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spk11: Good afternoon and thank you to everyone for taking the time to join us today. With me on today's call from Alpine are Dr. Mitchell Gold, Executive Chairman and Chief Executive Officer, Dr. Stanford Peng, President and Head of R&D, Paul Rickey, Chief Financial Officer, and Dr. Remy Durand, Chief Business Officer. Before I turn the call over to Mitch, I'd like to remind you that we'll be making forward-looking statements during today's call. These forward-looking statements represent our views as of today and are based on our current expectations and consequently involve risk and uncertainties. Actual results could differ materially from those anticipated in such forward-looking statements as a result of such risks and uncertainties. I encourage you to refer to the most recent SEC filings regarding the risk factors associated with these statements. Mitch, please go ahead.
spk05: Thank you, Tamrae, and thank you to all those who are participating in the webcast today. 2023 was a transformational year for Alpine. with initial IgA nephroscopy data presented at the American Society of Nephrology's Kidney Week, suggesting a best-in-class profile for Povatectin sets, our wholly-owned, next-generation, dual-VAC April inhibitor, with once-monthly dosing developed using our direct evolution platform. We are still only in the early stages of exploring the full potential of Povatectin sets. On the back of strong enthusiasm around ASN, we close an oversubscribed $150 million equity offering to accelerate multiple development activities. With our encouraging data set in IGAN, convenient once-monthly dosing regimen, and strong balance sheet, we are rapidly advancing development of POVI as a potentially meaningful new therapeutic option for patients living with IGAN, lupus, and multiple other autoimmune and inflammatory diseases. Looking ahead, we are well positioned for meaningful catalysts in 2024 and beyond. We plan to present additional data on pogutaxiceptin IgA nephropathy, including follow-up data from the 80 mg monthly and initial data from the IgAN 240 mg monthly dose cohorts at the Rural Congress Interfology meeting next month. Following these data, in the second half of the year, we plan to initiate Rainier, pivotal Phase III study of pogutaxiceptin IgA nephropathy, and Denali, a Phase II study of pogutaxiceptin SLE. In addition to updates in our clinical studies, we look forward to sharing translational data that further supports the best and best potential of Cova-Tachyceps in multiple diseases. I now hand the call over to Stanford to review our progress and provide updates on our development plan for Cova-Tachyceps in more detail. Stanford. Thank you, Mitch.
spk04: As Mitch has described, the emerging clinical findings with Cova-Tachyceps continue to inspire us to advance as rapidly as possible. At last year's kidney week meeting, we reported the first clinical observations with pulpitacicept and IGAN, where it was associated with a greater than 50% reduction from baseline and proteinuria at six months, as measured by urinary protein and creatinine ratio, or UPCR. In addition, the majority of patients met remission criteria as defined as reduction in UPCR to less than 0.5 grams per gram, at least a 50% reduction in UPCR from baseline, and stable renal function as assessed by estimated glomerular filtration rate, or EGFR. Importantly, these findings were associated with significant reduction in the key IgM biomarker, GGIGA1, supporting the concept of POVATAC-CEP as a disease-modifying therapy. As a reminder, the improvable efficacy target has historically been a 30% reduction in protein area at 9 months. While our very encouraging findings continue to hold up with additional patients and with longer follow-up, POVATAC-CEP could indeed be a particularly compelling therapeutic option for patients with IgM and other autoimmune diseases. Therefore, since ASN, we've been making every effort to prepare the program and the company for the next pivotal phase of development. We look forward to the opportunity to provide a formal clinical data update of Cova-Tac Accept and IGAN next month at the World Congress of Nephrology, which will take place in a late-raising poster. In the meantime, our primary development goal for Cova-Tac Accept is its advancement this year to a pivotal trial in IGAN, which we're calling Rehear. Of course, several other autoimmune and or inflammatory disease indications remain of great potential interest for Cova-Tachycept. First, lupus remains a key indication, second only to IgAIN, supported by the clinical validation of the pathway in the disease by BAC inhibition and wild-type Tachy-Ig molecules. We continue to plan to initiate a Phase II study in lupus, called the NAWI, later this year. Second, we continue to explore other renal indications in the Ruby 3 study, At last year's kidney week, we described a single patient with primary membranous nephropathy, or PMN, who had achieved an immunological remission on comatose. Such a finding suggests that other autoantibody-related diseases may benefit from comatose. Indeed, we continue to enroll additional subjects with PMN. As a reminder, Ruby 3 is also enrolling lupus nephritis and has just recently opened an ANCA-associated vasculitis cohort. In addition, we continue to explore autoimmune cytopenias in the Ruby 4 study. We look forward to future opportunities to share these collected data. Finally, ongoing and emerging preclinical and translational data continues to suggest additional therapeutic areas like neurology or allergies for COVID-19 test. Last year at Kidney Week, we observed a significant reduction in IgE in IgAN patients who have received COVID-19 test, suggesting potential applicability in IgE-related diseases like allergies. We also presented data on Cova-Tachycept in a mouse model of Myasthenia gravis at the American Association of Neuromuscular and Electrodiagnostic Medicine annual meeting. And next month, we will present data on Cova-Tachycept in a mouse model of autoimmune encephalitis at the American Academy of Neurology meetings. In the Myasthenia model, Cova-Tachycept appeared superior to clinically relevant comparators such as FCR inhibition or B-cell depletion. Weaknesses may in part be related to some unique biophysical and or other developmental characteristics of Clobatacacept, which confer greater tissue penetration and or distribution than wild-type tachy-IT. Data supporting this latter statement will be part of a poster later this week at the European Group's meeting. Altogether, these developments only reinforce the potential for Clobatacacept As a reminder, Phobatacacept was discovered in-house by our proprietary directed evolution protein engineering platform, which has been quite productive and continues to generate novel drug candidates that may be of great future interest. We therefore look forward to opportunities to provide further updates, not only on Phobatacacept, but also on our development pipeline in the near future. I'm now trying to call over to Paul Rickey, our Chief Financial Officer.
spk03: Thank you, Stanford. And now, I'll provide a brief overview of our financials for the year ended December 31st, 2023. For the year ended 2023, collaboration revenue was $58.9 million compared to $30.1 million for the same period in 2022. The increase in collaboration revenue relates primarily to a $24.9 million increase in AbbVie revenue, of which $20.4 million is due to a cumulative catch-up adjustment resulting from the completion of enrollment in synergy for the amendment with AbbVie, and a $4.5 million increase in Amgen revenue, driven primarily by the expiration of Amgen's option to select a third research program. These increases were partially offset by a $0.6 million decrease in Adaptimmune revenue as we completed our final deliverables under the agreement in June 2023. Research and development expenses for the year ended 2023, inclusive of non-cash expenses, were $80.9 million and $70.2 million for the same period in 2022. The increase of $10.7 million was driven by an $8.2 million increase in POVA-TACOSEP costs, primarily related to higher clinical, process development, and manufacturing expenses. A $1.3 million increase in the COSI-COLSEP costs personnel-related costs. General and administrative expenses for the year ended 2023 were $22.2 million compared to $18 million for the same period in 2022. The increase of $4.3 million was primarily attributable to increases in personnel costs and professional services. The company recorded net losses of $32.2 million and $57.8 million for the year ended 2023 and 2022, respectively. As of December 31st, 2023, Alpine's cash and investments totaled $368.2 million, which we anticipate should be sufficient to fund our planned operations into 2026. I will now hand the call back to Mitch.
spk05: Thanks, Bob. As Stanford highlighted, we are highly encouraged by the initial IGN data from COVID-19 access and are just beginning to explore the full potential of this unique, potentially best-in-class molecule. We look forward to a catalyst-rich year with data updates in IGaN and other indications, and the planned initiation of Rainier, our pivotal Phase III study in IGaN, and Denali, our Phase II study in SLE. In addition, we continue to evaluate the potential for pubic tachyceps in additional indications, and as Stanford mentioned, we continue to invest in our immunology discovery efforts to advance the next generation of programs from our directed evolution platform. Now I'll turn the call over to the operator for questions.
spk09: Thank you, Dr. Gold. If you would like to ask a question, please press the star key and the number 1. If you press star 1 a second time, it will remove your line from the queue. To be able to answer as many questions as possible, we ask that you please limit yourself to one question and one follow-up. And we will pause for just a moment to compile the Q&A roster. And we will take our first question from Tara Bancroft with TD Cowan. Your line is open.
spk07: Hi, good afternoon. Thanks for hosting this call. So I have a question on ITP expectations. So first, can you provide some potential conferences that the data might be presented, like how you mentioned for the kidney data, it might be at two different ones during the second half, and now you've leveled it down. you know, just some granularity around potential venues? And then what level of efficacy you're looking for to potentially start a phase three study?
spk05: Yeah. So for Ruby Forge, I think what we're looking at is just ITP. I mean, we have interest in other indicators beyond just ITP. So, you know, obviously you have ITP, we have WAHA, and we have cold and gluten disease. And our goal is to be able to, as we mentioned, to be able to present that data in the first half of this You had one other question? Remember what that was again? Yeah. That's what we want to see in ITP. Yeah. I'll remind you that these are highly refractory patients. So, you know, they're third or fourth line therapy patients. So, I think if we saw, you know, meaningfully improvement in platelet count, you feel like that 20% response rate, that would be meaningful.
spk12: Okay, great, thanks.
spk09: And we will take our next question from Mike Oltz with Morgan Stanley. Your line is open. And Mr. Oltz, your line is open. Please check your mute button.
spk13: Sorry about that. Hey, guys, thanks for taking the question. Maybe two on IGAN and the update at WCN. Can you maybe give us a sense of how many patients we should expect at the 80 and 240 milligram dose and the level of follow-up? And then maybe secondly, just what's your current thinking about selecting the go-forward dose and what would you need to see at the 240 milligram dose to bring that one forward? Thanks.
spk05: Yeah, thanks, Mike. So for WCN, what you should anticipate seeing is, for the first time, we'll get a look at nine-month data at the 80 milligram dose cohort level. Obviously, the nine-month data is really important because that's the end point that the regulators use for an accelerated approval. And I'll remind you that the benchmark there historically has been a 30% reduction in UPCR. And in six months, we were seeing over a 50% In addition, at WCN, you'll get your first look at the 240 milligram data. We expect that to be a relatively small number of patients thus far and with limited follow-up, but we will get a first look at 240. As we look at things now, things may need to look dramatically better with 240 over 80. At 80 milligrams, we're already seeing best-in-class reductions in prokaryote, and that continues to hold itself up at 9 months But if 240 were to exceed that, that obviously would be excellent for the company and for patients themselves.
spk13: Thanks. Very helpful.
spk09: And we will take our next question from Thomas Smith with Veroon Partners. Your line is open.
spk15: Hey, guys. Good afternoon. Thanks for taking the questions and looking forward to seeing the data updates at WCM next month. Can you just remind us what your expectations are with respect to the 240 milligram dose relative to the strong 80 milligram dose data that we've already seen out at three and six months? Should we be looking for deeper or perhaps more rapid reductions in protein area at these earlier time points? Are you expecting to see similar reductions with the 240 milligram dose?
spk05: Yeah, and I'm sure Sam is going to want to add on to this, but what I would say initially is I'll remind you that you go back to our healthy volunteer data. At 80 milligrams, we covered April for about three weeks, and then we lost coverage, even though we covered back through the continuum. So the 80 milligram data so far continues to look best in class. It's still early at 240 milligrams. It's something that we're going to continue to track. You'll get a quick peek at it at WCN, and then we'll have additional files that we'll the course of the year. We will also, as we mentioned, have a presence at ERA in May, so we look forward to sharing additional data and enroll a presentation at that time at ERA. Sanford, I don't know if you want to add on to that at all in terms of dosing it 240. Thank you, Gordon.
