NTM-006 / Neumentum, J&J - LARVOL DELTA

The Discovery and Preclinical Pharmacology of JNJ-10450232 (NTM-006), a Centrally Penetrant, Non-Opioid Structural Analog of Acetaminophen with Comparable Analgesic and Anti-Pyretic Properties but No Evidence of Hepatotoxicity. (PubMed, Regul Toxicol Pharmacol) - "Finally, following systemic administration, JNJ-10450232/NTM-006 and acetaminophen produced comparable peripheral levels of para-aminophenol and brain levels of pharmacologically active metabolite N-arachidonoyl-phenolamine (AM404), consistent with the hypothesis that both parent molecules are prodrugs and share the same central mechanism of analgesic action. Taken together, these results suggest JNJ-10450232/NTM-006 as a potentially clinically useful analgesic/antipyretic with improved benefit-to-risk ratio compared with current standards of care."

Journal • Preclinical • Cardiovascular • Gastrointestinal Disorder • Hepatology • Liver Failure • Pain

Study design for testing safety, tolerability, and efficacy of NTM-006 against pain symptoms associated with Fragile X Tremor/Ataxia Syndrome (FXTAS) (PAINWeek 2024) - "We will collect data on restless legs syndrome, severe cramps, disc/spine problems, and muscle pain. Migraine with and without aura, age of onset, and frequency will be collected along with symptoms of neuropathy, allodynia, back pain, and chronic pain in general. Activation ratio will be measured using ratios of signal intensity."

Clinical • Ataxia • Back Pain • CNS Disorders • Depression • Migraine • Mood Disorders • Musculoskeletal Pain • Pain • Parkinson's Disease • Peripheral Neuropathic Pain • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Exploring acetaminophen prodrugs and hybrids: a review. (PubMed, RSC Adv) - "Prime examples of APAP-based drugs such as propacetamol, benorylate, acetaminosalol, nitroparacetamol, and agent JNJ-10450232 weave well into this classification. The proposed classification is the first and original, giving a better understanding of the SAR studies for new pain relievers research and the design development for the analgesic APAP-(or NSAID)-based compounds."

Journal • Review • Musculoskeletal Pain • Pain

JNJ-10450232 (NTM-006), A novel non-opioid with structural similarities to acetaminophen, produces relatively long-lasting analgesia after a single dose in patients undergoing 3rd molar extraction. (PubMed, Regul Toxicol Pharmacol) - P2 | "These data support further evaluation of JNJ-10450232 (NTM-006) for the treatment of moderate-to-severe pain. CLINICALTRIALS.GOV ID: NCT02209181."

Clinical • Journal • Addiction (Opioid and Alcohol) • Hepatology • Pain • UGT1A1

Metabolism and disposition of JNJ-10450232 (NTM-006) in rats, dogs, nonhuman primates and humans. (PubMed, Regul Toxicol Pharmacol) - "Unchanged drug was the major circulatory component in all species investigated. Except for metabolic pathways unique to the 5-methyl-1H-pyrazole-3-carboxamide moiety, metabolism and disposition of JNJ-10450232 (NTM-006) are similar to acetaminophen across species."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Hepatology • Pain

Preclinical safety assessment of JNJ-10450232 (NTM-006), a structural analog of acetaminophen, that does not cause hepatotoxicity at supratherapeutic doses. (PubMed, Regul Toxicol Pharmacol) - "JNJ-10450232 (NTM-006) had no toxicologically relevant findings in safety pharmacology or genotoxicity studies. Together, these data supported progressing into safety and efficacy studies in humans."

Journal • Preclinical • Hematological Disorders • Hepatology • UGT1A1

Update on NTM-006, a Novel Orally-Active Non-Opioid Analgesic: Molecular-Modeling Consistent with Allosteric Modulation of the Adenosine A3 Receptor (PAINWeek 2022) - "NTM-006 was speculated to exert its primary action at Adenosine A3 receptors, possibly as an allosteric modulator. The results of the molecular modeling reported here supports this hypothesis. The combination of binding processes would be consistent with NTM-006's in vitro , animal model, and clinical characteristics of broad-spectrum and pronounced analgesic efficacy, and long-duration of analgesic action."

