NM21-1480 / CStone Pharma, Numab - LARVOL DELTA

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=52 | Terminated | Sponsor: Numab Therapeutics AG | N=406 ➔ 52 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2023 ➔ Feb 2024; A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.

Enrollment change • Metastases • Trial primary completion date • Trial termination • Trispecific • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Fallopian Tube Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=406 | Active, not recruiting | Sponsor: Numab Therapeutics AG

Metastases • Trial completion date • Trispecific • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Fallopian Tube Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=406 | Active, not recruiting | Sponsor: Numab Therapeutics AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Trispecific • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Fallopian Tube Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin. (PubMed, Oncoimmunology) - "In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Transplantation • MSLN

CStone Pharmaceuticals Reports 2022 Annual Results and Business Updates (PRNewswire-Asia) - "Early clinical programs: (i) CS2006: continuation of PoC expansion of CS2006 monotherapy in selected solid tumor indications; (ii) CS5001: plan to present CS5001 translational data at a major conference in 2023; (iii) CS5001: first patient enrollment in mainland China in Q1 2023; (iv) CS5001: data release from phase I trial for dose escalation in Q4 2023."

Clinical data • P1 data • Trial status • Oncology • Solid Tumor

First-in-human trial to evaluate safety, PK/PD and initial clinical activity of NM21-1480, an affinity-balanced PD-L1x4-1BBxHSA trispecific antibody: Results of Phase 1 dose escalation (SITC 2022) - "Encouraging early clinical activity across different dose levels was observed in a heavily pretreated population with advanced solid tumors, including those resistant to prior immunotherapy or typically less sensitive to ICIs. Enrollment into expansion cohorts will start in the second half of 2022."

Clinical • IO biomarker • P1 data • PK/PD data • Oncology • Solid Tumor

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=406 | Recruiting | Sponsor: Numab Therapeutics AG | N=147 ➔ 406 | Trial completion date: Jun 2023 ➔ Jan 2025 | Trial primary completion date: Jan 2023 ➔ Jan 2024

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trispecific • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Fallopian Tube Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

CStone Pharmaceuticals Reports 2022 Interim Results and Business Updates (PRNewswire-Asia) - "Early-clinical programs: CS2006: Initiation of PoC expansion cohorts of CS2006 monotherapy in selected solid tumor indications and data presentation from dose-escalation at SITC."

Clinical data • New trial • Oncology • Solid Tumor

Engineering of a trispecific tumor-targeted immunotherapy incorporating 4-1BB co-stimulation and PD-L1 blockade. (PubMed, Oncoimmunology) - "NM21-1480 inhibited PD-L1/PD-1 signaling with a potency similar to avelumab, and it potently stimulated 4-1BB signaling only in the presence of PD-L1, while exhibiting an EC that was largely independent of PD-L1 density. A GLP toxicology study revealed no evidence of liver toxicity at doses up to 140 mg/kg, and pharmacokinetic studies in non-human primates suggested a plasma half-life in humans of up to 2 weeks. NM21-1480 has the potential to overcome checkpoint resistance by co-activating tumor-infiltrating lymphocytes without liver toxicity."

Journal • Hepatology • Immune Modulation • Inflammation • Oncology

NM28-2746, a reduced affinity bivalent mesothelin-binding MATCH4 T cell engager, with half-life extension, increases selectivity for killing of mesothelin-overexpressing cells (AACR 2022) - "We also demonstrate dose dependent anti-tumor activity in in vivo efficacy studies in PBMC-reconstituted mice, and combination therapeutic activity with an anti-PD-L1, anti-4-1BB bispecific molecule (NM21-1480). Collectively, these data demonstrate an increased selectivity to mesothelin-overexpressing cells by this novel MATCH4 reduced affinity bivalent T cell engager. These data indicate the potential of this molecule to increase the therapeutic window by reducing safety concerns on normal tissue where mesothelin expression is low, and yet promote cytotoxicity on mesothelin over-expressing cancer cells."

IO biomarker • Oncology • MSLN

Dose selection investigations and combination strategies of NM21-1480, a PD-L1/4-1BB/HSA trispecific MATCH3 therapeutic clinical candidate (AACR 2022) - "In particular, we demonstrate that the combination of NM21-1480 with anti-CD3 T cell engagers is highly effective in T cell activation and tumor control. These data highlight the potential of NM21-1480 for the treatment of cancer patients and enable greater understanding of the relationship between dose, tumor exposure, immune activation and tumor growth inhibition."

Clinical • IO biomarker • Oncology • PD-L1

CStone Announces Presentation of Preclinical data on a Multi-Specific Antibody-based Therapeutic Candidate CS2006/NM21-1480 at the American Association for Cancer Research (AACR) Annual Meeting 2022 (PRNewswire-Asia) - "CStone Pharmaceuticals...announced that the preclinical data of multi-specific antibody CS2006/NM21-1480 has been presented at the American Association for Cancer Research (AACR) Annual Meeting 2022....CS2006/NM21-1480 was efficacious as monotherapy in both hot and cold tumor models; combination with a CD3-T cell engager resulted in enhanced anti-tumor activity, with increased CD8-positive T memory cells within the tumor. These data provide translational support for the ongoing clinical development of CS2006/NM21-1480 as a potential best-in-class, next-generation immune-oncology agent."

