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 3 Products   0 Diseases   3 Products   1 Trial   60 News 
  • ||||||||||  M1069 / EMD Serono, Domain Therap
    Preclinical, Journal:  Dual A2A/ A2B adenosine receptor antagonist M1069 counteracts immuno-suppressive mechanisms of adenosine and reduces tumor growth in vivo. (Pubmed Central) -  Nov 4, 2024   
    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.
  • ||||||||||  DT-7012 / Domain Therap
    Characterization of DT-7012, a highly differentiated anti-CCR8 mAb clinical candidate (Exhibit Halls AB - George R. Brown Convention Center) -  Oct 4, 2024 - Abstract #SITC2024SITC_1308;    
    The binding and killing activity of DT-7012 was specific to CCR8 and CCR8+ cells, without affecting the other immune cell populations, suggesting a good safety profile of the Domain's candidate. Conclusions These data demonstrate major competitive advantages over the competitive anti-CCR8 mAbs currently in clinical development making DT-7012 a potential novel best-in-class anti-CCR8 mAb candidate.
  • ||||||||||  ADX88178 / National Institute on Drug Abuse, Addex, foliglurax (PXT2331) / Lundbeck
    Preclinical, Journal:  Metabotropic Glutamate Receptor 4 (mGlu4) Positive Allosteric Modulators Lack Efficacy in Rat and Marmoset Models of L-DOPA-Induced Dyskinesia. (Pubmed Central) -  Mar 11, 2024   
    Given the weak efficacy and side-effect profile of amantadine, alternative strategies to reduce glutamate transmission are being investigated...We hypothesized that two mGlu4 positive allosteric modulators, Lu AF21934 ((1?S,2?R)-N1-(3,4-dichlorophenyl)cyclohexane-1,2-dicarboxamide) and ADX88178 (5-Methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine), would provide relief in rat and primate models of L-DOPA-induced dyskinesia...This study found no benefit of mGlu4 positive allosteric modulators in tackling L-DOPA-induced dyskinesia. These findings are concordant with the recent failure of foliglurax in phase II clinical trials supporting the predictive validity of these pre-clinical dyskinesia models, while raising further doubt on the anti-dyskinetic potential of mGlu4 positive allosteric modulators.
  • ||||||||||  M1069 / EMD Serono, Domain Therap
    Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Metastases:  MS201929_0032: First in Human Study of M1069 in Advanced Solid Tumors (clinicaltrials.gov) -  Oct 19, 2023   
    P1,  N=15, Terminated, 
    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.
  • ||||||||||  M1069 / EMD Serono, Domain Therap
    Enrollment closed, Metastases:  MS201929_0032: First in Human Study of M1069 in Advanced Solid Tumors (clinicaltrials.gov) -  Mar 22, 2023   
    P1,  N=30, Active, not recruiting, 
    Our results show that positive allosteric modulation of mGlu4 receptors with foliglurax provided neuroprotective effects in the MPTP mouse model of PD. Recruiting --> Active, not recruiting
  • ||||||||||  Anti-CCR8 antibody / Domain Therap
    Beyond CCR8: key epitopes targeting dynamic CCR8 conformational states and a diversity of monoclonal antibodies to modulate the tumor microenvironment for the treatment of cancers (Hall C) -  Oct 6, 2022 - Abstract #SITC2022SITC_1696;    
    In parallel, treatment of tumor-bearing mice with cell-depleting anti-CCR8 antibody indeed eradicated established tumors with induction of potent tumor-specific effector/memory T cells...Up to date, targeting selective CCR8 epitopes mimicking dynamic conformational CCR8 stage according to CCR8 positive cell subset or activation cellular state will be a key issue and differentiate therapeutic approach for the TME modulation in the treatment of cancer. Moreover, the use of depleting anti-CCR8 mAb with enhanced cytotoxic activity (i.e., ADCC, CDC, ADCP) can also reduce the number of CCR8 immune suppressive cells in a tumor.
