Hello, and welcome to Ascendis Pharma Third Quarter 2023 Earnings Conference Call and Webcast. Following the prepared remarks, there will be a question-and-answer period, instructions will be given at that time. I would now like to hand the conference over to Tim Lee, Investor Relations of Ascendis Pharma A/S. Sir, you may begin..

Thank you, operator, and thank you, everyone, for joining our third quarter 2023 financial results conference call. I'm Tim Lee, Senior Director, Investor Relations of Ascendis Pharma. Joining me on the call today is Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Executive Vice President and Chief Financial Officer; and Dr.

Stina Singel, Executive Vice President and Head of Clinical Development Oncology. 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.

Examples of such statements may include, but are not limited to, our U.S. commercialization and continued development of SKYTROFA for the U.S. and European market, as well as our expectations for 2023 SKYTROFA revenue, the expected timing of the approval and launch of TransCon PTH in the U.S. and the EU.

Our pipeline candidates and our expectations with respect to their continued progress and potential commercialization our strategic plans, our goals regarding our clinical pipeline, including the timing of clinical results, our ongoing and planned regulatory filings and our expectations regarding the timing and the results of regulatory decisions, our expansion into new therapeutic areas, our progress toward Vision 3x3 and our ability to become cash flow positive and create a sustainable, profitable and leading global pharma company.

These statements are based on information that is available to us today. Actual results and events can differ materially from those 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 that has changed except as required by law.

For additional information concerning the factors that can cause actual results to differ materially, please see our forward-looking statements section in today's press release and the risk factors section of our most recent annual report on Form 20-F filed February 16, 2023. TransCon Human Growth Hormone or TransCon hGH is approved in the U.S.

by FDA and the EU has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. Otherwise, please note that our product candidates are investigational and not approved for commercial use.

As investigational products, the safety and effectiveness of the product candidates have not been reviewed or approved by any regulatory agency. None of the statements during the conference call regarding our product candidates shall be viewed as promotional.

On the call today, we will discuss our third quarter 2023 financial results and will provide further business updates. Following some prepared remarks, we will then open up the call for questions. And with that, let me hand it over to Jan..

Thanks, Tim. Good afternoon, everyone. Our dedication to the values of patients, science and passion remains the foundation for us to create long-term value for all stakeholders. In the U.S., we achieved market value leadership for SKYTROFA within two-years by sticking to our belief that a premium product deserves a premium price.

Following the same strategy in German, we launched SKYTROFA in September and also expect to also launch TransCon PTH in January 2024 if approved by the European Commission in November. In select other European countries, we will use the same direct sales model to launch our portfolio as we have in the U.S. and Germany. We call this EU Direct.

In other markets, we will commercialize our portfolio to sales and distribution partners who are local experts in rare diseases. We refer to this as international indirect markets. In Japan, we intend to partner our endocrinology rare disease products.

We believe we have the organization and the manufacturing capacity to support expected launches of three independent endocrinology rare disease products by 2025. Driving further growth, we aim to continue to work to create highly differentiated TransCon product candidates, expanding into additional endocrinology rare disease indication.

Last quarter, we announced the expansion of our TransCon platform, a new type of carrier platform specifically designed to support new product opportunities in diseases with large patient population. I look forward to sharing more information with you about this in the near future. Let me provide more details on each of our programs.

For TransCon commercialized at SKYTROFA. We reported strong revenue growth, finished the third quarter with €47 million, including initial revenue from Germany. We now expect full-year 2023 SKYTROFA revenue to be between €170 million and €175 million.

To drive differentiation and market leadership, we continue to build out the times and data behind SKYTROFA. We recently announced results from our long-term Extension trial showing that the majority of patients treated with TransCon growth mix or exceeded average parental height at the time of their treatment completeness or last visit.

The data also demonstrated the long-term safety of SKYTROFA in patients treated up to six years. In adult growth hormone deficiency, we expect to share top-line results during the fourth quarter from our global Phase III foresight trial.

Today, we estimate less than 4% of adult patients suspected of having growth hormone deficiency are treated with growth hormone, making this an opportunity to both expand SKYTROFA labeled and expands the overall growth hormone market.

