Minerval (idroxioleic acid) / Laminar Pharma - LARVOL DELTA

Laminar Pharma Announces first open-label Progression-Free Survival data for LAM561 in combination with standard of Care in First-Line Therapy for Newly Diagnosed Glioblastoma MGMT-methylated patients (PRNewswire) - P2/3 | N=140 | CLINGLIO (NCT04250922) | Sponsor: Laminar Pharmaceuticals | "Laminar Pharma...announced today optimistic results from its ongoing clinical trial evaluating LAM561 for the treatment of newly diagnosed glioblastoma (ndGBM)...The trial, partially funded with an EU H2020 Grant (ClinGlio), has shown an improvement trend in progression-free survival (PFS) in MGMT-methylated patients receiving LAM561 in combination with chemoradiotherapy (radiotherapy plus temozolomide) as the standard of care (SoC) compared to placebo plus SoC treatment...MGMT-methylated patients treated with LAM561 and SoC currently show a trend towards longer progression-free survival (86,4 weeks) compared to placebo control SoC group (54,7 weeks, HR 0.53). The study will continue until 90 OS events when final analysis will be conducted, estimated by late 2026....Safety data showed that the treatment was well-tolerated, with adverse events consistent with previous trials and a well-known safety profile."

P2/3 data • Glioblastoma

Targeting the Notch-Furin axis with 2-hydroxyoleic acid: a key mechanism in glioblastoma therapy. (PubMed, Cell Oncol (Dordr)) - "These findings report that the inhibition of Notch signaling by 2OHOA plays a role in its anti-tumoral activity, an effect that may be driven through direct inhibition of furin, characterizing a novel target of this bioactive lipid to treat GBM."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • HES1 • NOTCH2 • NOTCH3

Last patient in: Laminar Pharmaceuticals S.A. completes recruitment for CLINGLIO, the phase 2b/3 Clinical Trial of idroxioleic acid (LAM561) in combination with RT and TMZ for adults with newly diagnosed glioblastoma (PRNewswire-Asia) - "Laminar Pharmaceuticals...is pleased to announce the recruitment of patients for the CLINGLIO (NCT04250922) study has been closed after 140 adult patients have been successfully enrolled. The CLINGLIO study is a multinational, phase 2b/3, randomized, placebo-controlled, double-blind clinical trial evaluating idroxioleic acid in combination with Standard of Care (combined tumour resection and chemoradiotherapy) for the treatment of newly diagnosed glioblastoma patients....'The trial is expected to reach the trigger event for interim analysis in July 2024, which would provide an unblinded readout the last quarter of this year'....These unblinded results will be submitted for EMA evaluation for Conditional Marketing Authorization in early 2025, and the trial will continue until final analysis of survival in 2026."

EMA filing • Enrollment closed • P2/3 data • Glioblastoma

CLINGLIO: LAM561 With RT and TMZ for Adults With Glioblastoma (clinicaltrials.gov) - P2/3 | N=140 | Active, not recruiting | Sponsor: Laminar Pharmaceuticals | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • MGMT

Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: Laminar Pharmaceuticals | N=18 ➔ 28 | Trial completion date: Nov 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Jun 2025

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Pediatrics • Solid Tumor

Incorporation of the antitumor compound 2OHOA and its metabolite into cell membranes (AACR 2024) - P1/2, P2/3 | "In conclusion, 2OHOA shows a different incorporation into cell membranes between tumor cells and non-tumor cells. Moreover, both 2OHOA and its metabolite C17:1n-9 have an antiproliferative effect and exhibit an appealing potential in the treatment of patients that develop GBM with unmet effective therapy."

Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

2OHOA-mediated furin inhibition: Disrupting Notch via processing, transcription, and ADAM downregulation (AACR 2024) - "In addition, considering the levels of Notch intracellular domain (NICD) obtained inJagged1 assays in conjunction with 2OHOA, we evaluated the second cleavage of the Notchprocessing, being also downregulated, as ADAM10 constitutes a furin substrate.Conclusions These findings elucidate that the antitumoral activity of 2OHOA involves theinhibition of Notch signaling, potentially driven by the direct inhibition of furin. This reveals anovel molecular target for this bioactive lipid in the therapeutic approach to treating GBM."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • ADAM10 • HES1 • NICD • NOTCH2 • NOTCH3

CLINGLIO: LAM561 With RT and TMZ for Adults With Glioblastoma (clinicaltrials.gov) - P2/3 | N=140 | Recruiting | Sponsor: Laminar Pharmaceuticals | Trial primary completion date: Feb 2024 ➔ Oct 2024

Combination therapy • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • MGMT

Laminar Pharmaceuticals S.A. receives recommendation from the Independent Data Monitoring Committee to advance to the next stage of CLINGLIO, the phase 2b/3 Clinical Trial of LAM561 in combination with RT and TMZ for adults with newly diagnosed glioblastoma (PRNewswire) - "Laminar Pharmaceuticals...is pleased to announce that the Independent Data Monitoring Committee (IDMC) after evaluating the interim clinical results of the CLINGLIO clinical trial, has recommended that the trial should 'continue without modifications'....CLINGLIO remains on track to have its open readout at 66 progression events, expected in summer 2024.....The CLINGLIO trial is considered pivotal in that results showing significant clinical benefit could be sufficient for a request for conditional marketing authorization in the EU late this year; and potential full marketing authorization in 2025, for which enabling pre-submission interactions with the EMA have been initiated."

