Alpine Immune Sciences Inc (ALPN) 2023 Q4 法說會逐字稿

Ladies and gentlemen, and welcome to the Alpine Immune Sciences fourth-quarter 2023 and full-year earnings call. Currently, all participants are in a listen-only mode. As a reminder, this event is being recorded.

I would now like to introduce Temre Johnson, Senior Director of Investor Relations and Corporate Communications at Alpine. Ms. Johnson, please go ahead.

Thank you, Ravi. 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 risks 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.

Thank you, Temre, and thank you all those who are participating in the webcast today. 2023 was a transformational year for Alpine, with initial IgA nephropathy data presented at the American Society of Nephrology's Kidney Week, suggesting a best-in-class profile for povetacicept, our wholly-owned next-generation dual BAFF/APRIL inhibitor with once-monthly dosing developed using our directed evolution platform.

We are still only in the early stages of exploring the full potential of povetacicept. On the back of strong enthusiasm around it, we closed an oversubscribed $150 million equity offering to accelerate multiple development activities.

With our there are encouraging data set in IgAN, convenient once-monthly dosing regimen, strong balance sheet, we are rapidly advancing development of povetacicept as a potentially meaningful new therapy adoption 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. In April, we plan to present additional data of povetacicept in IgA nephropathy, including the follow-up data from the 80-milligram monthly, and initial data from the IgAN 240-milligram monthly dose cohorts at the Royal Congress in Nephrology meeting next month.

Following these data, in the second half of the year, we plan to initiate RAINIER, a pivotal Phase 3 study of povetacicept in IgA nephropathy; and DENALI, a Phase 2 study of povetacicept in SLE. In addition to updates on our clinical studies, we look forward to sharing translational data that further supports the best-in-class potential of povetacicept in multiple diseases.

I now hand the call over to Stanford to review our progress and provide updates on our development plan in Povetacicept in more detail. Stanford?

Thank you, Mitch. As Mitchell described, the emerging clinical findings with povetacicept continue to inspire us to advance as rapidly as possible. At last year's Kidney Week meeting, we reported the first clinical observations with povetacicept in IgAN, where it was associated with a greater than 50% reduction from baseline in proteinuria at six months, as measured by urinary protein to creatinine ratio, or UPCR.

In addition, the majority of patients met remission criteria as defined as reduction in UPCR of 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 IgAN biomarker, Gd-IgA1, supporting the concept of povetacicept as disease-modifying therapy. As a reminder, the approvable efficacy target has historically been 30% reduction in proteinuria at nine months.

Our very encouraging findings continue to hold up. With additional agents and with longer follow-up, povetacicept could indeed be a particularly compelling therapeutic option for patients with IgAN 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 povetacicept in IgAN next month at the World Congress of Nephrology, which will take place in a late-release poster.

In the meantime, our primary development goal with povetacicept is advancement this year to a pivotal trial of IgAN which we're calling RAINIER. Of course, several other autoimmune and/or inflammatory disease indications remain of great potential interest for povetacicept.

First, lupus remains a key indication, second only to IgAN, supported by the clinical validation of the pathway efficacy by BAFF inhibition and wild-type TACI IV molecules. We continue to plan to initiate a Phase 2 study in lupus called DENALI 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, would achieve and immunological remission of povetacicept. Such a finding suggests that other antibody diseases may benefit from povetacicept.

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 cytopenia in the RUBY-4 study. We look forward to future opportunities to share these collected data.

Finally, ongoing and emerging preclinical and translational data seems to suggest yet additional therapeutic areas like neurology or allergies for povetacicept. Last year at Kidney Week, we observed a significant reduction in IgE in IgAN patients who received povetacicept, potentially getting potential applicability in IgE-related diseases like allergy.

We also presented data on povetacicept 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 povetacicept in a mouse model of autoimmune encephalitis at the American Academy of Neurology Meeting.

In the myasthenia models, povetacicept appeared superior to clinically-relevant competitors, such as SCR inhibition or B-cell depletion. We think this may in part be related to some unique biophysical and/or other developmental characteristics of povetacicept, which confirm greater tissue penetration and/or distribution than wild-type TACI-Ig.

Data supporting this latter statement will be part of a poster later this week at the European Lupus Meeting. Altogether, these developments only reinforce the potential for povetacicept to have broader clinical impact in multiple serious diseases.

As a reminder, povetacicept was discovered in-house by our proprietary direct evolution protein engineering platform, which has been quite productive, and continue 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 povetacicept, but also our development pipeline in the future. I'll now turn the call over to Paul Rickey, our Chief Financial Officer.

