Alnylam Pharmaceuticals, Inc. (ALNY) Q4 2022 Earnings Call Transcript

Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY) Q4 2022 Earnings Conference Call February 23, 2023 8:30 AM ET

Company Participants

Christine Lindenboom - Senior Vice President, Investor Relations and Corporate Communications

Yvonne Greenstreet - Chief Executive Officer

Tolga Tanguler - Chief Commercial Officer

Pushkal Garg - Chief Medical Officer

Jeff Poulton - Chief Financial Officer

Conference Call Participants

Ritu Baral - Cowen

David Lebowitz - Citi

Tazeen Ahmad - Bank of America Securities

Maury Raycroft - Jefferies

Paul Matteis - Stifel

Gena Wang - Barclays

Luca Issi - RBC

Myles Minter - William Blair

Eliana Merle - UBS

Operator

Thank you for opinionated by and invited to nan Alnylam Pharmaceuticals Fourth Quarter 2022 Financial Results Conference Call. As a reminder today's convention telephone is being recorded.

I would now for illustration to move nan convention complete to nan company. Please spell ahead.

Christine Lindenboom

Good morning. I americium Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications astatine Alnylam. With maine coming connected nan telephone are Yvonne Greenstreet, Chief Executive Officer; Tolga Tanguler, Chief Commercial Officer; Pushkal Garg, Chief Medical Officer; and Jeff Poulton, Chief Financial Officer. For those of you participating via convention call, nan accompanying slides tin beryllium accessed by going to nan Events conception of nan Investors page of our website, investors.alnylam.com/events.

During today’s call, arsenic outlined connected Slide 2, Yvonne will supply introductory remarks and wide context. Tolga will supply an update connected our world commercialized progress. Pushkal will reappraisal pipeline updates and objective progress, and Jeff will reappraisal our financials and guidance, followed by a summary of upcoming milestones earlier we unfastened nan telephone to your questions.

I’d for illustration to punctual you that this telephone will incorporate remarks concerning Alnylam’s early expectations, plans, and prospects, which represent forward-looking statements for nan purposes of nan Safe Harbor proviso nether nan Private Securities Litigation Reform Act of 1995. Actual results whitethorn disagree materially from those indicated by these forward-looking statements arsenic a consequence of various important factors, including those discussed successful our astir caller periodic study connected record pinch nan SEC. In addition, immoderate forward-looking statements correspond our views only arsenic nan date of this reporting and should not beryllium relied upon arsenic representing our views arsenic of immoderate consequent date. We specifically disclaim immoderate responsibility to update specified statements.

With that, I’d for illustration to move nan telephone complete to Yvonne. Yvonne?

Yvonne Greenstreet

Thanks, Christine, and convey you everyone for joining nan telephone today. 2022 was an fantabulous twelvemonth astatine Alnylam wherever we delivered awesome commercialized capacity and made important advancements crossed our wide pipeline of RNAi therapeutics. Commercially, arsenic preannounced successful January, we achieved afloat twelvemonth 2022 nett merchandise revenues of $894 cardinal which represents year-over-year maturation of 35% aliases 43% pinch changeless speech rates and 13% maturation betwixt nan 3rd and 4th quarters.

A tailwind to nan occurrence was nan support and motorboat of AMVUTTRA successful nan U.S., Germany, and Japan for hereditary hATTR amyloidosis patients pinch polyneuropathy wherever accelerated uptake among physicians and diligent reflects an charismatic merchandise profile. With our pipeline, notable advancement during nan twelvemonth included nan breathtaking results for APOLLO-B, our Phase 3 study of patisiran ATTR amyloidosis patients pinch cardiomyopathy. The sNDA based connected these results has been accepted pinch a PDUFA day of October nan 8th. And we look guardant to nan FDA's reappraisal and imaginable support later this year. Pushkal will supply much colour connected this later successful nan call.

Among our earlier programs, a item for nan twelvemonth was nan initiation of nan first-in-human study of RNAi therapeutic successful nan CNS pinch ALN-APP for Alzheimer's disease. We besides completed 3 CTA filings advancing to nan session promising programs specified arsenic ALN-KHK for type 2 diabetes, ALN-PNP for NASH and ALN-TTRsc04 for ATTR amyloidosis and we are announcing coming nan dosing has started successful a Phase 1 study pinch this program.

Looking guardant to nan remainder of 2023, we are excited for 7 important pipeline milestones, including 10 objective readouts from Alnylam and partner led programs, specified arsenic Phase 1 results from nan aforementioned ALN-APP study and Phase 2 results from nan KARDIA hypertension studies of zilebesiran. This execution is successful statement pinch our attraction connected nan pursuing cardinal drivers for Alnylam's group complete nan adjacent respective years.

First, is nan imaginable near-term description of our ATTR franchise opportunity wherever we purpose to go a world leader successful delivering impactful and highly differentiated medicines to patients. Second, is our description beyond uncommon diseases to besides reside much communal illness areas. And nan 3rd maturation driver for nan institution comes from our sustainable invention motor comprised of caller level enhancements, opportunities of extrahepatic transportation and our expertise to find caller genetically validated targets which tin thrust further pipeline description to 2025 and beyond.

We judge each of this positions america good to present connected our Alnylam P5x25 goals making Alnylam a apical tier biotech, processing and commercializing transformative medicines for uncommon diseases and beyond for patients astir nan world driven by a precocious yielding pipeline of firsts and/or best-in-class merchandise candidates from our integrated products motor each while delivering exceptional financial results.

With that, fto maine now move nan telephone complete to Tolga for a reappraisal of our commercialized performance. Tolga?

Tolga Tanguler

Thanks Yvonne and bully greeting everyone. Our commercialized operations had a beardown adjacent to 2022 delivering $262 cardinal successful mixed nett merchandise income successful Q4, which represented 13% maturation compared pinch Q3 2022. The beardown maturation was driven by an summation successful patients connected commercialized therapy crossed some our TTR and besides uncommon franchises. We stay peculiarly encouraged by respective signs indicating that nan ongoing motorboat of AMVUTTRA for ATTR amyloidosis patients pinch polyneuropathy some successful nan U.S. and now besides successful Germany and Japan, is expanding nan size of nan opportunity for our TTR franchise.

Now I will move to our circumstantial results starting pinch our TTR franchise. We saw robust maturation successful our TTR franchise successful Q4 achieving $191 cardinal successful world nett merchandise revenues for ONPATTRO and AMVUTTRA representing a 12% summation compared pinch nan first 4th and a coagulated 38% maturation compared pinch Q4 2021.

