Alnylam Pharmaceuticals, Inc. (ALNY) Earnings Call Transcript & Summary

Welcome, everyone, to the 39th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Tessa Romero and Matt Bannon from the team. Our next presenting company is Alnylam. And speaking on behalf of the company, we have CEO, John Maraganore. Before I turn it over to John, I just wanted to highlight for those listeners on the webcast to feel free to submit a question via the ask-a-question feature in the portal. John?

Thanks, Anupam. It's great to be here. It's especially great to put 2020 and even this past week behind us now and to be in 2021. Despite last year's adversities, Alnylam actually had one of its strongest years ever. And I'm so proud of our Alnylam employees who persevered with their challenge-accepted spirit and a commitment to the patients we serve. For example, we started 2020 with 2 products, 6 approvals and access in 14 countries. Then we ended 2020 with 4 products, 15 approvals, access in 41 countries and grew top line product revenues by over 100%, a remarkable year, indeed. And for 2021, Alnylam is poised to begin this transition toward becoming a leading biopharma company, a top 5 company in market cap in the next 5 years. So let's now move to Slide 2, and as a reminder, I'll be making forward-looking statements during my presentation. Let's now go to the next slide, please. At Alnylam, we've had a decade-long heritage of sharing our 5-year strategy and goals at this meeting. It started in 2011 with Alnylam 5x15 where we committed to build our clinical pipeline. We beat those goals. Since 2015, Alnylam's been executing on its Alnylam 2020 strategy, which was boldly aimed at our transition to a global multiproduct commercial company. We managed to beat those goals too. Next slide, please. So today, we're thrilled to announce our new 5-year vision for Alnylam. P5x25 marks our planned transition to a top 5 biotech in market cap in the next 5 years. The 5Ps of the strategy are: patients, products, pipeline, performance and profitability. The specific metrics are laid out on the bottom of this slide and also in the press release we issued yesterday. But in a nutshell, we aim to be one of the most successful biotech companies ever with transformative medicines in both rare and common diseases for patients around the world, supported by additional growth through label expansion, a robust and high-yielding pipeline of first and/or best-in-class product candidates from our organic product engine and exceptional financial performance with over 40% revenue CAGR through year-end 2025 and sustainable profitability achieved within the period. P5x25 strategy is indeed the exciting next chapter for Alnylam. So let's now go to Slide 5 and transition to the main part of my presentation. As all of you know, Alnylam is the leading RNAi therapeutics company. We are proud to have pioneered RNAi therapeutics as a whole new class of medicines. The data speak for themselves. RNAi therapeutics are indeed transformative for patients. And while we're entering our 19th year since founding, we're just really at the early innings of realizing the impact of RNAi for human health. Next slide, please. The key components of Alnylam's business are: first, transformational medicines helping patients around the world with rare and common diseases; second, a robust and high-yielding R&D pipeline of first and/or best-in-class product candidates; third, an organic product engine capable of delivering sustainable innovation. Next slide, please. Let's start with a discussion of the transformational medicines that we brought to market. Turning now to Slide 8. We are very proud that Alnylam homegrown innovation has resulted in 4 globally marketed products in just over 2 years, a truly remarkable achievement: ONPATTRO, GIVLAARI, OXLUMO and Leqvio, formerly known as inclisiran. These are all transformative medicines for patients with rare and common diseases that are or are expected to become market-leading products for many, many years to come. Turning now to Slide 9. We're very pleased with 2020 performance for ONPATTRO, the first RNAi therapeutic ever approved and our breakthrough medicine for treating the polyneuropathy of hATTR amyloidosis, a devastating rare disease. ONPATTRO is approved in 8 markets around the world, and we're pleased to report our unaudited full year results with about 1,350 patients on commercial drug and about $306 million in full year revenues at the top of our guidance range. Importantly, our Q4 results of about $90 million represent double-digit growth compared to Q3 and include double-digit growth in the U.S. driven by new patient demand. We achieved over 80% full year growth over 2019 even with the