Discovery Pre-Clinical Phase 1 Phase 2 Phase 3

Paltusotine (formerly CRN00808)


Paltusotine, our lead product candidate, establishes a new class of oral, selective, nonpeptide, somatostatin receptor type 2 (SST2) agonists designed for the treatment of acromegaly. Somatostatin is a neuropeptide hormone that broadly inhibits the secretion of other hormones, including growth hormone, or GH, from the pituitary gland. Acromegaly arises from a benign pituitary tumor that secretes excess GH that in turn causes excess secretion of insulin-like growth factor-1, or IGF-1, by the liver. This loss of homeostasis in the GH axis results in excess tissue growth and other adverse effects throughout the body.

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.

2021


Dose selection for paltusotine, a once-daily, oral, nonpeptide, somatostatin receptor 2 ligand (SST2), for the treatment of patients with carcinoid syndrome (CS)

Poster
NANETS 2021 Presentation

November 2021 – Interim results from the ACROBAT Advance open-label extension study showed that paltusotine lowered IGF 1 levels and maintained long term IGF-1 at levels previously achieved with injected SRLs, which was then stably maintained at prior treatment levels for up to 51 weeks. View the poster that was presented at the 2021 Society for Endocrinology BES meeting.

Initiated global Phase 3 PATHFNDR program in acromegaly patients.  Plan to initiate clinical trial in patients with NETs complicated by carcinoid syndrome.

October 2020


Late 2018


Initiated two global Phase 2 clinical trials of paltusotine in acromegaly patients: ACROBAT EVOLVE and ACROBAT EDGE. Both completed their recruitment phase and were conducted at the same centers in the U.S. and globally. Patients who completed either study were eligible to participate in an open-label extension study (ACROBAT ADVANCE).

EVOLVE: Double-blind, placebo-controlled, randomized withdrawal study to evaluate the safety, efficacy, and pharmacokinetics of paltusotine compared to placebo in subjects with acromegaly who respond to octreotide LAR or lanreotide depot monotherapy.

EDGE: Open-label exploratory study to evaluate the safety, efficacy, and pharmacokinetics of paltusotine in subjects with acromegaly treated with somatostatin analog-based treatment regimens but who do not respond completely to monotherapy.

August 2018


Submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA).

March 2018


Initial results reported from a Phase 1, double-blind, randomized, placebo-controlled, single- and multiple-ascending dose trial to evaluate the safety, pharmacokinetics, and pharmacodynamics of paltusotine in 99 healthy volunteers.

Paltusotine demonstrated POC by potently suppressing stimulated GH and baseline IGF-1 in these subjects. Plasma exposure of paltusotine indicated the drug was well-absorbed with a half-life of 42 to 50 hours, supporting once-daily administration in patients. The safety and tolerability of paltusotine observed in this trial was generally consistent with that of approved peptide somatostatin analogs.

Phase 2


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