PTC Therapeutics, Inc. Investor update

Please go ahead. Thank you all for joining this afternoon's call.

Before I begin, I refer you to our forward-looking statements on the slide posted on our website, as well as our risk factor section in our most recent 10-K. I am excited to share the details of our planned acquisition of the ST-920 Fabry gene therapy asset. This was an opportunity to advance our strategy of leveraging our accomplished existing rare disease global commercial infrastructure and accelerate short- and intermediate-term revenue growth. Our customer-facing teams have repeatedly demonstrated the ability to deliver rare disease therapies to patients worldwide regardless of treatment modality, including oral small molecule, ASO, and gene therapy. The ST-920 Fabry gene therapy program provided a unique opportunity to acquire a potentially transformative therapy at BLA stage without the need for significant investment or build-out of development, regulatory, or commercial capabilities.

This is a potential value-creative transaction that puts another innovative and valuable product in the demonstrated capable hands of our customer-facing teams. In fact, we have several commercial leaders at PTC with specific experience in marketing the existing approved Fabry therapies. We see the potential here for significant return on investment without impacting our potential to reach cash flow breakeven in 2026. PTC was selected as the winning bidder for the ST-920 asset through a competitive bankruptcy auction. The terms include a $111 million cash payment at deal closing and regulatory milestones of $80 million for FDA acceptance, FDA accelerated approval, and $20 million for FDA full approval. Of course, deal closing is subject to certain conditions. As one of the few companies to have gained FDA approval for an AAV-based gene therapy, we applied that knowledge and experience to a detailed diligence process.

In addition to review of the clinical efficacy and safety data, our teams focused on various aspects of product manufacturing and quality that we know are critical to regulatory approval. We are confident in the demonstrated safety and clinically differentiated profile of ST-920, as well as in the manufacturing and related quality processes. In addition, we believe there is clarity on the regulatory path and that our experience in gaining FDA approval for an AAV gene therapy product increases the probability of success. ST-920 is a one-time intravenously administered AAV gene replacement therapy that enables the production of the alpha-gal A enzyme deficient in Fabry disease. Notably, treatment administration does not require pre or concomitant immunosuppression. The BLA for accelerated approval is based on the findings of meaningful effect on alpha-gal A enzyme production, renal function, and other aspects of clinical benefit recorded in the phase I-II STAR study.

The STAR study included 33 adults with Fabry disease, both men and women, with a variety of subtypes and ERT treatment history. Based on discussions with FDA, the key efficacy endpoint for the BLA is the mean positive eGFR slope from baseline to week 52 following gene therapy administration. The finding of positive eGFR slope over 52 weeks is differentiated from other Fabry therapies which demonstrated improved renal function but still negative eGFR slope from baseline. Furthermore, all 18 study participants on enzyme replacement therapy at study start were withdrawn from ERT. Durability of effect has been demonstrated with sustained increased alpha-gal A activity maintained for up to 4 and a half years for the earliest treated study participant, with evidence of maintained improvements in renal function. Importantly, ST-920 has been demonstrated to be safe and well-tolerated.

The most common adverse events in the STAR study were fever, COVID-19, and headache. ST-920 has received Regenerative Medicine Advanced Therapy designation as well as Orphan and Fast Track designations from FDA. As I mentioned, the BLA submission for accelerated approval is based on the intermediate clinical endpoint of annualized eGFR at week 52, as aligned with FDA, with 104-week results from the STAR study planned to provide confirmatory evidence to support full approval. The non-clinical and clinical BLA modules have already been submitted as part of a rolling submission, with the CMC package expected to be submitted in Q4 2026. PTC also plans to pursue regulatory approval outside of the U.S., again leveraging existing regulatory and commercial rare disease infrastructure. From a commercial standpoint, we see this as a potential meaningful global opportunity.

There are an estimated 11,000 individuals with Fabry disease in the U.S., and a similar prevalence rate worldwide in countries where we intend to pursue registration. In addition, the disease community is well aggregated, and there are Fabry centers of excellence where the majority of patients are treated. Furthermore, there are several U.S. states and countries in which Fabry disease is included as part of newborn screening programs. In summary, we are excited to bring another meaningful rare disease therapy to patients in need worldwide. The terms of this transaction preserve our firepower as we pursue our strategy to leverage business development to complement our existing product portfolio and demonstrated rare disease development and commercial capabilities. I'll now turn the call over to the operator for questions on this transaction.

Thank you. Hi, Kristen. Let me take the second question first and then the first question second.

The study included only adults. We clearly realize that there's the potential, and one of the things we'll think about as we advance the program forward is to go into younger Fabry patients, certainly adolescent patients. So for right now, the main study included adults, so did not have rare pediatric designation. Again, I think we see a potential here to explore that following the completion of the transaction. Fabry is a pretty diverse and large population that includes individuals on ERT, not on ERT, as well as Galafold, and I think one of the things as we were doing diligence here that was very attractive to us is how differentiated this therapy is. The trial included all patients with different ERT history, different genetic subtypes, men and women.

As I mentioned in the prepared remarks, when we actually look at the patients who were on ERT during the study, 18 of them, they were withdrawn from the ERT during the study. So that's our way of saying that we believe it's a very differentiated therapy and has the potential to make meaningful impacts for all patients, whether those who are on existing therapies, not on existing therapies, and have different treatment histories.