pandemic. We expect strong growth in 2021, driven by many important market dynamics, including concomitant use with TTR stabilizers predominantly in the U.S., patient switches from stabilizer drugs due to disease progression along with continued new patient finding and improved disease awareness. Turning now to Slide 10. We are just at the beginning of our growth opportunity for ONPATTRO and our broader ATTR franchise, which includes an exciting molecule, vutrisiran. Today, depicted on the left, we have one drug ONPATTRO in its initial indication in a market that is ripe for expansion with disease awareness and patient diagnosis. We'll soon jump to a new stage depicted in the middle in 2022 with our second drug, vutrisiran. With a quarterly and then biannual subcu dosing regimen, vutrisiran can significantly grow our opportunity beyond ONPATTRO alone, especially in mixed phenotype patients and also provide clear category leadership. Around the same time, we expect to expand ONPATTRO into the cardiomyopathy setting, including wild-type disease, creating what we believe is the potential for the first multibillion-dollar anchor product for Alnylam, sort of like EYLEA was for Regeneron or Revlimid was for Celgene. Thereafter, as depicted on the right, with potential outcomes data for vutrisiran in wild-type ATTR and also studies in disease prevention, we envision even further growth. The bottom line here is that with our leadership, our innovation and our commitment to help patients, we have a compelling road map to enable impact for patients, outsized growth and significant value creation for our shareholders. Turning now to Slide 11. We're also very pleased with 2020 performance for GIVLAARI, our breakthrough medicine for treating acute hepatic porphyria, another devastating rare disease. GIVLAARI is our first GalNAc conjugate to reach the market. 2020 happened to be GIVLAARI's first full year of launch. And this high-impact medicine is now approved in 4 met markets with more on the way. Yesterday, we pre-announced our unaudited full year results with about 200 patients on commercial drug and about $55 million in revenues, a really excellent start for this game-changing medicine. We expect steady and continued growth for GIVLAARI in 2021, driven by significant geographic expansion and new patient-finding efforts. Turning now to Slide 12. Just over the last 60 days, we brought our third RNAi therapeutic to the market with the approval of OXLUMO first in the EU and then in the U.S. OXLUMO is the first-ever treatment for primary hyperoxaluria type 1, another devastating rare disease. It's also the first-ever RNAi therapeutic approved for a pediatric indication. 2021 will be the first full year of launch for this new medicine from Alnylam, and we're pleased to see strong early demand so far. Turning to Slide 13. In addition to ONPATTRO, GIVLAARI and OXLUMO, Leqvio was approved last year in the EU. Leqvio is the first RNAi therapeutic approved for a common disease and promises to be a blockbuster product for our partner, Novartis. As you can see on this slide, we're especially excited about the growth opportunity for our overall commercial profile. In addition to our 4 currently marketed products, we can expect 2 additional product launches over the next 12 to 24 months, meaningfully increasing the number of revenue-generating Alnylam assets, all of which are in a growth phase for the foreseeable future. Frankly, we believe this profile of organic growth generation of commercial medicines is nearly unprecedented in biotech history, and we expect to be positioned to expand on this profile in the years to come. Next slide, please. So let's now transition to a discussion of our R&D efforts where we're advancing Alnylam RNAi innovation for a wide range of rare and common diseases. Turning now to Slide 15. This is a summary of Alnylam's clinical pipeline. One thing you can clearly see from this slide is that our pipeline is, without a doubt, robust. It is arguably one of the most fulsome clinical pipelines in the biotech industry today with over a dozen programs spanning Phase I to Phase IV. You can also appreciate on this slide the substantial product ownership that Alnylam has retained for its pipeline, where we have global or 50-50 rights for the vast majority of our programs. Let's now turn to Slide 16 to make another very important point about Alnylam's R&D efforts, namely that we have delivered outsized success rates compared with industry norms, creating a high-yielding pipeline. We believe our success rate underscores the power of an organic, reproducible and modular platform that is turbocharged with human genetics. Indeed, our track record is now over 60% from IND to positive Phase