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spk05: Good day and thank you for standing by. Welcome to the Ascendus Pharma Third Quarter Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. We would also like to remind you that during this session, each person can ask only one question and one follow-up question. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Tim Lee, Senior Director, Investor Relations. Please go ahead.
spk17: Thank you, Operator. Thank you, everyone, for joining our third quarter 2022 financial results conference call. I'm Tim Lee, Senior Director of Investor Relations at Ascendance Pharma. Joining me on the call today is Jen Mickelson, President and Chief Executive Officer, Scott Smith, Senior Vice President and Chief Financial Officer, Dr. Steena Singhal, Head of Clinical Development Oncology, Dr. Brigitte Volk, Senior Vice President, Head of Clinical Development and Medical Affairs, Endocrinology Rare Diseases, and Joe Kelly, Head of U.S. Commercial Endocrinology. 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 Skytropa for the U.S. market, the commercialization of Transcon HGH for the EU market, or our progress on our pipeline candidates and our expectations with respect to their continued progress, statements regarding the expected timing of approval and launch of Transcon PTH in the U.S. market next year, statements regarding our strategic plans, our goals regarding our clinical pipeline, including the timing of clinical results, statements regarding the U.S. market approval of Skytrova and our pipeline product candidate statements, regarding our planned regulatory filings, are expansion into new therapeutic areas and statements regarding the ability to create a sustainable leading global biopharma company. 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. Our forward-looking statements do not reflect the potential impact of any licensing agreements, acquisitions, mergers, dispositions, joint ventures, or investments that we may enter into or terminate. We assume no obligation to update these statements 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 statement section in today's press release in the risk factor section of our most recent annual report on Form 20F filed with the SEC on March 2, 2022. Transcon Human Growth Hormone, or Transcon HGH, is approved by the FDA in the U.S. under the brand name Skytropha for the treatment of pediatric patients one year or older weighing at least 11.5 kilograms and have growth failure due to inadequate secretion of endogenous growth hormone. The European Commission has granted a marketing authorization for Lonefeg-Somatropin Ascentis Pharma, developed under the name Transcon HGH, as a once-weekly subcutaneous injection for the treatment of children and adolescents aged 3 to 18 with growth failure due to insufficient secretion of endogenous growth hormone. In general, we refer to this product as Transcon HGH, unless we're referring to the product in the context of a particular jurisdiction, such as the United States or the European Union. 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 made on the conference call regarding our product candidates shall be viewed as promotional. On today's call, we'll discuss our third quarter 2022 financial results and we'll provide further business updates. Following some prepared remarks, We will then open up the call for questions. I'll now turn the call over to Jan Mikkelsen, President and Chief Executive Officer.
spk10: Thanks, Tim, for this long introduction. Good afternoon and good evening, everyone. Again, an important quarter for Ascendix as we continue to achieve and approach new major milestones in our journey to fulfill them. Our vision, tree by tree, to become a sustainable, profitable, leading biopharma company. Earlier this week, we announced we had achieved another important milestone. As FDA has accepted for priority review our NDA for Transcon VTH for the treatment of adult patients with hypopara. FDA expects to complete the review of our NDA by April 30, 2023. We believe we will bring a totally new treatment paradigm to the Hypopera community. Today we are reporting Skytropha US revenue of 12.3 million euros this third quarter. Again, more than doubling our sales compared to last quarter. All patients continue in the Phase II accomplished trial for Transcon-CMP with no dropouts and the longest treatment duration now around two years. We are looking forward in the coming weeks to sharing top-line results, including OLE data in children aged 2 to 10 with achondroplasia. In oncology, we will have our first oral presentation at next week's Society of Immunotherapy in Cancer conference. We look forward to sharing our first in human safety and initial efficacy data supporting our recommended phase 2 dose for Transcon TLR78 agonist. Last quarter, I made the following statement. that we are on track to become cash flow positive, without the need for additional equity from investors. Given the successful launch of Skytober in the US, combined with the expected US launch of Transcon PTAs in the middle of next year, supported with our strong cash position of around 1 billion euro. After this quarter, my confidence that we will fulfill this belief has been reinforced. Okay, let me now share with you more details on our program. We designed Transcon Growth and More, now marketed as Skytrover in the US, to address the unmet medical need that results from children taking Data Growth and More. With a different set of products, we are building Skytober into the global market leading brand and at the same time expanding the overall value of the growth hormone market. For this quarter, we reported Skytober revenue of 12.3 million euros compared to 4.4 million euros in the second quarter. As we expect, the majority of patients will be on Skytropha treatment for at least three to five years. Revenue for each quarter becomes the new base for the next quarter. From that base, revenue continues to grow through the addition of new reimbursed patients. In Q4, we expect to grow the number of new reimbursed patients at a similar level to what we have saw in Q3, providing a strong base for revenue growth in 2023 and beyond. I believe with our improved commercial execution, we are achieving the goals we set out when we launched Skytropha in