prosetin / Project ALS, Columbia University, ProJenX - LARVOL DELTA

PRO-101: A Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of Prosetin in Healthy Volunteers and Participants with ALS (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: ProJenX | N=32 ➔ 72 | Trial completion date: Jul 2022 ➔ Oct 2026 | Trial primary completion date: May 2022 ➔ Jun 2026

Enrollment change • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

PRO-101: study design and interim results from a hybrid Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin in ALS (ALS-MND 2024) - "In healthy volunteers, no serious adverse events or abnormalities in any safety assessments were identified. Plasma levels of prosetin increased in a predictable manner, with low intra-subject variability and clear separation between doses. A growing body of evidence links MAP4K inhibition to neuronal survival in ALS (3,4), making it an attractive target for therapeutic intervention."

Clinical • P1 data • PK/PD data

Hepatitis B Virus X Protein Induces Reactive Oxygen Species Generation via Activation of p53 in Human Hepatoma Cells. (PubMed, Biomolecules) - "Additionally, HBx variants with Ser-101 increased p53 and ROS levels, whereas variants with Pro-101 did not. These dual mechanisms of HBx-induced ROS generation are likely significant in the pathogenesis of HBV and may contribute to liver diseases, including hepatocellular carcinoma."

Journal • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor • CAT

ProJenX and Unlearn Announce Partnership to Augment ALS Clinical Trial PRO-101 with Digital Twin Model (PRNewswire) - "ProJenX, Inc...today announced its partnership with Unlearn to augment PRO-101, its Phase 1 clinical trial of prosetin—a brain-penetrant, MAP4 kinase (MAP4K) inhibitor—with Unlearn's advanced generative artificial intelligence (AI) technology. Unlearn, a pioneering technology company innovating machine learning to revolutionize medical research, will implement its ALS-Digital Twin Generator (ALS-DTG) to produce digital twins of PRO-101 clinical trial participants living with ALS to evaluate the clinical outcomes of ALSFRS-R, Slow Vital Capacity, and plasma neurofilament light over a 52-week open-label extension."

Licensing / partnership • Amyotrophic Lateral Sclerosis • CNS Disorders

ProJenX Announces Receipt of $1M Hoffman ALS Clinical Trial Award from the ALS Association (PRNewswire) - "ProJenX, Inc...today announced the receipt of a $1M Hoffman ALS Clinical Trials Award from the ALS Association. The grant will help fund the development of prosetin, a novel, brain-penetrant, MAP4 kinase (MAP4K) inhibitor, in the Part 1c portion of the PRO-101 clinical trial of prosetin in participants living with ALS....ProJenX has completed the Part 1a and Part 1b portions of PRO-101 in healthy volunteers. Part 1c of the PRO-101 clinical trial is expected to initiate enrollment in Q3 2024."

Enrollment status • Financing • Amyotrophic Lateral Sclerosis • CNS Disorders

ProJenX Announces Removal of Partial Clinical Hold for Prosetin Program by FDA (PRNewswire) - "On track to initiate enrollment in participants with ALS in Q2 2024 at clinical sites in Canada and the Netherlands, with US sites to be added later this year...ProJenX...announced that the United States Food and Drug Administration (FDA) has removed a partial clinical hold on Study PRO-101, a hybrid Phase 1 clinical trial evaluating prosetin—a first-in-class MAP4 kinase (MAP4K) inhibitor—in healthy volunteers and participants with ALS. The healthy volunteer portions of the trial have been completed, and the company is initiating Part 1c of PRO-101, designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin in participants with ALS."

FDA event • Amyotrophic Lateral Sclerosis • CNS Disorders

ProJenX Receives European Authorization for First Study of Prosetin in People Living with ALS (PRNewswire) - "ProJenX...announced that it has received authorization in the European Union (EU) for study PRO-101, a hybrid Phase 1 clinical trial evaluating prosetin—a first-in-class MAP4K inhibitor—in healthy volunteers and participants with ALS."

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

ProJenX Receives Health Canada Clinical Trial Application Authorization for First Study of Prosetin in People Living with ALS (PRNewswire) - "ProJenX...announced authorization of its clinical trial application (CTA) by Health Canada for study PRO-101, a global, hybrid Phase 1 clinical trial evaluating prosetin—a first-in-class MAP4K inhibitor—in healthy volunteers and participants with ALS. The Health Canada CTA authorization supports initiation of Part 1c of PRO-101, designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of prosetin in participants with ALS."