The year-over-year maturation successful Q4 was driven by nan spot of nan AMVUTTRA motorboat successful nan U.S. pinch nan U.S. marketplace delivering an awesome 72% maturation compared pinch Q4 2021. At nan extremity of 2022, complete 2,975 patients were connected commercialized ONPATTRO aliases AMVUTTRA curen worldwide, an summation of astir 400 patients from nan extremity of Q3, which represents a doubling of nan quarterly inclination that existed anterior to nan motorboat of AMVUTTRA, a clear awesome of accelerating TTR franchise growth.

In nan U.S. mixed income of ONPATTRO and AMVUTTRA accrued 12% versus nan 3rd 4th and were chiefly impacted by nan following. A robust 19% summation successful request growth, which was driven by nan spot of nan AMVUTTRA diligent uptake, which is being driven some by switches from ONPATTRO and much importantly from increases successful patients caller to therapy. ONPATTRO inventory destocking successful nan transmission during nan 4th fourth reduced reported TTR maturation by astir 5%. This was anticipated arsenic request for ONPATTRO successful nan U.S. continues to alteration arsenic much patients switched to AMVUTTRA.

In our world markets, mixed income of ONPATTRO and AMVUTTRA besides accrued 12% versus Q3 2022, chiefly driven by nan occurrence of first world AMVUTTRA launches successful Germany and Japan pinch maturation favorably impacted some by accrued diligent request and first motorboat stocking. Finally, our world results continued to beryllium challenged by overseas speech headwinds pinch full TTR year-over-year reported maturation of 38% deflected nan overseas speech effect of 10 percent points owed to nan strengthening U.S. dollar.

Now I would for illustration to supply you pinch immoderate further colour connected our ongoing AMVUTTRA U.S. motorboat advancement arsenic good arsenic an update connected first world launches successful Germany and Japan. In nan U.S., we've received much than 750 AMVUTTRA commencement forms successful nan six positive months since motorboat pinch much than 50% of nan commencement forms representing caller patients and nan equilibrium representing switches from ONPATTRO.

Consistent pinch what we shared astatine Q3, nan monthly mean of caller therapy AMVUTTRA commencement forms remains astatine 60 per month, which is double nan complaint of ONPATTRO caller to therapy commencement forms that we were receiving anterior to nan motorboat of AMVUTTRA. Furthermore successful nan U.S. our request procreation has been patient and balanced betwixt organization accounts and centers of excellence and we person and we person seen an astir 30% summation successful our prescriber guidelines since launch, a clear awesome that AMVUTTRA is expanding nan opportunity for our TTR franchise.

Additionally, our diligent guidelines has broadened to see a assortment of recently and antecedently diagnosed patients starting connected AMVUTTRA pinch important enthusiasm being expressed for AMVUTTRA's merchandise floor plan including quarterly subcutaneous dozing. Meanwhile, connected nan entree front, fixed our parity motorboat pricing, we person not faced immoderate important entree headwinds. We've besides made important advancement pinch formulary approvals supporting soft entree to patients that are prescribed AMVUTTRA.

In our world markets nan first launches of AMVUTTRA successful Germany and Japan successful Q4 knowledgeable robust demands pinch caller diligent starts coming from some switches from ONPATTRO arsenic good arsenic caller to therapy patients that were accordant pinch what we knowledgeable successful nan U.S. successful our first motorboat quarters. The caller to therapy patients included a patient operation of naive to therapy and switches from nan title and ONPATTRO. Our adjacent anticipated world motorboat is expected successful nan UK successful precocious Q1 2023. To wrap up pinch AMVUTTRA, we are pleased pinch our first motorboat advancement and are encouraged by nan early signs that were expanding nan marketplace opportunity for our TTR franchise.

Moving to our ultra-rare illness franchise, first GIVLAARI, we achieved $47 cardinal successful world nett merchandise revenues successful 4th fourth representing a 3% summation compared pinch Q3 2022 and 16% maturation versus Q4 2021. At nan extremity of 2022, complete 520 patients were connected commercialized GIVLAARI treatments worldwide, up from complete 460 astatine nan extremity of nan 3rd 4th representing 13% quarterly diligent growth.

The reported 16% summation successful year-over-year world nett merchandise gross maturation of GIVLAARI reflected a overseas speech effect of 6 percent points owed to nan strengthening U.S. dollar. In nan U.S. income of GIVLAARI were level versus nan 3rd quarter, chiefly owed to nan request maturation of 3% driven by an summation successful patients connected therapy, which was offset by changes successful inventory stocking during nan quarter. In our world markets, GIVLAARI income accrued 10% compared pinch nan 3rd quarter, chiefly owed to nan maturation successful patients connected therapy and nan timing of orders successful partner markets.

Moving now to our 2nd ultra-rare illness merchandise OXLUMO. We achieved $24 cardinal successful world nett merchandise revenues successful nan 4th fourth representing a 45% summation compared pinch nan 3rd quarter. At nan extremity of 2022 complete 280 patients were connected commercialized OXLUMO curen worldwide, up from complete 230 astatine nan extremity of nan 3rd quarter, representing 22% quarterly diligent growth. In nan U.S. income of OXLUMO accrued 38% versus nan 3rd 4th owed to a maturation successful patients connected therapy and an summation successful mean diligent utilization during nan 4th driven by much patients connected nan monthly loading dose information of their first treatments.

In our world business income of OXLUMO accrued 50% compared pinch nan 3rd 4th owed to an summation successful patients connected therapy and owed to nan timing of orders successful partner markets. Additionally, arsenic pinch ONPATTRO and GIVLAARI, changes successful overseas speech rates besides negatively impacted OXLUMO Q4 2022 results pinch reported year-over-year maturation of 24% reflected a overseas speech effect of 9 percent points owed to nan strengthening U.S. dollar.

In conclusion, we are pleased pinch nan maturation successful revenues and diligent request achieved successful Q4 and peculiarly pinch our early signs of beardown capacity associated pinch nan AMVUTTRA launch, which we judge represents an important therapy action for hATTR amyloidosis patients pinch polyneuropathy and an accelerated maturation opportunity for our TTR franchise.

With that, I will now move it complete to Pushkal to reappraisal our caller R&D and pipeline progress. Pushkal?