the US. By building on the product strength of Skytropha, and providing patients with a differentiated treatment. Over the coming quarters, we will continue to provide updates on all our programs that support our efforts to build Transcon Growth Hormone into a leading global brand in a growing growth hormone market. Let us turn to Transcon PTH. a product candidate we are dedicated to bring to patients as soon as possible. Earlier this week, we announced that FDA has accepted for priority review our NDA for transplant PTAs for treatment of adults with hyperparalysis. This is our second product candidate in a row that we are taking all the way from product design to successful regulatory filing. These patients faced an urgent need for treatment to effectively address their disease. Its complications, and importantly, help restore normal life for them. We hope to have a regulatory decision by April 13 of next year from FDA in the US. Our view of the importance of PTH replacement therapy was confirmed by the recent guidelines updates for the management of hypopara. The authors suggested consideration of PTH replacement therapy for HB patients insufficiently controlled due to any one of the following. Symptomatic hypocalcemia, hyperfoscemia, venal, insufficient, hypercalcivoid, or poor quality of life. They also observed that patients with poor compliance, more absorption, or who are intolerant of large doses of calcium and active vitamin D might also benefit from PTH therapy. With the potential to treat all HP patients regardless of disease background and growing evidence for long-term clinical trial data showing durable responses, we believe that transplant PTA could address this major unmet medical need. With the US regulatory timeline set, and review underway. We are focusing on preparation for an expected US approval and launch in Q2 next year. Expanding our global reach for Transcon PTAs. We are on track to submit our MAA in Europe and we remain on track to report top-line results from our Phase III partway Japan trial. Both events expected to happen this quarter. We are dedicated to further optimizing treatment options for patients. With up to three years of follow-up data from our clinical trials of Transcon PTH, we believe that HB patients on stable PTH doses a once-weekly PTA product could be a potential attractive treatment option. Our data demonstrates that each patient goes to multiple titrations and reads normalization of calcium hemostasis at different times. We believe once patients obtain their stable doses of daily Transcon PTAs, That is when they become optimal candidates for switching to a once-weekly PTH therapy with the same mode of action. Our once-weekly Transcon PTH product candidate, now in preclinical development, is based on the same Transcon technology and PTH parent drug as daily Transcon PTHs, enabling, we believe, predictable and safe switching of patients from daily to weekly Transcon PTH. Turning now to Transcon CMP. We are looking forward in the coming week to sharing top line results from the accomplished trial. Our phase two randomized double-blinded placebo-controlled clinical trial of Transcon CMP in children aged 2 to 10 with acondoplasia. The COMPIS trial was designed to enroll four dose cohort with up to 15 patient ease, randomized 3 to 1, active to placebo, in sequential cohort of 6 micrograms per kilo, 20 micrograms per kilo, 50 micrograms per kilo, and 100 micrograms per kilo per week, followed for one year on double-blinded basis. A total of 57 patients were enrolled in the four cohort, with four zero of the patients younger than five years old. All 57 patients enrolled completed the blinded portion with no dropouts. After one year of double blind treatment, patients transitioned from the dose cohort to an open-label extension, OLE, portion of the trial. As of today, all patients have been transitioned to the 100 micrograms per kilo per week dose level and all continue in the open label extension at that dose. We continue to see on a blinded basis the same well-tolerated safety profile we reported to you last December. with the longest treatment duration now around two years without any dose reduction and 100% patient retention. The primary endpoint of the ACOMTIS trial is analyzed high velocity after one year of treatment. The primary analysis is to compare mean analyzed high velocity for Transcon-CMP cohort to that for placebo-treated patients. We also plan to report the mean analyzed high-velocity data for the two patient groups, patients aged 2 to 5 and 5 to 10 years. In addition to the top-line randomized double-blinded data, we also plan to report preliminary data from the open-label extension portion of the study. These data will provide information on treatment impact when switching from placebo or lower dose up to 100 micrograms per kilo weekly dose of Transcon-CMP. I get a lot of questions about what my expectations are for this trial. First priority. First priority. Treatment needs to be safe and well tolerated. From the perspective of outcome, analyzed height velocity, or call it analyzed growth velocity, has been validated as the regulatory primary endpoint. Just as with height velocity in other growth disorder trials, this endpoint in acroendoplasia is dependent on multiple demographic factors. In particular, the age of the patient is a major factor determining the outcome. For the only approved treatment in the US for acondyloplasia, the analyzed high velocity for patients aged 5 to 14 was around 5.4 cm per year. with a greater treatment effect in analyzed height velocity for the age group 8 to 11 compared to the age group 5 to 8. I estimate the benchmark for analyzed height velocity for the age group 5 to 10 in the accomplished trial will be slightly lower than the 5.4 centimeter per year. as the accomplished trials have fewer patients in the faster-growing age group of 8 to 11 compared to the age group of 5 to 8. To further evaluate Transcon-CMP at 100 micrograms per kilo per weekly dose, We have submitted a protocol to FDA to initiate a global randomized double-blinded placebo-controlled phase IIb trial in children with alcoholism from 2 to 11 years of age. This trial is expected to enroll about 80 patients and measure, analyze growth velocity after one year of treatment at the primary endpoint. Perhaps more important, we believe this trial will enroll sufficient patients to analyze additional secondary endpoints, which may help to explain why we see 100% patient retention in our trial. We expect to complete enrollment early next year of this trial. In summary, we remain on track with our vision 3x3 goal to obtain approval for three endocrinology rare disease products by 2025. Turning now to oncology. With our first two immunotherapy programs, we are levering both the Transcon systemic technology for Transcon IL-2 beta gamma, and for first time in humans, the Transcon hydrogel technology for Transcon TLR-7-8 agonist. TRANCON TLR78 agonist is designed to kickstart the immune system inside the tumor and using our intertumor hydrogel technology to provide sustained release of the TLR78 agonist over weeks, thereby activating the immune system within the tumor microenvironment without systemic toxicity. We recently completed dose escalation and declared the recommended Phase 2 dose for our Transcon TLR78 agonist candidate. With a favorable safety profile and early signs of clinical activity observed as monotherapy or in combination with a checkpoint inhibitor, we are pleased that our abstract for top-line dose escalation data was selected for an oral presentation at CITSI, the annual meeting of the Society for Immunotherapy in Cancer being held in Boston next week. Our second oncology product candidate, Transcon IL-2 Beta-Gamma, is designed to broadly increase systemic stimulation of the body's immune system, and we believe it has the potential to become a new backbone for cancer immunotherapy. Transcon IL-2 beta gamma continues to be well-tolerated as monotherapy or in combination therapy, and we're seeing promising pharmacodynamic responses and we're continuing dose escalation. We plan to share monotherapy top-line results later this quarter. As you can hear, there are so many great milestones we have achieved, but also so many, many more in the near term. With a cash position of €935 million, Ascentis is on track to achieve our vision 3x3 and I remain confident in our ability to drive continual progress. I will now turn the call over to Scott for additional details and a financial review before we open up for questions.
spk04: Thank you, Yen. So as you heard from Yen, we are making great progress on behalf of the patient across our entire portfolio. With Skytropa launched in the U.S. and expected to launch in Germany mid-next year, combined with the expected U.S. approval and launch of Transcon PTH in Q2 next year, our advancing pipeline of product opportunities addressing major unmet medical needs and our cash position, which is very strong. We are more confident than ever in our ability to become cash flow positive and to deliver sustainable, profitable long-term growth. Now on to our results. Today, we reported Skytropha U.S. revenue for the third quarter more than doubled sequentially to 12.3 million Euro from 4.4 million Euro in Q2. based on continued growth in the number of reimbursed patients. And in line with comments Yen made in May about doubling our revenue quarter to quarter, we believe we remain on track to achieve fourth quarter Skytropha U.S. revenue of at least 16 million euro, based on Yen's simple algorithm from May, compared to the company compiled cell side analyst consensus estimate of 11.9 million euro. This expected Q4 revenue would then provide us with a very strong base for Skytropa U.S. revenue in 2023 and beyond. Growth in U.S. Skytropa revenue during the third quarter primarily reflects the strong increase in reimbursed demand. The stronger U.S. dollar provided the minor benefit of approximately a half million euro. Now turning to operating expenses. Research and development costs for the third quarter were 97.4 million Euro compared to 58.8 million Euro during the third quarter of 2021. As a reminder, the third quarter of 2021 included the one-time reversal of previous write downs of pre-launch inventories, which reduced R&D costs by 54 million Euro. Overall, this reflects ongoing normalization of our overall R&D cost structure as more programs progress from early through late stage development and approval. Selling, general, and administrative expenses for the third quarter were 60.7 million euro compared to 39.3 million euro during the third quarter of 2021. These expenses primarily reflect higher commercial costs following the launch of Skytrofa and preparation for future product launches in the U.S., and Euro. Net finance expenses of 20.9 million Euro for the third quarter included a foreign exchange rate gain of 44.1 million Euro related to translation of our US dollar holdings of cash, cash equivalents, and marketable securities to Euro. Overall, we had a net loss for the third quarter of 169 million Euro or 3.03 euro per basic and diluted share compared to a net loss of 80.3 million euro or 1.47 euro per basic and diluted share during the third quarter of 2021. Importantly, we ended the third quarter with cash, cash equivalents, and marketable securities totaling 935 million euro. Let me now also provide an update on timing for selected key milestones for the remainder of the year. For Transcon HGH, we are on track to complete enrollment in the global phase three foresight trial in adult growth hormone deficiency in Q4. For Transcon PTH, we are on track for a planned MAA submission in Europe in Q4, and for Pathway Japan, top-line results are expected in Q4. For Transcon-CNP, we look forward to sharing the top-line results from the Phase 2 ACCOMPLISH trial in the coming weeks. For Transcon-TLR78 agonist, we plan to present top-line monotherapy and combotherapy dose escalation data from the Phase 1-2 TRANSCEND-IT101 clinical trial at the CITC conference next week. And for TRANSCON IL-2 beta gamma, monotherapy top line results are expected from the phase 1-2 IL-BELIEVE trial in Q4. As you can see, it's an incredibly busy time for Ascendus going into the end of the year with key catalysts across the pipeline, both in endocrinology rare diseases and in oncology. With a strong balance sheet, strong commercial progress, and disciplined cost focus, we believe we are well positioned to fulfill vision 3x3, have the capital to fund our growth initiatives, and become cash flow positive. With that, operator, we are now ready to take questions.
