Ascendis Pharma A/S Q4 2023 Earnings Call Transcript

Quartr
Provided by Quartr
February 7, 2024

There are 13 speakers on the call.

Operator

Good day and thank you for standing by. Welcome to the 4th Quarter 2023 Ascendis Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Tim Lee, Senior Director of Investor Relations, please go ahead.

Speaker 1

Thank you, operator, Thank you everyone for joining our full year 2023 financial results conference call. I'm Tim Lee, Senior Director of Investor Relations at Ascendis Pharma. Joining me on the call today are Jan Mickelson, President and Chief Executive Officer Scott Smith, Executive Vice President and Chief Financial Officer Doctor. Stina Single, Executive Vice President and Head of Clinical Development Oncology and Joe Kelly, Senior Vice President, Head of U. S.

Speaker 1

Commercial Endocrinology. Before we begin, I'd 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 statement may include, but are not limited to statements regarding our commercialization and continued development of SKYTROFA for the U. S. And European markets as well as certain financial expectations for 2024, our commercialization and development of YORVA path in the EU and expected timing of the FDA review of potential launch of TransCon PTH in the U.

Speaker 1

S, 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 ability to create value in multiple therapeutic areas outside of endocrinology rare disease, our progress towards Vision 2,030 and the potential success of Iconis. These statements are based on information that is available to us as of today. Actual results may differ could 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 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 Factors section of our most recent annual report on Form 20 F filed with the SEC later today, February 7, 2024.

Speaker 1

TransCon 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. The European Commission has granted marketing authorization for TransCon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. Otherwise, please note that our product candidates are investigational and not approved for Commercial use.

Speaker 1

As investigational products, the safety and effectiveness of product candidates have not been reviewed or approved by any regulatory agency. None of the statements during this conference call regarding our product candidates shall be viewed as promotional. On the call today, We'll discuss our full year 2023 financial results and we'll provide further business updates following some prepared remarks. We'll then open up the call for questions. With that, let me turn it over to Jan.

Speaker 2

Good afternoon, everyone. 2023 was a transformative year for Ascendis Pharma. We streamlined the company, including our structure, our processes and operating expense allocation. And at the same time, we believe we're on track to achieve our vision 3x3 by 2025. SKYTROVA is the leading growth hormone product in value in the U.

Speaker 2

S. The launch of EUROPET in Europe direct and international markets is underway beginning with Germany and Austria. And our clinical program for TransCon CNP is progressing to what pivotal data expected in Q4. We believe Ascendis is advancing to become a leading biopharma company with a strong focus on endocrinology rare diseases and capabilities to also create value in other therapeutic area as we doing in oncology, ophthalmology and metabolic diseases. Because of the decisions we took in 2023, we believe Ascendis is a leaner, more efficient organization in 2024, well positioned to fulfill Vision 2,030 with 3 independent endocrinology rare disease blockbuster products and expand our engine for future innovation.

Speaker 2

Now, Let me provide an update on each programs. From the beginning, we designed SCATOVO to be best in class growth hormone product by releasing unmodified somatope. By addressing the needs of the patient, Caregivers, physician and payers. Skytrooper achieved U. S.

Speaker 2

Market value leadership in 2023, just 2 years after launch. We estimated that scikitopo penetration in the U. S. Pediatric growth hormone deficiency patient population was around 16% at the end of 2023. With SKYTROFA expanding the U.

Speaker 2

S. Growth hormone market to the potential of US3 $1,000,000,000 We believe Sartofa has the potential to be a blockbuster on U. S. Revenue alone. Build on this value leadership, we expect our first label expansion to be adult growth hormone deficiency.

Speaker 2

For this, we plan to submit and supplement BLA to the FDA in the Q2 of this year. In addition, we expect top line data from our Phase 2 trial in Turner syndrome in the Q4 of 2024. Now turning to TransCon PTH. Last week, we initiated the launch of TransCon PTH in Europe direct and international market. Market as you all, Jorby packs, with full commercial availability in Germany and Austria at an initial list price of €105,000 per patient per year.

Speaker 2

An estimated 70,000 adult patient in Germany are living with chronic hypoparathybridism, And our initial launch will target 22,000 of dose. Europads Europe direct launch is off to a great start with our first prescription and orders perceived at the 1st day of launch, demonstrating the seriousness of the disease and the unmet medical need. We are continuing to expand our EU direct infrastructure and expect availability of Europe across Europe by the end of 2025. In parallel, to meet the needs of the patient, We plan to provide commercial reimbursed product to early access routes such as main patient programs. The U.

