Alnylam Pharmaceuticals, Inc.
Q3 2018 Earnings Call Transcript

Published: 8 Nov 2018

[Operator:]

Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals Conference Call Third Quarter Earnings. There will be a question-and-answer session to follow. Please be advised that this call is being taped at the company's request. I would now like to turn the call over to the company.

[Christine Regan Lindenboom:]

Good morning. I'm Christine Lindenboom, Vice President of Investor Relations and Corporate Communications at Alnylam. With me today on the phone are John Maraganore, Chief Executive Officer; Barry Greene, President; Akshay Vaishnaw, President of R&D; Manmeet Soni, Chief Financial Officer; and Yvonne Greenstreet, Chief Operating Officer. For those of you participating via conference call, the slides we have made available via webcast can also be accessed by going to the Investor page of our website, www.alnylam.com. During today's call, as outlined in slide 2, John will provide some introductory remarks and provide some general context; Akshay will review recent clinical updates; Barry will provide an update on our commercial progress, including the initial ONPATTRO launch performance; Manmeet will review our financials; and Yvonne will provide a brief summary of upcoming milestones before opening the call for your questions. I would like to remind you that this call contains remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purpose of the Safe Harbor provision under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those disclosed in our most recently quarterly report on file with the SEC. The press release and related financial tables, including a reconciliation of GAAP to non-GAAP measures that we will discuss today can also be found on the Investor page of our website. We believe non-GAAP measures provide useful information to management and investors regarding our financial condition and results of operations. In addition, 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. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to John.

[John M. Maraganore:]

Thanks, Christine, and thank you everyone for joining the call this morning. The third quarter of 2018 was, without a doubt, a major milestone quarter for Alnylam. In August, the U.S. FDA approved ONPATTRO, a first-in-class therapy for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. And in Europe, the EMA approved ONPATTRO for the treatment of hereditary ATTR amyloidosis in adult patients with stage one or stage two polyneuropathy. ONPATTRO was the first ever RNAi therapeutic to receive regulatory approval, representing the culmination of nearly two decades of work to transform Nobel prize-winning science into commercial reality; work that has been pioneered by the team here at Alnylam. I couldn't be more proud of the hundreds of Alnylam employees, both present and past, who made this happen. Barry will provide details on the initial launch in just a minute. But at a high level, we are pleased with the initial adoption (03

[Akshay K. Vaishnaw:]

Thanks, John, and good morning, everyone. It has indeed been a remarkable quarter marked with substantial progress across our late and early stage pipeline along with our pilot programs in addition to exciting progress on our platform efforts. Let me start with patisiran, now known by its commercial name ONPATTRO. In addition to the approval and subsequent launches of ONPATTRO in the U.S. and EU, we were very pleased in July that the results from the APOLLO Phase 3 study were published in the New England Journal of Medicine. We believe the publication of the APOLLO results in the journal underscores the clinical benefit and encouraging safety profile of ONPATTRO demonstrated in APOLLO, and reinforces the strong therapeutic potential of this medicine for people living with the polyneuropathy of hATTR amyloidosis. More recently, in September, we were pleased to see exploratory cardiac endpoint data from the APOLLO study published in the journal Circulation. We believe these data highlight the potential of patisiran to favorably impact certain cardiac manifestations of hATTR amyloidosis and we believe the results support further study of patisiran in hATTR amyloidosis patients with cardiomyopathy. I'll now move on to discuss ALN-TTRsc02, our follow-on program in development for ATTR amyloidosis which utilizes our ESC+ GalNAc conjugate technology, enabling infrequent low volume subcutaneous dose administration. We're pleased to announce HELIOS-A, a pivotal Phase 3 study for ALN-TTRsc02 in patients with hATTR amyloidosis has been aligned with the FDA and EMA feedback. HELIOS-A is designed as an open label study in approximately 160 patients with hATTR amyloidosis, with co-primary endpoint of mNIS+7 and the Norfolk Quality of Life scores at nine months comparing the effects of ALN-TTRsc02 to results from the placebo arm of the APOLLO Phase 3 study of patisiran. Secondary endpoints will support a comprehensive assessment of disease burden, importantly, given the findings from the exploratory post-hoc analyses conducted in APOLLO with respect to at least specifying (07

