Q3 2024 Alnylam Pharmaceuticals Inc Earnings Call
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Speaker Change: Please stand by your program as about to begin if you need assistance during your conference today. Please press star zero.
Speaker Change: Today everyone and welcome to today's nylon pharmaceuticals Q3-2024 earnings conference call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session.
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Speaker Change: Please note this call is being recorded and I will be standing by if you need any assistance. And it's not my pleasure to turn the conference over to the company.
Speaker Change: Good morning, I'm Christine Lindenboom, T-Colbert Communications Officer, Nell and Ilam. With me today are a long green street T-Pick executive officer, Tolga Tanguler, T-Commershel Officer, Pushkal Garg, T-Fernal Block is there and Jeff Poulton, T-Fernial Officer.
Speaker Change: For those who participate in the conference call, stay a company fly, can be accessed by going to the events section of the Investors page of our website, and drs.onl.com slash event.
Speaker Change: String today's call is outlined in slide 2. A vulnerable offer interdisciplinary marks and provides some general contact.
Speaker Change: will provide an update on our global commercial progress. Pushkal will receive pipeline updates and clinical progress in Jeffle Review Financials and guidance, held by Assembly of upcoming milestones before we open a fall for your question.
Speaker Change: A lecture on my view that this call will contain remarks concerning L. Nile and Teacher Expectations, Science and Prophets, which constitute for the key statements for the purpose of the safe Harble provision under the PISA Security for the case in the report map of 1997.
Speaker Change: Action results may differ material, as on those indicated by these four booking statements, as a result of various important factors, including those discussed in our most recent periodic report on file with the SEC.
Speaker Change: In addition, any forward looking statements represent our views only as a date of this recording, and should not be relied upon as a representing our views as of any subsequent date. We specifically explain any obligations to update such statements.
Speaker Change: with that, but let's turn the whole ritual barn, advance.
Speaker Change: Thanks Christine and thank you everyone for joining the call today.
Speaker Change: The third quarter of 2024 marked a period of continued progress from Nilem on all fronts.
Speaker Change: Commission, we achieved 34% year-by-year growth in global net product revenue, generating $420 million across our four marketer product.
Speaker Change: We made great progress with our TTR franchise, sharing additional results from the Helios P Study of Retriezeram and finding The Rake in A3 submission is the US and EU.
Speaker Change: We also hosted a TPR Investid Day, the Highlighter Appreporation in anticipation of a potential launch in ATPR Cardium and the next day.
Speaker Change: We believe that I'm good, sure, and our broader TTR port 30 will serve as our flagship franchise.
Speaker Change: Timber and potential impact was I layer has been for regeneran, or what the cystic fibrocyst plan tried to spin for vertex, delivering to those companies, durable growth, and enabling those companies to invest in R&D, new product development, and portfolio diversification to the long term.
Speaker Change: Lastly, our early pipelines will continue to momentum as well, particularly our efforts in CNS.
Speaker Change: We initiated a Phase 1 study of ALN HTT-02 in Huntington's disease and were pleased to announce today initial results from the multiders portion of the Phase 1 study of my BELTERAN in patients with already on the spec outside the disease.
Speaker Change: These results are encouraging for CNS platform as they provide early evidence that multiple doses of an intricately administered SIRNA are well tolerated.
Speaker Change: We're continuing to progress towards achievement by year end 2025, but we're on the Island Pizza Festival by 25 goals. And a steadfast and urbanize that we're on track to become a top-tier biotech, developing and commercializing transformative medicine for patients around the world with rare and prevalent diseases.
Speaker Change: Driven by a high yielding pipeline at first and or best in class product candidates, while organic product engine, all while delivering strong financial results.
Speaker Change: with that. Let me now turn the call over to Tolga, for a view of our commercial performance.
Speaker Change: Tolga?
Tolga Tanguler: Thanks, Yvonne and good morning, everyone.
Tolga Tanguler: Q3 was another strong corner for our commercial portfolio. Without combined commercial portfolio delivering year over year growth of 34% compared with the third quarter of 2023.
Tolga Tanguler: As you continue to consistently increase the number of patients on therapy in both our TTR and rare franchises.
Tolga Tanguler: Let me now turn to a summary of our third quarter, GTR Performance.
Tolga Tanguler: Our TTR franchise achieved $309 million in global net product revenues.
Tolga Tanguler: Representing a 34% increase compared to the third quarter of 2023 as it continues to increase the number of HATTR Poultoner
Tolga Tanguler: Partitially, Nautality, in the US, given the competitive environment.
Tolga Tanguler: We are approaching 5,000 patients on treatment with on-patthroids, or on-butthroglobaly, and there is still a significant growth of opportunity, given that our belief that 25,000 to 30,000 patients across the globe suffer from this devastating disease.
Tolga Tanguler: Now, let me provide highlights of our U.S. and rest of the world teach our performance.
