source [SID1234584132]). The study, entitled "Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade," showed that rigosertib synergistically enhanced the efficacy of ICB in a murine melanoma model via the induction of immune-mediated cancer cell death.

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"The data from this recent publication demonstrate rigosertib’s potential to address a pressing unmet need, as many patients do not respond to immune checkpoint blockade due to immunosuppressive tumor microenvironments," said Ann Richmond, Ph.D., Ingram Professor of Pharmacology and Medicine at the Vanderbilt University School of Medicine and lead author of the study. "By reversing immunosuppressive tumor microenvironments, rigosertib overcame pro-tumor resistance mechanisms and synergistically enhanced the efficacy of immune checkpoint blockade in a difficult-to-treat murine melanoma model. These compelling findings provide preclinical proof-of-concept for rigosertib-immune checkpoint blockade combination therapy and strongly support its evaluation in clinical trials."

Key data and conclusions from the recent publication include:

Rigosertib treatment enhanced the activation of anti-cancer immune cells and increased the frequency of these cells in the tumor microenvironment (TME).
Rigosertib treatment reduced the frequency of pro-tumor CD206+ M2-like macrophages in the TME.
Rigosertib monotherapy rapidly reduced PI3K signaling with induction of CD40 expression, leading to melanoma cell death and inhibition of tumor growth in vivo due to its ability to promote the tumor infiltration of activated anti-cancer immune cells.
Rigosertib’s ability to remodel the TME enabled it to synergistically combine with ICB and improve tumor growth inhibition and survival in a mouse model of melanoma that did not respond to ICB alone, or a clinically used combination of ICB plus BRAF and MEK inhibitors.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, added, "We are very pleased with these recently published results, which will inform the data driven approach guiding our clinical rigosertib investigator-initiated study program. They provide strong mechanistic support for both the ongoing KRAS mutated non-small cell lung cancer trial of rigosertib in combination with a check point inhibitor and a potential trial in patients with advanced melanoma evaluating a rigosertib-checkpoint inhibitor combination that is under active consideration. Looking ahead, we plan to continue leveraging our collaborations with leading institutions such as Vanderbilt University as we pursue opportunities for rigosertib while maintaining our primary focus and resources on our lead ON 123300 multi-kinase inhibitor program."

Foresight Diagnostics to Present a Vision of the New Standard of Lymphoma MRD Detection at the 16th International Conference on Malignant Lymphoma

On June 17, 2021Foresight Diagnostics, the emerging leader in blood-based lymphoma disease monitoring, reported that clinical performance of its minimal residual disease (MRD) detection platform in diffuse large B-cell lymphoma (DLBCL) will be presented at the 16th International Conference on Malignant Lymphoma (ICML) on June 18-22, 2021 (Press release, Foresight Diagnostics, JUN 17, 2021, View Source [SID1234584154]). The oral presentation demonstrates the utility of Foresight Diagnostics’ proprietary PhasED-Seq technology to improve MRD detection rates in DLBCL patients in low-disease burden settings.

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"Foresight’s MRD testing platform can detect relapsing disease 200 days earlier than current methods in DLBCL patients receiving first-line therapy," says David Kurtz, MD, PhD, a Stanford University professor and a co-founder of Foresight Diagnostics who will present the talk at ICML. "We believe that such early detection constitutes the future standard for ctDNA-guided patient monitoring and treatment in the clinic and for drug development applications. We’re proud that our abstract was selected for oral presentation at this year’s ICML meeting and are excited to share this impactful data."

The presentation, titled "Phased variants improve DLBCL minimal residual disease detection at the end of therapy" will be presented during Session 3: Aggressive Lymphomas (Channel 3) on Sunday, June 20 at 17:45-19:15 (CEST).

Circulating tumor DNA (ctDNA) detection has prognostic value in DLBCL and has the potential to change the management of lymphoma in the clinic. But detection is still challenging in low-disease burden states with existing methods, such as MRD detection at the end of therapy.

Foresight’s talk at ICML will introduce Phased Variant Enrichment & Detection Sequencing (PhasED-Seq), Foresight’s proprietary ctDNA technology that leverages a novel class of somatic alteration called "phased variants" (PVs). By identifying and tracking PVs, PhasED-Seq enables ctDNA MRD detection down to parts-per-million levels, providing levels of sensitivity that are significantly better than SNV-based methods. The talk will also demonstrate that PVs are common in B-cell lymphomas and occur in stereotyped locations, enabling an "off-the-shelf" approach to variant monitoring that does not require tumor tissue or patient-specific customization.

"While many patients with diffuse large B-cell lymphoma are cured using standard therapies, there remains a great need to accurately identify those who are not cured and would benefit from new therapeutic strategies," states Foresight Board Member Mark Lee, MD, PhD, a founding executive at GRAIL and most recently SVP and Global Head of Personalized Healthcare at Genentech. "The improved sensitivity for ctDNA-based MRD detection during and after treatment showcases the potential for PhasED-Seq as the new standard for lymphoma MRD applications, such as MRD-adapted clinical trials."

Foresight Diagnostics recently announced a $12.5M Series A financing to accelerate the commercialization of the PhasED-Seq technology and also presented clinical performance data on PhasED-Seq at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Foresight’s first commercially available test offering will be a CLIA-validated B-cell lymphoma MRD assay, and the company is initiating retrospective and prospective clinical studies with multiple partners to evaluate the utility of the assay in patients with a variety of B-cell malignancies.