III compared with industry metrics of less than 10%, a remarkable and, we believe, sustainable difference. Turning to Slide 17. We have a very recent case in point, another positive Phase III result to share. Just last week, we reported positive top line results for the HELIOS-A Phase III study of vutrisiran in hATTR patients with polyneuropathy. In this landmark study, a once quarterly subcu injection of vutrisiran demonstrated very impressive efficacy with highly significant results and an encouraging safety profile. In addition, vutrisiran demonstrated improvements in neuropathy impairment and quality of life relative to baseline, confirming that RNAi therapeutics can indeed achieve reversal of disease manifestations just like we observed with patisiran in the APOLLO study. We also observed significant effects on the 9-month cardiac end point of NT-proBNP, and we have additional cardiac data that are being collected as part of the 18-month end point, and we'll report those later in the year. With these exciting results in hand, we plan to file our NDA in early '21 and aim to bring our fifth RNAi therapeutic to market in early '22. And as I mentioned earlier, what's exciting about vutrisiran is the opportunity of expanding our overall opportunity, particularly in the mixed phenotype population. I'm now on Slide 18. The next important step in our ATTR amyloidosis franchise program relates to our cardiomyopathy studies, APOLLO-B and HELIOS-B, which we collectively call the Cardi Bs. These studies will extend our commercialization effort into a much larger patient population with at least 300,000 wild-type ATTR amyloidosis patients worldwide. We expect to complete enrollment in APOLLO-B with patisiran early this year setting us up for top line data in mid-'22. In the case of HELIOS-B with vutrisiran, the study has been enrolling very well, and we will continue to enroll in that study throughout 2021. Next slide, please. There are many reasons to be encouraged by the potential for patisiran and vutrisiran in ATTR cardiomyopathy. Across both programs, we have demonstrated evidence for improvements on biomarker, echocardiographic and/or functional end point measures. In a post hoc analysis of the APOLLO study, we were able to demonstrate a 50% reduction in all-cause hospitalization and mortality. More recently, cardiac imaging studies have shown evidence for regression of cardiac amyloid with associated improvements in 6-minute walk distance, which is the primary end point in the APOLLO-B study. So as we enter the next period with APOLLO-B and HELIOS-B trial readouts, we have a solid foundation to expect success. Let's now turn to Slide 20. One of the exciting parts of the Alnylam story these days is our efforts in advancing RNAi therapeutics beyond rare diseases into prevalent disease opportunities. Emboldened by our results from the Phase III studies of inclisiran, the ORION studies, we believe that the time is now to address many unmet needs in common disease settings such as hypertension, NASH, gout, diabetes, amongst others. Importantly, the pharmacological properties of RNAi therapeutics provide the foundation for success. Durable effects enable infrequent dosing to maximize adherence. Clamped pharmacology creates a potential for improved efficacy and outcomes. An established safety profile is now supported by tens of thousands of patients in clinical trials and improve patient access can be achieved based on HCP-administered therapy with lower patient co-pays. Next slide, please. Our program in hypertension represents an excellent example of how we can transform the treatment of a prevalent disease with RNAi. Hypertension is the #1 modifiable risk factor for CV morbidity and mortality where existing drugs fail to provide the needed tonic control of blood pressure and where patients lack required adherence. With RNAi therapeutics, we can reimagine the treatment of hypertension, providing tonic blood pressure control due to clamped pharmacology and a highly adherent treatment due to durability. Turning now to Slide 22 to look at some recent data. ALN-AGT is our RNAi therapeutic targeting angiotensinogen for the treatment of hypertension. Angiotensinogen is a genetically validated target. We reported interim Phase I data this past November at AHA and updated the results at our R&D Day in December. The results are very exciting. ALN-AGT demonstrated potent and highly durable knockdown of angiotensinogen of over 95% and reduction in blood pressure of over 15-millimeter mercury systolic as monotherapy, a highly clinically meaningful effect. The durability profile supports a once quarterly and likely a biannual dosing regimen. We're now transitioning to the start of our cardio 1 