Pushkal Garg

Thanks Tolga, and bully greeting everyone. Let maine statesman by updating you connected our efforts successful ATTR amyloidosis, wherever we are advancing 3 objective shape merchandise candidates, patisiran, vutrisiran, and arsenic I'll update successful a moment, TTRsc04. First, arsenic you've heard from Yvonne, we are delighted that our supplemental caller supplier exertion for patisiran for nan cardiomyopathy of ATTR amyloidosis has been accepted by nan FDA pinch a modular reappraisal and a PDUFA day of October 8th.

In their record acceptance letter, nan FDA stated that they person not identified immoderate reappraisal issues. The agency besides noted that they are readying to clasp an advisory committee gathering to talk nan application. If approved, this will let america to widen nan imaginable benefits of an RNAi therapeutic to nan galore patients pinch chaotic type and hereditary ATTR amyloidosis pinch cardiomyopathy. This filing is based connected nan pivotal APOLLO-B study, which demonstrated improved functional position and value of life successful patients pinch ATTR cardiomyopathy fixed patisiran for 12 months comparative to placebo.

The efficacy is besides supported by an encouraging information floor plan and exploratory information indicating that patisiran curen tin favorably effect illness progression. With nan sNDA now accepted, I'd besides for illustration to stock immoderate specifications connected our world filing plans for patisiran successful ATTR amyloidosis pinch cardiomyopathy. We are readying to taxable an sNDA successful Brazil successful early 2023. However, we do not scheme to prosecute explanation description successful different regions. This is simply a consequence of nan earlier than anticipated enrollment completion of nan vutrisiran and HELIOS-B study mixed pinch nan timelines for regulatory support and obtaining marketplace entree successful these countries. As a result, we will attraction our efforts successful different regions to submitting an sNDA for vutrisiran assuming affirmative results from nan ongoing HELIOS-B study.

As a reminder, HELIOS-B is studying a akin organization arsenic APOLLO-B, but is designed for a superior outcomes endpoint of all-cause mortality and recurrent CV events. We stay connected way to stock apical statement results successful early 2024. As you know, we person been evaluating a biannual dosing regimen of vutrisiran arsenic portion of nan HELIOS-A randomized curen hold aliases RTE, which was performed aft nan main information of nan study had completed. Our nonsubjective has been to spot if we tin supply a much convenient dosing regimen versus nan already fantabulous floor plan of nan 25 mg each 3 months regimen pinch maintained efficacy.

The superior endpoint of nan RTE was non-inferiority of TTR lowering pinch nan 50 mg biannual regimen versus nan 25 mg quarterly regimen arsenic good arsenic an acceptable information profile. Today we are reporting apical statement results of nan randomized curen hold done period nine. As expected non-inferiority of nan 50 mg biannual dosing regimen was so established arsenic demonstrated by mean serum TTR simplification complete 9 months. However, we did statement immoderate betterment of serum TTR simplification successful nan 50 mg limb towards nan very extremity of nan dosing interval astatine six months.

To exemplify this, astatine period six, 80% of patients connected nan 25 mg quarterly regimen achieved 80% knockdown aliases greater, whereas connected nan 50 mg biannual regimen, 63% of patients achieved that aforesaid grade of knockdown. In different words, 37% of patients did not get to 80% TTR knockdown pinch nan biannual regimen. Vutrisiran besides continued to show an acceptable information profile. No information signals regarding cardiac, hepatic aliases renal events were observed.

In nan RTE study location were six deaths of which 5 occurred connected nan 50 mg biennial limb and 1 occurred connected nan 25 mg quarterly arm, aft nan diligent dropped retired of nan study. None was considered related to nan study supplier and nan mostly occurred successful patients pinch notable preexisting cardiomyopathy astatine baseline successful nan discourse of known fierce mutations.

We're readying to coming much specifications connected these results successful a technological legislature successful early 2023. Despite nan supportive efficacy information and information information from nan RTE, we've made nan strategical determination not to move guardant pinch regulatory submissions for nan 50 mg biannual dosing regimen of vutrisiran arsenic antecedently planned. Several factors played into that decision.

First, nan dynamics of serum TTR betterment observed towards nan very extremity of nan biannual dosing interval, which we judge is suboptimal successful position of a merchandise floor plan wherever we spot clamped medicine science successful bid to execute maximal efficacy for patients. Second, arsenic you heard from Tolga, nan very beardown first commercialized capacity of AMVUTTRA successful its first 2 quarters connected nan market, fixed its compelling therapeutic floor plan pinch quarterly subcutaneous dosing, on pinch nan highly affirmative feedback it has received from patients and physicians, allows america to workout greater selectivity successful advancing an innovative offering.

And finally, we now person a caller molecule targeting TTR, TTRsc04 which I'm proud to denote that it has entered nan session and begun dosing successful a Phase 1 study. ALN-TTRsc04 is an investigational RNAi therapeutic based connected our IKARIA Platform and offers nan imaginable for much durable and potent TTR silencing pinch nan anticipation for yearly dosing. As such, we will attraction our continued invention connected advancing TTRsc04, which whitethorn connection a transformative profile. We expect apical statement results from nan Phase 1 study successful precocious 2023.

In summation to our precocious shape objective programs, we judge we person besides been making awesome advancement pinch our early and mid-stage programs. A notable item includes zilebesiran, our investigational RNAi therapeutic for hypertension which we judge could toggle shape nan curen of this illness and connection a highly differentiated floor plan from each existing antihypertensives including RAS inhibitors. We're thrilled to person announced that our KARDIA-1 Phase 2 study was afloat enrolled arsenic of December and connected way to present apical statement results successful mid-2023. We besides look guardant to KARDIA-2 apical statement results astatine aliases astir twelvemonth extremity 2023.

We're besides moving to grow transportation of RNAi therapeutics to tissues beyond nan liver. To that end, we are connected nan cusp of seeing important information from ALN-APP, which is our first investigational RNAi therapeutic directed to nan CNS, and successful improvement for nan curen of Alzheimer's illness and cerebral amyloid angiopathy. ALN-APP has nan imaginable to connection a highly differentiated attack successful Alzheimer's illness by targeting APP upstream of wherever antibodies presently target and has nan imaginable to enactment some intracellularly and extracellularly to trim disease-causing peptides.

We judge these first objective information pinch ALN-APP if affirmative will beryllium an important milestone, not conscionable for this peculiar program, but for our wide CNS level to show that RNAi tin execute clinically applicable degrees of target knockdown successful nan CNS pinch a information and dosing floor plan that supports further development. We stay connected way to study apical statement results from nan Phase 1 study successful early 2023.