spk05: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you'll need to press star 1 1 on your telephone and wait for your name to be announced. We would also like to remind you that each person can ask one question and one follow-up question. Please stand by while we compile the Q&A roster. Our first question comes from Jess Fai with JP Morgan. Thank you for standing by. Your line is now open.
spk14: Hey, guys. Good afternoon. Nice result tonight. How are you thinking about the potential for the Phase 2b CNP trial to be registrational?
spk10: That is a great question, Jess. And what we believe is the most important part for our Phase 2 trial, the accomplished trial, is really to prove that we're providing a meaningful benefit to the patients. that we really are hitting the target product profile that we lay out when we designed Transcon-CMP to be in best-in-class product opportunity for treatment of air contemplation. We designed it out from the perspective that it was not only focused on efficacy, but included everything related to safety, solubility, the once-weekly dosing profile, because we know from 20 years in growth hormone division that a daily dosing is not functioning. All that we incorporated, and that is the most important part that we want to see from the accomplished trial. When you come to the question that if we can some way file on this data, I think it depends what we see in the coming weeks. And I will be much better suited on for me to really answer this question when the data has been unblinded, I have looked at that, and we have reported to you. Then I think I will be really, really well positioned to come with my belief that can be a lot of difference between different geographic regions, that can be a lot of different elements with basic with someone saying we would like to wait for the 2B trial, and I need to wait to see the data.
spk14: Sorry, I was asking about the 2B. Could that be registrational?
spk10: That is what we believe, but the 2B was basic in the system being developed in such a manner that we hope in the 2B we can come with an explanation why we basically are seeing this 100% retention in our Accomplish trial because we must provide something more to this patient group that just analyzed growth velocity I don't believe this is the first time I see it right in a contemplation where you basically see 100% retention We hear stories about the patients we hear when we talk with the caregivers But we need to quantify that and that is what we hope we can quantify in the to be Thank you
spk05: Thank you. Our next question comes from Josh Shimmer with Evercore ISI. Josh, please go ahead.
spk08: Hey, thanks so much for taking the question. I just want to follow up on the one from Jessica. I guess given how close we are to the phase two results for TransConCMP, why not wait for them to be reported and then design a more fulsome phase three
spk10: protocol why kind of move quickly and why why specifically a phase two instead of phase three given how close we are to the data thank you hey just this is because we dedicated to bring this product out to the patient as fast as possible so what we basically are doing we are incorporating as in exploratory endpoint and huge menu list of all the elements we basically believe we are providing to the benefit of the patients. And as soon as we basically have gone through the entire complex trial, really understand what is the key element we're sitting on, we basically can iterate all one or two, three or four of this expository endpoint up to secondary endpoint. And therefore, that basically can be integrated in the labeling discussion. so we get so many patients and caregivers coming to us when can we get this product out to the market and this is why we dedicated to work in this way where we basically are cutting down about one year in development time before we look at the data go in and discuss it We basically will have enrolled basically all the patients in the beginning of next year. And then we basically can evaluate and basically achieve the same thing.
spk08: Got it. If I could ask another very quick one. Thank you. You've indicated that you'd disclose a new therapeutic category for the Transcon platform by year end. When can we expect that? In what form? And what are the gating steps for that announcement?
