Q4 2024 Alnylam Pharmaceuticals Inc Earnings Call
Good morning, ladies and gentlemen, and welcome to the O'Neill Pharmaceuticals 4th Quarter Full Year 2024 Earnings Conference Call. At this time, all lines are in a listen-only mode.
Following the presentation, we will conduct the question and answer session. If at any time during this call you require immediate assistance, please press 4 or 0 for the operator. I would now like to turn the conference call over to the company. Please go ahead.
Speaker Change: Good morning. I'm Christine Lindenboom, Chief Corporate Communications Officer at Elm Island.
Yvonne Greenstreet: With me today are Yvonne Greenstreet, Chief Executive Officer, Poulta Tanguler, Chief Commercial Officer,
Pushkal Garg: Pushkal Garg, Chief Medical Officer, and Jeff Poulton, Chief Financial Officer.
Pushkal Garg: During today's call, as outlined in slide 2, Yvonne will offer introductory remarks and provide some general context.
Speaker Change: Hopefully we'll provide an update on our global commercial progress, Pushkal will review pipeline updates and clinical progress, and Jeff will review our financials and guidance, followed by a summary of upcoming milestones, before we open the call for your questions.
Speaker Change: I would like to remind you that this call will contain remarks concerning El Nilem's future expectations, plans, and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor Provision under the Private Security Litigation Reform Act of 1995.
Speaker Change: Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file of SEC.
Yvonne Greenstreet: In addition, any forward-looking statements represent our views only at the date of this recording and should not be relied upon representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'd like to turn the call over to Yvonne. Yvonne?
Yvonne Greenstreet: Thanks, Christine, and thank you, everyone, for joining the call today.
Yvonne Greenstreet: 2024 was a fantastic year for our nylon with strong research, program development and commercial execution and significant progress across the business.
Yvonne Greenstreet: This includes the highly positive results in the Helios B Phase III study, leading to submission of global regulatory findings for vitreceran and ATTR cardiomyopathy. We also continue to advance and expand our robust and high-value pipeline of clinical programs.
and we continue to demonstrate strong commercial and financial performance.
achieving combined net product revenues of over $1.6 billion.
Yvonne Greenstreet: At the upper end of our revised guidance range, we delivered $95 million in non-gap operating income for the full year, marking a significant milestone for the company.
Yvonne Greenstreet: Furthermore, we maintained our award-winning culture, which has been a critical enabler of our success.
Yvonne Greenstreet: As we look to the year ahead, 2025 has the potential to be a landmark year for our Nylums.
Yvonne Greenstreet: We believe that there are three core elements of our business that will drive sustainable growth and value creation, not just in 2025, but for years to come. And we'll take our Nylem into its next exciting chapter.
Yvonne Greenstreet: The first is TTR leadership, where Butreceran, if approved, has the potential to become a new standard of care in ATTR cardiomyopathy and establish a flagship franchise for our company with the advancement of our next generation TTR asset, Nucreceran, following along.
Yvonne Greenstreet: Next is growth through innovation, including a pipeline with numerous multi-billion dollar opportunities and an R&D engine set up to deliver sustainable innovation and value creation.
Yvonne Greenstreet: The third pillar is strong financial performance, where we project that our robust commercial delivery and disciplined approach to capital allocation will enable us to sustain profitability going forward.
Yvonne Greenstreet: All of this is underpinned by a best-in-class team and our award-winning culture.
Yvonne Greenstreet: All of this represents tremendous progress against our nylon pizza 5th by 25 goals, launched back in 2021.
Yvonne Greenstreet: We are now on the cusp of turning these goals into reality, and believe that in doing so, we are on track to become a top-tier biotech.
Yvonne Greenstreet: Furthermore, the progress we make in 2025 will set us up for the second half of the decade and our next era of significant growth.
Yvonne Greenstreet: We are entering a new and exciting chapter in our Nylum's history and truly believe the best is yet to come.
Tolga: With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?
Tolga: Thanks Yvonne and good morning everyone. Q4 was another strong quarter for our commercial portfolio with our combined TTR and rare franchises delivering 30% growth compared with the fourth quarter of 2023.
Tolga: On a full-year basis, we delivered $1,646,000,000 in combined net product revenue at the very upper end of our 2024 Product Revenue Guidance Range.
which translates to 33% growth compared to 2023.
Tolga: as we continue to consistently increase the number of patients on therapy in both our TTR and rare franchises.
Tolga: Let me now turn to a summary of our fourth quarter TTR performance.
Tolga: Our TTR franchise achieved $343 million in global net product revenues during the quarter, representing a 35% increase compared with the fourth quarter of 2023, as we continue to increase the number of HA-TTR-PN patients on our therapies.
Tolga: In the U.S., during our first full year of competition in HATTRPN, combined sales of Ompatra and Almutra in the fourth quarter increased by 10% compared with the third quarter and finished the year with a robust 42% year-over-year increase, driving strong growth momentum.
The 42% year-over-year growth was primarily driven by the following.
Tolga: A 34% increase in demand, driven by the strength of ongoing Onbutra patient uptake, as well as continued switches from Onpetra.
Tolga: We are pleased with the growth in demand, which was consistent throughout the year, despite new competition entering the market at the end of 2023.
Tolga: The remaining growth in the quarter related to favorable adjustments and gross-to-net deductions.
Tolga: which were offset modestly by stoking dynamics as inventory in the distribution channel decreased in Q4.
Tolga: I'd like to take a moment to reflect on our full-year HATTR performance in the U.S., where we generated $705 million in full-year revenue, representing 39% growth compared with 2023, and almost $200 million in dollar growth.
