PF-07258669 / Pfizer, Nxera Pharma - LARVOL DELTA

A Study to Learn About the Study Medicine Called PF-07258669 in Older Adults Including Those at Risk of Malnutrition (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

A Study to Learn if the Study Medicine Called Itraconazole and if Food Changes How the Body Processes the Other Study Medicine Called PF 07258669 in Older Adults or Healthy Adults (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed

Trial completion

A Study to Learn if the Study Medicine Called Itraconazole and if Food Changes How the Body Processes the Other Study Medicine Called PF 07258669 in Older Adults or Healthy Adults (clinicaltrials.gov) - P1 | N=26 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting | N=14 ➔ 26

Enrollment change • Enrollment open

A Study to Learn if the Study Medicine Called Itraconazole Changes How the Body Processes the Other Study Medicine Called PF-07258669 In Older Adults (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

A Study of PF-07258669 In Healthy Adult Participants (clinicaltrials.gov) - P1 | N=120 | Completed | Sponsor: Pfizer | N=40 ➔ 120

Enrollment change

Tribute to teamwork: Vignettes of great collaborations (ACS-Fall 2024) - "Successful synthetic campaigns are not the work of one but the combination of progress, failures, learnings, and creativity of many to solve challenges, circumvent issues, and deliver results. The topics of this presentation will include the synthesis of spirocyclic lactams and sultams via a key Overman Rearrangement transformation, and large-scale synthesis of PF-07208254, a dithiophene carboxylic acid BDK inhibitor and a spirocyclic core towards the synthesis of an MC4R antagonist, PF-07258669."

MC4R

Modular, automated synthesis of spirocyclic tetrahydronaphthyridines from primary alkylamines. (PubMed, Commun Chem) - "Altogether, this provides a highly modular access to four isomeric THN cores from a common set of unprotected primary amine starting materials, using the same bond disconnections. The simplifying power of the methodology is illustrated by a concise synthesis of the spirocyclic THN core of Pfizer's MC4R antagonist PF-07258669."

Journal

A Study of PF-07258669 In Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed | N=150 ➔ 40

Enrollment change • Trial completion

A Study of PF-07258669 In Healthy Adult Participants (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Pfizer | Trial completion date: Apr 2023 ➔ Aug 2023 | Trial primary completion date: Apr 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date

Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss. (PubMed, J Med Chem) - "Introduction of a spirocyclic conformational constraint allowed for simultaneous optimization of MC4R potency and ADME attributes while avoiding the production of hERG active metabolites observed in early series leads. Compound 23 is a potent and selective MC4R antagonist with robust efficacy in an aged rat model of cachexia and has progressed into clinical trials."

Journal • Anorexia • Cachexia

Synthesis of MC4R antagonist PF-07258669: From first synthesis to development of scalable route for clinical studies (ACS-Sp 2023) - "Finally, the endgame required development of a safe and high-yielding borylation/Suzuki reaction and employed amidation conditions that avoid epimerization. This synthetic route consisting of total of 25 synthetic steps (15 linear) delivered API against tight deadlines."

Clinical • Anorexia • Cachexia • Fatigue • Geriatric Disorders • Muscular Atrophy • Oncology

A Study of PF-07258669 In Healthy Adult Participants (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Pfizer | N=70 ➔ 150

Enrollment change

A Study of PF-07258669 In Healthy Adult Participants (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Pfizer | Trial completion date: Jul 2022 ➔ May 2023 | Trial primary completion date: Jul 2022 ➔ May 2023

Trial completion date • Trial primary completion date

Discovery of PF-07258669: A selective and potent small molecule melanocortin-4 receptor antagonist (ACS-Fall 2022) - "Antagonism of MC4R signaling has the potential to mitigate decreased appetite and body weight loss in the setting of anorexia or cachexia due to underlying disease. We will report on the identification of a series of orally bioavailable, small-molecule MC4R antagonists using a focused hit identification effort and the optimization of these antagonists for potency, brain penetration, and ADME attributes leading to the identification of PF-07258669 as a clinical candidate."

Anorexia • Cachexia

A Study of PF-07258669 In Healthy Adult Participants (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Pfizer; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study of PF-07258669 In Healthy Adult Participants (clinicaltrials.gov) - P1; N=70; Not yet recruiting; Sponsor: Pfizer

Clinical • New P1 trial

A Study of Single Ascending Doses of PF-07258669 in Healthy Adult Participants (clinicaltrials.gov) - P1; N=29; Completed; Sponsor: Pfizer; Recruiting ➔ Completed

Clinical • Trial completion