spk10: The gating step is basic that we are executing on the preclinical candidates, we are building up the pipeline, we are building up what we need to do. As we did when we disclosed our rare disease endocrinology pipeline with TransConPTH and TransConCMP, we disclosed that in 2015. In 2018, we disclosed our oncology pipeline and we said we would go out and disclose our oncology pipeline and now we are disclosing our third therapeutic era. And I can guarantee I'm really thrilled to be going back again to a therapeutic area where there's a lot of really unmet medical needs, but also a lot of established target, established parent drug with well-functioning mode of action that really fit our Transcon technology systems. And it will be end of this year, potentially at J.P. Morgan, if we want to provide some benefit to where there's a lot of investors at that time.
spk08: Thanks so much.
spk05: Thank you. Our next question comes from David Lebowitz with Citibank. David, your line is now open.
spk09: Hello. Thank you for taking my question. An additional question on achondroplasia. When we look forward to the data coming out, given the the cross-trial comparisons and the different geographies, populations are going to be different. What is a way that we can benchmark what we are seeing and what its clinical meaningfulness is and how it might actually compare with the competing products?
spk10: So thanks a lot for the question, because as I said in the preferred remark, It's a question I really get a lot. And what we are building on when we're trying to benchmark our Transcon CMP to the only approved product here in the US, we're building on literature. We're building on science. For example, I'm looking on a publication just in front of me. safety and persistent growth-promoting effect of vasoatite in children with achondroplasia, two years' result from an open-lady phase 3 extension study. This publication is really interesting because there you have analyzed growth velocity, which is the same as analyzed height velocity. And basically, you have the analyzed growth velocity both from the patient population that got transferred up, got directly on vasoatite, but also the placebo arm that got transferred up to vasoatite. And in this publication, there is direct, the analyzed growth velocity on an absolute level, because that is how we can compare it. Then you go back and saying, how can you compare in trial, because there is always a dependency on outcome, analyzed growth velocity, depending on different demographic factors. And one of the key elements in Akron Blaze is clearly for all the literature there is, is the age of the patient population. And this is why, as I said in the prepared remark, we will split it up between 2 to 5, 5 to 10, because there's not really any good comparison for two to five, because there is not really data that really providing a good benchmark for the two to five. Where we have a good benchmark, mainly coming out from this publication and all the FDA filing documents, is for the five and up. And there is clearly a dependency if you look on the patient group between five to eight or eight to 11, because there's a much, much more treatment effect with Rosirotide in the 8 to 11 group. And therefore, if you adjust for this difference with that, you basically can pretty precise go in and make this comparison. And I actually will have no problem to show my own calculation how I do it. I have no problem by sharing that because it's built on science. It's built on peer-reviewed publication and not built on perception.
spk09: Thank you very much for taking my question. Appreciate it.
spk05: Thank you. Our next question comes from Lee Watsek with Cantor. Lee, your line is now open.
spk11: Okay, great. Thanks for taking my questions and congrats on the order. Maybe just one on TrustCom PPIH. Now you have a PDUFA date in April next year. I just wonder if you can maybe talk about your launch preparation right now and potential synergy with SkyTrofa in the U.S. And also, how should we think about your commercial strategy in Europe?
spk10: Yeah, thanks a lot. You said the right word, synergy, because it was why we built up the pipeline in rare disease endocrinology with three independent product opportunities where we expect to launch one product after another with an interim of two years. And that is what we have built 21 for Skytrofa, we hope 23 for Transcon PTH, and we hope the next one coming two years after. What we are also doing is that we do a global commercialization. We are dedicated to a global commercialization. Joe, that is sitting in front of me, he is responsible for the group here in the US that do commercialization for us. As you have seen, we have different strategies in different geographic regions. We are building up now the loan capabilities in Europe ourselves. We just opened a German headquarter in Munich, so we are ready to launch from there. We are doing in Greater China to our JV, or we can say our ownership in Vision Pharmaceuticals, so we are also creating value from that perspective. When we come to the U.S., yes, there is a lot of synergies. And this is why we have a pipeline approach where we have two things need to be fulfilled for really be checking into an Ascendis pipeline in Realities and Technology. First, there needs to be synergy between the product and the other thing is need to have at least 1.5 billion in sales revenue expectation. If anything is not on that, it's not really something we want to take on it because we come from system where we run P&L and not just streams. So therefore, we are building our pipeline on synergy. So when you think about synergy, then the logical word is infrastructure. And people don't actually think about infrastructure as a key element. I really believe IT solution, facilities, people, everything like that, this is really where you have so much infrastructure and synergy. Just conference. You go to one end of conference, you have one booth for three products. You know, this is meaning that your basic service safe to search. And out from that perspective, and Joe can comment about it, how we can do where people, some might think a little bit narrow-minded, they think about just Salesforce, they just think about medical affairs, which are running on a different part of the organization. How much do you really have synergy? And obviously, as synergy, we can switch between the from one to the other one. But perhaps, Joe, you can say how we are prepared. We are in the full lungs mode. We have been in the full lungs mode for six to 12 months now, and we want to be ready for Q2 next year. It's going to be our biggest problem ever, Transcontinental PTAs.