Tolga: The dollar growth in 2024 represents an increase relative to the dollar growth we generated in 2023 of $180 million despite the new competition that entered the market at the beginning of the year.
Tolga: We believe this is reflective of the leadership position we have established in the PN market over the last six years, the strength of Onwood Trust's safety and efficacy profile, which is underpinned by rapid knockdown of TTR and solid commercial execution.
Tolga: Now, let me turn to our international markets, where the TTR franchise grew 12% in the fourth quarter compared to the third quarter of 2024.
Tolga: and increased by 25% year-over-year compared with the fourth quarter of 2023.
Tolga: Similar to the U.S., the year-over-year growth was primarily driven by increased demand for Amutra as patient uptake remained robust.
Tolga: Before we discuss our rare business, I'd like to take a few minutes to review our readiness for our upcoming PDUFA target action date and the potential extended label and launch in TTRCM in late March.
Tolga: We're excited about the potential of bringing in RNAi therapeutics to a patient population that is desperately in need of a product with a new mechanism of action.
Tolga: We've been preparing for this opportunity, which may now be only weeks away pending successful completion of the ongoing U.S. regulatory review.
Tolga: We recently announced full year 2025 product revenue guidance at J.P. Morgan.
Tolga: Our guidance of over half a billion dollars in absolute growth versus 2024 is driven by mainly by our TTR franchise that includes our anticipated label extension into ATTR CM and reflects our confidence.
and excitement about the launch.
Tolga: For 2025, we've guided for TTR product sales of between $1.6 and $1.725 billion.
Tolga: This would represent a 36% increase in annual revenue compared with 2024 at the midpoint of our guidance, reflecting an acceleration from the 34% growth our TTR business achieved in 2024.
Tolga: Now, let me share with you a few reasons for our optimism and a sense of what's to come.
As we said before,
ATTR is an Orson disease.
The category is rapidly growing.
and is still largely underserved.
Tolga: This will be a market growth story, an opportunity to help more patients in need, whether they are newly diagnosed or currently on a stabilizer therapy and experiencing disease progression.
It is a category ripe for entirely new treatment options.
In this context,
We have the potential to introduce a disruptive treatment.
Tolga: Assuming approval, Awutra would be the first and only RNAi silencer approved for both ATTR-CM and HATTR-PN, one that delivers rapid knockdown of TTR, working upstream at the source of disease.
Tolga: demonstrated profound impacts on CV outcomes in heliospeed, including a 36% reduction in all-cause mortality versus placebo in a study population representative of today's patients.
Tolga: with 40% on a stabilizer and a significant number on other background therapies like diuretics and SGLT2 inhibitors.
Tolga: early and consistent preservation of functional capacity and quality of life impacts that are critically important to patients
and that they can feel.
All of this achieved with just four doses per year.
and uniquely positioned for seamless access for patients.
Tolga: And while there's still much work still in front of us.
Tolga: We are building on a strong foundation in HATTRPN and a demonstrated track record of consistent commercial execution, as you have seen from our Q4 and full year results.
As we approach this important launch,
Tolga: We are building for durable, long-term success of our TTR franchise, and building on our experience and success over the past six years in this category.
Tolga: This means taking the time to enable smooth access and to create a seamless experience for patients and providers alike.
Tolga: Toward that end, we have already been at work optimizing the access and patient onboarding experience.
This means?
Optimizing Access Pathways at Health Systems.
where patients are actively managed today.
Tolga: given 80% of the population is being treated at 170 health systems
Tolga: We are focusing on optimizing access pathways at these health systems so that healthcare professionals can easily prescribe Amutra with the knowledge that the patient will receive it at an optimal location.
Tolga: be it in office, at an infusion center, or at home.
Tolga: We made good progress laying the groundwork in this regard, and it is important to note that following FDA approval for the expanded indication, it can take several months for the product to be added to the system's formulary and for the access pathway to be fully optimized.
Tolga: which will result in a ramp-up in demand as the year progresses.
Tolga: In parallel, we've also been building a broad ecosystem of alternative sites of care to expand optionality for how patients can initiate therapy in a seamless way and adhere to it.
As we previously shared at our 2024 TTR Investor Day,
Tolga: There currently are over a thousand alternative sites of care available for patients.
Tolga: This is in addition to health systems, group practices and clinics, and at-home administration.
Tolga: Now our goal is to expand these provider sites and ultimately for greater than 90% of patients to be within 10 miles of a treatment site.
Tolga: With regard to our field readiness, we've already scaled up all our customer teams cross-functionally.
Tolga: That includes world-class sales, field reimbursement, key account management, and medical, and award-winning patient services teams.
Looking ahead to post-approval, we will pivot our focus to
Tolga: Securing health systems formulary approval via their Pharmacy and Therapeutics Committee Reviews.
and finalizing Access Pathway Optimization.
Tolga: Which again could also take several months once we have an approved label
Expanding our value-based agreement in ATTRCM.
Tolga: We've been an industry pioneer in establishing DBAs across our portfolio to deliver value and enable broad patient access.
Tolga: We are focused on expanding these existing ATTR VBA partnerships to cover our expanded label.
Tolga: Finally, driving disciplined and compliant execution across our teams following approval.
Tolga: In short, we see tremendous opportunity in this category. We are on the cusp of a regulatory decision for what has the potential to become a transformational product for patients in need.
Tolga: and we have an at-the-ready commercial organization deeply engaged and experienced in the ATTR markets.
Tolga: We plan to share relevant operational details over the course of the year to provide clarity on the progress of our launch.
