Q4 2023 Alpine Immune Sciences Inc Earnings Call
Operator: Ladies and gentlemen, welcome to the Alpine Immune Sciences fourth quarter 2023 and full year earnings call. Currently, all participants are in a listen-only mode.
Ladies and gentlemen, welcome to the Alpine immune Sciences fourth quarter, 2023, and full year earnings call.
Currently all participants are in a listen only mode.
Operator: As a reminder, this event is being recorded, and 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, Abby.
As a reminder, this event is being recorded and I would now like to introduce Camry Johnson Senior director of Investor Relations and corporate communications at Alpine MS. Johnson. Please go ahead.
Thank you Robby good afternoon, and thank you to everyone for taking the time to join US today with me on today's call from Alpine our Doctor Mitchell Executive Chairman and Chief Executive Officer, Dr. Stanford Peng President and head of R&D, Paul Rickey, Chief Financial Officer, and Dr. Remy Duran Chief business Officer.
Temre Johnson: 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 uncertainty. Actual results could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties.
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 uncertain.
I encourage you to refer to the most recent SEC filings regarding the risk factors associated with these statements.
Temre Johnson: 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 IL-5, with initial IJ nephropsy data presented at the American Society of Nephrology's Kidney Week, suggesting a best-in-class profile for COVID-19 success, our wholly-owned, next-generation, duovab-available inhibitor, with once-monthly dosing We are still only in the early stages of exploring the full potential of COVID-19. On the back of strong enthusiasm around ASN, we closed an oversubscribed $159 equity offering to accelerate multiple developments.
Mitch. Please go ahead.
Thank you Dan.
Thank you all participating.
Okay.
2023 was a transformational year for II VI.
With initial hygiene in Boston.
At the American Society of your fraud.
James Jamie, suggesting and best in class profile.
Our wholly owned next generation <unk> inhibitor with once monthly dosing developed using our direct evolution platform.
We are still only in the early stages of exploring all potential.
Yes.
On the back of strong enthusiasm around that.
We closed an oversubscribed $150 million equity offering took a salary multiple development.
But there are emerging data set and high yeah convenient once monthly dosing regimen strong balance sheet, we are rapidly advancing in development and potentially meaningful new therapeutic option for patients living with I guess a.
Mitchell H. Gold: With our encouraging data set in IGAN, a convenient once-monthly dosing regimen, and a strong balance sheet, we are rapidly advancing the development of POVI as a potentially meaningful new therapy adoption for patients living with IGAN, lupus, and other conditions, and multiple other autoimmune and inflammatory conditions. Looking ahead, we are well positioned for meaningful catalysts in 2024 and beyond. In April, we plan to present additional data on public attack, septic, and hygiene necrosis, including follow-up data from the 80 milligram monthly and initial data from the IgN 240 milligram monthly dose cohorts at the Royal Congress of Nephrology meeting next. Following these data, in the second half of the year, we plan to initiate Rainier, a Pivotal Phase III study of Pogon taxiseptic and IV anaphropathy, and Denali, a Phase II study of Pogon taxiseptic and IV anaphropathy. In addition to updates on our clinical studies, we look forward to sharing translational data that further supports the best-in-class potential of COVID-19 tax cuts in multiple areas. I now hand the call over to Stanford to review our progress and provide updates on our development plan to discuss DACA steps in more detail. Stanford
A little bit and multiple other autoimmune and inflammatory diseases.
Looking ahead, we are well positioned for meaningful catalysts in 2024.
In April we plan to present additional data.
In Iga nephropathy.
Yes.
No ma'am.
And initial data.
From the AGN 240 milligram monthly dose cohorts at the real economy.
The next month.
Following these data in the second half of the year you plan to initiate Rainier.
Phase III studies.
Yeah.
And Denali Phase III studies.
Yes.
In addition to updates on our clinical studies, we look forward to sharing translational data that further supports the basket.
Okay multiple diseases.
I'll now hand, the call over to Stanford give you our progress and provide an update on our development plans at both Jack Morton Stanford.