spk11: Okay, great. Maybe just... Oh, go ahead. Go ahead. Maybe just a quick follow-up on, you know, Transcon-CMP Phase 2b. I wonder if you can share some of the secondary endpoints that you talk about. My understanding is that, you know, your Phase 2 trial is still blinded. So I guess what insight, you know, can you gain from the Phase 2 trial to help you finalize the Phase 2b protocol?
spk10: The Phase 2b protocol is already filed by FDA. So we are full blown into our Phase 2b. We expect to enroll all the patients basically aligned now in our achieved trial, our national history. The patients are just waiting to be switched over in the beginning of next year in the trial. What we have in our protocol is pretty simple, that we have a huge menu list, a huge menu list of all different elements where we believe the benefit could be. But I think Begitte, which is in the call, and she is heading up the clinical development regulatory medical affairs of a rare disease endocrinology. Perhaps, Begitte, you will say some words about all the different exploitative endpoints we have built into the protocol, and we hope we can elevate them up to a secondary endpoint when we really have looked at all the data for accomplice.
spk16: Yeah, thank you so much, Jan. Thanks for the questions. Yes. So, I think we are very excited about the 2B protocol. And again, I mean, our objective is to hopefully provide timely access to this potential treatment opportunity. So, patient-relevant outcome measures is something we have included currently in exploratory measures. That was something we were very proud of having HPAS developed for our PGH program. we aim to have similar patient-relevant outcome measures for this program. And then we will also have other anthropometric measures, including body mass index, et cetera. So the relevant menu of of relevant incoherence are captured as exploratory and will be addressed appropriately as emerging insights into evidence in this relatively new field of medical intervention in that kind of patient.
spk10: Thanks, Birgitte.
spk05: Thank you. Our next question comes from Paul Choi. with Goldman Sachs. Paul, your line is open.
spk07: Hi. Thank you. Good afternoon, and let me add my congratulations on all the progress. Just a point of clarification, can you comment on whether, clarify whether you have seen anything from the blinded portion of the Phase II accomplished study has informed your decision with regard to trial design for the Phase 2b approach study, or was it just based solely on the available open-label extension data?
spk10: We, as have been comments before, we have looked on the blinded data. for the accomplished trial. And we also have been looking on the open label extension data. We believe we can do that without jeopardizing anything to the double-blinded nature on the trial. We're feeling confident this is a responsible way to do it. And when we look at the data, we're just looking very much forward to really disclose it to you in the coming weeks.
spk07: Okay, thank you for that. And then as a follow-up on the commercial side, maybe for Joe, can you maybe just provide us an update on what your payer conversations or feedback has been like with regard to potential pricing of TransCon PTH? You obviously launched Skytropha at a premium to the market average in the growth hormone category. So just maybe any, you know, qualitative or quantitative feedback you can provide would be great. Thank you for taking our questions.
spk10: Thanks a lot. I think I can just start that we are in a position that we basically are evaluating exactly the optimal price structure so we can really following the value we have in a patient first. And we came up with on a premium pricing. And I think we did it well, really respecting the value of what the product is providing, not only for the patient, the caregivers, but also for the society. And we believe we will do the same responsible thing when we come to Transcon PTH. Joe, will you comment on the more factual part on it? Yeah.
spk02: Sure, Paul. So right now, MIT says that we have around 60% coverage at this point. But really what we've seen so far since the launch is that's really not important because we are, HCPs are getting patients reimbursed whether they're covered or not. If they are willing, which most are, to put in the work to get that patient reimbursed, typically they're getting a thumbs up from the PBM and the payer.
spk10: I think Joe is coming a little bit about our Transcon Growth Mode Skytropha sales, but I think Paul wanted to hear more about the PTH pricing structure. Ah, okay. If you have any comments.
spk02: Yeah, I mean, there are synergies, you know, when we're out in the marketplace in front of the payers and PBMs that we'll certainly leverage between Skytropha and Transcon PTH once approved. And that's all I'm in about that.
spk15: Great. Thank you.
spk05: Thank you. Our next question comes from Vikram Kurohit with Morgan Stanley. Vikram, your line is now open.
spk06: Hi. Good afternoon. Thanks for taking our question. So first one on Skytropha. So we all know that obviously you provided a threshold for revenues for Skytropha. that you could achieve for 2022 last quarter. But I guess looking forward, do you plan to provide formal yearly SCAR-2 for sales guidance in 2023? Nope. Okay, understood. So follow-up question then, separate topic. The IL-2 beta gamma data expected by the end of the year, what could we expect to learn there? And then do you think that would be enough of a data set to make decisions on next steps for that program?
