Cothera Receives Authorization from the FDA to Conduct a Phase 2 Clinical Trial to Test Its Targeted MYC Mutation Inhibitor PC-002 for the Treatment of High-Grade B-cell Lymphoma

On June 17, 2021 Cothera Bioscience reported that it has received approval from the U.S. Food and Drug Administration (FDA) to initiate a global multi-center phase 2 clinical trial for the treatment of high-grade B-cell lymphoma that is resistant or refractory to first-line and second-line treatments with PC-002, an inhibitor that targets MYC mutations (Press release, Cothera Bioscience, JUN 17, 2021, View Source [SID1234618852]).

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PC-002 is a first-in-class small molecule drug targeting MYC- mutated tumors. With more than 50% of human cancers showing increased expression, MYC is regarded as one of the most important yet "undruggable" cancer targets. With a unique mechanism of action, PC-002 selectively induces MYC protein degradation and cell apoptosis in MYC-dependent tumors. PC-002 may potentially target multiple indications in cancer involving MYC dysregulation.

Dr. Alex Wu, Co-founder and CEO of Cothera Bioscience, said: "The FDA’s approval of PC-002 to initiate human phase 2 clinical trials is an important milestone for Cothera. I believe this is a good start, and the company will continue its effort to launch late-stage clinical trials for other cancer indications, bringing breakthroughs and better treatment options to more cancer patients."

Humanigen presented its corporate presentation

On June 17, 2021 Humanigen presented its corporate presentation(Press release, Humanigen, JUN 17, 2021, View Source [SID1234584092]).

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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.