Good morning, ladies and gentlemen, welcome to today's Dicerna Pharmaceuticals Q2 2021 earnings conference call. As a reminder, this conference is being recorded at the company's request. I will now turn the call over to your host, Tierney Souvik of Stern IR. Please go ahead. Thank you, operator. Good morning, everyone, and thank you for joining us to review Dicerna's Q2 2021 financial results and operational highlights. For anyone who hasn't yet had a chance to review our results, we issued a press release earlier this morning, which is available under the Investors and Media tab on our website at dicerna.com. You may also listen to this conference call via webcast on our website, which will be archived beginning approximately two hours after this call is completed. Speaking on today's call will be Dicerna's President and Chief Executive Officer, Doug Fambrough, who will review our program portfolio and strategy, and our Chief Financial Officer, Doug Pagan, who will review our Q2 financials. We also have Shreeram Aradhye, our Chief Medical Officer, Jim Weissman, our Chief Operating Officer, Rob Ciappenelli, our Chief Commercial Officer, and Bob Brown, our Chief Scientific Officer, available today to address questions during the Q&A session. Following our remarks, we will open the line for your questions. I'd like to remind listeners that management may make forward-looking statements on today's call pertaining to the company's finances, business, and operations, including the discovery, development, and commercialization of our product candidates and technology platform and the therapeutic potential thereof, the success of our collaborations, and any potential future collaborations. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Applicable risks and uncertainties include those relating to our pre-clinical research and clinical programs and other risks identified under the heading Risk Factors included in our most recent Form 10-Q and Form 10-K. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so if our views change. Now I'd like to turn the call over to Doug Fambrough, Dicerna's President and CEO. Doug? Thanks, Tierney. Good morning, everyone. Since we just did our PHYOX2 data call on Thursday, I'd like to start today at a high strategic level before discussing particular programs. RNAi is a powerful modality. The 24 years since its academic discovery encompassed a long period of technology maturation, leading to the breakthrough of GalNAc-mediated delivery of highly modified RNAi duplexes, which has led to multiple approved products with more product candidates at NDA stage. Last Thursday afternoon, Dicerna added our first to this list as our lead product candidate, Nedosiran, demonstrated a strong safety profile and impressive activity profile in the Primary Hyperoxaluria Type 1, or PH1 population. These data, we believe, sets up a high likelihood of PH1 approval in the U.S., Europe, Japan, and other markets, and we intend to submit an NDA to the FDA in Q4. The PHYOX2 pivotal data directly demonstrate the strength of our GalXC RNAi technology platform. I know everyone on the line today is highly sophisticated and can recognize that relative to other approved biotech modalities, such as monoclonal antibodies and AAV gene therapy, the ability to practice RNAi at a cutting-edge critical mass level is remarkably concentrated in a small number of companies, and we're proud to be one of them. It was less than four years ago that Dicerna was a microcap company, trading at a little over $3 per share, no collaborations, no GalXC clinical data, and less than $100 million on the balance sheet, t oday, we end Q2 with almost $710 million, the large majority coming from technology monetization with six collaborations, six different companies engaged in moving Dicerna GalXC molecules forward, six clinical stage programs, including Nedosiran- Nine more that have entered preclinical development, and our platform now extends RNAi delivery to tissues beyond the liver, opening a deep well of opportunities to exploit for years to come. That's a pretty good four years. What really excites me, though, is what we can accomplish over the next four years. In that time, we expect Nedosiran to be approved and available for patients in major markets around the globe. We expect to move Belcesiran for Alpha-1 Antitrypsin deficiency-associated liver disease, or AATLD, where we hold 100% of U.S. rights and which is now early in Phase II. We expect to move this deep into pivotal development w e anticipate the RG6346 program for chronic HBV, which is in Phase II combination trial being conducted by Roche, will have further progressed in clinical development and completed its Phase II cohorts, and with success, will have opted in to co-fund pivotal development, bringing a U.S. co-promotion option. We expect our DCR-AUD program for alcohol use disorder to achieve human proof of concept and have moved to advanced trials, potentially breaking open a vast underserved market. We expect multiple programs from our Novo collaboration to have entered development, and we expect to have opted in to two of those, but only after having seen positive human clinical evidence, which is to say we get to choose the likely winners after seeing some clinical data. We expect current development programs from Lilly, AZ/Alexion and Boehringer Ingelheim to be moving through the clinic. We expect new