DSMB • European regulatory • P2/3 data • Glioblastoma

Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Laminar Pharmaceuticals | Trial completion date: Jun 2024 ➔ Nov 2024 | Trial primary completion date: Jun 2024 ➔ Sep 2024

Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Pediatrics • Solid Tumor

Study of LAM561 Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Laminar Pharmaceuticals | Trial completion date: Mar 2023 ➔ Jun 2024 | Trial primary completion date: Mar 2023 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Pediatrics • Solid Tumor

A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma. (PubMed, Br J Cancer) - P1/2 | "2-OHOA demonstrated a good safety profile and encouraging activity in this difficult-to-treat malignant brain-tumour patient population, placing it as an ideal potential candidate for the treatment of glioma and other solid tumour malignancies."

Journal • P1/2 data • Brain Cancer • CNS Tumor • Gastrointestinal Disorder • Glioma • Oncology • Solid Tumor

Furin and Notch signaling pathway as part of the 2OHOA landscape against glioblastoma (AACR 2023) - "Finally, 2OHOA downregulated furin-like proteases activity by physical association, an enzyme responsible for the Notch processing first step. All together reveals that the inhibition of Notch pathway by 2OHOA plays a role in its antitumoral effect, and this event is unleashed by the direct furin enzyme inhibition, identifying it as a novel target for this drug in the GBM and other pathologies treatment."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • HES1 • NICD • NOTCH1 • NOTCH3

Study of 2-hydroxyoleic Acid in Pediatric Patients With Malignant Glioma and Other Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: Laminar Pharmaceuticals | Trial completion date: Mar 2022 ➔ Mar 2023 | Trial primary completion date: Mar 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Brain Cancer • Glioma • Oncology • Pediatrics • Solid Tumor

CLINGLIO: 2-OHOA With RT and TMZ for Adults With Glioblastoma (clinicaltrials.gov) - P2/3 | N=140 | Recruiting | Sponsor: Laminar Pharmaceuticals | Trial completion date: Oct 2023 ➔ May 2025 | Trial primary completion date: Apr 2022 ➔ Feb 2024

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IDH1 • MGMT

Anti-Tumorigenic Effect of a Novel Derivative of 2-Hydroxyoleic Acid and the Endocannabinoid Anandamide on Neuroblastoma Cells. (PubMed, Biomedicines) - "Finally, we observed that combined treatment of HU-585 with the senolytic drugs ABT-263 in vitro, and ABT-737 in vivo resulted in enhanced anti-proliferative effects and reduced neuroblastoma xenograft growth in comparison to treatment with HU-585 alone. Based on these results, we suggest that HU-585 is a pro-apoptotic and senescence-inducing compound, better than HU-600. Hence, it may be a beneficial option for the treatment of resistant neuroblastoma especially when combined with senolytic drugs that enhance its anti-tumorigenic effects."

Journal • Neuroblastoma • Oncology • Solid Tumor • CASP3

Multifaceted Analyses of Isolated Mitochondria Establish the Anticancer Drug 2-Hydroxyoleic Acid as an Inhibitor of Substrate Oxidation and an Activator of Complex IV-Dependent State 3 Respiration. (PubMed, Cells) - "This increased respiration probably allows mitochondrial oxidative phosphorylation to maintain ATP production against the 2OHOA-mediated inhibition of glycolytic ATP production. This work correlates 2OHOA function with its modulation of mitochondrial lipid composition, reflecting both 2OHOA anticancer activity and adaptation to it by enhancement of state 3 respiration."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

[VIRTUAL] Safety of idroxioleic acid in combination with standard of care (temozolomide and/or radiation therapy) in newly diagnosed glioblastoma patients: A phase Ib trial (ESMO 2021) - P1b | "Addition of 12 g daily of 2-OHOA to standard of care (RT/TMZ) in newly diagnosed GBM patients was generally well tolerated, offered a favourable safety profile (no 2-OHOA-related serious or high-grade AEs), and it is the recommended dose of 2-OHOA for phase III trials."

Clinical • Combination therapy • P1 data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

CLINGLIO: 2-OHOA With RT and TMZ for Adults With Glioblastoma (clinicaltrials.gov) - P2/3; N=180; Recruiting; Sponsor: Laminar Pharmaceuticals; Active, not recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IDH1 • MGMT

A Study to Evaluate the Safety of 2-OHOA Added to Standard of Care in Newly-diagnosed Glioblastoma Patients (clinicaltrials.gov) - P1b; N=18; Completed; Sponsor: Laminar Pharmaceuticals; Recruiting ➔ Completed; N=12 ➔ 18

Clinical • Combination therapy • Enrollment change • Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor