Dicerna Pharmaceuticals, Inc.
Q2 2021 Earnings Call Transcript

Published: 9 Aug 2021

[Operator:]

Good morning, ladies and gentlemen, and welcome to the Dicerna Pharmaceutical's Second Quarter 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, Attorney Solvix .Please go ahead.

[Tierney:]

Thank you, Operator. Good morning, everyone, and thank you for joining us to review Dicerna 's Second Quarter 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 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 second-quarter 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 collaboration 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 preclinical 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.

[Doug Fambrough:]

Thanks, Tierney (ph). 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 the 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. This 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 4 years ago that Dicerna was a microcap Company, trading at a little over $3 per share, no collaborations, no Galaxy clinical data, And less than $100 million on the balance sheet. Today, we are in Q2 with almost $710 million, the large majority coming from technology monetization with 6 collaborations, 6 different companies, engaged in moving Dicerna GalXC molecules forward, 6 clinical-stage programs, including Nedosiran, 9 more that have entered pre-clinical 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 4 years. What really excites me though, is what we can accomplish over the next 4 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 2, we expect to move this deep into pivotal development. We anticipate the RG6346 program for chronic HPV, which is in a Phase 2 combination trial being conducted by Roche, will have further progressed in clinical development and completed its 5 Phase 2 cohorts. And with success, we'll have opted into 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 had moved to advance trials, potentially breaking open a vastly underserved market. We expect multiple programs from our Novo collaboration to have entered development, and we expect to have opted into 2 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, 1 per quarter, over the next 2 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 the early development of 2 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 4 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. But first, let's come down from the high level to the actual corporate updates for the second quarter, 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 one study, which met our objective, demonstrating strong dose-dependent reductions in serum Alpha-1 Antitrypsin in healthy volunteers with the administration of a single dose of Belcesiran. In this analysis of the 4 completed active treatment dose cohorts at 0.1, 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 placebo-controlled Phase 2 ESTRELLA trial of Belcesiran in June. The ESTRELLA Phase 2 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 the study progresses, we're looking forward to having a better understanding of Belcesiran's potential to treat the underlying cause of AATLD. Also 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. And we are now clear to begin phase one. We plan to initiate a 24-week randomized double-blind placebo-controlled phase one 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 LY-3819469, targeting LPA for cardiovascular disorders or LP a, sometimes referred to. This is the second clinical-stage, investigational Galaxy 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 1 dosing of the compound, which began in June. There are also 2 Lilly partnered programs in IND enabling studies, in addition to the 2 clinical-stage programs. Also, in May, Boehringer Ingelheim accepted DCRLIP2, an investigational Galaxy RNAi candidate for the treatment of nash to advance to the development stage. This candidate acceptance triggered a single-digit, multi-million-dollar pre-clinical milestone to Dicerna, and pre-clinical work is underway. And earlier this year, we added, to the development pipeline, a 2nd candidate under the Novo collaboration. Finally, we have 2 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 we'll continue our development program, including the PHYOX7 and PHYOX8 clinical trials for patients with PH who have compromised renal function or our 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, pre-clinical 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 forgo 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 1 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?

[Doug Pagan:]

Thank you, Doug. I'd like to briefly walk through the key financial results for the second quarter of 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 second quarter of 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 second quarter totaled $41.3 million compared to $40.4 million in the same period last year. As of June 30, 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 second quarter 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 agreements. These increases were largely offset by a decrease in external direct R&D expenses. G&A expenses for the second quarter of 2021 totaled $25.5 million compared to $20.6 million for the same period last year.

[Doug Fambrough:]

The year-over-year change was driven primarily by increased professional services. We expect G&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 continued to guide to receiving 83 -- I'm sorry, $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.

[Doug Pagan:]

As of June 30, 2021, we had $709.6 million in cash, cash equivalents, and held-to-maturity investments, compared to $544.9 million as of March 31st, 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 the 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.

[Operator:]

. Your first question comes from Jonathan Miller with Evercore ISI, your line is open.

[Jonathan Miller:]

Thanks so much, guys. I guess I will start by asking what sort of commercialization partner or partners you're looking for, for PH1, is 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? And then 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? And obviously, you're still following those patients, but do you have any clarity for us on when we might expect to hear an update from you on what happened biologically there. And then thirdly, I know you mentioned you're waiting for PHYOX4 to make a final call on this, But assuming 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?