programs to be entering the clinic on average one per quarter over the next two years, and potentially beyond that at a similar rate. Amongst those, we expect to have taken multiple new GalXC and/or GalXC-Plus proprietary programs well into clinical development. Indeed, we initiated early development of two GalXC-Plus non-liver wholly-owned programs, which will debut when they are closer to clinical entry. It'll be quite a ride over these next four years, and we have the capital to execute on this because our current cash runway, with expected revenue from existing collaborations, runs into 2025. That's longer than we've previously disclosed. I'll return to that in a moment in the context of Nedosiran and PHYOX2 pivotal trial results. First, let's come down from the high level to the actual corporate updates for the Q2, as well as subsequent events. Starting with Belcesiran that we are developing for the treatment of AATLD. Last month, we announced interim results from our Phase I study, which met our objective, demonstrating strong dose-dependent reductions in serum Alpha-1 Antitrypsin in healthy volunteers with administration of a single dose of Belcesiran. In this analysis of the four completed active treatment dose cohorts at 0.1.0, 3.0, and 6.0 milligrams per kilogram, Belcesiran was found to have an acceptable safety profile and was generally well-tolerated. One more dose cohort, 12 milligrams per kilogram, is ongoing, and our objective is to present the results from all dose cohorts at an upcoming medical conference. We also began patient dosing in our randomized, multi-dose, double-blind, Phase II ESTRELLA trial of Belcesiran in June. The ESTRELLA Phase II study includes a 24-week cohort and a 48-week cohort to be conducted in parallel, each with up to 27 participants who have a diagnosis of PiZZ type AAT deficiency and AATLD. As this study progresses, we are looking forward to having a better understanding of Belcesiran's potential to treat the underlying cause of AATLD. Last month, we announced the FDA acceptance of our IND for DCR-AUD, our investigational GalXC RNAi therapeutic candidate for the treatment of alcohol use disorder. We had filed that IND in late June. We are now clear to begin Phase I. We plan to initiate a 24-week randomized, double-blind, placebo-controlled Phase I trial this quarter to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of DCR-AUD in healthy volunteers. The trial will also assess the interaction between DCR-AUD treatment and alcohol consumption using standardized ethanol interaction assessments, which will provide critical pharmacodynamic data to inform the development strategy for that high-potential program. From a collaboration standpoint, we announced in May the FDA's acceptance of Eli Lilly's IND for LY3819469, targeting LPA for cardiovascular disorders, or Lp(a), sometimes referred to, t his is the second clinical-stage investigational GalXC RNAi candidate from our collaboration with them. It triggered a $10 million milestone payment to us and paved the way for Lilly to begin Phase I dosing of the compound, which began in June. There are also two Lilly partnered programs in IND-enabling studies, in addition to the two clinical-stage programs. Also in May, Boehringer Ingelheim accepted DCR-LIV2, an investigational GalXC RNAi candidate for the treatment of NASH to advance to the development stage t his candidate acceptance triggered a single-digit multimillion-dollar preclinical milestone to Dicerna and preclinical work is underway. Earlier this year, we added to the development pipeline a second candidate under the Novo collaboration. Finally, we have two programs in our AZ/Alexion collaboration that are progressing through IND-enabling studies. Now let's turn attention back to Nedosiran. As you all know, we presented top-line data from our PHYOX2 pivotal clinical trial last week, and Nedosiran successfully and decisively hit both the primary and key secondary endpoints while showing a strong safety profile. The results were driven by strong oxalate reduction activity in patients with PH1, while patients with PH2 showed inconsistent results. Consequently, we see a path to approval in the U.S. and elsewhere for the PH1 indication, but not the PH2 indication. In PH1, we believe that Nedosiran is highly competitive with the currently approved product for PH1. We are reiterating our guidance of a Q4 NDA submission for Nedosiran and will continue our development program, including the PHYOX7 and PHYOX8 clinical trials for patients with PH who have compromised renal function or are pediatric, respectively. With a goal of subsequent supplemental NDA submissions to add those populations to the Nedosiran label. With respect to PH2, we are reviewing all of our data, preclinical and clinical, and conferring with experts in the PH field to understand this result. We will continue to monitor the patients with PH2 from the PHYOX2 trial, who have all rolled over into our PHYOX3 open label extension study. Extended observations may or may not provide additional insight. In any event, we do not see a near term path to including PH2 in a proposed Nedosiran drug label. In the meantime, we look forward to reading out our PHYOX4 single-dose study in patients with PH type 3. Upon review of that data, we will decide how to proceed in PH3. Up to now, we have articulated the strategy of fully integrating our company using