Speaker 2

S. PDUFA date for TransCon PTH is May 14. If approved, we plan to launch our uRPET as quickly as possible thereafter to our established U. S. Commercial infrastructure.

Speaker 2

Moving now to TransCon CNP. Our clinical program is designed to support approval of TransCon CNP as a treatment for patients of all ages with achondroplasia. TransCon CNP dosed at 100 micro gram per kilo per week has demonstrated superiority compared to placebo in 2 52 week trials. In the open label extension, we observed our expected strong patient retention of 97% for now up to 4 years. As a result of this unexpected finding, we continue to review our own data and scientific literature.

Speaker 2

We believe now that ACONDOC data is both a growth disorder and a muscle disorder. As presented at the JPMorgan Conference in January, we showed significant improvement in health and quality of life for children with achondroplasia treated with TransCon CNP compared to placebo. With this growing insight, We have designed our pivotal approach to evaluate meaningful benefits related to all aspects of achondroplasia, Including linear growth and improvements in comorbidity as measured by radiological endpoints, physical function, body compensation and quality of life. We expect to share top line data from this trial, and we plan to submit an NDA in the Q4 of this year. In addition, We are pursuing additional treatment opportunities in achondroplasia.

Speaker 2

Infant trial aged 0 to 2 years, 1st patient already had been enrolled. Combination trial with SKYTOLFA H2-eleven week 26 top line annualized growth velocity in the Q4 of 2024. Adults plan to file an IND or similar in the Q3 of this year. Switching now to oncology. Both TransCon IL-two beta gamma and TransCon TLR 78 agonist had shown favorable safety profiles and single agent clinical activity.

Speaker 2

We expect 2024 to be an extremely important year for oncology pipeline with data readout in well defined patient population in the Q4. Also in the Q4, we expect to have completed enrollment of our randomized Phase II trial in neuro adjuvant head endemic cancer. Longer term, To maximize this potential reach and value of these oncology product candidate, we aspire to commercialize our oncology assets through partnership with companies with specialized oncology experience and capability in late stage development and commercialization. Moving now to ophthalmology. We recently announced the formation and launch of an independent company, Iconis, to develop and commercialize TransCon ophthalmology products globally.

Speaker 2

We have received an equity position in the newly formed company, and we are electable to receive development, regulatory and sales milestone plus single digit royalties. In January, we introduced Vision 2,030, Our strategic roadmap to achieve blockbuster stages for each of our 3 endocrinology rare disease products and expand our engine for future innovation. With the broad applicability of the TransCon technology platform, Our goal, as laid out in Vision 2,030, is to apply our algorithm for product innovation to establish opportunities in greater than US5 $1,000,000,000 indication, as we did with the anti VEGF and DPL1 classes, where we believe we have designed the best in class programs. We are pleased with the interest our once monthly GPL1 program. And from our platform technologies, we expect to continue to generate many more opportunities in the future.

Speaker 2

I will now turn the call over to Scott for a financial review

Speaker 3

We continue making significant progress towards our financial goal of becoming operating cash flow breakeven on a quarterly basis by the end of 2024. I will touch on some key points surrounding our financial results, but for further details, Please refer to our Form 20 F filed today. As we previously announced in early January, Skytropha revenue for the Q4 of 2023 was €64,200,000 compared to €47,000,000 reported in the 3rd quarter and €17,100,000 reported in the same period last year. 37% sequential growth in Skytropha revenue from Q3 to Q4 was again driven primarily by strong underlying demand in the U. S.

Speaker 3

Total revenue for the Q4 was €137,700,000 including the one time $70,000,000 taejin upfront payment recognized as €63,700,000 of license revenue. Turning to expenses. R and D costs in the quarter totaled €90,900,000 down 18% sequentially from the Q3 of 2023, primarily driven by lower endocrinology rare disease related costs as trials and development complete and lower oncology related costs. SG and A expenses were essentially flat at €64,000,000 compared to the Q3 of 2023 reflecting commercialization synergies and expense controls. Total operating expenses were €155,000,000 for the 4th quarter, down 12% sequentially from the 3rd quarter.