[Barry E. Greene:]

Thanks, Akshay. In addition to the tremendous R&D progress over the past quarter, we made exciting progress with the launch of ONPATTRO. During the seven weeks between the U.S. launch of ONPATTRO on August 13 and the end of the third quarter, we received, as John highlighted, 125 U.S. patient start forms. Start forms are requests that come to our Alnylam Assist patient hub to guide fulfillment of an ONPATTRO prescription by a physician. We believe these are a reliable measure of demand, although they do not capture all demand, which might otherwise be fulfilled outside our patient hub through direct orders to our distribution channel. In addition, while we expect the vast majority of start forms to result in patients receiving commercial drug, there will be start forms that are ultimately not fulfilled. Of the 125 start forms we received in the third quarter, around 60% came from patients previously participating in the patisiran EAP. Now importantly, we've seen a diverse range of prescribers and physician specialties, including neurologists, cardiologists and hematologists, reflecting what we believe to be both polyneuropathy and mixed polyneuropathy/cardiomyopathy patient phenotypes. While we will not be providing any specific guidance on market assumptions or sales projections, it is important to note that we're in the early stages of the launch. We believe the initial start forms likely represent a bolus of patients with a significant number of patients converting from EAP and also diagnosed patients known to APOLLO investigators. Therefore we don't necessarily expect this rate to be reflective of the future run rate. We'll need several quarters to process the initial bolus of patients before we can develop a true understanding of the run rate of ONPATTRO demand. As we previously discussed, at this early stage of our launch, it will take a few months to get patients started on commercial drug after receiving the start form. We do expect this timeline to decrease significantly as our launch progresses. We appreciate there are many questions from you about payer mix, prescriber base, patient genotype and phenotype. We expect to provide additional insights on these questions in upcoming quarters. In the meanwhile, we're very pleased with our launch, our ability to supply product immediately after approval, the receptivity to our field-based team and the initial feedback from health care providers and patients. Our global rollout is also well on its way. We recently launched ONPATTRO in Germany and we're pleased with our initial performance. With over 30 patients in Germany on our Expanded Access Program, and while Germany represents an underdeveloped market for hATTR, we believe there are potentially several hundred patients in this market alone. Our commercialization efforts for the rest of Europe are also progressing well and we look forward to updating you on our fourth quarter call. In late September, we filed a Japanese NDA for ONPATTRO with the PMDA. Based on an accelerated review timeline for an orphan drug, we expect to receive a regulatory decision in Japan in mid-2019. If positive, it would represent ONPATTRO's expansion into a very important market. We're in the process of building on infrastructure in Asia with the initial focus on Japan. This includes building capabilities for sequencing the potential commercial launches in Asia starting with ONPATTRO in Japan in 2019 and givosiran and then subsequent products thereafter if approved. Further, as announced in our press release this morning, we'll soon be expanding into Latin America. We hired Norton Oliveira as our head of Latin America who joins us from Gilead. Norton's initial focus is on building capabilities in Brazil, another important market for ONPATTRO. Now turning to our medical education and patient diagnosis efforts, we believe that there's about 3,000 diagnosed patients in the U.S. and about 2,000 in Europe with hATTR polyneuropathy, and believe from epidemiology, there's 20,000 to 30,000 hATTR amyloidosis patients worldwide with polyneuropathy as a part of their clinical presentation. Of course, it will take time to educate the health care community, since early and proper diagnosis is the biggest challenge in this rare disease. Our Medical Affairs colleagues have been engaging closely with the hATTR amyloidosis community the last several years to raise disease awareness and improve diagnosis. As we've highlighted previously, our Alnylam Act program is a third-party genetic screening initiative aimed at facilitating diagnosis of patients suspected of having hATTR amyloidosis. As of October 31, more than 8,700 samples have been submitted and 584 have tested positive for pathogenic TTR mutation. We're also aiming to improve education in health care providers and patients with targeted websites that provide information, education and additional resources for disease awareness, accurate diagnosis and patient care. Metrics across our HCP and patient website demonstrate a strong interest in educational resources related to ONPATTRO and hATTR amyloidosis. When we look at metrics like e-mail sign ups, time spent on these website pages, there's notable engagement from key constituencies, including patients, caregivers, medical professionals from a spectrum of practice specialties and others. In summary, Alnylam is now a commercial stage company and while early, we're encouraged by our performance in our first seven weeks. Longer term, we aim to bring you the same excellence and innovation as a commercial company as you've seen from Alnylam over the past 16 years as an R&D company. With that, I'll now turn it over to Manmeet to review our third quarter financial performance. Manmeet?