These are conscionable a fewer highlights from our wide and innovative pipeline, driven by our underlying integrated merchandise motor that we expect will present sustainable invention and represents a cardinal maturation driver for Alnylam successful nan years to come. To wrap up these highlights, we're excited to person submitted a CTA filing for ALN-KHK successful type 2 glucosuria pinch a Phase 1 commencement expected imminently. In addition, our partners astatine Regeneron person begun dosing successful a Phase 1 proceedings of ALN-PNP successful NASH.

With that, fto maine now move it complete to Jeff to reappraisal our financial results and upcoming milestones. Jeff?

Jeff Poulton

Thanks Pushkal, and bully greeting everyone. I'm pleased to beryllium presenting Alnylam's Q4 successful afloat twelvemonth 2022 financial results, which underscore Alnylam's beardown commercialized capabilities and operational excellence. After commenting connected our 4th fourth and afloat twelvemonth results, I will besides supply our financial guidance for 2023.

Turning now to a summary of our afloat P&L results for nan 4th fourth and afloat year, full merchandise revenues for 2022 were $894 cardinal aliases 35% maturation versus 2021 aliases 43% connected a changeless speech complaint ground pinch maturation contributions from each 4 commercialized products. Net gross from collaborations for nan 4th fourth was astir $71 million, representing an 18% summation compared pinch Q4 2021, chiefly owed to accrued gross from our collaboration pinch Regeneron from accrued manufacturing activities successful nan quarter.

For nan afloat year, nett gross from collaborations was $135 million, representing a 25% alteration compared pinch 2021 chiefly owed to a alteration successful gross recognized successful relationship pinch our collaboration agreements pinch Regeneron and Vir, attributed to reduced investigation and manufacturing activities and timing of reimbursable activities. Our non-GAAP R&D expenses accrued 16% successful nan 4th fourth 2022 compared to nan aforesaid play successful nan anterior year, chiefly owed to increases successful headcount to support our R&D pipeline and improvement expenses associated pinch nan KARDIA-1 and KARDIA-2 zilebesiran Phase 2 studies.

Our non-GAAP SG&A expenses accrued 15% successful nan 4th fourth of 2022 compared to nan aforesaid play successful nan anterior year, chiefly owed to accrued headcount and different investments successful support of nan world motorboat of AMVUTTRA and different firm expenses to support nan scaling of our business. Our mixed non-GAAP R&D and SG&A expenses were astir $1.4 cardinal for nan afloat twelvemonth 2022, representing 14% maturation versus 2021 arsenic we proceed to beforehand our pipeline and present beardown apical statement maturation while maintaining subject and really we put successful our operations.

Our non-GAAP operating nonaccomplishment for 2022 was $554 cardinal aliases astir level versus 2021. We do expect reducing our non-GAAP operating nonaccomplishment successful 2023 arsenic you will perceive erstwhile I supply our 2023 financial guidance arsenic we stay focused connected achieving a self-sustainable financial floor plan by 2025, aligned pinch our P5x25 25 goals.

Finally, we ended nan twelvemonth pinch cash, rate equivalents and marketable securities of $2.2 cardinal compared to $2.4 cardinal astatine nan extremity of 2021 pinch nan alteration chiefly owed to our operating nonaccomplishment successful 2022, which was partially offset by astir $265 cardinal received from worker action grant exercises and astir $135 cardinal from our convertible indebtedness financing. We proceed to judge that our existent rate equilibrium will span america to financial self-sustainability, an enviable position successful today's marketplace environment.

Now turning to our financial guidance for 2023, starting pinch nett merchandise revenues, we are providing mixed nett merchandise gross guidance from ONPATTRO, GIVLAARI, OXLUMO, and AMVUTTRA. Our guidance assumes nan sNDA for patisiran for ATTR amyloidosis pinch cardiomyopathy successful nan U.S. will beryllium approved by nan PDUFA day connected October 8th, 2023, and besides assumes overseas speech rates arsenic of December 31, 2022.

We expect mixed nett merchandise revenues for these 4 products will beryllium betwixt $1.2 cardinal and $1.285 cardinal pinch nan projected study maturation scope versus 2022 of 34% to 44%. As you tin see, we are besides providing changeless speech complaint maturation guidance for our nett merchandise revenues this twelvemonth pinch a projected scope of 34% to 44%, highlighting nary existent quality betwixt our reported and changeless speech complaint maturation guidance.

Our guidance for nett gross from collaborations and royalties is simply a scope betwixt $100 cardinal and $175 cardinal pinch nan midpoint of nan scope of astir level versus 2022. We expect nan collaboration gross associated pinch our business pinch Regeneron and Leqvio royalties from Novartis will thrust nan mostly of our collaboration and royalty gross successful 2023. Our guidance for mixed non-GAAP R&D and SG&A expenses is simply a scope betwixt $1.575 cardinal and $1.65 billion. The midpoint of nan guidance scope represents a projected 13% summation compared pinch 2022.

Growth highlights for R&D disbursal successful 2023 see accrued finance successful zilebesiran arsenic we advancement nan KARDIA-1 and KARDIA-2 Phase 2 studies, first finance successful TTRsc04, arsenic good arsenic maturation successful pre-DC and IND enabling efforts crossed our preclinical portfolio arsenic we proceed to put successful creating caller integrated maturation opportunities for nan future. Growth Highlights for SG&A disbursal successful 2023 see accrued aesculapian and commercialized finance arsenic we hole for nan imaginable motorboat of patisiran successful nan U.S. for ATTR amyloidosis pinch cardiomyopathy.

Let maine now move from financials and talk immoderate cardinal goals and upcoming milestones slated for early 2023. We will, of course, beryllium executing connected nan world commercialization of our products connected ONPATTRO, AMVUTTRA, GIVLAARI and OXLUMO. We expect to complete enrollment successful nan KARDIA-2 Phase 2 studies of zilebesiran, topline results from our Phase 1 study of ALN-APP successful patients pinch early onset Alzheimer's illness is connected way for early 2023 pinch our partner programme Vir expects further results from Phase 2 operation tests of ALN-HBV02, and Regeneron plans to initiate a Phase 2 study of ALN-HSD successful patients pinch NASH.

Let maine now move it backmost to Christine and coordinate our Q&A session. Christine?

Christine Lindenboom

Thank you, Jeff. Operator, we will now unfastened nan telephone for your questions. To those dialed in, we would for illustration to inquire you to limit yourself to 1 mobility each and past get backmost successful nan queue if you person further questions.

Question-and-Answer Session

Operator

[Operator Instructions] Our first mobility comes from nan statement of Ritu Baral from Cowen. Your statement is now open.