In addition, we plan to launch SKYTROFA in certain markets in our international indirect region with initial revenue contribution expected to begin in 2024. Turning to TransCon PTA. In the European Union, EMEA, CHMP adopted a positive opinion in September.

Recommending approval of TransCon PTAs and replacement therapy for adults with chronic hypoparathyroidism. We expect the European Commission final decision on our marketing authorization application this month. If approved, we plan to launch TransCon PTH in Germany in January 2024.

In Germany alone, while the annual cost for currently approved PTH treatment is around per patient, our target population is 22,000 chronic hypoparath patients out of the overall patient population of around 17,000 patients. Our status team in Germany that launched it is ready to launch TransCon PTA if approved.

And EU approval we will also provide the basis for marketing authorization and initiation of commercial activities for TransCon PTAs in addition, markets in our international market segment where we expect through launch starting in 2024. And further launches in Europe direct in 2025, following standard price and reimbursement pathways.

By following our algorithm for product innovation, we will have taken transport PTAs from idea to expected regulatory approval all in about seven years. In the U.S., all documents have been finalized and we expect to resubmit the NDA for TransCon PTA for the hypoparathyroidism within a week.

We expect to know where the FDA has accepted our risk submitted NDA with 30 days from the risk submission date. If accepted, we expect the FDA to notify us at the time where the resubmission is class I or class II and provide a new PDUFA date. Besides this information, we will not comment further on the resubmission.

As this guide over, we continue to build of the science and data behind TransCon PTH. In September, we announced a post hoc analysis of Phase II and Phase III data, demonstrating substantial increase in estimated DFR in adults with hypothyroidism treated with TransCon PTH.

These data suggest that treatment with TransCon PTH can reverse impaired kidney function in patients with hypoparathyroidism. Turning to TransCon CNP, this is our third endocrine rare disease product candidate. Following our end of Phase II meeting with U.S.

at EU regulatory agencies, we have lined on the pathway to potential regulatory approvals in the U.S. and EU. We expect topline results from our Phase III approach trial with completed enrollment in Q3 in the second half of 2024. We continue to have strong patient retention in our trials.

And during the fourth quarter, we will provide an update and share with you one year follow-up data with the open label extension part portion of accomplished. We believe the strong retention in our clinical trial is a result of additional benefit of TransCon CNP in addition to height improvements.

As we have further evaluated the science behind achondroplasia and our own data, we now believe that achondroplasia is a disease of both skeletal growth and muscle function and that the continuous exposure to the CNP enabled by TransCon CNP may be able to address both elements.

At our upcoming update, we will disclose this additional potential benefit of TransCon CNP in addition to height. If we are right that is correct that achondroplasia is emphasis for both skeletal growth and muscle function.

This means that TransCon CNP could potentially offer value for adults living with achondroplasia, who experience muscle fatigue on all of medical and quality of life impacts. That may be potentially addressable with constant exposure to CNP.

We are in a constructive dialogue with later on how best to evaluate the pretended impact on TransCon CNP on comorbidity, quality of life and other important aspects of achondroplasia, in addition to height to support an indication for treatment of achondroplasia.

While our key focus in the treatment of achondroplasia is to address the co morbidities that are associated with this disease. We believe an even more effective way to address height if needed or desired could be CNP in combination with Protego. We believe that this combination therapy may provide greater analyte hypervelocity and CMP alone.

And at the same time address the comorbidity of achondroplasia. Our previously presented preclinical data demonstrate the attitude effect of combining TransCon CNP and growth hormone in animal models. Consistent with stimulation of different growth promoting signal pathway in the growth rate.

Supporting this idea, a group out of Osaka University in Japan presented a post during last month ASBMR, showing that a last group of 41 achondroplasia treated with [indiscernible] demonstrated first year annualized high velocity of around 7.4 centimeters with sustained growth benefit to five-years of treatment.

To export this concept, we plan to submit an IND amendment or similar to initiate a combination trial of TransCon CFP and SKYTROFA by the end of this year. Moving to oncology, for TransCon IL-2 beta/gamma, we recently reported new data from the IL-Believe trial of TransCon IL-2 beta/gamma as monotherapy and in combination with chemo at ESMO.

