Alnylam at BofA Healthcare Conference: Navigating New Launch Challenges

On Wednesday, 14 May 2025, Alnylam Pharmaceuticals (NASDAQ:ALNY) participated in the BofA Securities 2025 Healthcare Conference. The company shared insights into its strategic initiatives, highlighting both opportunities and challenges. A focal point was the launch of their new cardiomyopathy treatment amid evolving healthcare policies and market dynamics.

Key Takeaways

• Alnylam is concentrating on the launch of its cardiomyopathy treatment, focusing on market access and patient support.
• The company anticipates TTR (ATTR) revenue between $1.6 billion and $1.725 billion for the year, marking a 36% growth at the midpoint.
• Challenges include navigating the Most Favored Nation executive order and pharma-specific tariffs.
• Alnylam is expanding its network of infusion clinics to improve patient access.
• The company is strategically targeting first-line patients to enhance diagnosis rates.

Financial Results

• Revenue Guidance: Alnylam projects TTR revenue to reach between $1.6 billion and $1.725 billion, with the upper end indicating a $500 million growth.
• Centimeters Contribution: Approximately $200 million in revenue is expected from Centimeters.
• Pricing Strategy: A gradual reduction in net prices in the U.S. is anticipated, although no significant decrease is expected this year due to buy-and-bill dynamics.
• Gross-to-Net: The company forecasts a gross-to-net percentage in the mid-20s, aligning with existing products.

Operational Updates

• Cardiomyopathy Launch: Within five weeks, 50% of target health systems have added the treatment to their formularies. Revenue is expected to be more pronounced in the latter half of the year.
• Market Dynamics: There are 18,000 new patients initiating therapy annually, with a 20% diagnosis rate, presenting significant growth potential.
• Patient Access: 70% of PN patients incur no out-of-pocket costs, while Medicare Advantage patients face a median expense of $3,500.
• Manufacturing: Most manufacturing is outsourced to U.S.-based CMOs, offering a favorable tax position.

Future Outlook

• Provider Engagement: Alnylam continues to work with hospital networks to enhance formulary access.
• Market Expansion: Focus on first-line patients and expanding DTC marketing efforts.
• Revenue Reporting: Future reports will emphasize revenue growth, although separate reporting for PN and cardiomyopathy indications is not feasible.

Q&A Highlights

• Formulary Access: New P&T processes are required for the cardiomyopathy indication, with Alnylam actively engaging hospitals.
• Payer Dynamics: Approximately 80% of the market is Medicare, with commercial payers potentially implementing step edits.
• Patient Phenotype: Alnylam is uniquely positioned to treat patients with mixed phenotypes in the hereditary market.

Readers interested in more detailed insights can refer to the full transcript below.

Full transcript - BofA Securities 2025 Healthcare Conference:

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Good afternoon. Good morning still. I can’t tell what time it is. Welcome back to the Bank of America Healthcare Conference. I’m Tazeen Ahmad.

I’m one of the senior SMID biotech analysts here at the bank. It’s my pleasure to have our next presenting company with us, Alnylam Pharmaceuticals. Presenting for the company for the next thirty minutes up here with me is CFO Jeff Poulton. Jeff, thanks for flying out here to see us.

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Love it. This is one of my favorite spots for a conference. So happy to be here.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: And we got summer weather for you, too. So let’s maybe just start off with the macro questions that I think you’ve already had to answer a couple of times. Maybe The most recent would be the executive order that was announced earlier this week. Can you just talk in general about what you think the impact of the details which still are developing frankly of most favored nation means in general and in particular, any read through to Alnylam?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah. I mean, it’s a difficult question to answer because there were not a lot of specifics that were included in what was shared on Monday morning, but we were, like everybody else, we’re anxiously awaiting what we were going to hear. I think we understand what the administration is trying to accomplish, certainly, you know, if we need to, we’ll engage constructively in the process, but there’s not a lot of specifics, so it’s hard to frame, you know, what the potential implications or exposure for the company would be. I think one fact that at least is a positive for us, at least on the IRA side, whether or not it will be on the MFN side, depending on how this develops, is all the drugs that we have in the market today that are commercialized are orphan in The US, including the TTR business. And so on the IRA side, that means you’re excluded from future price negotiations.

