NTX1088 / Nectin Therap - LARVOL DELTA

KEYNOTE-E92: A Study of NTX-1088, a Monoclonal Antibody Targeting the Poliovirus Receptor (PVR, CD155), as Monotherapy and Combined With Pembrolizumab (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Nectin Therapeutics Ltd | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • PVR

GIBF invests $10 Million in Nectin Therapeutics to Advance Novel Pipeline of First-in-Class Immunotherapies and Antibody Drug Conjugates (PRNewswire) - "Guangzhou-Israel Biotechnology Fund (GIBF) announced today that it has invested $10 million in Nectin Therapeutics Ltd. Nectin is a biotechnology company developing novel targeted immunotherapies that address resistance to approved immune oncology treatments. The funds will be used to continue the development of Nectin's portfolio of novel immuno-oncology products, including the advancement of Nectin's ongoing NTX1088 global Phase 1 clinical trial targeting PVR and the preclinical development of its anti-drug conjugate (ADC) portfolio."

Financing • Oncology • Solid Tumor

First-in-class anti-PVR mAb NTX1088 advancing through Phase I: Safe and potent in restoring DNAM1 expression to enhance antitumor immunity (AACR 2024) - P1 | "NTX1088 is investigated as a single agent and in combination with the anti-PD1 mAb, pembrolizumab (Keytruda) in patients with advanced solid malignancies...Synergy was obtained when NTX1088 was combined with PD1 blockers, or with the anti-CD112R mAb, NTX2R13.Syngeneic models of PVRK.O, demonstrated a complete immune-mediated tumor regression...First-in-human (FIH) trial is currently ongoing and biomarker analysis is showing initial mechanistic proof of concept for NTX1088 mode of action, including the restoration of DNAM1 surface expression on patients' immune cells. This is the first case of surface DNAM1 elevation in clinical settings."

IO biomarker • Oncology • Solid Tumor • CD96 • IFNG • PVR • TIGIT • TNFRSF9

Nectin Therapeutics Advances Ongoing Clinical Trial and Expands Sites to Israel (PRNewswire) - "Nectin Therapeutics Ltd...announced today that it has progressed its Phase 1 clinical trial of NTX1088 to include a combination therapy arm with the immune-oncology drug KEYTRUDA (pembrolizumab)...and expanded the trial to four additional global sites to include Sheba Medical Center, Hadassah Medical Center, Ochsner Health, and City of Hope along with flagship site, MD Anderson Cancer Center."

Trial status • Oncology • Solid Tumor

Nectin Therapeutics Adds Combination Therapy Arm and Expands Sites in Phase 1 Clinical Trial of Its First-in-Class Anti-PVR Immune-Oncology Agent (PRNewswire) - "'As a leader in cancer care, Ochsner MD Anderson Cancer Center is committed to providing world-class care to the southeastern Louisiana community,' said Dr. Marc Matrana...'Part of that commitment is ensuring that our patients have access to clinical trials of innovative new cancer therapies. We are impressed by the promising preclinical data and the novel mechanism of action of PVR blockade, and we are delighted to join with Nectin Therapeutics to support the Phase 1 trial of NTX1088.'"

Media quote

Nectin Therapeutics Adds Combination Therapy Arm and Expands Sites in Phase 1 Clinical Trial of Its First-in-Class Anti-PVR Immune-Oncology Agent (PRNewswire) - "Nectin Therapeutics Ltd...announced today that it has progressed its Phase 1 clinical trial of NTX1088 to include a combination therapy arm with the immune-oncology drug KEYTRUDA^® (pembrolizumab), Merck's anti-PD-1 therapy, and expanded the clinical trial to five global sites. The clinical trial sites include City of Hope in California, Sheba Medical Center and Hadassah Medical Center in Israel, along with MD Anderson Cancer Center in Houston, Texas and Ochsner MD Anderson Cancer Center in Louisiana."

Trial status • Oncology • Solid Tumor

Myeloma Investment Fund Invests in Nectin Therapeutics to Evaluate Nectin’s Anti-PVR Lead Drug Candidate as a Treatment for Multiple Myeloma (Businesswire) - "Nectin Therapeutics...and the Myeloma Investment Fund (MIF)...announced that the MIF has invested in Nectin Therapeutics to explore the potential of NTX1088, Nectin’s first-in-class lead immunotherapy drug candidate, for the treatment of multiple myeloma....Together with the MIF’s investment, Nectin has raised over $33M supported by investments from aMoon, Peregrine Ventures, Israel Biotech Fund, Cancer Focus Fund and Integra Holdings."

