Good day. Welcome to the Ascendis Pharma update call. At this time, all participants are in listen only mode. After the speaker's presentation, there'll be a question and answer session. Instructions will be given at that time. As a reminder, this call may be recorded. I would now like to turn the call over to Tim Lee, Senior Director, Investor Relations at Ascendis Pharma. You may begin.
Thank you, operator. Thank you everyone for joining our conference call this morning. I'm Tim Lee, Senior Director of Investor Relations. Joining me on the call today is Jan Mikkelsen, President, Chief Executive Officer. Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act. Words such as believes, anticipates, plans, expects, indicates, will, intends, potential, suggests, assuming, designed, and similar expressions are intended to identify forward-looking statements. Examples of such statements may include, but are not limited to, statements relating to, one, our plans to seek to address the deficiencies identified by the Food and Drug Administration. two, the timing and results of our FDA decision on the new drug application for TransCon PTH.
Three, our intent to continue to make TransCon PTH available to patients participating in our ongoing clinical trials, and work with physicians and patients to provide TransCon PTH to eligible patients through our expanded access program. Four, our expectations regarding patient enrollment in a German expanded access program. Five, the timing and results of a European Commission decision on the marketing authorization application for TransCon PTH. Six, the timing of potential commercial launch for TransCon PTH in Europe. 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, and we may not be able to achieve our goals, carry out our plans or intentions or expectations or projections disclosed in our forward-looking statements, and you should not place undue reliance on these statements.
We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see our forward-looking statements section in today's press release and the Risk Factor sections of our most recent annual report on Form 20-F, filed with the SEC, the Securities and Exchange Commission, on February 16th, 2023. On today's call, we'll provide an update on the regulatory reviews for TransCon PTH. Following some prepared remarks, we'll open up the call for questions. With that, let me turn it over to Jan.
Thank you, Tim. Good morning, everyone. Last week, we received updates from regulatory authorities in both the U.S. and Europe. In the U.S., FDA notified Ascendis that as part of their ongoing review, they have identified deficiencies in our NDA for TransCon PTH in hypoparathyroidism. That, at this time, precludes them from holding further discussion with us about labeling and post-marketing requirements and commitments. The FDA also stated that this does not reflect their final regulatory decision on our NDA. The letter was brief and deficiencies were not disclosed. We are eager to learn, understand, and address the deficiencies identified by the FDA. This development, a month from the agency's PDUFA date, may lead to a delay in the FDA final regulatory decision on the TransCon PTH NDA. As always, the safety of patients remains our highest priority.
Since our NDA submission, no new safety signals have been observed to date in our ongoing TransCon PTH phase II and phase III clinical trials or in our EAP program, and these programs continue unchanged. In addition to making TransCon PTH available to the 145 patients who continue in our ongoing open-label extension, we will continue to work with decisions to make TransCon PTH available to new patients through our U.S. expanded access program, which remains open for enrollment for the eligible adult patient previously treated with short-acting PTHs. In Europe, regulatory review continues as planned. On Friday, we received a comprehensive day 120 response from the European Medicines Agency. We remain on track for an European Commission decision on our marketing authorisation application for TransCon PTH during the fourth quarter of 2023.
If approved, we expect our first European country launch in early 2024. In Europe, we also committed to address this unmet medical need as fast as possible, including to our early access program. This quarter, we expect to initiate and enroll the first patient in a German Expanded Access Program and look forward to make such access available elsewhere in Europe. There is not any additional information we can share with you at this time. We are happy to open the line for questions. Before doing so, however, just let me say, in our clinical work with TransCon PTH, patients, their caregivers, and physicians have shared with us improvements in disease control and in patients' well-being that have participated in the TransCon PTH clinical study. We believe TransCon PTH is a product that really are addressing the disease that is the hypoparathyroidism.
We feel a huge responsibility towards the hypoparathyroidism community to bring forward this potential new treatment option as quickly as possible and stand ready to work in a collaborative manner with FDA to that happen as soon as possible. Operator, we are now ready for questions.