Ritu Baral

Good greeting everyone. Thanks for taking nan question. Yvonne, I wanted to inquire astir conscionable nan imaginable topics of nan advisory committee meeting. What do you deliberation astatine this point, what is Alnylam readying connected addressing during nan Advisory Committee meeting? If nary review, I'm sorry, nary reappraisal issues person yet been identified successful nan connection are location points during nan sNDA reappraisal that by rule relationship is required betwixt nan sponsor and nan regulator to thief you suss that out? Thanks.

Yvonne Greenstreet

Ritu, convey you very overmuch for that question. I mean, arsenic you know, we were very pleased pinch nan results from nan APOLLO-B study and please that nan FDA accepted our application. And arsenic you constituent out, did not place immoderate reappraisal issues to date. You know, whether you person an ADCOM [ph] aliases not is wholly up to nan FDA. We person nary denotation astatine this constituent successful clip pinch respect to immoderate circumstantial areas to reside arsenic immoderate imaginable advisory committee. But we look guardant to engaging pinch nan FDA done this process and sharing our data. Beyond that there's not a batch other we tin opportunity astatine this constituent successful time.

Ritu Baral

So nary ineligible interactions required for nan sNDA process successful nan adjacent early pinch you guys?

Yvonne Greenstreet

Well, we will get accusation arsenic to much specifications astir nan advisory committee existent points successful time, but astatine this shape we person nary further accusation that we tin provide. I mean, nan only update that we are required to supply nan FDA is nan 120-day information update.

Ritu Baral

Got it. Thank you.

Yvonne Greenstreet

Next question?

Operator

One infinitesimal for nan adjacent question. And your adjacent mobility comes from nan statement of David Lebowitz from Citi. Your statement is now open.

David Lebowitz

Thank you very overmuch for taking my question. With respect to nan six-month dosing of AMVUTTRA, I'm falling short and being discontinued. What learnings are you taking from that to nan IKARIA programme and is it changing your strategy pinch respect to really you're looking astatine that peculiar therapy? And past conscionable a small tag on, do you deliberation that nan deficiency of nan biannual dose substantially changes thing for nan AMVUTTRA's prospects?

Yvonne Greenstreet

Right, truthful I'll commencement disconnected and past induce Pushkal to contribute. I deliberation really nan first point to opportunity is that nan quarterly regimen of AMVUTTRA has really been a crippled changer for patients pinch TTR Polyneuropathy, and we are really pleased pinch nan profile. You've heard from Tolga earlier, you cognize really good nan motorboat is going. So really nan determination to not move guardant pinch a six monthly regimen was a strategical one. We want to beryllium capable to attraction connected nan quarterly AMVUTTRA regimen successful nan near-term.

And past arsenic you've heard, and you've touched connected this, progressed TTRsc04 based connected our IKARIA platform, wherever we judge there's a existent imaginable for knockdown, TTR knockdown of adjacent to 90% and perchance yearly dosing arsenic well, which we deliberation is past a existent measurement guardant for patients. I mean, Pushkal immoderate commentary connected the, you know, learnings? I suppose what we've learned is you know, much astir nan floor plan of nan six monthly regimen. Anything other to add?

Pushkal Garg

Yes, no, I deliberation nan only point that I would adhd to what you said, Yvonne is, I mean, a it's reaffirmed nan potency and nan powerfulness of nan 25 mg quarterly regimen wherever we saw fantabulous clamped medicine science pinch nan quarterly dosing that reaffirms nan floor plan that we saw connected nan original HELIOS-A study. And I deliberation Dave, to your different point, I deliberation and arsenic Yvonne highlighted, we're really excited that TTRsc04 is now successful nan session and we will get information soon later this twelvemonth astir what that's looking for illustration successful nan Phase 1 study. And we're optimistic based connected nan preclinical information and nan powerfulness of nan IKARIA level that we will spot much potent and much durable knockdown and enabling a imaginable yearly dosing regimen pinch that. So I think, we're really successful a fortunate position that our investigation motor has been capable to bring guardant this sc04 molecule that we tin bring into nan clinic. It allows america to advancement invention for these patients.

Yvonne Greenstreet

Thanks. Thanks Pushkal. May I person nan adjacent question?

Operator

One infinitesimal for nan adjacent question. Your adjacent mobility comes from nan statement of Tazeen Ahmad from Bank of America. Your statement is now open.

Tazeen Ahmad

Hi, bully morning. Thanks for taking my question. Mine is connected APP for nan expected apical statement that's owed successful nan opening of this year, tin you conscionable springiness america immoderate colour connected what information precisely you're readying connected presenting and really we should construe that data? What would beryllium clinically meaningful? And do you besides scheme connected presenting immoderate plaque [ph] clearance information pinch that apical line? Thanks.

Yvonne Greenstreet

We didn’t really benignant of perceive each of nan questions. Do you mind possibly repeating it and possibly focusing connected conscionable 1 question?

Tazeen Ahmad

Yes. The mobility is connected what you're going to coming astatine nan apical line? What should we see successful that presumption of what you're going to beryllium presenting? So would you beryllium [indiscernible]

Yvonne Greenstreet

Fine, that's really clear, truthful apical line…

Tazeen Ahmad

Yeah.

Yvonne Greenstreet

Topline information from nan ALN-APP study. Pushkal?

Pushkal Garg

Yeah. Thanks, Tazeen. So, yes, we're really excited astir nan ALN-APP program. It's our first foray into nan CNS. We're still connected way to person apical statement information successful nan first half of this year. As a reminder, this is simply a study successful patients pinch early onset Alzheimer's disease. We're successful nan azygous ascending dose shape of that study. And what we are hoping to study retired connected will beryllium information and tolerability, which is nan superior endpoint. This is nan first clip we're giving intrathecal injection pinch nan C16 conjugate, and past looking for target engagement, a knockdown of soluble APP alpha and beta. So we person very bully pharmacodynamic markers that tin constituent to target engagement. And we will want to spot grounds of target engagement location that we're seeing bully medicine science successful nan brain. So those are really nan cardinal things that we'll beryllium reporting connected later successful nan first half of nan year.

Yvonne Greenstreet

Thanks Pushkal. Next question?

Operator

One infinitesimal for nan adjacent question. And your adjacent mobility comes done nan statement of Salveen Richter from Goldman Sachs. Your statement is now open.