[Manmeet S. Soni:]

Thanks, Barry, and good morning, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the third quarter of 2018. I would like to take this opportunity to provide a brief overview of three key areas

[Yvonne L. Greenstreet:]

Thanks, Manmeet. Without a doubt, 2018 has been a landmark year for our organization, but we still have some exciting milestones to look forward to before we close the books on the year. Starting with givosiran, we intend to initiate a rolling submission of a new drug application by the end of this year, with full clinical sections to be submitted in mid-2019, assuming positive end patient (29

[Christine Regan Lindenboom:]

Thank you, Yvonne. Operator, we will now open the call for questions. To those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions.

[Operator:]

Thank you. Our first question comes from Althea (sic) [Alethia] Young with Cantor Fitzgerald.

[Unknown Speaker:]

This is Irene (31

[John M. Maraganore:]

Absolutely.

[Unknown Speaker:]

On ONPATTRO on the identified patients, what percentage of them do you think are in TTR centers currently and that you might be able to reach by their next doctor visit? And then can you maybe speak to how frequently that might be so when we might see some turnover there? Thanks.

[John M. Maraganore:]

Sure. Good question. Barry, do you want to handle that?

[Barry E. Greene:]

Yeah, it's a great question. As we've talked about, this is a rare and often not looked for disease. Even in centers of excellence, patients can be misdiagnosed. And so what we're talking about are the potential number of diagnosed patients. Keep in mind that many of these patients are on ongoing or upcoming clinical studies. So they're not all available for commercial patients. We see physicians asking their patients to come in every 6 to 12 months for a checkup. So it's hard to give any specific numbers. Our teams out there are educating and we are seeing an uptick of awareness. We are seeing an uptick in centers of excellence and the actual start of amyloidosis centers across the United States. So we're encouraged by the work thus far and the continued growth of available patients.

[Unknown Speaker:]

Thanks so much.

[Operator:]

Our next question comes from Alan Carr with Needham & Company.

[Alan Carr:]

Hi, thanks for taking my questions. Wonder if you could talk a bit more about, in the process getting these patients ready and generating revenue from them, a bit more detail about how long this might take and the steps involved in that. And also can you talk about Europe, too, how you expect that to play out in terms of rollout across countries and that sort of thing? Thanks.

[John M. Maraganore:]

Great. Barry?

[Barry E. Greene:]

Yeah. So, Alan, we've talked about this a little bit before. So the way to think about patient availability really is in three different buckets. The first, our patients on the Expanded Access Program. As I mentioned, the current – the initial start forms represent about 60% of those start forms represented EAP patients. We've previously mentioned that over 100 patients from EAP were in the United States. So we see those continuations to roll out over the next several months. That requires the starts forms to be filled out, insurance to be verified, infusion centers including homing (33

[Alan Carr:]

Do you have a sense of timing in terms of working through these individual countries, which ones might come next, that sort of thing and a sense of when?

[John M. Maraganore:]

We do but we're not going to share that. I mean it's obviously a competitive landscape out there, Alan. And we have a specific staging strategy that we have formulated and we're executing on. And we have extensive discussions with HTAs to facilitate reimbursement in specific countries. But we're just not going to share those details for obvious competitive reasons.

