Timber Pharmaceuticals, Inc. presents preliminary results from the ASCEND trial in a late-breaking session at the 2024 American Academy of Dermatology (AAD) Annual Meeting. The results offer a first look at the safety, efficacy and pharmacokinetic (PK) data from 17 adult and adolescent participants (aged 12-64 years) enrolled in the open-label maximum use arm of the phase 3 ASCEND trial. These late-breaker results are part of a wide-ranging data program from LEO Pharma at AAD, with eight abstracts accepted in total for the meeting, showcasing an ongoing commitment to advancing the standard of research in medical dermatology.

ASCEND is a clinical trial of TMB-001, a polyethylene glycol (iPEG) based investigational topical isotretinoin being developed for the treatment of moderate-to-severe X-linked and autosomal recessive congenital ichthyosis (CI). CI is a group of rare genetic keratinization disorders that leads to dry, thickened, and scaling skin. Currently, no specific treatments are approved by the U.S. Food and Drug Administration (FDA) to treat CI.

Patients enrolled in the open-label maximum use arm of the ASCEND trial with 75-90% body surface area involvement and moderate-to-severe disease on the Investigator Global Assessment (IGA) scale (IGA scores =3) were included in this analysis. TMB-001 results showed that, from baseline to Week 12, the mean total Investigator Global Assessment (IGA) composite scaling and fissuring score decreased from 3.2 to 1.6 (p=0.0001). In the same timeframe, 59% of patients achieved a =2 point decrease in IGA scores from baseline, while 82% demonstrated a clinically significant (=1 point) improvement in IGA scores from baseline.

No serious adverse events (SAEs) were reported.1 65% of participants experienced at least 1 adverse event (AE), with a total of 35 events. The top three treatment-emergent AEs were erythema (N=7), pruritus (N=4), and stinging/pain (N=2). The results were taken from participants in the open-label maximal use arm of the ASCEND trial.

This arm aimed to analyze the PKs of TMB-001 by determining the level of systemic exposure of isotretinoin and metabolites. To do this, the change from baseline of isotretinoin (ISO), 4-oxo-isotretinoin (4-O-ISO), tretinoin (TR), and 4-oxo-tretinoin (4-O-TR) after 14 days of twice-daily application of TMB-001 was assessed. The data demonstrated low systemic concentrations across all four molecules examined after 14 days of twice-daily application of TMB-001.

The steady-state mean peak plasma concentrations (ng/mL) in the 17 participants were 4.5 for ISO, 9.0 for 4-O-ISO, and low to not calculable for TR and 4-O-TR. In January 2024, LEO Pharma finalized the acquisition of Timber Pharmaceuticals, a clinical-stage biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases. Upon completion, the Timber Pharmaceuticals lead investigational product candidate, TMB-001, was added to LEO Pharma?s pipeline.

TMB-001 is under investigation and has not been evaluated by any health authority. An ongoing, multicenter phase 3 study to evaluate the efficacy and safety of TMB-001 0.05% topical ointment in the treatment of congenital ichthyosis (CI) in subjects (aged =6 years) with either the autosomal recessive congenital ichthyosis (ARCI) or X-linked recessive ichthyosis (XLRI) subtypes. The clinical trial is divided into two parts.

The first is a randomized, double-blind, vehicle-controlled phase III study. Its objective is to ascertain the efficacy of TMB-001 0.05% topical ointment as a treatment for CI compared with vehicle during 12 weeks of treatment. In the second part of the trial, a subset of preselected centers will recruit subjects in parallel with either the ARCI or XLRI subtypes for enrollment into an Optional Maximal Use arm.

The primary objective of this part of the trial is to determine systemic exposure of isotretinoin and metabolites after single or multiple applications of TMB-001 0.005% ointment. Its primary endpoint is an assessment of individual concentrations of 4-oxo-isotretinoin (4-O-ISO), tretinoin (TR), 4-oxo-tretinoin (4-O-TR) and change from baseline. TMB-001, topical isotretinoin in the company?s investigational patented polyethylene glycol (IPEG?) delivery system, is being developed for the treatment of moderate-to-severe subtypes of congenital ichthyosis (CI).

During Fourth Quarter 2021, the positive topline results for its Phase 2b CONTROL Study were announced. In First Quarter 2022, TMB-001 received both Breakthrough Therapy Designation and Fast Track Status from the U.S. Food and Drug Administration (FDA). The Phase 3 ASCEND clinical trial was initiated in Second Quarter 2022.