Speaker 3

Overall, our operating loss for the Q4 declined sequentially by 73 percent to €37,000,000 from €134,000,000 in the Q3 of 2023. We ended the 4th quarter with cash, cash equivalents and marketable securities totaling €399,000,000 Last month, we announced the formation launch together with an investor syndicate of Iconis to develop, manufacture and commercialize TransCon ophthalmology assets globally. As a result, we expect minimal if any P and L burden from ophthalmology in 2024. As a reference point for Q4 2023 external ophthalmology project costs totaled €6,400,000 As previously announced for the full year 2024 based on current plans, we expect Skytropha revenue to be in the range of €320,000,000 to €340,000,000 at average 2023 exchange rates. Total operating expenses, SG and A and R and D together to be approximately €600,000,000 And we expect to be operating cash flow breakeven on a quarterly basis by the end of 2024.

Speaker 3

Let me now also provide a review of selected key program milestones. For TransCon Growth Hormone, We plan to submit an SBLA to FDA for adult growth hormone deficiency in the Q2 of 2024 And we expect to report top line results from our Phase 2 Turner syndrome trial in the Q4 of 2024. For TransCon PTH, in the U. S, our PDUFA date is May 14, 2024. If approved, we plan to launch it as YORVIPATH as quickly as possible thereafter.

Speaker 3

Outside the U. S, we initiated the launch last month of TransCon PTH marketed as YORVA Path With full commercial availability in Germany and Austria, we plan to roll out YORVAAPATH in our Europe direct and international markets segments throughout 2024 2025. For TransCon CNP, our clinical program evaluating TransCon CNP as a treatment for achondroplasia advances with top line results from the pivotal approach trial and an expected NDA submission for the treatment of children with achondroplasia both in the Q4 of 2024. In addition, during the Q4 of 2024, we expect to report week 26 top line data from the COACH trial in combination with TransCon Growth Hormone and submit an IND or similar for adults with achondroplasia. Within our oncology therapeutic area, we plan to provide a clinical update from indication specific dose expansion cohorts in the ILLEVE and TRANSCEND IT trials during the Q4.

Speaker 3

In addition, we expect to complete enrollment of our randomized Phase 2 trial in neoadjuvant head and neck cancer. With that operator, we are now ready to take questions.

Operator

Thank you. And at this time, we will conduct a question Our first question comes from the line of Jessica Fye from JPMorgan. Your line is open.

Speaker 4

Hey, guys. Good afternoon. Thanks for taking my questions. I realize it's early days, but What can you share with us about the German PTH launch so far? And the second one is, are you seeing any external interest in your TransCon GLP-1 program?

Speaker 4

And then can you remind us what the target profile you're looking to achieve is with that program? Thank you.

Speaker 2

Thanks, Jens. Yes, as I've said before, this is 1 week into a long. We know The unmet medical need is there for the patients. We know how we really are providing a treatment that really are providing Meaningful differentiation for the patient, both on short term and really also helping in eliminating the long term risk of the disease. And what we observed was that exactly as what we had hoped for, The physicians, the day one of the launch, make the prescription, got the material from our Distributor already the first day.

Speaker 2

In U. S, you need to go to a prescription and then reimbursement and then Typically to get the drug in Germany is different. At Medley, you get a prescription, you basically have access to be get the drug immediately at that time. So Belongs, we really look forward to provide Much better update when we come to Q1, much better after Q2 and much, much better again after Q3. So we're really, really feeling that the launch in Germany and Austria is the starting point for Basic being positioned to be everywhere on the globe where there is patients and we will reach them all over the places.

Speaker 2

Related to how we're using lysine of the TransCon technology outside rare disease. Endocrinology, yes, we have our oncology, which I'm really moving forward as we only have a platform. And we're really looking forward to 2024, where we can give you the proof really to patient data, how they are differentiated. You saw our Differentiation in ophthalmology, we made Iconis a spin out company and we really feel that they're really in an optimal value, both to create value and really help the patient in this era. When we come to the 3rd era that we have disclosed we are working on, We basically have the DPL1 class.

Speaker 2

We're going for the once monthly profile. And it's not only for BCC, there's also for metabolic But it's not a product, it's a platform, a platform that can be utilized basic for the class of GPL-1s.

Speaker 5

Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Tazeen Ahmad from Bank of America. Your line is open.

Speaker 4

Hi, guys. Good afternoon. Thanks for taking my questions. I wanted to get your updated thoughts about competition from recently approved Growth hormone therapies and in particular, what is your market data telling you about Novo's Zagroya? How is that, if in any way impacting your launch?