[Alan Carr:]

Understood. And I wondered if you can comment just quickly on ALN-AAT02, what sort of changes you made there, do you have some more confidence with this one compared to some of the safety issues that showed up with the previous one?

[John M. Maraganore:]

Yeah. Akshay, do you want to handle that?

[Akshay K. Vaishnaw:]

Yeah, hey, Alan. So ALN-AAT02 utilizes our ESC+ GalNAc technology. And essentially, this is some very nice sign from our research group to show how we can modify a single residue in the CEC, which is the critical part of the siRNA that allows for the cleavage of the target. And this modification, which we've published and shared extensively, allows for maintenance of the on-target effects, we expect very good and potent on kind of AAT, but diminishes the likelihood of any off-target effects which may be responsible for transient ALT changes of the type that we saw with previous molecule AAT01. We're very excited to take that into the clinic and test the hypothesis, but we'll see our modification increase the therapeutic index I've anticipated from the animal work.

[Alan Carr:]

Great. Thanks very much and congratulations on the launch.

[John M. Maraganore:]

Thanks, Alan.

[Operator:]

Our next question comes from Paul Mans (sic) [Matteis] with Stifel.

[Benjamin Burnett:]

Hi, this is Ben Burnett on for Paul Matteis. Thanks for taking our questions. Just one on ONPATTRO, understanding that it's early days, I guess do you have a sense of what your average price will be and how does this compare with what you were expecting from the value-based agreements and the $345,000 number that you cited back in August? Thank you.

[John M. Maraganore:]

Sure. Barry, you want to start?

[Barry E. Greene:]

Yes. As you said, it's very early on in the launch and we really will need several quarters to give you a true color on the dimensions that will matters, mainly payer mix, institutional ordering with prespecified government discounts. So it is very early. We think that the $345,000 number is the right number to use in your projections and as you analyze how many patients you think are commercial, that's the right number. In terms of impact of value-based agreements, we can say that very positively, we've had tremendous discussions with the payers and because of the proactive nature of our offering here, we've had enthusiastic reception to talk about medical benefits and patient finding and other dynamics. The potential discounts on the VBAs really won't kick in until four or five, sometimes six quarters in as patients become VBA patients. So that's going to be a next year thing.

[John M. Maraganore:]

I mean anything to add, Manmeet?

[Manmeet S. Soni:]

Yeah. We'll have to estimate some discounting on the VBA up front and we will do that, but we expect that $345,000 as still being the net effective price including the VBA discounting.

[Barry E. Greene:]

Yeah, and what I was talking about was actuals, not necessarily...

[Manmeet S. Soni:]

The GAAP accounting, yeah.

[Barry E. Greene:]

...about the GAAP, yeah.

[Manmeet S. Soni:]

Yeah. For GAAP accounting, we would be recording the discount as we do those sales and record revenue but $345,000 is a good estimate. As we mentioned in that launch call also that the 23% to 24% discount makes sense because of either 340B mix, right, which could be the primary and the other portion could be a VBA discounting if it comes in.

[John M. Maraganore:]

Does that help? Does that answer your question?

[Benjamin Burnett:]

Yeah. So if I could just clarify, so if these VBA agreements, as you get more quarters of experience and see like, for example, is there is a scenario where there is less discounting than you were expecting, would you restate past quarters? I guess how would you account that from an accounting perspective?

[Manmeet S. Soni:]

Sure. Obviously, we'll have to see the RBL experience, but all our VBAs will have our best price protection clause. So I think we'll have the higher number to be reserved at the beginning, but obviously, we'll release those results as we will have the actual experience. You're totally right.

[Benjamin Burnett:]

Okay. I understood. Thanks for the color.

[John M. Maraganore:]

Good. Thank you.

[Operator:]

Our next question comes from Anupam Rama with JPMorgan.

[Anupam Rama:]

Hey, guys. Thank you so much for taking the question. Can you remind us how many patients were enrolled into the EAP globally? I think you said there were 30 in Germany, but maybe you could give us some patient counts for some of the near-term launch countries like Canada and Brazil as well? Thanks so much.