And so whether or not that’s something that would also carry over on the MFN side is still up in the air. I think that’s a question that a lot of people have. But if it does, obviously we’re in good place there. I think as it relates to anything further, again, it’s difficult to know until we understand more of the details if it progresses in that direction. We’re just at the early stages, obviously, the cardiomyopathy side in terms of launch.

We’ve launched in The US, and I know we’ll have an opportunity to talk about progress there. We haven’t launched anywhere ex US yet, so we’re still in the process of some of the earlier markets of we’ll probably just be getting to discussions on price. And so, you know, how does that, you know, frame our thinking? I don’t know. We need to sort of pause and think about that a little bit.

And do we need to think about it differently? I don’t know yet, right? So we’ll be staying very close to this as will everybody else as it continues to evolve and we have a better understanding of where it may be going.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Okay, thanks for that. And then a similar question on tariffs.

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, this is one maybe that’s maybe a little easier to answer, at least on the specific tariffs that are in place today. We commented on our Q1 call a couple of weeks ago that based on, you know, what we see today, that there’s not a material impact of the existing tariffs that are in place, and we didn’t need to make any change to our guidance. We can absorb any increased cost within the guidance we had given back in February. The question, though, is about pharma specific tariffs, which everybody knows are still being considered and likely, it sounds like the administration’s going to do something there. A little harder to give you a specific answer there, but I do think a couple of factors for the company probably put us in a pretty good position.

One being that the vast majority of the product that we manufacture, which is all through CMOs today, we don’t have any in house commercial manufacturing. Majority of that is done in The US through our partners. And then secondly on a from a tax perspective you know where is our IP domiciled. The majority of our IP is domiciled in The US. And I think both of those factors probably position the company fairly well from a pharma specific tariff perspective.

But again, I think as we learn more details, can provide more color on that.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Do you have any transfer pricing that would be need to be?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, really what I’m signaling with the majority of the IP sitting in The US, that means any transfer pricing that’s coming into The US is likely coming in at a fairly low price, which if that’s what sort of gets tariffed, I think we’re in a pretty good position in terms of the impact of that.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Okay. All right. So now let’s talk about Alnylam.

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Let’s do it.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: So I think the focus of nearly every investor is on this launch in cardiomyopathy.

Jeff Poulton, CFO, Alnylam Pharmaceuticals: I’ve heard that. Yes.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: So, can you just talk to us about the very, very early metrics, that you’ve reported so far, and how should we be thinking about building off that?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, obviously, we certainly understand the interest here. It was a little bit challenging on our Q1 call. Product approval happened in the last week of the first quarter. So, there weren’t any results. There were no revenue results in the first quarter.

But when we reported our results, we were probably five weeks or so into the And obviously people were interested in what we could share in terms of color. I think probably the most substantial thing that we shared on the call was progress on the access front, which is really kind of that very near term focus. We’re a Part B buy and build drugs. There are a number of things that have to be sorted out from an access perspective to really enable demand uptake. There’s things we have to do on the payer side and there’s things that we have to do on the provider side.

I think the most encouraging thing that Tolga shared on the call was the progress that we’re making on the provider side. And the way this works in The U. S. Is the majority of the TTR business gets managed through about 170 health systems, which are like networks of hospitals. And what he shared on the call was that 50% of those health systems five weeks in, we had already been through the PNT process and were on formulary.

And what that allows those hospitals to do then is to start to engage in the buy and bill process. That happened faster than we anticipated. I think that first fifty percent we think that by the end of the year, you know, almost with certainty, we’ll have almost all of that done. But the fact that we got 50% of that done five weeks in is a good sign. We have been talking about this as a second half of the year story in terms of revenue, just because there’s a couple of steps involved here.