Thank you. If you would like to ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Jessica Fye with JP Morgan. Your line is open.
Hey, guys. Good morning. Thanks for hosting the call. Given that the deficiency or deficiencies were not outlined in the letter, and I guess recognizing the message you're sending on this call and with the press release that with the EAP open and the extensions open, it would appear to not be a safety issue that the FDA has. What can you say about how long you think this might take to resolve? Then I have a follow-up.
First, just thanks for the question, we agree with your conclusion. Going back to the question about how long time it will take, it will be dependent of us first to understand the nature of this deficiency. As soon as we have that, it can be something we potentially can address extremely fast, or it will potentially take longer time. I believe in the benefit and the safety we have seen until now in the treatment of patients with hypoparathyroidism and TransCon PTH.
Okay. Then just I'm sure people are wondering, had anything changed in the tone of the regulatory review or the topic of the FDA's questions they were focused on over the past couple of weeks?
We actually are now just trying to remind have received any interaction with FDA since our late-cycle meeting, which we had from multiple weeks ago. It's really hard for me to address this question because I really don't see a lot of interaction.
Thank you. As a reminder, to ask a question, please press star one one. We ask that you limit yourself to one question and a follow-up. Our next question comes from David Lebowitz with Citi. Your line is open.
Thank you very much for taking my question. Has the FDA, I guess, did the FDA conduct their CMC inspection? Have they provided any feedback on that? Could you comment on any specific questions that have been coming up in discussions recently with the agency?
To the NDA application, there have been inspection of both clinical site and also CMC-related site. After this inspection, it's custom for the inspector to issue a report that describes the findings on the inspection. We have not seen anything from either the clinical inspection or inspection of the CMOs that would reflect any kind of worry related to the approval of the NDA.
Thank you for that. How many patients do you have in the EAP at this point in time?
Currently, we have as a company policy not to disclose the number of patients in the EAP program. Just to remember, the EAP program is only addressing the hypoparathyroidism patient that has been previously treated with short-acting PTHs. We are enrolling patients, and we continue to enroll patients, and we will continue. It gives them a treatment option as long as we will not be launching TransCon PTH. We see this patient group observing the exact same benefit what we have seen in our clinical trial.
Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.
Hi. Good morning. Thanks for taking my question. Did you, Jan, already complete the late-cycle review for the application? I'm just trying to understand at what point these deficiencies came up. Also, I just wanted to clarify, is it one deficiency, or are they identifying multiple deficiencies? Thanks.
You are correct. We had the late-cycle review meeting. I'm a little bit blinding on exactly the date, but I believe it's about three, four weeks ago. That was addressing your first question. The second question?
Just on deficient. Is it one deficiency, or is there more than one deficiency that they've identified?
Yeah. This question is really hard for me someday to answer because we only have this very short letter that describe they have identified deficiencies. We do not know is that related to a single or multiple?
Thank you. Our next question comes from Li Watsek with Cantor Fitzgerald. Your line is open.
Hi, this is Rosemary on for Li. Thank you for taking our questions. Just very quickly, do you think this issue will be specific to the FDA and is not going to have any impact on EU approval, or you might hear something from them later?
We were so happy when we saw the comprehensive 120 days feedback from the European. We went to this intensive feedback because it's basic, reviewing all aspects of the application. The elements we are responding back to, we feel highly confident we have sufficient information, and they are not in the nature that it will restrict any kind of expected approvability of TransCon PTH in the European Union. Our expectation is still approval late this year, and we are getting ready already to launch TransCon PTH in the first European country early 2024. We said before, we are also installing a Named Patient Program in Europe. We are starting on the filing, and we expect to have the first patient already enrolled here in this quarter. This program is different compared to the U.S. program because it's both the.
Take both PTHs experienced patient but also naive patient. It's basic, addressing the entire patient population of hypoparathyroidism, which are much, much larger in Europe compared to U.S.
