On December 12, 2023 ChemDiv Inc., dedicated to partnering in discovery and development of breakthrough therapies based on its unique chem-bio platforms, reported the presentation of non-clinical summary data for the best-in-class selective FLT3 clinical candidate at the 65th ASH (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA (Press release, ChemDiv, DEC 12, 2023, View Source [SID1234638507]). "Therapeutic Targeting of FLT3 gatekeeper mutation with E2082-0047 in traditional and a novel Immunocompetent murine adoptive transfer model of AML" was presented by collaborators from University of Cincinnati, Ohio, Molsoft LLC and Expert Systems Inc of San Diego, California, and Eilean Therapeutics LLC from Dover, Delaware. The presentation highlighted best-in-class potency and selectivity against gatekeeper resistant FLT-mutant AML and compelling survival benefit superior to gilteritinib in a fully immunocompetent Nmp1CAFLT3ITD-F692L AML adoptive transfer model, supporting the clinical candidate’s ongoing clinical development.

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In collaboration with rational design groups of Molsoft and Expert Systems, John Byrd’s lab at University of Cincinnati, ChemDiv deployed a muti-targeting/multi-property optimization approach to achieve a 400-1000x selectivity of the resulting clinical candidate, which translated in best-in-class efficacy, safety, tolerability and developable pharmacology advantages delivered to partners at Eilean Therapeutics LLC.

On December 12, 2023 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported that it has partnered with K2bio (Houston, Texas) to implement novel analysis for cerebrospinal fluid (CSF) tumor and molecular biomarkers for CNS cancers (Press release, Plus Therapeutics, DEC 12, 2023, View Source [SID1234638505]). Initial clinical specimen processing and testing will begin in Q1 2024 in the Company’s ongoing Phase 1 ReSPECT-LM trial of rhenium (186Re) obisbemeda in patients with leptomeningeal metastases (LM). This trial is currently receiving grant funding through The Cancer Prevention and Research Institute of Texas (CPRIT). The Company expects testing costs to be partially covered under this grant.

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"The initial diagnosis, therapeutic selection and monitoring of patients with CNS cancers such as leptomeningeal metastases are significant problems in everyday clinical practice," said Marc H. Hedrick, M.D., President & Chief Executive Officer of Plus Therapeutics. "To turn these very lethal CNS cancers into treatable diseases, we must ideally address both the diagnostic as well as the therapeutic needs of caregivers and patients. This partnership with K2bio is the next part of our overall strategy to address both needs in parallel."

K2bio is a hybrid contract research organization (CRO) enabling life science companies to develop the next generation of innovative therapies. K2bio is based in Houston and is part of the Texas Medical Center life sciences ecosystem specializing in all aspects of translational cancer diagnostic and therapeutic research and development.

"K2bio is a leader in enabling rapid diagnostic and therapeutic progress for innovative companies such as Plus," said Colby Suire, PhD, acting President and CEO of K2bio. "We have all the necessary capabilities and expertise to accelerate and support Plus’ mission to be a leader in the development of targeted radiotherapeutics and related diagnostics for CNS cancers."

Plus’ tumor cell and molecular biomarker analysis is an exploratory endpoint in the ReSPECT-LM Phase 1 trial that has shown promise in early cohorts. In Phase 1/part A of the ReSPECT-LM trial presented at the 2023 SNO/ASCO Meeting in San Francisco, Plus data showed an average 53% reduction in CSF tumor cells 28 days after a single intrathecal administration of rhenium (186Re) obisbemeda in patients with LM.

The FDA has granted Fast Track designation to rhenium (186Re) obisbemeda for the treatment of LM, and the ReSPECT-LM Phase 1 program continues to be funded in part by a 3-year $17.6 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT). Patients interested in learning more about the ReSPECT-LM trial can visit ClinicalTrials.gov (NCT05034497).