and cardio 2 Phase II studies, which will start in mid-'21, and these studies will evaluate ALN-AGT as monotherapy and also in combination with RAAS inhibitors in about 1,000 patients with uncontrolled hypertension. Next slide, please. So I'll now turn briefly to the third key pillar of Alnylam, our organic product engine. This is the source of our sustainable innovation, something rarely seen in a top biotech. Let's now go to Slide 24. Alnylam's product engine will deliver 2 to 4 new INDs per year and per our P5x25 goals, we aim to achieve 4 or more INDs per year by the end of '25. Today, we're advancing over 25 preclinical programs with delivery in 4 tissues: liver, CNS, eye and lung. These programs span rare and common diseases and are advanced to be first-in-class and/or best-in-class medicines into targeted disease indications, and virtually all of these programs are supported by human genetics. We're very excited about the opportunity for RNAi therapeutics and CNS diseases, an area of enormous unmet need. At our first CNS program, ALN-APP, targeting amyloid precursor protein will start clinical testing this year. Let's now go to Slide 25. As I said earlier, we're just in the early innings of realizing RNAi's full potential for human health, and Alnylam will continue to be the technology leader and the innovation pioneer. Because of the Alnylam platform we've built, the opportunities for the future are plentiful, if not boundless by drug discovery standards and include leveraging our human genetics capabilities for enhanced success rates, conquering delivery toward new tissues like tumors for RNAi therapeutics in cancer, novel combinations with monoclonal antibodies creating market disruptive therapies, dual targeting Bis-RNAi technology to treat diseases in fundamentally new ways, controllable pharmacology with our Reversir technology and alternative less invasive modes of delivery like oral or trans blood-brain barrier approaches. So I think you can expect sustainable and disruptive innovation from Alnylam for many years to come. Next slide, please. In closing, let me now turn to a brief discussion of our goals and financials. Turning to Slide 27. We have a large number of specific 2021 goals in what promises to be a catalyst-rich year, including global commercial execution on 4 products, 3 driven by Alnylam and 1 by Novartis; a number of regulatory approvals in key markets; a new NDA in early '21 for what we expect to be our fifth marketed RNAi therapeutic, vutrisiran, based on our exciting new Phase III results. We expect many important data readouts throughout the year, including Phase III data from lumasiran in severe PH1, full 9-month Phase III data and then 18-month results for vutrisiran. And you can expect many other data readouts from our pipeline, including from our hypertension program. Finally, we aim to deliver 2 to 4 new IND filings, delivering on sustainable innovation. Let's now go to Slide 28 to touch on financials. In yesterday's press release, we announced strong preliminary 2020 product revenues. We also announced further improvement in our 2020 non-GAAP operating loss, confirming that 2019 was indeed our peak loss year. We'll report complete Q4 and full year 2020 in February and also provide revenue guidance for 2021 at that time. But the bottom line here on financials is that Alnylam is now on a clear path toward achieving a self-sustainable financial profile with strong revenue growth and disciplined investment in R&D with leveraged execution of SG&A. Consistent with our P5x25 goals, we aim to deliver over 40% revenue CAGR through year-end 2025 and also non-GAAP profitability within the period. With our current balance sheet of $1.9 billion and due to our 2020 strategic financing with Blackstone, we're positioned to achieve profitability without the need to ever go to the equity markets. Next slide, please. These are indeed exciting times for Alnylam, where we expect a remarkable transformation over the next 5 years. We'll be advancing our medicines for rare and prevalent diseases across many indications in over 4 strategic therapeutic areas to help patients around the world. We'll also continue leveraging our organic product engine as a source of sustainable innovation for many years to come. Indeed, with Alnylam P5x25, we're on a path to build a top 5 biotech company in market cap in the next 5 years with a commitment to patients, innovation, responsibility and excellence. Next slide, please. So in closing, I want to thank you for your support and commitment to our company. We're now going to transition to our Q&A session. I'll be joined by other members of the Alnylam management team, and I look forward to taking your questions at that time.

