Good day, ladies and gentlemen. Thank you for standing by. Welcome to Ascendis Pharma Regulatory Update Conference Call. At this time, all participants are on a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press Star one one on your telephone. You will then hear an automatic message advising your hand is raised. Please note that today's conference may be recorded. I will now hand the conference over to speaker host, Tim Lee, Senior Director of Investor Relations. Please go ahead.
Thank you, operator, and thank you everyone for joining our regulatory update call this morning. I'm Tim Lee, Senior Director, Investor Relations. Joining me on the call today is Jan Mikkelsen, President, Chief Executive Officer. Before we begin, I'd like to remind you that this call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Examples of such statement may include, but are not limited to statements regarding our plans to address and resolve concerns raised by the FDA and bring TransCon PTH to the market in the U.S., and statements regarding the potential approval of TransCon PTH in the EU. These statements are based on information that is available to us today.
Actual results and events could differ materially from those in the forward-looking statements, we may not be able to achieve our goals, carry out our plans, our intentions, our expectations, or projections disclosed in our forward-looking statements. You should not place undue reliance on these statements. Our forward-looking statements do not reflect the potential impact of any licensing agreements, acquisitions, mergers, dispositions, joint ventures, or investments that we may enter into or terminate. We assume no obligation to update these statements for circumstances except as required by law. For additional information concerning the factors that can cause actual results to differ materially, please see our forward-looking statement section in today's press release and the Risk Factors sections of our most recent annual report on Form 20-F, filed February 16th, 2023.
On today's call, Jan will make some prepared remarks, and then we'll open up the call for questions. With that, let me turn it over to Jan.
Thank you, Tim. Thanks to everyone for joining us. Late Friday, we received a complete response letter from the FDA for our NDA for TransCon PTH in hypoparathyroidism. The CRL stated that FDA cannot approve the NDA in its current form based on deficiencies related to the manufacturing control strategy for variability of delivered dose in our drug-device combination product. The FDA did not express concerns about the clinical data submitted as part of the NDA packet, and no new pre-clinical studies or phase III clinical trials to evaluate safety or efficacy were requested in the letter. Today's news does not change the safety and efficacy profile observed to date in our clinical trial and our expanded access programs.
We believe we are well prepared to address the FDA concerns related to control strategy, and we continue to have a high level of confidence that the concern raised by FDA can be resolved. We will request a Type A meeting with the FDA to agree on the best pathway forward. We are committed to work with the FDA to resolve the issues in the CRL and submit the response as needed as soon as possible to bring TransCon PTH to the market in the US. In the EU, we remain on track as laid out in our press release. With that, let us open the call for questions.
Ladies and gentlemen, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, press star one one again. In order to accommodate all participants in queue, we ask that you please limit yourself to one question and one follow-up. Please stand by while we compile the Q&A roster. Now, first question coming from the line of Jessica Fye with JPMorgan. Your line is open.
Hey, guys. Good morning. Thank you for taking my question. I have two. First, was manufacturing controls the only deficiency cited? Second, I think you mentioned no new preclinical nor phase 3 studies were requested. Were any phase 1 studies needed to back up the control strategy?
Let me answer your first question. Yes, there was only one deficiency cited in the letter. The second quest related to the element, how we are resolving the deficiency. We are working with FDA to find out exactly how we can resolve that. I'm convinced we can do it, and we will refer to our interaction with FDA to exactly find out how we will solve it.
Operator, next question.
Tazeen Ahmad, your line is open.
Hi. I think that might be me. Good morning, guys, and thanks for the update. Just to clarify, are any type of clinical studies gonna be requested as part of the path to get the drug approved? Secondly, uncertain, do you have a sense of how long this could take to resolve? Is this something you think can be done in less than 1 year? I know you have limited information, but I think people are just trying to assess how long of a delay this could be. Thanks.
The key question for me is that we now have an clarity related to the deficiency. That is the key question. The other key question for me is this deficiency is not really addressing the safety efficacy of anything what we have observed in our clinical trials. Don't demand new preclinical activities. What we're doing now is finding together with FDA the pathway forward to exactly resolve this issue. My belief is that we can resolve it, as I said before, in a fast manner because I believe this is element where we don't need to conduct additional clinical trials. I feel we are in a position that we can address this deficiency in the fastest possible time. I think this clarity exactly about the timing, we will have more knowledge about having the confirmation of our pathway forward when we have our Type A meeting.
Next question.
Our next question coming from the line of David Lebowitz with Citi. Your line is now open.
Thank you very much for taking my question. Understanding it's fairly early in the process, what is your expectation for the types of requests that you might have to, I guess, handle to be able to resolve the CRL? Is it an expectation of a shifting process, additional testing? What... Do you have any inkling at this stage of what it'll take to alleviate their concerns, or does that really need to wait for the Type A meeting?
Yeah. In the Type A meeting, we will discuss with FDA how we really address the issue. In the Type A meeting, we are preparing with our argumentation related to how we believe we can resolve this issue. When we have got this alignment and both FDA and Ascendis feeling comfort that is the way forward, I believe it's the time to come out and exactly disclose when we can have it.
Is there a typical timeline for how long a Type A meeting takes place?
Yeah. Yeah. That's pretty well regulated. In less than 3 months from today or Friday, we will request an Type A meeting, the Type A meeting will be granted in less than 30 days. You can say that the clarification will happen pretty fast on how to resolve it. After the Type A meeting, if there is an agreement on how to progress, there will be two way to move forward. There's one if it's related to... You can read it yourself. There is a different element related to an type one and type two way to move forward.
Thank you. Our next question coming from the line of Liisa Wang with Cantor. Your line is open.
Hey, good morning. Thank you for taking my question. Jan, you mentioned before that, you know, TransCon PTH is built on established products. In terms of the manufacturing control strategy, maybe help us understand how your process might differ from others on the market. At this point, do you anticipate any potential modification to the device itself, any possibility for additional human factors validation? Thanks.
Yeah. You're 100% right that when we look on the supply chains, it's built on what we call proven technology, proven site. Our drug substance manufacturing is being done by Bachem that have a DMF for PTH 1-34 in the US. Our filling is happening by Vetter, which are typical cartridges that fit into an insulin pen device, SKYTROFA. We basically have developed the SKYTROFA pen related to the specification that you typically use in the diabetes development. From that perspective, I believe we are coming from what we call an supply chains that is proven, and I have not seen any kind of indication that we will change that supply chains.
Thank you. Our next question coming from the line of Paul Choi with Goldman Sachs. Your line is now open.
Hi, good morning, and thank you for taking our questions. two from us, please. First, can you maybe comment on how your CDMOs may or may not already have some of the data you may require to satisfy the questions or requests that may come up during the type A meeting? Second, are you assuming that this is a Class two resubmission? Given your prior filing under a priority re-review, can you comment on whether you can expect a quicker re-review on the resubmission, or would you assume a 6-month re-review cycle? Thank you for taking our questions.
Yeah. I think the clarification related to type one and type two will somewhat be determined when we have the type A meeting. It's really a little bit hard for me to speculate about that. I think as I said before, we are convinced to get this type A meeting done as fast as possible. We need to write it together, our positioning, and then we will send it in as soon as possible. As said before, if they is what grant us the type A meeting in the framework of at least 30 days after we have done our submission.
I think there is such a clear pathway forward on this here, and I'm really convinced that we can find a resolution to this issue here so we basically can get TransCon PTH out to the patient here in the U.S.
Thank you. Our next question coming from the line of Josh Schimmer with Evercore. Your line is open.
Thanks for taking the questions. Have a few of them. Maybe starting with the device itself. It's been used, as you've noted, in other settings such as diabetes. Why do you think this issue is coming up with TransCon PTH? Does it have to do with the unique viscosity or are there differentiating elements of this product?
I don't think it's reflecting anything on viscosity because it's a pretty low viscosity product we have developed here in this way. You're right, this is both a device that you will see in diabetes product. You will also see it in other rare diseases like the Tezspire is also built on such a device. It's a general use device system you have. When I look also on the pathway forward in EU, the pathway EU is really straightforward, and I believe this potential build on the development that we have done, which are develop the device, the drug product, and the combination out from the current guidelines that some way are fulfilling the requirement for at least diabetes product and other product.
There can always be requests from regulatory agents that is very, very specific to one single product. I'm quite sure we can also be quite sure we can satisfy the specification in such a manner that we really can also bring this product out to the patients here in the U.S.
What kind of variability has been seen with TransCon PTH dose delivered? Is it more to do with that variability, or is it just more to do with tightening the release specs around what you have shown?
I think, just as we stated before, we have not seen any safety or efficacy concern in our ongoing clinical trial. We enrolling new patients every day in our ERP program. We are in a position that we are convinced about the safety of efficacy that we have observed in our both clinical trial, open-label extension, and our ERP program. We are taking this point here is to ensure that there is a control strategy that basically can take care of what we call, extremes, something that potentially can happen in the future in strict cases. I think that is where we working with the FDA to ensure that we getting sufficient control that we basically can ensure that we also can do this element in the future.
Thank you. Our next question coming from the line of Leland Gershell with Oppenheimer& Co . Your line is open.
Hi. Good morning. Thanks for taking our questions. It may be impossible to answer this based on the information you have at this point in, but wondering if you believe this is limited entirely to the manufacturing side or if there's any overlap with what could be human factors. If so, how long might a human factors study take for you to execute? Thank you.
That in the differences, there is no element referring into any human factor studies and any kind of human factor studies that not have been sufficient for approval. I will not protect this deficiency into the group of misconducted studies in this area.
Okay, thank you.
Thank you. One moment, please, for our next question. Our next question coming from the line of Joseph Schwartz with SVB Leerink Partners. Your line is open.
Hi. Thanks very much. I was wondering a couple things that are related. Are there any technical challenges associated with adjusting the dose administration? And it would seem like there's really just one way to resolve this, you know, by looking at PK/PD and then bridging to the, you know, bloods that you've already collected, unless I'm mistaken, and you can give us any insight into whether there might be a broader range of potential solutions. Thank you.
Yeah. I'm not quite sure I follow exactly the way you are thinking, because the PK/PD has been well established dose to our phase two, phase three additional studies and even from our phase one, phase two study and all the collecting on PK/PD to our open-label extension. We have a really intense, or what we can call modeling done on how we really look on the PK/PD related to different physiological response. As I said before, we are in a position, we have our Type A meeting where we will talk about how we resolve this deficiency, which are related to the control strategy for a product that is a combination product. I'm quite sure we will find a solution from that.
Are there any technical challenges associated with adjusting the dose increments?
No, it's actually. This is a diabetes pen system. You just click it as a normal way, as I think 1,000,000 U.S. patient do it every day.
Thank you. Our next question coming from the line of Andreas Argyropoulos with Wedbush Securities. Your line is open.
Thanks for taking our question. Just a quick one from us. What needs to be done prior to the Type A meeting, and how can that speed up the process to getting there? Thanks.
The main thing is that you need to have a briefing document, being written, structured and discussed, and that is basic the element of two. We're looking on different analysis we have done from already from data where we can use that as supportive. That is basic what we're spending on our time on now. We got it on Friday, so we now Monday, we have sure as obvious, work during the weekend to be quite sure we activated all the different work stream to get this type A request done as fast as possible. That is what we're waiting as our next step for.
Okay, great. Thanks. Congrats on the update.
Thanks.
Thank you. Our next question coming from the line of Yaron Werber with Cowen. Your line is open.
Hi, this is Jieun Choi for Yaron. Thanks for taking our question. Maybe just a couple from us. Once you refile, how long do you think the new review clock will be at that point? Secondly, just if you could clarify whether you saw this variability in dose delivered in your clinical studies. Thank you.
I can ask you answer the question, the last question pretty clearly. When we look on the strategy we have utilized for clinical batches and the commercial batches, they're pretty equivalent. The auto-injector is the same equivalent pen device we're using. It's the same manufacturing site we use for phase 2, phase 3. We basically have not changed the manufacturing setup. It's in the system. When I come over to the next element in your question is that depending on our discussion in the Type A, there is two ways you can conduct that review that take two months and as a review that take six months. We will get that clarification when we go to the Type A.
Thank you. One moment please for our next question. Our next question coming from the line of Caroline Palomec with Berenberg Capital Markerts. Your line is open.
Good morning. Thanks for taking this question. I was just wondering if you can elaborate more on your testing measures for the variability of dose. Actually, let me ask that in a different way. Is there an acceptable range of variability of delivered dose? I was wondering if you could just elaborate on your process there. Thanks.
Yeah. If I go back a little bit, in what we call the classical way in pharmaceutical developing is that delivered dose is the element of two part. One part is what we call the drug content, this is when you look in the tablet, what is the drug content? The other one is dose accuracy. This is basic for a tablet, is what is the weight or the volume of the tablet that you basic. You multiply them, you will have a variability, we call delivered dose. There need to be some specification there, and it's typical being controlled through the ISO standards. In an injectable, you have the same system which are pretty simple. You have drug content, which are basic, what is the content of your active drug in what or what you injected.
You have dose accuracy, which are basic is the volume of your injection. By looking on the ability of these two factors, you basically get specifications related to delivered dose. This is typical how you build up every control strategy.
Thank you. Our next question coming from the line of Suhasini Sharma with Company Line is open.
Okay, thank you for taking my question. Just to understand, if no preclinical studies or phase 3 studies are needed, what could be needed for approval? Also given that you are on a priority review track, Could you not just supplement the data package and go on a standard review timeline? Thank you.
The question you are asking me is exactly what we're starting and want to address in the Type A meeting, where we will get this clarification exactly how we move forward, from where we are today, and get it out to the patients. In the CRL, there is only one deficiency being cited. Meaning is that there are basic no other element that we need to continue the dialogue and discussion with FDA about.
Thank you. Our next question coming from the line of Josh Schimmer with Evercore. Your line is open.
Hey, thanks for taking the follow-up. Just wanna clarify. Jan, you talked about extremes of dose delivered. Have you seen significant outliers of the dose? Or is this more about ways to avoid extreme doses? If you can elaborate a little bit more on that. What are the gating steps on requesting a Type A meeting? I think you said within three months that you'd be able to request, but what's gonna happen over that period of time?
Just to clarify, the Type A or request need to be sent in the timeframe up to three months. You can send it in as fast as possible when you have the briefing document ready, but you have a time period of three months to send it in. I think that was the last part of your question, Josh.
Yes.
Going back to your first part of the question, Josh, related to. When we look at our clinical trials, we actually have a lot of data now. We have about nearly 145 patients, where many are now being treated up to more over three years. We have also patients in our ERP program now, and we have not observed any concern related to safety or efficacy. In a controlled strategy, you also go out and making what we call theoretical assumption about something that potential could happen in the future. This is what you're trying some way to discuss, and you can be more or less creative in the manner of different possibilities in the future. Is exactly some of the elements we are discussing, how we really control that in the future.
Thank you. I'm showing we have a follow-up question from Jessica Fye with JP Morgan. Your line is open.
Hey, guys. Thanks for taking the follow-up. Now that you have clarity on what the deficiency is, can you confirm whether or not you expect to need to pursue any further equity financings? Thank you.
I think, we are still, in a position that we are living up to the element we have come out from multiple times with, that we are not have any plans or have no desire to really to go out and make any dilutive equity financing.
Thank you. I am showing no further questions at this time. Ladies and gentlemen, that does end our conference for today. Thank you for your participation. You may now disconnect.