Q2 2020 Alnylam Pharmaceuticals Inc Earnings Call

Ladies and gentlemen, thank you for standing by welcome to be on Eilam Pharmaceuticals Conference call second quarter Twentytwenty.

Operator: Ladies and gentlemen, thank you for standing by. Welcome to the Alnylam Pharmaceuticals conference call, second quarter 2020. 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.

It would be a question and answer session to follow please be advised that this call is being takes up the company's request.

I would now like kind of Cowen <unk> company.

Go ahead.

Christine Regan Lindenboom: Please go ahead. Good morning, I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam. With me today on the phone are John Marganori, Chief Executive Officer, Barry Green, President, Akshay Vaishnaw, President of R&D, Jeff Poulton, Chief Financial Officer, and Yvonne Greenstreet, Chief Operating Officer. Andy Orr, Head of the U.S. Business, is also on the phone and available for Q&A. For those participating via conference call, the accompanying slides can be accessed by going to the events section of the investors page of our website, investors.alnylam.com slash events.

Good morning, I'm, feeling the bone senior Vice President of Investor Relations and corporate communications that align them.

Today on the phone or John Maraganore, <unk>, Chief Executive Officer, very Green President Occupational President of R&D Open Chief Financial Officer, the bonds Green Street, Chief operating officer, Andy or how do you want the adult all the phone and available for Q1 night.

For those people get beauty via conference call. The accompanying slides can be accessed by going to be event section the investor page of our website investors dot dot com.

During today's call is I would like to double somebody introductory remarks and general contact.

Christine Regan Lindenboom: The agenda for today's call is outlined in slide two, which will provide some introductory remarks and general context. Dario will provide an update on our commercial and medical affairs progress, Akshay will review recent clinical and preclinical updates, Jeff 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 will contain remarks concerning LLM'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. However, 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 quarterly report on file with the SEC. In addition, any forward-looking statements represent our view only up to the date of this recording, and they should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements.

Sure ill provide an update on our commercial and medical Affairs Barbara.

Okay. We'll review recent clinical and preclinical update Jeff will review our financial the bulk of about a brief summary upcoming milestones about opening the call for your question.

I would like to remind you that the goal of computer market burning alone future expectations plans and prospects.

Forward looking statements for the purpose of the Safe Harbor provision under the private Securities Litigation Reform Act like 90, but.

Actual results may differ materially from those indicated by these forward looking statements as a result at various important dr., including those discussed the number we've been quarterly reports on file with us.

And it isn't any forward looking statements.

Well I guess that either this recording it should not be relied upon the purpose and got views.

Okay.

We disclaim any obligation to update such statements.

I'd like to turn it over to John.

John Marganori: With that, I'd like to turn the call over to John. Thanks, Christine, and thank you, everyone, for joining the call today. Let me start by expressing Alnylam's support for Black Lives Matter and our support for the efforts to end systemic racism in our country. At Alnylam, we stand against all forms of discrimination, and at our core, we believe in justice, equity, and inclusion.

Thanks, Kristina. Thank you everyone for joining the call.

Let me start expressing my will support the black large matter.

Or support for the efforts and systemic racism in our country.

Well, we stand against all forms or discrimination.

Core we believe injustice equity and inclusion we staff to support a peaceful protest aimed at achieving real what's sustainable change enough is enough.

John Marganori: We stand in support of peaceful protests aimed at achieving real and sustainable change. Enough is enough, and it's time to finally cure the refractory scourge of hate. I'd also like to comment briefly on the Trump administration's recent announcement on drug prices. While we fully support the need to reduce or even eliminate patient out-of-pocket costs for prescription drugs, the administration's proposal to potentially introduce a so-called most favored nation executive order is both unfortunate and misguided. Importing foreign price controls will harm American innovation and hurt our patients. Even if this executive order is finalized, we don't believe it will stand.

Just wanted to finally cure the refractory scorched Earth age.

I also want to comment briefly on the call administrations recent announcements on drug prices well, we fully support the need to reduce or even eliminate patient blocker costs for prescription drugs. The administration's proposal to potentially introduced a so called most favorite nation executive order is both unfortunate I missed.

Got it importing foreign price controls will harm American innovation at heart and hardcore patients. Even if this executive order is finalized we don't believe it will step.

Let's now turn to our business as all of you know that cold and I can't pandemic remains dynamic circle and predictable that said, we continue to view the situation in the same framework, we discussed last quarter.

John Marganori: With that, let's now turn to our business. As all of you know, the COVID-19 pandemic remains dynamic, uncertain, and unpredictable. That said, we continue to view the situation in the same framework we discussed last quarter, a pandemic phase in Q2, a recovery phase in Q3, and a new normal starting in Q4. While the pandemic continues or even worsens in many states in the U.S., we believe Alnylam's business is benefiting from our broad global presence. In spite of the ebbs and flows, we are seeing healthcare systems now remaining open, and we don't currently expect a repeat shutdown of healthcare systems like what we're seeing in Q2, especially in the April-May timeframe. Our confidence in the second half is reflected in an upward revision in our patchwork revenue guidance range.

Phased in Q2.

These days in Q3 added new normal starting in Q4 wall pandemic continues or even worse since in many states in the U.S., We believe though miles business is benefiting from our broad global presence. It's part of the to have some flows we are seeing health care systems now remaining open and we don't currently exists.

Not to repeat shutdown of health care systems.

The same in Q2, especially on the April may timeframe.

Our confidence in the second half is reflected in upward revision.

Contra revenue guidance range.

Overall, we're really polymer field teams around the world and their ability to adapt quickly and safely to meet the needs of patients embodying our challenge accepted mentality.

John Marganori: Overall, we're really proud of our field teams around the world and their ability to adapt quickly and safely to meet the needs of patients, embodying our challenge-accepted mentality. We are extremely pleased with Global Ampato and Gidlari top-line performance in Q2, which Barry will elaborate on shortly. We're also proud of the significant progress we made across our pipeline in the quarter, as Akshay will discuss. Another highlight for the quarter was our landmark strategic financing collaboration and increase around royalty monetization we completed with Blackstone Life Sciences worth up to $2 billion. We believe this collaboration secures our bridge toward a self-sustainable financial profile without the need for any future equity financing.

We're extremely pleased with global accounts <unk> and good Lori topline performance in Q2, which Barry will elaborate on shortly we're also crowd other significant progress we made across our pipeline in the quarter.

Akshay will discuss another highlight for the quarter was our landmark strategic financing collaboration and cleese around royalty monetization, we completed with Blackstone life Sciences worth up to $2 billion.

We believe this collaboration secures our bridge toward a self sustainable financial profile without the need for any future equity financings.

So before sure My report close before share my closing remarks, I want to admit I want to take a moment to acknowledge the news we announced earlier this morning about very Greens plant departure from them, while at the end of the core.

John Marganori: Before I share my closing remarks, I want to take a moment to acknowledge the news we announced earlier this morning about Barry Green's planned departure from Almylam at the end of the quarter. Barry and I have been working side-by-side for over 20 years, first at Millennium and then for 17 years at Alnylam. And I know that I speak for everyone at Alnylam in thanking Barry for his exceptional contribution and dedication to the company. We all owe him tremendous gratitude for his outstanding leadership and track record, which have contributed to the delivery of RNAi therapeutics as a whole new class of medicines for patients. I have no doubt Barry will continue to be a highly impactful leader in the life sciences.

Very nice had been working side by side from over 20 years first of millennial.

And then for 17 years at all Marlin.

And I speak for everyone that allow them and thinking Barry for his exceptional contributions and dedication to the company. We all have tremendous gratitude for his outstanding leadership and track record that have contributed to the delivery of already I'd characterize it as a whole new class a medicines for patients I have no doubt very well continue to be.

Highly impactful leader you know life Sciences I'm grateful for his agreement to consult with L. marlim as needed for a two year period and I wish him all device that is next endeavor.

John Marganori: I'm grateful for his agreement to consult with Alnylam as needed for a two-year period, and I wish him all the very best in his next endeavor. We are also very pleased to share that Yvonne Greenstreet, our current Chief Operating Officer, will step into the expanded role of President and Chief Operating Officer on October 1st. We believe Yvonne is uniquely suited for this opportunity, given her strong command of our business, strategic leadership, and proven ability to drive results. We are initiating a search for a chief commercial officer, and during the search, we anticipate no disruption to our ongoing commercial execution.

We're also very pleased to share that they bodily injuries. Most current chief operating officer will step into the extend his role as president and Chief Operating Officer October 1st we believe a bond is uniquely suited for this opportunity given her strong demand of our business strategic leadership and proven ability to draw.

Hi results.

We are initiating a search for chief commercial officer and during the search we anticipate Noah.

Or ongoing commercial execution.

Please join me and wish him very well, let's see pursues the next chapter of a remarkable career and congratulating the bar or expanded role.

John Marganori: Please join me in wishing Barry well as he pursues the next chapter of his remarkable career and congratulating Yvonne on her expanded role at Albiol. I'd like to finish with my perspective on the big picture for the company. We continue to lead the advancement of RNAi therapeutics as a whole new class of medicines, and we remain on track to achieve and exceed our Alnylam 2020 goals, exiting 2020 as a multi-product global commercial company with a deep clinical pipeline for future growth and a robust and organic product engine for sustainable innovation. Without a doubt, we're excited for the promising future that Alnylam is poised to deliver as a top With that, I will now turn the call over to Barry for one last time, Barry, to review our commercial progress and medical affairs activities in more detail. Barry, take it away.

Oh.

I want to finished with my perspective on the Big picture for the company. We continue to lead the advancement of already I therapeutics as a whole new class a medicines and we remain on track to achieve and exceed oral my little 2020 goals exiting 2020, as a multiproduct global commercial company with a deep clinical part.

<unk> for future growth and a robust and organic product engine for sustainable innovation without a doubt we're excited for the promising future that'll mile of is poised to deliver as a top tier biopharmaceutical company focused on advancing medicines would transformative potential to patients around the world with that I'll now turn to call.

Forward for Barry for one last fund married to review our cost Talkers Medical affairs activities in more detail very taken away.

Thanks, John Good morning, everyone before I provide the quarterly highlights I'd like to make some brief remarks about my plan transition from alone first congratulations again football Threed shoot is remarkable person then well deserved the president and COO I know there Ron will make sure that Elba Island continues to be.

Eric Green: Thanks, Johnny. Good morning, everyone. Before I provide the quarterly highlights, I'd like to make some brief remarks about my planned transition from Long Island. First, congratulations again to Yvonne Greenstreet. She is a remarkable person and well deserves the President's CEO role.

Eric Green: I know that Yvonne will make sure that Alnylam continues to be a company doing the right things and focusing on patients, and I'm counting on it. As for me, it's been a tremendous privilege to serve as President of Alnylam for such a long period of time. I'm very proud of what we've been able to accomplish during my 17 years, and we built a global, fully integrated, multi-product company that is recognized for excellence in R&D and, recently, for commercial strength as well. My decision to transition is based on the desire to assume new leadership opportunities in the next chapter of my career. I'm fully confident Alnylam will achieve its ambitious goals with quality and excellence with the great team we have in place.

He's doing the right thing just focusing on patients when coming on it. It's for me it's been a tremendous privilege to serve as president of all my own for such a long period of time.

I'm very proud of what we've been able to posture and make 17 years, we'll see mobile phones integrated Multiproduct company, there's recognize for excellence in R&D and recently or commercial strength as well my decision to transition date, I'm, sorry, Pcvs understood.

The next chapter in my career.

Fully confident.

Cheap seats ambition schools quality nexsan, great teams have in place.

TV support Elba island throughout this transition and had no doubts about the company's future prospects at the top few platforms.

Eric Green: I'll continue to support Alnylam throughout this transition and have no doubts about the company's future prospects as a top-tier biopharmaceutical company. [inaudible] For Onpatro, we achieved $56.5 million in global net product revenues. As of June 30th, over 1,050 patients were on commercial Onpatro treatment worldwide, representing an increase of over 100 patients from the end of Q1, a very impressive accomplishment in the height of the global pandemic during Q2. Let's start with some more color on the U.S. As anticipated, the COVID-19 pandemic had an impact on our business in the second quarter. With patient demand decreasing, we can reduce adherence if some patients skip doses or confirm dose delays while moving to new parasites. Also, as anticipated, the pace of new patient initiation therapy flow in the U.S. spring quarter will reduce genetic testing, diagnosis, and patient flow through the healthcare system. Finally, our U.S. business was also impacted by inventory de-stocking and an increase in costs in the past three quarters.

This summer.

Yes.

Well I'm not sure you cheap 65 million global net product revenues as the June Thirtyth.

The 1050 patients when commercial and Patrick prudent worldwide, representing increases of over 100 patients into Q1.

Very impressive accomplishment.

And then during Q2.

Let's start with some more color on the U.S. as anticipated because when they see pandemic has impact our business.

The second quarter.

Patient demand decreasing due to do sit here and it's some patients get bases from certain situated well movie to parasites.

Oh.

So the pace at Newpage she therapy slow.

In order.

Do you see nice testing diagnosis and patient flow health care systems.

Finally, our U.S. business was also impacted but even trade you stop.

Recent.

Every quarter.

Jeff will provide more color and each of <unk> call.

Eric Green: Jeff will provide more color and details later in the call. But, as we enter Q3, we're now seeing what looks like a healthy return of genetic testing and patient flow into the U.S. healthcare system, even in states where COVID-19 cases are rising. In fact, our July numbers are nearly due to the January numbers we saw earlier this year, a really good sign.