Preclinical • Oncology

"#CStone received China #NMPA #IND approval for #CS2006/#NM211480, a #PDL1/#41BB/#HSA #multispecificantibody-based molecule, marking further expansion of its Pipeline 2.0 https://t.co/rCi5EqcK23" (@1stOncology)

CStone received China NMPA IND approval for CS2006/NM21-1480, a PD-L1/4-1BB/HSA multi-specific antibody, marking further expansion of its Pipeline 2.0 (PRNewswire-Asia) - "CStone Pharmaceuticals...announced that the investigational new drug (IND) application of multi-specific antibody CS2006/NM21-1480 has been approved by the National Medical Products Administration (NMPA) of China. CS2006/NM21-1480 represents a leading class of next-generation anti-PD-1/PD-L1 cancer immunotherapies and a new backbone molecule for combinations....The upcoming clinical study is designed to evaluate the safety, pharmacokinetics, and anti-tumor efficacy of CS2006/NM21-1480 in Chinese patients with various advanced solid tumors."

New trial • Oncology • Solid Tumor

CStone announces China NMPA acceptance of IND application for CS2006/NM21-1480, a PD-L1/4-1BB/HSA multi-specific antibody-based molecule, marking further expansion of its Pipeline 2.0 (CStone Pharma Press Release) - "CStone Pharmaceuticals...announced that the investigational new drug (IND) application of CS2006/NM21-1480 has been accepted by the Center for Drug Evaluation, National Medical Products Administration (NMPA) of China...The clinical program of CS2006/NM21-1480 will further deepen and expand CStone’s Pipeline 2.0 strategy. "

Non-US regulatory • Oncology

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors Estudio de NM21-1480 en pacientes adultos con tumores sólidos avanzados (clinicaltrialsregister.eu) - P1/2; N=167; Ongoing; Sponsor: Numab Therapeutics AG

Clinical • IO biomarker • New P1/2 trial • Cholangiocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=147; Recruiting; Sponsor: Numab Therapeutics AG; N=102 ➔ 147; Trial completion date: Aug 2022 ➔ Jun 2023; Trial primary completion date: Jul 2022 ➔ Jan 2023

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Numab Therapeutics Completes Oversubscribed CHF 100 Million Series C Financing (Businesswire) - "Numab Therapeutics...announced the closing of a CHF 100 million (approximately USD 110 million) Series C financing....Proceeds will support acceleration and expansion of the clinical development of Numab’s lead program NM21-1480 into multiple cancer indications...'The financing will help us to maximize the value of this asset by significantly expanding the clinical development program and accelerating toward phase 2 proof-of-concept.'"

Financing • Oncology

[VIRTUAL] Multispecific MATCHTM Antibodies – Design and Development of Next-Generation Cancer Therapeutics (PEGS 2021) - "NM21-1480 is a multispecific antibody fragment-based cancer therapeutic in phase 1 clinical testing, that potently stimulates anti-cancer immune responses through concomitant induction of 4-1BB-signaling and PD-L1 blockade in the tumor microenvironment. Careful selection of format, epitopes and affinities resulted in optimized activity and a favorable safety profile in non-human primates. Additional therapeutic approaches based on Numab’s MATCHTM platform are presented."

Oncology

CStone Pharmaceuticals Reports Financial Results and Business Highlights for Full-year 2020 (Yahoo Finance) - “our commercial team laid the groundwork for four 2021 commercial launches: pralsetinib (RET inhibitor), avapritinib (KIT/PDGFRA inhibitor) and ivosidenib (IDH1 inhibitor) in mainland China and avapritinib in Taiwan…CS2006 (NM21-1480, PD-L1×4-1BB×HSA tri-specific molecule)…We expect to submit an IND application to the NMPA in the second half of 2021. CS5001 (LCB71, ROR1 ADC)…We expect to submit IND/CTA applications for CS5001 by the end of 2021.”

Launch non-US • Non-US regulatory • Oncology

[VIRTUAL] Multi-Specific MATCH Antibodies Enable Novel Therapeutic Strategies by Targeting Synergistic Immunomodulatory Functions to the Tumor Microenvironment (IOS 2020) - "NM21-1480 shows superior efficacy over conventional CPI therapies and avoids dose-limiting toxicities of systemic 4-1BB agonism. Further, tetra-specific MATCH4 molecules are exploited to improve on safety and efficacy of conventional bispecific strategies."

Biomarker • Tumor microenvironment • Immune Modulation • Inflammation • Oncology

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=102; Recruiting; Sponsor: Numab Therapeutics AG; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=102; Not yet recruiting; Sponsor: Numab Therapeutics AG

Clinical • New P1/2 trial • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

[VIRTUAL] Preclinical development and mechanism of action studies of NM21-1480, a PD-L1/4-1BB/HSA trispecific MATCH3 therapeutic clinical candidate (AACR-II 2020) - "We report on the toxicity profile and pharmacokinetic properties of the molecule in non-human primates. We plan to initiate a first-in-human clinical study in the second half of 2020 to determine the safety, tolerability and first signs of clinical activity of the molecule."

Oncology • PD-1 • PD-L1

Numab Therapeutics closes series B financing at CHF 22M to advance portfolio of novel multi-specific antibodies in immuno-oncology (Numab Press Release) - “Numab Therapeutics announced today the closing of its Series B financing round at a total volume of CHF 22M (approximately USD 22.6M)…With the financing secured, Numab plans to further broaden its proprietary pipeline and accelerate the development for a number of programs towards the clinic. The company also plans to initiate a clinical trial for its lead oncology program ND021 during the course of 2020.”

Financing • Trial initiation date