Unidentified Analyst

Hi, this is Tommy connected for Salveen. Thanks truthful overmuch for taking our questions. For HELIOS-B tin you punctual america of nan rationale down utilizing all-cause mortality alternatively of cardiovascular mortality successful nan composite superior endpoint? And is location 1 that's preferred by physicians and regulators? Thank you.

Yvonne Greenstreet

Thanks. And I conjecture that's a mobility consecutive for you, Pushkal.

Pushkal Garg

Yeah. So Salveen I deliberation erstwhile we, you know, erstwhile we look at, erstwhile we designed nan HELIOS-B study, we really want to yet show nan use of nan supplier connected nan totality of nan acquisition of patients pinch this disease. And an all-cause mortality and recurrent CV arena endpoint really captures, maximizes nan number of events that we tin seizure successful nan people of nan study which immunodeficiency successful nan powering of nan study and besides becomes a very clinically meaningful effect. Certainly location tin beryllium analyses that are looked astatine nether that arsenic secondaries aliases station hocs that look astatine nan various types of mortality events. But that's nan basal explanation.

Yvonne Greenstreet

Next question?

Operator

One infinitesimal for nan adjacent question. The adjacent mobility comes from nan statement of Maury Raycroft from Jefferies. Your statement is now open.

Maury Raycroft

Hi, bully morning. Thanks for taking my question. I was wondering if you person a tentative day scheduled for nan adcom and you've mentioned adding nan 120-day information information from APOLLO-B unfastened explanation extension, but I'm wondering if you tin talk imaginable scenarios wherever you whitethorn beryllium capable to supplement nan sNDA pinch further efficacy aliases information information from APOLLO-B, unfastened explanation hold and aliases nan HELIOS-B study.

Pushkal Garg

Yes, truthful Maury, possibly a mates questions successful there. You know, we don't person a general day yet. That's thing again, we've released what we understand astatine nan infinitesimal from nan agency's correspondence pinch us. So we'll look guardant to getting further accusation connected that. And successful position of nan 18-month data, look we're successful nan process of getting and reviewing nan APOLLO-B unfastened explanation hold data. As a reminder, everybody crosses complete to progressive supplier astatine month-12. And we'll surely stock those information astatine an due technological meeting. And pinch respect to nan agency, we'll beryllium supplying immoderate they request to facilitate their review. And so, we're looking guardant to sharing things, nan information pinch them, some from nan main study and arsenic they request from nan unfastened explanation extension. The time 120 information update is chiefly focused connected information update data, truthful that will besides beryllium a parallel process.

Maury Raycroft

Understood. Okay, acknowledgment for taking my question.

Pushkal Garg

Sure.

Operator

And 1 infinitesimal for nan adjacent question. Your adjacent mobility comes from nan statement of Paul Matteis pinch Stifel. Your statement is now open.

Paul Matteis

Hey, acknowledgment truthful overmuch for taking my mobility and congrats connected nan progress. I was, I thought it was really absorbing that you included imaginable income from ONPATTRO successful TTR cardiomyopathy successful guidance, fixed that it's nether review, fixed that location is an adcom, and I conjecture is it nan correct mentation of that decision, that nan institution continues to person very precocious condemnation that nan APOLLO-B information should lead to an approval, and that was capable for you to scheme financially and guideline astir that? Thank you.

Yvonne Greenstreet

Yes, well, I mean, I'll commencement and past manus it complete to Jeff successful position of really we thought astir planning. I mean, clearly, we do judge that nan APOLLO-B study has delivered really very impactful results, some successful position of wellness position and illness progress. We've talked astir nan efficacy endpoints successful immoderate detail. And intelligibly we are readying for nan advisory committee arsenic notified by nan FDA. And evidently you know, we will person to await nan FDA's determination connected our submission. But you know, we judge that we person an efficacy and information package present that is beautiful compelling. Jeff, do you want to speak a small spot to really we thought astir ONPATTRO CM revenues?

Jeff Poulton

Yes, I mean, Paul, you're right. I mean, we flagged that successful nan guidance connected nan descent that we assumed that. Again, fixed nan timing of that, fixed that it's successful nan 4th quarter, nan effect of that from a gross perspective, that this twelvemonth is going to beryllium comparatively modest. And so, not, that doesn't really person a important effect connected nan financial guidance we've fixed for nan twelvemonth arsenic a result, if approved, we would expect much important effect adjacent year.

Paul Matteis

Thanks truthful much.

Operator

And 1 infinitesimal for your adjacent question. The adjacent mobility comes from nan statement of Gena Wang pinch Barclays. Your statement is now open.

Gena Wang

Thank you. I person 1 mobility regarding nan APP program. What will beryllium nan perfect objective floor plan regarding percent of knockdown and nan wave of dosing? Any antagonistic reappraisal from vutrisiran by immoderate dosing information regarding wave of dosing for nan APP program?

Pushkal Garg

Yes, Gina, acknowledgment for your question. So I conjecture a mates things successful there. You know, what's nan perfect profile? So look, I deliberation this is the, you know, we've said earlier that we don't person the, from familial data, we would ideate that we would want get to adjacent to astir 50% knockdown of ALN-APP of amyloid precursor protein. We deliberation that's astir apt astir nan target scope to get to a therapeutic effect, but astatine nan extremity of nan day, nary 1 really knows. And truthful that's benignant of wherever we're shooting for. But this is again an first azygous ascending dose study. We'll beryllium providing immoderate interim information and truthful we'll beryllium moving our measurement up to get to higher levels of knockdown arsenic nan information let and truthful that's constituent one.

In position of nan wave of dosing, look, nan preclinical information that we person suggests that this whitethorn beryllium a comparatively infrequently dosed molecule. We've seen knockdown lasting complete six months successful nan non-human primate studies that we've done pinch ALN-APP. So we're very encouraged pinch nan imaginable that this could beryllium a quarterly aliases perchance biannually dosed supplier successful nan CNS. But again, nan information will pass that. I don't deliberation there's immoderate peculiar read-through from nan accrued randomized curen hold that's a different molecule fixed to a different space. It's a different conjugate. And arsenic you know, we proceed to -- our scientists proceed to hone our chemistry each nan time, but a batch of that is besides molecule and target dependent. So we're very encouraged by nan information we person truthful acold non-clinically and really looking guardant to nan objective information emerging shortly.

Gena Wang

Thank you very much.

Pushkal Garg

Thanks, Gena.

Operator

For your adjacent question. Your adjacent mobility comes from nan statement of Luca Issi pinch RBC Capital. Your statement is open.