Tolga: as we aim to achieve or exceed our full-year revenue guidance.
Now, turning to our rare franchise.
Tolga: and the performance of Givlari Noxluma, which delivered $108 million in combined product sales in the fourth quarter, representing a 3% decline compared with the third quarter of 2024, driven by purchase patterns.
and 18% growth compared with the fourth quarter of 2023.
Tolga: For Givlari, Q4 product sales decreased by 9% compared with the third quarter of 2024, primarily due to the timing of a large order in the partner markets in Q3, which did not recur in Q4.
Tolga: on a year-over-year basis give large sales increase by 9% compared with the fourth quarter of 23 with the following regional highlights.
Tolga: A 14% increase in the U.S., primarily driven by growth in new patients on therapy, with additional growth driven by inventory stocking dynamics.
Tolga: a 1% decrease in our international market where demand growth in our European markets was offset by gross energy adjustments in our partner markets.
Tolga: For Oxlumo, Q4 product sales increased by 8% compared with Q3 of 2024, primarily due to continued demand growth, and increased by a solid 33%.
Tolga: compared with the fourth quarter of 2023 with the following year-over-year regional dynamics.
Tolga: Despite emerging competition, a 77% increase in the U.S., primarily driven by strong demand growth with additional growth driven by favorable gross-to-net pricing adjustments and inventory stocking dynamics.
Tolga: A 12% growth from rest of world markets, primarily driven by strong growth in patient demand.
Tolga: In conclusion, we delivered strong results in the fourth quarter with both our TTR and rare franchises.
Tolga: driven by continued robust growth in patients on therapy which enabled us to close the year at the upper end of our 24 product derivative guidance range.
Pushkal Garg: With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress.
Pushkal?
Pushkal Garg: Thanks, Tolga, and good morning, everyone. As you all know, 2024 was a very exciting year for our TTR franchise.
Pushkal Garg: We shared the landmark results from HELIOS-B at several conferences throughout the second half of the year. Together, these data presentations highlighted VUTRESA-RAN's potentially transformational profile in today's population of patients with ATTRCM, with benefits across a comprehensive series of assessments.
Pushkal Garg: Based on these compelling data, we have completed several regulatory submissions that are now under review.
Pushkal Garg: In the United States, we have a PDUFA date of March 23rd, and parallel filings were achieved in all major regions, including Europe and Japan. Our goal is to bring this new and important therapeutic option to patients around the world as quickly as possible.
Pushkal Garg: We also continue to look ahead and innovate in TTR beyond Voutrier Saran with NucriSaran, formerly known as ALN-TTR-SC-04.
Pushkal Garg: At AHA in November, we presented updated Phase I results showing rapid knockdown of serum TTR that was robust and highly durable, greater than 90% at six months.
Pushkal Garg: supporting the potential for an annual or biannual subcutaneous dosing regimen.
and an encouraging safety profile.
which, in addition to offering convenience for patients,
could enable broad payer coverage.
Together, we believe these data support a potential best-in-class profile.
Pushkal Garg: I'm also happy to announce today that the FDA has granted Nucreseran orphan drug designation for ATTR amyloidosis encompassing both polyneuropathy and cardiomyopathy.
Yvonne Greenstreet: As Yvonne announced at J.P. Morgan, we plan to quickly advance NucreSRAN to a Phase III study in ATTR amyloidosis with cardiomyopathy that is expected to start in the first half of 2025. Additional details regarding the study design will be shared at our R&D Day on February 25th.
Yvonne Greenstreet: Beyond TTR, our R&D efforts have enabled us to build one of the most robust pipelines in the biotech industry today, positioned to deliver strong growth and innovation across a broad range of disease areas and indications at all stages of development.
Yvonne Greenstreet: In the fourth quarter, we continue to make great progress in advancing our pipeline.
Let me highlight a few key milestones.
Yvonne Greenstreet: We continue to advance Zalbiciran, an investigational therapeutic for the treatment of hypertension through Phase 2 and towards initiation of a Phase 3 cardiovascular outcomes trial expected to start in the second half of 2025.
Yvonne Greenstreet: In fact, as announced this morning, we have recently completed enrollment in the CARDIA III Phase II study.
Yvonne Greenstreet: Velsiran, our investigational therapeutic for the treatment of cerebral amyloid angiopathy and Alzheimer's disease, continues to proceed as well. We presented multi-dose data showing high levels of knockdown with single and multiple doses along with good safety and tolerability.
Yvonne Greenstreet: We have an ongoing phase 2 study in cerebral amyloid angiopathy and plan to start a phase 2 study in Alzheimer's disease in the second half of the year.
Yvonne Greenstreet: And we started four new Phase I programs last year. The first was for Huntington's disease, where we have a unique exon-1 targeting approach that non-human primates has shown deep and sustained knockdown with encouraging safety and tolerability.
Yvonne Greenstreet: The Phase 1 trial is ongoing in the United States, Canada, and the UK.
Yvonne Greenstreet: The other programs initiated in Q4 include Zalbiciran plus Reversir for hypertension, ALN6400 for bleeding disorder, and ALN4324 for type 2 diabetes mellitus.
Yvonne Greenstreet: This remarkable and unique pace of innovation puts us in a great position to have a strong, self-sustainable pipeline that can deliver meaningful impact to patients for many years to come.
Yvonne Greenstreet: I encourage you to join or to tune in to the webcast of our R&D Day that we will host on February 25th, where we will provide more comprehensive reviews of the programs I've described and also highlight continued RNA platform innovation that will drive the next era of alnylam's growth.
Speaker Change: With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?
Jeff: Thanks Pushkal and good morning everyone. I'm pleased to be presenting on MILAM's full year 2024 financial results and providing our complete financial guidance for 2025.
Jeff: starting with a summary of our P&L results for the full year.
Jeff: Total global net product revenues for 2024 were $1,646,000,000 representing 33% growth versus 2023 with both our TTR and rare franchises reporting strong growth of 34% and 29% respectively.
Jeff: These results came in at the top end of our 2024 product revenue guidance, which we had raised more than 10% at mid-year from our original 2024 guidance.
Jeff: For the full year, net revenue from collaborations was $510 million, including a $60 million sales milestone in Q4 from Novartis, due to Lectio exceeding $600 million in annual sales.
Jeff: Compared with 2023, collaboration revenues decreased 7%, primarily attributed to differences in certain revenue items between 2023 and 2024.
Jeff: During 2023, we recognized $310 million of revenue from the upfront payment received from Roche in connection with execution of our Zalbi Saran collaboration.
Jeff: In comparison, during 2024, we recognized $185 million in revenues associated with the modification to our Regeneron collaboration, driven by providing Regeneron an exclusive license to develop, manufacture, and commercialize MD-Saran as a monotherapy.
Jeff: Royalty revenue for the full year was $92 million, or more than double what was recognized in 2023, driven by higher royalties from Novartis on sales of L'Equipe.
Jeff: Gross margin on product sales was 81% for the full year, representing a 3% increase compared with 2023.
Jeff: The improvement in margin was primarily due to non-recurring prior year expenses associated with cancelled manufacturing commitments from Patro and other adjustments to inventory.
Jeff: These decreases were partially offset by an increased rate of royalties payable on net sales of Imbutra.
Jeff: For 2025, we expect a decrease in gross margin on product sales, as the average royalty rate payable to Santa Fe on Imbutra is expected to be higher, as sales of Imbutra continue to increase.
Jeff: Our non-GAAP R&D expenses increased 10% for the full year compared with prior year, primarily due to increased costs associated with our preclinical activities as we develop our clinical pipeline of RNAi therapeutics targeting multiple tissues.
Jeff: increased clinical trial expenses associated with the Zalvisiran Cardio Free Phase 2 study, and increased employee compensation expenses.
Jeff: Our non-GAAP SG&A expenses increased 24% for the full year compared with 2023, primarily driven by increased investments in support of our TTR polyneuropathy business and in preparation for the potential launch of Invutra for cardiomyopathy, along with increased personnel costs.
Jeff: For the first time, we've achieved full-year non-GAAP operating profit of $95 million, representing a $156 million improvement compared with 2023, primarily driven by strong growth in product sales.
Jeff: This is a significant milestone for the company as achieving non-gap profitability has been a key goal associated with our P of the 5th by 25 growth strategy.
Jeff: This achievement will enable further investment in our R&D pipeline as we strive to deliver sustainable long-term top and bottom line growth.
Finally, we ended the year with cash.
Jeff: cash equivalents and marketable securities of $2.7 billion compared to $2.4 billion at the end of 2023, with the increase primarily driven by improved operating performance and net proceeds received from the issuance of common stock in connection with employee stock option exercises.
Now I'd like to turn to our 2025 financial guidance.
Jeff: Starting with net product revenues, we are reiterating our combined net product revenue guidance from Patro and Vutra Givlari and Oxlumo that was communicated in our JP Morgan press release dated January 12, 2025.
Jeff: We anticipate combined net product sales for our four commercial products will be within a range of $2.05 to $2.25 billion, representing combined full-year growth compared to 2024 of 31 percent at the midpoint of the guidance range, or more than $500 million in growth.
Jeff: On a franchise level, the guidance is broken down as follows. Total TTR, 1.6 to 1.725 billion, representing full year growth compared to 2024 of 36% at the midpoint of the guidance range.
Jeff: Importantly, this guidance assumes approval and launch of MBUTRA for ATTR cardiomyopathy in the U.S. by the PDUFA date of March 23rd. Additionally, we assume launches for MBUTRA and ATTRCM in Germany and Japan in the second half of 2025.
Jeff: Total rare, 450 to 525 million, representing full year growth compared to 2024 of 15% at the midpoint of the guidance range.
Jeff: Our guidance assumes foreign exchange rates as of December 31st, 2024, which are noted in the footnote of our guidance slide.
Jeff: We are also providing constant exchange rate growth guidance for our net product revenues with a projected range of 26% to 39%.
Jeff: Collaboration and royalty revenue guidance range is 650 to 750 million representing 16% growth compared to 2024 at the midpoint of the guidance range.
Jeff: Our guidance assumes achievement of a $300 million milestone payment from Roche associated with the initiation of our Phase 3 study for Zalvisiran, which we anticipate will occur in the second half of the year.
Jeff: We also expect that collaboration revenue associated with our partnerships with Roche and Regeneron, as well as Lekbio Royalties from Novartis, will drive the majority of our collaboration and royalty revenue in 2025.
Jeff: Let me now turn from financials and discuss some key goals and upcoming milestones for early 2025.
Speaker Change: This pushed Colm mentioned, we will host an R&D day on February 25 in New York City.
Speaker Change: The <unk> target action date for the NDA for <unk> March 23 2025.
Speaker Change: Please note that given the materiality of this decision we will be entering a quiet period beginning on March one.
Speaker Change: We intend to initiate a phase III study of <unk> in patients with <unk> amyloidosis.
Speaker Change: On my operating in the first half 2025.
Speaker Change: And our partners at Sanofi have at Paducah target action date for <unk> of March 28, 2025.
Speaker Change: Let me now turn it back to Christine to coordinate our Q&A session Christine.
Christine Lindenboom: Thank you Jeff Operator, we will now open the call for questions to those sell then we would like to ask you to limit yourself to one question each and then get back in the queue. If you have any additional questions.
Christine Lindenboom: Thank you.
Christine Lindenboom: Ladies and gentlemen, we will now begin the question and answer session should you have a question. Please press the star followed by the one you touched on filing.
Speaker Change: Jim will be taken into order receipt.
Speaker Change: If you wish to cancel your request. Please press the star followed by the tail.
Speaker Change: If you are using a speaker please lift the handset before pressing any case once again that is star one should you wish to ask a question.
Speaker Change: And your first question is from.
Speaker Change: <unk> from Bank of America. Your line is now open.
Speaker Change: Hi, good morning, Thanks for taking my question.
Speaker Change: To get a sense from your team about how long you think it's going to take to establish payer policies. After the profile of <unk>.
Speaker Change: Sri and how do you think that could impact the initial trajectory of the launch thanks.
Speaker Change: Thanks, That's a great question I mean, clearly we're in a strong.
Speaker Change: Long positions.
Speaker Change: Having already.
Speaker Change: GTR franchise supporting patients with Polyneuropathy and this really gives us a strong foundation on which to build towards perhaps you could answer the specific question around.
Speaker Change: Time to time.
Speaker Change: Approvals <unk>.
Speaker Change: <unk> look obviously, we're really excited about.
Speaker Change: Coming potential launch and are frankly excitement is confirmed by the guidance that we've already provided now when it comes to the payer policies and formulary uptake I think as you can see from my prepared remarks. This is really going to be a second half story.
Speaker Change: We're very much committed to the growth that we've already committed to.
Speaker Change: And we.
Speaker Change: We have value based agreements that we know it's going to be extended with some of these payer policies that's going to accelerate.
Speaker Change: But the formulary piece takes a little bit time, so I would expect the uptake really to be meaningful in the second half of the year.
Sylvain: Thanks Sylvain.
Sylvain: Thank you.
Sylvain: Your next question is from <unk> <unk> from.
Speaker Change: From BMO capital markets. Your line is now open.
Sylvain: Okay.
Speaker Change: Thanks for taking our question.
Speaker Change: A quick one on booted out through March.
Speaker Change: Assumed premium pricing for our wood <unk> co.
Speaker Change: On path to silence says, we've got approved already what I'd get a full panel on step edits for commercially insured patients who represent about 20% of the ATP cardiomyopathy population. Thank you.
Speaker Change: Okay. That's a question for you, yes, a great question look I mean first and foremost we really.
Speaker Change: I appreciate it and like the product profile that <unk> has to offer which is underpinned by the Helios b results and in our engagements with.
Speaker Change: Payers at the pre pricing discussions we're also encouraged that the.
Speaker Change: I see.
Speaker Change: One obviously the value of this product can bring to the market second of all the predictability of how we are actually being positioned as a part D product. So all these combined we actually expect our.
Uptake to be very close to 10 with what we have seen in the past with Pn in terms of how payers will cover this product.
Speaker Change: And as we've already shared very much <unk>.
Speaker Change: Committed to the guidance that we provided which again underpins how we really see the growth which is going to be accelerated.
Speaker Change: In 2025.
Speaker Change: Okay. Thank you very helpful.
Speaker Change: Thank you. Your next question is from Gena Wang from Barclays. Your line is now open.
Speaker Change: Thank you.
Speaker Change: You cannot comment on the actual price for Enzo.
Speaker Change: And keep the approval date, but.
Speaker Change: Wondering if you can share sectors in particular to sushi on pricing adjustment for Gucci and the late question I know a few already ask.
Speaker Change: Can you share with us what percentage of our current sites.
Speaker Change: Do you have a J code in place that you can use for HCR cutting ops.
Speaker Change: Thanks, Thanks, Jami for the question and recognizing that it's too early to be specific about price and as you know we have pay.
Speaker Change: Patient access principles and when we think about price. We obviously consider the value set of products is bringing to patients in the ecosystem as well as assuring.
Speaker Change: To access and I think we've done a great job in Pn.
Speaker Change: As I mentioned and we continue to plan to do an equally good job for <unk> do you want to add absolutely other than maybe the specific one maybe.
Speaker Change: So to your last point, we have got we already have a J code for <unk>, which is going to be used there.
Speaker Change: Therefore, we don't expect any changes already disruption on that and in respect to our coverage look.
Speaker Change: We shared earlier on our Ctr day in other forums.
Speaker Change: The makeup of our.
Speaker Change: Business.
Speaker Change: From Medicare perspective, as well as commercial we expect that to remain the same and therefore, which we believe is going to result in rather.
Speaker Change: Smooth cut.
Speaker Change: Coverage for our product as Ivan indicated.
Speaker Change: We're really excited about that we're talking to a mechanism and how that's going to actually bring additional value and alternative is a disruptor treatment for payers as well as patients and then we will actually frankly, most importantly.
Speaker Change: The affordability for the patients.
Speaker Change: No.
Speaker Change: 70% of our patients currently pay zero co pay and we expect that dynamic to remain the same which we believe is going to be an important driver for our patient uptake.
Speaker Change: Thanks program.
Speaker Change: Next question.
Speaker Change: Thank you.
Speaker Change: Your next question is from Maury Raycroft from Jefferies. Your line is now open.
Maury Raycroft: Hi, Congrats on the progress and thanks for taking my question.
Maury Raycroft: I'm just wondering if theres any perspective, you can provide on label discussion progress and in addition to reduction of mortality and hospitalization are you advocating to have anything unique on the front page of the label indications and usage section such as sporting related to preservation of quality of life and functional capacity.
Maury Raycroft: Yes. Thanks, Maury look first of all we're really very enthusiastic about how the FDA review is going and we remain fully on track.
Maury Raycroft: For an approval date by the by the Purdue fulfill we're excited about the progress that's been made in that front in terms of the label look we we believe that the study was designed and clearly demonstrated the benefit on mortality and hospitalization events and we expect that there'll be.
Maury Raycroft: That will be reflected in label as well as the ancillary.
Maury Raycroft: <unk> that we saw.
Maury Raycroft: In terms of preservation functional ability quality of life.
Maury Raycroft: And benefits across a series of endpoints there. So look at the end of the day, we want a label that reflects.
Maury Raycroft: The study that was designed and.
Maury Raycroft: And where we saw statistically significant results in pre defined endpoints across a whole series of attributes that we think are a benefit.
Maury Raycroft: And that we were able to actually then go and educate providers and patients on and so we look forward to sharing that win.
Maury Raycroft: And eventual approval occurs.
Speaker Change: Got it okay. Thanks for taking my question.
Speaker Change: Thank you. Your next question is from Ritu <unk> from JD Cowen. Your line is now open.
Speaker Change: Okay.
Speaker Change: Hey, guys. Thanks for taking the question My question was actually.
Speaker Change: Really good follow up Tim Morey.
Speaker Change: On label language.
Speaker Change: Can you think about the language in the label, specifically mortality, but potentially having that mortality clinical.
Speaker Change: Data later in the label and the clinical data section, what sort of potential advantage could that give you or not.
Speaker Change: Detailing the product.
Or with payers.
Speaker Change: Okay I read too.
Speaker Change: We have a pretty clear view of the understanding of how we're going to be able to promote communicate this.
Pushkal Garg: Mainly obviously, what what what Pushcart indicated.
Speaker Change: We had reach.
Speaker Change: Specifically significant results on all pre specified endpoints 10 out of 10, and our ability to communicate that is going to be.
Speaker Change: Relatively smooth, we're pretty confident in how we can actually differentiate the product from a product profile perspective, given that this is an orthogonal mechanisms of action that rapidly knocks down the disease, causing protein.
Speaker Change: And has the ability to actually demonstrate those clinical outcome benefits.
Speaker Change: Both mortality as well as hospitalization coupled with the fact that we actually have four times a year.
Speaker Change: Subcutaneous injectable that really provides greater adherence as we've seen on Paul neuropathy as well as our relatively smooth access given that 70% of patients pay zero copay all those.
Speaker Change: All of those.
Speaker Change: Perspective will be carried through.
Speaker Change: How we're going to actually communicate this exceptional medicine through the prescribers, which are very much in need of a disruptive treatments.
Speaker Change: Do you still expect that to be in the in the actual labeling language, though.
Speaker Change: Those data.
Speaker Change: Look at the end of the day, we think that the label will reflect the things that we've shown in the clinical trial. That's traditionally what is done and we would expect this as we've said with two that we had a whole series of pre specified endpoints that show the impact of this drug on this disease and so we would expect that to be generally reflected in the label.
Speaker Change: And again consistent with labeling told his team our medical teams will be able to speak about those attributes on the results of the Helios B study to providers and patients and payers.
Speaker Change: Next question please.
Speaker Change: Thank you. Your next question is from Greg Harrison from Scotia Bank. Your line is now open.
Speaker Change: Good morning, This is Chris and I tell him Greg Harrison Congrats on the update and thanks for taking our question and I was just curious to hear what your expectations are for interest there and potential revenue mix among naive patients and in the first line setting in and switches.
Speaker Change: And the families.
Speaker Change: Okay last question for you, yes, so I think.
Speaker Change: So our best of our abilities, we were able to provide a pretty clear and ambitious guidance that really shows how we're going to actually accelerate this.
Speaker Change: Our TCR franchise.
Speaker Change: And post.
Speaker Change: 36% now how that mix is going to happen is look we believe this is a product well positioned to be a standard of care and to be closer to first line, but like any.
Speaker Change: Categories. We do also know that there is.
Speaker Change: Our needs of another.
Speaker Change: Product with a novel targeted mechanism of action beyond the stabilizers. So we certainly expect a good mix of patients saw from naive patients that are coming in the door that are newly diagnosed and some.
Speaker Change: Perhaps eligible for switches.
Speaker Change: Or in rare instances some combination so we do expect that and obviously.
Speaker Change: As we built our guidance all of these elements were incorporated.
Speaker Change: Great. Thank you.
Speaker Change: Next question.
Speaker Change: Thank you. Your next question is from Gary Nachman from Raymond James Your line is now open.
Gary Nachman: Hi, Good morning, maybe you could talk about the competitive dynamics, you're seeing with way new.
Speaker Change: In Polyneuropathy with both products growing at this point.
Speaker Change: And how is the difference between part B and part D playing out.
Speaker Change: How do you think thats going to translate over to cardiomyopathy with that approval.
Speaker Change: Thanks for the question I mean, clearly we're very pleased with our strong <unk> performance in 2024 and that was with competition in the market. So I think we're doing it.
Speaker Change: Good job continuing to build the business to OCA, perhaps you want to add some color to this.
Speaker Change: Specific to the image, yes. So we just posted our full year results for 24, which happened to be the first year actually we faced competition in this relatively narrow category, where we always said this is going to be a growth story category growth story and I think what you can see.
Speaker Change: Particularly in our U S numbers, where U S business from a pretty good healthy base grew 42% year over year and that was with the competition and as far as I can tell a while new you're also getting their fair share of.
Speaker Change: Growth, which is again very consistent with the with the growth story that we've been telling you all along we believe we have a highly differentiated product profile versus why new year, given that it's four times a year and its HCP administered and we had not seen any significant access.
Speaker Change: Headwinds and.
Speaker Change: And we anticipate.
Speaker Change: This type of dynamic continue as we expand our.
Speaker Change: Expanding the indication to cardiomyopathy.
Speaker Change: Thanks Silicon next question please.
Speaker Change: Thank you.
Speaker Change: Our next question is from Jessica Fye from JP Morgan. Your line is now open.
Speaker Change: Hey, guys. Good morning, what do you think the early Aker eminent scripts imply for the TCR cardiomyopathy market dynamics and market expansion and interest in agents beyond <unk> as it relates to <unk>.
Speaker Change: And I.
Speaker Change: So it's been kind of trying to ask this in a few different ways.
Speaker Change: You should try it one more time, what's the right way to think about the evolution of Amtrust net price as you move into this much larger patient population. Thank you.
Speaker Change: Okay.
Speaker Change: Two questions there.
Speaker Change: Clearly as <unk> said I mean, we believe that.
Speaker Change: This is a market growth opportunity, which makes it very exciting category to be play and obviously become becomes the cardiomyopathy with.
Speaker Change: Our strong track record in the TCR space Toga, perhaps add some color. So first question and then the specific question around the accretion of that price Yeah, I mean, I think look.
Speaker Change: First a sentiment that comes to mind as encouragement.
Speaker Change: Effectively seeing another stabilizer coming into new markets.
Speaker Change: And Dave shared some numbers on the prescription that are early innings, obviously were.
Speaker Change: Very encouraged because it's another stabilizer that is four times a year with not really significant clinical data.
Speaker Change: <unk>.
Speaker Change: Obviously, Dave Dave Dave actually shown shown that this is actually a growth category now when I think about on which our product profile that has.
Speaker Change: Really strong clinical profile as well as.
Speaker Change: The fact that it's four times a year annual dosing.
We're really well positioned to be in.
Speaker Change: In the access.
Speaker Change: We're very excited about what on what Ken can do given that.
Speaker Change: The category is going to be continue to be growing.
Speaker Change: Given the undiagnosed patient numbers.
Speaker Change: Thank you.
Your next question is from Paul Mcginnis from Stifel. Your line is now open.
Speaker Change: Hey, Thanks, so much for taking the question on payer dynamics and how they evolve in this category are you expecting the average insurer to cross manage between part D and part D and I think again the underlying question that everyone's trying to get to a pricing as youre at a significant premium right now does that have to go down or not there is a lot.
Speaker Change: Moving parts right like the payer liability on part D is one of them, but just as it relates to how insurers are going to manage their formularies in this space.
Speaker Change: <unk> revenues to actually be a step at it or is that just not something thats normal and practice at this point. Thank you.
Speaker Change: Yes. Thank you for the question look I mean, there's a lot of noise around how the payers will be managing this what we've seen is.
Speaker Change: This is a rare condition highly devastating condition and we expect to payers to cover covers the product and how the market is going to evolve I think we have a pretty clear eyed view given how.
Speaker Change: We've been actually managing Polyneuropathy is a part D product and.
Speaker Change: How <unk> has launched in our part D product, we expect that.
Speaker Change: Similar dynamics in terms of our payer mix and we do anticipate that given the given the patient affordability is a key driver of heart patients stay on therapy is to be there.
Speaker Change: Favorable for them what's wrong.
Speaker Change: Thank you.
Speaker Change: Rick.
Speaker Change: Thank you.
Speaker Change: Next question is from Salvino Victor from Goldman Sachs. Your line is now open.
Salvino Victor: Good morning, Thanks for taking my question do you plan to initiate a phase III study for <unk> in.
Salvino Victor: In <unk> in the first half how are you thinking about the timing of enrollment and events.
Salvino Victor: <unk> ability of new options and how do you plan to conduct an interim here. Thank you.
Salvino Victor: Yes. So thanks for the question I mean, clearly we will be providing more detail around an increase around.
Program at R&D day at the end of this month.
Salvino Victor: So maybe you can shed a little bit about how we're thinking about.
Salvino Victor: Moving forward and increase rent, which we're very excited about solving.
Salvino Victor: <unk>.
Speaker Change: Look I think decreased around the profile that we've seen so far really sets. It up we think to be a best in class therapy for patients with this disease building on what we've seen with Patrice around this now is a derisked asset. We think we can get deeper knockdown, we've already shown that over 995% knockdown less frequent administration and we think that's going to help patient outcomes.
Speaker Change: When we think about the development plan for it.
Speaker Change: There's a number of factors a we wanted to develop brings to market as quickly as possible because of the value that it brings.
Two we want to think about how do we develop.
Speaker Change: Our clinical profile for that in a label that allows for broad uptake in a very durable franchise right and so youll see those how we've kind of brought those factors together.
Speaker Change: At R&D day, we will talk more about the development program there in <unk> in Pn in our overall approach to this disease. So.
Speaker Change: Stay tuned it'll just be a couple of weeks and we'll be able to share more.
Speaker Change: Next question.
Speaker Change: Thank you. Our next question is from Ellie Merle from UBS. Your line is now open.
Ellie Merle: Hey, guys. Thanks, so much for taking the question.
