octreotide intranasal (DP1038) / Dauntless Pharma - LARVOL DELTA

Dauntless-1: A Phase 2 Clinical Trial to Evaluate PMD-026, a First-in-Class Pan-RSK Inhibitor, Combined with Fulvestrant to Overcome Resistance to CDK4/6 Inhibitors in Advanced or Metastatic HR+/HER2- Breast Cancer (SABCS 2025) - P1/2 | "In addition, PMD-026 inhibits the nuclear translocation of RSK2 (with no change to levels of nuclear ERα), reduces ERα transcription as a single agent equal to or better than fulvestrant or elacestrant, and synergizes with fulvestrant, oral selective estrogen receptor degraders (SERDs) or vepdegestrant to substantially inhibit tumor growth in CDK4/6i sensitive and resistant models. RSK2 is highly expressed in most front-line mBC patients receiving CDK4/6i + ET therapy. PMD-026 inhibits ER signalling and is highly synergistic with fulvestrant in preclinical studies, the translation of which into potentially meaningful clinical benefit is being explored in the Dauntless-1 study."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • RPS6KA3 • TP53

Dauntless-1, a phase 2 clinical trial to evaluate PMD-026, a first-in-class pan-RSK inhibitor, combined with fulvestrant to overcome resistance to CDK4/6 inhibitors in advanced or metastatic HR+/HER2- breast cancer. (ASCO 2025) - P1/2 | "Inhibiting RSK with PMD-026, a first-in-class oral small molecule inhibitor, halts G2/M progression and blocks growth in CDK4/6i-resistant models, including those cross-resistant to abemaciclib and palbociclib. Secondary objectives include duration of response, overall response and overall survival. Exploratory objectives will evaluate PMD-026 in the context of mutations (ESR1, PIK3CA, AKT1, p53, KRAS) at baseline using ctDNA."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • KRAS • PIK3CA • RPS6KA3

PMD-026, a First-in-Class RSK Inhibitor, Overcomes Acquired Resistance to CDK4/6 Inhibitors or Aromatase Inhibitors in HR+/HER2- Breast Cancer Preclinical Models (SABCS 2024) - P1/2 | "Its emerging role in resistance is underscored by a study showing that RSK2 is the most highly induced protein in the MAPK pathway following the development of acquired resistance to the aromatase inhibitor letrozole. The synergistic effect observed with PMD-026 and fulvestrant supports Dauntless-1, our newly launched Phase 2 clinical trial (NCT04115306) for second-line patients with RSK2+ tumors. This trial is for patients who have progressed on one prior line of CDK4/6i and aromatase inhibitors."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • ER • HER-2 • PIK3CA • RPS6KA3 • RPS6KA6 • YBX1

Investigational drugs for the Treatment of Acromegaly: new agents to transform therapy. (PubMed, Expert Opin Investig Drugs) - "The aim of current review is to provide a detailed update about investigational drugs for acromegaly treatment currently under investigation as paltusotine, ONO-5788, AP102, GT-02037, ISIS 766,720, CAM2024, Lanreotide PRF, DP1038, MTD201, solid dose injection of octreotide. Current studies are addressing patient's needing for both new molecules and less invasive routes of administration for already existing drugs. It cannot be ruled out that drugs currently used for other disease such as cancers could be considered in the future for the treatment of acromegaly."

Journal • Review • Acromegaly • Endocrine Disorders • Oncology

Enhancement of the solubility of recombinant proteins by fusion with a short-disordered peptide. (PubMed, J Microbiol) - "In this study, we identified two highly disordered short peptides that were able to increase the solubility of an artificially engineered aggregation-prone protein, GFP-GFIL4, from 0.6% to 61% (D3-DP00592) and 46% (D4-DP01038) selected from DisProt database...Despite the small size, the highly disordered peptides were able to solubilize recombinant proteins as efficiently as conventional fusion tags and did not interfere with the function of recombinant proteins. Consequently, the identified two highly disordered peptides would have practical utility in protein biotechnology and industry."

Journal

"@US_FDA grants orphan drug designation to Dauntless Pharmaceuticals's DP1038, the company's investigational new drug, octreotide acetate for intranasal administration, for the treatment of acromegaly" (@NewAdisInsight)

IND • Orphan drug [duplicate] • Biosimilar