NY-303 / NAYA Therapeutics, CytoLynx Therap - LARVOL DELTA

NAYA Therapeutics Enters into Definitive Agreements to Regain Full Rights to Next-Generation Cancer Immunotherapies As It Advances Towards Clinical Milestones (ACCESSWIRE) - "NAYA Therapeutics...has regained its status as a privately-held company, separating from its recent merger with INVO Bioscience. This strategic decision enables NAYA Therapeutics to optimize its portfolio development strategy for value maximization and market attractiveness as it advances towards clinical development milestones for its portfolio of first and potential best-in-class candidates....Enrollment of HCC patients for Phase I/II clinical trials of NY-303, which shows unique potential to unlock the biology of checkpoint inhibitor non-responders, is expected in 2025. Next, we are aiming to initiate Phase I/II clinical trials of NY-500, positioned to be the first PD-1/VEGF to market in HCC, in 2026. Finally, NY-338, which shows a differentiated profile to daratumumab and T-cell engagers, is anticipated to commence enrolling patients in its Phase I/II clinical trials in multiple myeloma in 2026."

Commercial • Trial status • Hepatocellular Cancer • Multiple Myeloma

Reversal of resistance to PD-1 checkpoint blockade in hepatocellular carcinoma by NY-303, a GPC3 NK cell engager, inhibiting Wnt-GPC3-beta catenin signaling (SITC 2024) - "Background A retrospective biomarker analysis of the Phase III and Phase Ib clinical trials with PD-1 checkpoint plus angiogenesis inhibitor combinations (Atezolizumab + Bevacizumab) in Hepatocellular Carcinoma patients (HCC) (IMbrave150 and GO30140 studies respectively) have identified that increased expression of biomarkers GPC3, AFP and activated beta-catenin are associated with resistance to PD-1 checkpoint blockade.1 Vice versa decreased levels are associated with increased progression free and overall survival in responder patients...Conclusions NY-303 is able to down-modulate GPC3 expression and inhibit beta-catenin activation in HCC tumors resulting in a PD-1 checkpoint blockade sensitive biomarker signature. These results suggest NY-303 has the potential to reverse PD-1 checkpoint resistance in HCC patients and provides a rationale for combining or sequencing NY303 treatment with PD-1 immunotherapy in HCC."

Checkpoint block • Checkpoint inhibition • IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Leveraging graph AI to analyze the influence of GPC3 gene expression and NK-cell tumor infiltration on hepatocellular carcinoma survival rates (SITC 2024) - "By deploying Graph AI with a Graph database, our research not only underscores the roles of GPC3 and NK cells in improving prognostic assessments but also enhances the development of targeted immunotherapeutic strategies, offering crucial insights into the molecular and immune landscapes of HCC to refine predictive models and improve patient survival. Conclusions Utilizing graph-based features from PPI data, in combination with the analytical prowess of the fuzzy ECLAT algorithm, has led to a more sophisticated prediction of correlation between the presence of NK cells in the HCC tumor microenvironment and survival outcomes for HCC patients."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

NAYA Biosciences to Present Translational Insights to Support Phase I/IIa Clinical Trials for its GPC3-Targeting NK Engager Bispecific Antibody at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (GlobeNewswire) - "NAYA Biosciences...today announced that it is presenting novel insights into the mode of action of its GPC3-targeting NK engager bispecific antibody NY-303 to support phase I/IIa clinical trials in H1 2025 as well as into a predictive AI model of HCC survival rate at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) taking place November 6-10 in Houston, Texas....The company will present translational research data demonstrating that NY-303 can reverse resistance to PD-1 checkpoint blockage and turn tumors from a 'cold' into a 'hot' status, making the tumors susceptible to immunotherapy again."

Clinical data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

NAYA Biosciences Announces Initiation of Phase 1/2a Clinical Trial for its GPC3-targeted NK Engager Bispecific Antibody in Patients with Hepatocellular Carcinoma (GlobeNewswire) - "The Company received regulatory approval from the Israeli Ministry of Health in July 2024 and subsequent institutional review board clearance to initiate patient enrollment in up to 7 academic centers for its clinical trial evaluating the safety and efficacy of NY-303...The Phase 1 part of the trial will consist of a dose-escalation where patients responding to treatment will continue weekly administration as long as no disease progression is observed. Key endpoints include safety, pharmacokinetics, activity markers, preliminary clinical efficacy, and time-to-progression. NAYA is planning to start patient recruitment in early 2025 at leading medical centers in Israel including Hadassah Hospital, Sheba Medical Center, and Sourasky Medical Center....The Phase 2a part of the trial is anticipated to be expanded to the United States and Europe subject to additional regulatory approvals and will evaluate NY-303 at two dose levels selected in Phase I."