Stanford Peng: Thank you, Ben. As Mitch has described, the emerging clinical findings with COVITAX have continued to inspire us to advance as rapidly as possible. At last year's Kidney Week meeting, we reported the first clinical observations with POVATAC except in Igant, where it was associated with a greater than 50% reduction from baseline in proteinuria at 6 months, as measured by urinary protein to creatinine ratio, or UPCR. In addition, the majority of patients met remission criteria as defined as a reduction in UPCR to less than 0.5 grams per gram, at least a 50% Importantly, these findings were associated with significant reductions in the key IgM biomarker, TgIgA1, supporting the concept of POVATAC acceptance as a disease-modifying therapy.
You bet.
Can you describe the emerging clinical findings with Goldman Sachs.
With <unk> advances as rapidly as possible.
Lastly at kidney week meeting, we reported the first clinical observations with Goldman Sachs.
Whereas with associated with a greater than 50% reduction from baseline at six months.
Urinary protein <unk> ratio Pcr.
Yes.
The majority of patients better emission criteria as defined as reduction yards.
Five grams per Gram at least a 50% reduction in <unk> from baseline and stable renal function as assessed by SME filtration rate or Egfr.
Importantly, these findings were associated with significant reductions again biomarker T. Iga, one supporting the concept of <unk>.
Quantifying it or.
Stanford Peng: As a reminder, the Approvable Efficacy Target has historically been a 30% reduction in protein area at 9 months. Our very encouraging findings continue to hold up with additional patients and with longer follow-up. So a next step could indeed be a particularly compelling therapeutic option for patients with Bygones 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.
As a reminder, the approvable efficacy targets, that's historically been 30% reduction in proteinuria at nine months.
Alright, very encouraging findings continue to hold up with additional agents and with longer follow up but what's next step could indeed be a particularly compelling therapeutic option for patients with I guess in other autoimmune diseases.
Therefore, as Cynthia said, we've been making every effort during the program in the company for the next pivotal phase of development.
Stanford Peng: We look forward to the opportunity to provide a formal clinical data update on COVID-19 next month at the World Congress of Nephrology, which will take place in a late-break post-pandemic period. In the meantime, our primary development goal for COVID-19 tests is its advancement this year to a clinical trial to identify what we're calling renears. Of course, several other autoimmune and or inflammatory disease indications remain of great potential interest for Povatavice. First, lupus remains a key indication, second only to IgAN, supported by the clinical validation of the pathway in the disease by BAC inhibition and wild-type PET-TIG molecules.
We look forward to the opportunity to provide a formal clinical data update with excess D&O again next month at the World Congress of Nephrology, which will take place in a late breaking poster.
In the meantime, our primary genomic okay. Thank you.
This advancement of theoretical pivotal trial, which we're calling for here.
Several other autoimmune and inflammatory disease indications remain a great.
Trust over time.
First lupus remains a key indications second only to eylea.
The clinical validation of <unk> pathway, if it achieves by that integration and wildlife pesky height molecules.
Stanford Peng: We continue to plan to initiate a Phase 2 study in lupus called Denali later this year. Second, we continue to explore other immunotherapies 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 admission on COVID-19. Such a finding suggests that other autoantibody-related diseases may benefit from COVID-19 tests. Indeed, we continue to enroll additional subjects with PMS, and as a reminder, Ruby 3 is also enrolling lupus nephritis and has just recently opened an ANCA-associated vascularitis cohort. In addition, we continue to explore autoimmune Pantginis in the Ruby 4 study.
We need to plan to initiate a phase two study in lupus called Denali later this year.
We continue to explore other indications Ruby Tuesday at last year's kidney week can be described as a single agent with primary membranous nephropathy or PMA would achieve that gives me a lot of our mix it up overtime.
That's our findings suggest that other auto antibody related EBIT benefit from corporate tax.
Indeed, we continue to enroll additional subjects with PMA as a reminder, movies. Three is also enrolling lupus nephritis and has just recently opened anchor associated vasculitis cohort.
In addition, we continue to explore autoimmune cytopenia if it would be for say.
Stanford Peng: Finally, ongoing and emerging preclinical and translational data continue to suggest additional therapeutic areas like neurology or allergies for COVID-19. Last year at Kidney Week, we observed a significant reduction in IgE in IgAN patients with rescued Colgatec steps, suggesting potential applicability in IgE-related diseases like allergies. We also presented data on the COVID-19 test and a mouse model of Myasthenia gravis at the American Association of Neurovascular and Electrodiagnostic Medicine annual meeting. And next month, we will present data on the COVID-19 test and a mouse model of autoimmune cephalitis at the American Academy of Neurology meeting. In the Myasthenia model, COVID-19 is superior to clinically relevant comparators such as SPR inhibition or B-cell depletion.
We look forward to future opportunities to Sharon's question.
Finally, ongoing and emerging preclinical and translational data continues to suggest additional therapeutic areas like neurology or allergy overtime.
Last year at kidney week, we observed a significant reduction ITE I can't patients with acute overtaxed.
Is that suggesting potential applicability of ICU related diseases like allergy.
Presenting data on corporate taxes mouse model of myasthenia gravis at the American Association of neuromuscular electro diagnostic medicine annual meeting.
Next month, we will present data on corporate tax that's been around.
Auto autoimmune satellite at the American Academy of Neurology.
And to my senior model Overtaxed procured superior to clinically relevant comparator, such an SCRA inhibition or b cell depletion.
Stanford Peng: We think this may, in part, be related to some unique biophysical and or other developmental characteristics of COVID-19 tests, which confer greater tissue penetration and or distribution than well-designed test EIDs. Supporting this letter statement will be part of a poster later this week at the European Movement. Altogether, these developments only reinforce the potential for COVID-19 to have a broad clinical impact in multiple serious diseases. As a reminder, Copatagincept 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 a great future innovator.
We can pitch me on part D related to some unique biophysical and or other developmental characteristics overtime.
Okay for greater tissue penetration of Anti-war distributions, well, Hi Tech AIG.
He just supporting this letter statement will be part of a poster.
At the European meeting.
Altogether these developments only reinforced the potential for corporate tax fraud.
And multiple serious diseases.
As a reminder, Copenhagen snuff was discovered in house by our proprietary directed evolution protein engineering platform, which has been quite productive and continues right novel drug candidates to give you a brief future interest.
Paul Rickey: We therefore look forward to opportunities to provide further updates, not only on COVID-19 tests but also on our development pipeline in Canada. I'm now turning 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 31st, 2023. For the year ended 2023, collaboration revenue was $58.9 million, compared to $30.1 million for the same period in 2022.
We therefore look forward to opportunities to provide further update that helped me a pub attached to them, but also in our development pipeline and into the future.
I'll now turn the call over to already our Chief Financial Officer.
Thank you Stanford.
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.
Paul Rickey: 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 ADAPT Immune 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 COVID-19 tax-except costs, primarily related to higher clinical, process development, and manufacturing expenses. A $1.3 million increase in the cost of COSEP 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 in collaboration revenue related primarily to a $24 9 million increase in Abbvie revenue of which 24 million is due to a cumulative catch up adjustments, resulting from the completion of enrollment in synergy for the amendment without a.
And a $4 5 million increase in Amgen revenue driven primarily by the exploration of Amgen's option selected Bert Research program.
These increases were partially offset by a <unk> 6 million decrease in adopting <unk> 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 and <unk> seven.
$7 million was driven by an $8 2 million increase in overtime is that cost.
It really related to higher clinical process development and manufacturing expenses.
At $1 3 million increase in cost and a coffee close up cost 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.
Mitchell H. Gold: 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 years 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 initialing in data over TXA 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 high GAN and other education and the Plant Initiation of Rainier, our Pivotal Phase III study in IgN, and Denali, our Phase II study in SLE.
Increased to $4 3 million was primarily attributable to increases in personnel costs and professional services.
The company recorded net losses of $32 2 million at $57 8 million for the year ended 2023 and 2022, respectively.
And at December 31, 2023, alpine with 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 at Stanford highlighted we are highly encouraged by the initial angle of attack.
And are just beginning to explore the full potential of this unique potential best in class molecule.
We look forward to a catalyst rich year, the data uptick in <unk> in other indications and the planned initiation of Rainier, our pivotal phase III study in again and Denali our phase two study in SLE.
Mitchell H. Gold: In addition, we continue to evaluate the potential for public happy steps in additional individuals. 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. With that, I'll turn the call over to the operator for questions. Thank you, Dr. Gold. If you would like to ask a question, please press the star key and the number one. Press star 1 a second time; it will remove your line from.