It doesn’t happen quite as quick as it does with a pharmacy benefit or a Part D drug. But based on that progress on the payer side, I would tell you that we’re probably pulling, starting to pull some revenue into Q2 as a result of that, which is obviously a sort of a good fact right now at this point. More to come. Maybe I should talk a little bit about how we’ve guided the market. Yeah.

We took a little bit different approach this year on our guidance, given the focus on this. And so we actually guided earlier than we typically would. We guided at JPMorgan. Typically, we do that on our year end call. So when we gave guidance, we didn’t have an approval yet, but we were very confident based on the study and where we were on the regulatory process that we were going to get to an approval.

And historically, we’ve given combined product sales guidance. We’ve got four products in the market. But this year, we broke out TTR and the rare products separately because of the intense focus on the TTR business. And what we guided to in terms of revenue for TTR this year was 1.6 to a billion $7.25. That’s a 36% growth at the midpoint up rents at 41%.

Last year the PN business grew 34%. And just on an absolute dollar basis PN grew 300,000,000 last year. If you look at the range of revenue that we’ve given the upper end of that range would be 500,000,000 in growth for TTR. So if you assume PN grows roughly at the same rate we’re sort of guiding to a couple hundred million in revenue on on Centimeters. So you know, hopefully on the Q2 call, you know, now that we’re going to start to have some actual demand metrics, including sort of pull through to revenue, we’ll start to be able to give some a little bit more clarity on how we feel about that guidance at the second quarter.

And I know people will be really interested in that.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Yeah. Okay. So you’ve said a lot. So let me just ask a couple of points of clarification. So if MVUCHA was already on hospital formulary for PN, did it have to go through again, PNT to get on

Jeff Poulton, CFO, Alnylam Pharmaceuticals: this Yeah, do have to get it because it’s a new indication.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Is that expedited?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Look, varies system by system. Some of it will do it immediately. Obviously, five weeks, we fifty percent of them that had done it. On the PN side, we were already on formulary for about 50% of these health systems. But just given the larger network for Centimeters we want to get to we want to get to all of them.

But it really just depends on the scheduling. I don’t think it’s actually a challenge to get on formulary. These are entities that understand buy and bill. They want to do the buy and billing. They want to participate in the process, but you still have to go through this as a step in the process to enable those systems to start to do the buy and the bill.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: So who initiates it? Is it a physician at the hospital?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: It’s the hospitals. We’re obviously, you can’t initiate the process until you have an approval on a label. So, you know, the day after we had the approval, we were reaching out to these hospitals to sort of get on that next meeting, the earliest meeting that we could to facilitate the process. So I think we’re very confident that by the end of the year, we’re going to have nearly all of these, you know, on formulary.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Okay. The other question that you’ve probably gotten maybe once or twice is, how to think about Part D versus Part B in relation to the patient?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, we’ve been, you know, this has been a source of intense sort of focus and scrutiny for people to try and understand it. This is a complicated issue, I’ll tell you. Let me talk about the sort of the, from a patient perspective, what this means and how we’re positioned, and then we can talk about more from a payer perspective and how they might manage things as a result of some of the changes that are going on. First from a out of pocket perspective, let’s talk about Part B and where we are, experience that we’ve had in PN, which we think will carry over to Centimeters as we expand into the Centimeters part of the market. We’ve had about seventy percent of the patients, on drug in The US for PN that have zero out of pocket.

And that’s largely those patients that have Medicare fee for service. Most of them have Medigap insurance, sort of supplemental insurance that covers any responsibility that patients would have to pay. And then on the commercial side, we have a copay assistance program, as do all manufacturers in this space. So any commercial, patients, we will cover that for them. The part of the business that’s not covered with sort of zero out of pocket is the Medicare Advantage part of the market.

