pomaglumetad methionil (DB103) / Denovo - LARVOL DELTA

Modeling and optimization of direct dyes removal from aqueous solutions using activated carbon produced from sesame shell waste. (PubMed, Sci Rep) - "The results demonstrated that the adsorbent had high potential to remove direct dyes as 84.5% of direct brown 103 (DB103), 93.08% of direct red 80 (DR80), 93.37% of direct blue 21 (DB21) and 98.39% of direct blue 199 (DB199) under the optimal conditions of adsorbent dose 4.8 g/L, contact time 19 min, pH 3 and initial dye concentration 12 mg/L. The experimental results showed that kinetic data were best described by the pseudo-second-order model (R2 = 0.989) while isotherm data were best fitted by the Freundlich model (R2 = 0.994). In the present study, not only was the produced waste used as a useful and economically valuable material, but it was also applied as an effective adsorbent to remove direct dyes from industrial effluents and reduce environmental pollution."

Journal

Activation of mGlu2/3 receptors with the orthosteric agonist LY-404,039 alleviates dyskinesia in experimental parkinsonism. (PubMed, Behav Pharmacol) - "LY-404,039 and its pro-drug, LY-2140023, have previously been tested in clinical trials for psychiatric indications and could therefore be repurposed if they were shown to be efficacious in other conditions...These results provide further evidence that mGlu2/3 orthosteric stimulation may alleviate dyskinesia in PD and, in the specific case of LY-404,039, a possible D2-agonist effect might also make it attractive to address motor fluctuations. Because LY-404,039 and its pro-drug have been administered to humans, they could possibly be advanced to Phase IIa trials rapidly for the treatment of motor complications in PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • DRD2

The mGluR orthosteric agonist LY-404,039 reduces dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "LY-404,039 and its pro-drug, LY-2140023, have previously entered clinical trials as treatment options for schizophrenia...Our results provide additional support of the efficacy of mGluR orthosteric stimulation at alleviating dyskinesia, PLBs and parkinsonism. Because LY-404,039 has already been tested in clinical trials, it could be repurposed for indications related to PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia

Therapeutic effect of the mGlu2/3 orthosteric agonist LY-404,039 in the MPTP-lesioned marmoset model of Parkinson's disease (CAN-ACN 2023) - "In addition, the possible agonistic effect of LY-404,039 at D2 receptors might represent an additional therapeutic asset. As LY-404,039 and its pro-drug, LY-2140023, have previously entered clinical trials as treatment for schizophrenia, they could be quickly repurposed as a treatment for PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • DRD2

A Study Measuring Effect of LY2140023 (Pomaglumetad Methionil) on Electrocardiographs in Participants With Schizophrenia (clinicaltrials.gov) - P1 | N=86 | Completed | Sponsor: Denovo Biopharma LLC | N=60 ➔ 86

Enrollment change • CNS Disorders • Psychiatry • Schizophrenia

Prediction of the Renal Organic Anion Transporter 1 (OAT1)- Mediated Drug Interactions for LY404039, the Active Metabolite of Pomaglumetad Methionil. (PubMed, Pharm Res) - "OAT1- mediated DDIs can be predicted using in vitro measured IC and PBPK modeling. The effect of ibuprofen was predicted to be minimal (AUC ratio of 1.15) and not clinically relevant."

Journal

A Study of LY2140023 in Patients With Schizophrenia (clinicaltrials.gov) - P3 | N=567 | Terminated | Sponsor: Denovo Biopharma LLC | N=1100 ➔ 567

Enrollment change • CNS Disorders • Psychiatry • Schizophrenia

Effect of the mGlu2/3 orthosteric agonist LY-404,039 on dyskinesia, psychosis-like behaviours, and parkinsonism in the MPTP-lesioned marmoset (MDS Congress 2022) - "LY-404,039 and its pro-drug, LY-2140023, have previously entered clinical trials as treatment option for schizophrenia... The results of the present study further reinforce the paradigm of mGlu2/3 orthosteric stimulation at alleviating dyskinesia and PLBs in PD. Moreover, the possible agonistic effect of LY-404,039 at D2 receptors might represent an additional therapeutic asset; indeed, in previous experiments, with LY-354,740 in the MPTP-lesioned marmoset, the extra anti-parkinsonian effect obtained was 17%, when LY-354,740 was added to L-DOPA. Because LY-404,039 has already been tested in clinical trials, it could be repurposed for indications related to PD."