Speaker 4

And then, can you give us some data about what percent of adults Currently take growth hormone replacement therapy and on average, how long does the person stay on therapy? Thanks.

Speaker 2

Thanks, Sidney. It's really a pleasure to take up again the competitive landscape in the growth hormone market. And when we launched, we had a competition that's short acting. It was all the different 6 daily growth hormone that we were competing against. We showed how we were clinical differentiated to this established standard of treatment, How we provided a better outcome.

Speaker 2

We built the market basic to a lot to medical exception because of the product strengths of SKYTOLFA. Now we see 2 emergent therapies coming in, in the long acting spare, 2 product, 1, SAGORIA coming in. And we don't see really impacting us because we're still best in class. We actually believe that these two products have never proven that can show the same outcome as a normal daily growth hormone treatment that you get in the U. S.

Speaker 2

So for us, the barrier for medical exception is just improving. So for me and Ascendis, We don't see that it's really a changing anything about how we are progressing to continue and build us to a blockbuster potential just in the U. S. And we will continue to do it because of our product strengths. Related to the adult, the adult is different compared to the pediatric in many different ways.

Speaker 2

One of the things, the majority of pediatric with typical will have a treatment for a limit year, it can be 4, 5, 6, 7, 8, dependent on the initiation of treatment, where the adult is a chronic disease, Very typical will be needing a treatment for rest of your life. So I would call it a chronic disease when you're diagnosed and start the treatment. So there is a big difference related to that. We often talk about penetration degree with growth hormone treatment and what there is a huge difference between the pediatric and adult is the pediatric It's my view is penetrated up to 70%, 80%, where the adult potential is under 10%. And I think this is a big difference for basic your modeling how we need to see and how we can develop the adult growth hormone deficiency market.

Speaker 2

As you said, this is our first label expansion. We will buildup, so we basically have access to all places where it's possible to use growth hormone because all the patients deserve to have the best

Operator

Our next question comes from the line of Lee Wojtek from Cantor. Your line is open.

Speaker 6

Maybe just to follow-up on TransCon PTH is launching in Germany, understanding early days, but what could be a good framework for us to think about the ramp speed in that market? Any clarity that you can give us around that power experience patients and how quickly you may be able to onboard them? And then in terms of the patients that are enrolled in the early access program in Germany, do you have any color there as well?

Speaker 2

Thanks a lot for the question. I can be bullish now and saying that all patient in Germany that have hypoparatide arishma should be on treatment, because I think that is certain and hormone replacement therapy as everyone that had Type 1 diabetes. With all of them common treatment? Likely not. But what we want to do, We are dedicated to help the patient and building up to scientific clinical data, Our dedication to really to develop this market to ensure as many as possible will be treated with TransCon P2As or Europe parts.

Speaker 2

And this is not only in Germany and Austria, so rest of Europe, this is rest of the international market is basic also in U. S. So when we see this here, I think there is different element how we see the penetration will happen. We always see the benefit of physician really getting the benefit seen in their own eyes best take patient, take them on treating typical 2 to 5 really to see how the product function. The benefit with TransCon PTH After a few weeks, they will receive the benefit.

Speaker 2

So then there is some kind of logical thing, how to get patient in, how to ensure that its capacity in really from the different physician sites really to take the patients in. So when we come into Q2, Q3, I think we will start to see the trend coming in and you can follow our revenue development mainly coming from where we have full reimbursement in Germany and Austria. And then you can see how we penetrate rest of Europe Direct end of 2024, 2025 and how we basically are building up the international market in the later part of 2024 and really starting to be really penetrated in a much higher level in 2025 and 2026.

Operator

Thank you. One moment for our next question. And our next question one moment. And our next question will come from the line of David Lebowitz from Citi. Your line is open.

Speaker 1

Thank you for taking my question. Given the emergence of GLP-1s and their effect on lean muscle mass, Is there a potential role for growth hormone due to the success of the GLP-1s?

Speaker 2

This is a question that basic are going back to the mode of action and the benefit you see with the GPL1. I personally was a little bit skeptical about the entire GPEL1 class in obesity, but it's typical because I'm pretty conservative in many ways. But what I'm 100% sure now is going to be a huge, huge class. And we see the benefit coming out really on lot of different treatment aspect is not only just losing weight, there's a lot of other treatment benefit at this class. The negative part is that is you basically are in a position that you losing and large amount of muscle mass.