[John M. Maraganore:]

Yeah. There were over 200 patients globally in the EAP, and so obviously the majority of them were in the U.S. Right? So those patients, 60% of the 125 start forms that we received come from EAP patients directly, okay. So the remaining 40%, you can do the math, have not yet converted as of September 30. Of course, there's been conversions since September 30. And then, of course, we have over 40 patients that we commented on in Germany in the EAP, and we do expect those patients to convert to commercial drug in due course. So that EAP obviously has been put in place to help patients with ONPATTRO, but it also does represent an early source of patients for commercial drug.

[Anupam Rama:]

Great. Thanks for taking my question.

[John M. Maraganore:]

Great. Thanks, Anupam.

[Operator:]

Our next question comes from Ted Tenthoff with Piper Jaffray.

[Ted A. Tenthoff:]

Good morning and thanks for all the detail on the call. I wanted to ask about givosiran and sort of the filing? So with the decision to wait for the full data and seek full approval, how does that filing process work from here? Thanks very much.

[John M. Maraganore:]

Yeah. Thanks, Ted. Let me start and then Akshay should comment as well. After obviously the positive interim analysis results, which we're very excited about, we certainly met with the FDA to discuss the approach for the NDA filing. And we got full support from the FDA to start a rolling submission with our data, which is terrific. But as we discussed the timing for the full results with the FDA, which are now scheduled to be in the March timeframe of next year, there was really no time advantage, substantial time advantage to file with the interim analysis data for an accelerated approval in light of the timing for when the full results would become available, in light of the fact that the FDA would likely need to do a PDUFA extension to accommodate the full data results that they would see after they were available in March. So for all those reasons, it makes more sense for us, and the FDA concurs, to file with a full approval path as opposed to the interim analysis path. Of course, we'd be doing the NDA submission starting with a rolling submission this year. So that'll help hasten the review of certain nonclinical sections of the givosiran NDA. Anything else to add, Akshay?

[Akshay K. Vaishnaw:]

Yeah. I think the rolling submission, of course, will also allow earlier submission of the CNP sections and the agency can go in the review of that. And then in March also, when we get the full data, we then look forward to filing the final clinical sections. And so we'll guide exactly on the anticipation around the completion of the NDA filings. But as many of you know, we completed the patisiran filing within 90 days. So we look forward to an aggressive approach here as well, and we think we can do that. And we'll get a very complete label with all the data, incorporated label which I think is great for physicians, patients and payer.

[John M. Maraganore:]

Yeah. And also one other added benefit, Ted, is it aligns our U.S. and European filing strategy. Before, we were going to be submitting on an interim in the U.S. and then waiting for the full data for Europe. Now we'll be using the same single data set essentially to file both in the U.S. and Europe and that is much more efficient. So at the end, we're obviously committed to bringing givosiran to patients as quickly as possible. But the compression of time between our faster-than-expected enrollment in ENVISION and the interim analysis conducted just made it a bit of a moot point to file to the interim.

[Ted A. Tenthoff:]

Make sense. Thanks, guys.

[John M. Maraganore:]

Good. Thanks, Ted.

[Operator:]

Next question is from Gena Wang with Barclays.

[Gena Wang:]

Thank you for taking my questions, mainly on ONPATTRO launch. Just wondering did you get any like different feedbacks from doctors in Europe versus the U.S., especially in the patients with mixed phenotype? And also any impact from tafamidis Expanded Access Program?

[John M. Maraganore:]

Yes. Barry, do you want to comment?

[Barry E. Greene:]

Yeah, Gena. So I think the feedback from health care professionals across the world has been fantastic. It's been a while but the APOLLO data really resonated with people, when you have progressive, debilitating, fatal disease and we see a halting of disease progression and a reversal in certain disease symptoms, so that's resonated from across the world. The one difference – and you highlighted this – between U.S. and other parts of the world is that physicians in other parts of the world have had experience with tafamidis and have witnessed their patients progress on tafamidis. So there's a lot more enthusiasm for potentially earlier intervention where tafamidis might have been used. We'll have to see how that develops over time, and after we see what happens with Pfizer and their launch and their market entry. Right now people are enthusiastic about ONPATTRO in the United States and in Germany and we'll see as we launch in each country what the uptake looks like.