And that’s about 30% of the business. And the median out of pocket there for those patients in PN has been about $3,500 That does not include any third party financial assistance that those patients may have access to. We don’t have visibility to that.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: You mean like foundations?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah. So it’s likely what they’re actually paying out of pocket is less than $3,500 but that’s what we have visibility to today. On the Part D side with the IRA changes that have gone into effect this year, the out of pocket cap’s now down at $2,000 So that’s sort of where we are, on patient out of pocket. The other change, though, that comes along with the out of pocket cap on the Part D side is the design of the plans and who pays for what is also evolving pretty significantly on the Part D side. And so drugs that reach that catastrophic phase of coverage, which I think is at like $7,500 don’t quote me on that, but it’s kind of at that level.

Anything above that, there’s been a pretty significant change. Previously, the plans that administer the Part D benefits were responsible for 15% of the cost when you get into the catastrophic drug coverage phase. Now they’re responsible for 60%. So that’s a pretty big shift. And what we understand that means based on market research is they’re gonna pay more attention to those types of cost and those types of therapies.

And I think for a category that has two Part D drugs today, and will likely have a third for cardiomyopathy, when Ionis and AZ run out their study, they’re gonna focus on managing those products, right? And we are one of one on the Part B side. Just generally speaking, being in a category with three where the payers are sort of keeping track of costs and being in the Part B, one of one is a good place to be. Cross managing B versus D is not an easy thing to do. Positioning there.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Are you seeing in the, again, very early part of this launch, playing out?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, look, it’s early days, but on the payer side, I should talk about what we’re doing. Like the focus there is on working with the payers to sort of get policies in place, right? That’s what happens in the first couple of quarters of launch. Patients can get access to the drug before those policies are in place through a medical exception process. And that’s what’s happening today.

But again, let’s talk about the different types of payers here. First of all, again, it’s about 80% Medicare, right, for us and PN. We expect the same in Centimeters. And that’s split equally between fee for service and Medicare Advantage. Fee for service is the easy one, right?

There’s no policies that are put in place to manage, you know, that book of business. So immediately, that’s sort of a payer channel that’s open for us. And there won’t be any sort of management in terms of step edits there. Don’t have the ability to do that. Medicare Advantage, we do not expect any step edits in 2025 will be covered there and patients will have access to the drug through the policies that are put in place.

On the commercial side, I think we’ve been pretty consistent in saying if there’s a risk early on, that’s where it could materialize in terms of step edits. I don’t have anything to sort of report there today, but that’s where it would be more likely. And that’s just because from a payer perspective on the commercial side, that’s where you see a little bit more of sometimes cross management between B and D. You know, the other thing that makes us feel comfortable about this, and frankly was part of the calculus for how we price the drug, is just given the nature of this disease, it’s a rare disease, right? Let’s not forget this, we have an orphan designation.

That just means the size of the market and how focused payers are on it, right? For rarer, they generally speaking spend less time do less management there. And it’s also a progressive fatal disease. So typically payers are not wanting to get involved and dictate opportunities for patients to get on drugs or not. So we feel generally good about that from a payer perspective.

We haven’t seen anything different so far than what we assumed, but again, we’re early days and this typically takes a couple of quarters to play out to get all of the policies in place on the payer side. And the importance of having those policies in place is it just facilitates the process of the patients getting on the drug easier. Physicians can get patients on drugs without that happening, but it takes extra work. They don’t like that, right? So we want to get these policies in place as soon as we can.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: So, how initially should we be? You’ve talked about this before as well, but gross to net in the early innings versus where you expect it to kind of land?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, I mean, I think based on what we know right now, I don’t expect anything too terribly different than what we have in place in PN and what we’ve said historically on gross to nets. And this is really more of a global number I’m giving you rather than a U. S. Specific. But on our overall book of business, we’re sort of in the mid-20s on gross to nets off of list price.

I would expect something generally similar as we as we move into Centimeters. What we’ve said about U. S. Pricing is that over time we would expect that we will see a gradual reduction in our net price in U. And that really would be something that would evolve over time as uptake increases.

We haven’t given any more specifics as to what that means. I would not expect it to be a huge decrease in net price this year. Again, because this is a buy and build drug. We have to carefully manage the dynamics there because it could impact the providers. If you’re moving really quickly you could put people underwater in terms of the sort of the business aspect of this.