Luca Issi

Oh, great. Thanks truthful overmuch for taking my question, and congrats connected nan progress. I person a speedy 1 connected HELIOS-B. I deliberation there's a fewer docs retired location that are convinced that really nan supplier is making an effect for their patients pinch ATTR cardiomyopathy, but they are conscionable worried that this proceedings is not agelong capable to really show a convincing separation of nan curves. Is location a script wherever you tin amend nan protocol truthful you don't publication retired nan superior endpoint erstwhile nan past patients scope nan 30-month mark, but alternatively aft a pre-specified number of events? Any thoughts there? I overmuch admit it.

Pushkal Garg

Yes, Luca, I think, you know, there's, and first of all, it's awesome that you're getting that benignant of feedback. We're evidently encouraged wide by nan floor plan of vutrisiran and that we're seeing from patients retired there. In position of nan study design, I deliberation we've a, I'll conscionable punctual you, we person a way grounds of moving successful this abstraction for rather a while and executing successful studies. Our teams person gone done and we consciousness very bully astir nan creation of nan study and nan execution of this study.

As a reminder, we've sewage adaptable travel up for 30 to 36 months. And this study builds upon nan occurrence and what we've seen successful position of encouraging information coming retired of APOLLO-B wherever we saw affirmative impacts connected functional endpoints, value of life, grounds of imaginable delays successful illness progression and favorable impacts connected echocardiographic parameters, technicians, and there's a batch of affirmative information there. And HELIOS-B is doubly arsenic ample and astir 3 times arsenic long. So we consciousness bully astir nan creation and execution of that study, and we're not readying astatine this constituent to make immoderate changes.

Yvonne Greenstreet

Yes, spot connected Pushkal. I mean, correct now we're focused connected robust execution and bringing this location and sharing results pinch you successful early 2024.

Luca Issi

Got it. Super helpful. Thank you, guys.

Yvonne Greenstreet

Next question,

Operator

One infinitesimal for your adjacent question. And your adjacent mobility comes from nan statement of Jessica Fye pinch J.P. Morgan. Your statement is now open.

Unidentified Analyst

Hey, bully morning. This is Jail for Jess. So 2 questions from america connected nan sNDA of ONPATTRO, successful nan lawsuit that nan FDA will petition immoderate caller data, aliases successful nan lawsuit that you mightiness want to nonstop much information to nan FDA, do you expect immoderate type of PDUFA hold because of nan caller information submission? And past secondly, we cognize that nan cardiovascular result information from [indiscernible] proceedings will beryllium disposable successful July. So conscionable curious, would you beryllium watching for nan information from nan [indiscernible] CM and if immoderate thought you tin stock pinch america regarding nan benignant of imaginable effect connected nan tribute information connected your reasoning of nan alteration successful diligent organization and thing on those lines? Thank you very much.

Yvonne Greenstreet

Two questions for you really here, Pushkal. One connected nan sNDA was connected ONPATTRO and request for caller information and imaginable extensions, nan information and past I deliberation immoderate questions astir our perspectives connected [indiscernible] cardiomyopathy result study.

Pushkal Garg

Yes, convey you. Look, successful position of nan effect if we're asked to proviso further data, I really can't speculate. Certainly we will supply immoderate information nan agency requires to facilitate their review. And we look guardant to sharing that information successful nan people of questions that travel from nan agency and astatine nan advisory committee. The FDA has declared a PDUFA day of October 8, and I cognize they'll beryllium striving to execute that, and we'll update if there's immoderate changes to that based connected their requests.

In position of nan [indiscernible] data, look, we look guardant to seeing nan results. I deliberation it's scheduled for nan mediate of nan year, but I don't deliberation that really changes thing for america successful nan discourse of nan APOLLO-B sNDA. That study is completed and nether reappraisal and truthful we'll surely beryllium looking for those results, but -- and watching them, but there's, I don't spot immoderate really peculiar effect connected nan APOLLO-B sNDA.

Yvonne Greenstreet

Yes, truthful informative for nan field, yes. But of nary existent benignant of consequence to our circumstantial programs, correct, yes. Next question?

Operator

One infinitesimal for nan adjacent mobility and your adjacent mobility comes from nan statement of [indiscernible] pinch Morgan Stanley. Your statement is now open.

Unidentified Analyst

Good greeting and acknowledgment for taking nan question. May beryllium conscionable a speedy 1 connected AMVUTTRA successful polyneuropathy. I noticed you sewage a J-Code successful early January. Just funny what effect you deliberation that could person connected nan trajectory of nan motorboat and is it imaginable we could spot an inflection there? Thanks.

Yvonne Greenstreet

Yes, that's a bully short mobility for Tolga, implications of the, our receipts of nan J-Code.

Tolga Tanguler

Right. Hi Mike. Thanks for nan question. We're very pleased pinch nan truth that nan J-Code we received nan J-Code arsenic a, connected nan owed date. Prior to nan J-Code we already had a generic J-Code that allowed america to beryllium capable to person entree to supply nan correct entree to our patients successful nan U.S. Therefore, we wouldn't needfully beryllium expecting immoderate important change.

Now successful position of nan outtake is already itself has been, arsenic Yvonne put it, has been a crippled changer. We person doubled nan number of commencement forms that we would usually person successful a dependable authorities of ONPATTRO. Therefore, we're very pleased pinch nan accelerated maturation that our parity pricing astatine launch, arsenic good arsenic our bully worth based entree strategies that we were capable to found anterior to nan launch, that's really allowing america to person a soft sailing successful position of nan entree front, and nan maturation is really coming from acknowledgment to nan floor plan of nan merchandise arsenic good arsenic our efforts successful expanding nan prescriber guidelines for nan polyneuropathy crossed nan U.S. arsenic good arsenic now successful Japan and Germany.

Unidentified Analyst

Got it. Thank you.

Yvonne Greenstreet

Thanks, Tolga. Next question, please?

Operator

One infinitesimal for nan adjacent mobility and your adjacent mobility comes from nan statement of Myles Minter pinch William Blair. Your statement is now open.

Myles Minter

Hi, acknowledgment for taking nan question. Just connected nan HELIOS hold and nan 50 mg biannual dosing, did nan 5 patients that passed distant successful that limb each execute nan 80% TTR knockdown, aliases did they not? And did they each dice from cardiomyopathy? There conscionable again seems to beryllium an imbalance betwixt mortality connected nan 25 mg each 4th and nan 50 mg biannual. And we cognize that nan 25 mg quarterly is efficacious. So conscionable clarifying that would beryllium helpful.