Tolga Tanguler: In the US, combined sales of compact raw and omelette were increased by 8% compared with the second quarter, and the robust 37% year over year, as momentum and mutation apps continue to drive strong growth.
Tolga Tanguler: The US-37% year-over-year growth was primarily driven by the following.
Tolga Tanguler: A 31% increase in demand, driven by the strength of ongoing onboard trackation uptake, more than offsetting the decrease in patients on our patrol, who have switched to onboard track.
Tolga Tanguler: We are pleased with the growth in demand which has been closest and throughout the year despite new competition and to the market at the end of 2023.
Tolga Tanguler: Favorite ability is also driven by Gross to Net Adjustment.
Tolga Tanguler: Now, let me turn to our international market with the TTR franchise growth decreased by minus 9% compared to the second quarter of 2024 yet our quarter over quarter patient demand remains strong with the first time growth.
Tolga Tanguler: The 9% quarter on quarter decreased was driven by a gross net adjustment approachable.
Tolga Tanguler: That was booked in Chutri and larger orders of on-patrewing our partner markets in Chutri, including Australia, where we built inventory as we launched on-patrewing this market.
Tolga Tanguler: On a year over year basis, the TTR Business and International Market, groomed by 31% compared with the
Tolga Tanguler: As our recent TTR invested day, we shared our plans for the promising potential of Wutur's ran in addressing ATTR cardio-my-opunty, pending regulatory approval.
Tolga Tanguler: We're confident in our journey toward leadership in this field, driven by several T factors.
Tolga Tanguler: ATTR, Cardium Laiopathy is in rare and progressive disease where there is significant on metneed and substantial number of patients remain on diagnosis or not optimally treated.
Tolga Tanguler: with HDSB, we've shown very compelling results across key end points in a population with selective up-to-date patients.
Tolga Tanguler: We have a track record of success in Paul Naroffity, an experience operating in a competitive environment.
Tolga Tanguler: And our dedicated focus on ATTR will be instrumental as we scale for a successful launch, building online on flagship franchise and ushering a new phase of growth.
Tolga Tanguler: Now, moving to our rare franchise and the performance of the Lary Nox Global.
Tolga Tanguler: which delivered 11 million dollars in combined Nestra, Axel during the third quarter representing an 8% increase compared with the second quarter of 2024 and 34% growth compared with the third quarter of 2023.
Tolga Tanguler: Board G-Lari, Q3 product sales increased by 14% versus Q2, primarily due to the timing of orders in partner market, and a robust 31% compared with the third quarter of 2023, with the following year over year regional highlights.
Tolga Tanguler: A 9% increase in the US, primary and driven by growth in new patients on therapy, a 7% increase in our rest of world market, primary and driven by the timing of orders in our partner market, primarily Brazil, and increased demand growth across European markets.
Tolga Tanguler: For OXUMA, Q3 products sales were relatively flat versus Q2, 2024, while delivering robust 40% year-over-year growth compared to Q3, 2020, with the following regional dynamics.
Tolga Tanguler: A 54% increase in the US, primarily driven by strong patient demand growth, a 33% growth from our rest of world market, primarily driven by strong patient demand, growth across both EU and our partner market.
Tolga Tanguler: In conclusion, our third quarter results to reflect consistent strength with both our TCR and rare franchises, achieving impressive patience and revenue growth.
Tolga Tanguler: This performance positions us well to meet the midpoint of our full year revenue guidance, which we updated and raised during our second quarter earnings call.
Tolga Tanguler: We remain intensely focused on preparing for a potentially a teacher, cardiomyopathy, launch next year and with that I will now turn it over to Pushkal to review our recent R&D and pipeline programs.
Tolga Tanguler: Pushkal.
Pushkal: Thanks Tolga and good morning everyone.
Pushkal: i
Pushkal: As you all know, Q3 was very exciting for our TTR franchise. We shared the full results from the pivotal Helios Beast study at ESC in August, and additional exploratory findings at HFSA in September.
Pushkal: Together, these data presentations highlighted with tree serents potentially transformational profile in today's population of patients with ATTR Cardi-Malapathy.
Pushkal: with benefits across a comprehensive series of assessments. We started with Rapid Knockdown of TTR, characteristic of the RNA mechanism of action. We then saw favorable impact on cardiac biomarkers as well as a cardiac graphic assessments reflecting impact on the underlying pathophysiology of this disease.
Pushkal: This will then followed by impact on a number of important clinical measures of function and health status indicating delays in disease progression. And ultimately, we saw profound benefits on outcomes with a greater than 30% reduction in all cause mortality.
Pushkal: Based on these compelling data, we've now completed regulatory submissions in the United States, where we've used a prior to review voucher and an EU with additional global regulatory submissions to follow in late 2024.
Pushkal: Turning now to another important program for our island, we're excited today to share new results from the multiple dose portion of the phase one study of my VELCERANCE in patients with early onset Alzheimer's disease.
Pushkal: As you recall, my Välzeran is the leading program in our effort to expand our RNA platform to target organ systems beyond the liver and address the high-end metinede that exists for neurologic diseases.
Pushkal: The VELCERAN is a C-16 conjugator RNA at therapeutic targeting amoloid beta precursor protein or APP and is in development for the treatment of Alzheimer's disease and cerebral amoloid angiopathy or CAA.
Pushkal: APP is the upstream precursor of all Amolid beta peptides that form the Amolid deposits that are characteristic of these two diseases.
Pushkal: We believe that by lowering ATP production, we can reduce the substrate for new emerald deposition, potentially enable natural clearance and slow, halt or even improve the clinical manifestations of these devastating diseases.
Pushkal: Today we're sharing initial interim data from the first multiple dose cohort from the phase one study in the Delta R&D early onset Alzheimer's disease patients.
Pushkal: and the chart here in the dotted line. You can see the rapid robust and sustained target engagement. We achieved with a single 50 milligrams dose during the single dose part of the study, as measured by the target engagement by a marker, soluble APP beta.
Pushkal: After single dose on day zero, mean reductions of approximately 75% in solubly of VP beta were seen at month 1 with sustained reduction of approximately 50% to apparent at month 6. And the slow return towards baseline thereafter.
Pushkal: In pink, you can see the initial intramdate up from the multiple dose portion of the study, where patients were administered 50 milligrams at month 0 and 6, and then followed through month 7, where 30 days after that second dose.
Pushkal: You can see that APP made up also a very similar trajectory to the patients after the single dose of 50 milligrams of the first six months.
Pushkal: But then, after the second 50-millogram dose at month 6, we see further reductions of APP beta at month 7, with patients achieving about 90% lowering of APP beta.
Pushkal: So these are very encouraging data. As they indicate we can achieve sustained, robust lowering of the APP with relatively low doses.
Pushkal: Importantly, the Velstron has been generally well tolerated in both the single and multiple dose parts of the study.
Pushkal: Known you safety signals have been identified in phase one and those significant abnormalities have been seen on CSF safety labs such as total protein and CSF white cell count or on the exploratory biomarker neurofilament like chain.
Pushkal: Given these encouraging results, we continue to aggressively advance this program through clinical development.
Pushkal: Specifically, we have continued dose escalation in the single ascending dose portion of the study to fully explore the safety and pharmacology profile of the Mvalt's ran.
Pushkal: who now also initiated multiple ascending dose cohorts in the study to explore additional dose regiments.
Pushkal: As we announced earlier this year, we've begun at Phase 2 study in CAA, the second leading cause of hemorrhage stroke, and for which there is no existing disease-modifying treatment. And in parallel, we're defining next steps for a Phase 2 study in Alzheimer's disease, and provide updates into courts.
Pushkal: Moving to another exciting pipeline update, we removed our third CNS program into the clinic with initiation of a phase one study of ALN-H-T-O-2, which targets the disease causing hunting and protein, in-patient with hunting and disease.
Pushkal: In Q3, we shared non-clinical data supporting the broad CNS distribution, as well as the tolerability of deep and sustained lowering of ACT in non-human primates, after single and repeated intrathequism administration of ALN-HT-02.
Pushkal: We look forward to sharing updates on the succeeding program in the future, and we seek to address this progressive and fatal neurodegenerative disease.
Pushkal: As we've discussed, our potential upcoming launch in ATTK, our cardiomyopathy, the assuming regulatory approval, and near-term achievement, the sustainable profitability.
Pushkal: are going to give us a strong foundation to continue investing in the promise of our nanottheraputics, to treat a broad variety of diseases with critical, unmet needs.
Pushkal: But as we've also discussed, we continue to be disciplined about research allocation in this key phase of growth.
Pushkal: As part of that ongoing commitment to optimize our efforts, we've announced today a decision to stop clinical development of ALNKHK. An investigational RNA-I therapy to target in keto hexachynes for the treatment of type 2 diabetes melons.
Pushkal: The decision furtheres our efforts to allocate clinical, managerial, and financial resources carefully to bring transformative medicines to patients, including our other programs in the metabolic space, which is an exciting one for our NI-3 appearance.
Pushkal: We continue to explore multiple targets from metabolic disorders and look forward to sharing updates in the future.
Pushkal: So in some we've made great progress in advancing our pipeline and platform with much more to come.
Pushkal: As a reminder, we're working towards filing the proprietary INDs for 9 programs by the end of 2025, against Targets and the liver, CNS, Muscle and Adapose.
Pushkal: If we include partner programs, we anticipate the potential for 15 new INDs by the end of 2025, representing a near-doubling of our clinical pipeline by the end of next year.
Pushkal: Disremarkable and unique pace of innovation puts us in a great position to have a robust self-sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas.
Speaker Change: With that, let me now turn it over to Jeff to review our financial results and upcoming milestones.
Speaker Change: Jeff?
Jeff Poulton: Thanks Pushkal, I'm Gomori and everyone. I'm pleased to be presenting a summary of Outmiles Q3 2020 for financial results and discussing our full year guidance.
Jeff Poulton: Starting with the summary of our PNL results for Q3 2021 compared with the same period in 2023.
Jeff Poulton: Total product revenue for the quarter was 420 million or 34% growth versus 2023. With both our TTR and rare freight chises reporting strong growth of 34% primarily driven by continued strong demand has told that previously highlighted.
Jeff Poulton: Net revenue from collaborations for the quarter was 57 million representing a $370 million decrease when compared to last year.
Jeff Poulton: The decrease was primarily driven by the recognition in Q3, 2020-3.
Jeff Poulton: of the 310 million upfront payment from Rose.
Jeff Poulton: as well as the 65 million in revenue recognized from a $100 million milestone, earned for achieving certain criteria during early clinical development for my Belseram.
Jeff Poulton: Royalty revenue for the quarter was 23 million, or more than double what was recognized in the third quarter of 2023. The increase was driven by higher-leck VO sales as Navarra continues to grow demand for lecvia worldwide.
Jeff Poulton: Rose margin on product sales was 80% for the quarter compared with 75% in the third quarter of 2023.
Jeff Poulton: The improvement in margin is primarily due to higher costs in 2023 associated with canceled manufacturing commitments for unpatthrowed and other adjustments to inventory, for which similar expenses did not occur this year. Offset by an increased rate of royalties payable on net sales of input truck.
Jeff Poulton: I expect our gross margin on product sales will be lower in Q4, driven by a higher royalty rate table on sales of Invout's track.
Jeff Poulton: Our non-gap R&D expenses increased 12% in the third quarter compared to the same period last year.
Jeff Poulton: primarily due to increased costs associated with our preclinical activities as we progress our 225 strategy to expand our clinical pipeline by the end of 2025, as well as clinical activities which mainly grew with expenses associated with Elby Seran Cardi three phase two clinical study.
Jeff Poulton: and increase personnel costs.
Jeff Poulton: Our non-gap SG&A expenses increased 19% in the third quarter compared to the same period in 2023.
Jeff Poulton: Primarily due to an iron cost associated with marketing investments to promote our TTR therapies.
Jeff Poulton: and preparations for the potential launch.
Jeff Poulton: of the Emboude Trevor Cardio-Mathty, along with increased personnel costs.
Jeff Poulton: Our non-gap operating loss for the porter was 31 million, representing more than a $300 million decrease compared with Q3 2020-3. Primarily driven by the recognition of collaboration revenue related to our Roche agreement and achievement of a Mavelceran milestone last year as previously highlighted.
Jeff Poulton: We ended the quarter with cash, cash equivalents and marketable securities of 2.8 billion, compared with 2.4 billion, as of December 31, 2023.
Jeff Poulton: With the increased primarily due to improved operating performance and net proceeds received from the issuance of common stock and connection with employee stock option exercises.
Jeff Poulton: Now I'd like to turn to our financial guidance for 2024.
Jeff Poulton: Today we are reiterating our 2024 guidance that was updated on our Q2 earnings call.
Jeff Poulton: We anticipate combined net product revenues for our four commercial products will be within a range of 1.575 and 1.65 billion.
Jeff Poulton: Our collaboration royalty revenue guidance ranges 575 million to 650 million.
Jeff Poulton: And lastly, our guidance for combined non-gap R&D and SGNA expenses remains a range of between 1.775 and 1.875 billion.
Jeff Poulton: Let me now turn from financials and discuss some key goals and upcoming milestones for late 2024.
Jeff Poulton: We announced that we'll present additional findings from the ongoing phase one study of ALN TTRSCO for in patients with ATTR, AMOLEDosis at the American Part Association Scientific Sessions in November.
Jeff Poulton: We plan to share our Phase 3 development plan for ALN TTRSCO4 and the first quarter of 2025.
Jeff Poulton: We also intend to initiate a Phase 2 study for mobile serenetations with Alzheimer's disease, at or around year end.
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. Those dialed in, we would like to ask for you to limit yourself to one question each and then get back into a few if you have any additional questions.
Speaker Change: Thank you. At this time, if you would like to ask a question, please press the star in one on your telephone keypad. You may remove yourself from the queue at any time by pressing star to...
Speaker Change: Once again, that is Star in one to ask a question. We will pause for a moment to allow questions to cue.
Speaker Change: And we'll take our first question from Ellie Murl with UBS. Your line is open.
Ellie Murl: Hi, guys. Thanks for taking my question. Just in terms of your earlier stage pipeline, can you elaborate a bit on some of the work that you've done to improve the ability to deliver our AI to out-of-post tissue and muscle? And how are you thinking about what makes the most sense as initial targets or diseases in these tissues and any specific advantages to your approach versus other modalities? Thanks.
Speaker Change: Yeah, thanks, Ellie.
Speaker Change: Teds.
Speaker Change: Jeff Highlight, we've talked about, you know, we are very excited about the emerging profile of RNA therapeutics, right? What we're seeing is that these therapies are period of be well tolerated and we can get sustained knockdown of a disease causing protein that allows for infrequent administration.
Speaker Change: and we're guided by human genetics in terms of the diseases that we pursue, which can allow us to validate both efficacy and safety using population genetics.
Speaker Change: as well as preclinical work. So, at a post and muscle are two of the areas that we've highlighted in our two to five strategy as new tissues to pursue.
Speaker Change: We highlighted a little bit at R&D day early in the year, some of the approaches that we're taking.
Speaker Change: and we remain on track to progress.
Speaker Change: Um... uh...
Speaker Change: Those we actually will be talking about an R&D day early next year and we'll give the specific timing of that and that's probably the best time for us to give a more substantive update on those programs. We're making good progress and you know, for competitive reasons, we're probably not going to say a lot more at this point.
Speaker Change: Thanks for the Scar that's great. I think in one of the opportunities of our platform release, continue delivering ongoing innovations. We start to make progress in some of these extra and perfect issues. Thank you, Eddie. Next question.
Speaker Change: Thank you. We'll take our next question from Gina Wang with Barclays. Your line is open.
Speaker Change: Thank you for taking my questions. I wanted to ask her.
Gina Wang: Long question regarding the LNHT-02, it seems like very impressive data in non-human planets. I believe this is the one with very few.
Speaker Change: Shoe is actually knocking down in Nansilam Pradesh, Brains instead of the most of others Shoe in Baudent Brains. So you know everyone is using 50% as a benchmark. Is that something you are looking for? What else you are looking for regarding the face one data?
Speaker Change: Yeah, thanks, Gina. I'm glad you're highlighted the Huntington's program because it's one that we're particularly excited about. This now represents our third.
Speaker Change: CNS program that we're moving into the clinic and...
Speaker Change: You know, what we're seeing here is that many of the insights that we learned from our APP program in terms of being able to have sustained knockdown of a disease causing gene and appears to be well tolerated in preclinical studies is very encouraging, you know, so we believe we will have something that will allow sustained knockdown as well as
Speaker Change: Hopefully be well tolerated in the clinic as we've seen with our APP program today.
Speaker Change: The non-clinical findings were actually quite benign in the pre-clinical studies that we saw, so highlighted in the slide, was well-tolerated, both in rodent and non-climic species.
Speaker Change: and then the targeting approach we're taking is quite unique. We're going after an upstream portion of the gene which includes the X on one fragment.
Speaker Change: and emerging amount of data.
Speaker Change: in the literature that suggests that beyond targeting the full length mutant protein, the targeting the X-on-1 fragment may also help.
Speaker Change: and progression of this otherwise very, very rapidly progressive and fatal disease. So we think we may have an opportunity for unique efficacy with this molecule. So we're moving forward in our single-assembling dough study.
Speaker Change: These are patients with symptomatic disease. We'll be looking at safety and tolerability.
Speaker Change: PKPD will be looking to change the meeting hunting themselves level.
Speaker Change: Mutant Huntington levels and we'll also have in that as we go forward clinical and imaging and biomarker measures. Negris such as NFL, etc. that can be very useful in looking at progression in this disease.
Speaker Change: The study is an active startup mode in the UK, Canada and then in the United States, we've also have a green light to proceed. I'll note that we do have a dose cap in the United States.
Speaker Change: and so we still have a green light to proceed in all three territories and we're moving forward so I'm very excited that we'll be able to do that and we'll work with the FDA going forward if and when we need to sort of lift that dose cap it may give us enough coverage as it is to cover the doses that we're interested in.
Speaker Change: but we'll work with the FDA in terms of lifting that dose cap over time. And so we're very excited about this program.
Speaker Change: Nice question.
Speaker Change: Thank you. We'll take our next question from David Leibowitz with City. Your line is open.
David Leibowitz: Thank you very much for taking my question. In terms of Pauline or Opusy at this point in time, how would you say the impact of the second silence that has been on the market in the overall trajectory? And additionally, I know the point of your prior prescribed, we're exploring Pauline or Opusy at Cardiologists.
David Leibowitz: Have you noticed an inflection in the number of questions coming regarding the ATTR's cardinal myopathy data?
Dave: I Dave.
Speaker Change: Yeah, look, I mean, now we have nine months under our belt with another competitor in the marketplace in the United States and what you will see in our quote over quote or growth in the US.
Speaker Change: which is 8% up as well as our year-over year growth that is 37% up is a good indicator of actually not only
Speaker Change: How this category still does a significant on my needs.
Speaker Change: But how we've been able to actually...
Speaker Change: Competitor. And we believe the fact that our, you know, route of administration is quarterly with a number of optionalities in terms of where those patients actually can receive their treatments.
Speaker Change: The fact that our patients remain on treatments due to this quarterly dosing at our patient's services as well as obviously what you'll see in our platform that the ability to provide rapid knockdown.
Speaker Change: and quickly as within the first dose at 6% or at 88% after the second dose are important differentiators and we believe this is really getting good traction both with patients as well as physicians. In terms of the cardiologist, the second part of your question,
Speaker Change: Look, we've put established.
Speaker Change: We are in clear guardrail to make sure that we are promoting.
Speaker Change: Compliantly and making sure that the launch is ahead of us.
Speaker Change: We're not in the launch phase. And when there is questions around the heliospeak, we appropriately address that in three hours that with our medical affairs colleagues.
Speaker Change: But in terms of the number of patients that are coming in with that indication that would not be something that we would allow us in organization.
Speaker Change: But overall, again, I'm very pleased with the performance of Q3.
Speaker Change: and we are seeing we're continuing to see if this robust demand in our Poulton Roper to hear the detailed indication. That's terrific, Tolga. I think it's an industry that we've actually built a really high performing commercial engine and we have a compelling profile.
Speaker Change: from Boot Truss, who are very excited about the future. Thank you, next question.
Speaker Change: Thank you. We'll take our next question from Paul Mitya's whip-steefle, your line is open.
Speaker Change: Great, thanks so much. I wanted to ask one more follow-up question just on recent for describing dynamics and TTR in light of the helios B data and Tolga, I totally understand where you're coming from right, as you guys promote.
Speaker Change: Solion Paulinger opethe, but just as it relates to a cardiologist that they want to prescribe.
Speaker Change: and Bootsha right now. What are the prior author requirements that you see?
Speaker Change: See, do they need to have a neurologist?
Speaker Change: Offer corroboration of a polynoropathy diagnosis, like are there kind of significant impediments in place that really can find this drug to that true mixteen type population at this point before getting an expanded label? Thank you.
Speaker Change: [inaudible]
Speaker Change: Yeah, Paul, that's great question and you clearly grasp some of the complications and how the patients are actually getting diagnosed. So if you're in a cardiomyopathy,
Speaker Change: You, if you're suspecting of having a cardiomyopathy, physicians, especially in the United States, tend to go through its integrity.
Speaker Change: and his impatient actually is determined to have.
Speaker Change: The condition is as suspected.
Speaker Change: They would then be quickly put on the treatment now in Poulton, Rhyperty.
Speaker Change: Not only because of our indications, it's very deterrent that you would actually go to a genetic testing to validate that. And then you would also have an additional neurological workup.
Speaker Change: to make sure that that patient actually has the neurological manifestations of the disease. And then you would be put on on the treatment. Now in terms of the access challenges.
Speaker Change: Nearly all of our patients actually end up getting good sustainacces regardless of what source of reimbursement a channel they have.
Speaker Change: It's mostly, is the challenge on the diagnostic pathway. Poulton Roper, you heard it say being the last stage of that pathway, rather than the first stage that we see in Cardio Myopathy.
Speaker Change: The End
Speaker Change: 3.
Speaker Change: and we'll take our next question from Ritu Bural with PD Gowan, your line is open.
Ritu Bural: Hi guys, thanks for taking the question. I wanted to ask just how...
Ritu Bural: and maybe Jeff, how you are thinking about payer discussions now, even ahead of potential label expansion. What are the levers?
Ritu Bural: Well, what are the topics that you're discussing and how are you viewing the potential for a volume-based discount upon potential label expansion and increasing number of patients on control?
Tolga Tanguler: That's a great question, Ritwa. I think it's actually Tolga. So Ritwa is we shared at the TTR Day, one payer's care is they should be is the value proposition, which is really driven by the clinical outcome. And as we have demonstrated in the Hulu SP.
Tolga Tanguler: The product really does provide an incredible, an important differentiator in terms of CVS coming to date patient population.
Tolga Tanguler: So that's what we're so far seeing is, here's understanding, acknowledging that this remains a rare, albeit growing disease.
Tolga Tanguler: and the fact that the Helios beer results outcomes are compelling.
Tolga Tanguler: In terms of how we're going to be able to navigate the access landscape, has a lot to do with.
Tolga Tanguler: Our patient access philosophy, I think what we've been able to demonstrate within the Poulton Roppet indication, how we've been able to get seamless access to our patients.
Tolga Tanguler: and the majority of them not having any co-pay burden in.
Tolga Tanguler: About 33% of them end up having about $2,000 on less co-pay burden.
Tolga Tanguler: and Part of Artificial Access to those of you who have to do with value-based agreements and appropriate rebates. This is an area where obviously we're going to be disclosing more. I have to be understanding if we shade.
Tolga Tanguler: Why there is interest in this, but we will actually communicate that as we get more closer to our to do for date, which is not set yet.
Speaker Change: I'm going to squeeze this in. Follow us there. How is the cardiologist and neurologist understanding of compressive neuropathy?
Speaker Change: Carpool Tunnel, Spinos Tunnel, Spinos Tunnel, in there.
Speaker Change: Look, I mean, I think TTR is a systemic disease and that's why you have multi-centres that actually treat multidisciplinary physicians that actually treat this disease. Now, this doesn't also, of course, exist in every market, every...
Speaker Change: Academic, even though every academic student, but in most centers, you have a good collaboration between cardiologists and enrollees and in some cases even orthopedic surges.
Speaker Change: Because the disease has been involved in the genesis of the disease evolved by the cardiologists, the first stop tends to be in the cardiologists where they actually do the synchigraphy and do the preliminary diagnosis. And if there is not suspicion of additional manifestations of disease,
Speaker Change: Day 10 to go with the only approved product that's available today. And we believe that's always going to change over time.
Speaker Change: I think it's a great question I see.
Speaker Change: Be sure because these red flag symptoms I think are going to be an important part of position education and awareness going forward. So thanks for the question. The two questions. Let's take the next question.
Speaker Change: Thank you. We'll take our next question from Selven Richard with Goldman Sachs. You're on his open.
Selven Richard: Thanks for taking your questions. Just tell me on for a thousand. So you talked about how there is this initial focus on a frontline for current malpathy. But wondering if what you're thought for is there could be a bowl of some cast of grassers in a second half of next year who are wearing kind of want something new. Thank you.
Speaker Change: Yeah, I mean, in our CTR day, we delay the strategy. And the reason why we explained that strategy is a lot to do with...
Speaker Change: What the data suggests and where today's patients are. So as we highlight it, this is a fast progressing and severe disease.
Speaker Change: So our understanding is the treatars are really focusing in to make sure that they as soon as they diagnose these patients, they would have died as I'm early.
Speaker Change: and they want to hit start.
Speaker Change: It's hard with a product that we believe is going to be providing data with today's patient population, where the subgroup patients where portion of them are on the only stabilizers that is available or with GLP1 or their own dieted against hand situation.
Speaker Change: Those are the patients that they are currently seeing. And if you look at the dynamic of the market, we see a larger number of patients that are coming into the category.
Speaker Change: So, you want to be able to establish yourself as a first-line product because of the data and because of the fast progress of the nature of the disease, so those patients actually can get treated. Now, in terms of patients that might be progressing on a stabilizer,
Speaker Change: Of course I'm sure the physicians will be starting.
Speaker Change: Identifying those patients if they have an already done so, and will probably eventually either depending on the access limitations or challenges that they may have.
Speaker Change: either put them switch them on those patients or use a combination carefully. Now, it's important to highlight that...
Speaker Change: Until, to families will become, will become generic.
Speaker Change: Division O'erab.
Speaker Change: Switch behavior that's going to establish in the category. Therefore, we do believe that will take some time.
Speaker Change: To establish and obviously we will be doing our part to make sure that those patients are identified, those patients that are progressing.
Speaker Change: are well identified, but I think it's important to highlight that given the number of patients that are coming into the category in the dynamic and the data that we have, we believe our Mootra will be well positioned to become a first line, instead of care therapy.
Speaker Change: Thanks for assuming you're through a lot of yass circles. Thank you for answering my question. Next question. Thank you. We'll take our next question from Jessica Phi with JP Morgan. Your line is open.
Jessica Phi: Hey guys, good morning. Thanks for taking my question. I got another one on TTR. Is there anything that you're going to be watching for in the Aquarium at a label?
Jessica Phi: with their produce of coming up. And I guess stepping back, do you see any of the potential labels scenarios for that product as relevant to your expectations for your own launch in TTR Cardio My Opity? Thank you.
Speaker Change: I don't like anybody, obviously, where interested in seeing the accramates label assuming.
Speaker Change: A proof of all, I mean we feel very confident about the data that we've generated with TVSB and we're looking forward actually to moving.
Speaker Change: through the regulatory process and both the US and Europe and using our priority review voucher, assuming
Speaker Change: Central Approval, Renexster, so we feel really good about where we are and I think we've also talked about the way to see exactly what gets delivered with respect to our parameters.
Speaker Change: The only thing I would add is obviously, you know.
Speaker Change: to comment on their label would be speculative, but from a broader market dynamic perspective.
Speaker Change: We believe our chromatists will be a twice daily stabilizer and how that market dynamic will shape, I think we'll have to do a lot to do with.
Speaker Change: Our orthogonal mechanism of action and how we will be able to compete in the patient population that are still, you know, again, is the first by-nation or those patients that are progressing on a stabilizer.
Speaker Change: For Essex, thank you. Next question, please.
Speaker Change: Thank you, we'll take our next question from Gary Nalkman with Raymond James. Your line is open.
Gary Nalkman: Thanks for watching. So as we anticipate the launches of Bootree and ATTRCM next year, in both the US and then the EU, how shall we think about spending levels in the US and ATTRCM?