Speaker 2

And specific, if you're not adhere to the treatment and make period of break, start up again period of break, you can basically in position that when you're not treatment, you build up the fat tissue faster than the massive way. And I think it's a really, really interesting perspective At basic, you can see growth hormone treatment because that is really where the benefit of growth hormone is that it's really can build up the muscle mass in a much, much stronger mass in a very, very normalized manner. And I think you are right and I would like to explore such a possibility.

Speaker 1

Thanks for taking my question.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Joseph Schwartz from Leerink Partners. Your line is open. Joseph from Leerink Partners, your line is open.

Speaker 7

Hi there. Thanks very much. I was wondering if you could talk about the

Speaker 8

work you did to arrive at your estimate that 70 adults have chronic hypoparathyroidism in Germany. And who are the 20,000 patients that you're targeting there? And how does the target population in the United States compare to the total hypopara population in the U. S, Where we have some guidelines, wondering if that influences the proportion of the market that you think is most addressable here in the United States? Thanks.

Speaker 2

Thanks. I think I got all the question And when we compare the demographic between Germany and U. S, it consists of the basic the 2 group, the post surgical with our 1 group and then you can say the more immunological genetic idiopathic background where your typical will see it arise most earlier in states of life. Germany potentially is a little bit unique with the last number of patient because And I think it potentially is built on the high level of intensive head and neck operation because of really, really strong focus of diagnosis. And from that perspective is, yes, there is potentially more positive patient in Germany than you see in the U.

Speaker 2

S. And other for example, if you take a country like France, France will much more relate to what you will see of treatment way that you see in the U. S. So When we see this different patient population, all of them will benefit of the TransCon PTH treatment or uropads. It's not like one group of the other one are less beneficial in the treatment on it.

Speaker 2

So all of them deserve to have a life with TransCon PTH. Going back to what you say when we talk about the 22,000 patients. And it's not because we see subpopulation that see more benefit or less benefit from that. When we talk about the 22,000 patients, which we try to address first is the patient that from a pharmacoeconomic perspective, have a really, really

Operator

hard

Speaker 2

type on the society that can be potentially come to the state of renal impairment, that can come to a state that we visit hospitalization a lot, that come to a state where they cannot function because of cognitive effect that cannot get a normal life. So out from that perspective is not really a treatment benefit, This is more that the burden for this society and this is where we always need to be. We need to benefit the patient, the society and everyone as all stakeholders. And this is the burden for society as much, much higher for these 22,000 patients.

Speaker 8

Very helpful. Thank you.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Derek Archila from Wells Fargo. Your line is open.

Speaker 9

Hey, good afternoon and thanks for taking the questions. Just 2 from us. I just wanted to clarify, is Gytropha a $1,000,000,000 product The U. S. Just on pediatrics alone or does that assume contribution from adult GHG as well?

Speaker 9

And then just in terms of the cost structure of the endo business, Is this $600,000,000 cost base now how we should be thinking about it for the future? And just how your thoughts about profitability of that business? Thanks.

Speaker 2

Thanks. I will take the first question and then Scott is really happy today now because the actual has an opportunity to come to some of the financial numbers is running, so dedicated all the time. When we look on the potential market, yes, You can see we will have adult growth hormone deficiency. We will pursue some of the other indication too. But we also need to say that we are liberating a normal somatopy molecule, which are well known entity for all different indication that seeing the benefit on growth hormone.

Speaker 2

And if you go to the market of the daily growth hormone and see what is the dynamic there, the dynamic is that none of the daily growth hormone basic Because they're all so much for PHYM2, all of them basic are in a position, none of them have all the indication where the active being reimbursed or used today, because none have really take the effort to go through all the different indication. So it could be potential, the same thing will be applied also on the long acting products that are providing the same So much OP molecule. Scott, will you talk a little bit about expenses and numbers In just 10 minutes.

Speaker 3

How much time do we have? Thanks, Derek. So it's good to get a finance question. So as you saw here in the Q4,

Operator

we're

Speaker 3

realizing now the benefits of streamlined operation operational changes and processes that Jens talked about with OpEx going down to about 155 total. And then of course next year you'll see more come off as a result of basically no P and L burden from ophthalmology. I think you should look at this as a product of the way that we've developed our portfolio and how efficient it can be. Think if you look at our costs for TransCon Growth Hormone and realize the stage of that product and how mature it is, the cost should be dropping pretty substantially in the coming years. And overall, we're going to be pretty efficient in R and D.