spk10: First of all, when I look on our IL-2 beta gamma, we have a dream not to make something that can combine with a checkpoint inhibitor, but make a treatment regime available for the patient that is basically providing better efficacy, better safety than what you can achieve with checkpoint inhibitors. And our program is progressing on a speed and with data that's really supporting this stream. I'm really pleased to see it because the Transcon technology together with our protein design of an optimal high-potent non-alpha compound is an optimal combination to achieve this stream. And what Stine and her team really executing on and I'm really happy that we not have a recommended phase 2 dose yet because we still dose escalation to complete behind what we expected to do because the profile is so extremely safe. So Stine, your comments?
spk01: Thank you Jan. We are in the middle of monotherapy dose escalation and also dose escalating in combination with the checkpoint inhibitor. By the end of this year, we hope to have some initial first results for you on the clinical data. Most impressively, I think, as Yen has mentioned, is that the safety is as we have designed with the TransCon technology to do, which is to make cytokine therapy very tolerable for patients. And I think the key thing we are looking for is the pharmacodynamic effect, how far we can push it beyond what we have seen with any other IL-2 variants out there.
spk10: So, how we typically just mentioned to give you a little bit more concrete flavor on, we look on ALT. And we have a target we need to be plus five in ALC compared to, and no one else have ever managed to do that. Why do we believe that? Because if you do on Proloquine, if you really have a patient that can tolerate the treatment, they're about two to three fold in ALC. And then you start to see monotherapy effect. So all the companies that developing and non-alpha and have an ALC under two or three levels, There is no expectation ever for them to see monotherapy effect because their biology, their science is not really supporting it. This is why we want to go up as fast as possible to an ALC that's higher than anyone else that do because then we know that the immunological system is really primed to fight and kill the cancer.
spk05: Thank you. Our next question comes from Leland Gershel with Oppenheimer.
spk13: Hey, good afternoon. Thanks for taking the questions. The line is open. Hey, good afternoon. Thanks for taking the questions, and good to see the progress. Just two questions for me. One on Transcon CNP, just again drilling down further on the regulatory side. You know, the other company that's out there with its own 800-plasia product now has said that The accelerator approval pathway would be closed to any new entrance given their approval. So should we take that to mean that that you would need to face to be that you've planned at least to get approval. Or do you think that through discussions with FDA or other agencies, you may be able to file off of the accomplished data just to be just to clarify that and also want to ask respect to Skype trophy in the absence of any guidance expectation for next year. Could you comment if you're comfortable with the current quarterly run rate as you've indicated for Q3 to Q4 of this year as we go into 23? Thank you.
spk10: Yeah, let me start on the last question. Because what is the great thing with the scratch office sales is that we're building on last quarter's baseline. So if you're, for example, saying is that this quarter here, we have 12.4. We basically are keeping patients on treatment for three to four years. Meaning is that we already have 4.4 million for Q4. So when Joe and his team go out and getting new patients, new reimbursed patients, it's just adding up. So if you, for example, saying if he do the same speed as he did in this last quarter in Q4, he will end with 16 to 18. million in q4 it's a simple calculation even i can calculate it without an mba and if you just take four times for example 17 in the middle and then you can say that is basically baseline we already have an expected expectation to see in 2023 so everything we add of new reimbursed patient is at on this baseline And this is really nice calculation and nice way to look at it. And I like mathematic algorithm a lot. And it gives me an easy way to some way make my own prediction about what I see of expected revenue for 2023. The last question is a big, big, big, big question for me because I really don't understand this question. I've got it about 20 times now. And I think it's somewhere being generated out from a lack of knowledge, a lack of understanding of regulatory pathway in the U.S. What is happening is that the primary endpoint is getting validated as utilizing analyzed height velocity as the endpoint. It's just meaning is that it's not closed for anyone else. So I'm totally lost in this question, and I don't think there is any kind of scientific regulatory element that really in some way is supporting this kind of statement.
spk13: Okay, thank you very much.
spk05: Thank you. Our next question comes from Joseph Schwartz with SVB Security. Thank you for standing by. Joseph, your line is now open.
spk03: Great. I think that's me. Congrats again. I was wondering, since you alluded to updated guidelines being a meaningful driver for TransCon PTH when it's hopefully launched, I was wondering if you can expand on that a bit and discuss how much this versus other factors might improve the reimbursement positioning, which we've heard was very different for NetPara when it was launched. And what are your current estimates for the revenue potential of TransTime PTH?