Our focus today, it's on Q2 as into Q3 and now see see except the healthy return of genetic testing patient flow that's up your system, even in states where <unk>.

Oh.

In fact, our July Oh, no less than others.

Do you generally number if you start really you're really good sun.

Second quarter.

Eric Green: In the second quarter, great progress, and good credit. In the second quarter, 40% of submitted teleforms came from new writers, a unique mix of neurologists and cardiologists. Unknown Speaker.

Great progress.

The second quarter, 40%.

Can you can be writers you can mix it neurologists and cardiologists.

So I think.

Let me use one patchy teacher Seaboard, you see the quarter. We believe this trend will continue to grow its physicians, who progression propelling dropped the I'm stabilizers and treat.

Eric Green: We believe the trend will continue to grow as physicians see progression of polyneuropathy on stabilizers and treat the different manifestations of HATTR. So compared to the rest of the world, we've made very positive progress with our patchwork in the second quarter. The test of world sales for our patchwork is $34.2 million, and relative steam has benefited from continued geographic expansions, with launches in Spain, Italy, and other countries. In addition, we saw relative strength in the ex-U.S. partners, including Europe and Japan, working with their management of the pandemic.

And then for stations H.T. on those.

Turning to the rest of world. The very positive progress was I captured in second quarter.

The world sales from past.

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Extensions Lucky in Spain, Italy, and other countries.

In addition, we sell both substrates and actually yes.

Eric Green: As John noted, this is a nice validation of the decision to build a global, fully integrated business. With today's announcement of achieving a pricing and reimbursement agreement in France, we're pleased to report that access has been secured in all private markets in Western Europe. Notably, our team has secured pricing and reimbursement approval in all major European markets in under two years, post approval by the EMA. This is a much faster rate than most orphan medicines are able to achieve. The panel is, again, a country of strength from Patrick. Japan has now become our second largest country after the U.S. for our compatriots, and we expect continued growth in patient health. Unstable logic is there.

The address is jurgen, all priority markets and mustard Europe.

Notably T. The secret price you can remember the food all major European markets and under two years post approval by the GMA. This is a much faster rate than most orphan medicines are able to achieve.

Japan was again, a country strength from Patrick Japan has now become our second largest country after the U S.

Pets correctly, let me check continued growth.

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Funny.

Stabilizer therapy.

And the medical care side, a team remains committed to addressing the challenge of reasons disease awareness improving diagnosis.

H into your amitosis, including with a normal amount a third party genetic screen English to the U S. Canada in Brazil as of July over 27000 samples that would be submitted to whichever 1600 per person positive for pathogen mutation with the tracking at her store, 6% to 8% Pleasant City Ray <unk>.

Number show the testing the slow down and Q2 mentioned on Ah.

Eric Green: On the medical care side, our team remains committed to addressing the challenge of raising disease awareness and improving diagnosis of HNTG-RMO doses, including with Alnylam Act, a third-party genetic screening initiative in the U.S., Canada, and Brazil. As of July, over 27,000 samples have been submitted, out of which over 1,600 have tested positive for a pathogenic feature mutation, which is tracking at a historic 68% positiv These numbers show the testing slowdown in Q2 dimensions on our last earnings call.

Last name please call the good news and that sort of a party work those numbers are picked up the near January <unk>.

Alrighty.

We were really pleased with the progress in our lunch most of which isn't done virtually.

$11 and global net product grilled onions, we received or 85 start for them to me, but over 100 patients globally commercial treatment from lunch June 30th.

As we have now begun to open extra most territories and also because currently 25% to 30% of yours patients come from outside to start from channel will discontinued providing start for metrics and future quarters. As we did last you for I'm Patrick.

Eric Green: The good news is that they're already marked, and those numbers have picked up in January. Moving on to Glory, we are really pleased with the progress in our launch, most of which has been virtual. Reaching 11 million in global net product revenues, we received over 85 initial forms in the U.S., with over 100 patients globally on commercial treatment from launch through June 30th. As we have now begun to open territories outside the U.S., and also because currently 25-30% of U.S. patients come from outside the Stark Film Channel, we'll discontinue providing Stark Film Metro in future quarters, as we did last year for Unpatched. In the U.S., we observe a broad prescriber mix, including hematologists, gastroenterologists, and other specialties, both in preferred centers of excellence and in the community. Of note, 76% of our Q2 starts were from new writers. Our progress with value-based agreements has been extremely strong, with seven VBAs completing with U.S. payers, and we now have confirmed access for over 75% of our VBAs, with coverage and slides across the official Medicaid and other government payers. We've not experienced any care handling so far.

And the U S E. A broad prescribed mixed included do the colleges Guestroom floods. Some other specialties, both and Prefigure Center does excellent and in the community.

Nope, 76% of are cute to start we're from new writers.

Progress with valued disagreements has been extremely strong 70, vba's completing W. S players.

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Just me or even saw strong pischel performance as well with a successful and is noted virtual launch in Germany as well as named patient sales in other countries, including French cohort 18 program.

We've been positively encouraged by their spots interested European pairs. Despite the Kobe 19 pandemic of no goodbye received.

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Eric Green: Please concede plans to adopt medical policies not more restrictive than our latest indication. Tommie Reerink saw strong initial performance as well, with a successful and, as noted, virtual launch in Germany, as well as main patient sales in other countries, including the French cohort ATU program. We're positively encouraged by the responsiveness of European payers despite the COVID-19 pandemic. Of note, Gavrari received an Improvement of Medical Benefit, or ASMR, score of 2 in France, concluding that Gavrari offers significant additional therapeutic value. This is an enormous accomplishment since, in context, only two new commercial medicines were granted an ASMR rating of 2.8.

H.

As of mid July she'll and continued 10% positivity right.

A notable diagnosis trend emerging as the robust use a urinary PPG test inform diagnosis and you expect patient identification efforts with me for the past I. This non genetic testing of it.

Of course, we're now also prepared so much of a mess around later this year.

Shortly will deleveraging or existing commercial infrastructure for this launch the small editions of resources fulfill this teams.

Getting approval.

Civic organizations.

Medicine or therapeutic from except the market.

Hey confusion.

Second quarter with challenging to be <unk>, United States, We said much better than the downside case, we anticipated and entered Q too.

The credit and that goes where teams around the world basically obstacles to.

Deliberate isn't medicines to our patients to me.

I'll turn the call over the Akshay recent Orange D. A python progress akshay.

Eric Green: Our medical affairs team is also focused on improving awareness and diagnosis of AHP. Through our model maps, we can report 937 tests submitted in 92 patients with positive AHP as of mid-July, showing a continued 10% positivity rate. A notable trend emerging is the robust use of urinary PPG tests to inform diagnosis, and we expect patient identification efforts will need to be enhanced by this non-genetic testing method.

Oh sure you're on mute.

Alright, Yeah [laughter] good morning, everyone and thank you buried.

I should say, thank you berries with guiding me, so I'm, hoping build our company most of all working tirelessly to.

Oh, the patient's music to set up.

But with that I'll start with a S. A N a T T or I'm going downstairs, where where advancing out to product candidates concern and boutrous right.

Awesome pattern is currently approved and multiple markets around the world to treat polyneuropathy associated with HFC tabloid doses.

With tomato to expanding the products label to include the treatment cardiomyopathy, and both hereditary N wildfire 18th hamburgers as patients.

Eric Green: Of course, we're now also preparing for the official launch of Mass Ground later this year. Importantly, we'll be leveraging our existing commercial infrastructure for this launch with small additions of resources for field-based. When we gain approval, we'll be more specific on commercialization. [inaudible] In conclusion, the second quarter was challenging due to the pandemic, particularly in the United States, but we did much better than the downside case we anticipated as we entered Q2.

This and we continue to enroll patients in a polar b and continued to expecting completion of enrollment in 2021.

We've seen enrolling pick up over the last month, because clinical sides thought to open up around the world.

In addition, we're also advancing Beatrice ran an investigation Lauren L. A therapeutic delivered biquarterly subcutaneous injection, but sauce and development of treatment of 18 paranoid doses.

Yeah, we're conducting two phase three studies. The first is hearsay, which is evaluating Beatrice round in H, a T condyloid dialysis patients with Polyneuropathy.

Akshay K. Vaishnaw: The credit here goes to our teams around the world who faced the obstacles head-on to deliver these important medicines to our patients. With that, I'll now turn the call over to Akshay to review our recent R&D and pipeline progress. Akshay? I'm sure you're on mute.

Enrollment is complete and Helio say and we remain on track to report topline yourselves early next year.

The second phase three study of Boutrous run is Helios, Thingy, which is being conducted in inherited and what type of eight 818, 80 terribly versus patients with cardiomyopathy.

With the polar be fine activation enrollment in Helios B, a now picking up.

Akshay K. Vaishnaw: All right. Yeah. Good morning, everyone.

<unk> P as positive.

It allows of your true friends entry into the very large ball type 18th amyloidosis market opportunity with the product labeled that includes cardiovascular outcomes.

Akshay K. Vaishnaw: And thank you, Barry. I should say thank you, Barry, for guiding me, for helping build our company, and, most of all, for working so tirelessly to help all the patients we seek to serve. So with that, I'll start with our effort in ATTR amyloidosis, where we're advancing our two product candidates, Papisaran and Butrystrin. While Tompato is currently approved in multiple markets around the world to treat polyneuropathy associated with HIV-Tamboidosis, we're committed to expanding the product's label to include the treatment of cardiomyopathy in both hereditary and wild-type AT-Type myodosis patients.

Let's move to give Laurie which is approved in the U S U and married Brazil to treat acuity practical Syria in adults.

Of course the highlight.

Of course the highlights.

They'll give lori in the recent Karen with a Brazilian approval and we're continuing angiographic expansion for this product with MAA submitted in Switzerland, and Israel implants, the submission in Japan and becoming months.

During the second quarter, we also present, a new 12 months and trimmed data from the invasion facing study demonstrating sustained efficacy unacceptable safety Tacoma treatment with evidence for potential proved efficacy over time.

Akshay K. Vaishnaw: To this end, we continue to enroll patients in Apollo B and continue to expect completion of enrollment in 2021. We've seen enrollment pick up over the last month as clinical sites start to open up around the world. In addition, we're also advancing Dutriceram, an investigational RNAi therapeutic delivered by a quarterly subcutaneous injection that's also in development for the treatment of ATGY amyloidosis, and here we're conducting two phase three studies. The first is Helios A, which is evaluating utriceran in HAT family doses patients with polyneuropathy. Enrollment is complete in GISA, and we remain on track to report top-line results early next year. The second phase 3 study of Rutger Strang's Helios B is being conducted in inherited and wild-type AT-caromyidosis patients with cardiomyopathy.

Addition, we're proud to publish triple results from the envision phase three studying and the New England Journal Medicine.

It's nine paper on R&R Therapeutics published in the journal.

I'll know tend to recent paragraphs with Lemass run an investigation already I therapeutic, but we're developing for the treatment primary high school Hydroxyurea type one Oh P. H one.

That'd be E. R. E E T. H E. N June reported the full set a positive results from a give me a which demonstrated that lemass friends significantly reduce your new York's light levels the cause of progressive kidney failure N P. H one.

The dishes in the Master and showed me encouraging safety profile.

Overall the mouse around program also includes our illuminate been studying pediatric patients under six years of age.

It is complete and remain on tract report topline resolved soon and May 2020.

Akshay K. Vaishnaw: As with Apollo B, fight activation and enrollment in Helios B are now picking up. If Helios B is positive, it could allow for Vutrisran's entry into the very large wild type A-T type amyloidosis market opportunity with the product label that includes cardiovascular out. Let's move to Givlari, which is approved in the US, EU, and now in Brazil to treat acute hematopoietic ulcerative colitis in adults. Of course, the highlight... Of course, the highlight.

Eliminate C study severe P. H, one continuous enroll and it's been sitting well even during the pandemic.

We completed NBA and MAA submissions and the second quarter.

Yeah, Yeah granted Pronto review for the MBA and a set an action date of December 320 20.

[noise] has gone to the accelerated assessment of DMA.

You know we have two additional late stage programs that are in development with partners.

This includes in close around in the development and development Ah transfer Alenia pump with Novartis, which is currently under review for approving the U S. M U.

Akshay K. Vaishnaw: For Giblari, in the recent period, we received our Brazilian approval, and we're continuing our geographic expansion for this product with MA submitted in Switzerland and Israel and plans to submit in Japan in the coming months. In the second quarter, we also present new 12-month interim data from the ENVISION phase 3 study demonstrating sustained efficacy and acceptable safety through 12 months of treatment, with evidence for potentially improved efficacy over time. In addition, we're proud to have published critical results from the Envisioned Phase 3 study in the New England Journal of Medicine. This is our ninth paper on RNAi therapeutics published in the journal.

N D. A N N a fun and it's been accepted Novartis expects initial approval in the U S in late twenties.

Novartis as indicated that they remain on track for approval. This year with a December action date in the U S.

Ah late stage pipeline also include for Tucson, and development for him for you a O b with or without inhibitors poverty fantasy.

And if he has recently disclose the two of the three outlets phase three studies have completed enrollment and that they remain on track to report topline atmosphere three days in the first half of 2021.

Fantasy also presented new positive results from an infidel analysis of the face early studies for Tucson, Shang impressive reductions an annualized meeting right with encouraging safety.

Now in addition to our late stage clinical programs. We believe we have also been making great progress without early and misplaced programs.