Speaker 3

So I would expect more shift from sixty-forty R and D SG and A in 2023 to maybe fifty-fifty or so in 20 24. Longer run, We'll be efficient in R and D. And as we expand globally, I would expect some increase in SG and A as we add People in 30, 40, 50 countries, but it should be pretty minimal. And as you saw going from Q3 to Q4, Our SG and A was basically flat even if we launched an additional product and got ready to launch a second product in Germany.

Speaker 1

Thank you.

Speaker 2

One comment. What you see the result of something was basic element that happened in 2023. You don't suddenly change the company. You don't suddenly streamline the company. It takes a lot of effort.

Speaker 2

It took us Started beginning on 23, really find out how can we build a leaner Essentes more productive, really focus on really optimizing processes, administration and everything like that. And we worked very, very, very successful to that. It was a hard task, not already always pleasant, But we're there now. We are where we want to be now. We're still optimizing our processes because we're scaling for potentially having 5,000 to have 50,000 processes.

Speaker 2

And you cannot use the same PV system that you use for 5,000 to 50 1,000. So this is why we really are still optimizing process, changing the company, because we cannot be a leading biopharma company So we are still transforming. We're still changing our processes and that is what we need to continue to be truly competitive in this landscape.

Operator

Thank you. One moment for our next question. Our next question will come from the line of Kelly Hsieh from Jefferies. Your line is open.

Speaker 10

Thank you for taking my questions. Maybe Switch topic to TransCon CMP. You have talked about the improvement on muscle function And other companies will feel like talk about more proportionality or like upper to lower body ratio. I'm just curious, Have you also looked at proportionality as well? And also when it comes to the combination with SKI Tofa, What would be the most differentiated clinical benefit compared to TrussCon's NPL alone?

Speaker 10

Thank you.

Speaker 2

Thanks. I will start from the back because if you have a child Born with achondroplasia being started treatment as a newborn. Our belief is that Ubasic will nearly have normal growth in this period of time where you have growth related to linear growth. You will not really address and stop or can stop to address the co morbidities, because there exist rest of the life. And this is when we see on the integrated aspect of adchondroplasia, We see the linear growth as one part of the disease and we see the other impact of the hyperactive pathway have on other aspect like for example, muscle weakness and other aspect, which are really from a mode of action is different for compared to what you see on the Contoplast that really are limit in the way they get linear growth.

Speaker 2

So when we think about how we are positioning our combination trial is that What everyone as I have seen of data for the impressive amount of clinical data that's come down from BioMarine related to vosoritide, all of that showing that you normalize growth for the waste waste majority of the patients. But if you have a child that got born and first started treatment of 8 years, they still have a lack of growth. So when we saw all the data that has been generated by daily growth hormone, More than 30, 40 publication, really intensive trial with 40, 50 children. And we see that that basically can induce catch up growth as you can do in growth hormone deficiency, because that is what we do in growth hormone deficiency. The mode of growth hormone is that you can reset the growth to be normal as a final height, If you are on a good adherent treatment, but you can only do that in also growth hormone deficiency If you have a cash up growth, meaning that you grow more in the 1st 2, 3 years, then your basic will see of a normal growth.

Speaker 2

That is why when you think about a child with growth hormone deficiency not had been treated for 8, 9 years starting potential treatment and then suddenly hit the parents' height as expected. This is because of cash outgrowth. And you see the same thing in achondroplasia, if you start to give them growth hormone. I see Growth effect up to 7, 8 centimeters, not as much as you see in growth hormone deficiency and it's likely because they still have a block down on the contour place because they also need CNP. So when we think about the perspective of combination trials, This is the children that not got treated and this is basically all the majority of children today that is not got treated from the gut newborn and really need some cash outgrowth really to get a burst in the growth.

Speaker 2

And this is why we are running this trial. My expectation and now I can be trying to do something that is very, very dangerous. But I believe you can potentially grow them up to 8, 9 centimeters just by combination treatment, because you get the cash out growth for the 1st 1, 2 years. And this is the rationale really for us to go out and make that treatment regime because we do the same as rosuvertide, we normalize growth. So proportionality, yes, We see the same positive trend in proportionality that we have seen and expected to see.