CNS Disorders • Neuralgia • Pain

First-in-human study to evaluate the safety, tolerability and pharmacokinetics of a novel analgesic and antipyretic drug with structural similarity to acetaminophen. (PubMed, Regul Toxicol Pharmacol) - "JNJ-10450232 (NTM-006) is a new molecular entity that comprises structural similarities to acetaminophen and provides comparable analgesia in animals and humans without causing the hepatotoxicity associated with acetaminophen overdose in preclinical models. Transient increases in indirect bilirubin were noted at post-baseline timepoints due to UGT1A1 inhibition, without any evidence of adverse hepatic effects. Macular rash and generalized erythema were the most common drug-related adverse events after multiple doses."

Journal • P1 data • PK/PD data • Dermatology • Hepatology • Pain • UGT1A1

Update on In Vivo Testing of NTM-006 (formerly JNJ-10450232), a Novel Orally-Active Non-Opioid Analgesic: CFA and Paw Edema (PAINWeek 2021) - "NTM-006 previously demonstrated oral antinociceptive and antipyretic activity in a variety of animal models predictive of analgesic efficacy against acute pain conditions. Based on in vitro assay screens, the compound is non-opioid, and non-NSAID (does not inhibit COX-1 or COX-2 cyclooxygenase isozymes) at doses that produce its antinociceptive and antipyretic effects. Based on in vitro assays, NTM-006 appears to exert its primary action at adenosine A3 receptor sites, possibly as an allosteric modulator (A3RM)."

Preclinical • CNS Disorders • Pain

Update on In Vivo Testing of NTM-006 (formerly JNJ-10450232), a Novel Orally-Active Non-Opioid Analgesic: Neuropathic Pain Model (PAINWeek 2021) - "Gabapentin was used as the positive control. NTM-006 was previously shown to have oral acute antinociceptive and antipyretic activity in a variety of animal models predictive of analgesic efficacy against acute pain. It was recently found to have efficacy in the Complete Freund’s adjuvant and carrageenan paw models of inflammatory pain (see companion poster). Based on in vitro assays, NTM-006 appears to exert its primary action at adenosine A3 receptor sites, a mechanism that is suggestive of possible efficacy against neuropathic pain."

Preclinical • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

Neumentum Announces Two Poster Presentations for Novel Non-opioid, Non-NSAID Analgesic Drug Candidate at PAINWeek 2020 (GlobeNewswire) - "Neumentum Inc....will present two posters with data on NTM-006, a new chemical entity (NCE) non-opioid, non-NSAID analgesic candidate that may have the potential to replace opioids, at PAINWeek 2020 Live Virtual Conference, being held on September 11-13, 2020."

P2 data • Preclinical • CNS Disorders • Neuralgia • Pain

Neumentum Provides Corporate Update on Company’s Pipeline of Non-opioid Analgesic Programs (GlobeNewswire) - P2, N=269; NCT02209181; Sponsor: McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.; "Neumentum Inc....today provided a corporate update on notable business accomplishments and priorities for...NTM-006....Clinical results from the Proof of Concept (PoC) Dental Surgery Phase 2a study in moderate to severe pain showed significantly superior efficacy of NTM-006 to acetaminophen 1000mg...Based upon the presumed MOA and PK/PD analyses...Neumentum’s development program for NTM-006 will optimize the opportunity in neuropathic pain....The company will meet with the U.S. Food and Drug Administration (FDA) during a Type C meeting scheduled for October 2020 to discuss the next steps in the development of NTM-006."

FDA event • P2a data • CNS Disorders • Pain

Neumentum’s CEO discusses deal with J&J for non-opioid acute pain treatment (BioSpace) - "Chief Executive Officer Scott Shively said the acquisition of an oral analgesic from Johnson & Johnson will be transformative for California-based Neumentum Inc....In addition to getting NTM-001 ready for Phase III, Shively said the company will complete the transition of the J&J asset over the next few months and begin some pre-Phase III work on the asset ahead of seeking approval to launch a late-stage trial. Shively predicted JNJ-10450232 could enter into Phase III in early 2021 if all goes well."

Licensing / partnership • New P3 trial

Neumentum enters into global licensing agreement for a novel class of investigational pain treatments (Businesswire) - "Neumentum Inc....today announced it has entered into a global licensing agreement with Janssen Pharmaceutica NV and McNeil Consumer Pharmaceuticals Co....for the rights to a novel oral analgesic, JNJ-10450232, plus a portfolio of backup compounds."

Licensing / partnership