Egetis concludes that demonstrating treatment effects on T3 levels in MCT8-deficiency could provide a basis for marketing approval for Emcitate® in the US

• Emcitate® (tiratricol) is the first potential treatment of MCT8 deficiency, a rare genetic disease with high unmet medical need and no available treatment

• In recent positive regulatory interactions, FDA acknowledges that a treatment effect on T3 levels and the manifestations of chronic thyrotoxicosis in MCT8-deficiency could provide a basis for marketing approval also in the US.
• An NDA in the US is targeted to be submitted in mid-2023 under the Fast Track Designation.
• A small, 30-day, placebo-controlled study in 16 treated patients, to be identified through the existing named patient program, will be conducted to verify the results on T3 levels seen in previous clinical trials and publications in a randomized controlled setting
• This is a major step towards a marketing application and increases the likelihood of success for Emcitate and the probability for Egetis to receive a US Rare Pediatric Disease Priority Review Voucher (PRV).
• Egetis will host a webcast today at 15:00 CET (9:00am ET)

Stockholm, Sweden, January 18, 2022 – Egetis Therapeutics AB (publ) (Nasdaq Stockholm: EGTX) (the “Company”) today announced that in recent regulatory interactions, the US Food and Drug Administration (FDA) acknowledges that demonstrating a treatment effect on thyroid hormone T3 levels and the manifestations of chronic thyrotoxicosis could provide a basis for marketing approval also in the US. Consequently, the Company now has an aligned regulatory strategy for EU and US. The Company intends to submit a New Drug Application (NDA) in the US for Emcitate® (tiratricol) for the treatment of monocarboxylate transporter 8 (MCT8) deficiency in mid-2023 under the Fast Track Designation granted by the FDA in October 2021. This follows the announcement in December 2021 of intention to submit the Marketing Authorisation Application (MAA) for Emcitate to the European Medicines Agency (EMA) based on existing clinical data on the manifestations of chronic thyrotoxicosis in MCT8 deficiency.

Data demonstrating significant and clinically relevant effects on T3 and manifestations of chronic thyrotoxicosis in MCT8 deficiency with Emcitate is already available from the Triac Trial I (Groeneweg et al. 2019), as well as a recently published long-term cohort study looking at treatment effects in 67 patients for up to 6 years (van Geest et al. 2021). To complete the clinical package for the US NDA, a randomized controlled study in 16 patients treated with Emcitate will be conducted to verify the results on T3, as demonstrated in the previous trials. Patients will be randomized to continued Emcitate treatment or placebo for 30 days or until meeting a rescue criterion of T3 level above ULN (upper limit of normal), whichever comes first. The primary endpoint of the study is the proportion of patients meeting the rescue criterion within the randomized treatment period.

“Today’s announcement increases the likelihood of success for Emcitate and its potential to become the first approved treatment for MCT8 deficiency, a rare genetic disease, with high unmet medical need, and the probability for Egetis to receive a US Rare Pediatric Disease Priority Review Voucher (PRV) upon approval of the NDA.

We have now agreed with the FDA to perform a small study randomizing treated patients to continue treatment with Emcitate or to receive placebo for up to 30 days to verify our previous T3 results in a randomized controlled setting. It is well-established that the T3 levels in untreated MCT8 patients are significantly elevated, and we have previously shown that Emcitate is able to rapidly and durably normalize these levels. The primary source for patient selection will be through our existing named patient program. We target submission of the NDA for Emcitate in mid-2023 under the Fast Track Designation. This is a substantial opportunity for Egetis and the patients in the US suffering from MCT8 deficiency.” said Nicklas Westerholm, CEO, Egetis Therapeutics.

In light of the revised regulatory strategy for submission in US and Europe (as earlier communicated), work is ongoing to confirm the content of the other components of the regulatory dossiers. The Company intends to communicate timelines during first half of 2022 for regulatory submissions of Emcitate globally.

The ongoing Triac Trial II will continue to further establish the effects of early intervention on the neurocognitive development aspects of the disease, previously seen in the Triac Trial I. Given the possibility to proceed with regulatory submissions in both EU and US prior to data available from the Triac Trial II and following discussions with regulatory agencies, Egetis will no longer conduct an interim analysis based on 48-week data but will perform the statistical analysis on the complete dataset after the full 96 weeks of treatment making the data more robust. Results are expected in Q1 2024 and data from the Triac Trial II is expected to be submitted post-approval to regulatory authorities shortly thereafter.

Emcitate holds Orphan Drug Designation (ODD) in both the EU and the US and was granted Rare Pediatric Disease Designation (RPD) in November 2020 and Fast Track designation in October 2021 by the US FDA.

Egetis will host a webcast today at 15.00 CET (9:00am ET). Please find call-in details and links below:
Weblink
https://tv.streamfabriken.com/egetis-therapeutics-presskonferens
Participant dial in numbers
SE: +46 856642651
UK: +44 3333000804
US: +1 6319131422
Participant pin code
58317375#

About Emcitate Clinical Trials
Results from Triac Trial I (clinicaltrials.gov identifier NCT02060474) were published in the Lancet Diabetes & Endocrinology in 2019 (Groeneweg et al. 2019), showing clinically relevant and highly significant results on serum T3 concentrations and secondary clinical endpoints following one-year treatment with Emcitate in 46 MCT8 deficiency patients of all ages. The clinical data published in the Journal of Clinical Endocrinology & Metabolism in October 2021 (van Geest et al. 2021) comes from the investigator-initiated real-life cohort study at 33 sites conducted by the Erasmus Medical Center, Rotterdam, The Netherlands, where the efficacy and safety of Emcitate was investigated in 67 patients with MCT8 deficiency treated with Emcitate for up to six years. The primary endpoint, the mean serum T3 concentrations, decreased significantly from baseline to the last visit. Several clinically relevant and highly significant improvements were reported among secondary endpoints covering key measurements of clinical complications of chronic peripheral thyrotoxicosis, replicating the findings from the Triac Trial I and confirming the long-term durability of the treatment effects. No drug-related serious adverse events were reported.

Triac Trial II (clinicaltrials.gov identifier NCT02396459) is an ongoing international, open label, multi-center study in children with MCT8 deficiency, conducted in both Europe and North America, investigating neurocognitive effects of early intervention with Emcitate in very young patients (<30 months of age). The first patient was dosed in December 2020 and recruitment is proceeding well and is expected to be completed during Q1 2022. Results are expected in Q1 2024.

References:
van Geest et al. J Clin Endocrinol Metab 2021 https://doi.org/10.1210/clinem/dgab750
Groeneweg et al. Lancet Diabetes Endocrinol 2019;7(9):695-706