spk15: Anything else, Tom? Got it. That's helpful. Yeah, and then just in terms of continuing to enroll IGAM patients in Ruby 3 at that 240 milligram dose, is the expectation here that you're going to keep enrollment open until you can get the phase three Rainier trial off the ground later this year? Or is there a target enrollment that you're looking for? And I guess maybe lastly, how much overlap is there between the Ruby 3 trial sites and the planned sites for Rainier?
spk05: So what I can tell you is that after we shared the data at ASN at Kidney Week last year, enrollment in the Ruby 3 IGAN cohort has been incredibly robust. In fact, we have exceeded our enrollment expectations at the 240-milligram cohort. So there's been a tremendous amount of investigator interest and a tremendous amount of patient interest participating in the Ruby 3 trial. I think that's a testament to the fact that these patients want disease-modifying treatments that are going to alter their disease. So we're pretty excited about that. In terms of the overlap, there will be some overlap there in terms of the sites that are in Ruby 3 and what we're doing for our pivotal Rainier trial. But I would also emphasize we're kind of, we're in a really bit of a kind of perfect situation where we expect that both phase three studies that are ongoing at IGN right now will be wrapping up enrollment just as we're launching our phase three. So, we anticipate that we'll be the only phase three trial out there enrolling during that timeframe. So, hopefully that'll make for a fairly robust enrollment timeline for COVID-19 acceptance for your study. Got it. That makes sense. Super helpful. Thank you, guys.
spk09: And we will take our next question from Gregory Renza with RBC Capital Markets. Your line is open.
spk12: Hi, congrats on the progress. This is support on for great. I have a question on Rubyfall. Could you remind us the rationale? And if you have any preclinical evidence that Bob and April should work synergistically or additively in this indication, and if they are better than the current standard of care? Thank you.
spk05: I'll let Stanford take that. Stanford?
spk04: Yeah, there are several published studies demonstrating elevated levels of VASC and APRIL in these various cytopenias, in many cases correlating with disease activity or severity of the cytopenia. We actually showed in some of our preclinical publications last year that in some preclinical models, for example, in the New Zealand black-white lupus model, which includes an autoimmune leukemia manifestation, that treatment with clove attack can be beneficial. And similarly, I've shown that in such models that inhibition of both BAS and APRIL, such as with probitacacept or other dual inhibitors, can be superior to either cytokine alone. So that's why it's actually some of that preclinical data that can tell us to look at these indications. And then, of course, there's the general rationale that there's a heavy dependence on B cells. And I might just also remind you, those studies also did compare against some standard pair
spk06: or clinical models. Got it. Thank you.
spk09: And we will take our next question from Matt Beigler with Oppenheimer. Your line is open.
spk14: Okay, Mitch and team. Good to hear from you. Do you guys plan to provide any analysis on anti-drug antibody development or ideally lack thereof at WCN, I guess maybe to address some of the nagging questions on immunogenicity? Thanks.
spk05: Yeah. You know, we have not seen any clinically significant ADA to date. That's something that obviously we're continuing to monitor. And as we have a more complete data set, we'll share that as we update on BOVI's developments.
spk14: Is it also possible, maybe, you know, with further follow-up that, ostensibly, if the data mature nicely, that we can kind of put that idea to rest?
spk05: I think one of the, you know, this is different than a lot of other recombinant proteins that are administered subcutaneously in the sense that the mechanism of the drug actually is almost designed to inhibit ADAs. So, in a certain sense, you know, it's something that POBE kind of sets itself up well for, I think if you look at the data that we changed the data and you'll see the nine-month data that we present at WCN, you know, we're not seeing anything of clinical significance to coming up. Great. Looking forward to it. Thanks.
spk09: And we will take our next question from Joe Pant. Jim is with HC Wainwright. Your line is open.