Nedosiran as the vector and rationale for building out a commercial function in the U.S. That strategy was based on achieving a label with at least PH1 and PH2. With both of those indications and data in PH1 comparable to what was achieved in PHYOX2, we were projecting the ability to ramp sales to where our commercialization efforts would be cash flow positive in a reasonably short period of time. Without PH2 on the label, however, ramping our commercial efforts to cash flow positive is more uncertain, with substantially more capital investment required along the way. I do not believe that is the right choice for Dicerna and Dicerna shareholders. Consequently, we have decided to seek a commercial collaboration partner or partners to make Nedosiran available across all major markets, including the U.S., subject to approvals. Accordingly, we plan to forego investment in commercial infrastructure at this time. This approach will reduce our planned spend and is the basis for extending our runway guidance from the prior into 2024 to into 2025. Importantly, this does not signal any reduction in investment in our pipeline. On the contrary, we may choose to increase investment in our pipeline as we fully process the PHYOX2 data and refine our plans. Normally at this point, I'd be turning over the call to Shreeram Aradhye, our Chief Medical Officer, for additional color on our programs. However, having just had our PHYOX2 top line data call last Thursday, and recently having spoken to many of you about our Belcesiran Phase I data, we are instead going to proceed to the financial discussion. Shree is here with me and is available for questions after the prepared remarks. I will now turn the call over to Doug Pagan, our Chief Financial Officer. Doug? Thank you, Doug. I'd like to briefly walk through the key financial results for the Q2 2021 and direct you to our press release outlining these results and to our quarterly report on Form 10-Q, which was filed with the SEC this morning. Net loss for the Q2 2021 was $40.8 million, or $0.53 per share, compared to $31.8 million or $0.43 per share for the same period last year. Revenue for the Q2 totaled $41.3 million, compared to $40.4 million in the same period last year. As of 30 June 2021, we had approximately $160.2 million of current deferred revenue and approximately $268.6 million of non-current deferred revenue. Additionally, we have recorded deferred income related to our sale of royalty rights to Royalty Pharma, $1.1 million of which is current and $178.7 million non-current. R&D expenses for the Q2 totaled $56.1 million, compared to $53.4 million for the same period last year. The year-over-year change was primarily driven by increases in facilities and employee-related expenses resulting from the higher R&D headcount necessary to support our expanding pipeline and collaboration agreement. These increases were largely offset by a decrease in external direct R&D expenses. SG&A expenses for the Q2 of 2021 totaled $25.5 million, compared to $20.6 million for the same period last year. The year-over-year change was driven primarily by increased professional services. We expect SG&A expenses to remain comparable with the current period as we cease our plans to build in-house commercial operations for Nedosiran. Year to date, we have received $74.5 million in milestone fee and reimbursement payments from our collaboration partners, primarily Novo and Roche, and continue to guide to receiving $83 million for the full year 2021. These payments represent an important source of proceeds and demonstrate the value we expect these collaboration programs to continue to generate as they mature. As of 30 June 2021, we had $709.6 million in cash equivalents and held to maturity investments, compared to $544.9 million as of 31 March 2021. This cash balance, with our revised operating plans and projected proceeds from existing collaborations, should provide us runway into 2025. As Doug mentioned, we will be seeking one or more partners for global commercialization of Nedosiran. Economics from any potential arrangements have not been factored into our stated runway projections. Our strong balance sheet will allow Dicerna to continue to invest in advancing our clinical pipeline, supporting our collaboration partners, and expansion of our platform technologies. That concludes my review of the financials. I would now like to open the call for questions. Operator? Your first question comes from Jonathan Miller with Evercore ISI. Your line's open. Thanks so much, guys. I guess I'll start by asking what sort of a commercialization partner or partners you're looking for PH1 i s this more of a major pharma co-promoter, co-commercialization sort of a deal? or are you looking for contract sales? Can you give us a little bit more color about what you're looking for on that global commercialization? Secondly, also on PH, I guess now that you've had the weekend to think it over, do you have any hypothesis on PH2 failure at this point? Obviously you're still following those patients, do you have any clarity for us on when we might expect to hear an update from you on what happened biologically there? Thirdly, I know you mentioned you're waiting for PHYOX4 to make a final call on this but, a ssuming PHYOX4 and PH3 look good, would your plan at this point be to include PH3 in the same NDA as PH1, or would that be a separate submission? Hey, Jonathan, it's