[Rob Ciappenelli:]

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 we will be looking at and have continued to speak with both global biopharmaceutical companies, as well as significant regional players. All they have great acumen in the rare disease space. We'll continue those conversations and provide updates as soon as we got to the conclusion of those discussions.

[Doug Fambrough:]

Thanks, Rob. So, John, you asked for clarity on PH2. The PH2 result was a shock to the whole PH field. Certainly have interactive with some KOL s, and there was, I think, a fairly broad expectation that there will be activity in PH2 and 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 not possible for me to give guidance on when some clarity may be provided, but I don't see a path in the near term for there to be any clarity, and this is going to take some time to understand and I think it's going to trigger some biochemical level work in academia where we'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. But I think anyone planning or projecting should assume the NDA filing is just PH1.

[Rob Ciappenelli:]

Thanks, Doug.

[Jonathan Miller:]

Thanks so many guys.

[Operator:]

And your next question comes from Mani Foroohar with SVB Leerink. Your line's open.

[Rick:]

Hey, good morning. This is Rick on the line for Mani. Thanks for taking our questions. First, what are some of your expected timelines for getting visibility into establishing commercial partnerships for PH1? Is there any guidance you can provide us here? And 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?

[Rob Ciappenelli:]

Hey Rick, it's Rob. In terms of our partnership discussions, those are ongoing both as I've 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. The NDA is a key resource document for filings beyond the U.S. So think about it this way. We're on track, as guided, to the 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 gonna be doing with Nedosiran outside the United States, and as well with a partner in the U.S.

[Rick:]

Got it. Thanks. That's helpful. And I guess also taking a step back, what is 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?

[Doug Fambrough:]

So Rick, I don't think there's any read-through for the subsequent programs but the next one likely to come down to that stage would be the A1AT program, which has a focus call point. Similarly, DCR-AUD, which will be further out, has a focus call point and addiction medicine, both of which would be appropriate for us to build out, especially the sales force when that comes to pass. The key thing we're looking at, in deciding to fully -- forward integrate, become a commercial Company, is that we are confident that investments are going to generate a return and that we're going to be cash-flow positive. And as I -- I think we said a reasonably short period of time, and then that will be a source of cash for the Company. If we don't have confidence in that, then it doesn't make sense to make that investment. That will be made on a case-by-case basis, but the next opportunities could support building out that infrastructure.

[Rick:]

All right, perfect. Appreciate the detail here, and thanks for taking our questions again.

[Operator:]

Your next question comes from Madhu Kumar with Goldman Sachs. Your line's open.

[Madhu Kumar:]

Hey, everyone, thanks for taking our questions. So I want to start with alpha-1 antitrypsin, so can you walk through the big -- the plan for choosing Belcesiran over the Alnylam ATRNAI drug. Is there something that's not publicly available about the Alnylam ATRNAI drug that kind of makes you favor Belcesiran, or how should we think about the election Belcesiran over that other drug?

[Doug Fambrough:]

So Rob, that took into account -- the decision between Alnylam and Dicerna took into account all of the pre-clinical, clinical data to date, as well as the logistics of working with our own compound, versus working with Alnylam 's compound, there 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.

[Madhu Kumar:]

Okay. And then thinking about the extrahepatic space, can you give more visibility of where you're thinking about pursuing? I mean, I noted we've previously discussed the CNS space, how are you thinking about that now or how are you thinking about timelines for extrahepatic compounds into the clinic?

[Doug Fambrough:]

So I am really pleased that the breadth of delivery to other issues that we're seeing. So in the CNS, we are partnered with Lilly. And so I think much of the CNS work will be under that collaboration. But we've talked about adipose tissue and muscle and tumor-associated immune cells and there are other issues, we haven't mentioned that we're achieving delivery. I do notice that certain other tissues are a focus for other companies. Notably, the muscle would fall into that category. And I think overall there is probably a relatively fewer number of opportunities in muscle. I would like to see Dicerna in more of a whitespace, open field running room. So you -- when we reel the programs, I think we'll see that we are probably attacking in a slightly different direction than some of other early going to tied companies going outside deliver. Drawing on the strength of Galaxy Plus to get to other tissue types. The pre-clinical timelines are now -- we have planned the best we can, but COVID has really disrupted pre-clinical timelines, with respect to things like non-human primate availability. And 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. So what I can say, is that we have 2 programs that we have initiated development on. We've locked the clinical candidates, gone into manufacturing. All of AAT planning to pre-clinical entry is underway and we'll give more detail in a couple of quarters probably.