Lineage Announces Exclusive Option Agreement With Amasa Therapeutics for Supply and Use of Clinical-Grade Hystem®

On June 17, 2021 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported it granted an exclusive option to Amasa Therapeutics, Inc. (Amasa), a privately-held biopharmaceutical company focused on the development of novel cell-based targeted biological therapeutics to treat cancer patients with unmet need, to acquire an exclusive, royalty-bearing license to use Lineage’s HyStem technology for the development and commercialization of therapies for local treatment of solid tumors under pre-negotiated terms (Press release, Lineage Cell Therapeutics, JUN 17, 2021, View Source [SID1234584170]). Under the option agreement, Amasa will purchase certain amounts of Lineage’s existing supply of clinical-grade HyStem biomaterial and has the right to purchase additional amounts in connection with its up to 12-month option to acquire the exclusive license. Lineage will receive an upfront cash payment and, if the option is exercised, would be entitled to additional payments, including event-specific payments, royalties on net sales and sublicense fees and royalties.

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"Lineage is a clinical-stage cell therapy company supported by a vast intellectual property portfolio. From this portfolio, we continue to find opportunities to unlock value from non-core assets through option and license agreements for assets such as HyStem"

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"Lineage is a clinical-stage cell therapy company supported by a vast intellectual property portfolio. From this portfolio, we continue to find opportunities to unlock value from non-core assets through option and license agreements for assets such as HyStem," stated Brian Culley, Lineage CEO. "Many tissue engineering and regenerative cell-based therapies will require the delivery of therapeutic cells in a matrix or scaffold for accurate anatomical placement, cell retention, and engraftment. This option agreement represents an opportunity to provide Amasa with access to our clinical-grade HyStem material for future development of oncology-related products delivered via HyStem and, alongside a previously announced deal with Advanced BioMatrix, is the second HyStem-related transaction we have entered into."

HyStem is a patented biomaterial that is made from and structurally mimics naturally occurring extracellular matrix, the structural network of molecules surrounding cells in organs and tissues that is essential to cellular function and tissue structure. The technology underlying the HyStem hydrogels is based on a unique thiol cross-linking strategy. Building upon this technology, the HyStem family of hydrogels are novel biomaterials that offer unique strategies for cell therapy and bioactive molecule delivery. A distinctive feature of the HyStem hydrogel is that it allows the mixture of cells with the matrix in a liquid form such that the cells and matrix can be injected easily through a small gauge syringe, and then the matrix can polymerize around the cells to create a three-dimensional tissue within the body. When implanted in HyStem hydrogels, cells remain attached and localized within the hydrogel and slowly degrade the implanted matrix and replace it with their natural extracellular matrices. Current research at leading medical institutions has shown that HyStem is compatible with a wide variety of cells and tissue types including brain, bone, skin, cartilage, vascular and heart tissues.

"We believe use of Lineage’s clinical-grade HyStem hydrogels will allow us to quickly move candidates into the clinic with our novel approach of using receptor-targeted cell therapies to address intractable solid tumors such as glioblastoma," stated Arthur Hiller, Amasa CEO. "The physiochemical properties of the HyStem hydrogel and its ability to provide a suitable extracellular matrix give our cell therapies the best opportunity to remain viable, be retained in the targeted tumor resection cavity, and eradicate residual tumor cells," stated Khalid Shah, founder of Amasa.

About HyStem

Lineage has developed a family of hyaluronan based hydrogels (HyStem) that mimics the natural extracellular matrix and has potential applications in 3-D cell culture, stem cell propagation and differentiation, tissue engineering, regenerative medicine, cell-based therapies, and as delivery vehicles for bioactive molecules. HyStem hydrogels were designed to recapitulate the minimal composition necessary to obtain a functional extracellular matrix (ECM). The individual components of the hydrogels are cross-linkable over time, and thus may be seeded with cells prior to in vivo injection, without compromising either the cells or the recipient tissues. HyStem hydrogels have been shown to support attachment and proliferation of a wide variety of cell types in both 2-D and 3-D cultures and provide timed release of proteins and other bioactive moieties. HyStem hydrogels exhibit a high degree of biocompatibility when implanted in vivo and are readily degraded in vitro and biodegrade in vivo through hydrolysis via naturally occurring enzymes. When implanted in HyStem hydrogels, cells remain attached and localized within the hydrogel and slowly degrade the implanted matrix and replace it with their natural ECMs. When used as a delivery vehicle, bioactive molecules are released by both diffusion as well as degradation of the hydrogel. The patented technology underlying Lineage’s HyStem hydrogel products in development, such as Renevia, has been exclusively licensed to Lineage for human therapeutic uses. Since the first published report in 2002, there have been over 300 academic scientific publications supporting the biocompatibility of thiol cross-linked hyaluronan-based hydrogels and their applications as medical devices and in cell culture, tissue engineering, and animal models of cell-based therapies. Due to the unique cross-linking chemistry, HyStem hydrogels have the ability to be formulated with cells and can be injected or applied as a liquid and form a gel in situ, which allows the hydrogel to conform to a cavity or space. This property of HyStem hydrogels is expected to offer several distinct advantages over other hydrogels, including the possibility of combining bioactive materials with the hydrogel at the point of use.