Ellie Merle: Just a couple from me so how would you characterize the mix of growth and the PTR got patents from Polyneuropathy or cardiomyopathy.
Speaker Change: And then Paul you mentioned that close to approval.
Ellie Merle: Finalizing Bayou based agreements.
Speaker Change: The amount of the.
Speaker Change: Can you elaborate a bit on how these could work.
Speaker Change: This could look like for cardiomyopathy relative to opine.
Speaker Change: Thanks.
Speaker Change: So the two questions that mix of growth for Europe, with the cardiomyopathy, and then a little bit more detail on how we're thinking about buying bell post approval look unusual to our tradition, we exited jpn broke down our guidance between ctr and rare, but I think we'll stop there we'll obviously can.
Speaker Change: To provide more color about how the launch is going in the particularly in the second half of the year, where we do see we do anticipate the growth to to take place now the can.
Speaker Change: Can you remind me the second question post approval, how we're thinking about buy and bill.
Speaker Change: <unk> agreements right. So look we're very very proud about the value based agreements that we set at approximately we have about.
Speaker Change: 60% of the lives that are currently covered on the Pn is dependent on the value based agreements and the value based agreements are actually essentially really provides our commitment to the clinical outcomes. So we have this experience already with pn and we anticipate that to actually also carryover in most.
Speaker Change: Distances for cardiomyopathy, which should actually provide a level of predictability for the for the payers about how.
Speaker Change: The product is going to perform and the clinical outcomes that the payers. They expect us to achieve so I think thats a great one of the great best practices that we've established over the years and we anticipate that to carryover without cardiomyopathy indication in most cases.
Speaker Change: Thank you.
Speaker Change: Next question.
Speaker Change: Your next question is from Mani <unk> from Leerink Partners. Your line is now open.
Speaker Change: Now ill turn my question and congrats on great results commercially and otherwise.
Speaker Change: I know that Theres, probably 20 more questions around <unk> and pricing in the line. So I'm going to ask an actual financial question.
Speaker Change: You clarify the driver of the tax benefit that was noted here and would that be recurring is the NOL dynamic O U S. If you could just dig into how what drove that benefit and how it might recur or not flash over the course of the year.
Speaker Change: That's a question for you Brian.
Speaker Change: Good question Mani we noted in the press release that we had a release of evaluation allowance ex U S and that's really related to our Swiss entity. This is something that we have to do every quarter with our deferred tax assets as we have to assess whether or not it's more likely than not that that value is going to ultimately be recognized.
Speaker Change: The Swiss entities had profitability for a number of periods now so that gave us the confidence to release that.
Speaker Change: We have not released all valuation allowances either in Switzerland, and we've not released anything in the U S. Yet it's very difficult at this point to predict further.
Speaker Change: So I would probably just leave it at that for now.
Speaker Change: Thanks, Mike I think we've got I think we've got time for one more question I think we kept our last question coming up.
Speaker Change: Yes. Your last question is from <unk> from RBC capital markets. Your line is now open.
Speaker Change: Oh, great. Thanks, so much for squeezing me in maybe a follow Mani here I guess.
Speaker Change: Jeff how should we think about gross margin here going forward I mean, the sanofi royalty fees year and meaningful FCC, 30%, but we obviously don't know the exact hearing of that royalty fees.
Speaker Change: <unk> seen that modeling gross margin compressing from 80% now I think it's low <unk> now to like low seventy's or even upper sixties.
Speaker Change: A reasonable assumption in your mind any.
Speaker Change: Let me call it they're much appreciate it thanks so much.
Speaker Change: Yes, I appreciate the question. So in my prepared remarks, I mentioned that we expect gross margin on product sales to be lower in 2025, Youre right 2020 for our gross margin on product sales was 81% and I do think that will be the direction of travel for a period of time really driven by two things that relate to <unk>.
Speaker Change: It's our lowest margin product right now given the royalty burden to Santa fee and it's our fastest growing products. So that will put pressure on margins as we move forward and secondly, as that business grows. We also start to move up higher in the royalty tiers. So the average royalty rate will likely also increase over time the royalty that we paid on average.
Speaker Change: <unk> across 2020 for Fran Butera was 21%.
Again my expectation as this moves forward is over time that number is going to probably be mid to high <unk>. So that's just sort of the incremental amount that I would expect there's a couple of things that will move the other way I would say on margins. If you look at our gross margin on a total revenue basis that also includes the impact of collaboration of royalty revenue.
Speaker Change: Yeah.
Speaker Change: That's revenue that's very high margin, probably close to a 100%.
Speaker Change: As an example in 2020 for the margin on product sales was 81%, but if you looked at margin on total revenue was 86% so that uplifted it.
Pushkal Garg: And then secondly, I think the most important thing is that the issue with this higher royalty burden. If we're successful in developing new <unk> ran well hear more about that at our R&D day as push coal said theres no royalty burden to Santa fee on that so that would obviously offset this in the future. If we're successful in bringing that to market. So hopefully.
Pushkal Garg: That gives you a little more clarity on on direction of travel on margins.
Speaker Change: Super helpful. Thanks, so much.
Very good.
Speaker Change: Sure.
Speaker Change: Thanks, everybody for joining the call.
Speaker Change: It's really a very good year for <unk>, but really as I said just the beginning.
Speaker Change:
Speaker Change: The success, we believe we are on track to realize in 2025, so thanks, everybody and have a great day.
Speaker Change: Goodbye.
Ladies and gentlemen, the conference has now.
Speaker Change: Thank you all for joining you may all disconnect your lines.