Okay. John, if you want to introduce the broader team on the line, we can get started. I also want to listen -- remind all the listeners on the line that feel free to use the ask-a-question feature in the portal, and I'm happy to ask the question on your behalf. John?

Okay. Good. It looks like I'm missing one of my team members. But no bother, we'll continue. So on the call here, we've got Jeff Poulton, who's our Chief Financial Officer. We've got Akshay Vaishnaw, who's our Head of R&D, President of R&D, long time colleague of mine here at the company; Pushkal Garg, who's our Chief Medical Officer; and our newest member of our team, Ms. Tolga Tanguler, who joins us as our Chief Commercial Officer most recently from Alexion and prior to that, many years at Pfizer, amongst other engagements around the world. So it's really a pleasure to be here. And I don't know if Yvonne was able to join by phone. Yvonne, if you're on the phone, please identify yourself, but not seeing her, I think we should just continue and she'll join when she can.

John, I'll start out by the P by 5 2025 strategy here. You've talked about 6-plus approved products, right? ONPATTRO, GIVLAARI, OXLUMO, vutrisiran, fitusiran and inclisiran. I guess the question is, with what you mentioned about probability of success and phase transition, right, is that being -- and the power of the platform being more derisked now, why wouldn't it be greater than 6, given all the INDs that you filed? Are you planning on...

It's -- obviously, it's a 5-year guidance, and the guidance is over 6. Six or more is the guidance. And keep in mind that what's exciting about this pipeline profile that we're generating here, and here I see Yvonne joining us now, is that we're also going to have significant label expansion of existing brands. So for example, Anupam, with, obviously, as you know, with patisiran, we're doing the APOLLO-B study to expand that opportunity. With vutrisiran, we're doing the HELIOS-B study. With lumasiran, currently marketed as OXLUMO, we're expanding the opportunity into severe PH1, but we're also doing a really exciting study in recurrent renal stones to expand that opportunity. So this -- the over 6 -- the 6 or more products does not include the potential for a significant expansion of existing brands with label expansion. And so that is certainly something which we do expect will grow the Alnylam profile significantly over the years to come. And now I see our President and COO, Yvonne, has been able to rejoin, which is terrific. Thanks for joining, Yvonne.

And maybe I'll ask a question that's just come in from the portal, but what is your strategy for in-licensing assets, given that you have a platform, yes?

Well, Yvonne should comment as well. But we have this organic product engine. We have this abundance of riches, which is extraordinarily rare in company -- in companies. And so we are very confident to be able to build a top 5 biotech company organically without the need to go to the outside whatsoever to look for things. We obviously always look at technologies. We always look at opportunities, but we don't have a need to do that whatsoever. Yvonne, do you want to comment any further on that question?

No, I think, John, you covered it well. I mean, obviously, we're always open to areas where there's a strong strategic fit with our business and impacts patients positively and adds value to our business. But as John said, we have this remarkable product engine as well as 3 Alnylam-led programs that we've launched as medicines and need to continue to drive commercial performance there. So we have a lot to do commercially as well as in our R&D pipeline. So no need to do anything, but we continue to look at the landscape and assess opportunities. But strategically, absolutely no need to achieve our 5-year guidance.

We've got another e-mail question here. Please give us an update on the COVID antibody development program you have with Vir Pharmaceuticals.

Yes. Well, it's not an antibody program to start. It's a small interfering RNA molecule. We're advancing and maybe, Akshay, you can comment in just a minute. We're just to provide context. We're advancing 2 siRNAs targeting 2 different sites of the SARS COVID-2 virus, which, by the way, we've confirmed is preserved in these new variants that are coming out. And we've been able to advance them into preclinical, pre-IND testing. We've done some preclinical studies. So Akshay, do you want to comment a little bit about where the program is and our plans for that?