So we have to be careful and thoughtful about that. But I do just think direction of travel over time is you’ll likely see a gradual reduction in that price in The US.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Okay, thanks. That’s good color. What is the profile of patients that doctors are writing scripts for so far? I think Tolga had

Jeff Poulton, CFO, Alnylam Pharmaceuticals: given some

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: color on that on the call. Mainly I’m interested, for example, in new patients versus Let’s say.

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Maybe before I talk about what we’ve seen so far, I just want to talk about the market, which is we’ve talked about this in the past in terms of the size of the segments and kind of where we’re focusing things, at least initially. First line versus second line, we think first line in terms of the number of new patients on an annual basis based on what we’ve seen in the market over the last couple of years, there’s probably somewhere close to 18,000. That’s a global number. New patients that are initiating therapy on an annual basis. It’ll be interesting to see how that evolves now with a second and a third player in the market, spending money to educate and drive awareness that likely will be something that will increase, but it’s been at about an 18,000 patient clip, and let’s say about half of that’s in The US.

We’re only at about a twenty, we think, at about a twenty percent diagnosis rate for this disease. So there’s a massive opportunity longer term to drive diagnosis rates, And that’s why we’re very focused on the first line opportunity because long term, you got to play in that part of the market and you got to win there, right? And so that’s one of the reasons why we’re very focused on first line. We’re also focused on first line because we think we’ve got data from the HELIOS B study that allows us to persuasively position the product as the best product in the market. Again, it’s a progressive fatal disease.

This is a disease where patients, for sure, and physicians as well, they want to reach for the best product as early as they can to help these patients. And so we’re very focused now in terms of driving demand to compete very effectively there. The second line opportunity, based on what we know, we think there’s probably somewhere around forty thousand patients that are on TAF being treated today. And based on, you know, a look at claims, probably half of those patients are progressing on the disease. So there’s a fairly significant second line opportunity today.

I do think we’re very well positioned for that. If you think about how cardiologists typically make decisions to move patients from one product to another, typically when they’re not working on a drug in a particular class, they’re gonna wanna move them to a different class of medicines. The first two products in the market are in the same class. So patients that we think are progressing on tafamidis, likely when that switch occurs, they’re going to want to move them to an orthogonal mechanism so that we’re really well positioned for that being the first silencer in the space. And so I think we’re going to get a lot of that business when that happens.

The question is how quickly does that evolve because there really hasn’t been a switch dynamic in market. And that likely will take some time in terms of formalizing the definition of progression. But I think we’re really well positioned to get that business when it happens. So yeah, again, more to come on that. I think what Tolga said based on the first five weeks is what we were excited about in terms of the demand signals that we’ve seen is that there’s a nice breadth across all this.

So we’ve seen first line initiation. We’ve seen second line initiation. We’ve seen physicians at these sort of large academic institutions writing the product. We’ve seen physicians in the community writing the product. We’ve seen hereditary patients.

We’ve seen wild type patients. That has been our expectation given the label and given the data that we have that we’re well positioned, frankly, for all comers. And I think early days, we were, I think we’re encouraged by what we see in those early signals.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Okay. So some of the doctor feedback we’ve gotten is clearly, the silencer mechanism has a lot of excitement around and the ability to offer patients another way to treat ATTR. Some have also said that from the vantage point of patients, it may take some time for some of them to opt to do an injectable as opposed to an oral. So how is Alnylam thinking about that dynamic of the market?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, again, I think, fortunately for us, we’ve got a once a quarter sub q now, which is a pretty convenient way for these patients to get treated. So hopefully that overcomes some of that resistance that you might see. Again, first gen product ONPATTRO was in every three week IV. I’m glad that we’re onto the second gen, and we’re also working on a third gen, which would be an even less frequently, injectable, you know, once every six months. So I don’t think that we see that as a barrier given the convenience factor.

And frankly, these are patients that go see their physicians on a quarterly basis. But a number of things that we’re doing on the buy and bill side to make sure that that’s not a barrier in terms of the convenience factor of kind of where they have to go to get it. You know, the way these patients are getting the drug today is it varies, frankly. There’s options that they have. A lot of them are going into these hospital systems, these networks of hospitals.