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

ProJenX Announces Initial Closing of $15M Series A Financing and Appoints Rick Hartz to Board of Directors (GlobeNewswire) - "ProJenX, Inc.today announced the initial closing of a $15 million Series A financing. Led by Medical Excellence Capital, which also led the company's seed financing round and created ProJenX in collaboration with Project ALS and researchers at Columbia University, the Series A will fund the continued development of ProJenX's lead compound, prosetin, for the treatment of ALS."

Financing • Amyotrophic Lateral Sclerosis • CNS Disorders

Characterization of the Pro101Gln mutation that enhances the catalytic performance of T. indicus NADH-dependent d-lactate dehydrogenase. (PubMed, Structure) - "The role of the conserved residue Pro101 in d-LDH was further probed in site-directed mutagenesis experiments. We introduced d-LDH1 into Bacillus licheniformis yielding a d-lactic acid production of 145.9 g L within 60 h at 50°C, which was three times higher than that of the wild-type enzyme. The discovery of d-LDH1 will pave the way for the efficient production of d-lactic acid by thermophilic bacteria."

Journal • APOD

Pharmacoinformatics-Based Approach for Uncovering the Quorum-Quenching Activity of Phytocompounds against the Oral Pathogen, Streptococcus mutans. (PubMed, Molecules) - "Notably, specific amino acid residues, including ASP86, ARG182, ILE179, GLU143, ASP237, PRO101, and VAL84 from CiaR, LepC, OppC, SecA, SMU1784c, SpaR, and YidC2, respectively, exhibited significant interactions with their respective ligands. While the docking study indicated favorable binding energies, the MD simulations and ADMET studies underscored the substantial binding affinity and stability of the ligands with the target proteins. However, further in vitro studies are necessary to validate the efficacy of these top hits against S. mutans."

Journal • Dental Disorders • Infectious Disease • CORIN

New hybrids based on benzimidazole and diazepine moieties: design, synthesis, characterization, molecular docking studies and their in vitro interactions with benzodiazepine receptors. (PubMed, J Biomol Struct Dyn) - "To achieve deeper insight into their interactions with benzodiazepine receptors, molecular dynamics simulation was employed. According to the results obtained from the molecular dynamics simulation, Pro85, Leu103, Pro101, Gln102, Ile79, Ser80, Pro17, Leu82 and Val84 interact with the most potent ligand by hydrophobic interactions and Asp86 and Leu87 interact with the ligand by hydrogen bond interactions.Communicated by Ramaswamy H. Sarma."

Journal • Preclinical • CNS Disorders • Epilepsy • Insomnia • Mood Disorders • Movement Disorders • Psychiatry • Sleep Disorder

Dosing Begins in Phase 1 Trial of Prosetin (ALS News Today) - “A Phase 1 clinical trial investigating ProJenX‘s oral therapy prosetin in healthy volunteers and people with amyotrophic lateral sclerosis (ALS) has started dosing participants. The first-in-human PRO-101 trial is divided into three parts. In parts 1a and 1b, researchers will investigate the safety, tolerability, and pharmacokinetics of single and ascending doses of prosetin versus a placebo in healthy volunteers. Pharmacokinetics refers to the movement of a drug into, through, and out of the body. After those parts are completed, Part 1c will evaluate the same measures in people with ALS. According to an August webinar by Project ALS, this portion of the trial will take place at Columbia University Medical Center, in New York.”

Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders

PRO-101: A Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of Prosetin in Healthy Volunteers (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: ProJenX

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

"Project ALS’ Prosetin Receives the US FDA’s Orphan Drug Designation for Amyotrophic Lateral Sclerosis @ProjectALSorg https://t.co/XXz7kKygn0" (@Pharmashot)

Orphan drug • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders

Project ALS Granted FDA Orphan Drug Designation for Prosetin for the Treatment of Amyotrophic Lateral Sclerosis (PRNewswire) - “Project ALS…announced today that the Food and Drug Administration (FDA) has granted orphan drug designation to prosetin for the treatment of ALS. Prosetin is an oral, brain penetrant MAP4 kinase inhibitor developed by scientists at Columbia University for the treatment of ALS."

Orphan drug • Amyotrophic Lateral Sclerosis • CNS Disorders

Prosetin Granted Orphan Drug Designation for ALS (ALS News Today) - “The U.S. Food and Drug Administration has granted Prosetin orphan drug designation for the treatment of amyotrophic lateral sclerosis (ALS)….Project ALS’ goal is to initiate human clinical studies by the end of this year.”

Orphan drug • Amyotrophic Lateral Sclerosis • CNS Disorders