Thank you, Stanford. And now, I'll provide a brief overview of our financials for the year ended December 31, 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 noncash expenses, were $18.9 million and $70.2 million for the same period in 2022. An increase of $10.7 million was driven by an $8.2 million increase in povetacicept costs, primarily related to higher clinical process development and manufacturing expenses; a $1.3 million in acazicolcept costs, due primarily to process development and manufacturing; and a $7.7 million increase in 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 it 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 31, 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.

Thanks Paul. As Stanford highlighted, we are highly encouraged by the initial IgAN data for povetacicept, 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 for data updates in IgAN and other indications. And the planned initiation of RAINIER, our pivotal Phase 3 study in IgAN; and DENALI, our Phase 2 study in SLE.

In addition, we continue to evaluate potential for povetacicept in additional indications. And as Stanford mentioned, we continue to invest in our immunology discovery efforts, to advance the next-generation programs from our directed evolution platform.

With that, I'll turn the call over to the operator for questions.

Thank you, Dr. Gold. (Operator Instructions)

Tara Bancroft, TD Cowen.

Hi, good afternoon and 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. But just some granularity around potential venues? And then what level of efficacy you're looking for to potentially start a Phase 3 study?

Yes. So for RUBY-4, Tara, I think we just look at it as just ITP. I mean, we have interest in other indications beyond just ITP. So obviously, you have ITP. We have cold agglutinin disease.

And our goal is to be able to, as we mentioned, be able to present that data in the first half of this year. So we haven't yet determined which conference that's going to be at, but there's a couple of that we have our eye on in that.

And you had one other question. Remind me what that was again? [That's what we want to see in ITP?] (multiple speakers)

Yes, I'll remind you that these are highly refractory patients, so they're third or fourth line therapy patients. So I think we saw a meaningful improvement in platelet count really like that 20% response rate that would turn out to be be meaningful for us.

Okay, great. Thanks.

Okay.

Mike Ulz, Morgan Stanley.

Mister Ulz, your line is open. Please check your mute button.

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.

Yes, 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 very important because that's the endpoint that the regulators use for accelerated approval.

I'll remind you that the benchmark there historically has been a 30% reduction in UPCR. And in six months we were seeing over 50% reduction in UPCR. 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, we'll get a first look at 240 milligrams. As we look at it now, things would need to look dramatically better with 240 milligrams over 80 milligrams. At 80 milligrams, we're already seeing best-in-class reductions in proteinuria, and that continues to hold until about at nine months. We think we have a very clean path forward at the 80 milligram dose level.

But if 240 milligrams will exceed that, that obviously would be excellent for the company and for patients themselves.

Thanks. Very helpful.

Thomas Smith, Leerink Partners.

Hey, guys, good afternoon. Thanks for taking the questions, and looking forward to seeing the data updates at WCN next month.

Can you just start 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 proteinuria, at these earlier time points? Are you expecting similar reductions with the 240 milligram dose?

Yes, I'm sure Stanford is going to want to add to this, but what I would say initially is I'll remind you that if you go back to our healthy volunteer data, at 80 milligrams, we've covered APRIL for about three weeks, and then we lost coverage, even though we covered BAFF in the continuum.

So the 80 milligram data so far continues to look best in class, but 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 an additional follow-up that we can share of 240 milligrams through as we move throughout 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 all the presentation at that time in ERA. Stanford, I don't know if you want to add to that at all in terms of dosing at 240 milligrams.

I think you've covered it.

Anything else, Tom?

Got it. That's helpful. Yes.

And then just in terms of continuing to enroll IgAN 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 3 RAINIER trial off the ground later this year? Or is there their 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?

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 -- really a bit of a kind of perfect situation where, we expect both Phase 3 studies that are ongoing in IgAN right now will be wrapping up enrollment, just as we're launching our Phase 3.

So we anticipate that we'll be the only Phase 3 trial there enrolling during that timeframe, so that hopefully that'll make for a really robust enrollment timeline for povetacicept in this RAINIER study.

Got it. That makes sense. Super helpful. Thank you, guys.

Okay, Tom.

Gregory Renza, RBC Capital Markets.

Hi. Congrats on the progress. This is [Okorshan] for Greg. I have a question on RUBY-4. Could you remind us the rationale, and if you have any preclinical evidence that BAFF and APRIL should work synergistically or additively in this indication, and if they are better than the current standard of care? Thank you.