That’s probably, at least on the PN side, forty percent to fifty percent of the business gets treated there. We have about a quarter of the patients that get it in home. They can’t do it themselves because it’s a Part B drug, so they would have somebody come into the home and do it for them. And then we’ve got about another quarter of the patients that are going to third party infusion clinics. And that’s actually, I think, quite important, particularly when you think about the community physician, right?

And most physicians are not there’s a very small percentage of physicians that are doing the buy and bill themselves because a lot of them don’t want to do it. They’re not sort of set up to do it. They don’t want to take the financial risk. And so those third party infusion clinics allow physicians to continue to treat the patient but effectively outsource the injection to these third party infusion clinics. And the team significantly expanded the number of clinics that are in our network that can do that from 1,000 to about 2,000 in advance of the Centimeters launch.

The benefit of that is we think that we’ve probably got ninety percent of patients within 10 miles of one of those infusion clinics. So that’s an easy thing for physicians to do is just refer them to the clinic. And again, from a business perspective, these clinics are set up to do that. They understand the buy and build model. They want to do that business.

And so I don’t think it’s going to be a problem for us. I think the other thing that’s frankly a little bit underappreciated is compliance, right? So we’ve seen very good compliance on Invutra, and frankly, on ONPATTRO, which was pretty amazing given the burden of treatment on ONPATTRO. But we’ve seen our patients stay on therapy and be really good about once a quarter, the injection. So we know that they’re getting the benefit of the drug.

I think one of the challenges with oral drugs, and this is even for serious fatal diseases like this, is patients are not reliably taking the drugs, right? And so they’re not always getting the benefit of the drug as a result of that. And that’s probably part of the story of what you see with Tefamidis in terms of that progression, right? And the second product’s gonna be a twice a day oral. So you sort of question whether or not, you know, compliance may be even worse than on a once a day oral.

So I don’t know that everyone appreciates that maybe as much as they should, particularly in the real world. And so that’s something that we’ll need to do. I mean, one of the things that we’ve done, I think, on the payer side that’s been well received is we’re extending these VBAs, these value based agreements that we’ve put in place for all of our drugs. But the way those VBAs work in PN, we’re extending that to Centimeters, is it’s really about adherence and compliance to therapy. If the patient stays on therapy, there’s no payment that we make.

There’s no rebate payment that we give the payers. It’s if they get on therapy and they stop for whatever reason, that’s when a rebate kicks in. So the payers like that for a couple of reasons. One, it’s easy for them to measure, right? Because they’ve got to measure and watch this and sort of submit claims for rebates if the patients aren’t staying on drug.

That’s easy for them to track, so they like that. But also it allows them to know that they’re getting the benefit of what they’re paying for, right? Because the patients are staying on drug. And so we’ll continue to do that, and I think that will probably help us as well in terms of the advantage of patients getting the benefit of the drug.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Okay. How should we be thinking about DTC? Because even though this is rare disease, there’s the other companies have invested quite a bit.

Jeff Poulton, CFO, Alnylam Pharmaceuticals: Yeah, mean, think we are doing some DTC. We’re not probably doing DTC in a way that it’s showing up on Sunday morning network programming. Actually, ’re seeing some of that today, we are doing some DTC. We actually did some pilots in PN to start to get some experience with it. But I would say we’re doing it in a more targeted way today.

I think that’s something that we’ll continue to monitor and determine whether or not that’s worth expanding further and investing more in. But we are doing some DTC, just not probably in the same way that some of the competitors are doing it.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: So when you report, next quarter 2Q sales, what metrics should we

Jeff Poulton, CFO, Alnylam Pharmaceuticals: be looking out for on I’m glad you asked this because I know there’s a lot of interest in this. I mean, I think certainly one of the things that we’ll continue to talk about are progress in access because we know how important this is and people are interested in that. So we’ll continue to update you on the provider front, how far we’ve gotten with those sort of hospital networks. We’ll provide some details on physicians in terms of what we’re seeing in terms of expansion, probably, again, academic centers versus what we’re seeing in the community. And then on demand, I think these uptake trends like first line versus second line, what are we seeing?