[Madhu Kumar:]

Excellent. Thanks very much.

[Operator:]

And your next question comes from Stephen Willey with Stifel. Your line is open.

[Stephen Willey:]

Yeah, good morning. Thanks for taking the questions. Maybe just a couple of quick clinical ones. In Estrella can you talk about the extent of fibrosis that you're allowing a patient who will be eligible to enroll into that study. Is -- are these going to be F3s, F4s? Are you allowing serratic (ph) patients into that study? And then 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 attempts to, just for the first Phase 1 experience?

[Shreeram Aradhye:]

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 we 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 the difference in the size of the study that we have designed. the worst-case patients that will be compensated, so I think, are not like -- are not a part of this trial. But other than that, it will be on a broad range. And Stephen, could you repeat your question on AUD, for me, please?

[Stephen Willey:]

Yeah. 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 curious if there is 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.

[Shreeram Aradhye:]

We -- Yes, I think we expect to do this in a stepwise manner and that the first goal of Phase 1 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. On-going in our guidance will, of course, be for people to avoid alcohol intake. My expectation is that, over time, the Phase 1 study will give us a read on what people's reactions to drinking alcohol outside of the trial might be. But coming in, in the initial safety, the single ascending dose, our goal is on making sure that the exposure of ethanol is in a controlled setting to make sure that we have a clear read on what the TD of the drug is. But over time, I make sure that in the multiple ascending doses we should be able to gather more reads on efficacy.

[Doug Fambrough:]

In essence, Steve, 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. The approvable endpoint will be likely harm reduction in patients who have AUD. That's sort of loss control and harm reduction being an assessment of their ability to regain more control over their consumption of alcohol. So on that direct approvable endpoint, we're not going to get anything. But there is believed to be a very clear linkage between the physiological response and that behavior as seen by the rates of AUD, and people with naturally occurring ALDH2 mutations. Not exactly the same thing we're doing, but closely related. So we should get important physiological feedback. And that's something we'll discuss and look forward to talking about it when we see it.

[Stephen Willey:]

All right. Thanks for taking my questions.

[Operator:]

Your next question comes from Yaron Werber with Cowen. Your line's open.

[Brandon:]

Hi guys, this is Brandon on for Yaron. Thanks for taking the question. Just a quick one from, I guess, really looking at the A1ATD program. So 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 2 that you think are going to really be necessary to differentiate the drug. I guess my point is really, given that there are other competitors a bit ahead of you in development in that space as well, where you really see the bar for Belcesiran there to stand out? And maybe what gives you the confidence you can meet that. Thanks.

[Doug Fambrough:]

Hi, Brandon. So there is one other Company in Phase 2 to 3 AATLD. So not exactly a crowded field. And I'm sure you're aware almost every pharmaceutical market has multiple entrants. But one does think about how the various products are differentiated. In this case, because the mechanism of action is the same, there isn't a mechanistic differentiation. In the PH1 indication we have a -- what I think is a very positive differentiation based on the mode of administration with our pre-filled syringes. that is 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's heads into pivotal trials, what those regimens are. And so that will assess how we want to present the product, relative to a competitor. But 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 is a natural pairing between augmentation as a therapy for the long and RNAi as a therapy for the liver. And you in fact see that the competitor product has collaboration with an augmentation provider. It is, as it happens a minor interest in the augmentation market. And so I think that presents a fairly obvious counter strategy for us with respect to hearing, our RNAi compound with augmentation that we intend to pursue. There 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 will be to one's advantage to be with the market leader, as opposed to with a more minor player.

[Brandon:]

All right, great. Thanks very much.

[Operator:]

Your next question comes from Luca Issi with RBC Capital. Your line is open.

[Luca Issi:]

Luca Issi from RBC Capital Markets. Just a few questions here. Maybe the first one. Nedosiran If I recall correctly, you previously of your estimated peak revenues, to your peak sales, I should say, between $500 thousand and a billion, dollars. Wondering if you can comment on how you're thinking about peak market opportunities here now that you've seen Phase 3 and then maybe on business development? Wondering if there's any appetite to broaden the scope of your extrahepatic (ph) delivery via BD. We've seen recent deals between Ionis and Bicycle, Alnylam, and PeptiDream. So wondering if this is something that you're also considering? And then finally, maybe on A1AT, wondering if you can comment on the timeline here for seeing the actual data in patients here? Thanks so much.