Rob Ciappenelli. I appreciate the questions. I'll tackle the first one. Related to partnerships for Nedosiran, I think, the best way to look at it is we're looking at this as an out-licensing opportunity, not as a contract sales strategy so w e will be looking at and have continued to speak with both global biopharmaceutical companies as well as significant regional players, all that have great acumen in the rare disease space. We'll continue those conversations and provide our updates as soon as we've gotten to a conclusion of those discussions. Thanks, Rob. John, you asked for clarity on PH2. The PH2 result was kind of a shock to the whole PH field, certainly have interacted with some KOLs and there was, I think, a fairly broad expectation that there would be activity in PH2. There isn't at the current time a leading hypothesis for why we didn't see consistent results with a monthly dosing regimen of Nedosiran, particularly after the apparent signal from a single dose in patients. That means it's really not possible for me to give guidance on when some clarity may be provided. I don't see a path in the near term for there to be any clarity. This is going to take some time to understand, and I think it's going to trigger some biochemical level work in academia w e're not going to be doing that here. With respect to PH3, I think the base operating assumption should be our NDA will be for PH1 only. We will see what the results are from a single dose of PH3 and assess them. I think anyone planning or projecting should assume the NDA filing is just PH1. Thanks, John. Thanks so much, guys. Your next question comes from Mani Foroohar with SVB Leerink. Your line's open. Hey, good morning. This is Rick on the line for Mani. Thanks for taking our questions. First, what are some of the expected timelines for getting visibility into establishing commercial partnerships for PH1? Is there any guidance you can provide here? I guess also, do you anticipate that timelines would be different based on whether you choose to have a single partner for commercialization or multiple partners here? Hey, Rick, it's Rob. In terms of our partnership discussions, those are ongoing, as I had mentioned, both globally and with regional players. I don't see it as a rate-limiting step in terms of making Nedosiran available. We're continuing first and foremost with filing the NDA t he NDA is a key resource document for filings beyond the U.S. Think about it this way. We're on track as guided to Q4 filing of the NDA. Concurrent to that, we're continuing the discussions with both global and regional players. I would expect us to, in the next couple of quarters, be able to come back with clear conclusions in terms of what we're going to be doing with Nedosiran outside the United States and as well with a partner in the U.S. I got it t hanks t hat's helpful. I guess also taking a step back, what does this change in strategy mean for commercialization plans for the rest of the wholly owned pipeline? I guess I'm just trying to think, is there any read-through here to the rest of the pipeline? Is there a certain threshold you'd like to meet to start building commercial infrastructure? or is it more likely that we're going to see commercialization partners here for the rest of the pipeline? Rick, I don't think there's any read-through for the subsequent programs. The next one likely to come down to that stage would be the A1AT program, which has a focused call point s imilarly, DCR-AUD, which would be further out, has a focused call point in addiction medicine, both of which would be appropriate for us to build out a specialty sales force when that comes to pass. The key thing we're looking at in deciding to fully forward integrate and become a commercial company is that we're confident that investment's going to generate a return, and that we're going to be cash flow positive in the, as I think we said, a reasonably short period of time. That will be a source of cash for the company i f we don't have confidence in that, then it doesn't make sense to make that investment t hat'll be made on a case-by-case basis, but the next opportunities could support building out that infrastructure. All right, perfect. Appreciate the detail here, and thanks for taking our questions again. Your next question comes from Madhu Kumar with Goldman Sachs. Your line's open. Hey everyone, thanks for taking our question. I want to start with Alpha-1 Antitrypsin. Can you kind of walk through the plan for choosing Belcesiran over the Alnylam AAT RNAi drug? Is there something that's not publicly available about the Alnylam AAT drug that kind of makes you favor Belcesiran? How should we think about the kind of election for Belcesiran over that other drug? Madhu, that took into account the decision between Alnylam and Dicerna, took into account all of the preclinical clinical data to date as well as the logistics of working with our own compound versus working with Alnylam's compound t here are quite a few things that are not publicly available about the Alnylam compound and our own, frankly, that weigh on that decision, and it's not a decision we're going to revisit. Okay, and then hinking about the kind of extrahepatic space, can you give more visibility about where you're thinking about pursuing? I know you've previously discussed the CNS space. How are you thinking about that now? and how are you thinking