Discovery Pre-Clinical Phase 1 Phase 2 Phase 3
Paltusotine (SST2 Agonist)
Acromegaly (PATHFNDR-1)
Acromegaly (PATHFNDR-2)
Carcinoid Syndrome

Paltusotine (formerly CRN00808)


Paltusotine is the first oral, once-daily, selectively targeted somatostatin receptor type 2 (SST2) agonist being developed for the treatment of acromegaly and carcinoid syndrome.

For the Treatment of Acromegaly


Somatostatin peptide analogs are the primary pharmacotherapy for those acromegaly patients who are candidates for chronic pharmacological intervention. Currently marketed peptide drugs require painful monthly or daily injections, or a strict twice-a-day oral dosing regimen. In the case of somatostatin peptide drugs, therapies often fail to fully control the disease in many acromegaly patients.

FOR THE TREATMENT OF CARCINOID SYNDROME


Carcinoid syndrome is a group of symptoms some patients may present when they have a specific type of cancer called neuroendocrine tumors, or NETs. NETs are a rare, slow-growing type of cancer – they only represent about 1% of all cancers – and can occur in any number of places in the body, most often in the digestive tract.

Not all neuroendocrine tumors cause carcinoid syndrome, but it commonly develops if the NET spreads from the small bowel (or other locations) to the liver. In these cases, the hormones the NET secretes cannot be filtered out by the liver as they normally would, so they get into the body’s circulatory system and cause the symptoms of carcinoid syndrome.

Most NETs express SST2 receptors and injected depots of peptide somatostatin analogs have become the first-line standard of care for many NETs patients.

Phase 2


Paltusotine Maintains IGF-I, GH, and Symptom Control in Patients With Acromegaly Switched From Injected Octreotide or Lanreotide Monotherapy: Topline Results From PATHFNDR-1, a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
Monica R. Gadelha, MD, PhD; et al.
Poster Presentation: The Society for Endocrinology SfE BES, 2023

Oral Once-Daily, Paltusotine (Non-Peptide Selective Somatostatin Receptor Subtype 2 Agonist) Therapy in Patients With Acromegaly is Associated With Long-Term Biochemical and Symptom Control and is Preferred Over Injectable Somatostatin-Receptor Ligands.
Monica R. Gadelha, MD, PhD
Oral Presentation: Annual Meeting of the Endocrine Society (ENDO); 6/15/2023

A Phase 2, Randomized, Parallel Group Study to Evaluate the Safety, Pharmacokinetics, and Dose Response of Paltusotine Treatment in Subjects with Carcinoid Syndrome.
Aman Chauhan, MD; Shagufta Shaheen, MD; Keith Usiskin, MD; et al.
Poster: European Neuroendocrine Tumor Society (ENETS) meeting; 3/22/2023

ACROBAT Edge: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients with Acromegaly.
Monica R. Gadelha, MD, PhD; Murray B. Gordon, MD; Mirjana Doknic, MD, PhD; et al.
Article: The Journal of Clinical Endocrinology & Metabolism, 2022

ACROBAT Advance: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients with Acromegaly.
Harpal Randeva, MBChB, FRCP, FAcad TM, PhD; Monica R. Gadelha, MD, PhD; Murray B. Gordon, MD; Mirjana Doknic, MD, PhD; Emese Mezősi, MD, PhD, DSci; Miklós Tóth, MD, PhD, DSci; Cesar Boguszewski, MD, PhD; Christine T. Ferrara-Cook, MD, PhD; Alessandra Casagrande, MD, PhD; Alan Krasner, MD; et al.
Oral presentation: The Society for Endocrinology SfE BES, 2022

A Phase 2, Randomized, Parallel Group Study to Evaluate the Safety, Pharmacokinetics, and Dose Response of Paltusotine Treatment in Subjects with Carcinoid Syndrome.
Aman Chauhan, MD; Shagufta Shaheen, MD; Keith Usiskin, MD; et al.
Poster: North American Neuroendocrine Tumor Society (NANETS) meeting; 10/18/2022

Paltusotine Shows Long-term Safety and IGF-1 Maintenance in the ACROBAT Advance Study
Monica R. Gadelha, MD, PhD; Murray B. Gordon, MD; Mirjana Doknic, MD, PhD; et al.
Oral presentation: Brazilian Congress of Endocrinology and Metabolism (CBEM); 9/7/2022

ACROBAT Advance: Long-term Safety and Efficacy Results of Paltusotine for the Treatment of Acromegaly.
Harpal Randeva, PhD; Monica R. Gadelha, MD, PhD; Murray B. Gordon, MD; et al.
Poster: Society for Endocrinology Annual SfE BES; 11/10/2021

ACROBAT Edge Phase 2 Study: Safety and Efficacy of Switching Injected Long-Acting Somatostatin Receptor Ligands (SRLs) to Once-Daily Oral Paltusotine
Monica R. Gadelha, MD, PhD; Murray B. Gordon, MD; Mirjana Doknic, MD, PhD; et al.
Poster: Annual Meeting of the Endocrine Society (ENDO); 3/23/2021

Phase 1 and Discovery


Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Oral Paltusotine, a Non-Peptide, Selective Somatostatin Receptor Subtype 2 Agonist
Rosa Luo, MS; Alessandra Casagrande, MD, PhD; Sonic Oun, BA; et al.
Poster: Annual Meeting of the Endocrine Society (ENDO); 6/17/2023

Discovery of Paltusotine (CRN00808), a Potent, Selective, and Orally Bioavailable Non-peptide SST2 Agonist
Jian Zhao, PhD; Shimiao Wang; Stacy Markison; et al.
Article: ACS Medicinal Chemistry Letters Article ASAP (2022)

Paltusotine, a Novel Oral Once Daily Nonpeptide SST2 Receptor Agonist, Suppresses GH and IGF1 in Healthy Volunteers.
Ajay Madan, PhD; Stacy Markison, Stephen F. Betz, PhD; et al.
Article: Pituitary 25, 328–339 (2022)

Pharmacokinetics and Safety of an Improved Formulation of Paltusotine, a Selective, Nonpeptide Somatostatin Receptor 2 (SST2) Agonist for the Treatment of Acromegaly.
Rosa Luo; Gerald Burk; Cosina Mui; et al.
Poster: Annual Meeting of the Endocrine Society (ENDO); 3/23/2021

Absolute Oral Bioavailability and Absorption, Metabolism, Excretion of [14C]-Labeled Paltusotine (CRN00808), an Orally Bioavailable, Nonpeptide, Selective, Somatostatin Receptor 2 (SST2) Biased Agonist for the Treatment of Acromegaly.
Ajay Madan, PhD; Rosa Luo; Christine Ferrara-Cook, MD, MhD; et al.
Poster: European Congress of Endocrinology (ECE); 9/9/2020

Final Results from the First in Man Phase 1 Clinical Trial of CRN00808, an Orally Bioavailable SST2-Selective, Nonpeptide Somatostatin Biased Agonist for the Treatment of Acromegaly: Safety, Pharmacokinetics, Pharmacodynamics, and Midazolam Drug Interaction in Healthy Volunteers.
Ajay Madan, PhD; Yun Fei Zhu, PhD; Stacy Markison; et al.
Poster: Annual Meeting of the Endocrine Society (ENDO); 3/29/2019