Tolga Tanguler

Thanks, miles. Maybe I tin conscionable springiness you a small spot of discourse of nan decease events that happened successful this study. I mean, conscionable taking a measurement back, nan wide information successful position of adverse events, superior adverse events, cardiac, renal, hepatic events, laboratory, that was each really rather balanced betwixt nan arms. We did spot this numerical quality successful position of deaths. They were each unrelated arsenic deemed by nan investigator. They had aggregate consequence factors for mediocre prognosis successful position of precocious NYHA Class, elevated BNP aliases fierce mutations.

As an example, 3 retired of nan 5 patients successful nan 50 mg biannual regimen who passed distant had glue 89 glen [ph] and Serine 77 [indiscernible] mutations, which are peculiarly aggressive, truthful make nan causes too, immoderate CB, but immoderate were non-CB. As an example, 1 of nan patients who passed distant successful nan biannual regimen was diagnosed pinch acute myeloid leukemia and died aft chemotherapy. And past we looked you know, location was nary narration to pharmacokinetics aliases arsenic you were asking pharmacodynamics a knocked down that we observed. So we'll supply much specifications successful upcoming technological meetings. But we're very reassured from nan elaborate information analysis, which did not, did not to our minds look to beryllium immoderate narration to nan drug.

Myles Minter

Right. Thanks.

Operator

One infinitesimal for nan adjacent question, and your adjacent mobility comes from nan statement of Joseph Stringer from Needham and Co. Your statement is now open.

Unidentified Analyst

Good morning. This is Barbara connected for Joey, and our mobility is astir nan large picture. Can you springiness america a consciousness of what you deliberation ONPATTRO and AMVUTTRA's mixed marketplace penetration of nan TTR polyneuropathy and mixed phenotypes is astatine this time?

Yvonne Greenstreet

Yes, I think, I deliberation conscionable benignant of taking a measurement backmost and reasoning astir nan TTR marketplace arsenic a whole, I mean, there's nary uncertainty that it's a quickly increasing marketplace pinch accrued expert awareness, accrued test of patients, and evidently that's translating into accrued curen of patients. So we are very excited that we person 2 RNAi therapeutics participating and helping patients who person ATTR Amyloidosis astatine nan infinitesimal pinch polyneuropathy, and past of course, hoping to widen nan explanation to patients who besides person cardiomyopathy. We deliberation it's a marketplace that besides has room for aggregate players. It really is each astir benignant of marketplace maturation alternatively than marketplace share.

And I deliberation what's peculiarly pertinent pinch respect to our portfolio is, we really spot our portfolio driving maturation wide going guardant for Alnylam. So, you know, we're very pleased pinch our advancement frankincense far. And you know, we look to proceed helping physicians, dainty patients arsenic due pinch some ONPATTRO and AMVUTTRA. I mean, Tolga is location thing you want to adhd successful position of conscionable stepping backmost and reasoning astir nan TTR market?

Tolga Tanguler

Yes, I mean, on nan aforesaid lines we're very pleased to beryllium capable to supply now we do person a franchise. We person 2 products that are disposable successful nan US? and soon for nan remainder of nan world successful polyneuropathy. And what we cognize is contempt nan truth that it's a uncommon disease, location is still important unmet need, it's a devastating disease. If nan patients are not treated, they do extremity up pinch mortality attraction mobility successful a timeframe of 5 to 7 years. And contempt that, test and curen is still comparatively debased numbers. And what AMVUTTRA motorboat has demonstrated to america is nan truth that having a very compelling merchandise floor plan and pinch nan convenience of subcutaneous injectable each 4th really does alteration nan crippled successful position of really it allows america to beryllium capable to scope much patients done by really uncovering more, much physicians.

So we do person this prevalence number that's anyplace betwixt 40,000 to 50,000 crossed nan world, including nan mixed genocide patients. We're still scratching nan aboveground and arsenic Yvonne indicated pinch these products coming into nan marketplace will let america to really summation nan awareness, some connected nan expert broadside arsenic good arsenic connected nan patient's side. And nan astir caller motorboat of AMVUTTRA intelligibly demonstrates that.

Yvonne Greenstreet

Thanks, Tolga. So we've sewage clip for 1 past question.

Operator

One infinitesimal for nan past question, and your past mobility comes from nan statement of Eliana Merle pinch UBS. Your statement is now open.

Eliana Merle

Hey guys, acknowledgment for taking nan question. Just connected nan ONPATTRO ADCOM, I conjecture conscionable from nan interactions and feedback from nan FDA truthful far, do you get nan consciousness that this ADCOM is much circumstantial to nan APOLLO-B data, specified arsenic being astatine 12 months, aliases do you deliberation it benignant of is much broadly astir nan ATTR scenery successful cardiomyopathy and nan objective value successful different subgroups? I mean, I conjecture for illustration successful different words, really overmuch do you deliberation nan ADCOM would effect AMVUTTRA imaginable labeling chat versus this being much of an APOLLO-B circumstantial related chat astatine nan ADCOM? Thanks.

Tolga Tanguler

Thanks Ellie for your question. Again, arsenic we've said astatine nan beginning, we don't person immoderate peculiar feedback from nan agency connected nan specifics of what nan ADCOM will beryllium aliases nan questions there. And we'll surely look guardant to proceeding much from nan agency. We're committed to supporting their reappraisal successful immoderate measurement we can. I do expect that nan ADCOM is going to beryllium focused connected nan APOLLO-B information however. That's nan sNDA that we revenge and that would beryllium nan taxable of nan review. Those would beryllium nan information that we'd beryllium sharing and talking astir successful nan discourse of that -- nan reappraisal and nan advisory committee arsenic well. But again, we'll look guardant to seeing much from nan agency erstwhile they get backmost to america pinch details.

Yvonne Greenstreet

Yes, and again, I deliberation conscionable to underscore that we judge nan APOLLO-B information actually, you cognize has demonstrated nan presumption that RNAi therapeutics tin person a meaningful effect connected patients pinch TTR amyloidosis pinch cardiomyopathy.

So we shall extremity there. Thank you everybody for joining nan call. We're really happy pinch nan advancement that we've made successful nan 4th fourth and nan afloat twelvemonth 2022. We've had beardown commercialized results. We've continued to beforehand our divers pipeline of programs and developments, and we've besides sewage a number of breathtaking catalysts connected platform successful 2023. So we look guardant to updating you on nan measurement arsenic we proceed to present connected these goals. So convey you everybody, and person a awesome day.

Operator

Goodbye.