PTC Therapeutics Inc PIVOT-HD Results Call Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Kristen Kluska - Cantor Fitzgerald - Analyst : Hi, good morning, everyone. Thanks for taking the questions. First on the 24 month data, do you have any HTP lowering data there? And then because it is a small subgroup, I'm wondering if you can comment on any of the inter-inter inpatient variability from 12 months to 24 months just given that the data looks so clean at this stage, do you suspect that it was just the disease severity getting worse over time where the effects could perhaps shine a little bit better at this time point?

Question: Kristen Kluska - Cantor Fitzgerald - Analyst : Okay, thanks. And based on the interactions that you had with the FDA late last year, what is the next step for you now that you have this data on hand?

Question: Kristen Kluska - Cantor Fitzgerald - Analyst : Thank you.

Question: Brian Abrahams - RBC Capital Markets - Analyst : Hey guys, good morning, thanks for taking our questions. Maybe to from me, I guess looking at the mHTT reductions, any sense as to why I guess in this newer cohort you didn't necessarily see the same sort of relationship between the blood, a plasma mHTT and CSF, and is that something that might. Prompt you to consider looking at higher doses just given the clean safety. And then secondly, can you elaborate a little bit more on why you think the Stage 3 patients are less responsive and why the data is less interpretable for those patients despite the fact that they had similar CAG repeat numbers. I noticed that they looked a fair amount older. Could that be a reason that, their disease be much more progressed and that might be why and maybe just help quantify the size of the Stage 2 market overall relative to the overall Huntington's population. Thank you.

Question: Brian Abrahams - RBC Capital Markets - Analyst : Thank you.

Question: Judah Frommer - Morgan Stanley - Analyst : Yeah, hi guys, thanks for taking the question. Kind of wanted to take the opposite angle of that one, I guess based on what you've seen thus far, could you make the argument that perhaps, treatment should start earlier in Stage 2, and could that be part of the conversation with your partner Novartis and or FDA and then separately just as you go back to FDA, how are you thinking about kind of benefit conferred in the sub scales of cUHDRS do you think you'd be able to tie Huntington lowering to subscales or would they like to see benefit across the entire scale? Thank you.

Question: Judah Frommer - Morgan Stanley - Analyst : Thanks.

Question: Eliana Merle - UBS Equities - Analyst : Hey guys, thanks for taking the question. Just want to clarify a bit when you talk about associations between mutant Huntington lowering and efficacy, what specifically will you look at? Have you seen, in terms of the patients that have had a greater mutant Huntington lowering a greater clinical benefit? And just any kind of clarity on maybe some of the variability that you're seeing in the (inaudible) Huntington lowering and if, this has been predicted of say greater clinical benefit and the patients that might have seen greater lowering. Thanks.

Question: Eliana Merle - UBS Equities - Analyst : Alright, thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Gena Wang - Barclays - Analyst : Thank you for taking my questions. So maybe follow the previous questions and also (inaudible) you made a quite a few comments, right, regarding the lowering correlation or association with functional data, but when we look at it there are a few data points was not -- some data points there are some association there, but there are other data points through a new association there and I can give you several examples like Huntington lowering we did see the CSF numbers, right, lack of dose response 5 milligrams and 10 milligrams you did explain partially, but on the other hand, why we did not see this time what we saw last time. And why, 5 milligrams show pretty similar to the blood level but not the 10 milligrams. And I have another question regarding the neurofilament, when we look at the numbers, also 5 milligrams seems to be better both in the Stage 2 and the Stage 3. And I have a related question on month 24 because you did see further improvement, but when we look at back, last June 2022, sorry, last June data and neurofilament placebo arm actually had the highest reduction we would like to know, what is the trend there. And then TMS now at the 24 months was not maintained. So my question is like, do you think minimum -- at the minimum level Stage 3 is off the table for acceler approval because the functional trend did not show consistent. And then second, regarding the Stage 2, what kind of data point, if you emphasizing two year or longer timeline like what data point will be important when you talk to the FDA that will help you emphasizing the acceler approval path could still be open.

Question: Gena Wang - Barclays - Analyst : Thank you.

Question: Jeff Meacham - Citigroup - Analyst : Oh great, thanks so much for the question. Yeah, I just have a couple on the regulatory side, so I guess the first one, is there a way to weight some of the all the biomarkers that you're looking at in this -- in the phase two study. Just to maybe confer an argument for accelerated approval, I wasn't sure if there's a composite that you could do to kind of maybe separate more signal from noise and maybe that will tell you some difference between Stage 2 and Stage 3. And the second question, I know it's sort of hard to answer with respect to, a full approval and a pivotal, but do you -- would you expect to do a separate Stage 2 and Stage 3? I wasn't sure in a pivotal what the value would be to add both if Stage 3 is going to add a lot more a lot more variability and looking to the Stage 3 from a functional standpoint, do you see pretty wide variability in those patients from natural histories versus Stage 2 I guess that has some regulatory consideration. Thank you so much.

Question: Jeff Meacham - Citigroup - Analyst : Awesome thank you so much.

Question: Joseph Tomy - TD Cowen - Analyst : Hi there, good morning. Thank you for taking my questions. Just a couple on the TMS measure because this does look to be the one that is driving the dose dependent benefit in the Stage 2 patients but then also saw a little bit of a dose dependent worsening in the Stage 3s. Can you talk a little bit about the overall variability of TMS as a measure, and then maybe in the 24 month data, if you exclude those two TMS patients that had the large increases. I guess what did TMS look like for the remaining patients? And is there anything to explain those large jumps on TMS for the patients that did see that large worsening? Thank you.

Question: Joseph Tomy - TD Cowen - Analyst : Great. And then maybe one quick housekeeping question. I know you have fast track for this agent. Have you discussed breakthrough therapy designation with the agency and, or do you anticipate, requesting that after this data set? Thanks.

Question: Joseph Tomy - TD Cowen - Analyst : Perfect thank you.

Question: Joseph Schwartz - Leerink Partners - Analyst : Great, thanks very much. There are some big changes in caudate volume in the placebo patients, which were not attenuated to that much of a degree in the drug arms. Given the community, and I think FDA views caudate volume as a potentially valuable surrogate biomarker for clinical development in HD. I was wondering if we could get your thoughts on what story that picture is telling.

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, thanks. And then is this the full extent of statistical analysis you'll be performing on the PIVOT-HD data when you bring your case for accelerated approval to the FDA or will anything else be done to assess associations between Huntington lowering and functional benefit in terms of things like our value which we usually think of as being typical statistical tools to evaluate and demonstrate an association, in a rigorous manner. Thanks.

Question: Joseph Schwartz - Leerink Partners - Analyst : Great, thanks again for taking my questions.

Question: Samantha Corwin - William Blair & Company - Analyst : Thanks for taking my question. I just was curious if there's any scenario in which FDA might want to see more data at 24 months in order to have more productive conversation regarding accelerated approval, and if they do kind of want to see that additional data at 24 months for accelerated approval, would you kind of think about running a, phase 3 trial still that would not be hinging on that and would be hinge on a full approval instead. And then I was wondering if you could also provide us some more granularity in terms of the milestone payments you still expect from Novartis and how much of them are tied to clinical milestones versus regulatory. Thank you.

Question: Samantha Corwin - William Blair & Company - Analyst : Alright, thank you.

Question: Joel Beatty - Baird - Analyst : Hi, thanks for taking the question. Can you discuss what doses you see planning ahead? Would it be, one dose moving ahead or multiple doses and could it be different doses for different patient populations?

Question: Joel Beatty - Baird - Analyst : Thank you.