On December 12, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova" or "the Company"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported preclinical data, highlighting narazaciclib’s preclinical activity in Bruton’s kinase inhibitor (BTKi)-resistant mantle cell lymphoma (MCL), in a poster presented on December 11, 2023 at the 65th Annual Meeting of the American Society for Hematology (ASH 2023) in San Diego (Press release, Onconova, DEC 12, 2023, View Source [SID1234638504]).

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"We are pleased to have shared data at ASH (Free ASH Whitepaper) 2023 from preclinical studies with narazaciclib in MCL models. These results, which are consistent with data presented this year at the international MCL conferences, demonstrate that treatment with narazaciclib led to significant tumor growth inhibition when used as a single agent and that combination with ibrutinib demonstrated synergy, in both ibrutinib-sensitive and -resistant in vitro and in vivo settings," said Steve Fruchtman, M.D., President and Chief Executive Officer. "These data are important because they provide further evidence for the potential use of narazaciclib in cancers with cyclin over-expression and elaborate our understanding of narazaciclib’s mechanism of action, including its ability to promote G1 cell cycle blockade."

Dr. Fruchtman continued, "We believe that these data, along with the preclinical data presented on Friday, December 8th at the San Antonio Breast Cancer Symposium (SABCS), further underscore the impressive and differentiated profile of narazaciclib. The data presented at SABCS highlight narazaciclib’s multi-kinase activity, its ability to target resistance pathways missed by other CDK4/6 inhibitors, and its differentiated anti-tumor and immunomodulatory activity. The data presented at ASH (Free ASH Whitepaper) 2023 show that narazaciclib, in combination with BTKi’s such as ibrutinib, also trigger metabolic reprogramming alongside DNA damage."

"The totality of these data is helping us to shape the clinical program for narazaciclib, including the lead indication of LGEEC, with further potential to expand into additional investigator-sponsored studies in breast, ovarian, and other cancers. We are pleased with the early Phase 1/2 data for narazaciclib monotherapy and in combination with letrozole, showing lower levels of neutropenia and diarrhea, and the potential for once daily dosing. Both of these attributes could position narazaciclib as a differentiated and improved CDK4/6i. Looking ahead, we are enthusiastic to advance the clinical program for narazaciclib in 2024 and to update our stakeholders regarding our progress, including the planned completion of dose escalation studies, definition of an RP2D, and development of our registrational trial plans for LGEEC. The data presented at ASH (Free ASH Whitepaper) suggest narazaciclib is a drug with the potential to target a variety of cancer indications with an unmet medical need, including MCL," concluded Dr. Fruchtman.

Poster Highlights

Title: Narazaciclib, a differentiated CDK4/6 antagonist, prolongs cell cycle arrest and metabolomic reprogramming, enabling restoration of ibrutinib sensitivity in BTKi-resistant mantle cell lymphoma

Objectives: To evaluate the activity and mechanism of action of narazaciclib as a single agent and in combination with ibrutinib, in comparison to the standard-of-care ibrutinib, in preclinical models of MCL that are sensitive and resistant to ibrutinib treatment.

Snapshot of the Results and Conclusions:

Tumor Growth Inhibition: Narazaciclib showed safety and efficacy as a single agent in preclinical MCL models, including ibrutinib-resistant settings, with significant reductions in cell viability.
Combination Synergy: The narazaciclib plus ibrutinib combination showed synergy in vitro and in vivo, especially in ibrutinib-resistant models, with overall greater synergy, measured by lower "Combination Index" values, versus ibrutinib-sensitive cells.
Cell Cycle Blockade: The combination of narazaciclib plus ibrutinib induces a superior G1 cell cycle blockade in both ibrutinib-sensitive and ibrutinib-resistant MCL cells.
Metabolic programming: In ibrutinib-resistant cases, the synergy between narazaciclib and ibrutinib triggers metabolic reprogramming alongside DNA damage, mediated by the USP24 and P53 axis, as evidenced by several assays to assess mitochondrial metabolism.
Together, these preclinical data suggest that narazaciclib has important single agent activity and the potential to restore ibrutinib sensitivity in BTKi-resistant models, successfully meeting the primary objective of the study.

