M1069 / EMD Serono, Kainova Therapeutics - LARVOL DELTA

Preclinical pharmacokinetics and biodistribution of the dual adenosine A2A/A2B inhibitor muvadenant (M1069) in rats. (PubMed, Xenobiotica) - "Muvadenant is a selective, dual A2A/A2B adenosine receptor antagonist that demonstrated anti-tumour efficacy in preclinical in vitro and in vivo models.In rats, 14C-muvadenant related radioactivity was quickly and widely distributed throughout the body with highest exposure observed in metabolic/excretory and melanin containing tissues and the gastrointestinal tract and lowest in the central nervous system.Following single oral administration, 6.27% of the radioactive dose was excreted via urine and 90.3% via faeces with a total recovery of 97.6%. After single intravenous dosing, the amounts of radioactivity excreted via urine and faeces were 13.7% and 80.2%, respectively, with a total recovery of 94.6% within 7 days.Whereas the parent compound accounted for the majority of the circulating radioactivity (>50%), metabolism plays the dominant role in the elimination of muvadenant.Metabolite structures derived from in vivo profiles in rats and in vitro incubations across..."

Journal • PK/PD data • Preclinical • Gastrointestinal Disorder • Oncology

First-in-human study of the dual A2A/A2B adenosine receptor antagonist muvadenant (M1069) in patients with advanced solid tumors. (PubMed, ESMO Open) - P1 | "Muvadenant was generally well tolerated; however, no antitumor activity was observed. A potential dose-response could not be determined due to limited number of patients per DL."

First-in-human • Journal • P1 data • Fatigue • Oncology • Solid Tumor

TARGETING ADORA2B TO HALT METASTASIS IN UNDIFFERENTIATED PLEOMORPHIC SARCOMA: FROM MULTI-OMICS TO THERAPEUTIC INHIBITION (CTOS 2025) - "Our findings identify ADORA2B as a central regulator of metastatic progression in UPS and support adenosine signaling as a viable therapeutic target. The efficacy of the dual ADORA2A/ADORA2B inhibitor M1069 reinforces its potential as a candidate for future clinical trials in UPS patients.Even more, our transcriptomic analyses provide a large database for further target identification."

Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • ADORA2A • ADORA2B

Dual A2A/ A2B adenosine receptor antagonist M1069 counteracts immuno-suppressive mechanisms of adenosine and reduces tumor growth in vivo. (PubMed, Mol Cancer Ther) - "In vivo, M1069 decreased tumor growth as a monotherapy and enhanced anti-tumor activity of bintrafusp alfa (BA) or cisplatin in syngeneic adenosinehi/CD73hi 4T1 breast tumor model, but not in the CD73 knockout (KO) 4T1 tumor model or in adenosinelow/CD73low MC38 murine colon carcinoma model. In summary, our dual A2A/A2B AR antagonist M1069 may counteract immune-suppressive mechanisms of high concentrations of adenosine in vitro and in vivo and enhance the anti-tumor activity of other agents, including BA and cisplatin."

Journal • Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD73 • CXCL1 • CXCL5 • IL12A • IL2

MS201929_0032: First in Human Study of M1069 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=15 | Terminated | Sponsor: EMD Serono Research & Development Institute, Inc. | N=30 ➔ 15 | Trial completion date: Dec 2023 ➔ Aug 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2023 ➔ May 2023; Overarching portfolio-level review of the company's oncology pipeline resulted in early termination of the study. The study was not terminated due to safety.

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

MS201929_0032: First in Human Study of M1069 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Solid Tumor

A first-in-human study of the dual A2A/A2B adenosine receptor antagonist M1069 in patients with advanced solid tumors (AACR 2022) - P1 | "The target dose-limiting toxicity probability for the MTD is 30% which will be estimated by the BLRM. Pharmacokinetic parameters will be calculated using noncompartmental analysis.The study is open and patients are being treated at the first dose level."

Clinical • P1 data • Oncology • Solid Tumor

Domain Therapeutics Receives a Single Digit Multimillion Development Milestone Payment from Merck for M1069 Clinical Development in Immuno-Oncology (Businesswire) - "Domain Therapeutics...announced that it obtained a single digit multimillion milestone payment from Merck as part of the €240m ($261m) milestone payments and undisclosed royalties collaboration and license partnership signed in 2017...'We were extremely pleased to see M1069 entering the clinical stage earlier in 2022. Reaching first-in-human & single ascending dose phase 1 constitutes a significant step towards the delivery of a novel drug for the treatment of cancer patients....Following the launching in the clinic of M1069 by Merck, Domain is very proud to prepare the entrance into the clinic, at the end of 2022, of its first fully proprietary product, the EP4R antagonist candidate DT-9081.'"

Clinical • Financing • Trial status • Oncology • Solid Tumor

M1069 as dual A2A/ A2B adenosine receptor antagonist counteracts immune-suppressive mechanisms of adenosine and reduces tumor growth in vivo (AACR 2022) - "These findings were further corroborated with the results from in vivo studies in a murine CD73hi/adenosine-rich 4T1 syngeneic breast tumor model, in which M1069, but not an A2A-selective antagonist, reduced tumor growth as a monotherapy and enhanced anti-tumor activity with chemotherapeutic agents. In summary, M1069 is a potent, dual A2A/A2B adenosine receptor antagonist, which is expected to counteract immune-suppressive mechanisms in the presence of high concentrations of adenosine and enhance the anti-tumor activity of chemotherapies."

Preclinical • Breast Cancer • Oncology • Solid Tumor • CXCL1 • CXCL5 • IL12A

MS201929_0032: First in Human Study of M1069 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor