Q2 2023 Alnylam Pharmaceuticals Inc Earnings Call
Okay.
Good day, and thank you for standing by and welcome to the out nylon Pharmaceuticals, Q2, 2023 earnings conference call.
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I would now like to hand, the conference over to the company.
Good morning, unforeseen limit them senior Vice President Investor Relations and corporate communications that alone with me today are Yvonne Greenstreet, Chief Executive Officer, a rectangular Jakarta Lafleur with regard Chief Medical Officer, and Jeff <unk> Chief Financial Officer.
Would those be preceding via conference call. The accompanying slides can be accessed by going to the events section of the investors page of our website that first thought on island dotcom lots of that.
During today's call as outlined in slide two of them offer introductory remarks and provide some general context.
Paul will provide an update on our global commercial progress.
Well 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.
I'd like to remind you that today's call will contain remarks concerning all my life.
The patients plans and prospects, which constitute forward looking statements for the purposes of the safe Harbor provisions of the private Securities Litigation Reform Act of 90 to 95.
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 with SEC.
Any forward looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date.
The security frame any obligation to update such statements to.
With that I'd like to turn the call over to Yvonne.
Thanks, Christine and thank you everyone for joining the call today.
In the second quarter of 2023, we continue to make great progress across our business starting with our commercial performance. The <unk> Richard launch once again drove strong growth in our pizza, our franchise with 46% year over year growth in total product sales with 43%.
Year over year growth compared to the second quarter of 2022.
We also delivered strong execution across our clinical pipeline with notable results included positive 18 month data from our Apollo B Phase III study reaffirming the potential of <unk> in <unk> amyloidosis cardiomyopathy.
In July we shared updated positive interim results from the phase one study of a L. A P. P. In patients with early onset Alzheimer's disease, showing rapid and robust target engagement with sustained effect over six months with a single dose and an encouraging clinical safety and Tolerability profile.
<unk>.
Additionally, our team executed on the business development side, most notably we entered into a strategic partnership with Roche for the development and commercialization of <unk>, providing us with what we believe is a remarkable opportunity to bring forward a potentially transformative program with the potential to this.
The global treatment paradigm for hypertension.
We're also pleased to announce this morning that following a full cooperation with the government. The U S. Attorney's office for the district of Massachusetts has now concluded and close the case regarding the marketing and promotion of <unk> in the U S with no action.
Operating with integrity has always been and will continue to be core to our nylon and we will continue to hold our business conduct and in particular, our interactions with health care providers and patients the highest ethical standards.
As we move into the back half of 2023, we have several important catalysts, including the initial data from Ekati, a phase II program, SRP Swan and pending a successful outcome and positive regulatory review the potential launch of on Patriot and ATT amyloidosis with cardiomyopathy.
We believe all of this puts us on track with our nylon pizza fits by 'twenty five goals, making all nine of our.
A top tier biotech company, developing and commercializing transformative medicines for rare diseases and beyond for patients around the world driven by a high yielding pipeline of first and best in class product candidates from our organic product engine.
All while delivering exceptional financial results.
Further before I hand, the call over.
I'm very pleased to share that Akshay <unk> our president.
President and key scientific leader will be transitioning to a new and exciting role within the organization, serving as our first chief Innovation Officer.
It's been at the helm driving songs that innovation with our nylon for nearly 18 years and that effort has yielded an entirely new class of medicines in his new role actually it will become the company's key innovation leader focused on the future of our R&D engine, which is the lifeblood of how we have and will continue to drive our re.
Such in development programs into transformative medicines as we continue to build a top tier biotech company with that let me now turn the call over to <unk> for review of our commercial performance toga.
Thanks, Steve.
And good morning, everyone.
Q2 was another strong quarter for all island, driven by our TCR franchise and the strength of our ongoing launch of our mature across several markets.
Which has started with the U S where it has now been available for over a year.
Our total net product revenues across all products grew 43% year over year in Q2.
Let me now review our teach out performance during Q2.
The TCR franchise achieved $224 million in global net product revenues for <unk> and onwards drop representing a 9% increase.
Paired with the first quarter.
46% growth compared with the second quarter of 2022.
At the end of the second quarter over 30, 490 patients were on Petro automotive systems worldwide up from over 3100 60 patients at the end of the first quarter, representing 10% quarterly patient growth.
With respect to our international performance.
It'll TCR second quarter.
Product sales increased 6% versus the first quarter driven by strong demand in Japan, and the U K U.
UK being our most recent launch markets.
After more than six months since launch.
What sort of demand growth in Japan is particularly encouraging.
With new patient growth being driven by a mix of switches from <unk> as well as patients naive to therapy.
Importantly on Patrick continues to deliver steady growth in markets, where there is not yet available.
<unk> robust demand generation activities as we position these markets for upcoming upcoming launches.
Now, let me turn to the U S, where combined sales of on petrol and <unk> increased by 12% versus the first quarter and a robust 72% year over year growth, representing the fourth consecutive quarter of achieving ctr growth in <unk>.
<unk> of 70% on a year over year basis in the U S. Since the launch of our truck in the third quarter of 2022.
This significant growth was primarily driven by a 15% increase in demand, which more than offset the decrease in patients on on Petro that switch to ultra and.
And the robust demand was slightly offset by inventory dynamics, which decreased reported growth by approximately 2% with channel inventory reductions to both products.
Okay.
<unk> continues to expand the overall GTR polyneuropathy franchise as reflected by our year over year growth.
The steady growth of <unk>, which our performance in the U S is a testament to the significant unmet need of patients with <unk> polyneuropathy.
Our commercial capabilities.
And naturally the product profile of <unk>.
Our leading performance indicators also continue to trend favorably.
Including the expansion of our prescriber base and favorable access, resulting in patient compliance rates of over 90%.
A year into launch we have increased our prescriber base by almost 50% through a balanced mix of academic centers and community based specialists, while switching a majority of the patients who are on Petro at the time of our water launch.
Now update on our ultra rare franchise.
We are proud to have developed and commercialized two ultra rare products transforming small patient populations that's suffered greatly.
Give laurie Zuma together delivered $82 million in combined product sales during the second quarter, representing a 14% increase compared with the first quarter and a solid 37% growth compared with the second quarter of 2022.
We ended the quarter with more than 570 patients don't give laurie commercial therapy and more than 350 patients on <unk> commercial therapy, representing 8% combined quarterly growth in patients on our ultra air products compared with the first quarter of 2023.
Forgive Laurie global revenue growth of 21% in Q2 compared to first quarter was driven by the following.
In the U S. We had an increase in the number of patients on therapy, and an increase in patient compliance rates.
A robust 29% in our international markets, which was impacted positively both by demand growth as well as order timing and our partner markets.
For example.
Flat quarterly revenue was a result of fewer U S patients on a loading dose regimen, which offset modest patient growth.
Growth in international markets was primarily driven by order timing and partner markets, which was partially offset by an unfavorable pricing mix in our European markets.
Overall Q2, 'twenty three was another quarter of healthy growth in revenues.
Quest to serve more patients with.
With over a year since launch we are particularly pleased with the steady growth of our withdrawal, which represents an important therapy option.
For <unk> amyloidosis patients with Polyneuropathy.
With that I will now turn it over to push call to review, our recent R&D and pipeline progress Pushcart.
Yes.
Thanks, Tom and good morning, everyone.
Let me start by updating you on our TCR franchise, whereas you know were conducting two large studies Apollo b and Helios b to evaluate the efficacy and safety of <unk> and <unk>, respectively, and atti cardiomyopathy.
<unk> is under FDA review based on the positive results of the Apollo B study and as we recently announced the application will be discussed at the cardiovascular and renal drugs Advisory Committee on September 13.
We also announced today that enrollment in the U S expanded access protocol for Pity's ran that was opened shortly after the Apollo B readout last August as completed the EAP was established to provide access to <unk> for patients with <unk> amyloidosis with cardiomyopathy, who have had an inadequate response to or cannot tolerate currently available treatment.
The A&P was offered at 20 centers in the United States and the pre specified enrollment target of 200 patients was met in about 10 months, indicating significant demand for this potential therapy.
Another important <unk> recent update on Patese trend was the presentation of 18 month results from Apollo B at the recent ESC heart failure meeting.
And the new analysis, we were very encouraged to see that favorable effects on functional capacity as assessed by the six minute walk test as well as on health status and quality of life as assessed by the Kansas City Cardiomyopathy questionnaire, where sustained in patients receiving <unk> through 18 months.
According to both of these endpoints the teacher and appeared to slow the decline in functional ability and health status that is typical for this.
And similarly in patients who had received placebo during the double blind period initiation of the teeth straightening. The only period was associated with initial evidence of stabilization both six minute walk test and Casey Q relative to the double blind period.
Importantly, <unk> continued to demonstrate encouraging safety profile 18 months of treatment with no new safety concerns identified.
Sure.
We saw encouraging evidence of efficacy with other secondary and exploratory endpoints as well continued treatment with <unk> through 18 months was associated with relative stability in both NT pro BNP, a measure of cardiac stress and <unk> a measure of cardiac injury.
And patients rolled over from placebo to active treatment during the only saw slowing in relative to stabilization of the rapid increases that we've seen during the double blind period.
In addition, while the Apollo B study was not designed to show benefits on outcomes of hospitalizations or death, we were encouraged to see non significant trends favoring <unk> treatment in these outcome endpoints with extended follow up during the early period.
As we previously as previously announced we've submitted the 18 month results to the FDA as an amendment to our F&B April T strength, we look forward to continuing our engagement with the agency, including at the upcoming Advisory Committee and if <unk> is approved expanding its label to bring <unk> to patients with <unk> amyloidosis cardiomyopathy.
We were also very excited to share initial human proof of concept data on <unk> and APB. Our first RNA therapeutic designed for CNS delivery, which is in development for the treatment of Alzheimer's disease and cerebral amyloid angiopathy.
At the AIC Congress in July we presented updated positive interim results from the phase one study in patients with early onset Alzheimer's disease at the time of this interim look 20 patients had been enrolled in three single dose cohorts in part a of the ongoing phase one study.
To date, we've studied three dose levels $25 $50 75 milligrams with 46 patients dosed in each cohort excitingly <unk> treatment resulted in rapid dose dependent and sustained reductions of both soluble ABP alpha and beta.
Io markers of target engagement in the CSF.
We saw rapid knockdown as early as day 15, and observed maximum knockdown of $84, 90%, respectively, Precycle <unk> Alpha and beta and.
And at the highest dose tested 75 milligrams. The median knockdown was greater than 55% for both biomarkers and sustained for at least six months.
The safety of single doses of ailing ATP has been encouraging as well.
All adverse events were mild or moderate in severity and CSF parameters have not revealed any significant abnormalities to date.
Further exploration of single doses of Elan AP is ongoing in part day. In addition, part b the multiple dose part of the study has been initiated in Canada, where the majority of the part of a clinical trial patients were enrolled.
The multiples the multiple dose part of the study remains on partial clinical hold in the United States due to findings observed in prior non clinical chronic toxicology studies.
In sum Im thrilled about these impressive human data that provides the first ever evidenced that we may be able to use RNA hy to silence disease, causing transcripts in the CNS and look forward to providing additional program updates in the future.
Let me now turn to recent progress with <unk> in development for the treatment of hypertension. We're very excited to recently announce the phase one data were published in the New England Journal of Medicine.
Highlighting the medical importance of a substantial and durable lowering of blood pressure seen with single doses of Easter in this.
This now marks islands, 11th publication in this prestigious medical Journal.
Ivan has already highlighted the exciting collaboration with Roche, We recently announced the development commercialization of Zalviso and on the basis of these impressive phase one data.
We're now looking forward to results of the cardio one dose ranging study, which is on track for top line data in Q3.
In addition, we're also pleased to have recently completed enrollment in the cardiac phase II cardiac two phase II study, which aims to evaluate the safety and efficacy of <unk> in patients with uncontrolled hypertension when added on top of other antihypertensive medications. We expect to report topline results from this study in early 2024.
These are just a few highlights from our broad and innovative pipeline driven by our underlying organic product engine that we expect will deliver sustainable growth for our <unk> island in the years to come.
With that let me now turn it over to Jeff to review, our financial results and upcoming milestones Jeff.
First call and good morning, everyone I am pleased to be presenting a summary of <unk> Q2, 2023 financial results and discussing our full year guidance.
Starting with a summary of our P&L results for the second quarter.
Total product revenues for the quarter were 306 million, 3% growth versus Q2 2022.
As <unk> previously indicated the increase is primarily related to the growth in TCR product revenues driven by the launch of <unk> in the U S. In the third quarter of 2022 as well as increased patients on give laurie and auxilium of therapies the.
The impact of foreign exchange rates on our product sales has moderated on a year over year basis with constant exchange rate growth and only 1% higher than our reported 43% year over year growth.
Net revenues from collaborations for the quarter were $6 million or <unk>, 35% decrease compared with the second quarter of 2022, primarily due to operating variability, including the level of work reimbursed in our collaboration with Regeneron.
Royalty revenue during the quarter was $7 million, which was driven by Novartis and sales of <unk>, which launched in the U S. In the first quarter of 2022.
Despite the modest growth for revenues from collaborations and royalties we remain confident in achieving our full year result, with our $100 million to $175 million guidance range, primarily driven by our regeneron collaboration and Latvia royalties and milestones.
Gross margin on product sales was 75% in the quarter, representing a 9% decrease compared with the second quarter of 2020 to.
The decrease was primarily due to fees incurred associated with canceling manufacturing commitments from Petro and other adjustments to inventory as demand demand from Patrick continues to decrease driven by ongoing patients switching to <unk>.
Our non-GAAP R&D expenses increased 11% in the second quarter compared to the same period in 2022, primarily due to increases in head count to support our R&D pipeline and development expenses associated with the Carty, one cardiac two phase III clinical studies.
Our non-GAAP SG&A expenses increased 14% in the second quarter compared to the same period in 2022, primarily due to increased head count and other investments supporting our strategic growth, including the global launch of <unk>.
Our non-GAAP operating loss for the quarter was 154 million, representing a $7 million improvement compared with Q2 2022, driven by strong topline growth.
Set by more moderate growth in operating expenses.
Finally, we ended the quarter with cash cash equivalents in marketable securities of $2 1 billion compared to $2 2 billion at the end of 2022 with the decrease primarily due to our operating loss year to date.
We continue to believe our current cash balance is sufficient to bridge us to a self sustainable financial profile.
Now I would like to turn to our full year 2023 financial guidance, where we are reiterating our previously issued guidance.
Starting with net product revenues, we continue to anticipate combined net product revenues for our four commercialized products will be between one two and $1 two a $5 billion.
Our guidance for net revenue from collaborations and royalties remains a range between 101 hundred $75 million.
And our guidance for combined non-GAAP R&D and SG&A.
Expenses remains unchanged and is a range between $1 $5 75, and $1 65 billion.
Let me now turn from financials and discuss some key goals and upcoming milestones slated for mid and late 2023.
Question for those Taliban, who would like to ask you to limit yourself to one question.
And get back with you, but there's no question.
Thank you we will know conduct a question and answer session. As a reminder to ask a question. Please press star one one on your telephone.
Please stand by while we compile a Q and a roster.
Our first question comes from Michael's of Morgan Stanley . Your line is now open.
Thanks for taking the question maybe.
Maybe just just quickly any updated thoughts on the upcoming AD come from patrolling and a T. T. R. C. M. In terms of why the F. D. A decided to host the pay at all and then where do you expect the focus to be thanks.
And thank you for that question could you are actively preparing for the Advisory Committee and we're really looking forward to presenting.
The data that we have from Apollo to be.
<unk> specific questions at this time, we believe that the topics are gonna be focused on the clinical meaningfulness of changes in the six minute will test then Casey C Q, particularly given.
The fatty recent FDA guidance.
Uhm around the utility of these endpoints in patients with heart failure.
We we really do.
Leave that we have compelling data.
So I'll probably be study across in a wide range of and points and.
So it was supported by additional validation from the recent 18 months data that is prisco describes we have submitted to the F. D. A push call anything else the to add I think he really covered it on I think it really is.
<unk> underway, we feel really good about the data set that's been generated with Apollo B and what we're seeing is evidence of stabilization across a series of endpoints, which is really.
Critically important patients with this disease really value their functional ability and their quality of life and what we're seeing across multiple measures is that <unk> appears to enable that and thats reconfirmed with the extended a holy data that we submitted we look forward to prevent presenting that to the advisory committee as they do their review.
Thanks, <unk> next question.
One moment and the next question.
Our next question comes from Luca is C. F. R. B C line is now open.
Oh, great. Thanks for taking our questions. This is <unk> I just wanted to dive into some specifics on the roast Yale first I'll be <unk>, we know that <unk> $310 million upfront plus.
Stance on your term milestones your partner, Russia said that they expect to invest another $275 million to get to the end of phase. Two so just wondering if you can add any clarity on the 275 and if this is part of the substantial near term milestones that you're expecting thanks.
So that's a great question and a good opportunity for clarification I'll pass the answer to Jafar in a moment, but I just wanted to.
Remind everybody that that really what we feel that we have here.
<unk> is a game changing therapy for patients with hypertension resent to maximize the value.
Drive a successful global product launch when it comes to the market with.
Cardiovascular outcomes data.
To help inform the various stakeholders and notify the significance endeavor.
The collaboration with reddish allows us.
It brings together our leadership analogy is what is that.
Proven global commercial footprints and capabilities and help us maximize the resources and capabilities in order to be successful here, but I think it is important to us and you'll be specific about the about.
About some of the details the mountains with Jeff maybe you could yeah. Let me just clarify that service substantial near term development milestones that we had reference when we announced the deal or there's actually $365 million in potential development milestones because our next broken down as $65 million for the initiation of.
Party of <unk>, which is the additional phase two study that pushed call talked about on the on the deal call and we expect that studied his initiate next year.
And then an additional $300 million for the first patient in on the <unk>. The phase III study. So taken together that's the $365 million when you look at that in combination with the.
Development cost sharing where <unk>, 60% of the bill and on the island put 40 per cent of the Bill clearly from an out of pocket perspective from island to take this drug forward to the market really minimises the financial burden for US, which allows us to then reallocate capital across our pipeline and hopefully drive additional growth.
That's great Jeff Thank you.
Next question.
One moment for our next question.
Our next question.
From city.
With David Leibowitz. Your line is now open.
Thank you very much for taking my question question on the submission of the 18 months data for patrols.
<unk> I know the Paducah date stands in October is there any consideration by the FDA to consider this a major an amendment and move the date three months down the road or had they not it did any central tend to this point and on.
Franchise gross mm, while you know there's no question the overall franchises growing.
Quite well how is on par TRO.
Maintaining as much share as it is to this point, given how well Abu <unk> two weeks.
You got two great question, So I'll I'll I'll take the question on the proof of data and then I'll hand over to <unk>.
Uhm speak to your April franchise question around Lima isn't the dynamics between <unk>.
We're continuing to anticipate that produce the date is October the eighth and we're working towards that.
Changes of course will communicate.
Uhm any new information, but as of this moment, we are continuing to expect that the different days of Oxford.
Okay do you want me to answer the question on Nash on sure dynamics.
Happy too so the way I think we should think about this is U S N R.
The recently I'm with the launch markets and those markets that are continuing to have only on petrol as an option within the franchise.
As I indicated on the call. If you look at our U S growth.
<unk> category 70 per cent quarter over quote.
Growth what are the last four consecutive quarters, which is quite substantial then that's really primarily driven by literally in fact, the number of home Petro patients that remains in the U S. At the time when we launched.
<unk>.
Getting smaller and smaller so we're very pleased with how patients are switching over to <unk>.
And we've also seen in other markets like Japan.
Now, where we start seeing in France with a very.
Very creative Eighty-two program, the named patient program as well as in the UK, we're getting accelerated approvals.
And those several key markets to make sure that we're providing arbitrators adoption now than the reason why you see a good persistent growth on on petrol, albeit.
Albeit a smaller portion of our businesses because markets like Italy, and Spain, where which I still have it available we're seeing a good robust growth and that's again, a testament to Denise of an option in this market and polyneuropathy as well as our commercial the abilities that we've been able to drive.
A good strong robust growth, which obviously positions us very nicely at the time of which were launching these other markets, we're going to start seeing we'd like to see.
Good strong uptake of <unk> and subset of subsequent switches Chromone Patrick <unk>.
Thanks for telling about thanks for your question Yeah. Thanks, Thanks, Sir Thanks payments, that's fine that sounds the next question.
One moment for the next question.
Our next question comes from Tom Madness.
Your line is now open.
Hey, Thanks, so much I wanted to ask about the timing and any reason behind Akshay sprawl change I think Oxford became president just 18 months ago.
And it's such a pivotal time for all my island with the AD Tom coming up the Helio speed data I haven't heard him at all on this call. So I was just curious if you could expound upon this a little bit and clarify if there's anything else behind the decision or this announcement today. Thanks, so much.
Okay. Thank you for that question <unk> said that.
Actually it's going to take on this opportunity to become my first Chief innovation officer in that Sir.
In that capacity continued to focus on on helping sensitive. The continued success with respect to R&D organization, we will send the lines that we build some really strong robust capability across the the the research and development organization and that's allowed.
<unk> to be able to.
To.
Focus more specifically on innovation uhm as we build a top tier biotech company. So I think this is you know a terrific step forward for the company that's no.
Specific.
Reason for this timing other than the fact that I actually felt that you know we're now in a position where we have a really strong capability, which allows them to take on a much more focused role for the company and he'll continue to be involved in all the important upcoming capital S. At milestones that you've just described.
He's not on the call today cause he's actually on vacation, but I'm I'm sure.
We may well here I'm on on our upcoming cool in the future. So thanks for that question Paul.
Okay. Thank you.
One moment for our next question.
Mmm.
Our next question comes from Rita R. O F. T D. Colleen your line is now open.
Good morning, guys. Thanks for taking the question.
Mm mm.
Go down a little bit more on the preparation.
<unk> that's right.
What is yours or ours or S. T a.
Right now are you planning to be able to discuss any additional cuts later than 18 months from Apollo b or any data out of that for you know expanded access plan and.
Can you believe that there's any shift in understanding around and points given the reason, which bio data and how all of these coins and other endpoints like outcomes sort of link together.
Mm thanks be to the kind of few questions. Then instead of you know maybe.
<unk>.
And Sandra add com preparations any additional data that we're providing the F. D. A beyond the 18 months data that we've ready reference.
And then secondly, it kind of has any shifts and understanding with respect to add the endpoint.
<unk> I mean, <unk>, maybe you could you could take those two questions yeah, absolutely. Thanks for it to look in terms of the AD com preparations.
We're getting into the period.
We're really pulling together aspects of our preparation we feel very good about how the team is preparing for this and it's all based on an incredibly strong data coming out of Apollo B and reaffirmed by the only data that we talked about early in earlier and really it's the fact that across multiple measures within the study looking at <unk>.
Slight functional ability and quality of life. The biomarker data that are predictive of longer term outcomes. We're seeing evidence of relative stability patient to get on this drug for you to have less progressive decline and we'd shared data last year at R&D day, knowing favorable impacts on progression on N Y H a class in ATT or to these days to all of us really.
Paint a picture of delayed progression when patients are put on a silencer with this disease.
And that's really important that we keep hearing from conditions in the field that that's really important to patients. These are patients in their seventies and eighties.
Either functional ability and their quality of life and and so these changes are meaningful to them and I think when.
What I can say is that the outcome will be pulling together of those various arguments.
A lot of support both from the data side, but also from external keeping and leaders et cetera, and and so will look forward to making those points at the advisory Committee and interacting with the agency and the panel there.
Be bridged bio look I think what I would say is.
First of all it's great news for patients that it looks like there may be potentially an additional medicine as we kind of learn more about this data and that's just an additional stabilizer for.
For patients with this disease and you know I think it hats off to the patients the investigators and colleagues at bridge <unk> because it was it's been a challenging time and it's great to see that they've.
Pulled out what looks to be a very positive study in that regard I think as it relates to our franchise. We really remain excited about what the silencer profiled looks to be again building on what I, just said about all of the emerging data that we're seeing.
Again, not statistically significant but emerging trends with regard to outcomes coming out of Apollo be both on mortality and hospitalization and I think the.
Key will be looking for more data at the ESC meeting, but I think one of these results highlight is that in a.
While we are diagnosing patients earlier with this disease and that's been a big question in the field. These patients still indoor ongoing progression so that in the fall of the it looks like that's reaffirmed in the bridge five data in an effective therapy.
Show a benefit in that population and I think that reaffirms the design elements appeals to be very excited about that as well.
Great. Thanks.
One moment for our next question.
The next question is coming from solving richer at Goldman Sachs. Your line is now open.
Thanks for taking our question. This is Tommy on for solving and congrats on all the progress. Our question is also on French violin Hulio speeds. So we saw from French file that there is this imbalance in taft dropping rates between the two arms that have this impact on separation. How are you thinking about the risks, they're taking ESP, given the dropping allowance and kind of on the.
Other hand, what he'll just be be able to give physicians insight into potential additive benefit when you combine a file insurance stabilizer. Thank you.
Okay. So two questions to ask you a couple of maybe I'll just.
Start off by by saying that we're actually really pleased to see the bridge by.
Results, because it really kind.
Kind of reaffirms that even if patients to diagnose the disease continues to have disease progression where in effect to therapy.
Is is able to.
Demonstrate benefits in these in these areas stage patient. So I think we're actually really kind of pleased with this gives us increased confidence actually in delivering a successful here sp.
This call maybe you can talk specifically about.
The imbalance in Taft dropping rates central impact on.
On <unk> and also you know thinking about combination approaches.
Stabilizes and silences.
Look I think.
To tap dropping right I think as we've talked about in the past.
We've got careful measures in place and the way that the study was designed.
And we feel good about the dropping right that's their it's substantially below our internal assumptions as we design the study.
About any more specific updates on that but we are very encouraged by what we're seeing with regard to that and about the overall design. The study. The study allows for a proportion of patients.
To be on background to <unk> entering into the study just like we did in the <unk> study.
We have set our targets were around 50%, but we've operationally come in below that and so.
Think we will get interesting data emerging from that study in terms of how the drug functions as a mono therapy, but as well as on top of background to families.
Next question please.
One moment for our next question.
Our next question comes from Lori Ray costs Red Cross is Jeffrey your line is now open.
Hi, Thanks for taking my question.
For the 200 patients expanded access program study can you talk about the types of patients you've enrolled timeline data and how the data will be leveraged as it relates to regulatory your commercial plans.
Yeah, I'm, just calling to ask a question for you around the.
AP types of patients and then also thinking about how does have these dates and maybe use going forward.
Yeah. Thanks.
When the Apollo B data came out.
Posted about forward and the potential for an alternative mechanism for patients with this disease as we talked about multiple times during the call.
Patients.
Despite available standard of care therapy with defamatory.
Continue to progress.
And so what we did was establish an expanded access program.
At 2000 U S centers that enabled patients who were experiencing progression or otherwise tolerant of available therapy to avail themselves of the <unk>.
There.
Their physician support.
Cause that was open at 20 centers.
And as I mentioned.
That would actually relatively rapidly we had 200 patients it was actually on the order of about three.
Three patients every two days that was enrolled two patients every three days sorry that was enrolled in this EAP program and it really highlights I think what we've been saying and we've been hearing a lot from the clinical community of the patient communities that patients continue to progress with this disease and they need additional therapist. So I think that's important as we <unk>.
Think about bringing.
Bringing forward Patese Saran and this disease and then hopefully Patrice ran as well based on the results of Helios B.
Yeah. Thanks for asking I think the points about continued on my medical need is it's really the important one here.
Patients who are continuing to progress in patients that need authentic therapeutic approaches.
Next question please.
One moment for our next question.
Our next question comes from Eileen Merle M. UBS airline is now open.
Okay. Thanks, so much for taking my question.
Yeah can you elaborate on your rationale for Ya.
Anderson.
Uh-huh.
The insurance paralyze analysis that link to you.
Gotcha.
<unk> data.
So I can't check in terms of the avant Ray How're you thinking about the proportion have cardiovascular hospitalization that will come from.
Heart failure that comes on it.
The apartment that including the urgent heart failure as part of that definition. Thanks.
Scott two questions for you sure.
So I think there's there's a multitude of approaches to conducting survival analysis and outcome analyses that take advantage of the fact that.
You are looking at recurrent events and events over time.
And our statisticians, obviously spent a lot of time thinking about what's the optimal way to demonstrate clinical benefit.
Highlighted in a statistical analysis plan, that's a line with the agency.
In this instance, one of the reasons for preferring the Anderson Gil is the fact that there we allow for variable follow up.
Context of the outcomes analysis.
And the Anderson Gill really allows us to fully leverage that whereas other approaches.
Would allow us to use a fixed time, a follow up and frankly, the shortest amount of follow up. So we think it gives us a little bit of an analytic or a power advantage to do it that way.
With regard to the various components of the endpoint I think I think what's really important Elliot maybe just a larger picture.
We're trying to capture clinically relevant events.
Two heart failure worsening and the need for care in patients with this disease. So that's why.
There is increasingly provided and different geographies in different places, including in hospitals and urgent care urgent.
Care centers et cetera, and so we look at the totality of all of that as indicating clinically relevant heart failure events that we may have an opportunity to effect with an effective therapy and that's why that we've captured that aspect and the end point structure.
Okay. Thanks, so much.
One moment for our next question.
Our next question comes from William Pickering Bernstein, Your online account open.
Good morning, Thanks for taking my question I was wondering what per cent of Andrew to your patients are getting dosed at home so far and.
You look ahead to future competitive dynamics versus upon tourists and what is your market research tell you about how patients are thinking about the tradeoffs between physician delivered therapy quarterly versus monthly self injection. Thank you.
Okay, There's a few questions for.
<unk> the first relating to.
Home infusion of a second <unk> kind of an atheist.
<unk>, how we're thinking about.
Differentiation.
Yeah no. Thank you great. Great question look I think the way we should be thinking about this is our third will be the only disease reversing treatment for pulling the raw <unk> those four times a year.
And not only I think this really positions the product well throw him a convenience perspective, but there are a number of important features that we believe will will make ultra incredibly competitive.
Having a unique him away erupted and sustained disease reversal, obviously with a few stores and we should also remember we have five years of experience now in this category wonderful year in the U S.
Promoting on the truck that we really have been able to establish numbering of important patient and physician.
Physician capabilities starting from the fact that this is a part of the product and where we have excellent coverage of reimbursement benefits and then going into the patients with a side of care and and providing various options not just in the home but also.
In other different sites of care, whether it's an infusion center or in a hospital care and and more importantly than supporting the patient benefits. So one of the the question that you ask is.
Since we launched the <unk> we have over.
Nearly a third of our patients are getting home care and what's really also important.
To to remember that almost all of our patients over 90 per cent stays on Tennessee, not only get you.
Good convenience access to these medicines, but also is able to stay on Tennessee, we have a very very minimal dropouts. So with all these other features that we offer we believe this is going to remain.
Very significant benefit and another important one is obviously to remember.
Unlike party until 2025, our patients nearly 70 per cent of them has zero copay and this will continue to be unimportant benefit.
So we are very we feel very good about how all which resulted in any position in the market first with the values that we bring on the table as well as some of the some of the services that we set out there for the last five years.
Very helpful. Thank you so much.
One moment for our next question.
Mmm.
Our next question comes from Genie Yang at Barclays. Your line is now open.
Thank you for taking my questions. I also have one question regarding females B.
I think push going to pass you comment on <unk> dropping may I think the early all whereas in the low single digit I don't I I'm pretty sure now increase but.
But do you think you know so far.
Cracker, Jack clinical statistical team, they're responsible for monitoring of study.
And ensuring the quality of the data that come in and integrity to study in detail again really positive about what we're seeing overall.
And we have a long history of.
Of people and that's in those teams is designed and executed really successfully team.
Studies in this field, including Apollo B.
And so again, we feel very good about what we're doing here with with Helio speed.
Thanks for the question.
One moment for our next question.
Our next question comes Sam Lealan shall as Oppenheimer. Your line is now open.
Hey, Thanks for taking the question just a question for me as we look forward to the <unk>.
Data, obviously is being looked at and type two diabetes and you'll be looking quite semic indices will see presumably data there, but just wondering you know where that targets six could be useful for other related conditions weight loss obesity essentially Nash just wondering what your thoughts may be with respect you're taking that that Kansas in one of those.
<unk> directions.
As you will be looking at overweight obese patients in the study and even though you may have to other programs and Nash. Those are both partnered wondering if you have freedom to pursue Nash if you'd like for <unk>. Thank you.
Yeah, that's a great question.
Just.
Mind everybody's attack H K, so genetically about a day target involves the metabolism of.
And that's relevant to the development of diabetes and as you point out that the city as well clearly we're focused.