Speaker 2

And we will see more and more when we see more data from longer part of treatment because it takes longer time to really to see the right benefit on this or change of disproportionality, but we definitely are seeing the same positive development.

Speaker 5

Thank you.

Operator

Thank you. One moment for our next question. Our next question will come from the line of Paul Choi from Goldman Sachs. Your line is open.

Speaker 11

Hi, good afternoon and thanks for taking our questions. I also want to ask on TransCon CNP For the your Phase 3 APPROACH study, can you maybe just share what metrics or details you'll provide with the top line results? And what is your medical conference presentation plans for that data? And then second on the regulatory strategy, Can you maybe just help us understand the urgency to file the NDA in the same quarter? Just kind of what the reasoning Behind that is, are you just potentially concerned about a full approval for BioMarin's Voxogo and just maybe some color there would be helpful?

Speaker 11

Thank you very much.

Speaker 2

It's pretty simple about the filing. A sentence approach is to do it as fast as possible in the highest quality. And if anyone else is working in the company and not living out to this aspect, they should leave. So if I can get someone to do the finding in the same quarter we get the data, we should do it. When we come to the Phase 3 data, yes, we have a primary endpoint because that got established as a Traditional weight of a primary endpoint is that really ARM and Rational endpoint for achondroplasia?

Speaker 2

I have my doubt. I think it's more a surrogate marker analyzed high velocity. A treatment is to change the comorbidity of the disease. So the primary endpoint for me is like surrogate marker as Trungal fat is for adult growth hormone deficiency. This is not really the key treatment objective in adult growth hormone deficiency.

Speaker 2

You see other aspect of the treatment that's more important, but it's established endpoint. So when we go to the secondary endpoint, And I said it's really very, very, very simple in my text. We going in and look on the effect on comorbidities. And we do it on lot of different angles. And we want to be sure that we're covering them in the best possible way.

Speaker 2

And the best possible way we can do it is to look On the comorbidities basic that is developed into what we can measure in different physical function, daily function. We do a lot of radiology because we know the texture of the child need to be perfect. So we're 100% sure. We had developed different health related outcome measuring. And I believe that taking all this aspect into it, we will find benefit that never had been See, and I hope it will both come for quality of life, body composition, physical function And also the radiological endpoint that basic providing different way of how then improve the texture.

Speaker 11

And on the medical meeting?

Speaker 2

I think the summary are not driven by medical meetings. So there are some people that are saying they delay data out Because of medical meeting, I think when you have material data, you should come out it, so everyone can see the data. We are not waiting with disclosing data just

Operator

Our next question comes from the line of Andreas Argueraj from Wedbush. Your line is

Speaker 12

open. Great. Hey, guys. Congrats on all the progress and thanks for taking our questions. Just a couple here from us.

Speaker 12

When you think about CNP, can you

Speaker 2

give us a little bit

Speaker 12

of your thoughts around the rationale to expand into adults With achondroplasia instead of going into hypochondroplasia like the other companies in this space. And then Looking at Voxogo and the growth that they've seen primarily driven by ex U. S,

Speaker 2

Maybe you can give us

Speaker 12

a sense of why it's offered off to a slower start in the U. S? And is it driven by the Fact that they have been focusing on height versus other quality of life measures? And then just one last one on the oncology programs. If you Don't find a partner to bring these programs forward, would you consider spinning them off like you did with the ophthalmology programs?

Speaker 12

Thanks.

Speaker 2

Okay. Let me start on the last one because it's very easy. We are here to do the optimal for the patient to get our product being penetrated to as many as possible patients. And we believe that we are in a position when we have seen all the data that will come out end of this year. We already have seen the interest in our program staff.

Speaker 2

We feel pretty confident we would do the optimal where we see the fastest, best way to come out to the patient and we create most value for Ascendis shareholders. That will be the driver from our decision. Then you had 2 comments to CNP. The first one was

Speaker 3

Why not hypochondriplasia?

Speaker 2

Why not hypercontemplation? That is pretty good interesting perspective for us because it's something we are discussing a lot. Because hypochondroplasia is a mild form for abchondroplasia. And I think we will not move over to hypochondroplasia Before we really have provided the optimal treatment, the best treatment that really addressing comorbidity in adchondeblates. Why jump over to something where you basically have not provided a treatment option, but potentially only providing some few linear growth.