Akshay K. Vaishnaw: I'll now turn to recent progress with Lumasaran, an investigational RNAi therapeutic that we're developing for the treatment of primary hydroxyurea type 1 or PH1. At the ERA EDTA meeting in June, we reported the full set of positive results from Illuminae A, which demonstrated that Lumastran significantly reduced urinary oxalate levels, the cause of progressive kidney failure, in pH 1. In addition, Lumastran showed an encouraging safety profile. Overall, the MassRAM program also includes our Illuminate Bee study in pediatric patients under six years of age.

Highlights of the quarter was the pasta topline results from a L. M. A G T Crazy one study and patients with hypertension, specifically, Alan AGP demonstrates and over 90%, Montana, Vanja 10, Synergen integrated them 10 millimeters Mercury lowering systolic blood pressure with a deal with a durability, that's caused a coffee or even less frequent.

Cutaneous dosing rational.

We're also encouraged by the Tolerability profile for L. M. A G T.

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Complete data from your own Dang Fazon study at a scientific meeting in the second half assuming I check acceptance.

Akshay K. Vaishnaw: Enrollment is complete, and we remain on track to report top-line results soon in mid-2020. Illuminate C Study, Severe PH1 Continuous Enrollment, and has been proceeding well even during the pandemic. We completed our NDA and MA submissions in the second quarter. The FDA granted priority review for the NDA and has set an action date of December 3, 2020. EMAA has granted accelerated assessment of the EMAA

We're very excited about potential for Alan agency to rematch if the treatment of hypertension Pretonic control blood pressure that we believe could result in important benefit from patients.

Ah next clinical program is L. N H S D. An investigation laundry night therapeutic for the treatment of match.

Which we recently father Cta This program is being advanced in collaboration Regeneron.

We're also making a strong progress on our many already I started opportunities be on the 11th.

Coke with 19, Orange therapeutic collaboration with fear, we selected the development candidate aliens theory or via 273 with Potanin highly cross-react of activity towards sauce Kobe to the virus that causes Kervick 19.

Akshay K. Vaishnaw: As you know, we have two additional late-stage programs that are in development with partners. This includes Inquisiran in development for hypertrustful EMEA, partnered with Novartis, which is currently under review for approval in the US and EU. Both NDA and MAA findings have been accepted, and Novartis expects initial approval in the US in late 2020, and Artis has indicated that they remain on track for approval this year with a December action date in the U.S. Our late-stage pipeline also includes Cetuceran in development for hemophilia A or B with or without inhibitors, partnered with SAMHSA.

Continue to expect 90, finding around year and 2020.

Oh, so pleased to announce today, but regeneron neglected to obtain to the L. N. A P. P program.

We aim to get in <unk> for file for L. M. A P. P and mid 2021 and this is expected to be out first thing in this program to enter clinical development.

And with that let me know turn it over to Jeff to review financial results Jeff.

Thanks, Akshay and good morning, everyone I'm pleased to be presenting Ala islands cute to 2020th resolved [noise].

Akshay K. Vaishnaw: Sanofi recently disclosed that two of the three Atlas Phase III studies have completed enrollment and that they remain on track to report top-line Atlas Phase III data in the first half of 2021. Vanity also presented new positive results from an interim analysis of the phase 2 early studies for 2-SRAM showing impressive reductions in the annualized bleeding rate with encouraging safety. Now, in addition to our late-stage clinical programs, we believe we've also been making great progress with our early and mid-stage programs. Highlights of the quarter were the positive top-line results from our LNA-GT Phase 1 study in patients with hypertension. Specifically, LNA-GT demonstrated an over 90% knockdown of angiotensinogen and a greater than 10 milliliters mercury lowering in systolic blood pressure with durability that matched a quarterly or even less frequent subcutaneous dosing regime.

[noise] has already highlighted it was a very strong quarter of commercial execution outstanding results for both on Patrollers Laurie.

Trying to our results for a strong tatro generated 66 $5 million in global not on Cacho revenue for the quarter, which was impacted by the pandemic, particularly in the U S with global growth being plot versus the first quarter of 2020, 74% increase compared with cute to 2019.

S growth decreased 13% during the quarter compared with Q1 was primarily impacted by the following.

4% decrease in demand from reduce patient adherents Cove at 19 pandemic is very previously mentioned.

8% reduction due to inventory destocking during the quarter.

And in inventory now at one and a half weeks in the distribution channel at the end of cute too and a 1% decrease do a modest increase in gross Tonight productions and a quarter continue to expect gross Tonight deductions will remain in the mid twenties globally foreign patch throw in 2020.

Akshay K. Vaishnaw: We're also encouraged by the tolerability profile for LNAGT. We now look forward to presenting more complete data from the ongoing Phase 1 study at a scientific meeting in the second half, assuming abstract acceptance. We're very excited about the potential for ALNAGP to reimagine the treatment of hypertension with tonic-controlled blood pressure, which we believe could result in an important benefit for patients.

And our international markets performance was very strong in spite of the pandemic.

Growth of 16% purchase Q1.

[noise] in Europe is highlighted by strengthen recently launched markets in Italy, and Spain, while in Asia growth in Japan romance robust with Japan, now representing our second largest Margaret from Tatro based on dollar sales, it's very mentioned.

Akshay K. Vaishnaw: Our next clinical program is ALNHSB, an Investigational RNI Therapeutic for the treatment of MAP, for which we recently filed a CTA. This program is being advanced in collaboration with Regeneron. We're also making strong progress on our many RNAi therapeutic opportunities beyond the liver. For example, for our COVID-19 RNAi therapeutic collaboration with VIA, we selected a development candidate, LN-CRE, or VIA2703, with potent and highly cross-reactive activity toward SARS-CoV-2, the virus that causes COVID-19.

First time this quarter the contribution of our international markets to global on Patrick sales exceeded the U S. Contribution. We are pleased to have a strong and global brand, which we believe it's beneficial to long term growth.

Turning to our results forgive Laurie we had a strong second quarter generating 11 million and global net revenue and a quarter representing over 100% growth compared to the first quarter.

Akshay K. Vaishnaw: We continue to expect an IMD finding around year-end 2020. Also, pleased to announce today that Regeneron has elected to opt-in to the ALN APP program. We aim to get an IMD file for LNAPP in mid-2021, and this is expected to be our first CNS program to enter clinical development.

This growth was driven by ongoing success it'd be less launch, where we did not experienced reductions in patient adherence at the same level is on Petro as well as an additional contribution from our international markets with a successful launching Germany and named patient sales in other countries, including France.

Ah combined product sales <unk> get watery or 77, and a half million for the quarter, representing 6% growth versus Q want a strong resolve given the challenges associated with Cove at 19 and a quarter.

Jeff Poulton: Thanks Akshay. Good morning, everyone. I'm pleased to be presenting Alnylam's Q2 2020 results. As Barry has already highlighted, it was a very strong quarter for commercial, with outstanding results for both Onpatio and Yuvlari. Turning to our results first for Onpatro, we generated $66.5 million in global net Onpatro revenue for the quarter, which was impacted by the pandemic, particularly in the U.S., with global growth being flat versus the first quarter of 2020 and a 74% increase compared to Q2 2019. U.S. growth decreased 13% during the quarter compared with Q1 and was primarily impacted by the following.

Turning now to a summary of our full P&L results for the quarter.

Revenue from collaborations for the second quarter was 26 4 million significantly increased from last year, primarily do the revenue recognized from our regeneron in here collaborations.

Gross margin as a percentage of total total revenue was 81% for the quarter down from 90 per cent and Q2 2019, primarily due to the current utilization of on Petro full cost inventory last year benefited from zero cost unnatural inventory as well as having a higher proportion of sales and the second quarter of 20.

20, coming from lower margin international markets, and a write off of them patio inventory at our contract manufacturer.

Our R&D expenses decreased on a non gap basis, and the second four of 2020 compared to the same period and the prior year, primarily due to nonrecurring expenses in 2019 from licensees related to the execution of our collaboration agreement Regeneron as well as a decrease in expenses associated with material many manufactured for clinical trials.

Jeff Poulton: 4% decrease in demand due to reduced patient adherence due to the COVID-19 pandemic, as Barry previously mentioned. Additionally, an 8% reduction due to inventory de-stocking during the quarter, with ending inventory now at 1.5 weeks in the distribution channel at the end of Q2, and a 1% decrease due to a modest increase in gross-to-net deductions in the quarter. We continue to expect gross-to-net deductions to remain in the mid-20s globally for Ampatro in 2020. In our international markets, performance was very strong in spite of the pandemic, with growth of 16% versus Q1. Growth in Europe was highlighted by strength in recently launched markets in Italy and Spain, while in Asia, growth in Japan remains robust, with Japan now representing our second largest market for Ampatro based on dollar sales, as Barry mentioned. For the first time this quarter, the contribution of our international markets to global Onpatra sales exceeded the U.S. contribution.

Conversely, SG&A expenses increased modestly on and on that basis, and the second quarter of 2020 compared to the same period and the prior year, primarily due to increased investment in commercial and medical affairs activity to support the ongoing launches of on Petro and give Laurie an initial launch preparation activities for the bathroom.

Importantly are non gap operating boss for a second quarter decreased by approximately 40 million compared with the same period in 2019, driven by a combination of strong top one growth and very moderate growth and operating expenses.

You remain confident that 2019 represents our peak non gap operating last year as we.

Expect the trend a strong topline growth.

Jeff Poulton: We are pleased to have a strong and global brand which we believe is beneficial to long-term growth. Turning to our results for Gidlari, we had a strong second quarter, generating $11 million in global net revenue in the quarter, representing over 100% growth compared to the first quarter. This growth was driven by the ongoing success of the U.S. launch, where we did not experience reductions in patient adherence at the same level as on Patro, as well as additional contribution from our international markets, with a successful launch in Germany and main patient sales in other countries, including France. Our combined product sales from Patreon and GetLorry were $77.5 million for the quarter, representing 6% growth versus Q1, a strong result given the challenges associated with COVID-19 during the quarter.

Or a growth and operating expenses will continue for the balance of the year.

He ended the quarter of cash in investments of 195 billion, which includes $600 million and proceeds received and the second quarter kind of partial sale of future include Serrano royalties and issuance of common stock to Blackstone.

Finally, turning to our financial guidance, we believe our results for the second quarter demonstrate the strength of a commercial teams and challenging circumstances as a result of a strong commercial performance upon patrollers exceeded our initial expectations back in the earlier phase of the pandemic and May you are further revising are full year revenue guy.

From Tatro with an increase in the middle point of our guidance as narrow the range from 270 $300 million to $280 million to $300 million.

Guidance range for combined non gap R&D and SG&A expenses as well as our guidance for net revenue from collaborations remain unchanged.

Jeff Poulton: Turning now to a summary of our full P&L results for the quarter. Net revenue from collaborations for the second quarter was $26.4 million, a significant increase from last year, primarily due to revenue recognized from our Regeneron and Deere collaborations. Gross margin as a percentage of total revenue was 81% for the quarter, down from 90% in Q2 2019, primarily due to the current utilization of on-patrol full-cost inventory, which last year benefited from zero-cost on-patrol inventory, as well as having a higher proportion of sales in the second quarter of 2020 coming from lower-margin international markets and a write-off of on-patrol inventory at our contract manufacturer.

Please note that we've revised the midpoint of our gap combined Orange D. N S. T N a operating expense guidance download about 25 million, reflecting a reduction unexpected stock-based compensation during the year.

Regarding cash we believe our strategic financing collaboration with Blackstone I didn't have to to build any cash secures thousand island bridge towards a self sustainable financial profile without the need for future equity financing.

And with that I'll know turn the call over to a bond to review our goals for a member of the year Yvonne.

Jeff Poulton: Our R&D expenses decreased on a non-GAAP basis in the second quarter of 2020 compared to the same period in the prior year, primarily due to non-recurring expenses in 2019 from license fees related to the execution of our collaboration agreement with Regeneron, as well as a decrease in expenses associated with material manufactured for clinical trials. Conversely, SG&A expenses increased modestly on a non-gap basis in the second quarter of 2020, compared to the same period in the prior year, primarily due to increased investment in commercial and medical affairs activity to support the ongoing launches of Ampatro and Gibralari, and initial launch preparation activities for the master, Importantly, our non-GAAP operating loss for the second quarter decreased by approximately $40 million compared with the same period in 2019, driven by a combination of strong top-line growth and very moderate growth in operating expenditures.

Thanks, Jeff and Hello, everyone looking I had to the second half of 2020, and we have a number of important mouth friends lined up a coffee time to continue I'll global commercialization of both on patio and get Barry and we're looking forward to Wanna get married launching Brazil, and an upcoming NDA filing forget about it in Japan.

Can.

We're also expecting two additional regulatory approvals by the end of the for the Master and and in case around the plan to continue enrollment in our atti cardiomyopathy studies, specifically I, probably would be with the T threat and he would just be with the tree surround.

Because it massaranduba on track to share topline results. They didn't make these days three study and May 2020 [noise].

And of course will also continues bouncing the rest of about pipeline. That's what it's exciting preclinical athletes symbol highlights. These milestone throughout the year is there a car among these there'll be a presentation of additional chemicals out from the ongoing phase one trial F. L N agency and hypertension, a programmer very excited about <unk>.

Jeff Poulton: We remain confident that 2019 represents our peak non-gap operating loss year as we expect the trend of strong top-line growth and moderate growth in operating expenses will continue for the balance of the year. We ended the quarter with cash and investments of $1.95 billion, which included $600 million in proceeds received in the second quarter from the partial sale of future Inclisiran royalties and issuance of common stock to Blackstone.