And in a phase one study addressing targets engagements and safety and also looking at a range of Biomarkers with respect to glucose metabolism and insulin levels, but I think you raise an interesting question, which is the brood potential of in a K it's K.
And metabolism general physical maybe want to provide some perspective, yeah, Lou and I think it's a really insightful question in the sense that.
We've seen epidemiologically that with rising consumption, we've seen parallel increases both and diabetes.
Overweight Nash.
Nash and a number of metabolic syndrome type diseases that all traveled together and it's entirely possible that by perturbing. This pathway.
With a RNA mechanism that we actually may have beneficial effects and a number of these different domain. So what's exciting here that we have what we think is a is a really potent.
And based on frequently durable.
Way to silence cage, K that we can elaborate and we have a number of biomarkers that we can measure in the clinic that will help guide us along the path in terms of which of these indications to pursue how to pursue them et cetera, and so and this is also then a proprietary target within alnylam that we're advancing.
And so we have really freedom to operate across a full range of diseases.
And take it where the science and the unmet need.
Drives us so so look forward to sharing more data on that in the future. So.
Thank you thank you Sir.
Highlighting I think another exciting opportunity in our pipeline and more to come.
Towards the end of the year.
Next question.
One moment for our next question.
Our next question comes from miles nature Williams later and company airline is now open.
Hi, you've got Sarah on for miles. Thanks for taking my question is there any clarity you can give on the timeline at the dancing Alan H T T.
Clinic or any other athletes that are using a C 16 conjugate technology and how does this been informed by the clinical Allen a P. P data the forest. Thank you.
The timeline.
A P P and any other programs.
Sorry.
Yeah, Oh HGT yeah. So.
Thanks, Sarah for the question I think.
Okay as I said in the remarks and as you've heard from US in a couple of recent calls I think what we've seen in the CNS space with Alan a P. P has been.
Really.
We think groundbreaking.
It really opens up a whole new vista or we can take our nai therapeutics too.
To affect a wide variety of neural degenerative diseases and beyond and the CNS.
When you look at what we see there we see with.
With the levels of up to 80, 490% lower flowering of Seibel, AVP Alpha and beta that really signifies that we're getting deep brain penetration and that's always a big question is you are trying to think about additional targets that you can pursue can you get into the deeper brain structures and that level of knockdown signifies that.
And then you have durability, where we're seeing knockdown free.
Preclinically, that's now translating clinically in comparable to what we saw in the liver and we think these drugs can be dose six months, a year or every six months or even less frequently and so.
That's exciting and then the third and most critically frankly is the fact that so far the solubilities safety.
Safety and Tolerability.
Is really encouraging as well and so this really opens up for us the opportunity to pursue multiple targets with our colleagues that regeneron.
Who've been we've been working on it in terms of this.
Groundbreaking science and so to your point H T T as.
Is another molecule that we recently announced his development, Canada, we're doing preclinical work now.
Enabling work to bring that into the clinic, we haven't formally announced the timeline for that but you can imagine that we're pursuing that rapidly our colleagues that regeneron or advancing.
Molecule against for AOS.
Against sod.
Also in preclinical development right now and we have additional targets behind that that we're going to bring bring forward.
I think we have time for one last question.
One moment for our last question.
Our last question comes from many.
You are.
Your neck.
Your line is now open.
Hi, Good morning. This is Lily <unk> I've got a question in terms of the commercial <unk> what will be your strategy to protect your assets from the upcoming at <unk> station and do you expect the need for potential Postapproval head to head studies.
Uhm talk I'm gonna hang that question straight over to you.
Yeah first of all thank you for that question I guess the question is specific okay. Four to five minutes for cardiomyopathy indications, which we have yet to receive and and obviously how is in a position to product is gonna be dependent on on the heliosphere results, but one thing to really remind ever.
Otherwise if you look at art Polyneuropathy experience, where the product is is a different value in Europe and in other markets Oh, sorry, it's been a game changer, and we've been able to accelerate growth in demand quite substantially in the markets that now on what's available versus differ.
That's N, where we've seen an accelerated switch, particularly in Japan, where they have the pull neuropathy vacation I'd like the U S.
Any you know company that wants to confuse drive patient value in patient growth, we will of course be looking into it.
Post Genericization and and we will subsequently close is there any alternative in terms of clinical trial and others in other options, but it's I would say, it's a little too soon for us too close to the vet and we will obviously keep you abreast of any important decisions that we would eventually.
And now showing no further questions at this time I would like to turn the conference back to an island for closing remarks.
Thank you and thanks, everybody for joining us on this call where Katie very happy with the continued execution that we've seen in 2023 across multiple elements of our business commercial R&D and business development and we look forward to sharing will progress in the coming months as we continue to deliver on <unk>.
Thank you everybody and have a great day.
This concludes today's conference call. Thank you for participating you may now did a tie.
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