paltusotine (CRN00808) / Crinetics - LARVOL DELTA

CAREFNDR: Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen (clinicaltrials.gov) - P3 | N=141 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

New P3 trial • Carcinoid Syndrome • Carcinoid Tumor • Gastrointestinal Cancer • Liver Cancer • Neuroendocrine Tumor • Pancreatic Cancer • Small Intestinal Carcinoma • Solid Tumor

Once-daily Oral Paltusotine In The Treatment Of Patients With Biochemically Uncontrolled Acromegaly: Interim Results Of The PATHFNDR-2 Open-label Extension (ENDO 2025) - "In conclusion,IGF-I levels decreased rapidly in patients who had received placebo during theRC phase and patients with elevated IGF-I who were directly enrolled into theOLE, and the previously observed decrease was sustained in patients whocontinued on once-daily oral paltusotine. Paltusotine was well tolerated duringlong-term treatment."

Clinical • Late-breaking abstract • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • IGF1

Disease Control in Patients With Acromegaly Switching From Injected Somatostatin Receptor Ligands to Once-Daily Oral Paltusotine: Interim Results of the PATHFNDR-1 Open-Label Extension (ENDO 2025) - "PATHFNDR-1 was a randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of switching to paltusotine in patients whose acromegaly was controlled (IGF-I ≤1.0× ULN) with injected depot somatostatin receptor ligands (SRLs; octreotide LAR or lanreotide depot). In conclusion, once-daily oral paltusotine maintained biochemical and symptom control and was well tolerated during long-term treatment in patients with acromegaly who switched from injected SRLs. Support: Crinetics Pharmaceuticals"

Clinical • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • Fatigue • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Pain • IGF1 • SSTR

Effects of Paltusotine Treatment on Patient-Reported Symptoms of Acromegaly in Phase 3 Randomized Placebo-Controlled Studies (PATHFNDR-2 and PATHFNDR-1) (ENDO 2025) - "ECDFs also showed that in PF-2, greater percentages of patients treated with paltusotine – regardless of prior treatment history – experienced improvement or stability of acromegaly symptoms, as compared to patients on placebo.Treatment with oral paltusotine promotes improvement and/or stability of acromegaly symptoms relative to placebo, as measured by the ASD. These findings demonstrate the benefit of paltusotine in addressing core symptoms of acromegaly that are most relevant to patients, in addition to its GH and IGF-1 lowering effects."

Clinical • P3 data • Acromegaly • Endocrine Disorders • Fatigue • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Orthopedics • Pain • Rare Diseases • IGF1

Paltusotine Results in Improved Symptom Stability in Biochemically Controlled Acromegaly (ENDO 2025) - "We hypothesized that patients switched from injected long-acting octreotide or lanreotide (SRLs) to once-daily oral paltusotine would experience maintenance of biochemical and symptom severity control with reduced frequency of symptom exacerbations. A simple daily symptom-assessment tool provided important information pertaining to acromegaly disease control that was not apparent from IGF-I measurements. Support: Crinetics Pharmaceuticals"

Acromegaly • Endocrine Disorders • IGF1

Oral, Once-Daily Paltusotine in the Treatment of Acromegaly (ESPE-ESE 2025) - "Sponsored by Crinetics Pharmaceuticals sponsored Mini-satellite session."

Acromegaly • Endocrine Disorders

Advancing GPCR Science Toward Future Treatments in Acromegaly, Congenital Adrenal Hyperplasia, and ACTH-dependent Cushing’s Syndrome. A Crinetics Pharmaceuticals sponsored Mini-satellite session. (ESPE-ESE 2025) - "Funded by Crinetics Pharmaceuticals has developed a distinctive science platform centered around nonpeptide small molecules targeting G protein-coupled receptors (GPCRs) to address endocrine diseases and related tumors. This platform leverages Crinetics' deep expertise in cell receptor biology to create orally administered therapeutics with improved specificity and pharmacokinetics compared to traditional peptide-based drugs.Crinetics’ pipeline will be reviewed, and results from clinical studies of paltusotine (an investigational oral SST2 agonist for acromegaly and carcinoid syndrome) and atumelnant (an investigational oral MC2R/ACTH antagonist for ACTH-dependent Cushing’s Syndrome and Congenital Adrenal Hyperplasia) will be presented."

