PTC Therapeutics at Bank of America Conference: Strategic Growth and Challenges

On Tuesday, 13 May 2025, PTC Therapeutics (NASDAQ:PTCT) presented at the Bank of America 2025 Healthcare Conference, outlining its strategic initiatives and growth prospects. The company highlighted its readiness for the global launch of its PKU drug, sepiaterin, and discussed regulatory challenges and opportunities in the European market. Despite competitive pressures, PTC remains confident about its pipeline and commercial infrastructure.

Key Takeaways

• PTC is preparing for the global launch of sepiaterin, targeting the PKU market with a focus on Germany.
• The company is leveraging Article 117 to maintain Translarna’s presence in Europe despite regulatory setbacks.
• The PTC518 program for Huntington’s disease is progressing, with promising data and a partnership with Novartis.
• Management expressed minimal concern over executive orders and tariffs, emphasizing a global pricing strategy.
• PTC is optimistic about FDA approvals for its pending applications, with no significant regulatory hurdles anticipated.

Operational Updates

Global Launch of Sepiaterin:

• PTC is set to launch sepiaterin in Germany, taking advantage of six months of free pricing.
• The company has initiated an early access program and is preparing for a broader US launch with a dedicated patient services team.
• Sepiaterin is positioned as a premium product, potentially capturing a significant market share due to its efficacy and safety.

Translarna in Europe:

• PTC is implementing a country-by-country strategy to continue commercializing Translarna, despite a negative CHMP opinion.
• The company expects to achieve 25-30% of previous European revenue and has seen unexpected interest in new patient starts.

Regulatory Landscape and FDA Interactions

• PTC anticipates minimal impact from executive orders and tariffs due to its ex-US revenue focus.
• The FDA review for the PKU NDA is progressing well, with confidence in approval by the PDUFA date.
• Interactions for the Friedreich ataxia NDA are typical, with ongoing inspections and no advisory committee meeting expected.

Future Outlook

PTC518 for Huntington’s Disease:

• The PIVOT HD study shows dose-dependent reduction in toxic huntingtin protein and positive safety data.
• PTC’s partnership with Novartis aims to explore accelerated approval pathways, with an emphasis on oral therapy advantages.

Competitive Landscape:

• PTC targets 85-90% of PKU patients not currently on existing therapies, highlighting limitations of current treatments.
• The company aims to capture a billion-dollar opportunity in the US, with significant revenue potential ex-US.

In conclusion, PTC Therapeutics is poised for growth with multiple catalysts on the horizon. For more details, readers are encouraged to refer to the full transcript.

Full transcript - Bank of America 2025 Healthcare Conference:

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Conference, I’m Tazeen Ahmad. I’m one of the senior Smith Biotech Analysts here. It’s my pleasure to have our next presenting company with us, PTC Therapeutics. Sitting next to me and presenting for the next thirty minutes will be Matt Klein, who is the CEO of the company, as well as Pierre Bravia, who is CFO. Gentlemen, good morning.

Thanks for coming over from New Jersey to see Good

Matt Klein, CEO, PTC Therapeutics: morning. Thanks for having us, Azim.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: So I’ve been starting off all the conversations with macro questions. I’ll ask you in order of most recently occurred macro, events. Can you talk about the executive order that was announced yesterday Sure. To the extent that you can.

Matt Klein, CEO, PTC Therapeutics: Yeah. I I think as as you put very clearly in your note about the executive order, it it was a lot of, let’s just say, bark without a lot of clear indication of of Yeah. Of what, if any, ramifications there would be for for companies. So, you know, this is gonna be a let’s see what develops. I I think from our standpoint given, again, as you also highlighted in your note, our current revenue is more ex US than US.

And then also as we think forward, to our PKU launch, and this is a product where for a rare disease, there’s a disproportionate high, commercial mix. And, also, whenever we think about pricing and a launch, we think very carefully about a global pricing corridor to ensure that we can be commercializing the drug and maintaining the value of the product. So these are things we always think about. So all that is to say, while there are no details now, if if there would be any potential impact, we we imagine very little if anything were to involve evolve in terms of more specific m a MFH type pricing constructs.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. So just to clarify, for PKU, are you expecting to price this at a narrow range?