Financing • Hematological Malignancies • Multiple Myeloma • Oncology

Myeloma Investment Fund Invests in Nectin Therapeutics to Evaluate Nectin’s Anti-PVR Lead Drug Candidate as a Treatment for Multiple Myeloma (Businesswire) - "Nectin Therapeutics... today announced that the MIF has invested in Nectin Therapeutics to explore the potential of NTX1088, Nectin’s first-in-class lead immunotherapy drug candidate, for the treatment of multiple myeloma....'We look forward to our partnership with Nectin Therapeutics to evaluate NTX1088 as a potential therapy for multiple myeloma.'...'We are delighted to join forces with the Myeloma Investment Fund, allowing us to collaborate and explore the potential of our lead candidate, NTX1088, in the treatment of multiple myeloma.'...Together with the MIF’s investment, Nectin has raised over $33M supported by investments from aMoon, Peregrine Ventures, Israel Biotech Fund, Cancer Focus Fund and Integra Holdings."

Financing • Multiple Myeloma • Oncology • Solid Tumor

Phase I trial of first-in-class anti-PVR mAb NTX1088: Restoration of DNAM1 expression as MOA for enhanced antitumor immunity (AACR 2023) - P1 | "NTX1088 will be investigated as a single agent and combined with the anti-PD1 mAb, pembrolizumab (Keytruda) in patients with locally advanced and metastatic solid malignancies.NTX1088 is a humanized, IgG4-S228P mAb that binds PVR with sub-nM affinity and blocks all known interacting receptors with a single nM EC50...Synergy was observed when NTX1088 was combined with PD1 blockers, or with the anti-CD112R mAb, NTX2R13, in line with the restoration of DNAM1 expression.Numerous humanized murine xenograft models were investigated...In conclusion, PVR blockade by NTX1088 has a remarkable pre-clinical efficacy, suggesting a potential clinical breakthrough, based on the ability of simultaneously overcome multiple tumor escape mechanisms. First-in-human (FIH) trial is currently ongoing and biomarker data is analyzed to assess clinical impact of the drug and prepare for patient stratification."

IO biomarker • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD96 • IFNG • PVR • TIGIT • TNFRSF9

First-in-class anti-PVR mAb NTX1088 restores expression of DNAM1 and augments antitumor immunity (SITC 2022) - P1 | "Synergy was observed when NTX1088 was combined with PD1 blockers or with the anti-CD112R mAb, NTX2R13, in line with the restoration of DNAM1 expression. Tumor-infiltrating lymphocytes, harvested from NTX1088-treated mice, demonstrated a significantly higher prevalence of CD137+, DNAM1+, CD8+ T cells compared to all other interventions. Conclusions These promising preclinical findings, together with a clean safety profile in cynomolgus monkeys, paved the way to a Ph1 clinical study in which NTX1088 is tested as a monotherapy and in combination with pembrolizumab, in patients with locally advanced and metastatic solid tumors ( NCT05378425 )."

IO biomarker • Oncology • Solid Tumor • CD8 • CD96 • IFNG • PVR • TIGIT • TNFRSF9

First-in-class anti-PVR mAb NTX1088 restores DNAM1 expression and enhances antitumor immunity (AACR-NCI-EORTC 2022) - P1 | "Synergy was observed when NTX1088 was combined with PD1 blockers or with the anti-CD112R mAb, NTX2R13, in line with the restoration of DNAM1 expression. Moreover, the ability of NTX1088 to induce non-specific cytokine release was ruled out when tested in vitro. NTX1088 has an open IND, enrolling patients with locally advanced and metastatic solid tumors NCT05378425 No"

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • CD96 • IFNG • PVR • TIGIT • TNFRSF9

Nectin Therapeutics to Collaborate with Merck on a Clinical Trial of Anti-PVR Antibody NTX1088 in Combination with KEYTRUDA (pembrolizumab) in Patients with Locally Advanced and Metastatic Solid Tumors (PRNewswire) - "Nectin Therapeutics Ltd...announced today that it has entered into a clinical trial collaboration agreement with Merck...Under this collaboration, Nectin will evaluate the safety, tolerability, and antitumor activity of its novel anti-PVR antibody, NTX1088, in combination with KEYTRUDA® (pembrolizumab), Merck's anti-PD1 therapy, in patients with locally advanced and metastatic solid tumors....We look forward to advancing the clinical trials for NTX1088, as we pursue the development of new treatment options for patients who do not respond to existing therapies."