Yes. As you said, an si-based approach is highly advantageous because it's sequence-based. We can monitor the mutational escapes that might be happening out there. And I think it's really good news that we still maintain specificity and potency against all the variants out there. We have preliminary data in a hamster model. We're excited about that. We're following up on with additional work in animal models that -- I think we're expecting that in the coming weeks or so now. And following review of that, we'll be moving forwards to an IND because there's still a tremendous need for both therapeutic and vaccine departments despite all the progress the industry has made in the last year. And so our commitment is unchanged. In the background, of course, from a toxicology and CMC viewpoint, we've continued to make progress there. So we're advancing as quickly as we can. It's a potent specific approach, and we'll certainly have a place in the armamentarium should we be able to advance that into the clinic.

And maybe I'll ask a question based on the press release yesterday. You talked about this year-over-year operating loss improvement. What type of improvement should we be thinking about here not just for this year but as we look out to 2025, like how should we be thinking about that?

Jeff, do you want to take that?

Yes. Hi, everybody. Anupam, we're not providing specific guidance on this call. We'll do that on the '21 call. But the commitment around profitability and the P to the fifth goals that we've just shared is that we would achieve profitability within the 5-year period. So that's the expectation.

Got it. Got it.

And obviously, with strong -- Anupam with the strong -- it goes without saying that with this very strong revenue growth that we're projecting and we're confident that we'll achieve and with the continued discipline growth in our investments whether it's in R&D or leveraging of our existing SG&A infrastructure, we're very much, as I said in my prepared remarks, very much on our path toward that profitability profile in the coming years absolutely.

Another question that we've just gotten from the portal is, as you're thinking about the top line revenue growth and sort of the profitability to 2025 -- by 2025, what contribution are you expecting from ATTR cardiomyopathy franchise, I guess?

Yes. Well, let me just maybe remind everybody that obviously, the ATTR cardiomyopathy opportunity is really one of the exciting opportunities within the portfolio. And we have 2 studies, APOLLO-B and HELIOS-B that are well under way. APOLLO-B will start -- complete enrollment early this year and provide top line in mid-'22. And those are really important opportunities for the company. There's no doubt about that. We're excited about that. And those are opportunities where we have very strong data supportive of the likelihood of success. Specifically, we've got biomarker, echocardiographic functional data. We've got scintigraphy data as well. So there's just quite a bit of strong data that gives us confidence about the cardiomyopathy. But our revenue generation is a portfolio at the end of the day. And it doesn't reflect any one specific asset. It is a portfolio. It includes the current labels for ONPATTRO, the current expected label that we'll get for vutrisiran. It includes OXLUMO and GIVLAARI as well as royalties from other third parties. I don't know, Yvonne, if you want to add anything to that or Jeff as well. Yvonne, why don't you start first?

No, I think you've actually covered that very nicely, John. It's -- the cardiomyopathy studies were a critical driver for our performance. But I think one of the remarkable attributes of Alnylam is the fact that we do have this portfolio of marketed products and continued introduction of innovation over a period of time. So I think we're in a very strong position. I don't know, Jeff, if you want to add anything?

Just, I think, recap what both of you said. We think that expansion to the cardiomyopathy setting will be a meaningful contributor to that top line growth goal that we've put out. But we're not going to sort of break that down and provide specifics product by product.

I think Tessa from the team has a question?

Yes. I think on your slide, the HELIOS-B study now has a planned interim analysis versus I think you all noting it as optional prior. So I guess, given what has been shown in post hoc analysis from the original APOLLO study, what are the gating factors to understanding the timing of that decision with respect to when we could see an interim analysis?