The plan to initiate that phase one trial F. A L N H S. P for Nash, having now filed the Cta for that program and our partner Regeneron I'm trying to initiate a phase one study a fancy surrounding combination because it anyhow, having now filed the Cta cause that study.

We also hope that you'll join us while remaining already I round tables focused on the master and the best friend and our PTR programs later in August and September Let me know turned it back to Christine's coordinator Q&A session Christine.

Jeff Poulton: Finally, turning to our financial guidance, we believe our results for the second quarter demonstrate the strength of our commercial teams in challenging circumstances. As a result of the strong commercial performance of Toronpatro that exceeded our initial expectations, Back in the earlier phase of the pandemic in May, we are further revising our full-year revenue guidance from Patro with an increase in the midpoint of our guidance as we narrow the range from $270 to $300 million to $280 to $300 million. The guidance range for combined non-GAAP R&D and SG&A expenses, as well as our guidance for net revenue from collaborations, remain unchanged. Please note that we have revised the midpoint of our GAAP combined R&D and SG&A operating expense guidance downward by $25 million, reflecting a reduction in expected stock-based compensation during the year.

Thank you were born and just wanted to quickly now to sound issue with berries prepared remarks, there's some some better Burlington with area that impacted the audio quality and we will plan to have Barry Rerecorded remarked for the replay of this call. So.

The operator look now open the call for question to those out and we'd like to asking to limit yourself. The one question each and then get back in the <unk>. If you have any additional black Janet.

[noise]. Thank you if you would like to ask a question. Please signal by pressing starved one on your telephone keypad, if you're using a speaker phone. Please make sure your mute function as turned off she will now you're sick naturally chocolate mint.

Jeff Poulton: Regarding cash, we believe our strategic financing collaboration with Blackstone, adding up to $2 billion in cash, secures Alnylam's bridge towards a self-sustainable financial profile without the need for future equity financing. And with that, I'll now turn the call over to Yvonne to review our goals for the remainder of the year.

That's star one ask a question.

I'm Gonna take our first question from Paul My teeth Stifle. Please go ahead you line is open.

Great. Thanks, so much and Ah Congrats furry, you're you're definitely gonna be <unk> and the ball and congratulations to you as well I guess just a couple quick commercial thing so on on the dynamics of impacted on Packer. This quarter you grew patients on drugs, but revenues were down as you think about inventory.

Yvonne L. Greenstreet: Thanks, Jeff. And hello, everyone. Looking ahead to the second half of 2020, we have a number of important milestones lined up. Of course, we plan to continue our global commercialization of both Patro and Givlare. And we're looking forward to our Givlare launch in Brazil and an upcoming NDA filing for Givlare in Japan.

Net crisis, you expand globally in compliance and the second half given the pandemic can you just help us understand have you variables are looking maybe in July and and what you expect later this year and then just on the commercial transition it'd be helpful. If you could comment on your confidence that there's more disrupt pickle a bar relaunch. This is obviously along that requires a lotta block.

Yvonne L. Greenstreet: We're also expecting two additional regulatory approvals by the end of the year for Lumastaran and Eclutaran. We plan to continue enrollment in our ATTR cardiomyopathy studies, specifically Apollo B with the T-Saran and Helios B with the T-Saran. With Maserand, we're on track to share top-line results from the Illuminate B Phase III study in mid-2020. And, of course, we'll also continue advancing the rest of our pipeline, as well as exciting pre-clinical efforts, and we'll highlight these milestones throughout the year as they occur. Among these will be our presentation of additional clinical results from the ongoing Phase 1 trial of ARN, AGT, and hypertension, a program we're very excited about. We also plan to initiate a Phase 1 trial of ALN-HSP for NASH, having now filed the CTA for that program, and our partner Regeneron plans to initiate a Phase I study of Sembisaran in combination with Cozumelimat, having now filed the CPA for that study.

And tackling in finding patience and you're really in the midst of of ramp up. So how do you can kinda manage that the transitioning in the midst of that thanks. So much.

Yeah, Paul Thanks, Great a great question so on the on the.

Let's start with you and then maybe Andy or if you can comment as well on some of them.

Virginia, two three dynamics and a coffee and is there such as you want to start.

Yeah sure I I think they're very made a couple of Congress and has prepared remarks that we did stuff to see some encouraging signs towards the end of the second second quarter and in that into the third corner, notably on genetic testing wrong idle Mac and solve recovery rates that we're close to what they were prior to the pandemic setting and I think we're also seeing improvements in it.

Parents, which was the major headwind that we saw on the earlier part of a quarter in the U S.

And then lastly, I think there's a question about stocking and there were at the lower end of the rain. So distribution partners contractually hold between one three weeks and we're at one and a half weeks right now so there could be some some additional build in the second half a year.

Yvonne L. Greenstreet: We also hope that you'll join us for our remaining RNAI roundtables focused on Maseran, Dvoseran, and our PTR programs later in August and September. Let me now turn it back to Christine to coordinate our Q&A session.

Great and did you want to call it a little bit further on the the dynamics here is we enter the third order.

Christine Regan Lindenboom: Thank you, Yvonne. I just wanted to quickly acknowledge a sound issue with Barry's prepared remarks. There are some storms that are rolling through his area that have impacted the audio quality, and we will plan to have Barry re-record his remarks for the replay of this call.

Sure sure and pause you mentioned here even have missed the health care shut down in the U S. We were able to increase the patient's on on Petro. It was the adherents which was the the main driver of the demand impact is since Jeff just mentioned as well.

Operator: So, operator, let's now open the call for questions. To those that have been, we would like to ask you to limit yourself to one question each and then get back in the queue if you have any additional questions. Thank you. If you would like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment.

And in June and July we have seen dramatic progress and both the resumption of a patient closer to the health care system in Ohio, Mac volumes and other things we metric.

As well as the adherence right.

Proving across all of a <unk>.

Yeah, and I I would just add a pastoral that for example, Paul P Y piece gas isn't important way that patients get diagnosed with this disease and if they have polyneuropathy then they become appropriate patients for a patch O N N or July typ's gas, we're comparable to what we saw.

Operator: Again, that's star number one to ask a question. We will now take our first question from Paul Matteis from Stifle. Please go ahead, your line is open. Great, thanks so much. And congratulations, Farrah, you're definitely going to be missed.

Eric Green: And Yvonne, congratulations to you as well. I guess just a couple quick commercial things. So on the dynamics that impacted Petro this quarter, you grew patients on drugs, but revenues were down. As you think about inventory, net prices, expanding globally, and compliance in the second half given the pandemic, can you just help us understand how these variables are looking maybe in July and what you expect later this year?

January for example, this is what things are we can track across the country. So that's a good sign but let's trying to think of lottery question.

Barry do you want to comment a little bit other question as far as of our confidence in the second half of the launch given given you know the absolute froze the pandemic.

Absolutely my audio better the storm has pets.

Much better [laughter].

That's as I was speaking my wife's normally we went out as I hope he's like starting remarks I apologize for the muffling, yeah. So pumped great question on the wall you know I'll remind you that in these kinds of rare diseases were diagnosis streets, a very low because physicians aren't really looking patients come from three different buckets they come from.

Eric Green: And then just on the commercial transition, it would be helpful if you could comment on your confidence that this won't disrupt the Glovari launch. This is obviously a launch that requires a lot of blocking and tackling and finding patients, and you're really in the midst of the ramp-up. So how do you kind of manage the transition in the midst of that?

[noise] patient transition to EVP tastes, none of the sites in a brand new.

Most patients and as we Michigan.

English dependent we were highly prepared with Digitization virtualization already from you've already given the diverse subscriber base in the fact that patients can be anywhere in the world. So in fact have done virtual launches <unk> very well.

Eric Green: Thanks so much. Yeah, Paul, thanks. Great, great question. So on the Alpatro, let's start, Jeff, with you and then maybe Andy, or if you can comment as well on some of the emerging Q3 dynamics and our confidence there. So, Jeff, do you want to start?

And have not being really a detriment is machine based upon results to our success in <unk>.

Getting health care providers in educating then we should be reaching out the patient advocacy groups and <unk> because patients who are prescribed to get access to the players so often.

Jeff Poulton: Yeah, sure. I think that Barry made a couple of comments in his prepared remarks that we did start to see some encouraging signs towards the end of the second quarter and into the third quarter, notably on genetic testing. Alnylam Act, we saw recovery rates that were close to what they were prior to the pandemic setting in. I think we're also seeing improvements in adherence, which was the major headwind that we saw in the earlier part of the quarter in the US, and then lastly, I think there was a question about stocking there. We're at the lower end of the range, so our distribution partners contractually hold between one and three weeks, and we're at one and a half weeks right now, so there could be some additional build in the second half of the year.

I've been have been that's going very well.

Other kind of and I'll have is the fact that the healthcare Provider's now G tube coded situations are also being forced to get online is that C. H.

Strategy, we've had the digital in virtual interaction because now they're more useless.

To do it and you've had really remarkable icon and seafood programs with numbers that you'd never seen before when they were local and lives. So.

While nothing as good as in person usually taken.

Advantage to help patients invest weekends during the Sun.

And I'll just add one last point I'd give lori which is that we do benefit from a drunk that's been proven in clinical studies to decrease hospitalizations.

[noise] related to the annualized attack rate reductions, let me see in obviously is is good in this current circumstance. So Paul does that extra <unk>.

Andy Orr: Great. And Andy, do you want to comment a little bit further on the dynamics here as we enter the third quarter? Sure, sure. And Paul, as you mentioned here, even amidst the healthcare shutdown in the U.S., we were able to increase the number of net patients on Onpatro. It was adherence which was the main driver of the demand impact, as Jeff just mentioned as well.

Yeah. It does thanks, so much bright color I appreciate it.

Thank you.

On that take our next question for my nephew Young some contour. Please go ahead you line is okay.

Hey, guys. Thanks for taking my classroom and congrats Mary Matilda.

And.

Alright, you're working with you further.

He's a pleasure so I just wanted to ask a little bit about kind of a little bit off kilter here Uhm. How are you thinking about kind of thing hemophilia landscape. The tastes are and and how 'bout physician there might have what's going on with Jane therapy, I know, it's a fantasy product, but I just wanted to kinda get your perspective on that since we're getting relatively close the day to thank you.

Andy Orr: And in June and July, we saw dramatic progress in both the resumption of patient flows through the healthcare system and Alnylam Act volumes and other things we measure, as well as, you know, the adherence rate improving across all the sites of care. Yeah, and I would just add on Alpatro that, for example, Paul, PYP scans are an important way that patients get diagnosed with this disease, and if they have polyneuropathy, then they become appropriate patients for Alpatro, and our July PYP scans were comparable to what we saw in January, for example. These are things that we can track across the country, so that's a good sign. But let's turn to the Gavlari question.

Yeah, absolutely, let me make some comments and then I I I'd welcome.

Milkshakes perspectives as well.

Let's see that hemophilia market is is is a multi pot a multi company.

Market. There are many players already there are thousands of overdose on products that are available for patients with hemophilia, a or b with or without an hamburgers, which is great.

[noise], where I am really fits in as as the only <unk> monthly subcutaneous Ah medicine that shows AVR levels annualized bleeding levels that are around one and that really is a unique positioning for the for the for the product and argue in Santa Cruz do.

John Marganori: Barry, do you want to comment a little bit on the DuBlois question in terms of our confidence in the second half of the launch given the ebbs and flows of the pandemic? Absolutely. Is my audio better?

Eric Green: The storm has passed. It is much better now. As I was speaking, the lights literally went out as I opened my opening remarks, so I apologize for the muffled sound. Yeah, so, Paul, great question on Dvorak.

Yes that holds up in the pastry trials are the same thing continues to hold off.

As was encouraging we've shown in there.

Dated open labels honey this could be a very important medicine and that landscape and offer competitive profile compared to Henry Perez the actually only really effective what's monthly subcutaneous medicine Akshay do you want to come with any further on that.

Eric Green: Now, I'll remind you that in these kinds of rare diseases where diagnosis rates are very low because physicians aren't really looking, patients come from three different buckets. They come from patients transitioning from EAP, patients known as sites, and then brand new, newly diagnosed patients. And as we mentioned at the beginning of the pandemic, we were highly prepared with digitization and virtualization already for Dvorak, given the diverse prescriber base and the fact that patients can be, you know, anywhere in the world. So we, in fact, have done virtual launches, and they've done very well and have not been, as we've seen based on results, a detriment to our success in getting to healthcare providers and educating them, reaching out to patient advocacy groups, and ensuring that patients who are prescribed get access to the payer. So all three of these have been going very well. I think the other comment I'll have is the fact that healthcare providers are now, due to the COVID situation, also being forced to get online. This has actually aided the strategy we've had for digital and virtual interactions because now they're more used to it. They're willing to do it,

Yeah.

It's a very interesting dynamic time, a name of failure landscape.

Lee Burba gene therapy, I I think you know at premium with all of these approaches causes safety. That's a very delicate population wetherbee insignificant safety events in the past then.

I think both with a hambly, Brian gene therapy.

You need to be a discussion obviously.

Completed their face Grease studies.

And the barbarian phase three studies for.

For the eighth therapy, but.

Drew ability of effect with gene therapy long-term safety, including the potential for home for Genesis. This remains the question in our opinion have been recent dog studies that showed the very late long-term cancer events kanaka routines between the Sylvia.

But look <unk>.

Good time for patients that have more therapies come on his Jones said.

Therapy for Haemophilia, a N b, that's convenient and safe once a month, so cute with obviously be very attractive seem to Tucson can offer that bill for on demand.