spk10: It's what I really were extremely pleased. What really are giving Joe a much easier life. I tried to make his life pretty hard. But what really giving him a much easier way to get the right market assets in the US is the updated guidelines. Because when I read the guidelines, the guidelines is basically justifying that you are taking the majority of the patient on PTH3. And to my knowledge, even, I have not really With the case studies I have seen, it's very, very hard for US market assessed system to avoid something that already are taken into guidelines. So I actually feel when we discuss the sales revenue protection of this year, I always start on one single thing, the unmet medical need. The unmet medical need is really dramatical for the patient with hypoperia. not only the short-term symptoms, but also the long-term complications. And the problem with conventional therapy, it basically makes the disease worse. It's basically making the disease worse and worse because the treatment with a huge amount of cancer supplements and activated vitamin D, it basically is increasing all the complications, late stage complications, and not really providing a relief for short-term symptoms. So when I look on the number of patients in the U.S. that is available for treatment, 80 to 100,000 in a broad perspective, I believe the majority of these patients should be on PTH treatment. With all of them, we commercially reimburse life. I cannot guarantee that. but I think the majority should be it. And the price structure, as we said before, we will be responsible. We will still saying is that we are providing a huge benefit, not only for the patient, the caregiver, but also for the society. And this is why we believe in a premium pricing for our best-in-class product opportunities.
spk03: Okay, and thank you. And then I have a question about the pen device for Transpond PTH. which I think is important but hasn't really been discussed much. So I was wondering if you could talk about the pen and how it compares to what's used for scitropa and maybe, you know, how does it help patients titrate to the right dose of
spk10: Yeah, you're right. We don't talk so much about the pen device for Transcon PTH compared to Skytrover because with Skytrover we developed a complete new pen auto-injector for this. It's actually really boring in Transcon PTH because we're using a pen device that's getting utilized million and million and million of times in the U.S. every day because it's a basic classical insulin pen device. And it's a pre-filled liquid formulation for room temperature. Optimal, optimal, optimal for the patient. So it's pre-filled. You only need to prime it. And then you use the pen device for two weeks, 14 days. And then you take a new pen. And it's basic is built on a low dose, medium dose, high dose. And each pen, the low dose, medium dose, and high dose have three different strengths. So we basically are covering nine different presentations or nine different ways. So each subject, each patient can be optimized to the treatment. But Joe, why we don't talk about it? Because it's really a proven technology, a technology that is used in the insulin era a million times every day.
spk03: Sounds good. Thank you for taking my question.
spk05: Thanks, Joe. Thank you.
spk15: our next question comes from andreas at wedbush securities thank you so much for standing by please go ahead oh thanks for taking that question congrats on the progress during the quarter and then skytro for b can you provide an update on the status of filing skytro for internal syndrome uh
spk10: We just need to do the clinical trial first. When we have done the clinical trial, we will provide you a date on that. So we will provide that when we basically have done the clinical trial. We will provide an update when we expect to file and what is the next step.
spk15: Okay. And then for pediatric HP as well?
spk10: Pediatrics XP is an interesting element for us because we actually initiated this trial. We have designed our taking the insulin pen into a new configuration because we have a pediatric pen system for the pediatric population. And I believe and I'm a little bit perhaps, Birgitte, you can help me here because I cannot really exactly remember is what time next year we start the clinical trial.
spk16: I don't have the exact details to be shared now, but we are working our path forward for these studies. So no additional details for that.
spk10: Sometime next year we will start the clinical trial. It's a very, very, very small clinical trial, single arm. This is what we got all the regulatory feedback with. I think it's about between 20 to 25 patients, not a last for six months, not a last trial at all.
spk15: Okay, great. Thanks for the update, and congrats again, Nikolai.
spk10: Thanks so much.
spk05: Thank you. Our final question comes from Jaron Verver with Cohen. Thank you for standing by.
spk12: Great. I'd like to take my question. Yeah, hi, thank you. Thanks for taking my question. Jan, maybe just an integrated question relating to CNP. So the 5.4 centimeter per year, you're obviously referring to the two-year extension on Vaxogo in patients older than five. The placebo did about 3.8 centimeters per year at baseline, and then when it switched over, they did 5.4, obviously, on Vaxogo. Is 3.8 sort of a good comp to what to expect from the placebo And that's all in the five-year-olds plus. What about the two to five-year-olds? How should we think about that when we see the data? Thank you.
spk10: Yeah. This is where the two to five is really not a patient population where there's good benchmarking at all. All the data I have seen is building a huge amount of variability. And I actually hate to benchmark against anything that basic are already built on a huge amount of variability without solid data, because then you take two data sets, one data set that is built on a limit number of patients, compare it and benchmark it to another data set that also builds on a limit number of patients with huge variability. So this is why I separated between two to five and five and up, because there is a really solid, solid data set in the patient population from five and up, for example, the publication that you are referring to. And this is why I don't believe it's meaningful really to do a lot of comparison from the two to five because of the lack of real benchmarking.
spk05: Thank you so much. The question and answer session is now finished. This does conclude today's conference call. Thank you for participating. You may now disconnect.
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