Speaker 2

And the linear growth, you could get that for the last 20 years just by giving daily growth hormone. So I don't see that is really a treatment benefit that is just providing linear growth. What we're trying to address is basic the comorbidity of the disease and we will continue to do that until we find the best possible solution to give them a meaningful improvement in quality of life. And the other thing is that, I think these two things are related to each other. I don't believe being short is a disease, even though I'm pretty tall.

Speaker 2

So I actually don't believe being short is a disease. And I like to think you should never consider short to PNPCs. I believe that taking just a linear growth It's some way it's more appealing in some countries than others and definitely in U. S. It's not a disease to be short.

Operator

Thank you. One moment for our next question. And our next question will come from the line of Yaron Werber from TD Cowen. Your line is open. Hey,

Speaker 5

guys. This is Joyce on for Yaron. Thanks for taking our question. Just maybe hoping to get your thoughts On the emerging competitive landscape for hypopara, you're clearly ahead to market, but there's another one, daily PTH analog in Phase 3. And then there are a couple of others in the pipeline behind it, some looking to develop oral candidates or once weekly candidates.

Speaker 5

So just any thoughts or comments there would be great. Thank you.

Speaker 2

Thanks a lot. When I took a look from endocrinology's perspective and look on the biological system in the body. The complexity of that, how really to provide an Treatment of an hormone replacement therapy in a situation where the pathology has been extremely, extremely multiple organs effect, having the right dose not too hypo and See what we did in with Xaltropha. We provided with Somatopine the same molecule that really are being produced by the endogenous gland. And I believe When I also go to hypopara, this patient need to have a physiological level of PTHs Then providing the same mode of action.

Speaker 2

I actually went to a conference and heard some of the questions for physician on some of the other competitive product. And one of the key questions that came up. We know PCAs have effect on so many, many different organs. When you change the entire mode of action, how can you really prove and believe you can create the same normal physiological system that you will expect to get with a normal endogenous PTAs. Here's how we defined Transco PTH to provide a normal same as industrious PTH Exactly the same part that give the mode of action in the physiological levels.

Speaker 2

And I don't think any treatment that changing that will provide the same holistic benefit on all aspects of hypopara for any patient.

Speaker 5

Thank you.

Operator

Thank you. One moment for our next question. And our next question comes from the line of Leland Gershell from Oppenheimer. Your line is open.

Speaker 8

Thanks for taking our questions. 2 from us, Manish on Skytropha and Transcon PTH. On Skytropha, again, you mentioned in past commentary about the Decreasing investment among the daily growth hormone companies and products. I wanted to just hear any updated color you may Be able to share with respect to the marketplace, in terms of the dailies if that's a continuing trend that you're seeing. With respect to TransCon PTH as we anticipate approval and then launch Q3 of this year, if you could remind us the number of patients you have available in the states between both those who may be in the open label studies as well as those who are in the EAP?

Speaker 8

Thank you.

Speaker 2

Yes. You're right. We have discussed a lot what we call the long term or many years perspective of the consolidation in the growth hormone market. And the trend is happening exactly as expected. Specific with the entrance of the 2 other long acting, The basic the daily growth hormone is starting to disappear more and more, because These two company that is providing them the key element where we have seen them take in market is basically taking their own product, their own product on the daily growth hormone class and then transform over to the long acting, where we take it from everywhere because our improved treatment outcome.

Speaker 2

So I see our market share being Basic, the same as we someway predicted from 3, 4 years. What is happening is that the 2 oils are long acting, but just take part of the daily growth hormone. We never thought we actually will basic having access to. And so our market penetration, our market share, Our market value of Xyaltrofen is basic unaffected to what we have seen. Go to T6, TransCon, PTH and the U.

Speaker 2

S. Specific. The question you are providing me is the team, because our both Phase II and Phase III would have We should be high retention and continue to have extremely high retention now on 4th or 5th years. I cannot remember now more. The problem is that I cannot really remember how many patient that is in Europe and U.

Speaker 2

S. Between the different trials. So therefore, my numbers are a little bit weak in that. I would think it's about 40, 60 or something like that, But I am not 100% sure about that. So please, Scott can give you the number when he's finished here and send it to you.

Speaker 8

Great. Thank you very much.

Operator

Thank you. And that's all the time we have for Q and A today. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Operator

Everyone, have a great day.

Powered by Quartr
Earnings Conference Call
Ascendis Pharma A/S Q4 2023
00:00 / 00:00