New P1/2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

INVO Bioscience and NAYA Biosciences Close Merger, Combined Company to Operate as NAYA Biosciences (NASDAQ: NAYA) (GlobeNewswire) - "INVO Bioscience...announced it has closed its merger with NAYA Biosciences...The combined company expects to change its name to NAYA Biosciences and trade on the NASDAQ under the 'NAYA' ticker. The combined company will continue to operate the revenue-generating fertility business as well as expand its focus to the development of first-in-class clinical-stage assets in oncology and autoimmune diseases...'We are excited about the growth potential of NAYA as a public company with improved access to capital and shared resources to accelerate the development of its pipeline.'....Under the terms of the amended and restated merger agreement, INVO acquired 100% of the outstanding equity interests in NAYA by means of a reverse triangular merger of a wholly owned subsidiary of INVO with and into NAYA, with NAYA surviving as a wholly owned subsidiary of INVO (the 'Merger')."

M&A • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Multiple Myeloma • Oncology • Solid Tumor

CYT-303 FLEX-NKTM engager dose response efficacy mechanisms in HCC tumor model and safety in cynomolgus monkey toxicology studies support clinical evaluation in hepato-cellular carcinoma (AACR 2023) - "CYT-303 efficacious doses identified in the HCC model together with safety in cynomolgus monkeys and planned human pharmacokinetic modeling studies support clinical evaluation of CYT-303 in first in human HCC clinical trials."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Improved anti-tumor immune functions of iPSC-derived NK cells with TGFβR2 knock-out and/or IL-15 knock-in by TALEN® editing for use alone or in combination with GPC3 Flex-NKTM bispecific antibody (AACR 2023) - "This work demonstrates that KI of IL-15 and KO of TGFβR2 is a promising strategy for TALEN®-engineered iNK cell therapies to overcome the immunosuppressive TME and mount a potent and persistent anti-tumor immune response. The data also provide a solid foundation for combining these edited iNK cells with CYT-303 to address the immunosuppressive TME towards a cure for HCC."

Combination therapy • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3 • IL15 • NKG2D • TGFB1 • TGFBR2

Derivation and Preclinical Characterization of CYT-303, a Novel NKp46-NK Cell Engager Targeting GPC3. (PubMed, Cells) - "In vivo, CYT-303 showed no toxicity or cytokine release in cynomolgus monkeys up to the highest dose (60 mg/kg), administered weekly by intravenous infusion for 28 days. These results demonstrate the potential of CYT-303 to be a safe and effective therapy against HCC."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Non-clinical characterization of CYT-303 FLEX-NK™ engager antibody supports clinical evaluation. (SITC 2022) - "Conclusions CYT-303 demonstrated potent ADCP and CDC against Hep3B tumors as well as Hep3B tumor spheroid and serial killing activities in the presence of PBNKs. Preclinical pharmacokinetics and safety study results in cynomolgus monkeys support CYT-303 clinical development."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

Preclinical characterization of CYT-100 iPSC derived NK cells alone and in combination with CYT-303 NK cell engager for hepatocellular carcinoma (HCC). (SITC 2022) - "The cytotoxicity of this iNK product is further enhanced by combination with the NK cell engager antibody CYT-303. These data support further development of the combination of iNK cells and NKEs as therapeutics for HCC."

Combination therapy • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CXCR3 • GPC3 • NCAM1 • PTPRC • STAT5

Cytovia Therapeutics Presents New Data on TALEN Gene-Edited iNK Cells and GPC3-Targeted Flex-NK Bispecific Antibodies at 2022 SITC Annual Meeting (PRNewswire) - "The presentations show that Cytovia's allogeneic iNK cell product CYT-100 demonstrated increased time-dependent killing of Hep3B tumor spheroids and sensitivity to cytokine activation & expansion potential. Cytovia's GPC3-targeted bispecific antibody CYT-303 demonstrated potent ADCP and CDC against Hep3B tumors as well as Hep3B tumor spheroid and serial killing activities in the presence Cytovia's allogeneic iNK cell product CYT-100 and PBNKs in a dose-dependent manner. Preclinical pharmacokinetics and safety study results in monkeys fully support CYT-303 clinical development....The data shows that iNK cells edited with an IL-15 knock-in and TGFβR2 knock-out result in enhanced antitumor activity. The editing and manufacturing process will enable clinical evaluation of these product candidates, both alone in combination with CYT-303."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Cytovia Therapeutics To Present New Data on TALEN Gene-Edited iNK Cells and GPC3-Targeted Flex-NK Cell Engagers at 2022 SITC Annual Meeting (PRNewswire) - "Cytovia Therapeutics...announced today that it will be presenting new preclinical data for its TALEN® gene-edited, iPSC-derived NK cells and GPC3-targeted Flex-NK™ cell engager antibodies at the Society for Immunotherapy of Cancer's 37th Annual Meeting (SITC 2022) taking place in Boston, MA, and virtually November 8-12th, 2022."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Glypican-3 (GPC3) and NKp46 directed FLEX-NK engager antibody (CYT-303) recruits natural killer (NK) cells to tumors in a preclinical hepatocellular carcinoma (HCC) mouse model (ESMO 2022) - "Conclusions Pharmacologically active CYT-303 doses were identified. CYT-303 can help recruit NK cells to the tumor site to achieve tumor growth inhibition."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • AFP • GPC3 • IL15

