Date: 09/14/2024

Dear FIRST community, As you have perhaps seen in the press release sent out on August 21, 2024, the results of the ASCEND phase 3 study of TMB-001 in congenital ichthyosis were unfortunately not what we were hoping for. The study did not show any benefit of applying TMB-001 instead of just plain ointment without the active ingredient in it. We are still investigating why it did not go as we had hoped, but wanted to share a short update on what we know at this point.

We, at Timber and LEO Pharma were very surprised and disappointed with these results because we had seen a difference between TMB-001 and the plain ointment in previous, smaller studies. The much larger ASCEND study was designed to show the size of the effect of TMB-001 in a larger number of people living with congenital ichthyosis.

In the first half of the ASCEND study treatment with TMB-001 was compared with treatment with plain ointment, and this is the part that would have formed the basis for a submission to the FDA. Although many patients showed improvement as per the physician’s assessment in this part of the study, the percentage of patients improving when treated with the plain ointment was not different from the percentage improving when treated with TMB-001.

Since it did not matter whether patients were treated with the plain ointment or TMB-001, there will unfortunately not be a submission to the FDA.

The second half of the ASCEND study was designed to look at whether it would be better to apply TMB--001 once or twice per day. Treatment with TMB-001 in this part of the study is over for all patients in North America, but in Europe, a few patients are being treated in this part of the study for another few weeks. The results of this part of the study will be analyzed towards the end of this year.

Importantly, we have not seen any serious side effects related to the study treatment to this date. The main side effects seen so far were stinging, burning, and redness of the treated skin.

For your information, the active ingredient in TMB-001 is a compound called isotretinoin which was dissolved in an ointment consisting almost exclusively of polyethylene glycol, also called PEG. The plain ointment in the ASCEND study was just the PEG without isotretinoin.

We are currently working to understand the reasons behind the unexpected result where the plain ointment showed the same level of effect as TMB-001. Once the second half of the study is completely done, and the results have been analyzed, we will be able to share details of all the study findings with the scientific and public communities.

We once again would like to sincerely thank all the trial participants and healthcare professionals that formed part of this trial. FIRST has been a great partner for us and a strong champion for this community. Through our partnership with FIRST, we will continue to keep the community informed of any development in this program.