These data confirm that TransCon IL-2 beta/gamma dosed every three weeks demonstrated clinical activity as monotherapy or combination therapy of course late line heavily preceded patient in multiple tumor types. Further strengthening our confidence in its best in class potential.

In two out of three small lung cancer patient treated with combination therapy in the trial and confirm partial response and unconfirmed complete response in the first tumor assessment of an ongoing patient were observed.

We believe these data are intriguing despite the very small sample size considering the treatment history of the responders and the substantial on with medical needs. Enrollment is ongoing in the indication specific cohort of IL-Believe.

Where we are now enrolling 20 to 40 patients in each indication, and we expect interim results in the second half of 2024. In summary, with growing revenue, by showing up our pipeline, we continue to progress to our goal of becoming profitable.

With our Vision 3x3 on track to be achieved in 2025, we are preparing for our next vision for growth to 2030. In our next vision, which I look forward to sharing with you at the beginning of 2024, we will work to lever our fully integrated capability to become the leading endocrinology rare disease company.

Taking product from contact out to patients on a global scale with a highly productive organization. In other areas where we believe TransCon can deliver best in class product candidate as we have been oncology ophthalmology.

We plan to pursue partnership or business model to take out our product candidate to late date development to commercialization. Such future partnership in oncology and ophthalmology along with the maturation of our endocrinology program should result in lower expenses in the coming years.

By staying focused on achieving valued market leadership globally for our endocrinology rare disease portfolio. We believe Ascendis will deliver sustainable value over the long-term for patients, shareholders and society. I will now turn the call over to Scott for a financial review before we open for questions..

Thank you, Jan. As Jan noted, we believe we are making significant progress towards our goal of becoming cash flow positive with SKYTROFA revenue growing is in each quarter combined with diligent expense control. I will touch on some key points surrounding our financial results. But for further details please refer to our Form 6-K filed today.

Total revenue for the third quarter of 2023 was €48 million. SKYTROFA revenue for the third quarter was €47 million compared to €35.9 million reported in the second quarter and €12.3 million reported in the same period last year. The sequential growth in Skytrophy revenue was primarily driven by increased demand in the U.S.

with minimal foreign currency impact of around €100 million. Exiting the third quarter, we estimate we have low double-digit penetration into the U.S. pediatric GHD patient population, and we see a large opportunity in front of us to grow our patient share in pediatric GHD, which we estimate to be only half of the addressable U.S.

growth hormone market. Turning to expenses, R&D costs in the third quarter totaled €111.4 million, up 6% sequentially from the second quarter of 2023, primarily driven by higher endocrine rare disease related costs, including clinical expansion and PPQ manufacturing costs related to TransCon CNP partially offset by lower oncology related costs.

SG&A expenses declined 9% sequentially to million compared to the second quarter of 2023 primarily related to lower commercial and G&A external costs. Total operating expenses were €175 million for the third quarter less sequentially from the second quarter of 2023.

Overall, our operating loss declined sequentially by 5% to €134 million for the third quarter from €141 million in the second quarter of 2023. We ended the third quarter with cash, cash equivalents and marketable securities totaling €455 million, including proceeds from the previously announced $150 million royalty funding agreement.

Looking ahead with continued momentum for SKYTROFA in the U.S., we are increasing full-year 2023 SKYTROFA revenue expectations to €170 million to €175 million. Let me now also provide a review of selected key program milestones.

For TransCon Growth Hormone, we expect to report top line data from the global Phase III Foresight trial in adult GHD in December. Potentially opening an opportunity to both expand SKYTROFA's label as well as expand the overall growth hormone set.

For TransCon PTH, as Jen noted, we are on track to resubmit our NDA for TransCon PTH for adults with hypoparathyroidism before mid November. We expect a European Commission decision on TransCon PTH this month. If approved, we plan TransCon PTH as our second product launch in Germany starting in January 2024.

For TransCon CNP, we expect to submit and IND amendment or similar for a new clinical trial evaluating TransCon CNP in combination with TransCon Growth Hormone in children with achondroplasia. We plan to share follow-up data from the open label extension of our Phase II ACcomplisH trial later this quarter.