Again, community versus academic centers, probably hereditary versus wild type, what are we seeing? But the most important thing that we’ll start to report is on revenues, right? That’s sort of the ultimate test of demand. And one of the things that I want to clarify, because I’ve seen a little bit of confusion in the market over this, is there’s a hope that we’ll report revenue as Ambutra PN and Ambutra Centimeters, and we don’t have the ability to do that. I mean, it’s the same product.

We got one label that has both PN and Centimeters in it. We have one SKU, SKU. We have one price for both products. So the way this works with our distributors who purchase the product from us, and then obviously move it to patients, we actually book the revenue when wholesalers order the product and we ship it to them. They’re ordering Ambutra, right?

They’re not ordering Ambutra Centimeters separate from Ambutra PN. So we don’t have the data to report this separately, and that’s not at all unusual. I think that’s actually the norm when you have multiple indications for the same product. I won’t be able to report it that way, but I do think we’ve got a pretty, well known understanding of how the PN business is growing today. And if you look back in The U.

S. At the last number of quarters, it’s pretty consistent in terms of the growth that we’re seeing there. I think when we start to report results with Centimeters, you’re gonna see a different growth rate and you’re gonna be able to isolate, okay, how much of that is PN and how much of that is Centimeters? And we’ll certainly do our part to make sure that’s as clear as possible. So I do think people are gonna get a good sense of what’s happening from Centimeters.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: I did wanna ask you, about mixed phenotype patients because that’s also kind of in the mix in the early portion of your uptake. How have doctors been, treating those patients, and do you expect that particular subset of patients to also have a continue to play maybe an important

Jeff Poulton, CFO, Alnylam Pharmaceuticals: mean, I certainly think that’s a category patient that we’ll do very well with. We don’t have super clarity on that, that I can give you specifics on it. But if you think about the label that we have, we’re the only product right now in the market that has for hereditary patients, both PN and Centimeters in the label. We’ve got the Ionis AZ product that’s got hereditary PN only, they don’t have Centimeters, and the silencers have hereditary Centimeters and wild type Centimeters. So we’re the only product for the hereditary variant patient that has both PN and Centimeters, and so, yeah, I would anticipate that we’re going to do really well in that part of the market.

I expect that we will. Mean, again, Tolga talked about the breadth of early demand signals that we’re seeing in Centimeters. Hereditary is part of that. We’re seeing a lot of hereditary demand, but it’s not only hereditary. We’re seeing a lot of wild type demand as well.

So I think we’re really uniquely and well positioned that we’ve got this broad label. It’s almost again all comers regardless of what kind of patient you’ve got. Hereditary PN, hereditary Centimeters, wild type Centimeters. It’s on label for us. That’s not the same with the competitors in the market right now.

So we do anticipate that we’re uniquely positioned to sort of take all comers.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: And then, last question. What do think is general awareness among physicians about the differences that you and I just talked about?

Jeff Poulton, CFO, Alnylam Pharmaceuticals: We’re early days. I mean, I think the fact that we’ve been in the market for PN and we’ve been, you know, promoting the product to cardiologists because they oftentimes are the ones that make the initial diagnosis in the hereditary part of the market, and then it gets referred to a neurologist for treatment. There’s a pretty good knowledge of Alnylam and our mechanism and our product. Obviously, there’s a lot more work to do because we’re expanding the number of prescribers that we’re calling on, but we’re starting from a pretty good place. But you can imagine that we’ve got a very motivated sales team to be out there talking to physicians and really educating them on the data that supported the expansion of the label.

So that’s what they’re doing right now.

Tazeen Ahmad, Senior SMID Biotech Analyst, Bank of America: Okay. With that, we’re out of time. So I’ll say thanks, Jeff, for sitting with for the last half hour. Everybody, for listening, and we’ll talk soon.

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