spk08: Hey, everybody. Thanks for taking the question. Good afternoon. So I was curious the extent of the translational data that's also coming up that you alluded to earlier. And then also now that you're going to be going pivotal, if you could just remind all of us sort of your capacity to address the manufacturing needs for the pivotal programs and early potential commercialization. Thanks a lot.
spk05: Thanks, John. I'll let Stanford take those and maybe deal with the translational data as ended later on this week and then we can talk about manufacturing and clinical supply.
spk04: Yeah, we have some data at the BRPM lupus meeting later this week that will highlight some of the translational data, like expanding on some of the studies we showed at ACR last year, showing the rationale of APRIL and BASC in lupus, but also preclinical studies looking at the and distribution into end organs compared to wild-type tachy, which we think is part of why the drug, at least frequently, appears to look better than wild-type tachys. Great.
spk05: And then, Joe, just on the manufacturing questions related to clinical trials, we've been fortunate that we've had a very straightforward manufacturing process. We have all the plants and supply that we need to conduct our clinical trials. Fantastic. Thanks for the info.
spk09: And we will take our next question from Robert Driscoll with Wedbush Securities. Your line is open.
spk02: Hey, good afternoon, guys, and thanks for taking the question. It may be a little premature at this point, but how are you guys thinking about the ultimate kind of length of treatment in IGAM for pulchritacis sets? I think you've mentioned, you know, nine months is kind of the important endpoint here for regulatory. You know, how long are you looking at Ruby 3 patients for on follow-up? Thanks. Thanks.
spk04: Well, I think like most therapies in this pathway, I think we're looking right now at indefinite treatment for at least initial treatment since we don't know yet what the optimal duration is. And the drugs appear to be quite limited, so there's not necessarily a need to limit treatment due to potential side effects. That being said, of course, we're very interested in the mechanism of the disease-modifying therapy that may induce long-term remission. So perhaps as a subsequent live investigation, we would then think about exploring different lengths of treatment that may result in long-term responses or hopefully cure.
spk06: Got it. Thanks, guys.
spk09: And we will take our final questions from Andy Chen with Wolf Research. Your line is open.
spk00: Hey, thank you for taking the question. So regarding Ruby 3 enrollment, can you remind us if enrollment is staggered by indication? So we've seen a few patients in IGAN. We've seen one patient in MN. We haven't seen LN data. Are we going to see progressively higher ends and newer indications? So are we going to see more patients in MN? And a few months later, we're going to see another wave of data in LN and then ankylovesculitis. How does that work?
spk04: Yeah, I mean, it wasn't not for protocol, but in the way we operate my study, we focused almost exclusively on IgG nephropathy initially, given part of the prior rationale of the pathway in that disease. And then, you know, ANCA has actually only recently been formally added to the study, so that's the only protocol-related restriction and timing. But it was after we saw the encouraging initial data at ASM that we really started
spk05: in terms of the different indications. You will see a continuous flow of updates coming out of both Ruby 3 and Ruby 4. And I think that's one of the benefits we get out of the baskets. Obviously, we'll get longer-term follow-up from IGAN at both the 80 and 240 dose levels. But we'll continue to get data in TNRAN and LN. We'll see the initial incubators data come out. So it will be a trial that continues to support You know, it's a robust data flow coming out of those basic studies.
spk04: We did enroll in 80 milligrams. It is a multiple ascending dose study, so 80 milligrams were enrolled first. That's why that was the first data set that we announced last fall, and the 240 is lagging behind that. This is, you know, an ascending dose design, and that's per indication.
spk00: Thank you. That's helpful. Thank you.
spk09: And there are no further questions, so this brings us to the end of our time for questions. Dr. Gold, I'll turn the call back over to you for closing remarks.
spk05: Thanks, operator. I'd like to thank everyone that participated today in the call. We look forward to seeing many of you at upcoming investor and medical meetings and providing updates in the months ahead. Thank you again.
spk09: And ladies and gentlemen, this concludes today's call and we thank you for your participation. You may now disconnect.
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