about more granularly timelines for putting extrahepatic compounds into the clinic? I am really pleased at the breadth of delivery to other tissues that we're seeing. In the CNS, we are partnered with Lilly, and so I think much of the CNS work will be under that collaboration. We've talked about adipose tissue and muscle and tumor-associated immune cells, and there are other tissues we haven't mentioned that we're achieving delivery. I do notice that certain other tissues are a focus for other companies. Notably, muscle would fall into that category, and I think overall there are probably a relatively fewer number of opportunities in muscle. I would like to see Dicerna in more of a white space, open field running room. When we reveal the programs, I think we'll see that we're probably tacking in a slightly different direction than some of the other oligonucleotide companies going outside the liver, drawing on the strength of GalXC-Plus to get to other tissue types. You plan the best you can, but the COVID has really disrupted preclinical timelines with respect to things like non-human primate availability. We're not going to guide right now on the clinical entry timing, and we do want to be fairly close to clinical entry before we talk about what we're doing, because we do expect people to jump into the programs we're doing. What I can say is that we have two programs that we have initiated development on w e've locked the clinical candidates, gone into manufacturing, all of that planning to preclinical entry is underway w e'll give more detail in a couple of quarters probably. Excellent. Thanks very much. Your next question comes from Stephen Willey with Stifel. Your line's open. Yeah, good morning. Thanks for taking the questions m aybe just a couple of quick clinical ones. In ESTRELLA, can you talk about the extent of fibrosis that you're allowing in patients who will be eligible to enroll into that study? Are these going to be F3s, F4s? Are you allowing cirrhotic patients into that study? With respect to AUD, in terms of patient eligibility, obviously this is a healthy volunteer population. Healthy volunteers, I guess, do consume alcohol. Is there any kind of restriction or do you have some kind of guardrails around consumption in that study, or at least attempt to, just for the first Phase I experience? Yeah. Hi, it's Shreeram. In ESTRELLA, our goal is to enroll the population that gives us a good read on the benefits of knocking down the mutant protein and potential consequent benefits on liver histology so w e are enrolling a broad population with representative fibrosis. That's ongoing. Our goal there is to make sure that we've designed the study in a manner that gives us a good read on seeing a difference in the size of the study that we have designed. So- I think the worst case patients, so the decompensated cirrhotics are not a part of this trial. Other than that, we'll be on a broad range. AUD? Stephen, could you repeat your question on AUD for me, please? I'm just kind of curious. In the healthy volunteer experience for AUD, is there some kind of eligibility criteria around alcohol consumption in those patients who are going to enroll? I'm just kind of curious if there's going to be any kind of early efficacy signal that could emerge out of that study just based on the fact that you're going to see healthy volunteers consume alcohol during a 24-week period post-dose. Yeah. I think we expect to do this in a stepwise manner, and that the first goal of the Phase I single ascending dose is to establish safety and tolerability and, as Doug said, do a very controlled exposure to ethanol as a way of gathering the pharmacodynamic data that confirms for us whether or not we have established the biological state in a human of achieving the necessary knockdown in the liver and what effect that has. Going in, our guidance will, of course, be for people to avoid alcohol intake. My expectation is that over time, the Phase I study will give us a read on what people's reaction to drinking alcohol outside of the trial might be, but coming in in the initial safety single ascending dose, our goal is on making sure that the exposure to ethanol is in a controlled setting to make sure that we have a clear read on what the TD of the drug is. Over time, I make sure that in the multiple ascending dose, we should be able to gather more reads on efficacy. In essence, Steph, we do expect to learn a lot about the physiological response of someone who has taken DCR-AUD to the intake of alcohol. That's not the approvable endpoint t he approvable endpoint will be likely harm reduction in patients who have AUD, that's a sort of loss control and harm reduction being an assessment of their ability to regain more control over their consumption of alcohol so o n that direct sort of approvable endpoint, we're not going to get anything. There's believed to be very clear linkage between the physiological response and that behavior as seen by the rates of AUD in people with naturally occurring ALDH2 mutations. Not exactly the same thing we're doing, but closely related. We should get the important physiological feedback, and that's something we'll discuss and look forward to talking about it when we see it. All right. Thanks for taking the questions. Our next question comes from Yaron Werber with TD Cowen. Your line's open. Hi, guys. This is Brendan on for Yaron t hanks for taking