[Gena Wang:]

Okay. Any impact from tafadimis (sic) [tafamidis] Expanded Access Program?

[John M. Maraganore:]

Yeah. Barry?

[Barry E. Greene:]

Yeah. Again, it's very early in the launch. But, Gena, we do expect that there will be some patients who might have been, with nothing else available, might have been an ONPATTRO patient, but with potential EAP available for tafamidis, their physician may choose the EAP for tafamidis. It's hard to know what that number looks like. Tafamidis in general, we do anticipate that being used for wild-type and for TTR cardiomyopathy patients. We believe that based upon data and physician enthusiasm that ONPATTRO's clearly the choice for polyneuropathy or the mixed phenotype.

[Gena Wang:]

Okay. Just one quick question regarding this quarter revenue. I think a rough calculation about like 10, 15 patients, maybe a revenue from 10, 15 patients. Just wondering if you can share your estimate processing time to receive insurance coverage?

[John M. Maraganore:]

Yeah, do you want to handle that, Barry?

[Barry E. Greene:]

So I can't really comment on numbers of patients. Keep in mind that we understand patient demand from start forms and from other orders that happen to our channel that come outside the start forms. When a start form comes in, insurance processing can move very quickly and site selection can move very quickly; others take a bit of time, as we understand patient insurance background and infusion site. As I mentioned, right now from start form to order fulfillment can be very quick or, in some cases, because of patient and location can take months. We do anticipate those timelines shortening as we refine the process. And clearly, once the patient is on drug, has a site and ordered, we are seeing reorders come in which is very gratifying to see.

[Gena Wang:]

Thank you very much.

[John M. Maraganore:]

All right. Thanks, Gena.

[Operator:]

Our next question is from Terence Flynn with Goldman Sachs.

[Terence Flynn:]

Hi. Thanks for taking the question. Was just wondering if you can give us any more color on U.S. reimbursement dynamics thus far with respect to what you're seeing on the coverage side at either the commercial or government level? And then any color you can provide on October start forms? Thanks.

[John M. Maraganore:]

Well, we can't help you with October start forms, Terence. That'll be the fourth quarter results which we may provide color at the beginning of the year in concert with one of the key investor conferences that happen at the beginning of the year. But the full results will be in February. Barry, do you want to handle the other question?

[Barry E. Greene:]

Yeah. So I can tell you that government reimbursement is going well and it's fast. And then on the commercial payer side and remember we've highlighted that with the VBAs signed or in discussion, we anticipate having about 70% of commercial patients covered under VBAs. We have been enthusiastically met with payer conversations. We have not seen headwinds on the payer side. And in fact, just a little color, we've actually been reviewing medical benefits with several payers so that they make sure that they're getting it right and can speed product to patients. I think they understand the debilitating and devastating nature of this disease and appreciate the potential that ONPATTRO brings to the patients that they're covering.

[Terence Flynn:]

Okay. Can you give us a sense of where you stand in terms of coverage of commercial lives right now versus where do you think you'll be like year-end or first quarter?

[John M. Maraganore:]

Yeah. That's a level of color that, given just this very, very early stage of the launch, Terence, we're going to wait a little bit further into our commercialization efforts before we provide that type of visibility. We obviously have internal numbers for the 125 patient start forms we've received, we know the mix but that's a level of granularity that we'll wait until probably a quarter or two before we provide that type of color.

[Terence Flynn:]

Okay. Thanks a lot.

[John M. Maraganore:]

Thank you.

[Operator:]

Next question from Vincent Chen with Bernstein.

[Unknown Speaker:]

Hi. This is Peter (50

[John M. Maraganore:]

Thank you.

[Unknown Speaker:]

Just one quick question. What are the gating factors to starting the ALN-TTRsc02 study in the cardiomyopathy patients? And when are we likely to learn more about the design, for example, whether it's head-to-head or whether it would have a comparator arm? Thank you.

