PTC Therapeutics, Inc. (NASDAQ:PTCT) Q4 2023 Earnings Call Transcript

Matthew Klein: Yes, for the open-label portion? Yes. No, there was no specifics there. There was nothing prescriptive. I think this is viewed as the — in regulatory framework, we have persuasive evidence of effectiveness we would be putting together an NDA based on our ability to demonstrate persuasive evidence of effectiveness in the placebo-controlled portion of the MOVE-FA study along with confirmatory evidence that we said will consist of comparing the open-label data to natural history, showing that there’s a benefit over a longer period of time from both MOVE-FA as well as I mentioned earlier to Eric’s question also with data — open-label data with the natural history compassion from the first FA study that was in a slightly different population that consisted mostly of adults, both ambulatory and non-ambulatory where we’ve previously done these types of analyses to show significant long-term benefit relative to the natural history.

Gena Wang: Okay. Thank you.

Operator: Thank you. One moment for our next question, please. And it comes from the line of Paul Choi with Goldman Sachs. Please proceed.

Paul Choi: Hi, good afternoon and thanks for taking our questions. I want to change gears for a moment and maybe ask about utreloxastat and ALS. And I was wondering if you could maybe had the CARDINAL study readout later this year, sort of frame your thoughts on potential treatment effect and/or areas of differentiation versus the approved therapeutic relative from amlac [ph]? And my second question is under a scenario where amlac [ph] has a positive phoenix confirmatory study for [Indiscernible], can you maybe just comment on what your regulatory strategy might be because they get are full approval there filling as part of the confirmatory study? Thanks for taking our question.

Matthew Klein: Yes. Thanks very much, Paul. Thanks for the question on the utreloxastat ALS program. This is a program we’re very excited about given what’s become very clear now as a link between theraptosis and ALS. I think that theraptosis pathway is now seen as really an important pathway in disease progression. And of course, utreloxastat was developed to specifically target that pathway. We did a lot of the preclinical development work with utreloxastat benchmarking to a [Indiscernible], which is also another approved therapy for ALS that it has a much more sort of generic non-specific effect on elements of utreloxastat pathway. And as we’ve talked about, we’ve been able to show 25 to 30 times the potency in the final ASH site model.

We’ve also been able to show important protective effects from benchmark against a number of other disease-relevant preclinical test models. In terms of the study design, I think, again, we’re in an element, as I mentioned with David’s question on PKU, where there’s clearly precedent for the design of an ALS study and our discussions with the FDA were very constructive and ensure that this is a protocol that could support registration if positive. We designed the study with a 2:1 randomization with the treatment effect of roughly a 2.5 treatment difference between the treatment groups and the placebo groups, which gives us roughly 85% power to detect that difference. And I think that positions us very well to capture significant treatment benefit.

I think the regulatory pathway doesn’t change at all based on what happens with [Indiscernible] compound. And obviously, the commercial opportunity and the differentiation will be based on the data, what we see on ALS mFARS score what potentially we could see in terms of pulmonary function and also what we might see in terms of mortality. You’ll recall that the FDA has always been very keen in understanding both changes in ALS FRS and mortality risk. I think it’s also become very well accepted in the ALS community that given the aggressiveness and the complexity of ALS that this is probably not going to be a single therapy disease. I think it’s probably going to require more than one. But again, I think the specifics of return in terms of head-to-head comparison, well with analysis compound is really going to be data-driven, and we look forward to seeing the results from the CARDINAL study.

Paul Choi: Great. Thanks for that, and thank you for question.

Operator: Thank you. One moment for our next question, please. And it’s from the line of Danielle Brill with Raymond James.

Unidentified Analyst: Hey guys. This is Alex on for Danielle. Just looking to Huntington’s, just kind of curious about what assay you’re using for CSF mutant Huntington detection. Wondering if you have — if you expect to have similar issues that a recent competitor had and how reliable the results are in an early HD population? Thanks.

Matthew Klein: Yes, it’s great question. I think there’s two separate issues. There’s as a reliability and then assay sensitivity based on the population. Let me take them in turn. We’ve worked very hard ensuring that we have robust assays that are accurate and precise — and I think one of the things we know very well about assays in clinical studies is it’s not just the assay itself is making sure that you have care and sample acquisition, sample processing, sample storage, sample transport, and then ultimately, sample analysis. And those are things that will pay very close attention on the we minimize any confounding elements that could influence the assay results. We know the other part is important as well as these assays tend to work much better when you have a larger number of samples.

So, something that we’ve been very thoughtful about is ensuring that we have batch channel. So, each time we run these analyses we’re doing in as many samples as makes sense at that time. So again, all things that we can do to try to reduce the variability and increase the stability of those assay results. You bring up another point that’s very, very important, which is assay sensitivity based on disease stage. Now, it’s well known that a very early stage or pre-symptomatic HD patients, mutant Huntington’s protein is not detectable in CSF because it’s incredibly — the concentration is incredibly low. We talked about picomolar concentrations and maybe even lower. As we move into the Phase 2 patients, we have in the Huntington trial, of course, these are patients we believe there is detectable Huntington protein in the CSF.