That's a great question, Tessa. Let me say a few things and then maybe, Pushkal, you could comment on it directly. As you know, the HELIOS-B study is a very important study. It is a study that's very actively enrolling. We're really happy with the enrollment that we've been seeing lately from it. It will be enrolling throughout 2021. It's a 600-patient study looking at outcomes, looking at CV events and mortality over 30 months. And we are planning on doing an interim analysis. That is the plan. We engineered the protocol at the beginning to include the potential for an IA, but we certainly are planning to do one. So -- and that obviously has the benefit of potentially accelerating the time line for getting vutrisiran into the cardiomyopathy market segment. We expect patisiran, i.e., ONPATTRO, to get there first. But we certainly want to follow up with vutrisiran, which has many positives. So Pushkal, do you want to comment a little bit on thinking and timing and all that?

Sure. Yes. And thanks, Tessa, for the question. Good morning, everyone. Yes. So as John mentioned, we are absolutely planning to do interim analysis with HELIOS-B. There have already been a number of derisking events in terms of probability of success in cardiomyopathy, as John highlighted earlier. So we're in the process of aligning with regulators on the specific details. And the exact aspects of the IA will also be informed by some additional data that are forthcoming. Specifically, we will have 18-month data from HELIOS-A with a number of exploratory cardiac end points in that study as well as the APOLLO-B data, which are expected to read out mid-'22. So all of that will go into -- together to inform that interim analysis, which we plan to do for HELIOS-B.

We've got a question from the portal. You mentioned success with subcutaneous durable drug delivery and then talk about moving towards more noninvasive novel administration. Is there the intent to move away from subcu dosing forms? And could you speak more about the focus on the direction of more novel administration?

Yes. Well, let me make some comments and then maybe Akshay can follow up. We obviously are very excited about the profile of subcutaneously delivered RNAi therapeutics, especially when -- in these common prevalent disease opportunities that we're advancing, where you can have a biannual dosing regimen. I mean it is unbelievable. Take a step back and imagine that we are achieving, in the case of inclisiran, for example, which is being advanced by our partners, Novartis, a once every 6 monthly treatment for hypercholesterolemia. It's like a vaccine for managing hypercholesterolemia with a small volume injection in twice a year. And so it's really our belief set that, that type of profile, frankly, is more attractive even than oral -- once oral, which, of course, one of the major problems with orally administered medicines is patient adherence and patients tend not to be compliant, unfortunately, with their drugs, especially in chronic disease settings that are managing long-term complications of underlying disease as opposed to sort of acute issues. And so this is something which we think makes a subcu delivered infrequently administered drug the best approach at the end of the day. Now at the same time, we've also advanced oral administration. We have data all the way into nonhuman primates, looking at robust oral administration. But candidly, we just haven't found the opportunity that says that approach for delivery for oral is better than the once every 6 monthly approach and -- with subcu. So we just -- we have a technology. We can deploy it in the future should we choose, but we just haven't found that opportunity. To me, the more exciting aspect of where our platform advances are aiming for would be areas such as trans blood-brain barrier administration, which as we think about enabling our neuro CNS pipeline, which is given with intrathecal administration right now, being able to do that systemically while a long shot, let's be clear, in terms of all that, it is an area that we're focusing on. Akshay, I went on longer than I expected, but do you have anything to add to that?

Yes. I mean oral blood-brain barrier is a major, major area to think about. I think the other is topical and, of course, in that regard our inhalational program for COVID signals a new route of delivery. Of course, inhaled is a convenient way to deliver drugs as parenteral. And not so much convenience or ease, but an important route of administration we work on is intra-occular, of course, with our Regeneron colleagues. So you can see that we are really leveraging the potential for RNAi across every portal of entry into the body and basically as many organs as we can get to, which is a very significant [ path and ] compared than only a couple of years back, we were focused predominantly on liver. So I think very exciting for the next decade.

Good. Well, Alnylam team, John, Jeff, Pushkal, Akshay, Yvonne, Tolga, newest member, I want to thank you guys so much for taking the time. We're coming up just about 20 minutes here. So thank you for this super informative session, and I hope you guys have a great meeting.

Yes. Thank you. Be well, everybody. Stay safe.

Thank you. Bye.

Bye. Thank you.

Bye-bye.