CNS Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • DRD2

Glutamate Reducing Interventions in Schizophrenia (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: New York State Psychiatric Institute; Suspended ➔ Completed; N=50 ➔ 16

Enrollment change • Trial completion • CNS Disorders • Psychiatry • Schizophrenia

[VIRTUAL] Effect of the mGlu2/3 orthosteric agonist LY-404,039 on abnormal involuntary movements and parkinsonism in the 6-OHDA-lesioned rat (MDS Congress 2021) - "LY-404,039 and its pro-drug, LY-2140023, have previously entered clinical trials for psychiatric endpoints and could therefore be repurposed if they were shown to be efficacious in other conditions... These results provide further evidence that mGlu2/3 orthosteric stimulation may alleviate dyskinesia in PD and, because LY-404,039 and its pro-drug have been administered to humans, they could possibly be advanced to Phase II trials rapidly. Of note, as LY-404,039 did not improve the anti-parkinsonian efficacy of L-DOPA, it remains unclear if it activates D2 receptors in vivo."

Preclinical • CNS Disorders • Parkinson's Disease • Psychiatry • DRD2

A Study of LY2140023 in Hepatically-Impaired Participants (clinicaltrials.gov) - P1; N=37; Completed; Sponsor: Denovo Biopharma LLC; N=60 ➔ 37

Enrollment change • Hepatitis C • Hepatology • Liver Failure

A Study of LY2140023 in Schizophrenia Patients With Prominent Negative Symptoms (clinicaltrials.gov) - P2; N=167; Completed; Sponsor: Denovo Biopharma LLC; N=280 ➔ 167

Enrollment change • CNS Disorders • Psychiatry • Schizophrenia

A Study of LY2140023 in Healthy Participants (clinicaltrials.gov) - P1; N=27; Completed; Sponsor: Denovo Biopharma LLC; N=18 ➔ 27

Clinical • Enrollment change

A Study in Schizophrenic Patients (clinicaltrials.gov) - P2; N=82; Terminated; Sponsor: Denovo Biopharma LLC; N=200 ➔ 82

Clinical • Enrollment change • CNS Disorders • Psychiatry • Schizophrenia

A Study of Safety and Tolerability in Subjects With Schizophrenia (clinicaltrials.gov) - P1; N=75; Completed; Sponsor: Denovo Biopharma LLC; N=120 ➔ 75

Clinical • Enrollment change • CNS Disorders • Psychiatry • Schizophrenia

Behind Suoyuan Biology’s plan to raise 1.6 billion yuan on science and technology innovation board: unique business model, core R&D pipeline depends on purchase [Google translation] (China Economic Net (CE.cn)) - "Among the aforementioned research and development drugs, DB102, DB103 and DB104 are fund-raising projects of Suoyuan Bio, and the funds to be raised and invested are about 600 million yuan, 270 million yuan and 700 million yuan, respectively....Suoyuan Bio's research on the drug is still at the 'biomarker search stage'. 'DB103 is currently in the biomarker search stage. The company has completed the whole genome scan of DB103 related samples and is currently analyzing the results of the whole genome scan.'"

Biomarker • Financing • CNS Disorders • Schizophrenia

Peripubertal mGluR2/3 Agonist Treatment Prevents Hippocampal Dysfunction and Dopamine System Hyperactivity in Adulthood in MAM Model of Schizophrenia. (PubMed, Schizophr Bull) - "Pomaglumetad methionil (POM), a group 2 metabotropic glutamate receptor (mGluR2/3) agonist, showed promise as a novel antipsychotic in preclinical research but failed to show efficacy in clinical trials, though it has been suggested that it may be effective in certain patient populations, including early in disease patients...No significant differences were observed across treatment groups in SAL rats. These results suggest that peripubertal mGluR2/3 agonist administration can prevent the emergence of vHPC pyramidal neuron hyperactivity and increased DA neuron population activity in adult MAM rats."

