TD-1211 / Innoviva - LARVOL DELTA

Axelopran and Nivolumab in PD-1-Refractory Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=28 | Not yet recruiting | Sponsor: John Kirkwood | Initiation date: Jul 2026 ➔ Oct 2026

First-in-human • Trial initiation date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

MORALE-HN01: A Phase II Trial for MOR Antagonism With Axelopran to Enhance Immunotherapy in Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=18 | Not yet recruiting | Sponsor: Glycyx Therapeutics

IO biomarker • New P1/2 trial • Head and Neck Cancer • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Axelopran in Patients With Anti-PD-1 Refractory Metastatic or Locoregionally Unresectable Cutaneous Melanoma (clinicaltrials.gov) - P1/2 | N=28 | Not yet recruiting | Sponsor: John Kirkwood

First-in-human • New P1/2 trial • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

AxeCan: Axelopran for Advanced Cancer in Patients Receiving Opioids (clinicaltrials.gov) - P2 | N=34 | Recruiting | Sponsor: HealthPartners Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Receptor Negative Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • PGR

AxeCan: Axelopran in Advanced Cancers (clinicaltrials.gov) - P2 | N=34 | Not yet recruiting | Sponsor: HealthPartners Institute

New P2 trial • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor

New developments in the treatment of opioid-induced gastrointestinal symptoms. (PubMed, United European Gastroenterol J) - "This review summarises current and emerging treatment options for OIC based on an extensive bibliographical search. Efficacy data for laxatives, lubiprostone, prucalopride, linaclotide, oxycodone/naloxone combinations, methylnaltrexone, alvimopan, naloxegol, naldemedine, axelopran, and bevenopran in OIC are summarised."

Journal • Review • Biosimilar • Pain

Theravance announces plan to separate late-stage partnered respiratory assets from biopharmaceutical operations (Marketwire) - "Theravance...announced today that its Board of Directors approved plans to separate its businesses into two independent publicly traded companies...The key product and product candidates in Theravance Biopharma's portfolio will include VIBATIV®...TD-1211...and TD-9855."

Commercial • Pain

Investigational opioid antagonists for treating opioid-induced bowel dysfunction. (PubMed, Expert Opin Investig Drugs) - "...TD-1211 is currently being evaluated in Phase II clinical trial...Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature."

Journal • Biosimilar • CNS Disorders • Oncology • Pain

Clinical Overview and Considerations for the Management of Opioid-induced Constipation in Patients with Chronic Noncancer Pain. (PubMed, Clin J Pain) - "Health care providers should be aware of this complication in patients receiving opioids and should monitor and address constipation-related symptoms to optimize pain management and improve patient quality of life.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/."

Clinical • Journal

Discovery of Axelopran (TD-1211): A Peripherally Restricted μ-Opioid Receptor Antagonist. (PubMed, ACS Med Chem Lett) - "Gastrointestinal dysfunction is an additional serious consequence of opioid use, and this can be treated with a localized drug distribution of a non-CNS penetrant, peripherally restricted opioid receptor antagonist. Herein, we describe the application of Theravance's multivalent approach to drug discovery coupled with a physicochemical property design strategy by which the N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenyl carboxamide series of μ-opioid receptor antagonists was optimized to afford the orally absorbed, non-CNS penetrant, Phase 3 ready clinical compound axelopran (TD-1211) 19i as a potential treatment for opioid-induced constipation."

Journal

Efficacy of Treatments for Opioid-induced Constipation: A Systematic Review and Meta-Analysis. (PubMed, Clin Gastroenterol Hepatol) - "In a systematic review and meta-analysis, we found μ-opioid receptor antagonists to be safe and effective for the treatment of OIC. Prescription-strength laxatives (prucalopride, lubiprostone) are slightly better than placebo in reducing OIC."

Journal • Retrospective data • Review