Eric Green: And we've had really remarkable ad comms and featured programs with numbers that we'd never seen before when they were local and live. So while nothing as good as in-person, we've really taken advantage of it to help patients as best we can during this time. And I'll just add one last point on DiBiLauri, which is that we do benefit from a drug that's been proven in clinical studies to decrease hospitalizations related to the annualized attack rate reductions that we see, and that obviously is good in this current circumstance. So Paul, does that answer your question? Yeah, it does.

Both license and inhibitor patients.

Even beyond that in the other bleeding disorders.

Definitely unique and differentiated offering and we are equally late price for data.

Early early next year as you said, a Alicia which is exciting does that extra question. Yeah very helpful. Thank you guys.

Great. Thank you.

Cleveland Avenue try next question from a new Panorama from J P. Morgan. Please go ahead you line is open.

Okay. Thanks, so much for taking the question and for Apollo E close the primary endpoint analysis, there's a 12 month extension.

John Marganori: Thanks so much for being on the call. I appreciate it. Thank you. We will now take our next question from Alicia Young from Kantor. Please go ahead, your line is open.

Trial, we continue that on a blinded basis, so that you'll be able to get sort of awesome data in a placebo controlled Nana oh, you'd really be relying on the two slant to get some of those longer term outcomes beyond 12 months and for Barry.

Akshay K. Vaishnaw: Hey guys, thanks for taking my question and congrats, Barry; you killed it. And Yvonne, we look forward to working with you further. I just wanted to ask a little bit about how you think about the hemophilia landscape and how that's positioned in light of what's going on with gene therapy. I know it's a Sanofi product, but I just wanted to kind of get your perspective on that since we are getting relatively close to data. Yeah, absolutely. Let me make some comments, and then I'd welcome Akshay's perspectives as well. Obviously, the hemophilia market is a multi-product, multi-company market. There are many players already. There are dozens of, over a dozen products that are available for patients with hemophilia A or B, with or without inhibitors, which is great.

Always admired the hustle on them.

Alright, so so akshay I think for your policy question is right up your alley.

Yeah.

Principal third control Apollo B as in you said.

Is on the 12 month analysis on Beatrice friend will be coming in clothes succession off the bat reader upbeat 12 months read out for participating in Nepal, it'd be and so it goes back will form the principal demonstration about P. Taylor and approaches and what they can do in terms of morbidity and mortality in the long term.

Yeah, I'll just add I'll I'll, just add Odyssey, we are capturing mortality it shouldn't be hospitalization.

Data hobby.

So well, obviously collect those data and see what they report.

Akshay K. Vaishnaw: You know, Pitucaran really fits in as the only once-monthly subcutaneous medicine that shows ABR levels, annualized bleeding levels, that are around 1. And that really is a unique positioning for the product, in our view, and in Sanofi's view. And so, if that holds up in the phase 3 trials and the safety continues to hold up, as was encouragingly shown in their updated open-label study, this could be a very important medicine in that landscape and offer a competitive profile compared to Hemlibra as the potentially only really effective once-monthly subcutaneous medicine. Akshay, do you want to comment any further on that? Yeah, you know, it's a very interesting and dynamic time in the hemophilia landscape, hemolibra, and gene therapy. I think, you know, at the premium with all of these approaches is safety, of course. It's a very delicate population where there have been significant safety events in the past.

One year's worth of treatment is probably not in the power's off the size of power to show something there, but we will certainly be collecting those data and those type of data made for how we pick him up in the interim analysis for Helios B, which is arbitrary surround study and that's obviously gonna be a nice helpful set of data is <unk>.

Sure what that it looks like.

Thanks for taking my question.

Uh-huh.

Yeah My Magic. Our next question from caffeine, how much from Bank of America. Please go ahead you line is open.

Alright, good one day and thanks for taking my classroom quick one as of midnight, So I'm pats ourselves with extra <unk> now higher than the U S. Thank you relate that at least near term.

As in as an impact home Cove in and do you expect that time for <unk> for the duration of that covered his aminophenol Doctor <unk>.

Akshay K. Vaishnaw: And I think both with hemolibra and gene therapy this will continue to be a discussion. Obviously, they've completed their phase three studies. And the primary and phase three studies would be hemophilia therapy. But, you know, durability of effect with gene therapy, the long-term safety, including the potential for oncogenesis, this remains a question, in our opinion. There have been recent dog studies that show that very late, long-term cancer events can occur with gene therapy for hemophilia.

And then I don't Wanna get your early thoughts about Regeneron Apple N for your a L. N a P P program.

You plan on starting development, you know that program that will give us a little bit of color on what you think the opportunity can't be in <unk>.

Okay. So let me let me start with the second half, which the second part of the question, which I think was was mixed two different programs and <unk> and they're very you should you should ask you. The first question I'm, sorry, [noise] Yep, Yeah regarding regarding a P. P. That's our amyloid precursor protein program that they opted into and that's gonna that's gonna be.

Akshay K. Vaishnaw: But look, it's a good time for patients to have more therapies come on. As John said, a therapy for hemophilia A and B that's convenient and safe, once a month, subcu, would obviously be very attractive. And we think the two strands can offer that both on-demand and even beyond that in other bleeding disorders. So this is an absolutely unique and differentiated offering, and we eagerly await pay-through data. Early next year, as you said, Alethea, which is exciting.

That's on track to have the files.

Or Cta in Middle 2021, that'll be are for C. N. S program. So the opposite into that program. That's different that's M. D surround which is R. C. Five program, which they already had opted into that's part of our original agreement with them, which is currently to face to study and I create a prophecy.

We're also doing as they are doing combination studies with somebody Saran.

John Marganori: Does that answer your question? Yes, very helpful. Thank you, guys. Great. Thank you. We will now move to our next question from Anupam Rama from J.P. Morgan. Please go ahead, your line is open.

Cause allomap, which is there a sad to see if I may antibody to get the benefit of a infrequent subcutaneously delivered treatment for many kaufman medium diseases like PNA myasthenia amongst others. So that's that's that part of the questions Zain Barry do you want to parents or the first one on.

Akshay K. Vaishnaw: Hey guys, thanks so much for taking the question and for Apollo B, post the primary endpoint analysis, there's a 12 month extension in the trial. Will you be continuing that on a blinded basis so that you'll be able to get sort of outcome data in a placebo-controlled manner? Or will you really be relying on Batustran to get some of those longer-term outcomes beyond 12 months? And Barry, you know, always admires the hustle man.

And you asked rest of the World patrol and how about how we see that going forward.

Yeah, absolutely you know is just provided on the call. We we've after mid guidance, reflecting our beliefs us that we're in recovery face. So in particular, we believe that would be a contingency groceries in the U S. I'll remind you. This is a mature Marcus.

Akshay K. Vaishnaw: Alright, so Akshay, I think the Apollo P question is right up your alley. Yeah, you know, the principal focus for Apollo B, as you said, Anupam, is on the 12-month analysis, and the vitreous strand will be coming in close succession after that readout of the 12-month readout for the T-strand in Apollo B. And so of course, that will form the principal demonstration of how PTL-O approaches and what they can do in terms of morbidity and mortality in the long run. Yeah, I'll just add, obviously, you know, we are capturing mortality and CP hospitalization data in Apollo B autobombs. So, you know, we'll obviously collect those data and see what they report. You know, one year's worth of treatment is probably not enough, and the study's not powered to show anything there, but we'll certainly be collecting those data. And, you know, those types of data may inform how we think about the interim analysis for Helios B, which is a Boutry-Saran study.

S as really pure patient find market right now and it's places are again flowing through the healthcare systems were finding the proportionate patients.

Ctr that a hereditary was calling the off with them. So we can to to see goes to the U S. In terms of rest of world. Many countries continued benefit by patients known site as well as finding new patient and then we are opening territory. So every time the country openings, we benefit by E. P. As in those countries and patients done the site. So again I mean, we see growth in or.

All reasons around the world convenient.

Yeah.

<unk> anything do you want to add or Andy to that.

Ah nothing for me to add.

And you know I agree that's a great I think Barry got it.

Right. Okay. So you're telling me I'm, sorry, I think about I think John just one thing about it says on here I think I think the increasing use a combination therapy in the USA the dynamic but.

That I think at the very interesting one for us, but yeah, I think they'd be getting to see physician depreciates the profile of patterns. In this mixed population phenotype. So I can that's something to keep an island as well yeah absolutely.

John Marganori: And that's obviously going to be a nice, helpful set of data as we consider what that IA looks like. Thanks for taking my question. Thanks a lot.

And I I did wanted to I'm, sorry, a number with my second class and I didn't want to ask Y a P. P. Let's start development X E y.

Jeff Poulton: We will now take our next question from Tazeen Ahmad from Banks America. Please go ahead; your line is open. Hi, good morning, guys. Thanks for taking the time to answer my questions. A quick one as it relates to on-patrol sales; with XUS now higher than the US, would you relate that, at least near term, as an impact on COVID? And do you expect that trend to continue for the duration of COVID as a meaningful factor, at least here in the US? And then I do want to get your early thoughts about Regeneron opting in for your ALN APP program. You know, your plan for starting development of that program, can you give us a little bit of color on what you think the opportunity could be in IGA necropathy? Okay, so let me start with the second half, which is the second part of the question, which I think was mixed up with two different programs in it, Tazeen, and then, Barry, you should you should answer the first question. Sorry.

Oh.

There's no there's no <unk>.

Plan to do it actually less necessarily cause they we often start studies in different parts of the world pretty sometimes of the U S. So there's no it's not a plan to do it actually less per se.

Okay.

Okay. Thank you.

You Wanna take our next question from Mommy Raycroft from Jeffries. Please go ahead to your line is open.

Hi, everyone. The morning, Indata come back on the progress and thanks for taking my question, what's the one.

And Ah Apollo B. So we know from your exploratory endpoints in the day three Palo a yep.

<unk>.

Picture and showed activity and cardiomyopathy.

I'm wondering if you're collecting data from the commercial patient Denon Padro that provides read through to your power B.

And when you.

Present, those data at some point and can you comment on.

<unk> similarities between patients evening drug commercially.

Those involvement apology.

Eric Green: Yep. Yeah, regarding APP, that's our amyloid precursor protein program that they opted into. And that's going to that's going to be on track to have the file IMD or CTA in the middle of 2021. That'll be our first CNS program. So they chose that program.

Yeah. That's that's a great question I'm Gonna maybe provide some contacts maybe I'm sure you can comment as well I'm married you know what were you know obviously in India original Paula studying and <unk> She said.

There were very encouraging exploratory data generated and patience with cardiomyopathy Prespecified cardiomyopathy.

John Marganori: That's different than some D-Saran, which is our C5 program, which they already have opted into. That's part of our original agreement with them, which is currently a phase two study in IGA nephropathy. What they're also doing is they're doing combination studies with some D-Seran together with Pazolimab, which is their anti-C5 antibody, to get the benefit of an infrequent, subcutaneously delivered treatment for many complement-mediated diseases like PNH and myasthenia, amongst others. So that's that part of the question, Tazeen.

That our hypothesis generating there they formed a foundation of our confidence Pablo B and I think for your flight there's been some interesting data that have been generated.

<unk> in the field and patience that have polyneuropathy, but also with cardiomyopathy work. It tastes right is being used specifically looking at cardiac gambling imaging and some of the data that had been in one case published by a Dutch grew up and then the National Amyloidosis Center in the UK is presented some data.

Eric Green: Barry, do you want to answer the first one on the U.S., the rest of the world, Onpatro, and how we see that going forward? Yeah, absolutely. As Jeff provided in the call, we've upped our mid-guidance, reflecting our belief set that we are in the recovery phase. So, in particular, we believe that we're going to continue to see growth in the U.S. I'll remind you that, as a mature market, the U.S. is really a pure patient-friendly market right now, and as patients are, again, flowing through the healthcare systems, we're finding a proportion of patients with TTR that are hereditary with polyneuropathy.

Really quite encouraging and give us give us encourage before.

<unk> B of course.

The results of that study before we can comment definitively on on the T surrounds activity and cardiac patients akshay anything to add to that from your perspective.

No I think your coverage huh.

Yeah, Great and you know I'll just add that you know there are always investigational studies that are done by by you know individual centres or you know groups are physicians that that might explore these type of features and that's something which does occur out there very anything else to add on a commercial side.

Eric Green: So we continue to see growth in the U.S. In terms of the rest of the world, many countries continue to benefit from patients known to the site, as well as finding new patients, and then we are opening new territories. So every time a country opens, we benefit from EAPs in those countries and patients known to the site. So, again, we see growth in all regions around the world continuing. Yeah, and Jeff, anything you'd want to add, or Andy to that?

No I think you covered it well.

Right. Thank you.

Okay that does it very I'll forward this could follow up or a G. P. So in your topline day do you guys reported and I'm 48 patients her dad and you're gonna have additional data at the end of this year I think you can enroll up to 184 or that study just wondering if you can comment more how many patients.

Jeff Poulton: Nothing for me to add. No, I agree. I think Barry got it.

Weighing on enrolling and.

How much pull data couldn't see at the end of the year.

John Marganori: John, just one thing to add, this is Yvonne here. I think the increasing use of combination therapy in the US is a dynamic that I think is a very interesting one for us, but I think we're beginning to see physicians appreciate the profile of Ompatro in this mixed population phenotype, so I think that's something to keep an eye on as well. Yeah, absolutely. And I did want to just, I'm sorry, I mangled my second question. I wanted to ask why APP would start development at CUF. Oh, there's no plan to do it necessarily at XUS necessarily because we often start studies in different parts of the world, including sometimes in the U.S., so there's no, it's not a plan to do it at XUS per se.

Yeah, I mean, we you know a lot of these days my studies or or engineer with Arsenal cohorts that allow us to add additional subjects patients in this case to to the studied design I think it's still we're still haven't decided you know at one point, we will have completed that study, but we are still last <unk>.

<unk> important question's, including potentially on combination with.

Apprehensive mess to explore that in the study both from activity and safety perspective, akshay anything else to add to that.

No I think that covenant yep.

Alright.

Alright.

Yeah that up thing for day My question.

Thanks Marty.

Hi, My name is to our next question from reach you. They're Awesome Cohen. Please go ahead you line is open.

John Marganori: Okay. Okay, thank you. We will now take our next question from Maury Raycroft from Jeffrey. Go ahead, your line is open. Hi everyone, good morning, and congratulations on the progress and thanks for taking my questions. The first one is just on Apollo B.

Hi, guys. Thanks for taking the question buried late to work with you over the years and best of luck in Yvonne.

Congratulations looking forward to working with a few more.

I'd like to ask about training home administration for an Tatro.

Akshay K. Vaishnaw: So we know from your exploratory endpoints in phase three Apollo A that Onpatro and Pertusserin shared activity in cardiomyopathy phenotypes. I'm wondering if you're collecting data from the commercial patients on Onpatro that provides read-through to Apollo B and will you present those data at some point, and can you comment on some key baseline factors or similarities between patients using the drug commercially versus those involved in Apollo Yeah, that's a great question. I'm going to maybe provide some context.

Alright is there any difference between what you're seeing.

And what is being done in the U S. It's fine, allowing Pittsburgh, Kobe, and and and reimbursement in and uptake is this something.

That'll be any better going forward to stabilize and do that.

Yeah, I mean, it's a great question very do you want to give the global view and then maybe and and you can add additional Colorado U S dynamics on that.

Akshay K. Vaishnaw: Maybe, Akshay, you can comment as well. And Barry, you know, look, we're obviously in the original Apollo study, Apollo A. As you said, there were very encouraging exploratory data generated in patients with cardiomyopathy, pre-specified cardiomyopathy, that are hypothesis-generating and form the foundation of our confidence in Apollo B.

Yeah, absolutely and can great question Homey G as in it.

Care of site that we'd utilizing depend on it so.

Recently homey issues about 70, 217% pre pandemic doubled to about 35% and the agents endemic.

Akshay K. Vaishnaw: And I think, to your point, there's been some interesting data that have been generated, investigatively, in the field in patients that have polyneuropathy but also with cardiomyopathy, where patisseride is being used, specifically looking at cardiac amyloid imaging. And some of the data that have been published in one case by a Dutch group, and then the National Amyloidosis Center in the UK has presented some data, are really quite encouraging and give us encouragement for Apollo B. Of course, we'll await the results of that study before we can comment definitively on plaquessand activity in cardiac patients. Akshay, anything to add to that from your perspective? No, I think you covered that.

And extra France.

Stabled.

Cohort of patients.

G E. One one of the slice of important infectivity with reported system very important.

Oh, it's coming from all the U S is also doubled from 9% about 20, you mean globally in countries that allow home infusion U S digital Canada most of the European countries.

<unk> effectively been able to new patients too on the T. V. There are times, where a dose delay to his nose skiffs and that transition, but as we.

<unk> no got the capability down mostly statements a movie without.

Interruption rollinson is very important.

Alright.

Akshay K. Vaishnaw: Yeah, great. And you know, I'll just add that, you know, there are always investigative studies that are done by, by, you know, individual centers or, you know, groups of physicians that might explore these types of features. And that's something that does occur out there.

Does that sound growing like.

Mm Hmm interesting right.

Yeah, and maybe I can I can touch on the U S without specifically I'm gonna be entered yeah. She's very mentioned, we doubled it from nine to 20th essentially from the end of 2019 to currently and we expect that to continue to grow our teams had been in.

Eric Green: Barry, anything else to add on the commercial side? Nah, I think you covered it well. Perfect, thank you.

Side of care optimization mode since the onset of Kobe and that's both home care as well as more local infusion centers. If they were going into the large institutions. So we expect our patients and physicians to continue to take advantage of of home care.

Maury Raycroft: Maury, did that answer your question? Yes, it's very helpful. And just a quick follow-up for AGT. So in your top line data, you guys reported on 48 patients for that, and you're gonna have additional data at the end of this year. I think you can enroll up to 184 patients for that study.

And could you just get Tuesday.

In terms of elaborate goodbye.

Thank you.

So.

Just in terms of growth we.

As as the pandemic ebbs and flows both the United States in other countries, we see patients moved home infusion and then when possible back to a local infusion center keep in mind that patients really like getting out of their house and social aspect of your choosing center, so I want to.

Akshay K. Vaishnaw: Just wondering if you can comment more on how many patients you plan on enrolling and, I guess, how much cold data we could see at the end of the year. Yeah, I mean, a lot of these phase one studies are engineered with optional cohorts that allow us to add, you know, additional subjects, patients, in this case, to the study design. You know, I think that we still haven't decided at what point we will have completed that study, but we are still answering important questions, including potentially a combination with other antihypertensive meds. No, I think that you covered that. Yeah. Great. Does that help, Maury?

[noise] prefer vanilla.

Alright, Thanks Berry Richard does that answer your question.

Yeah, and and I just wanted to could you just review reimbursement like.

Okay.

Yeah, Yeah, do you want to handle that Eddie.

Yeah, certainly certainly.

So the reimbursement clearly on the commercial side of our population is very straightforward.

Akshay K. Vaishnaw: We have it all. Thanks for taking my question. Thanks, Maury. We will now move to our next question from Ritu Baral of Cohen. Please go ahead, your line is open.

Many patients they're taking advantage of it.

But we also know like that CMS released in late June.

A regulation that allowed a temporary reimbursement scheme for Medicare or be patient and we also have many hospitals that are beginning to take advantage of that and that's an area, where we expect to see more growth and utilization of that going forward.

Eric Green: Hi guys, thanks for taking the question. It's been great to work with you over the years and best of luck in Kizan. Really, congratulations. Looking forward to working with you more. I wanted to ask about trends in home administration for FONPATRO. Is there any difference between what you're seeing in the US and Europe?

Okay.

I'm ready to come up.

Thank you from us.

We went down there to my next question from David Legal extra Morgan Stanley. Please go ahead take your line is open.

Eric Green: And what is being done in the US as far as allowances for COVID? Yeah, I mean, it's a great question. Barry, do you want to give the global view and then maybe, Andy, you can add additional color on the US dynamics on that? Absolutely, and a great question. Home infusion has been a critical care site that we've utilized in the pandemic. So, in the Samia region, home use was about 17% pre-pandemic, and it's doubled to about 35% in the age of the pandemic. There's an anecdote, France, in fact, was able to move a key cohort of patients into home infusion when one of the sites reported any activity with COVID. So, it's been very important. In common, the U.S. has also doubled from 9% to about 20. And then globally, in countries that allow home infusion, the U.S., Brazil, Canada, most of the European countries, we've effectively been able to move patients to home infusion. [inaudible] And is that still growing? Is that still growing, like the home infusion rate? Yeah, and maybe I can touch on the US with that specifically.

Thank you very much for taking my question.

Given you experienced that far keep Larry.

Have you I guess made any decisions and I'm a mess around what you might want to keep them like you might want to modify as far as the lunch given the similarities in the market.

Yeah, Great Great question, Let me, let me make some interest the initial comments and then very you shouldn't comments as well I mean, obviously and the last ran like give Lori is addressing a very.

Devastating disease, that's an ultra rare orphan population based on prevalence you know as with give Laurie there are.

The other diagnosis rates and N P. H, one or also well well known and soldiers from the need for patient finding work. We we have a commitment is you know David too.

The focus out of the value of that are medicines deliver.

And we have been very successful and that approach proactively engaging with payors, forming value based agreements and that effort will occur with all medicines and our pipeline, including lemass around and so as we begin to get ready for launch and get ready for.

It's important to Madison to come in the Playbooks at we developed for a pastor of the playbook that we've been executing off forgive Lori is one that we will absolutely they use it for for the mass around.

Ritu Baral: And the answer is yes. As Barry mentioned, we doubled it from nine to 20, essentially from the end of 2019 to now. And we expect that to continue to grow. Our teams have been in site of care optimization mode since the onset of COVID. And that includes both home care as well as more local infusion centers if they were going into larger institutions. So we expect our patients and physicians to continue to take advantage of home care. And could you just go through reinforcement, allow reinforcement for that?

Of course would be leveraging importantly, leveraging the existing infrastructure that we built now globally for the company very anything to add to that.

No that's.

The only color I'd add.

Gotten very very good now as the digital virtual instead of care optimization that was messy.

Eric Green: Yes. Thank you. So just in terms of growth, as the pandemic ebbs and flows, both in the United States and other countries, we've seen patients move to home infusion and then, when possible, back to a local infusion center. Keep in mind that patients really like getting out of their house and the social aspect of the infusion center.

<unk>.

Mmk used to launch a disease like P H, one where again.

Diagnosis rates, 50%, there are 50% of patients up their home diagnose to being able to reach them.

Virtual meat means the highly advantageous.

Yeah. Thanks very.

David does that answer your question.

Yes. Thank you for taking my question.

Alright, thank you.

[noise], we will damage to our next question from 10 Qichen from Bernstein. Please go ahead you line is open.

Eric Green: Alright, thanks Barry. Richard, does that answer your question? Yeah, and I just wanted to, could you just review the reimbursement side of it? Do you want to handle that, Andy?

Thank you very much for taking the questions two quick ones, one commercially oriented and while I'm yanji aside for for July 4th of already when you realize you're not gonna providing guidance, but I'm curious what you're seeing as far as the trajectory to start forms coming out of cute too and going into Q3, I know a good incremental sort form slowed and two two grilled, but you want.

Andy Orr: Yeah, certainly, certainly. So the reimbursement, clearly, on the commercial side of our population is very straightforward. And we have many patients that are taking advantage of it. But we also know, right, that CMS released in late June a regulation that allowed a temporary reimbursement scheme for Medicare Part B patients. And we also have many hospitals that are beginning to take advantage of that, so that's an area where we expect to see more growth and utilization. of that going forward. Did that answer your question, Ritu? Yes, thank you so much. We will now move to our next question from David Lebowitz, Director of Morgan Stanley. Please go ahead, your line is open. Uh, given your experience thus far, Steve Lari, um, have you... on Lumassaran?

I imagine some business because you know the initial bowls of patients and cute one somebody's impaction probity, but adversely impact your cue to just trying to get a sense of was unreasonable near term run right. My might look like between those two and then fucking the only decided a quick one it'll be a O M. A P. P I N D filing.

It's only watching very closely for moving to CNS delivery, we're supposed to open up a range of three large and I am that medium <unk>.

So it seems like it's taken some fun what are the didn't doctors only Zealand ADT <unk>. What's left we've done before you can interested any trials.

John Marganori: modified, Yeah, great, great question. Let me make some initial comments and then Barry, you should comment as well. I mean, obviously, lumacaran, like gibblari, is addressing a very devastating disease. That's an ultra-rare orphan population based on prevalence.

Yeah. Those are great questions, let me start with the first one akshay you'll get the second one.

As a minute.

But your question I get Laurie I mean, we're extremely pleased with the performance that we saw <unk>.

Thank you too even even even though we were going through the pandemic keep in mind isn't that.

Eric Green: You know, as with gibblari, there are other diagnosis rates, and in pH, one is also, you know, well, well known. And so there's a need for patients and for people to find work. We have an commitment, as you know, David, to be focused on the value that our medicines deliver. And we have been very successful in that approach, proactively engaging with payers, and forming value-based agreements. And that effort will occur with all medicines in our pipeline, including lumacaran. And so as we begin to get ready for launch and get ready for this important new medicine to come in, the playbook that we developed for Alpatro, the playbook that we've been executing on for gibblari is one that we will absolutely be using for lumacaran. Of course, we'll be leveraging, importantly, leveraging the existing infrastructure that we've built now globally for the company. Barry, anything to add to that?

This to start forms that we saw pier one of course, we're benefited greatly by patients that were either indie UFC AP or that were known to site sort of that initial bowlus. If you will.

But we do expect growth you know from that point or were saying continued girl.

In the U S about 25% of of our patients in the U S are also coming outside of our patient Hot and therefore, you know they're not on.

To start form metric if you will.

And you got that it caused for the over 100 patience every believer now on on give Lori commercial treatment not that includes a small part of the U S were as we said in our in our prepared remarks were now gonna stop for providing star four metrics forgive Laurie just like we did with a patch old last year, because we know haven't.

Global source of patients Rochester U S alone, we still have a significant number of patients that are coming outside of our patient hot but you'll see the growth in our total patient number quarter on quarter forgive Laurie and we are optimistic.

John Marganori: Now, John, the only color I'd add is that we've gotten very, very good now at the digital, virtual, and cellular care optimization that was meant to be made necessary by COVID. That's advantageous to a launch of a disease like PH1, where, again, while the diagnosis rate is 50%, there are 50% of patients out there undiagnosed. So being able to reach them through virtual means is going to be highly Thanks, Barry. David, does that answer your question? Great, thank you. We will now move to our next question from Vincent Chen of Burns. Please go ahead; your line is open.

With that grow up in the U S and also another markets around the world.

Now Europe of course has now been.

Launched in Germany, and they may patient sales around any countries. So I think that we don't even say anything more or less provocative Lori do you want to know Akshay talk about ATP and what's between now and our filing.