In addition, we continue to evaluate potential the potential for property taxes in additional indications and as Stanford mentioned, we continue to invest in our hematology discovery efforts. The advantage. The next generation of programs from a directed evolution.
With that I'll turn the call over to the operator for questions.
Yeah.
Thank you Dr. <unk>, if he would like to ask a question. Please press the star key M. A number one.
If you press star one a second time it will remove your line from the queue.
Operator: 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 room. And we will take our first question from Tara Bancroft with TD Cowan. Your line is open. Hi, good afternoon.
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 Cowen Your line is open.
Hi, good afternoon, thanks for hosting this call.
Tara A. Bancroft: 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 at, like how you mentioned for the kidney data? It might be at two different ones during the second half, but you've leveled it down, but
I have a question on I T. P expectations. So first can you provide some potential conferences with the data might be presented like how you mentioned for sure that the kidney data had Mike yeah at two different ones during the second half ammonia levels down but.
Stanford Peng: 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. Yeah, so for RUBY4, Tara, I think what we're looking at is just ICP. I mean, we have an interest in other indicators beyond just ICP. So, you know, obviously, you have ICP, we have WHA, we have cold and flu 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 that we have our eye on in that. You had one other question. Remember what that was?
Yeah, just some granularity around a potential venues and then what level of efficacy you are looking for to potentially start a phase III study.
Yeah, so for movies sports right.
It looks like it is just I C. P. I mean, we are interested in other yeah, yeah, Yeah, I just I P. P. So you know obviously you have ICP and we have one and we have cold agglutinin disease and our goal is to be able as we mentioned to be able to present that data in the first half of this year. So we haven't yet which conference is going to be up but there's a couple that we have right.
Uh huh.
You had one other question remember what that was again.
Stanford Peng: Yeah, so... That's what we want to see in ITP. You know, if you look at these patients, 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, meaningful improvement in placement times, if you felt like that 20% response rate would be durable, that would be meaningful. Okay, great, thanks. And we will take our next question from Mike, with Morgan Stanley. Your line is. And Mr. Ulz, your line is open. Please check your mute button. Sorry about that.
Yeah.
That's what they want to see in ITV.
When you look at it if you look at it.
Yeah.
I'll remind you that these are highly refractory patient. So you know their third or fourth line therapy patients. So I think we saw a meaningful improvement in platelet coffee really like that 20%, that's great that mature well that would be meaningful for us.
Okay, great. Thanks.
Thank you.
Okay.
And we will take our next question from Mike <unk> with Morgan Stanley. Your line is open.
Okay.
And Mr. <unk>. Your line is open please check your mute button.
Sorry about that.
Michael Eric Ulz: Hey guys, thanks for taking the questions. Maybe two on IGAN and the update WCN: can you maybe give us a sense of how many patients we should expect at the 80 and 240 milligram doses and the level of follow-up? And then, maybe secondly,
Hey, guys. Thanks for taking the question.
Maybe two on ICANN and the update.
WCS can you maybe give us a sense of how many patients we should expect that 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 $2 40 milligram dose to bring that one forward. Thanks, yes.
Stanford Peng: What's your current thinking about selecting the go-forward dose? need to see at the 240 milligram dose. Yeah, thanks, Mike.
Yeah, Thanks, Mike So for WCS.
Stanford Peng: So for WCN, what you should anticipate seeing is, for the first time, we'll get a look at nine months of data at the 80 milligram dose cohort level. Obviously, the nine months of data is really important because that's the end point that the regulators use for accelerated approval. And I'll remind you that the benchmark there historically has been a 30% production in UPCR, and in six months, we were seeing over 50% production in UPCR.
What you should anticipate seeing is for the first time, we will get a look at nine months data at the 80 milligram dose cohort level, obviously in the nine months that is really important that the endpoint is the regulators use for accelerated approval and I'll remind you that the benchmark. There historically has been a 30% reduction this year.
And at six months, we were seeing over a 50% reduction.
Stanford Peng: In addition to 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. You know, as we look at things now, things would need to look dramatically better with 240 over 80.
In addition, as WCS and 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 when we look at our first look at 240 <unk>.
As we look at things now are things, we need to look dramatically better with 240 overheating at 80 milligrams of always being best in class reductions in proteinuria.