Got it. Thank you. If I could ask just a follow-up question. Where are you in the launch preparation in the U.S., and how does this potentially impact those activities?
What we are as a specialty pharma, we launched SKYTROFA, and we are establishing the launching of TransCon PTHs out from this established infrastructure. This is a product opportunities that's coming directly into the same therapeutic area in the chronology. It take us to a unique position because half of the small, the part of the sales force now we have dedicated to PTHs, half of them are coming with TransCon PTH experience SKYTROFA here in the U.S. We basically can take that path and take the period where if we get an later approval than the PDUFA date, we'll be utilizing this sales force and the infrastructure to really build up the SKYTROFA to a much higher level that we have already seen how it's accelerating month by month, quarter by quarter.
By utilizing that, we are from a revenue perspective, easily can compensate from the one product to the other product because we are in this unique position in building up pipeline in each single therapeutic area. We both have the economy of scale of synergy to deal with this position without having anything to do with these people. We're basically utilizing them in our big effort in trying to promote it, but still we will go out and promote TransCon PTH. We still will build the awareness of hypoparathyroidism because that is a part of our long strategy, and because we, to our best knowledge, our expectation to get TransCon PTH out to the patient as fast as possible. This is our responsibility for the patients.
Thank you. Our next question comes from Paul Choi with Goldman Sachs. Your line is open.
Thank you. Good morning, and thanks for hosting the call. Can you comment if, as part of the late cycle review, the agency asked for any additional data, even if it's minor or trivial, in your opinion, or any additional analyses?
I believe in every time you have an interaction with FDA, you have a constructive dialogue. Sometimes in this constructive dialogue, you are presenting science and also data. Often to every time we have a meeting with the agency, they often ask for getting access to this data packet on a date of stakes. Every time we have interaction with FDA, there will always be material data presentation being filed to FDA. I think this is a part of having a constructive dialogue.
Okay. Then as a follow-up, maybe relating to an earlier question, can you comment on when you would specifically ask for either a Type B or Type C meeting, or Type A or Type C meeting, depending on what you think is appropriate, and when you would potentially expect scheduling of that to occur? Any more precision on that?
I think we're not waiting for that. I think we will continue our constructive dialogue with FDA and as soon as it's possible, set up a call so we can continue this dialogue and find a resolution for how to bring TransCon PTH out to the market as soon as possible. I think this is everyone's interest. Everyone recognize the unmet medical need and the benefit that TransCon PTHs give to the patients.
Okay. Thank you. I'll hop back in queue.
Thank you. Our next question comes from Derek Archila with Wells Fargo. Your line is open.
Hey, good morning, and thanks for taking the question. Just one from us. I mean, we've seen the agency use this type of language before with other companies in their press releases. Just wanted to kind of get an understanding from you how you might think this situation is different from you. Ultimately, I think all those cases that we found led to a CRL. Yeah, any differences would be helpful. Thanks.
My question is that or I really don't have the knowledge where I have looked on all company that have got an letter that describe a deficiency under an priority review or not under a priority review and look what is really happening with these companies. It's really hard for me to comment on some element where I'm basically not feeling confident I have done a sufficient analysis for coming with a valid answer.
That's fair. Maybe just one follow-up for me. I guess, I think just, you know, piggybacking on the last question. Have you spoken with the agency to set up that meeting yet, or is that still something that you have not yet done? Thanks.
This is what we are doing here in the near future, initiate and collaborative discussions with them and finding a way forward. I think it will be initiated as soon as both parties are ready and have the time to do it. We will definitely be ready and have the time to do it.
Thank you. Our next question comes from Josh Schimmer with Evercore ISI. Your line is open.
Yeah, Thanks for taking the question. Has there been any discussion or do you now anticipate a potential 3-month extension to the due date? Thanks.
The only element we have got at feedback from FDA was the letter. There was no indication of anything else than that short writing about the deficiencies. We have not received any further information.
Okay, thank you.
Thank you. Our next question comes from Leland Gershell with Oppenheimer. Your line is open.