Sure Yeah I mean.

Sort of an accent.

He liked the replacement card real soon.

It's about a year since you signed up due to the general.

Next year.

Is is exciting and we thank rep sounds good progress what we have to do now is sent to complete the tongue psychology and CMC packages.

Akshay K. Vaishnaw: Thank you very much for taking the questions. Now, two quick ones, one commercially oriented and one on the R&D side. First, for Galari, we realize you're not going to provide any guidance, but I'm curious what you're seeing as far as the trajectory of start forms coming out of Q2 and going into Q3. I note that incremental start forms slowed in Q2 relative to Q1. I imagine some of this is because you've got an initial bulge of patients in Q1, and some of it is the impact from COVID that adversely impacted Q2. Just trying to get a sense of what a reasonable near-term run rate might look like between those two.

Already had good engagement with regulators and so we're looking forward to to finding them <unk> 2021.

Does that helps Vista.

Yeah very helpful. Thank you very much.

Alright, thank you.

[noise] Mmm into my next question question from having with Caffeine Goldman Sachs. Please go ahead you line is open.

Good morning, Thanks for taking my questions bearing with me yeah.

<unk> are you thinking about your upcoming looking <unk>, what would be meaningful to differentiate.

John Marganori: And then second, on the R&D side, a quick one on the ALN, APP, and IMD filing. We've certainly been watching very closely for a move to the CNS delivery, which could open up a range of very large and high-end medications. So it seems like it's taken some time. What are the gating factors on the ALN, APP, and IMD filings? What's left to be done before you can enter a human trial?

When you put for one and the treatment paradigm among people come on time.

Milwaukee.

Tissues, where you feel nice optimistic.

Great. Thank solving.

Let me, let me start and then I'm sure you can comic as well. The first question with the combo work that Regeneron is leaving with somebody Saran and because I'm I'm am I mean look there there is no.

Akshay K. Vaishnaw: Yeah, those are great questions. Let me start with the first one. Akshay, you'll get the second one just in a minute. But your question, I give it to Laurie. I mean, we're extremely pleased with the performance that we saw in Q2, even though we were going through the pandemic. And keep in mind, Vincent, that, you know, the initial forms that we saw in Q1, of course, were benefited greatly by patients that were either in the US EAP or that were known to sign sort of that initial bolus, if you will. But we do expect growth, you know, from that point onwards, you know, in the US; about 25% of our patients in the US are also coming outside of our patient hub. And therefore, you know, they're not on the start form metric, if you will. And you know, that accounts for the over 100 patients that we believe are now on, giving Laurie commercial treatment. Now, that includes a small part of the US.

Q alternative that's currently approved today. This is a this is an opportunity to having a stop to treatment for a couple of immediately diseases with a very frequent those recommend.

Even with a potential for co formulation of the two of the truth drugs, we feel very.

Very encouraged by data that that from both animal studies, but even from human studies that would suggest that combination of an already I based approach with an antibody approach would would provide very significant protection and I guess accomplish pathway with a infrequent such a desk regimen.

So I'll stop there Akshay, maybe you can comment on that but also on our extrahepatic work and where where most comfortable these days.

Yeah. So certainly you know.

And frequent presentation I I also think but we have the opportunity to.

The most complete blockade with the compliment system and hopefully the best I could see profiling now the current drugs already have good efficacy, but we'd like to see no breakthroughs for these patients in for them to be able to maintain their hemoglobin levels without meat for any transfusion Apple.

John Marganori: We're, as we said in our prepared remarks, we're now going to stop providing star four metrics for give Laurie, just like we did with our Patro last year, because we now have a global source of patients, not just the US alone. And we still have a significant number of patients that are coming outside of our patient hub. But you'll see the growth in our total patient number, quarter on quarter, for give Laurie, and we are optimistic, you know, with that growth in the US and also in other markets around the world. Now Europe, of course, has now been launched in Germany and in patient sales in many countries. So I think that we don't need to say anything more about give Laurie, do you want to actually talk about APP now? And what's the difference between now and our filing?

<unk> think complete located in the form of a combination product could also that.

Looking beyond PNA H and at the extra hypnotic pipeline.

We just touched on the C N S.

It is indeed exciting but within a year of announcing that day with your jammy Lemon CNS and Akila. We've now now that would be finally get an idea next shifts the nervous system that'd be the first of many we thing.

We have very exciting dates and you also a component as well.

And most recently of course, we shouldn't beta on lung delivery. So I I can't really say one is my favorite but.

Recurring theme for us over the years has been but when we had strong replicable data animals systems, first and rodents and many Monongahela primate.

Akshay K. Vaishnaw: Sure, yeah, I mean... [inaudible] It's about a year since we signed the deal with Regeneron. Next year is exciting, and we think represents good progress. What we have to do now is simply complete the toxicology and CMC packages. We've already had good engagement with regulators, and so we're looking forward to filing that IND in due course in mid-2021. Does that help, Spencer?

That has invariably led to translation in the human setting and so we do three compartments.

<unk> hit the clinic, we're looking forward to replicating a.

Perhaps getting the success of are working to live with evidence of miltown clinical efficacy and safety and the Brian.

Vincent Chen: Yeah, very helpful. Thank you very much. All right, thank you. And we'll now move to our next question from Salveen Richter from Goldman Sachs. Please go ahead, your line is open.

Malone et cetera, and we don't put a stop there because we have many other assets ongoing so for all the components, which we will get in due course.

John Marganori: Good morning, thanks for taking my questions. And Barry, you'll be next here. So in the context of competitive dynamics in TNH, how are you thinking about your upcoming study looking in this setting? And what would be meaningful to be differentiated here or where you could fit in, in the treatment paradigm?

So that's just a little bit on the extra hypnotic thinking.

I would just I would just and to that to that part that you know what's exciting about the CNS opportunity of course is that there are many neurodegenerative diseases that our data function protein off of fees with with genetic validation and you know we have show in human primates some exciting.

Akshay K. Vaishnaw: And then just a comment on, you know, based on your work in extrahepatic tissues, where you feel most optimistic at this point. Thanks, Salveen. Well, let me start and then, Akshay, you can comment as well on the first question about the combination work that Regeneron is leading with some D-Seran and Pazellumab. I mean, look, there is no sub-Q alternative that's currently approved today. This is an opportunity to have a sub-Q treatment for complement-mediated diseases with a very infrequent dose regimen. Even with the potential for co-formulation of the two drugs, we feel very encouraged by data from both animal studies but even from human studies that suggest that combination of an RNAi-based approach with an antibody approach would provide very significant protection against a complement pathway with an infrequent sub-Q dose regimen.

Data that we fully expect will will replicate in the human setting based on our past experiences.

And what's really key there is a durability that we see you know that is gonna be important because with interest faithfully administered drugs.

Being able to have a significant knocked out of the pathogenic protein with infrequent Doser administration is going to do something which is highly differentiated.

Not only for the a P. P program that'll be the first one to go but the Huntington program that will come shortly thereafter at programs that we're obviously dancing and diseases, like AOS, and Parkinson's and and an old timers et cetera. So this is really gonna be.

Exciting story for the company and we do expect starting at 2021 to have one to two why these per year that are coming out of that CNS archive over Janet rock pipeline together with them. So it is a exciting new frontier for the company.

Akshay K. Vaishnaw: So I'll stop there. Akshay, maybe you can comment on that, but also on our extrahepatic work and where we're most confident these days. Yeah, so certainly, you know, in Frequent Presentation. I also think that we have an opportunity.

Alright, thank you.

Thanks have a extra pickle.

[noise] Hello May I take our next question from Gina Wang from back East. Please go ahead you line is open.

Akshay K. Vaishnaw: We just touched on the CNS. It is indeed exciting that, within a year of announcing that deal with Regeneron on CNS and Ocular, we've now announced that we'll be filing an R&D application next year for the nervous system. That'll be the first of many, we think.

Thank you for taking my questions.

I'm Gonna go to working with you have many many years on my best Vicious Checkbooks journey, Alright, <unk> suddenly looking forward to working with you anymore.

Two questions here one is the on Patrick just wondering.

Sure how much you Avenue has contributed from home on it so at the truth to them when they.

John Marganori: And so with all three compartments, as these R&Ds hit the clinic, we're looking forward to replicating the success of our work in the liver with evidence of knockdown clinical efficacy and safety in the brain, in the eye, in the lung, et cetera. And we're not going to stop there. Of course, we have many other efforts ongoing for other compartments, which we will get to in due course. But I would just add to that part that, you know, what's exciting about the CNS opportunity is that there are many neurodegenerative diseases that are gain-of-function proteinopathies with genetic validation. And, you know, we have shown in non-human primates some exciting data that we fully expect we'll replicate in the human setting based on our past experiences. And what's really key there is the durability that we see.

Cool, they're going to impact on collecting up everywhere.

Great Great question, So, let's Jeff why don't you answer the first question and then Akshay you can actually Helios a question Secondly go ahead Jeff.

Yeah I heard the question correctly question was about chip Japanese contribution to on Tatro revenue in the quarter, we don't break out the detail bike by country, Gina, but but Japan was a meaningful contributor to the growth that we saw outside the U S and the quarter and we highlighted in a in a prepared remarks that Japan now has become the second large.

Just market for on Tatro on a dollar sales basis based on the cute to resolve.

And Akshay do you want a comic a little longer butchery Serein management of the study.

John Marganori: You know, that is going to be important because with intrathecally administered drugs, being able to have significant knockdown of the pathogenic protein with infrequent dose administration is going to be something that is highly differentiated, not only for the APP program that'll be the first one to go, but the Huntington's program that'll come shortly thereafter, programs that we're obviously advancing in diseases like ALS and Parkinson's and Alzheimer's, So this is really going to be an exciting story for the company. And we do expect, starting in 2021, to have one to two INDs per year that are coming out of that CNS Ocular Regeneron Pipeline together with them. So it is an exciting new frontier for the company. Great, thank you. Thanks, Salveen.

Yeah, I mean, both for victory surround surround.

Respect to.

Cardiomyopathy studies.

Maintaining studying type deals has been at the highest priority. During this code repaired and we've used a variety of approaches successfully Italian medicine with physicians and slices of pizza patients over the phone. Another means we've had home administration of drugs.

And there's of course.

The ability to take blood samples at home and finally for key visits that requiring clinic assessments, we always building a little bit of Buffalo around the timing of the business. So they're gonna have to come in exact thing I'm gonna give them. The date that can be a few days or a few weeks before or after depending on the end point. So using these different means it's not been trivial.

Jeff Poulton: Thanks, Paul. We will now take our next question from Gena Wang from Barclays. Go ahead, your line is open.

But we've sent me maintain studying tiger too.

Pleased with that and rules. So pleased with the fact that things opening up.

Akshay K. Vaishnaw: Thank you for taking my questions. It was very great working with you over the past many, many years. My best wishes for your next journey. Yvonne, I'm certainly looking forward to working with you more. I have two questions here.

<unk> seen on the commercials side, we're seeing very good pick up in the room is probably my studies.

Yeah, and I wish I would just seemed like cause I think for you to your question was also focus on Helios a.

Of course was completed Oh.

Yeah completed enrollment we're still on track for early 2021 data from that and we've obviously all the things that are actually just kind of it out of course I've been critical in terms of making sure that we've maintained did integrity and no Miss doses are minimal Miss doses. During the course of that study so that that's what it applies to Helios a.

John Marganori: One is, Patrick, just wondering if you can share how much revenue is contributed from GitHub? And then for Bichir Suran, wondering whether there is any COVID-19 impact on collecting the data? Great, great question. So let's, Jeff, why don't you answer the first question, and then Akshay, you can answer the Helios A question secondly. Go ahead, Jeff. Yeah, if I heard the question correctly, the question was about Japan's contribution to Anpatro revenue in the quarter. We don't break out the detail by country, Gina, but Japan was a meaningful contributor to the growth that we saw outside the US in the quarter.

Thank you.

Alright, Thanks Gina.

It was I moved to my next question from Alencar from medium <unk> Company. Please go ahead you line is open.

Hi, Thanks for taking my questions and.

Go ahead creation theory on this.

So you mentioned.

So my money for me interesting.

Oh that's available.

Jeff Poulton: And we highlighted in the prepared remarks that Japan has now become the second largest market for Anpatro on a dollar sales basis based on the Q2 result. And Akshay, do you want to comment a little on the Boutry Saran management of the study? Yeah, I mean, both for Vitrisran and Patisran in their respective cardiomyopathy studies, maintaining study integrity, obviously, has been the highest priority during this COVID period. And we've used a variety of approaches successfully, telemedicine, where physicians and psychiatric staff speak to patients over the phone and other means. We've had home administration of drugs, and there is, of course, the ability to take blood samples at home. And finally, for key visits that require an in-clinic assessment, we always build in a little bit of buffer around the timing of the visits so they don't have to come in exactly on a given date.

Uh-huh mansion.

Tennessee.

HM HM HM HM HM HM HM HM HM HM HM HM HM.

Great. Thanks, Allen So akshay that question was on Ayelet, HST and Nash at our plans there or do you want to comment further.

Yeah, it's Alan Weird sides of the <unk>, Cta and get going with this program we.

Alright excited about the target because it's a genetically validate your target.

And uniquely so I think in the match landscape compared to many of the other targets that'd be an address debate and most of which have fallen short Unfortunately, and Ah HST something be 13 seems to be a gateway to the later consequences of due to mention that kind of crap, so 50% milltown, because we know heterozygous lots of fun.