A copy of the poster is available on the "Scientific Presentations" section of the Onconova website.

On December 12, 2023 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported that the U.S. Food and Drug Administration (FDA) has granted an orphan drug designation (ODD) to Nana-val (nanatinostat in combination with valganciclovir), the company’s all-oral investigational therapy targeting Epstein-Barr virus (EBV)-associated cancers, for the treatment of nasopharyngeal carcinoma (NPC) (Press release, Viracta Therapeutics, DEC 12, 2023, View Source [SID1234638503]). This represents the first ODD granted for Nana-val in Epstein-Barr virus-positive (EBV+) solid tumors and outside of EBV-associated lymphomas. The FDA previously granted Nana-val ODD for the treatment of T-cell lymphoma, post-transplant lymphoproliferative disorder, plasmablastic lymphoma, and EBV+ diffuse large B-cell lymphoma, not otherwise specified.

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"This orphan drug designation highlights the urgent need for new targeted treatment options for patients with rare diseases such as nasopharyngeal carcinoma, which is highly associated with EBV," said Mark Rothera, President and Chief Executive Officer of Viracta. "We are encouraged by the interim data from the Phase 1b/2 study of Nana-val in patients with recurrent or metastatic EBV-positive nasopharyngeal carcinoma, supporting the continued advancement of the study with a new split daily dosing regimen at higher doses. With sites open and enrolling the sixth dose cohort of the study, we are on track to expand into the Phase 2 portion in 2024. The growing clinical data in both the lymphoma and solid tumor settings, further validates the therapeutic potential of Nana-val to treat EBV-positive cancers, an underserved area of high unmet medical need."

The FDA’s Office of Orphan Products Development grants orphan status to drugs and biologics being developed to treat, diagnose, or prevent a rare disease or condition affecting fewer than 200,000 people in the U.S. ODD is designed to provide drug developers with various benefits to support the development of novel drugs, including the potential for seven years of market exclusivity upon FDA approval for the disease or condition for which the drug has ODD, eligibility for tax credits toward qualified clinical trial costs, exemptions from certain FDA application fees, reduced annual product user fees, clinical trial protocol design and drug development assistance, and potential qualification for expedited drug development programs.

About the Phase 1b/2 Study of Nana-val in R/M EBV+ NPC and Other EBV+ Solid Tumors
This Phase 1b/2 trial (NCT05166577) is an open-label, multinational clinical trial evaluating Nana-val alone and in combination with pembrolizumab. The Phase 1b dose escalation part is designed to evaluate safety and to select the recommended Phase 2 dose (RP2D) of Nana-val in patients with recurrent or metastatic (R/M) Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinoma (NPC). Along with the U.S. Food and Drug Administration’s Project Optimus initiative, at the start of Phase 2, up to 40 patients with R/M EBV+ NPC will be randomized to receive either the RP2D or a dose level below the RP2D in a dose-optimization cohort. Once the RP2D has been confirmed, up to 60 patients with R/M EBV+ NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to further evaluate antitumor activity, safety and tolerability, pharmacokinetics, and potential pharmacodynamic biomarkers. Additionally, patients with other advanced EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort.

About Nana-val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed or refractory (R/R) EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other EBV+ solid tumors.

About EBV-Associated Cancers
Approximately 90% of the world’s adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.

On December 12, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported that Marc Stapley, chief executive officer, and Rebecca Chambers, chief financial officer, will present at the 42nd annual J.P. Morgan Healthcare Conference on Monday, January 8, 2024, at 1:30 p.m. Pacific Time (Press release, Veracyte, DEC 12, 2023, View Source [SID1234638502]).

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A live audio webcast of the company’s presentation will be available by visiting Veracyte’s website at View Source A replay of the webcast will be available for 30 days following the conclusion of the live broadcast.