And as a reminder, we expect to report top-line results from ApproaCH, our Phase III trial of TransCon CNP, in the second half of 2024. Within our oncology therapeutic area, enrollment continues in the Phase II portion of our IL-Believe trial of TransCon IL-2 beta/gamma in indication specific cohorts.

We expect initial data from indication specific cohorts in the second half of 2024. With that, operator, we are now ready to take questions..

[Operator Instructions] Our first question comes from Jessica Fye with JPMorgan..

This is Nick on for Jess.

Can you talk to us a bit more around your strategy with the oncology and ophthalmology programs and kind of what that means in terms of OpEx over the near-term and maybe more so over long-term and how like to change?.

The question related to what do we do as a company with a very, very strong platform technology that basic have application in yearly every therapeutic area. We at Ascendis will be focused on rare disease endocrinology, this is where we will be integrated from idea state up to the patient where we are building up all the efforts.

We also know that the TransCon technology would provide paradigm shift product, best-in-class product outside our own focus area. And we also feel that we need really to be part of that value creation also to the benefit of the patients. We will have different business models that will fit exactly to each single therapeutics.

Some areas we will basic out licensing on an early stage, where the feeling is that it is the optimal thing, it could be potentially large patient indications where we basically never can succeed with running all the big clinical trial.

It can be areas like ophthalmology where we maturate the two states and then we change to give it out either to a spin out or an out licensing or a combination of both where we feel that an independent management team really with the focus on, for example, ophthalmology really, really can mature.

It is not the same thing Ascendis not really continually be involved. We will still provide service to this entity, we will be part of the upside both related to royalties, milestone payment and equity. In other areas like oncology where we feel that we really can make issue is different from the patient.

We made an investment in it and we will continue to make an investment into it until we see that we can get the full value on this and when I see how we progressive with this oncology effort, I'm really, really proud about it..

And maybe can you help set the stage for the update from the Phase II accomplish trial and what you hope to see when you have all the patients on 800 micrograms for the full-year?.

Yes. What we hope to do that we will provide you with the element that we really believe it is essential for the patients.

We will provide you with the sustainability of how we keep the positive benefit on growth but we've also come in and trying to give you the explanation both from a scientific base but also true data how we feel that we are providing a benefit to the treatment besides just providing the analyzed height velocity.

We are 100% in the belief that the key element for us is to address the co-morbidities associated with this disease and that is our focus on that.

And this is why we believe that annualized high velocity is an element, if it is desired and if the patient really want to have it, that can always go into perhaps the most powerful combination of treatment is CMP to move the brake growth hormone to speed up the accelerator and you basically will have what we call the wanted, desire, analyze, high velocity compared to the patient's needs and desire..

The next question comes from Paul Choi with Goldman Sachs..

My first question is just with regard to TransCon PTH positioning in the major European markets, specifically, Germany and just how you think position will be particularly given surgical complication rates there and then just the pace of reimbursement access? And then I had a follow-up question..

You are right. The European and the international market as we call it is what we call much more diverse way of reimbursement. The fastest one is Germany where already from January where we expect to launch TransCon PSA will be fully reimbursed.

The patient population in Germany is actually pretty large compared to the size of the country, mainly driven by and higher treatment on head and neck operations. So you are right, it is a post surgical patient that is much higher. And we believe the addressable element of patient not the total patient population is about 22,000.

At the same time, we are in a position where the only approved treatment for Hypopara in Germany is being taken away from the market.

So we are in an intensive discussion with all the key centers how we really can help more than the 400 patients that basically already eyes that this on the PTH treatment, how to take one on treatment in 2024? Besides that, for many years, there have been a long, long layout of patients that want to be on a PTH treatment but never had the opportunity to do it.

And this is why the European approval give us a fingerprint starting immediately on a full blown commercial effort in Germany.

At the same time, European or EC approval give us the opportunity to go to a named patient program and addressing more than the 400 plus NATPARA patients that still is in all European countries, which we feel a huge responsibility for also helping and also the patient that didn't come into any treatment in the last nine-years.

Rest of EU will take 12 to 24-months to be fully reimbursed, fully running commercial perspective. At the same time, the EU approval, which we expect to get here in the coming week will provide us with an approval system for addressing patients in the international market. Some markets, we will have an independent application.