And can protect people from match, we thank you I'm, 50% milltown should be sufficient, but we know from our labor programs, we can do a lot better than that.

No we can achieve presence of keeps them from animal work with a trung candidate so.

Great to get this to the clinic phase one will be all about safety P. K.

Akshay K. Vaishnaw: There can be a few days or a few weeks before or after, depending on the endpoint. So using these different means, it's not been trivial, but we've certainly maintained study integrity, and we're pleased with that. And we're also pleased with the fact that, as we've seen on the commercial side, we're seeing a very good pickup in enrollment as well. Yeah, and I would just point out, because I think, Gena, your question was also focused on Helios A, which, of course, was completed. Oh, sorry.

And will collect a number of exploratory biomarkers agencies 17 be 13 itself is not a target secreted into circulation, but we have some very good excellent tree biomarkers that will help us us.

Target engagement and then from that will go into into phase two and that's where.

We'll have it there's some regiment select which I imagine move b.

Ah load those given rather than frequently given the personal with the drug were singing animals.

Once every three months for six months or so.

And that's the rule plastiki hypothesis of prevention progression preventing progression.

John Marganori: Yeah, completed enrollment. We're still on track for early 2021 data from that. And we've obviously, all the things that Akshay just commented on, of course, have been critical in terms of making sure that we maintain data integrity and no missed doses or minimal missed doses during the course of that study. So, that applies to Helios A.

To match itself.

But those details about to come from now.

Focus on the fries one.

Okay, that's N or something.

Thanks salad.

[noise] Hello May I take our next question for money through her from SBB Leerink. Please go ahead you line is open.

Thanks for taking the question congrats very involved as well.

Akshay K. Vaishnaw: Thank you. All right, thanks, Gina. We will now move to our next question from Alan Carr from Needham & Company. Please go ahead, your line is open.

Although with Bury Gonna get the bond you Gotta Gotta get much bedroom, telling me hongdong all the time about everything.

[laughter].

Right.

A quick commercial parts of our Petra obviously, there was a little bit of a decline in terms of they should've adherence, it's not surprising I know the P. P. M already I asked that's very neat because they're pharmacokinetics or the other drugs, but is there an avenue that any ketchup do thing or your station potentially getting back temporarily on an Ivy Bill can schedule.

John Marganori: Hi, thanks for taking my question. Congratulations Gary, I'll miss you. Development and Regulatory Challenges around NASH. I don't know if you can hear this, an update on their new plans and strategies on how we differentiate. Great, thanks Alan. So Akshay, that question was about ALNHSD and NASH and our plans there.

You want it could be a little more frequent.

With labor.

I you could you be capture something that lost revenue.

You think people will end up back on the labeled built in frequency.

Akshay K. Vaishnaw: Do you want to comment further? Yeah, Alan, we're excited to have filed the INDCTA and get going with this program. We are excited about the target because it's a genetically validated target, and uniquely so, I think, in the NASH landscape compared to many of the other targets that have been addressed to date, and most of which have fallen short, unfortunately. And HSD17B13 seems to be a gateway to the later consequences of the accumulation of hepatic fat. So even 50% knockdown, because we know heterozygous loss of function protects people from NASH. We think even 50% knockdown should be sufficient, but we know from our liver programs we can do a lot better than that. And we know we can achieve better than 50% from our animal work with our drug candidates, so it's great to get this to the clinic. Phase one will be all about safety, PK, and we'll collect a number of exploratory biomarkers. HSD17B13 itself is not a target that's secreted into the circulation, but we have some very good exploratory biomarkers that will help assess target engagement.

And then secondarily and I'm thinking about Syria B, Yeah, you got to talk about potential in for a friend that would look like how do you think about timing.

To make a decision on whether or not that shake that voluntary interim.

And and what time horizon, you'd be telling us hey, we're gonna be taken interim or not in terms of just giving giving us. Some some kind of when you should expect that event.

Yeah.

Those are great questions.

Maybe on the first one too many I mean, you're quite quite sure makes sense of course, but.

You know I think I think that with our expectation that patients worth stay off label and and do two three weeks ago, saying, we we have no reason to believe that that would change whatsoever.

And we've heard nothing about back in the field, so, but I think the good news is that adherence rates you know with some miss doses that occurred and cute too.

Are showing great strength is reenter Q3, and we don't expect to see any you know a significant impact like was zachary experienced during that time debit credit. So I think I think that's really behind us at this point in time and did you want to come with any further on that I I think I covered it but you might have some other perspective.

Akshay K. Vaishnaw: And then from that, we'll go into phase two, and that's where we'll have a dose from the regimen selected, which I imagine will be a low dose given rather infrequently given the profile of the drug we're seeing in animals once every three months or six months or so. And that's where we'll test the key hypothesis of preventing progression to match it. But those details will have to come. For now, you know, we have to focus on phase one. Thanks, y'all. We will now take our next question from Mani Faruhar from SCB Learinc. Please go ahead; your line is open.

No. John you you covered it right and everything we're hearing is is a resumption to be original schedule for.

For any folks who were.

Pause for whatever reason.

Yeah, and then your second question I Helios Me also also one that makes a lotta sense.

A bunch of us very specifically on Helio see we will do an interim analysis, we made the commitment to do that now we we've left it open with the agency on exactly how that will be designed and we're not we're not gonna comic yet Ah timing and I'll, just say again that one of the benefits that'd be a policy study is that as we read.

John Marganori: Thanks for taking the question and congratulations Yvonne as well. Although we're very gone, I guess you're going to have to get much better at telling me how I'm wrong all the time about everything. A quick conversion question about Alpatra.

[noise] data from that study and we'll have form.

How we should take about the interim analysis for Helio speeds, specifically Akshay do you have anything else to add to that.

John Marganori: Obviously, there was a little bit of a decline in terms of patient adherence, which is not surprising. I know that PKM RNAi assets are very unique because of pharmacokinetics or these other drugs, but is there an avenue for any catch-up dosing, any patients potentially getting back temporarily on an IV dosing schedule that could be a little more frequent than what's labeled? [inaudible] Yeah, those are great questions. You know, maybe on the first one, Manny, your question makes sense, of course, but, you know, I think I think that it's our expectation that patients would stay on label and do Q3 weekly dosing. We've, we have no reason to believe that that would change whatsoever, and we've heard nothing about it in the field.

No no nothing nothing town.

Okay. Good.

Okay. Thanks, guys.

Thank you.

[noise] Cleveland May I take our final question from laughing Jacob from UBS. Please go ahead you line is open.

Hi, everyone. Thanks for taking the question. This isn't that this is sugar.

<unk> Jacob I'm, just on on Petro Yvonne mentioned combination therapy, and previously stated that 15th.

[noise] they're on both.

It's in our bedroom can you give us an update what percentage patients on both now and can you tell us anything on the outcomes of these patients versus patients on just monotherapy.

And then just on pricing since mentioned some reduction in girls to net how shall we think about pricing trends as a year goes on thanks very much.

Okay. So.

Let me start.

Andy Orr: So, you know, but I think the good news is that adherence rates, with some of those that occurred in Q2, are showing great strength as we enter Q3. And we don't expect to see any, you know, significant impact like what we experienced during the pandemic phase. So I think that's really behind us at this point in time. Andy, do you want to comment any further on that? I think I have covered it, but you might have some other perspective.

Combo nation use a comedy you said that's occurring out there as we as we hear from the marketplace. <unk>. These are these aren't.

These are studies worth specific date or being generated we're just aware that patients that have a next phenotype, where they've got.

Polyneuropathy are receiving on <unk> and it's on places those patients are also on a few tiara stabilizer. So we're just aware of that and we have market research that says that it's somewhere in the range.

Andy Orr: No, John, you covered it, right? Everything we're hearing is a resumption of the original schedule for any folks who were paused for whatever reason. Yeah. And then your second question on Helios B, also one that makes a lot of sense, but very specifically on Helios B, we will do an interim analysis. We've made the commitment to do that now, but we've left it open with the agency on exactly how that will be designed.

15% to 30% now and if they could double by the end of the year. We we just recently published some data.

Combination use with from our previous face you with a label study and that publish paper showed that the combination was safe and the level of take care of knockdown was as good as as model therapy.

Akshay K. Vaishnaw: And we're not going to comment yet on timing. And I'll just say again that one of the benefits of the Apollo B study is that as we read out data from that study, it will inform how we should think about the interim analysis for Helios B specifically. Akshay, do you have anything else to add to that? No, no, nothing. I have nothing to add.

But there was no formal assessment of of worst there was a powered michelle or anything on the efficacy side. So I don't think anything can be concluded at this point in time quantity improved.

Activities, but did you want to comment a little bit further on dynamic how can accommodate you. So we're saying in the marketplace I'll just yeah.

Akshay K. Vaishnaw: Okay, good. Thanks, guys. Thank you. We will now take our final questions from Navin Jacob from UBS. Please go ahead, your line is open.

I'm sorry, just one thing is I want to highlight also that this is really a U S phenomenon, we don't see this and the rest of world, but and you go ahead.

Right, Yeah happy happy too so since the fourth quarter of 2019, and the U S. We've been seeing growing evidence of reimbursement for <unk>, we're used concomitantly with PPR stabilizer products, which at the end of the positive for patients with multiple manifestations of the belief.

John Marganori: Hi, everyone. Thanks for taking the question. This is a Sugar Daddy Forum for Nazeem Jacob. I've just done it on Patro.

John Marganori: Yvonne mentioned combination therapy and previously stated that 15, there, Thank you very much. Okay, so let me start on the combination use that's occurring out there as we, Here from the marketplace, these are studies where specific data are being generated. We're just aware that patients that have a mixed phenotype where they've got polyneuropathy are receiving Onpatro, and in some cases, those patients are also on a PTR stabilize

And barring any unforeseen changes do to Colgate or other we expect to concomitant used to continue to increase in the U S. Over time for patients whose disease manifestations include Polyneuropathy and is John said right outside of the U S. It's more of a switch dynamic.

Alright, and then your pricing question, Jeff do you want to handle that for yeah sure.

Andy Orr: So we're just aware of that, and we have market research that says that it's somewhere in the range of 15 to 30% now. And it could double by the end of the year. We just recently published some data on combination use from our previous phase two open-label study. And that published paper showed that the combination was safe, and the level of PTR knockdown was as good as monotherapy. But there was no formal assessment of, you know, or was it powered to show anything on the efficacy side.

Comment on on on Tatro for Q2 was the thing with a very modest increase in gross to nuts relative to Q1, which created a slight heads lemon grove quarter to quarter.

There is variability and gross and that's quarter to quarter, we've talked about that on the last several calls it's just based on the way the accounting works in the estimates and a true up about both of those estimates, but but we're very confident that the full year roast and that's from Petro will be very consistent with what we experienced in 2019 and the expectation is mid twenties.

Andy Orr: So I don't think anything can be concluded at this point in time about any improved activity. But Andy, do you want to comment a little bit further on the dynamic of concomitant use that we're seeing in the marketplace? I'm sorry, Andy. Just one thing: I want to highlight also that this is really a U.S. phenomenon. We don't see this in the rest of the world.

A year.

Great because that into your questions.

Yeah, Thanks very much.

Okay. So with that we're gonna close our call. Thank everyone for joining us on the call and again, so all of our employees for their dedication and they're they're hard work.

Andy Orr: But Andy, go ahead. Right, right. Yeah, happy, happy to. So since the fourth quarter of 2019, in the US, we've been seeing growing evidence of reimbursement for Ampatro when used concomitantly with TPR stabilizer products, which is, at the end, positive for patients with multiple manifestations of the disease. And barring any unforeseen changes due to COVID or other, we expect concomitant use to continue to increase in the U.S. over time for patients whose disease manifestations include polyneuropathy. And as John said, right outside of the U.S., it's more of a switch dynamic.

Of course, Barry we wish you all the best and your next chapter and Yvonne So excited for you and this expanded role.

So with that we look forward to updating you in future calls on our progress and please stay safe and please stay healthy.

[noise] [noise], sorry, everyone's ladies and gentlemen. This concludes today's call. Thank you for your package. The patient you may know disconnect.

[music].

John Marganori: Great. And then your pricing question, Jeff. Do you want to handle that? Yeah, sure. The comment on Patro for Q2 was that there was a very modest increase in gross to nets relative to Q1, which created a slight headwind for growth quarter to quarter. Now, there is variability in gross to nets from quarter to quarter. We've talked about that on the last several calls. It's just based on the way the accounting works and the estimates and the true up of those estimates.

Andy Orr: But we're very confident that the full year gross to nets from Patro will be very consistent with what we experienced in 2019, and the expectation is mid 20s for the year. Does that answer your question? Yeah, thanks very much. Good. Okay.

John Marganori: So with that, we're going to close our call. Thank everyone for joining us on the call. And again, to all of our employees for their dedication and their hard work. Of course, Barry, we wish you all the best in your next chapter. And Yvonne, so excited for you in this expanded role at Al-Madalim. So with that, we look forward to updating you in future calls on our progress. And please stay safe and please stay healthy. Bye bye now. Ladies and gentlemen, this concludes today's call. Thank you for your participation. You may now disconnect. Thanks for watching! ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? Tazeen Ahmad, Paul Matteis, Ritu Baral, David Lebowitz, Jessica Fye, Salveen Richter, Gena Wang, Maurice Raycroft, Leland Gershell, Myles Minter, Eric Green, Joseph Stringer, Eliana Merle, Simon Fox, Ellie Merle, Tommy Reerink, Karen O, Rhian Touyz, Alnylam Pharmaceuticals Inc