Matt Klein, CEO, PTC Therapeutics: Yeah. So we will have a pricing corridor that will keep, again, allow us to maintain the the pricing that we’ve talked about and and getting the value for the therapy.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. And then can you talk to us about tariffs in general?

Matt Klein, CEO, PTC Therapeutics: Sure. Again, a lot not known, and we think in any scenario, we’re in a very good position. First of all, most importantly, the IP for our US products is domiciled in The US. That means there’s no issues in terms of transfer pricing. It’s a US owned product.

So even for those that are manufactured or have raw materials which come from outside of The US, At worst, you’re talking about a tariff on COGS or a portion of COGS, which would be quite low. So really minimal, if any, impact, to the bottom line.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. And then lastly, on your interactions with FDA.

Matt Klein, CEO, PTC Therapeutics: So we’ve had a lot of actions interactions with the FDA with three applications pending. And as we’ve talked about, we have seen, no impact really of any of the FDA changes. Impact we haven’t seen impact in terms of the people with whom we interact. We’ve also not seen any impact in terms of cadence or nature of interactions. Our PKU NDA, which is under review, we’ve talked about having the the typical con contact and back and forth with the agency.

We’ve moved through most of the review. We we held our late cycle meeting with FDA last week on schedule, and it was clear from there that we are mostly through the review with just agreement and alignment on post marketing commitments left. So for us, it’s a really good sign that the review has progressed well, probably ahead of schedule, and we remain confident of an approval, if not before the PDUFA date, certainly by the PDUFA date. And similarly with, Friedreich ataxia NDA, the interactions have been very typical in terms of the cadence and nature for a priority review application. Inspections are ongoing.

So everything is looking exactly as it should look, which gives us, again, confidence that we have, not going to have an impact of any changes that have occurred at the agency.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. When we spoke on Zoom a few weeks back, there was one thing that you had mentioned about, you said all these things about hasn’t really changed with FDA, but in relation to AdComms, you had made a comment along the lines of potentially the folks who arranged for advisory committee meetings might have been somewhat impacted by changes. Is that something that you’ve been able to get color on?

Matt Klein, CEO, PTC Therapeutics: We have not gotten color on it. That was just based on our understanding of some of the changes in staffing that had occurred.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay.

Matt Klein, CEO, PTC Therapeutics: In terms of our programs, there was never an expectation of an AdCom for PKU. When we had the application accepted for Friedreich’s ataxia, the agency said they had not yet decided on AdCom. They had given us the feedback in the mid cycle meeting. They don’t anticipate an AdCom. And similarly, we don’t anticipate we do not anticipate an AdCom for the Translarna NDA, just in part because I think the neurology division understands the disease quite well, understands the endpoints quite well.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. So let’s talk about Translarna as it relates to Europe. So it’s a drug that doesn’t exist but yet exists, is what I like to say. So you continue to record sales. Yes.

How how are those sales occurring now?

Matt Klein, CEO, PTC Therapeutics: Yeah. So I I again, this is once again with Translarna, a unique situation The negative opinion, from CHMP was formally adopted by the European Commission on March 28. As part of their adoption of the opinion, the commission, as far as we can tell, for the first time, invoked the ability of countries to leverage a pathway known as article one one seven of, the European armament, which basically says that countries can import and sell a drug that’s no longer licensed. And what that had allowed us to do is to pursue a strategy that we had long planned for, which was to try to work country by country to see if we can continue to commercialize the drug. Now to be clear, what article one one seven does is it enables the individual countries to find their own individual mechanisms by which the drug can be commercialized, and that can be in early access pathway and the inpatient pathway.

And what we’ve seen thus far, I think Eric alluded to this on the on our earnings call last week, is about 50%, five o percent of countries have expressed an interest thus far in continuing to commercialize the drug. We have begun, shipping the drug, receiving payments for the drug in several countries, and unexpectedly, we’ve also heard about interest in new patient starts, again, which is something we didn’t anticipate. And, you know, for as you said, for a drug that doesn’t exist, the the dollars or the euros are real. They exist. And and we said, look.