Other market, we can directly refer into our European application. So we are dedicated really to help patients everywhere in the world, which have a need for the treatment because of the Hypopara patient situation that exists today..

And just as a quick follow-up, with competing hGH products approved here in the U.S.

Can you maybe just comment on maybe what mix of formulary access might be up for renegotiation this year? And any general comments you've had into the 2024 renegotiation period?.

I've been asked in the last 3, 4 months a lot. What is really the impact on having to our long-acting product in the U.S. market.

And clearly, we never have seen more interest, we have not seen better numbers ever since it got clear with really best-in-class property SKYTROFA has compared to the other products, really building up on what we have established in the last two-years, how we really are changing the treatment we see in treatment of pediatric growth hormone deficient with a better outcome.

And that is not going to change with any other long-acting. Basic is just providing, I believe for some of them and lower far to exceed and overcome compared to for example medical exception..

The next question comes from Joseph Schwartz with Leerink Partners..

So a couple of questions on TransCon CNP, if I could. First of all, I was intrigued by your commentary about achondroplasia being not only a bone disease but having a muscle component.

And I was curious if you could just talk a bit about how you intend to illustrate the benefit of TransCon CNP on those aspects of the disease? And then also, in terms of, TransCon CNP's potential comp to be combined with TransCon or SKYTROFA rather, as it is now called.

I was wondering given I thought a lot of the earlier science suggested that growth hormone supplementation in achondroplasia had just an ephemeral benefit.

What are your thoughts on the potential for the combination to show a more sustained response in achondroplasia?.

Thanks for the question. Let me start with your last question about the annualized high velocity. We always have known that growth hormone had a positive effect on achondroplasia. Sometime it has been a little bit unclear what has been the magnitude on that because it typically have been small trials.

When we saw the trial coming out from the Japanese group, pretty well controlled, falling patient up to five-years, the number is nice, 41. Everything looks great.

They have one year before treatment follow on what is the annualized high velocity before treatment and it is about 4.2 exactly what you will expect to see out from this kind of demographic. And the first year, annualized high velocity up on 7.3, 7.4. That is more than I've seen any kind of CMP treatment ever give it.

And when you have 41 patient, I always feel that it is a number that gives me some pretty good comfort. And it is the best analyzed high velocity I have ever seen in any hype trial with achondroplasia patients. We went back and analyzed 20 publications about all small trials, some of them all of them.

And if we have been smart, really have gone to the literature in-depth, then we could actually have seen it because often these 20 publications, we nearly got the same number when we added everyone out. So this is not surprising. It is something that has been in the literature, have potentially been understated, undervalued.

But there is no doubt, best Analyze high velocity you can get in that contemplated today is on growth hormone. The problem with that is we could really address co-morbidities, I don't believe that. I believe that the biology behind the achondroplasia is a much more complicated by logical impact on the hyperactive FDR to U.S. Sector.

And there it comes in because in the end, we are just starting the beginning of the beginning of achondroplasia treatment. We are not in the end of the beginning even. We are in the beginning of the beginning because we need to address the comorbidities. So this is why we believe the treatment is potentially moving to a combination treatment.

Well, CMP will address some of the biological systems where we believe achondroplasia, the hyperactive FDL3 pathway are modifying and disease that basic are also of muscle impact. And you asked me why did we see that? It was basically the patients, the parents, the caregivers that came back to us. We got in the patient reported outcome.

We can see after one or two months that suddenly say that patient providing much better, function much better and we said it cannot be growth. And then we started to analyze this and we realized that is a strong muscle component of that.

And what we would like to do when we have our CMP update, we will give you the biology behind it, explain why we do that.

And also, we believe that it is important for us also to provide you with data with the combination therapy, because I believe in the combination therapy, you can get whatever analyzed high velocity potentially the same as you can see in growth hormone deficient up to 10, 12 centimeters..

The next question comes from Yaron Werber with TD Cowen..

Maybe one very quick one and the second one is a little bit bigger. Just on the PTH, the refiling is going to be sort of in the next week or so.