Cytovia Therapeutics Presents New Preclinical Data for Its GPC3 Flex-NK Cell Engager Antibody in Combination With Natural Killer Cells at ESMO 2022 in Paris (PRNewswire) - "CYT-303 showed dose-dependent HCC tumor growth inhibition in PBNK and iNK cell injected HCC tumor models. Dose-dependent increases in CYT-303 concentrations in tumor and blood were observed in the PBNK injected HCC tumor model showing the potential for CYT-303 to penetrate solid tumors. CYT-303 treated animals showed significant decreases in blood PBNKs suggesting CYT-303 may facilitate trafficking of these cells from blood to the tumor. Bell shaped dose-response observed with CYT-303 monotherapy in the PBNK injected HCC tumor model is consistent with CYT-303 in vitro studies showing similar dose-responses for PBNK and HCC tumor binding and tumor cytolysis. The linear dose-response observed with CYT-303 combination therapy with iNK cells in the HCC tumor model is consistent with the in vitro linear dose-response observed with iNK combination for cytolysis of HCC tumors....These CYT-303 preclinical proof-of-concept studies support clinical development of CYT-303 in HCC."

Preclinical • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Cytovia Therapeutics to Present at AACR Special Conference on Advances in the Pathogenesis and Molecular Therapies of Liver Cancer (PRNewswire) - "Cytovia Therapeutics, LLC...announced today that it will be presenting at the AACR Special Conference on Advances in the Pathogenesis and Molecular Therapies of Liver Cancer, to be held from May 5-8, 2022, at the Westin Copley Place in Boston, Massachusetts."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

Isleworth Healthcare Acquisition Corp. and Cytovia Therapeutics Announce Agreement for Business Combination to Create Publicly Listed Company Focused on Empowering Natural Killer Cell Therapeutics to Fight Cancer (PRNewswire) - "Cytovia plans to focus on multiple milestones, including: Filing the first two INDs for Flex-NK™ CYT-303 and iNK CYT-100; Initiating Phase I/II clinical trials to evaluate CYT-303 and CYT-100, alone and in combination, for the treatment of HCC; Obtaining and presenting initial clinical data for CYT-303 and CYT-100 in HCC; Filing INDs for CYT-150 and CYT-503 and initiating Phase I/II clinical trials."

Clinical data • IND • New P1/2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Preclinical characterization of FLEX-NKTM tetravalent NKp46 engager directed against GPC3 (CYT-303) alone or in combination with iPSC derived Natural Killer cells (iNKs) against hepatocellular carcinoma (HCC) (AACR 2022) - "CYT-303 greatly enhanced the cytotoxic activity of iNKs and cytolysis of Hep3B tumor cells in-vitro. CYT-303 and iNK cells, alone or in combination, demonstrate anti-tumor activity against HCC that warrants clinical development."

Combination therapy • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3 • NCAM1 • NKG2D

Cytovia Therapeutics Reports Preclinical Activity of its iPSC-derived NK (iNK) Cells and Flex-NK Cell Engagers at the 2022 AACR Annual Meeting (PRNewswire) - "Cytovia Therapeutics...announced today that the novel data it is presenting at the American Association of Cancer Research's annual meeting in New Orleans on April 12th, 2022 is now available on both the AACR and Cytovia websites....First in vivo data demonstrates anti-tumor activity of Glypican-3 (GPC3) Flex-NK™ cell engager (CYT-303) in combination with iNK cells in an animal model of Hepatocellular carcinoma (HCC). First in vitro data evaluating CD38 Flex-NK™ cell engager (CYT-338) demonstrates a favorable profile compared to daratumumab."

Preclinical • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Liver Cancer • Multiple Myeloma • Oncology • Solid Tumor

Cytovia Therapeutics to Present Preclinical Data for iPSC-derived NK Cells and Flex-NK Engager Multispecific Antibodies at 2022 AACR Annual Meeting (GlobeNewswire) - "Cytovia Therapeutics...announced today that it will present two posters at the upcoming American Association for Cancer Research (AACR) Annual Meeting, to be held in New Orleans April 8-13.'We are pleased to present preclinical validation of our two proprietary technology platforms (unedited inducible pluripotent stem cell derived NK (iNK) cells and Flex-NK™ engager multispecific antibodies) as well as their potential synergy for the treatment of glypican-3 (GPC3) expressing tumors and CD38 expressing multiple myeloma"

Preclinical • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Multiple Myeloma • Oncology • Solid Tumor

Cytovia Therapeutics Files New Patents for its Natural Killer Cell Engager Multifunctional Antibodies (FLEX-NK) for the Treatment of Hematological and Solid Tumors (GlobeNewswire) - "Cytovia Therapeutics...announced today that it has filed two provisional composition of matter patent applications for its FLEX-NK® platform, consisting of NKp46-based NK cell engager multifunctional antibodies targeting GPC3 for the treatment of solid tumors, including Hepatocellular carcinoma, and CD38 for the treatment of hematological malignancies, including Multiple Myeloma...'Cytovia is committed to building a strong intellectual property portfolio to support further development of our first-in-class NK engager candidates, with clinical trials starting in the first half 2022'."

New trial • Patent • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Multiple Myeloma • Oncology • Solid Tumor