In terms of guidance, we we said, look. We believe we can do somewhere around 25 achieve about 25 to 30% of European revenue the rest of this year. I I think that’s a number we’re comfortable with for now. As we see how this evolves, we can certainly update that.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: I mean, it could be higher.

Matt Klein, CEO, PTC Therapeutics: Sure. Look. I I I again, I think it’s sort of this moment where you say, well, the fact that we’re talking about revenue for a no longer authorized drug is incredible. And and and, you know, from our standpoint, we’ve really talked about wanting the European business, as well as the Emflaza business, to really bridge us to the PKU launch, which it’s done. And now we’re in a situation where we’re getting ready the global launch of sepiaterin, which will be significant revenue for us and really the foundation for future growth, and yet this bridge still gives.

I mean, we’re continuing to garner revenue, which is great, and being able to provide patients with a drug because there really is nothing else in terms of therapy for nonsense mutation boys. So it’s it’s it’s a great situation to be in, and we’ll continue to bring the drug to as many patients as we can.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. So you talked about PKU and that would have a a large commercial contribution both dollar wise and in terms of how it’s reimbursed commercial payers. DMD on the other hand does have a significant Medicaid component, right?

Matt Klein, CEO, PTC Therapeutics: Yeah, I think that’s a higher Medicaid population due to just the disability of the patients.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: So then if approved, would that complicate The US launch as it relates to that first question we started off with on MFN?

Matt Klein, CEO, PTC Therapeutics: I think very hard to know. Again, I think one of the questions that has come up is if there’s MF first of all, we’d welcome the opportunity to launch in The US, and we Mhmm. We’ve said we have about a 50 boys on drug now that we could convert comer commercial drug very quickly. And with our Emflaza database, we have insights into additional nonsense mutation boys and young men that we can get on the drug. And and, obviously, our team knows the community very well.

So that would be a very meaningful opportunity. In terms of a potential impact of MFM, look. I I think it’s unclear whether there would be anything for would it be Medicare Part b? Would it be Medicare Medicaid and Medicare Part b? And if it’s Medicaid, what’s not really clear is with this basically with the end would would you end up charging the same amount as you would now take into consideration discounts?

So it’s because there’s a rebates that we do now for Medicaid patients, so it’s unclear if there’d be any impact.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. Got it. So then how should we be thinking about, you know, expectations? You’ve talked about the strength of the Translarna data. We I go back with Translarna to the very beginning.

Matt Klein, CEO, PTC Therapeutics: Yes. Before before my time, know.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: And so if this is if this makes it the this last attempt to get it approved, does get it approved, how should we be thinking about investments of resources from PTC into this launch?

Matt Klein, CEO, PTC Therapeutics: Yeah. So look, I we we believe the dataset as we told we talked about it last year. We’ve talked about it that we believe it supports approval, and I think the the functional data for the drug are are stronger than any Duchenne drug that’s been approved by the FDA, and the safety record is very clear. We’ve also been very clear that we’re realistic. The the history is long.

It’s challenged, and we are you’ve certainly not seen any of us running out saying, you know, this is a high probability event. This is should be your investment thesis in PTC. We see it as a a, you know, a very valuable free call option. Because if it is approved, we know the community quite well. Our infrastructure’s in place.

There’s nothing more we would have to do. We’d be able to ramp quite quickly having a 50 patients on drug that we could convert to commercial drug. We understand their payer. We understand how that works. We’re very well connected with the Duchenne community.

And and I think right now in the Duchenne community due to recent developments, there really is an increasing desire. It’s always been there. But the desire for a safe therapy that’s known, that has shown to be effective and durable, think is a very important those are very important factors to the patients and families in the community.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: And what about the comments that Doctor. McCary has made about continuing to focus on rare disease? Do you find that encouraging for transcribers prospects as well?

Matt Klein, CEO, PTC Therapeutics: Yeah. Hate it’s funny that we say it. I mean, it’s it’s it’s it’s, again, a long a long road. But, yes. I mean, the short answer is yes.

And I think even, you know, I think doctor Prasad’s comments, which scared a lot of people when they first made and his subsequent comments softened quite a bit. But I think that there is this desire to get safe therapies out to patients with rare diseases where there’s unmet needs. And I I think that’s important for for Translarna. I think that’s important for vortiquinone as well where you have an unmet need and a and a drug that has a strong safety record for children.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. So let’s move on to the PKU launch, which is much more traditional launch for the company. Can you just remind us on where you are with that?

Matt Klein, CEO, PTC Therapeutics: Yeah. So we’ve been planning for this. We’re ready. We’re ready for the global launch. We talked about how the CHMP opinion was a great first step.

Mhmm. We expect adoption within sixty days. We will launch first in Germany to take advantage of the six months of free pricing. So we expect shortly after adoption, the price we publish in Laertex, and we’ll begin commercialization. To accelerate launch in Germany, we initiated an early access program.

That’s been very successful both in terms of getting patients in Germany on drug, who by law, as soon as it’s commercial, get turned over to commercial drug. But it’s also been great to get us into the top centers in Germany, increase physicians’ awareness, get their use of the drug, all of which will allow us to ramp quite quickly in Germany. We’re also exploring other other countries where we can avail ourselves of early access. In terms of infrastructure, this is the Translarna infrastructure. They can easily handle PKUs.

There’s a lot of center overlap. And I think based on our earlier discussion, there’s there’s no question about the ability of this team to execute under the most challenging circumstances with a data package that probably is not as strong as the PKU data package. So I I think all that bodes really well. In The US, we have built the team. We’ve, it’s in place.

We have everything ready to go, not only in terms of the sales team, in terms of our patient services team. This is a really important component of what we do. People have asked us, how have you been able to maintain Emflaza revenue in the face of generics, and also other competitors, non generic competitors? And one of those, you know, secret sauces, if you will, is this patient services team that’s well integrated with the patients and the families and the physicians, walking them through prior audits, walking auths, walking them through step edits. All in that team we’ve bulked up and is ready for PKU.

And on the medical side, we’ve been working not only with the commercial teams to map the 103 centers of excellence in The US, understand the dynamics at those centers, who are the decision makers. It’s often not only the physician, but also nutritionists and dietitians. We’ve added them, nutritionists to our medical team so we can do a lot of peer to peer interactions and support, appreciating how important those folks are in the decision making, understanding at each center how are the teams at those centers viewing the priority for launch. Is it the existing Kuvan patients since they know that we’re gonna have a superior effect in terms of feed lowering based on our data? And so it’s basically switching a one one once daily therapy to one that should be much better for patients.

Or is it the therapy naive patients who are classical patients who we believe we can treat based on our data to date in the trial and our mutation data? And so just understanding where each of those centers wanna go. So this is way down the road. And in fact, we’ve said if the approval were to come early, we’re ready.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Now can you talk to us about the competitive landscape as in like what do patients currently take?

Matt Klein, CEO, PTC Therapeutics: Yes.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: And we’ll talk about the some potential advantages.

Matt Klein, CEO, PTC Therapeutics: Yep. Absolutely. So there’s about seventeen thousand, individuals with PKU in The US. It’s newborn screening, so there’s no patient identification. These are, patients who are diagnosed at birth.

There’s the two therapies. There’s saproteren, which is basically giving BH four directly. It’s both the branded form of Kuvan and now the generic forms which are available. And Palynziq, which is indicated for only for adults, which is an injection, which has become, you know, thought of as a second line or last line therapy. What we understand is at about ten to fifteen percent of patients, most are on one of those therapies.

So you’re talking about eighty five to ninety percent of patients not on those therapies. And and why is that? For any number of reasons. I think first, you know, for patients with PKU, the goal is to be able to liberalize diet, to be able to get off or at least have a break from their highly restrictive low protein diets. And so if you’re gonna take a therapy, it’s gotta be able to bring you a benefit in terms of diet liberalization.

And our understanding is the experience with saproteren, either branded or generic, hasn’t been such that it’s allowed patients to do that. And so that’s why not a lot of patients are on that. And then in terms of, Palynziq, first of all, it’s adults only, and it’s while it has efficacy that’s been shown, its tolerability profile is challenging. I think all patients have to carry an EpiPen with them due to the high risk of of anaphylaxis. I think somewhere between eighty and ninety percent of all patients have adverse events with the drug.

It can sometimes be a two year period for titration to actually get to maximal therapy. And so it’s a very hard drug to use. And so then when you think about Cefiance or sepiaterin, this is a oral drug once a day, well tolerated, with very strong evidence of, Phe reduction and diet liberalization. So it’s all there in terms of what the patients would want in a therapy.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Yeah. So as you describe it, this seems sort of like a layup in terms of launch. So, but nothing ever is.

Matt Klein, CEO, PTC Therapeutics: Is it right, yeah.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Right? So what is it that you’re focusing in on? Are you trying to switch patients from the two drugs that you just mentioned initially? Or are you trying to get to those, let’s say eighty five percent of patients that are not on anything?

Matt Klein, CEO, PTC Therapeutics: Yeah, the short answer is yes. And so I think, you know, if you think about this launch, and and we’ve talked a lot about the opportunity and believing that it could be a billion dollar plus opportunity because of the size of the population, the percentage of patients on drug a therapy currently, which is quite low, so a significant unmet need, The strength of our dataset in terms of showing that anyone who’s been on saproteren, whether branded or not and had a benefit, those patients consistently have 50 plus percent greater benefit on our drug. And the team. We talked about the team, the ability to execute, in a competitive and genericized environment, which we we can do. And we think, we have the data support, our ability to penetrate each of those segments.

And we’ve heard some physicians say, look, for us, the switches will be the easiest thing to do. Mhmm. Patients who are on saproteren can switch very easily and into another once a day therapy. It could be that large segment of of those who’ve tried and failed, didn’t get enough benefit so that they could liberalize their diet. Those patients want a drug and the therapy naive who are typically the classical PKU patients or those with what are known as non BH4 responsive mutations, mutations that don’t allow them to have a benefit from saproteren.

And we’ve shown in our trial, most recent data from our pivotal trial, that over seventy percent of the patients in that trial had those types of mutations. And of course, we have a tremendous response rate and magnitude of response. So each of those are playing out as groups of patients that the physicians want to treat and the patients themselves are speaking. We see them on social media, we hear their feedback of wanting to try. So exactly which will be the first segment to get on drug is gonna vary center by center and position by position, but we know we have the data to support.

Each of those segments are gonna work, obviously work to get as many patients on as quickly as possible.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: So most recently you talked about just general ideas about pricing. You talked about pricing at a premium to Palynziq. So to me that was a little bit on on the new side relative to what you’ve been talking about So I guess what’s changed that gives you the confidence that that that kind of price premium is justified and would be reimbursed?

Matt Klein, CEO, PTC Therapeutics: Yeah. And I I I think it that the our talking about it came as a result of our discussions with payers. Mhmm. And the payers’ realization that you know, for payers, it’s all about value. And for PKU, it’s a known entity, and and phenylalanine lowering equates to value for the payers.

And when you look at our data showing, you know, sixty three percent lowering in the pivotal trial in the overall population, sixty nine percent lowering in the classical patients, eighty four percent of patients coming in with good guideline of target benadolamole level of less than 360. That’s value. And when you take that efficacy along with the safety and tolerability profile, that package together supports the the pricing at a a premium to Palynziq. Mhmm.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: So if you do the math, I mean, you only need, like, you know, low double digit percent penetration into this population to, you know, be not that far away from a billion dollars in sales.

Matt Klein, CEO, PTC Therapeutics: Yeah. And that’s why we’ve said, you know, we obviously will be more granular about pricing once we get the label But we that’s why we said we believe this could be a potential billion dollar plus opportunity in The US alone because if you do the math on the size of the population, what would be typical penetration for a differentiated orphan product, multiply that by price, and know that we have a team that’s able to execute, those numbers become very real very quickly. And that’s The US alone. And then you say, look.

We have a global commercial infrastructure. We’re gonna be very thoughtful about launch sequence and pricing corridor. We’ve talked about what we’re doing in Europe. We have the JNDA for Japan pending in we expect approval in December of this year, which would enable a q one Japan launch of 2026, and that’s a, you know, very valuable market as well, you start appreciating that, you know, the the the global opportunity here is is is is very strong.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: And how are you thinking about well, what is the IP estate for this as well?

Matt Klein, CEO, PTC Therapeutics: Yeah. So we’ve guided that we have IP out to 02/1938 and then with patent term extension even conservatively to 02/1939, potentially beyond. Okay. And we’re continuing to build it.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: And how is the population split US and ex US? Is it equal?

Matt Klein, CEO, PTC Therapeutics: So it’s about 58,000 globally in markets where we commercialize. We said it’s about 17,000 in The US. For our own forecast, we’ve said we believe the ex US revenue opportunity could be, you know, close to 50% the US opportunity.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. Are you gonna be ready to launch on day one after approval?

Matt Klein, CEO, PTC Therapeutics: We’re we’re gonna be ready to go. Okay. We’re we again, this is a lot having the experience of the teams and understanding what we need to do and how, what start forms look like Yeah. What prior auths might look like in the cases where we there are payers who are gonna ask for step edits, how that can look, and we’re we’re we’re ready for it.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. So maybe let’s move on to PTC five eighteen, which actually a lot of people say if you’re excited about PTC, this is the reason to be excited. So would you agree with that comment?

Matt Klein, CEO, PTC Therapeutics: I think there’s a lot to be excited about. I think if you’re talking about, you know, a product the size of PKU and the opportunity of PKU in our commercial engine, that’s that’s, you know, revenue level for a company like us. You should be very, very excited about. And I think PTC five one eight is a product of our splicing platform that can be the first ever disease modifying therapy approved for Huntington’s disease. I’d be excited about that too.

So I think there’s a lot to be excited about.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Can you maybe just talk to us about there’s several companies that are trying to do treatments for Huntington’s and it’s kind of been a graveyard. It’s a challenging disease to really drug. So can you talk to us about the data that you’ve presented so far? And the most recent dataset, do you think that there was, did the market not appreciate a certain to a certain level what you were going to show versus what they expected you to show?

Matt Klein, CEO, PTC Therapeutics: Yeah. Very good questions. I I I think your premise, Tazeen, is exactly right. This is a hard, hard therapeutic area, and it has been a graveyard. And when we started the PTC five eighteen program, we believed that this could be a promising therapy because we have a drug for neurodegenerative disease that is targeting the cause of the disease.

It’s very rare in neurodegenerative. First of it’s very rare in a neurodegenerative disease that we actually know what causes it in the majority of patients. In this case, it’s a toxic mutant huntingtin protein, and we have a drug that can directly address that. So that was a very promising start. When we designed this program, it was really about saying, look.

This is gonna be tough. And as we move through the development program, let’s make darn sure that each step of the way, we’re learning the things we need to learn to increase our probability of success. And when we designed the PIVOT HD study, this was all about understanding, does the drug work? Does it do what it’s supposed to do in terms of lowering cellular hydrogen protein? Does the drug go where it needs to go to have that effect?

In other words, are we seeing CNS exposure that we need to see for it to work in the brain? Three, is it safe and well tolerated? And that’s been a big question in Huntington lowering therapies. And fourth, can we learn how to study it? What is the optimal population?

Because when we started this program, we said, gosh, a lot of therapies are going really late in Huntington’s disease. And it’s hard to think about modifying the disease if it’s been churning along for fifty years and the patient’s at end stage. And so we set this up studying stage two patients who we thought would be the optimal population, adding a cohort of early stage three patients to really test that hypothesis. And so when we look at the data readout, including last week, we’ve ticked all those boxes. And this is a dataset now that’s shown that the drug is working how it’s supposed to work with dose dependent cellular huntingtin protein levels.

We’re getting exposures in the CSF greater than in the plasma. Great. It’s safe and well tolerated, and the data out to twenty four months shows that. We have early signs of clinical effect at twelve months seeing things move that should move in the stage two patients. We learned that probably stage two is the right population.

And I think people’s reaction to those data were, oh my God, it doesn’t work in stage three. There’s no way to, No. That’s actually a incredibly valuable learning and what you need to learn in phase two. Who to study the drug in? And so we actually that that was a great learning for us and our partner Novartis.