Acromegaly • Carcinoid Syndrome • Congenital Adrenal Hyperplasia • Cushing’s Disease • Endocrine Disorders • Oncology

Long-Term Safety and Efficacy of Once-Daily Oral Paltusotine in the Treatment of Patients With Acromegaly: ACROBAT Advance Year 4 Analysis (ESPE-ESE 2025) - "In Edge, at enrollment all patients were candidates for combination drug therapy: either sub-optimally controlled on an injected SRL (octreotide or lanreotide) alone or in combination with cabergoline, or required combination therapy or pasireotide to achieve normal IGF-I levels...Adjunctive treatment with cabergoline or pegvisomant was allowed in patients who did not attain normal IGF-I levels on the maximum dose of paltusotine... Long-term results (up to ~4 years) show that once-daily oral paltusotine treatment was well tolerated, with stable biochemical and symptom control relative to that observed with injected SRLs."

Clinical • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • Gastroenterology • IGF1

Crinetics Pharmaceuticals Announces European Medicines Agency (EMA) Validation of Marketing Authorization Application (MAA) and Orphan Drug Designation (ODD) for Paltusotine in Acromegaly (GlobeNewswire) - "Crinetics Pharmaceuticals...announced that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for paltusotine, the first once-daily, oral, selectively-targeted somatostatin receptor type 2 nonpeptide agonist, for the proposed treatment and long-term maintenance therapy of acromegaly, a serious, rare and progressive endocrine disorder characterized by consistently elevated levels of growth hormone. The MAA will now be reviewed by the Committee for Medicinal Products for Human Use (CHMP). Additionally, the EMA on February 27, 2025 granted paltusotine Orphan Drug Designation (ODD) for the treatment of acromegaly....The MAA submission is supported by data from 18 clinical trials, including two Phase 3 trials that evaluated paltusotine for the treatment of acromegaly in medically untreated and treated patients."

EMA filing • Orphan drug • Acromegaly

CAREFNDR: A phase III, randomised, parallel group, placebocontrolled study to evaluate the efficacy and safety of paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumours (ENETS 2025) - No abstract available

Clinical • P3 data • Carcinoid Syndrome • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Oral paltusotine, a nonpeptide selective somatostatin receptor 2 agonist: Mass balance, absolute bioavailability and metabolism in healthy participants. (PubMed, Br J Clin Pharmacol) - "Oral dosing with paltusotine is associated with efficient absorption from the gastrointestinal tract. Most of the administered dose is excreted unchanged. Pharmacokinetic properties of paltusotine are supportive of once-daily dosing."

Journal • Acromegaly • Carcinoid Syndrome • Endocrine Disorders • Gastrointestinal Disorder • SSTR • SSTR2

Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: Safety and exploratory efficacy results from a phase II, randomised, parallel-group study (ENETS 2025) - "No new safety signals were identified. CONCLUSION In this phase 2 study, treatment with once-daily, oral paltusotine reduced the frequency and severity of CS symptoms and was well tolerated, justifying further clinical development."

Clinical • P2 data • Carcinoid Syndrome • CNS Disorders • SSTR

Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: Safety and exploratory efficacy results from a phase 2, randomised, parallel-group study (ENETS 2025) - No abstract available

Clinical • P2 data • Carcinoid Syndrome

Crinetics Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Key Upcoming Milestones: FDA Prescription Drug User Fee Act (PDUFA) target action date of September 25, 2025 for paltusotine NDA for the treatment and maintenance therapy of acromegaly."

PDUFA • Acromegaly

Crinetics Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Key Upcoming Milestones: Enrollment of the first patient in the pivotal Phase 3 trial of paltusotine in carcinoid syndrome is anticipated in the second quarter of 2025."

New P3 trial • Carcinoid Syndrome

"Cold" Somatostatin Analogs in Neuroendocrine Neoplasms: Decoding Mechanisms, Overcoming Resistance, and Shaping the Future of Therapy. (PubMed, Cells) - "This paper provides a comprehensive analysis of the cellular and molecular mechanisms of SSAs. SSAs remain integral to the management of NENs, providing effective tumor stabilization and symptom control. However, resistance mechanisms and tumor heterogeneity necessitate innovative approaches, including high-dose regimens, combination strategies, and next-generation formulations. Future research should focus on refining these strategies to optimize patient outcomes, enhance long-term efficacy, and expand the therapeutic landscape for NENs."

Journal • Review • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

New treatments for acromegaly: Is a revolution underway? (PubMed, Ann Endocrinol (Paris)) - "We report results for new compounds that may be used in the near future as alternatives to first-generation somatostatin receptor ligands, with data on efficacy and tolerance: oral octreotide, paltusotine and long-acting subcutaneous octreotide are reviewed in detail, together with potential new compounds under investigation. We also discuss their potential role in the therapeutic armamentarium for acromegaly."