Hi, good morning. Thanks for the update, and for taking my question. Any expectation you may have on when you may have your meeting with the FDA? Thanks.
I think, as I said before, we are trying to plan for a call as soon as possible to initiate the dialogue and getting a constructive outcome so we can bring TransCon PTHs out to the patients and get the expected approval as soon as possible. Thanks.
Thank you. Our next question comes from Andreas Argyrides with Wedbush. Your line is open.
Good morning, and thanks for taking our question. I'll try to ask, you know, in a different way here. Again, given the proximity to the PDUFA, it leads us to believe at least that this is... There are probably some minor deficiencies and that the FDA is not necessarily coming out and wanting to state that they want to extend the PDUFA, though that may be the case. To what extent, given the timing and the fact that there's prior review, do you get the sense that these are readily addressable? If you can just kind of comment there, appreciate it. Thanks.
Yeah. I have to think there's multiple question in your question. First of all, we cannot really speculate of the nature of the deficiencies because we don't know it. The second question is that, when I also integrating the feedback we have received from EMA, active belief that is a product opportunity that have all prospects for really should be approved as a pharmaceutical product. We have for many years observed the huge benefit this product opportunity have given to the patient, the physician, and caregivers. We have listened to the patients about the unmet medical need. We just need to find a pathway to get this product out in collaboration with FDA here in the U.S.. I'm thrilled that we still can help patients in our EAP program.
Sadly enough, it's only the patient that have been PTH experienced here in the U.S. that can, through their physician, sign up for this program. At least I feel we're helping the patient in this way. You know, when I look at our values about the patients and the science, you could be dedicated that we will try to get this product as fast as possible, also in the U.S.. I see a clear pathway to have this product out in Europe in the beginning of next year. Also would like to see the clear pathway to get it into the U.S. market because the hypoparath patients in the U.S. need it.
Okay, great. A quick follow-up here. Do you think, or do you have any knowledge as to whether, you know, what's going on with the FDA as to whether maybe they, you know, are experiencing delays in reviewing and this may be part of the, of a, of a delay on their end as opposed to, you know, anything specific, again, back with the, with the filing? Thanks.
I really don't believe I can really speculate or address any element from how FDA is functioned and how they are responding. What I observed, we also observed a small delay for SKYTROFA. It's always a little bit more burdensome for every agency to deal with a product opportunity that is a combination product because it's not at what we call a simple filing because it typically involves much more elements in the regulatory approvability in it because it's a combination product.
Thank you. Our next question comes from Joseph Schwartz with SVB Securities. Your line is open.
Hi. Thanks so much. We see two examples recently where this occurred, led to CRLs, but also two examples where it led to approval nonetheless. In one of those examples for the CRL, one of the reasons, for the deficiencies was attributed to a human factors study. I was wondering if you could talk about what you've done there, and if you think that your work is sufficient. One of the examples where it led to approval, it was related to a bone mineral density study. I was wondering if you could comment on how you feel you're positioned on that front.
Thanks for the question. It's really hard for me to comment on this question because I can only speculate, and I have no knowledge what really there is in the deficiencies. For me it's really impossible to answer the question. I can answer partly for example, building up in Europe, the device is actually being approved on an independent agency or independent pathway than the main one. We already basically got the approvability on the device, which includes the factor studies. Some way, we have got regulatory's feedback to that part. About the element you are asking about is that all element we are seeing both related to bone markers and bone density changes where we normalizing the normal development of bone health.
It has never been a part where there have been raised any safety concern to it. Also from the aspect we are continue also here in the U.S. to enroll new patients in our EAP.
Thank you.
Thank you. Our next question comes from Yaron Werber with Cowen. Your line is open.
Hi, thanks for taking our question. This is Joyce on for Yaron. I guess sort of just depending on what might be the reason for the delay, assuming that you refile, would it then be sort of a six-month review process or a more traditional 10-month review process or a three-month extension? I was just wondering how you're thinking about the timeline for that.