Speaker Change: for all the commercial activities you'll be doing just order of magnitude. And then remind us of the infrastructure you have in Europe and how you think of the CM opportunities there relative to the US.
Speaker Change: In terms of both accessing patients and also pricing, thanks.
Speaker Change: That's a great question. Thanks. I think Jeffrey will take the first part of it and then close and we'll spot off with his plans for making sure he kind of executes on our plans for...
Speaker Change: and Cedant.
Speaker Change: Yeah, I would say we upgraded our guidance this year at Q2 on Op-Ax, right, and that reflected confidence that we had in the yellows B results and sort of playing the win.
Speaker Change: You'll see in the second half of the year this year in increase in investment and the commerce team has made very good progress in starting to prepare for the launch, particularly in the U.S. with the hiring that's been done.
Speaker Change: So with a lot of that happening in the second half of the year, that's obviously going to create growth for next year.
Speaker Change: and we'll continue doing this more broadly even than just in the U.S.
Speaker Change: As we move towards the second half of the year in launches in Europe, I don't have specific guidance, but I would expect that.
Speaker Change: [inaudible]
Speaker Change: Gross to make sure that we're active in the well-position, to be successful in the CM indications. But it's not going to go anything else. The only thing I would add is, from an organizational focus perspective, we have a establishing an end to an organization.
Speaker Change: which actually demonstrated.
Speaker Change: Excellent results, not only in TTIO, but also in RARE, so our TTIO organization, not only in Europe , but also in Japan.
Speaker Change: has been demonstrating really robust growth numbers. I mean, we've, you know, just posted a 31% year-over-year growth. If you look at the performance on the demand side of our international business,
Speaker Change: is been up at 6% quarter over quarter. Now that's been done in a market where there's significant price sensitivity.
where we have a PN product that's priced for the narrow indication and we've been able to become a market leader at 80%.
Speaker Change: versus Tefamilis in that specific pn-indication where we also compete with them in that indication.
Speaker Change: So we actually are quite pleased with the structure that we've established.
Speaker Change: And as Jeff indicated, we're going to play to win.
Speaker Change: and make sure that we are providing the right...
access, you know, options in those markets and so far we've been able to compete well and we believe we'll be able to do that with the Helios B data, you know, as a tailwind. Great. Thank you, Tolga. Next question.
Speaker Change: Thank you. We'll take our next question from Kotes Billioris with BMO Capital. Your line is open.
Kotes Billioris: Good morning everyone. Thanks for...
Kotes Billioris: and outside of your pipeline, acknowledging that your pipeline is large and very robust and can drive growth. I'm wondering whether you can comment on potential bid activities that could potentially support even additional growth in addition to your internal efforts. Thank you.
Speaker Change: Yeah, no, that's a that's a great question. Look, we're very we're very privileged, actually, to have.
kind of an incredibly rich pipeline. I mean, we think it's, you know, one of the most exciting pipelines in the industry. And
Speaker Change: Pushkal touched on the fact that we'll be doubling the pipeline by the end of 2025. So we've got a lot of really, really interesting opportunities in the company. And clearly, we're also going to make sure that we focus on a successful Avutra launch.
Speaker Change: And so, you know, we're really focused on driving both our internal pipeline, as well as continuing to optimize the platform.
When we think about BD, we're also very open to considering opportunities that really enable
Speaker Change: our platform and help us, you know, continue to access.
Speaker Change: you know all the other tissues and Pushkal describes some of these. And so really that's our focus at the moment. Clearly we, you know, we obviously, you know, pay a lot of attention to what's happening in the innovation landscape around us, but really we have
We're in a very privileged position to have an awful lot that we can progress within the company and we're excited to move all of that forward.
Speaker Change: Next question.
Speaker Change: I think this is our last question. We'll take our last question from Tazina Mott with Bank of America. Your line is open.
Tazina Mott: Great, thank you for squeezing me in. Maybe this last one is for Tolga, going back to the launch. In terms of expectations,
Tazina Mott: For the early part of any rare disease launch, I think companies talk about the time it's gonna take from the time the script is written to the time that the script is dispensed to the patient. But since this is gonna be the second indication for your product, do you expect those traditional, sometimes conservative timelines as to extended time periods, at least initially, to hold true here, or do you expect that to already have been?
Speaker Change: moved out from your p.m. lunch. Thanks.
Speaker Change: Yeah, thank you Tazine. We recognize that this is an area where we do need to provide some additional color, and we will do that closer to our launch timelines and the respective engagements that we will have. And we should be able to provide additional context as we get closer to the launch.
Speaker Change: Thank you, Tolga. And look, thank you to everyone for joining us on the call. We feel very pleased with the third quarter of 2024. It was one of continued progress. We've delivered robust national growth as well as advancements in our pipeline. So thank you, everybody, and have a great day.
That concludes today's teleconference. Thank you for your participation. You may now disconnect.