Journal • Acromegaly • Endocrine Disorders • SSTR

Are Oral Somatostatin Receptor Ligands Moving Closer to Becoming a Reality? (PubMed, Clin Endocrinol (Oxf)) - "The iSRLs require intramuscular or deep subcutaneous injection with a wide bore needle that can be complicated by injection site pain, erythema, subcutaneous nodule formation, and for most individuals require attendance with a healthcare professional every 28 days to safely administered the medication. Two oral SRL (oSRL) formulations, Oral Octreotide Capsules and Paltusotine have been developed with clinical studies showing them to have promise as a therapeutic alternative to iSRL."

Journal • Acromegaly • Dermatology • Endocrine Disorders • Pain • IGF1 • SSTR

Crinetics Announces FDA Acceptance of New Drug Application for Paltusotine for Adult Patients with Acromegaly (GlobeNewswire) - "FDA Assigns a Prescription Drug User Fee Act Target Action Date of September 25, 2025...Crinetics Pharmaceuticals, Inc...announced the U.S. Food and Drug Administration (FDA) accepted its New Drug Application (NDA) for investigational candidate paltusotine for the treatment and long-term maintenance therapy of acromegaly in adults....The NDA submission for once-daily, oral paltusotine included data from the PATHFNDR-1 (NCT04837040) and PATHFNDR-2 (NCT05192382) Phase 3 clinical trials..."

FDA filing • PDUFA • Acromegaly

Advances in the Oral Administration of Somatostatin Receptor Ligands in Acromegaly: A Systematic Review Focusing on Biochemical Response. (PubMed, Pharmaceutics) - "While long-term maintenance was confirmed for OOCs, no data are yet available for paltusotine. Several gaps remain, such as the need for head-to-head comparisons between OOCs and paltusotine, and clinical trials in patients who have not received prior injectable SRL treatment."

Journal • Review • Acromegaly • Endocrine Disorders • Gastrointestinal Disorder • SSTR

Paltusotine May Address Unmet Need in NETs Patients With Carcinoid Syndrome (Cancer Therapy Advisor) - "Paltusotine can alleviate symptoms of carcinoid syndrome in patients with neuroendocrine tumors (NETs), according to results of a phase 2 study presented at the 2024 NANETS Multidisciplinary NET Medical Symposium....These findings suggest that paltusotine may address unmet needs in patients with carcinoid syndrome, according to study presenter by Aman Chauhan, MD..."

Media quote

"Paltusotine and CRN09682: Novel NonPeptide Approaches to Treating Carcinoid Syndrome and Neuroendocrine Tumors" (NANETS 2024) - "sponsored by Crinetics."

Carcinoid Syndrome • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

Once-daily Oral Paltusotine in the Treatment of Patients With Carcinoid Syndrome: Results From a Phase 2, Randomized, Parallel-Group Study (NANETS 2024) - "No new safety signals were identified. CONCLUSIONS In this phase 2 study, treatment with once-daily, oral paltusotine reduced the frequency and severity of CS symptoms and was well tolerated, justifying further clinical development."

Clinical • P2 data • Acromegaly • Carcinoid Syndrome • CNS Disorders • Neuroendocrine Tumor • Pain • SSTR

UPDATE: Crinetics Pharmaceuticals to Showcase Pipeline Advancements with Neuroendocrine Tumor Candidates at The North American Neuroendocrine Tumor Society (NANETS) Annual Meeting (GlobeNewswire) - "Data for paltusotine and CRN09682, along with additional information on NDCs, will also be featured in a Crinetics-sponsored symposium titled 'Paltusotine and CRN09682: Novel Nonpeptide Approaches to Treating Carcinoid Syndrome and Neuroendocrine Tumors' at the conference...Dr. Aman Chauhan..."

Crinetics Pharmaceuticals to Showcase Pipeline Advancements with Neuroendocrine Tumor Candidates at The North American Neuroendocrine Tumor Society (NANETS) Annual Meeting (GlobeNewswire) - "Preclinical data to be presented at NANETS 2024 demonstrate the potent and selective anti-tumor activity of CRN09682, potentially providing a novel alternative for the treatment of NETs and other SST2-expressing tumors. Another abstract will be featured as both an oral and poster presentation, which includes follow-up from an open-label Phase 2 carcinoid syndrome study of investigational candidate paltusotine, a once-daily, oral, nonpeptide, selective SST2 agonist being developed for the treatment of acromegaly and carcinoid syndrome. The NANETS presentation includes findings from all 36 trial participants, with new analyses that show paltusotine reduced the frequency and severity of carcinoid syndrome symptoms and was well tolerated, justifying further clinical development."

P2 data • Preclinical • Carcinoid Syndrome • Neuroendocrine Tumor • Oncology • Solid Tumor