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Timber Pharmaceuticals’ late-stage study of TMB-001 in patients with moderate-to-severe congenital ichthyosis failed to meet its primary and key secondary endpoints, dealing a blow to parent company LEO Pharma.TMB-001 is an investigational topical ointment formulation of isotretinoin, which LEO gained earlier this year via its acquisition of assets from Timber after its chapter 11 bankruptcy filing. Following the deal, Timber was reformed as a fully owned subsidiary of LEO.Higher vehicle responseThe Phase III ASCEND trial evaluated TMB-001 in around 200 patients aged 6 years or older with either the autosomal recessive congenital ichthyosis (ARCI) or X-linked recessive ichthyosis (XLRI) subtypes. Timber noted that the study did not show a statistically significant difference between the proportion of patients treated with TMB-001 responding to treatment after 12 weeks compared with those treated with vehicle.John Koconis, CEO of Timber, remarked “we are disappointed and saddened by the results,” explaining that “after encouraging Phase IIb results, we observed an unexpectedly high vehicle response in [the ASCEND] trial.” The company added that the majority of adverse events observed in the study were non-serious localised skin reactions of mild or moderate severity.

There is currently no treatment approved for ichthyosis by the FDA. Image credit: Shutterstock / JHVEPhoto. A year after hedging its bets on Timber Pharmaceuticals’ dermatology pipeline, Leo Pharma has reported a Phase III failure for the lead asset it acquired at the time. TMB-001, a topical ointment formulation of isotretinoin, came up short in the late-stage trial for patients with moderate to severe congenital ichthyosis. Ichthyosis is an umbrella term for congenital skin conditions that cause dry and scaly skin. In the Phase III ASCEND trial (NCT05295732), Leo stated the therapy did not demonstrate a statistically significant improvement in patients compared to those treated with a vehicle. This meant the primary and key secondary endpoints were not met. The results do not support US regulatory submission, the Danish privately owned company stated in a 21 August press release. There is currently no treatment approved for ichthyosis by the US Food and Drug Administration (FDA). Instead, the condition is managed by hydrating the skin with creams and lotions. See Also: A comprehensive guide to supply chain management for specialty drugs Codiak BioSciences gets grant for extracellular vesicles for disease treatment and prevention The ASCEND trial had a three-week induction, a nine-week treatment period, and – for eligible patients – a 12-week open-label maintenance regimen. A total of 209 patients aged six years and over were enrolled in the study. Timber’s CEO John Koconis said: “We are disappointed and saddened by the results of the Phase III trial. After encouraging phase 2b results, we observed an unexpectedly high vehicle response in this trial.” A previous Phase IIb trial evaluating the ointment achieved its primary endpoint of a 50% reduction in the Visual Index for Ichthyosis Severity scale score versus baseline. Leo Pharma spent $36m to acquire a bankrupt Timber in August 2023, including a $14m upfront payment.  At the time, Timber had received orphan, fast-track, and breakthrough designations from the FDA. Following the acquisition, the company became a fully owned subsidiary of Leo Pharma. Leo Pharma’s chief development officer Kreesten Meldgaard Madsen said the company remains committed to dermatologic diseases but added “as is the case for all pharmaceutical research, not all trials are successful”. Leo Pharma stated the trial results will not impact its 2024 financial results. The company had a regulatory win elsewhere in the dermatology space in June this year, when its single-dose autoinjector for atopic dermatitis Adbry (tralokinumab-ldrm) received FDA approval . Whilst the clinical journey of TMB-001 stutters, Timber also has TMB-003 (sitaxentan) – a topical ET-A receptor antagonist in preclinical testing for sclerotic skin diseases.

MADISON, N.J.--( BUSINESS WIRE )-- NOT FOR UK USE – NOT INTENDED FOR UK MEDIA Timber Pharmaceuticals Inc., a LEO Pharma company, today announced the results for the randomized, double-blind 12-week period of the ASCEND trial. The trial did not show a statistically significant difference between the proportion of patients treated with TMB-001 responding to treatment after 12 weeks compared with patients treated with vehicle. ASCEND is the phase 3 clinical trial of TMB-001, an investigational topical ointment formulation of isotretinoin for the potential treatment of patients with moderate to severe congenital ichthyosis. The trial evaluated the efficacy and safety of TMB-001 in the treatment of congenital ichthyosis in patients (aged 6 years or older) with either the autosomal recessive congenital ichthyosis (ARCI) or X-linked recessive ichthyosis (XLRI) subtypes. LEO Pharma acquired TMB-001 from Timber Pharmaceuticals in January 2024 following Timber’s Chapter 11 bankruptcy filing. Timber Pharmaceuticals was a clinical-stage biopharmaceutical rare disease dermatology company focused on the development of treatments for rare and orphan dermatologic diseases, and TMB-001 had received orphan, fast-track, and break-through designation by the FDA. As a consequence of the acquisition, Timber Pharmaceuticals was reformed as a fully owned subsidiary of LEO Pharma. “ There are currently no topical treatments specifically developed and approved for the treatment of congenital ichthyosis in the United States, making it a challenging disease to treat. We are disappointed and saddened by the results of the phase 3 trial. After encouraging phase 2b results, we observed an unexpectedly high vehicle response in this trial. We had hoped that TMB-001 could have been a new potential treatment to help children and adults suffering from moderate to severe congenital ichthyosis and to allow them to live a quality life they had previously not known,” said John Koconis, Chief Executive Officer of Timber Pharmaceuticals. Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma added: " LEO Pharma remains fully committed to innovative research in dermatologic diseases with a high unmet need as we strive to make a difference for people living with skin diseases and their families. This means investing in trials to explore potential new treatments that can address the high unmet need these people face every day. Unfortunately, as is the case for all pharmaceutical research, not all trials are successful.” The results of the analysis will not have material impact on the 2024 financial results for the LEO Pharma group. Detailed results from ASCEND are planned to be submitted for scientific publication at a later date. About ASCEND ASCEND is the pivotal phase 3 clinical trial of TMB-001, an investigational topical ointment formulation of isotretinoin for the potential treatment of patients with moderate to severe congenital ichthyosis. The trial program represents the first vehicle-controlled Phase 3 trial program of any topical retinoid in this condition. The phase 3 trial evaluated the efficacy and safety of TMB-001 in the treatment of congenital ichthyosis in patients aged ≥6 years with either the autosomal recessive congenital ichthyosis (ARCI) or X-linked recessive ichthyosis (XLRI) subtypes. For more information on the ASCEND trial (NCT05295732) go to clinicaltrials.gov . 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 4,200 people, serving millions of patients across the world. In 2023, the company generated net sales of DKK 11.4 billion. For more information, please visit www.leo-pharma.com .