Can you just comment, did you sort of by this point work out all the analysis that FDA is going to want you to do? Or do you feel like you have good clarity? And then secondly, on the preclinical GLP-1, if the data with some obviously looks interesting on a monthly basis.

What are sort of the next steps as you see them before you can start IV enabling study? Is it you are still trying to fine tune the construct? Or is it potentially trying to figure out, is this something you want to take yourself? Or is it something that you want to ultimately potentially partner?.

This is Tim. Let me take the first part. As Jan on his prepared remarks, and besides the information that we just discussed, we are not going to provide, we are not going to comment further on the resubmission process..

Related to the GPL-1, we are in a great space. We came out with the data provided the interest that people could see the value in it both as an improved one weekly treatment, but also on a once month is treating for this important segment going up. And we basically continue the dialogue with companies that interested in [indiscernible]..

The next question comes from Li Watsek with Cantor Fitzgerald..

Just first one, we've seen daily products continue to retreat and reduce output in Q3.

Can you just talk about how much of a tailwind has been for SKYTROFA and where do you see that trend to track in the coming quarters?.

The question you are addressing, what is really happening in the growth hormone market? And I think what we are seeing is the results of the consolidation that we had predicted, had expected to happen and that is basically what you see in the marketplace today.

Four years ago, when we came up with our Phase II data and we didn't out licensing our TransCon growth hormone, a lot of this established player basically said, okay, let us find out how we can milk this here in the best possible way. And you don't milk by investing in production capacity.

You don't really get the highest property to investing in anything. So this is why you are seeing a daily growth hormone market. Basic only have three players left now with a sales force, infrastructure and other things like that.

So instead of having a six player, you are down to three player and likely there will be a fewer player in the coming year when really the real consolidation will happen.

So some way, you are saying is that it is the shortest, but the shortage is also indicated in the way that the consolidation of the market promoted of it, because in the old days with many more company really could provide more capacity and other things, there will not have been a shortage.

It is not changing the fact why SKYTROFA is the leading company, leading brand in value is because we are providing best-in-class purposes and it is getting realized by physician, by caregivers, by patient and I hope and we know that also by the reimbursement system..

And then maybe just a question on TransCon IL-2. You show some pretty nice data in small cell lung cancer.

So is there any plan to that is indication to our expansion cohort?.

That's a great question Li. Yes, we were very encouraged by our initial signal in small cell lung cancer and we are exploring adding additional indication cohort in lung cancer to our, both extension cohort..

The next question comes from Leland Gershell with Oppenheimer..

Just wanted to ask further on the plans to for TransCon CNP for benefit outside of high velocity in terms of other comorbidities.

Wondering, that if you could just maybe go into, maybe beyond muscle? Are there other measures or endpoints that you are contemplating to include in upcoming studies?.

We are exploring a lot of different elements. We want, I would like to group it a little bit. One is the patient reported outcome where you have both our own developed way to look at it. You have established one as a 10 and other way that really are catching how you potentially have a physical benefit of this treatment or not.

So this is one what we call the patient reported outcome. The other one we are looking for is dedicated co-morbidities. Are there a clear pattern where we see less co-morbidity over a year period because you need to go through some season to be quite sure you picking up what kind of element of coal or other thing could influence it.

The other one is more hardcore element where we basically have a lot of x-rays of could patient, are they really changing the scoliosis, are they changing other elements and we are looking on all different kinds of bone development and other things like that. This is in the older children.

When we go to the newborn we started now, we go for much more hardcore facts how to, for example benefit in sphinosis. Do we see the same element of fast fusion of the [indiscernible] or other things like that.

And I think this is where we take a different age group finding out what can we really do that and that is what we are analyzing and building into our pivotal Phase III trial. So we are quite sure when we have the unblinding on that, we basically have already the element of discussion with regulatory agencies how we basically can iterate that..

And then one further question, if I may. As we look forward to the update from the one year follow-up from accomplish open label extension.

Just wondering, would you be able to provide the retention rate in terms of patients who persisted in the OLE?.

At the one the data we will have to have all 47 patients..

57..

57 patients..

This does conclude today's Ascendis Pharma third quarter earnings call. You may disconnect your lines at any time and have a wonderful day..