Licensing / partnership • Oncology • Solid Tumor

A Study of NTX-1088, a Monoclonal Antibody Targeting the Poliovirus Receptor (PVR, CD155), as Monotherapy and Combined With Pembrolizumab (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Nectin Therapeutics Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2022 ➔ Sep 2022

Enrollment open • Metastases • Monotherapy • Trial initiation date • Oncology • Solid Tumor • PVR

Nectin Therapeutics Announces Extended Series A Financing to Over $25M and Initiation of Patient Dosing in Phase 1 Clinical Trial of NTX1088, First-in-Class Anti-PVR Targeted Immunotherapy for Treatment of Patients with Advanced Solid Tumors (PRNewswire) - "Nectin Therapeutics...announced today dosing of the first patient in its Phase 1 clinical trial of NTX1088, Nectin's first-in-class PVR (CD155) blocker, in cancer patients with locally advanced and metastatic solid tumors. The trial is being conducted at The University of Texas MD Anderson Cancer Center (MD Anderson) with an investment from the Cancer Focus Fund, LP. The trial will include up to 90 patients treated with NTX1088 as a monotherapy and in combination with a PD-1 blocker. Additionally, Nectin announced that it has extended its Series A financing to over $25 million....The funding will be used to support the ongoing clinical evaluation of NTX1088, and to further advance the company's pipeline of targeted immunotherapies and Antibody Drug Conjugates (ADCs)."

Financing • Trial status • Oncology • Solid Tumor

A Study of NTX-1088, a Monoclonal Antibody Targeting the Poliovirus Receptor (PVR, CD155), as Monotherapy and Combined With Pembrolizumab (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: Nectin Therapeutics Ltd

Monotherapy • New P1 trial • Oncology • Solid Tumor • PVR

NTX-1088, a first-in-class anti-PVR mAb mediates DNAM1-dependent antitumor immunity (AACR 2022) - "Synergistic effect was obtained when NTX-1088 was combined with the anti-CD112R mAb, NTX-2R13...Furthermore, NTX-1088 in combination with pembrolizumab, was superior to the combination of pembrolizumab with tiragolumab...This is a step change in antitumor immune activation that provides a remarkable and differentiated addition to the armamentarium available to patients and their treating oncologists. An IND will be open during 2Q2022."

IO biomarker • Oncology • Solid Tumor • CD8 • IFNG • PVR • TIGIT • TNFRSF9

Nectin Therapeutics Announces $5.4 Million Investment from Cancer Focus Fund to Support Phase 1 Study of First-in-Class Anti-PVR Targeted Immunotherapy (PRNewswire) - “Nectin Therapeutics Ltd.,…and Cancer Focus Fund, LP, a unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) to provide funding and clinical expertise to advance promising cancer therapies, today announced a Cancer Focus Fund investment of $5.4 million to finance a Phase 1 clinical trial of Nectin's PVR blocker, NTX1088, in cancer patients with locally advanced and metastatic solid tumors….The Phase 1 trial is expected to begin enrolling patients around mid-year of 2022.”

Enrollment status • Licensing / partnership • Oncology • Solid Tumor

NTX-1088, A POTENT ANTI-PVR MAB INDUCES DNAM1-MEDIATED ANTITUMOR IMMUNITY (SITC 2021) - "When tested in combination with pembrolizumab, NTX-1088 further increased all measured activation parameters, suggesting a potential synergistic effect. A synergistic effect was obtained when NTX-1088 was combined with the anti-CD112R mAb, NTX-2R13, superior to TIGIT-CD112R combinations. When compared to anti-TIGIT mAb (tiragolumab), NTX-1088 demonstrated clear superiority in activating T and NK cells as stand-alone agent...NTX-1088 shows, for the first time, exclusive triple mechanism of action, whereby simultaneous and effective blockade of TIGIT and CD96 is complemented by the efficient restoration of DNAM1. This is a step change in antitumor immune activation, which will be validated in the clinic starting early 2022."

IO biomarker • Oncology • Solid Tumor • CD8 • IFNG • TIGIT • TNFRSF9