ALM201 / Almac Discovery, Shin Poong Pharma - LARVOL DELTA

FKBPL: A Novel Regulator of NF-κB Signalling in Obesity-associated Breast Cancer (EACR-AACR 2024) - "Specifically, FKBPL-based preclinical and clinical peptides (AD-01 and ALM201) are effective in reducing p65 phosphorylation and cytokine mRNA expression and secretion in bone-marrow derived macrophages ex vivo along with preventing LPS induced lethality in vivo (4)...Overexpression of FKBPL in MDA-231 and MCF-7 cells did not alter expression of NF-kB gene targets, however 100 nM AD-01 treatment potentially reduced mRNA levels of TNF (p ≤ 0.05, n = 2) and IL-6 (p ≤ 0.05, n = 2). Conclusion In conclusion, FKBPL may be a crucial regulator of TNFα induced NF-κB transcriptional activity in obesity associated TNBC."

Breast Cancer • Genetic Disorders • Obesity • Oncology • Solid Tumor • Triple Negative Breast Cancer • FKBP5 • IL6 • TNFA • VCAM1

Quest for clues: early insights into the complex association of FKBPL in obesity-induced oesophageal adenocarcinoma (EACR-AACR 2024) - "A peptide based on the antiangiogenic domain of FKBPL, called ALM201, demonstrated an excellent safety profile in a human Phase 1a "first in man" clinical trial and it obtained FDA orphan drug approval in ovarian cancer...Conclusion To conclude, a deficiency in FKBPL is associated with the development of obesity. Moreover, this preliminary investigation suggests that a deficiency in FKBPL in adipose tissue from Fkbpl +/- mice results in enhanced clonogenicity in a BO cells and suggests a link to disease progression from BO to OAC that warrants further investigation."

Barrett Esophagus • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Genetic Disorders • Obesity • Oncology • Ovarian Cancer • Solid Tumor

Pre-clinical assessment of nanoparticle-mediated FKBPL gene therapy for High Grade Serous Ovarian Cancer (HGSOC) (EACR-AACR 2024) - "A peptide fragment of FKBPL (ALM201) showed potent anti-angiogenic and anti-stemness properties in HGSOC...Preliminary in vivo data supports in vitro data with lower metastatic spread the diaphragm of the animals receiving pFKBPL NPs. Ex vivo analysis will determine the impact on angiogenesis, cellular and acellular components of ascites."

Gene therapy • Preclinical • Gene Therapies • Gynecologic Cancers • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRCA2 • TP53

Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders. (PubMed, Ophthalmol Sci) - "Furthermore, topical ALM201 significantly improved vessel leakiness (leakage scores: 2.1 ± 0.7 vs. 2.9 ± 0.1; P = 0.0274) and lesion size (144,729 ± 33,239 μm vs. 187,923 ± 28,575 μm; P = 0.03) in the rat laser CNV model when compared with topical PBS vehicle. ALM201 is a promising novel molecule with anti-inflammatory and antivascularization activity and is a strong candidate to meet the clinical need of a new, topically delivered therapeutic agent for treating inflammation and pathologic vascularization in the anterior and posterior segments of the eye."

Journal • Age-related Macular Degeneration • Immunology • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

A first-in-human Phase I dose-escalation trial of the novel therapeutic peptide, ALM201, demonstrates a favourable safety profile in unselected patients with ovarian cancer and other advanced solid tumours. (PubMed, Br J Cancer) - "Doses up to 300 mg of ALM201 subcutaneously are feasible and well-tolerated. Further investigation of this agent in selected tumour types/settings would benefit from patient-selection biomarkers."

Journal • P1 data • Cardiovascular • Fatigue • Hematological Disorders • Musculoskeletal Pain • Oncology • Ovarian Cancer • Pain • Solid Tumor • Thrombosis

FKBPL as a novel therapeutic target and prognostic biomarker in high grade serous ovarian cancer (AACR 2018) - "ALM201, a peptide fragment of FKBPL, has potent anti-CSC and anti-angiogenic activity in an HGSOC xenograft which is dependent on angiogenesis for growth; an important finding for the clinical development of ALM201. Our data also strongly suggest that FKBPL is a potential novel prognostic biomarker in HGSOC, supporting its endogenous anti-tumor activity."

Biomarker • Ovarian Cancer

FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer. (PubMed, Br J Cancer) - "FKBPL-based therapy can (i) dually target angiogenesis and CSCs, (ii) target the CD44/STAT3 pathway in tumours and (iii) is effective in highly vascularised HGSOC tumours with low levels of IL-6."

Cancer stem cells • Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4. (PubMed, BMC Cancer) - "This study demonstrates, for the first time, the pre-clinical activity of novel systemic anti-cancer therapeutic peptides, ALM201 and AD-01, in the metastatic setting, and highlights their impact on endocrine therapy resistant CSCs; both areas of unmet clinical need."

Cancer stem cells • Journal