I think we will start to think about that as soon we understand the nature of the deficiencies. We can start to think about how we, in collaboration with FDA, can work together, resolve it, and potentially, if it's needed, refile.
Great. Thank you. Then maybe just one quick follow-up. What could this maybe mean for your cash guidance?
Currently, we are always running Ascendis out from an perspective is that we have been a very fortunate position to have a large cash holding. What we are doing now, we are in a position that we continue to accelerate the re-revenue generation from SKYTROFA here in the U.S., and we will start to accelerate the SKYTROFA revenue generation in Europe later this year. We are in a position where we basically are coming to what we really believe is our goal to be a sustainable, profitable leading biopharma company. If I see a potential small delay on launching on TransCon PTH in the U.S., it's not changing the big picture. We are on track to what we want to be. That is not changing the perspective for us.
We have synergy in our sales force, we will continue utilizing our commercial infrastructure to build up the awareness of hyperparathyroidism in the U.S. At the same time, we can also enforce it as a signal, the effort we do on SKYTROFA. This is the idea by having multiple product in one single therapeutic area. This is not our first product that get approved. We have product in the market that already give us the more than the expected revenue.
Thank you. Our next question comes from Caroline Palomeque with Berenberg. Your line is open.
Good morning. Thanks for taking the question. Just wanted to ask about manufacturing process for TransCon PTH and just how confident are you in its scalability? Thanks.
The great thing by TransCon PTH is that it builds on a product that has basically been established for more than 20 years, Forteo. That is the producer of our drug substance is basic utilizing the DMF for, Forteo, and this is where we're getting the product from. Rest of the supply chains are built on [Fareva], which make the drug product a while, which I believe is one of the best recognized drug product producer. The pen injector is built on an Ypsomed pen, which I have to believe is getting utilized million of times every day. It's basic an insulin device.
When I look on the supply chain, to my knowledge, it's actually is what I call a supply chain that is built on established, proven products in established, proven CMOs that have the quality to really deliver on a global basis to all countries, including U.S.
Thank you.
Thank you. Our next question comes from Sushila Hernandez with Van Lanschot Kempen. Your line is open.
How are you doing?
Thank you for taking my question. Were there certain topics, during your label discussions that were controversial? Thank you.
Just could you repeat the question? Sorry.
Were there certain topics during your labeling discussions that were controversial?
I don't think we had any kind of controversial discussion with FDA during our label discussion. We were following the normal procedure that we are sending in a proposal to the label, and we got the feedback from FDA, which we actually think was really reasonable. It didn't include any element related to boxed warning or various program or other things like that. Then we have responded back again, and this is the correspondent we have related to our daily discussion.
Okay. That's clear. Thank you.
Thank you. Our last question is a follow-up from Tazeen Ahmad with Bank of America. Tazeen Ahmad, your line is open.
Sorry about that. I was on mute. Thanks for taking my follow-up. Again, I just wanted to clarify, did you receive any 483s as a result of your pre-approval inspections?
No. We both have been inspected from different clinical site. We also been inspected in our CMOs or supply chain, as I call it.
Okay, great. Thank you.
We have a follow-up question from Leland Gershell with Oppenheimer. Your line is open.
Hi. Thanks for taking the follow-up. As we sort of try to tease apart what we can here based on the limited info, again, can we, you know, at least delineate, you know, this being a substantive review, re-review issue with the content of the NDA versus what may be a technical issue with the filing, given that you didn't get an RTF, presumably your NDA itself is intact. Would there be any reason to believe that perhaps there's some missing section or module of the NDA that could be addressed in relatively short order? Thank you.
I think you're not missing anything. The question is that I cannot answer your query in any kind of valid manner before I really have got the direct feedback from FDA what is basic the nature of these deficiencies. We believe we will have this constructive dialogue as fast as possible, and we still continue here in the U.S. with our EAP group. I have to think we are on a good way forward.
Thank you.
Thank you. There are no further questions. This does conclude the program, and you may now disconnect. Everyone, have a great day.