[John M. Maraganore:]

Yes, thanks for that. It's a very important question. Obviously, we are very, very keen on getting ALN-TTRsc02 evaluated in the cardiomyopathy setting, both for wild-type and hereditary ATTR. We do currently believe that a study that compares ALN-TTRsc02 to tafamidis is the right type of study that makes the most sense for clinicians and patients. That is a study that requires the approval of tafamidis before we can provide tafamidis as a study drug comparator. So we await that approval. So we'll start next year, is really the timeframe and we'll just have to wait till tafamidis is approved. Anything to add there, Akshay?

[Akshay K. Vaishnaw:]

No, I think that's – you got it. Yeah.

[Unknown Speaker:]

Great. Thank you very much.

[John M. Maraganore:]

Good.

[Operator:]

Next question is from Madhu Kumar with B. Riley FBR.

[Madhu Kumar:]

Hello. Good morning, everyone. Thanks for taking my questions.

[John M. Maraganore:]

Sure.

[Madhu Kumar:]

So I'm going to ask a naive (52

[John M. Maraganore:]

Yeah, Barry, do you want to handle that?

[Barry E. Greene:]

Yeah. No. Yes, I can handle that. The start forms are pretty simple. It's patient name, insurance information, genotype and the fact that they have documented neuropathy. We do offer through Alnylam Assist access to patient education and genetic counseling. And we are working with the centers that are recommending genetic counseling. And we are seeing a more favorable uptake by patients in now receiving genetic counseling now that therapies are available.

[Madhu Kumar:]

And following from that, to what extent do – like do you sort of index patient and then genetic counseling, which has (53

[John M. Maraganore:]

Yeah. Barry?

[Barry E. Greene:]

Yeah. So for all players involved in hereditary genetic disease, as you called it, the index patient, genetic counseling is a critical part of what we will see. We believe that there will be siblings, there will be children of patients found. But again, majority of patients are out there and not diagnosed. So most of the launch and the run rate will come from newly diagnosed or newly found patients that have symptoms but were wandering in our health care system before appropriately diagnosed.

[Madhu Kumar:]

And to that point, is that the same both in the U.S. and Europe or is – because I mean like class people say (54

[Barry E. Greene:]

I think it's universal across geographies. Even in endemic areas where diagnosis rates are good relative to the rest of the world, the experts believe that they're still only catching about 50% of patients. And yeah, as you mentioned, Portugal is a unique situation. There's a number of diagnosed patients that just aren't on any therapy because of the country's affordability. So those are all dynamics that will play into the commercial side of our equation.

[Madhu Kumar:]

Okay. Thank you for taking my questions.

[John M. Maraganore:]

Thanks, Madhu.

[Operator:]

Our last question will come from Do Kim with BMO Capital Markets.

[Keith Tapper:]

Hi, there. This is Keith Tapper on for Do. Just wanted to know – well, first congratulations on the launch. I wanted to know the kind of patients that you're seeing that are the early adopters on ONPATTRO, like severity of disease, level of PN versus CM, the ones that are not coming from the EAP program. Thank you.

[John M. Maraganore:]

Yeah. Barry, do you want to handle that?

[Barry E. Greene:]

Yeah, I think it's too early to give any color on that other than, as I mentioned, we are seeing a variety of patients both polyneuropathy and mixed phenotype coming from a broad range of prescribers – neurologists, cardiologists, hematologists. So it gives us a sense as to the broad range out there that are finding these patients.

[Keith Tapper:]

Okay. That's helpful. Thank you.

[John M. Maraganore:]

Thank you.

[Operator:]

Thank you, everyone. This concludes today's question-and-answer session. I will now turn the call back over to today's speakers.

[John M. Maraganore:]

All right. Well, thanks, everyone, for joining us on the call. These are exciting days for Alnylam, for RNAi therapeutics and most importantly for patients. We are pleased with the R&D and commercial progress we're making, and we look forward to updating you on our continued progress in the coming weeks and months. Thank you very much.

[Operator:]

Thank you, everyone. This concludes today's teleconference. You may now disconnect.