• The late-breaking session at the American Academy of Dermatology (AAD) Annual Meeting offers a first look at 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.¹
• Preliminary findings were positive for TMB-001, an investigational treatment of moderate-to-severe X-linked and autosomal recessive congenital ichthyosis (CI).¹
• Results demonstrated minimal systemic absorption of isotretinoin and its metabolites.¹
• Currently, no specific treatments are approved by the U.S. Food and Drug Administration (FDA) to treat CI, highlighting the critical unmet need for those living with CI.²

NOT FOR UK USE – NOT INTENDED FOR UK MEDIA

Timber Pharmaceuticals, Inc., a LEO Pharma company, today presents preliminary results from the ASCEND trial in a late-breaking session at the 2024 American Academy of Dermatology (AAD) Annual Meeting.¹ 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.¹

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).³ CI is a group of rare genetic keratinization disorders that leads to dry, thickened, and scaling skin.^4-7 Currently, no specific treatments are approved by the U.S. Food and Drug Administration (FDA) to treat CI.²

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.¹

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.¹

No serious adverse events (SAEs) were reported.¹ 65% of participants experienced at least 1 adverse event (AE), with a total of 35 events.¹ The top three treatment-emergent AEs were erythema (N=7), pruritus (N=4), and stinging/pain (N=2).¹

“The preliminary findings from the ASCEND trial are encouraging and indicate the potential of TMB-001 to provide hope for those living with X-linked and autosomal recessive CI,” said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. “We know that the management of this disease can be incredibly challenging and, given the limited treatment options available, we remain focused on pushing the development of TMB-001 forward with the goal of helping to address this considerable unmet need.”

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.¹ 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.¹

The data demonstrated low systemic concentrations across all four molecules examined after 14 days of twice-daily application of TMB-001.¹ 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.¹

“X-linked and autosomal recessive CI can be incredibly challenging to live with, and in my experience patients are often impacted both psychically and psychologically by a host of symptoms,” said Dr. Christopher Bunick, Lead Author and Associate Professor of Dermatology, Yale School of Medicine. “With no specific treatment currently available, CI patients are currently having to deal with their condition with minimal support. I hope that the data and insights presented today can help provide new knowledge and support for this patient community.”

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.

About the ASCEND Trial

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.³

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.³

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.³

About Congenital Ichthyosis

Congenital ichthyosis (CI) is a group of rare genetic keratinization disorders that can lead to dry, thickened, and scaling skin.^4-7

Most cases of ichthyosis are inherited, but some types develop in association with genetic syndromes or diseases, such as Hodgkin's Lymphoma.^8,9

People living with CI may have limited range of motion, chronic itching, an inability to sweat normally, high risk of secondary infections, and impaired eyesight or hearing.^4-7

About TMB-001

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 Q4 2021, the positive topline results for its Phase 2b CONTROL Study were announced. In Q1 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 Q2 2022.

About LEO Pharma

LEO Pharma is a global company dedicated to advancing the standard of care for the benefit of people with skin conditions, their families and society. Founded in 1908 and majority owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, and today, the company offers a wide range of therapies for all disease severities. LEO Pharma is headquartered in Denmark with a global team of 4,400 people, serving millions of patients across the world. In 2022, the company generated net sales of DKK 10.6 billion.

References

1. Bunick CG, et al. Efficacy, Safety and Pharmacokinetics of First 17 Adult and Adolescent Subjects in Maximal Use Portion of Vehicle Controlled ASCEND Trial of Polyethylene Glycol (iPEG™)-Based Topical Isotretinoin 0.05% (TMB-001) for Treatment of Congenital Ichthyosis. Presented at American Academy of Dermatology (AAD) 2024 Annual Meeting, San Diego, Ca., March 8-12, 2024.
2. Hernández-Martin A, Aranegui B, Martin-Santiago A, Garcia-Doval I. A systematic review of clinical trials of treatments for the congenital ichthyoses, excluding ichthyosis vulgaris. J Am Acad Dermatol. 2013;69(4):544-549.e8.
3. ClinicalTrials.gov. National Library of Medicine (U.S.). The ASCEND Study: Evaluating TMB-001 in the Treatment of RXLI or ARCI Ichthyosis (ASCEND). Identifier: NCT05295732. https://classic.clinicaltrials.gov/ct2/show/NCT05295732
4. Oji V, Traupe H. Ichthyosis: clinical manifestations and practical treatment options. Am J Clin Dermatol. 2009;10(6):351-364.
5. Takeichi T, Akiyama M. Inherited ichthyosis: Non-syndromic forms. J Dermatol. 2016;43(3):242-251.
6. Vahlquist A, Gånemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol. 2008;88(1):4-14.
7. Lilly E, Bunick CG. Congenital Ichthyosis: A Practical Clinical Guide on Current Treatments and Future Perspectives. Clin Cosmet Investig Dermatol. 2023;16:2473-2479.
8. Haber R, Feghali J, Nadir U, Yi MD, Cahn BA. Acquired ichthyosis: a clinical review. Arch Dermatol Res. 2023;315(9):2529-2543.
9. Mishra K, Jandial A, Gupta K, Prakash G, Malhotra P. Ichthyosis: A Harbinger of Lymphoma. BMJ Case Rep. 2018;2018:bcr2018224229.

MAT-71602 March 2024

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