[Rob Ciappenelli:]

Hi. Trying to write -- to tackle the questions there. I think Nedosiran sales potential was the first one. 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 1/2, but a significant amount. For PH3, relatively small fraction. But PH2 was a -- has a significant minority thus taking it 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 forecasts, which obviously it's 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 we're not feeling a particular need at this point to form a collaboration with someone who can help us get to other tissues. We are already in a situation where the number of opportunities we're considering far outstrips the number of programs that we can plausibly prosecute. So it's definitely in the mix and there are some really interesting approaches out there. But the strategy that we have taken in our research labs has been paying off, and we're really pleased with our in-house work.

[Luca Issi:]

And maybe the timing of the A1AT data for -- from ESTRELLA, is there any guidance that we should think about it?

[Rob Ciappenelli:]

I forgot about that one. Shree, you want to just quickly

[Shreeram Aradhye:]

Yeah. This is Shree. You can do the math. We're enrolling a study that has 2 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 potential interim analysis. The study started enrolling earlier this year. We are getting some sites on board in Europe. So I think it will be some time. We will need to have a decent number of subjects. Having had the right number of -- with paired biopsies to be able to meaningfully present information that is interpretable and from which we can draw reasoned conclusions. So I'll -- that's above the guidance I can give you right now.

[Luca Issi:]

Got it. Super helpful guys. Thanks so much.

[Operator:]

Your next question comes from Yigal Nochomovitz with Citigroup, your line is open.

[Yigal Nochomovitz:]

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 Galaxy technology platform? And 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?

[Doug Fambrough:]

Sure, Yigal. Happy to take this one. We've got 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. And with an excess of opportunities in candidates, to me, and I think to the whole team here, it makes sense to have someone else take things forward that were not going to take forward. So there is still, I think, the rationale in our strategy to enter into collaborations on opportunities that we don't intend to pursue on our own. Our capabilities to pursue opportunities are a lot broader than they were in 2018 when we did our Alexion and Lilly deals. And our pressure to bring in cash, which was fairly strong at that period of time, now is -- we have a lot of luxury of choosing our spots. And so our posture is a little different with respect to collaborations now. It is to really spend our time figuring out what we're 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're working in, we've mentioned adipose tissue, there are clear metabolic and obesity indications associated with that, that probably are not right for Dicerna. I would note, we are already collaborating with the two largest players in the metabolic space. It would be nice to perhaps extend those collaborations into GalXC Plus. It wouldn't burden the logistics anymore, but it would satisfy the goal of bringing in capital and making sure those programs move forward. So I see a role for the collaborations. But whereas in 2018, 2019, it was a primary part of a strategy. It's really a secondary part of strategy now. And the primary is building out our own pipeline. And then the collaborations will fit in a secondary role, but it's still an important piece, I think. One of the things that all of us would like to do per our -- what we have as our vision statement here at Dicerna is maximize the impact of RNAi on medicine. That means getting a lot of drugs. We can make candidates. We 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. So I hope that gives you some perspective, that's the -- well short of any sort of guidance, but I think does -- it is informative to what our mindset is, about how we're going to think about collaborations.

[Yigal Nochomovitz:]

Thank you. That's very helpful. Thanks, Doug.

[Operator:]

And your next question comes from Mayank Mamtani with B. Riley Securities, your line is open.

[William Wood:]

This is William Wood on for Mayank Mamtani. Thank you again for taking our questions. Glad to see you being proactive with your corporate strategy and follow-up from PHYOX2 last week. I was curious about what learnings might be applied for your ex-U.S. licensing process and now that you've made the choice to make global rights available?

[Rob Ciappenelli:]

Hey William, it's Rob. In terms of some insights, I'll provide a couple. A high degree of interest. And William that interest not only was in Nedosiran beyond the U.S., but a number of parties kept coming back to us and saying we'd vote the U.S. So I think that puts us in a really good spot to continue these conversations both through global and regional players. The bottom line is that Dicerna is going to do wherever 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. So 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.

[William Wood:]

Thanks

[Doug Fambrough:]

I didn't have anything more to add. And I think we're going to wrap up at this point. An operator is there any additional questions?

[Operator:]

That concludes our question-and-answer session. I would now like to return the call over to Doug Fambrough for closing remarks.

[A - Doug Fambrough:]

I want to thank everyone for participating this morning. I want to reiterate that PHYOX2 is an important milestone, and I am really pleased with our platform. It 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.

[Operator:]

Ladies and gentlemen. This concludes today's conference. Thank you for your participation and have a wonderful day. You may all disconnect.