And then when we got out to twenty four months, we say, wow, we’re seeing continued trends of clinical benefit versus natural history. We’re seeing NFL, a well acknowledged marker of neuroprotection, going in the right direction in a dose dependent fashion. And so, you know, we walked away from this saying we did everything we needed to do in phase two to give us confidence of phase three. I think a lot of people were looking at these these data as a mandate on accelerated approval. You know, I we all would like to get this approved as quickly as possible, and I think it you know, we have to bear in mind this is a hard disease, but I I think in many ways, was underappreciated.

This dataset gives us more options to think about evidence that hondrogen lowering is having an impact. We continue to see the early twelve month dose dependent clinical signal we saw earlier, and now we’re seeing stuff at twenty four months that not only shows in the in probably the optimal patient population stage two, we’re having clinical benefit, but we’re also now having clear objective biological evidence of neuroprotection, which is is absolutely supportive of what we think Huntington mullering needs to do if it’s gonna ultimately be efficacious.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Yeah. You brought up Novartis that’s your partner in

Matt Klein, CEO, PTC Therapeutics: this

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: I guess given the timing of when that partnership was announced, some had thought that was based on maybe Novartis feeling a sense of confidence, if you will, on an accelerated path being a, you know, highly likely scenario. So when you were in discussions with Novartis, was where was that in the mix outside of them looking at the science and trying to understand the product?

Matt Klein, CEO, PTC Therapeutics: Yeah. I I I don’t think that understanding was this was a deal done based on the base case being a full development program. Novartis had a a therapy in Branaplan, which was an oral small molecule splicing agent that had a lot of issues in terms of lack of selectivity and specificity, which we know is really important for splicing. They clearly, with ZOLGENSMA, have had a front row seat to IVRISTI and the potential for oral small molecules for CNS diseases. And so for them, they were interested in having a safe huntingtin lowering drug.

That’s what their diligence focused on. That’s what they paid for, and that’s what they had. Mhmm. I think I think the partnership, the Joint Development Committee is continuing to think about how we can look at accelerated approval pathways. I think that’s still there.

That’s all on the table as we move forward and think about phase three. But this was a deal done, we believe, Novartis believing that this is a potential first ever disease modifying therapy for Huntington, assuming that the standard phase three trial would be the base case and Accelerate would be a great upside.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. And so how do you just to wrap things up, think about the competitive landscape for HT. If you have to take a traditional path to approval versus Accelerate it, how does that change where this product could be relative to the competition?

Matt Klein, CEO, PTC Therapeutics: Yeah. So I think probably when we think about the competitors that could be in a position for earlier approval if if an accelerated path is open, which, again, I think they’re the accelerated path for the gene therapy is based on twenty four month natural history and FMFL, which, by the way, our dataset now has in addition to the peripheral biomarker. But if they were to get ahead first, I continue to believe that having an oral therapy, that gets to the entire brain, that has durability, you you can’t redose a gene therapy, is gonna be safe and well tolerated, I think will always be in a more attractive therapeutic option for this very large population. And keep in mind, in HD, you’re talking about forty thousand diagnosed patients. But there’s multiples of that that are undiagnosed, that are earlier stage.

And that’s really where there’s a significant opportunity, and having an oral small molecule that can be given to individuals in their very early stages, maybe even before they’re showing symptoms, that’s what the physicians say would be the holy grail for the patients and what the patients want. I don’t see that ever being a population where gene therapy is going to go. And then when you add on top of that, there’s always a concern with gene therapies, even ones infused in the brain, which we clearly know a lot about. The durability long term is a serious question. You can’t re dose.

So I think this this therapy would still really be able to be the leader in terms of disease modifying therapies. And bear in mind, this will be commercialized by Novartis. This is a bone crushing machine, right? So good luck getting against them.

Tazeen Ahmad, Senior Smith Biotech Analyst, Smith Biotech: Okay. With that, we’re out of time for today. So thank you for joining us on Everybody in the room, thanks for listening, and we’ll talk soon.

Matt Klein, CEO, PTC Therapeutics: Thanks. Thank you, Jazeen. Thank you.

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