Clinical • Journal • Anesthesia • CNS Disorders • Psychiatry • Schizophrenia

[VIRTUAL] The Perils of Placebo: Developing Medications for Persons with Schizophrenia (ASCP 2021) - "In the past several years this has been observed with novel compounds such as pomaglumetad methionil, bitopertin, and encenicline...For example, asenapine was approved for the treatment of acute schizophrenia on the basis of 2 out of 4 placebo-controlled trials, where one of the studies considered 'positive' for asenapine was actually a Phase 2 study where the active control, risperidone, failed to demonstrate efficacy despite a therapeutic dose. Iloperidone was also approved for schizophrenia based on 2 out of 4 clinical trials, with disagreement between the US Food and Drug Administration and the manufacturer as to which studies were considered ‘positive’ for iloperidone...Be aware of the challenges in studying persons with schizophrenia in placebo-controlled trials 2. Understand some of the ways to increase the probability of differentiating study drug from placebo in clinical trials in persons with schizophrenia"

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Antipsychotics with no dopamine receptor blockade; promise or hype? (PubMed, Ned Tijdschr Geneeskd) - "So far, all antipsychotics block the dopamine-2 (D2) receptor in the brain, including recently available antipsychotics such as lurasidone, cariprazine and brexpiprazole...Hitherto, the effects of molecules that do not block the D2 receptor for the treatment of psychotic disorders are either disappointing or equivocal, e.g. glutamate system modulators as the metabotropic mGLu2/3 agonist LY2140023...This is encouraging, although the duration of the RCT and relatively selected group of patients preclude firm conclusions on its efficacy. We may be hopeful that antipsychotics with a novel mechanism of action are investigated, but only the future will learn whether SEP-363856 will have true added value to improve the life of patients suffering from psychotic disorders."

Journal • CNS Disorders • Psychiatry • Schizophrenia

POMA-MA-Ph1: Study of Pomaglumetad and Methamphetamine (clinicaltrials.gov) - P1; N=19; Terminated; Sponsor: University of California, Los Angeles; Recruiting ➔ Terminated; Deemed unable to enroll targeted participants in part due to COVID-19 shut downs

Clinical • Trial termination

The mGluR2/3 agonist pomaglumetad methionil normalizes aberrant dopamine neuron activity via action in the ventral hippocampus. (PubMed, Neuropsychopharmacology) - "Administration of POM prior to 2 h restraint stress prevented the restraint-induced increase in DA neuron population activity, and this effect was blocked by pretreatment with an mGluR2/3 antagonist. Thus, the ability of POM to reduce the hyperdopaminergic activity in both MAM rats and in wild type rats following restraint stress suggests that it can indirectly regulate DA neuron activity, which may underlie its potential therapeutic effects."

Journal • Anesthesia • CNS Disorders • Psychiatry

Pomaglumetad Methionil Normalizes Vta Dopamine Neuron Activity in the Methylazoxymethanol Acetate Model of Schizophrenia (SIRS 2019) - "Discussion We posit that the lack of efficacy in clinical trials may be due to interference from DA supsersensitivity induced by prior drug treatment. Preliminary data suggest that pomaglumetad methionil indirectly regulates DA neuron activity by reducing increased ventral hippocampal activity, which may contribute to its potential therapeutic effects."

CNS Disorders • Schizophrenia

A study of LY2140023 in healthy participants (clinicaltrials.gov) - P1, N=18; Not yet recruiting -> Recruiting

Enrollment status • Schizophrenia

A study in schizophrenic patients (clinicaltrials.gov) - P2, N=200; Recruiting

Schizophrenia

A study of safety and tolerability in subjects with schizophrenia (clinicaltrials.gov) - P1, N=120; Recruiting -> Completed; Completion date: Jul 2012 -> Mar 2012

Trial completion • Trial completion date • Schizophrenia