the questions. Just a quick one from us, I guess really looking at the A1ATD program. I guess looking at the landscape here, what can you tell us maybe about Belcesiran specifically and maybe more so your kind of goals and expectations for Phase II that you think are going to really be necessary to differentiate the drug? I guess my point is really kind of given that there are other competitors a bit ahead of you in development in that space as well, where do you really see the bar for Belcesiran there to stand out? maybe what kind of gives you confidence you can meet that? Thanks. Hi, Brendan. There is one other company Phase II to treat AATLD. Not exactly a crowded field. I'm sure you're aware almost every pharmaceutical market has multiple entrants. One does think about how the various products are differentiated i n this case, because the mechanism of action is the same, there isn't a mechanistic differentiation. In the PH1 indication, we have what I think is a very positive differentiation based on the mode of administration with our prefilled syringes that for administration by patients with PH1 at home on their own compared to the competitor product which has a healthcare professional involved and is weight-based and so variable volume and so not in prefilled syringes. We shall see in A1AT as we head into pivotal trials and our competitor heads into pivotal trials what those regimens are, and so that will assess how we want to present the product relative to a competitor. I think the most important dynamic has to do with the fact that most of the diagnosed patients with AAT liver disease- -are in fact patients of AAT lung disease as well because that has a clearer diagnostic path currently and with approved products has had a fair amount of patient finding that's gone over for a long period of time and i think there's a natural pairing between augmentation as a therapy for the lung and RNAi as a therapy for the liver. You in fact see that the competitor product has formed a collaboration with an augmentation provider. It is, as it happens, a minor entrant in the augmentation market. So i think that presents a fairly obvious, counter sort of strategy for us with respect to pairing our RNAi compound with augmentation that we intend to pursue t here isn't any particular time pressure to do that. But, there, I think that solution providing associated with lung and liver is going to be very interesting, and it'll be to one's advantage to be with a market leader as opposed to with a more minor player. All right, great. Thanks very much. Your next question comes from Luca Issi with RBC Capital Markets. Your line's open. Oh, terrific y eah, Luca Issi from RBC Capital Markets. Just a few questions here. Maybe the first on Nedosiran. If I recall it correctly, you previously guided that you estimated peak revenues here or peak sales, I should say, between $500,000 and%1 billion. Wondering if you can comment on how you're thinking about peak market opportunity here now that you've seen the Phase III. Then maybe on business development, wondering if there's any appetite to broaden the scope of your extrahepatic delivery via BD. We've seen recent deals between Ionis and Bicycle and Alnylam and PeptiDream. Wondering if this is something that you're also considering. Then finally, maybe on A1AT, wondering if you can comment on the timelines here for seeing the actual data in patients here. Thanks so much. Hi. I'll try to write to track the questions there i think the doser and the sales potential was the first one. I'm not going to get into detailed numbers here, but we had PH2 in our forecast as being a significant minority of the total sales. Less than half, but a significant amount. For PH3, relatively small fraction. But PH2 was, as a significant minority, does taking an off the label or not getting it included in the label, it's a significant effect. I'm not going to get more specific than that on our prior forecast, which obviously is no longer applicable given PH2 is no longer included. Shifting to business development around delivery. That is something that we are considering, and we've had conversations with players in the field. Having said that, we are very pleased with the delivery we're getting with our in-house technology, which as I mentioned, is getting us to a pretty broad array of tissues so w e're not feeling a particular- -need at this point to form a collaboration with someone who can help us get to other tissues w e are already in a situation where the number of opportunities we're considering far outstrips the number of programs that we can plausibly prosecute. It's definitely in the mix, and there are some really interesting approaches out there. The strategy that we have taken in our research labs has been paying off, and we're really pleased with our in-house work. Perfect m aybe timing of the A1AT data from ESTRELLA i s there any kind of guidance that we should think about it? All right. I forgot about that one. Shree, you want to just quickly- Yeah. Luca, Luca, it's Shree. You can do the math i mean w e are enrolling a study that has two cohorts with paired biopsies that happen at 24 weeks and 48 weeks with up to 27 subjects. We haven't yet fully decided on the timing of a potential interim analysis. The study started enrolling earlier this year. We are getting some sites on board out in Europe. I think it'll be some time. You