Pipeline
| Discovery | IND-Enabling | Phase 1 | Phase 2 | Phase 3 | Approved |
|---|---|---|---|---|---|
Paltusotine (formerly CRN00808)
Paltusotine is the first once-daily, oral, selectively-targeted somatostatin receptor type 2 agonist in development for the proposed treatment of people with acromegaly.
TherapeuticAreas
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.
Our Research
PHASE 3
Monica R. Gadelha, MD, PhD; Alessandra Casagrande, MD, PhD; et al.
Poster Presentation: Congress of Endocrinology and Metabolism (ENDO); 6/3/2024
Monica R. Gadelha, MD, PhD; Harpal Randeva, MBChB, FRCP, FAcad TM, PhD; et al.
Poster Presentation: Congress of Endocrinology and Metabolism (ENDO); 6/3/2024
Beverly M.K. Biller, MD; Alessandra Casagrande, MD, PhD; et al.
Poster Presentation: Congress of Endocrinology and Metabolism (ENDO); 6/3/2024
PHASE 2
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
Harpal Randeva, PhD; Monica R. Gadelha, MD, PhD; Murray B. Gordon, MD; et al.
Poster: Society for Endocrinology Annual SfE BES; 11/10/2021
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
Aman Chauhan, MD; Shagufta Shaheen, MD; Keith Usiskin, MD; et al.
Poster: North American Neuroendocrine Tumor Society (NANETS) meeting; 10/18/2022
Our Research
Phase 3
CAREFNDR: a Phase 3, Randomized, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Paltusotine in Adults With Carcinoid Syndrome Due to Well-Differentiated Neuroendocrine Tumors
Richard Kim, MD; et al.
Poster Presentation: The 22nd Annual European Neuroendocrine Tumor Society Conference (ENETS), 3/5-7/2025
Efficacy and Safety of Once-Daily Oral Paltusotine in Medically Untreated Patients with Acromegaly: Results from the Phase 3, Randomized, Placebo-Controlled PATHFNDR-2 Study
Beverly M.K. Biller MD; et al.
Poster Presentation: The Annual Meeting of the Endocrine Society (ENDO), 6/03/2024
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
Phase 2
Once-Daily Oral Paltusotine in the Treatment of Patients With Carcinoid Syndrome: Safety and Exploratory Efficacy Results From a Phase 2, Randomized, Parallel-Group Study
Lukasz Hajac, MD, PhD; et al.
Poster Presentation: The European Neuroendocrine Tumor Society (ENETS) meeting; 3/5-7/2025
Long-Term Safety and Efficacy of Once-Daily Oral Paltusotine in the Treatment of Patients With Acromegaly: Update From ACROBAT Advance
Monica R. Gadelha, MD, PhD; et al.
Poster Presentation: The Annual Meeting of the Endocrine Society (ENDO); 6/03/2024
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: The 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