I'll let Stanford take that. Stanford?

Yes, there are several published studies demonstrating elevated levels of BAFF/APRIL in 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 light lupus model, which includes autoimmune hypoglycemia manifestation, that treatment with povetacicept can be beneficial, and similarly have shown that in such models, that inhibition of both BAFF and APRIL, such as with povetacicept or other dual inhibitors, can be superior to either cytokine alone.

So that's why it's actually some of the preclinical data that is to look at these indications. And then, of course, there's the general rationale that there is a heavy dependence on B-cells. And I may just also remind you, those studies also, if you compare against some standard of care therapeutics like B-cell depletion, at least in translation, or preclinical models.

Okay. Thank you.

We will take our next question from Matt Biegler with Oppenheimer. Your line is open.

[Oh, hey, Alpine team]. Good to hear from you. Do you guys plan to provide any analysis on antidrug antibody development, or ideally lack thereof at WCN? I guess maybe to address some of the nagging questions on immunogenicity? Thanks.

Yes, we have not seen any clinically significant ADA data on there. Obviously, we're continuing to monitor it as we have. Remarkably dataset will share that as we update on Povy's development.

Is it also possible, maybe with a further follow-up that, ostensibly if the data matures nicely that we can kind of put that idea to rest?

I think one, this is different than a lot of other recombinant proteins that are administered subcutaneously in a 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 povetacicept kind of sets us up well for.

But I think if you look at the data that we've seen to date, and you'll see the nine month data that we'll presented at WCN, we're not seeing anything of clinical significance coming up.

Great. Looking forward to it. Thanks.

Joe Pantginis, H.C. Wainwright.

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.

Thanks, Joe. I'll let Stanford take those. But maybe to deal with the translational data. As we've said it, maybe around this week, maybe wev can talk about manufacturing and clinical supply.

Yes, we have some data at the European lupus meeting later this week tht will highlight some of the translational data, like expanding on some of these studies we showed at ACR last year, showing the rationale of APRIL and BAFF.

But also preclinical studies looking at the distribution of the drug in different end organs, demonstrating that povetacicept actually has quite good penetration and distribution in end organs compared to wild-type TACI VI, which we think is part of why the drug, at least preclinically, appears to look better than wild-type TACI.

Great.

And then Joe, just on the manufacturing questions related to the clinical trials, we've been fortunate that we've had a very straightforward manufacturing process for [Povy] and we have a lot of [clinical supply] that we need to conduct our clinical trials.

Fantastic. Thanks for the info.

Robert Driscoll, Wedbush Securities.

Hey, good afternoon, guys, and thanks for taking the questions.

Maybe a little premature at this point, but how are you guys thinking about the ultimate kind of length of treatment in IgAN for povetacicept? I think you've mentioned nine months is kind of the important endpoint here for regulatory. How are you looking at RUBY-3 patients for follow-up? Thanks.

Well, I think like most other therapies in this pathway. I think we're looking right now, I think, definite treatment for at least initial treatments since we don't know yet what the optimal duration is. And the drug appeared to be quite limited, so there's not necessarily a need to limit the treatment due to potential side effects.

That being said, of course, we're very interested in the mechanism of 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.

Got it. Thanks, guys.

Andy Chen, Wolfe Research.

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 ANCA vasculitis? How does that work?

Yes. I mean, it was not per protocol, but I think the way we operationalize, we focused almost exclusively on IgA nephropathy initially, given part of the prior rationale of the pathway in that disease. And then ANA is actually only recently been formally added to this study.

So that's the only, maybe, protocol-related restriction in timing. But it was after we saw the encouraging initial data in ASM that we really started pushing on other indications and of course, that eventually added in ANCA vasculitis in the study.

So like I said, not so much a protocol restricted timing, but more operational focused in terms of the different indications.

And just to add to that, 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 that. Obviously, we'll get a longer-term follow-up for IgAN and both the 80 milligram and 240 milligram dose levels.

But we'll continue to get data in TMN and LN, and we'll see the initial ANCA vasculitis data come out. So it will be a trial that continues to support a robust data flow coming out of those basket of studies.

And then, we did enroll at 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 then the 240 milligram lagging behind that, since it's an ascending dose design.

And that's per indication.

Thank you. That's helpful. Thank you.

And There are no further questions. And 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.

Thank you operator. I'd like to thank everyone that participated in today's 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.

And ladies and gentlemen, this concludes today's call and we thank you for your participation. You may now disconnect.