know, we will need to have a decent number of subjects having had the right number with paired biopsies to be able to meaningfully present information that is interpretable and from which we can draw recent conclusions. That's about the guidance I can give you right now. Got it. Super helpful, guys. Thanks so much. Your next question comes from Yigal Nochomovitz with Citigroup. Your line's open. Hi, Doug. Thank you very much for taking the questions i just had a high-level question. At this point, do you believe you have an optimal number of pharma partnerships, or are you willing to entertain additional partnerships to further extend the footprint for the GalXC technology platform? If the latter is the case, are there certain disease areas that you believe would be better suited for partnering versus developing on your own? Sure, Yigal h appy to take this one. We've had a really nice set of collaborations, and they're good partners to work with. There is a logistical challenge in adding more names to that list. Our ability to make clinical candidates definitely outstrips our development capabilities, and I think that's true for the foreseeable future. With an excess of opportunities and candidates, to me, and I think to the whole team here, it makes sense to have someone else take things forward that we're not going to take forward. There is still, I think, rationale in our strategy to enter into collaborations on opportunities that we don't intend to pursue on our own, o ur capabilities to pursue opportunities are a lot broader than they were in 2018 when we did our Alexion and Lilly deals. Our pressure to bring in cash, which was fairly strong at that period of time, now we have a lot of luxury of choosing our spots. Our posture is a little different with respect to collaborations now i t is to really spend our time figuring out what we are going to do, and then later we'll take the things that we're not going to do, and we would like to find a path forward for those. Some of the spaces that we are working in, we've mentioned delivery to adipose tissue, t here are clear metabolic and sort of obesity indications associated with that probably are not right for Dicerna. I would note we're already collaborating with the two largest players in the metabolic space. It would be nice to perhaps extend those collaborations into GalXC-Plus. That wouldn't burden the logistics anymore, but it would satisfy the goal of bringing in capital and making sure those programs move forward. I see a role for the collaborations, but whereas in 2018, 2019, it was a primary part of strategy, it's really a secondary part of strategy now, and the primary is building out our own pipeline. The collaborations will fit in a secondary role but i t's still an important piece, I think, o ne of the things that all of us would like to do, per what we have as our vision statement here at Dicerna, is maximize the impact of RNAi on medicine t hat means, again, a lot of drugs, w e can make candidates, w e can make a lot of candidates. It's very modular. We want a lot of candidates to move forward i 'm really pleased there are 15. We want that number to keep growing and growing. I hope that gives you some perspective t hat's well short of any sort of guidance, but I think it is informative to what our mindset is about how we're going to think about collaborations. Thank you. Yeah, that's very helpful t hanks, Doug. Your next question comes from Mayank Mamtani with B. Riley Securities. Your line's open. Hi. Yes, this is William Wood on for Mayank Mamtani. Thank you again for taking our questions g lad to see you being proactive with your corporate strategy in the follow-up from PHYOX2 last week. I was curious about what learnings might be applied from your ex-US licensing process and now that you've made the choice to make global rights available. Hey, William, it's Rob i n terms of some insights, I'll provide a couple. High degree of interest. William, that interest not only was in Nedosiran beyond the U.S., but a number of the parties kept coming back to us and saying, "What about the U.S.?" I think that puts us in a really good spot to continue these conversations both with global and regional players. Bottom line is that Dicerna is going to do whatever we can to most appropriately put this into the market so that patients have an option, not only in the U.S., but globally. And, frankly, these conversations, I feel put us in a good place to work towards that. The key insight is that a number of the players that we've been talking to have some, or some have had some interest in the U.S. as well, but we'll be continuing to look specifically across all the different stakeholders and proceed accordingly. Back to Doug. Thanks, Rob. Awesome. Oh, go ahead. I didn't have anything more to add. I think we're going to wrap up at this point O perator, is there any additional question? All right. That concludes our question and answer session. I would now like to return the call over to Doug Fambrough for closing remarks. I want to thank everyone for participating this morning. I want to reiterate that PHYOX2 is an important milestone, and I'm really pleased with our platform that bodes very well for the future, and I look forward to updating the additional GalXC programs as they mature in subsequent calls. Thanks, everybody. Bye-bye. Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all disconnect.