  • ||||||||||  foliglurax (PXT2331) / Lundbeck
    Preclinical, Journal:  A positive allosteric modulator of mGlu4 receptors restores striatal plasticity in an animal model of l-Dopa-induced dyskinesia. (Pubmed Central) -  Sep 14, 2022   
    This study aimed to clarify the effects of foliglurax, a selective mGlu4-PAM, on the loss of bidirectional synaptic plasticity associated with l-DOPA-induced dyskinesia (LID)...Moreover, this co-treatment rescued striatal bidirectional plasticity and attenuated the intensity of l-DOPA-induced dyskinesia. This is the first demonstration in an animal model of PD and dyskinesia that a mGlu4 PAM can restore striatal synaptic plasticity.
  • ||||||||||  Journal:  Clinical investigations of compounds targeting metabotropic glutamate receptors. (Pubmed Central) -  Sep 14, 2022   
    Antagonists of mGlu2/3Rs (decoglurant and TS-161) have been studied in depression where TS-161 has advanced into a planned Phase 2 study in treatment-resistant depression...The mGlu4R potentiator, foliglurax, did not meet its primary endpoint in patients with Parkinson's disease. Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders.
  • ||||||||||  foliglurax (PXT2331) / Lundbeck
    Clinical, P2 data, Journal:  A Randomized, Double-Blind, Controlled Phase II Study of Foliglurax in Parkinson's Disease. (Pubmed Central) -  May 25, 2022   
    Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders. There was no evidence in this study that foliglurax has efficacy in improving levodopa-induced motor complications in PD.
  • ||||||||||  M1069 / EMD Serono, Domain Therap
    Enrollment open, Metastases:  MS201929_0032: First in Human Study of M1069 in Advanced Solid Tumors (clinicaltrials.gov) -  Apr 1, 2022   
    P1,  N=24, Recruiting, 
    There was no evidence in this study that foliglurax has efficacy in improving levodopa-induced motor complications in PD. Not yet recruiting --> Recruiting
  • ||||||||||  M1069 / EMD Serono, Domain Therap
    M1069 as dual A2A/ A2B adenosine receptor antagonist counteracts immune-suppressive mechanisms of adenosine and reduces tumor growth in vivo (Section 37) -  Mar 9, 2022 - Abstract #AACR2022AACR_5472;    
    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.
  • ||||||||||  foliglurax (PXT2331) / Lundbeck
    Journal:  Improved Synthesis of the Thiophenol Precursor N-(4-Chloro-3-mercaptophenyl)picolinamide for Making the mGluR4 PET Ligand. (Pubmed Central) -  Aug 26, 2020   
    Recently [C]mG4P012 (previously [C]KALB012 and presently named as [C]PXT012253 by Prexton Therapeutics) had been used as a biomarker during the preclinical development of a potential therapeutic drug, PXT0002331 (an mGluR4 PAM), for PD and L-dopa-induced dyskinesia...To support the translational research of [C]mG4P012 and the other potential applications, we have developed a new route for synthesis of the thiophenol precursor and optimized the reaction conditions. The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales.
  • ||||||||||  foliglurax (PXT2331) / Lundbeck
    Enrollment change, Trial termination:  Study Investigating Effects of Foliglurax in Patients With Parkinson's Disease (PD) and Healthy Subjects (clinicaltrials.gov) -  Jul 7, 2020   
    P1,  N=6, Terminated, 
    The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales. N=30 --> 6 | Recruiting --> Terminated; Study termination due to efficacy results of another study
  • ||||||||||  foliglurax (PXT2331) / Lundbeck
    Journal:  An mGlu4-Positive Allosteric Modulator Alleviates Parkinsonism in Primates. (Pubmed Central) -  Oct 18, 2019   
    This work provides a demonstration that a positive allosteric modulator of metabotropic glutamate receptor 4 can alleviate the motor symptoms of PD and the motor complications induced by l-dopa in primates. PXT002331 is the first compound of its class to enter phase IIa clinical trials.
  • ||||||||||  foliglurax (PXT2331) / Lundbeck
    Trial completion:  What the Body Does to Foliglurax in Healthy Volunteers (clinicaltrials.gov) -  Sep 5, 2019   
    P1,  N=6, Completed, 
    PXT002331 is the first compound of its class to enter phase IIa clinical trials. Not yet recruiting --> Completed