Stanford Peng: At 80 milligrams, we're already seeing best-in-class reductions in protein area, and that continues to hold itself up. At nine months, we think we have a great, clean path forward at the 80-milligram dose level. But if 240 were to exceed that, that obviously would be excellent for the company and for patients themselves. Thanks for your help. And we will take our next question from Thomas Smith. Partners, ShareLine.
And that continues to hold itself up at nine months. We gave you a very clean path forward to getting back on dose level, but it was 240 or exceed that that obviously would be absolutely the company and for patients themselves.
Yeah.
Thanks very helpful.
And we will take our next question from Thomas Smith with <unk> Leerink partners. Your line is open.
Yeah.
Hey, guys. Good afternoon, thanks for taking the questions and looking forward to seeing the data updates at WCS next month.
Thomas Jonathan Smith: 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?
Can you just remind us what your expectations are with respect to the 240 milligram dose relative to that.
Strong 80 milligram dose data that we have 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 to see similar reductions with.
Stanford Peng: Are you expecting to see similar reductions with the 240 milligram dose? Yeah, I'm sure Stanford's going to want to add on 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 covered April for about three weeks, and then we lost coverage, even though we covered back through the continuum. So, you know, the 80 milligram data so far continues to look best in class, but it's still early at 240 milligrams.
<unk> hundred 40 milligram dose.
Yeah, I mean, I'm sure San Fran if you wanted to add on to this but what I would say initially if I remind you that you could go back to our healthy volunteer data.
At 80 milligrams is recovered in April for about three or three weeks and then we lost coverage, even though they cover bad through the continuum. So.
The 80 milligram data so far continues to look best in class.
Early at 240 milligrams, it's I've never going to continue to attract you'll get a quick peek at it at WCS.
Stanford Peng: It's something that we're going to continue to track. You'll get a quick glimpse at it at WCN, and then we'll have, you know, additional files that we can share for 240 throughout the year. We will also, as we mentioned, have a presence at ERA in May, so we look forward to sharing additional data in an enrollment presentation at that time at ERA. Stanford, I don't know if you want to add on. [inaudible] Garden.
And then we'll have additional about the vintage year for 240 throughout as we move throughout the course of the year.
We will also as we mentioned type of credit Suisse.
So we look forward to Australia additional data in an oral presentation at the time of inherit San Fran I was going to add on to that at all in terms of dosing at 240 <unk>.
I think you got it.
Stanford Peng: Anything else, Dad? Got it. That's helpful. Yeah. In terms of continuing to enroll IgAN patients in RUBY3 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 a target enrollment that you're looking for?
And the <unk> got it.
That's helpful. Yeah, and then just.
In terms of continuing to enroll <unk> patients in Ruby three at that 240 milligram dose as the expectation.
The expectation here that youre going to keep enrollment open until you can get the phase III Rainier trial off the ground later this year or is there.
Target enrollment that Youre looking for and I guess.
Stanford Peng: And I guess maybe lastly, how much overlap is there between the RUBY3 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 RUBY3 IGAM cohort has been incredibly robust. In fact, you know, we have exceeded our enrollment expectations for the 240 milligram cohort. So there's been a tremendous amount of investigator interest and a tremendous amount of patient interest in participating in the RUBY3 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, you know, we're pretty excited about that. In terms of the overlap, you know, there will be some overlap there in terms of the sites that are in RUBY3 and what we're doing for our pivotal Rainier trial.
Maybe lastly, how much overlap is there between the Ruby three trial sites and the planned site for radio.
So what I can tell you is that after we shared the data at kidney week last year enrollment in the <unk> cohort has been incredibly robust in fact.
We would have exceeded our enrollment expectations at 240 milligram cohort. So theres been a tremendous amount of investigator interest in a tremendous amount of patient interest just bidding and the movies. We tried I think that's a testament to the fact that these patients want disease modifying treatments that are going to alter their disease. So you know 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 three and what we're doing.
For our pivotal <unk> trial.
Stanford Peng: But I would also emphasize we're in a really bit of a kind of perfect situation where we expect that both phase 3 studies that are ongoing at IGAM 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 out there enrolling during that time frame. So hopefully that'll make for a fairly robust enrollment timeline for COVID-19 acceptance for in-year studies. That makes sense.
But I would also emphasize we're kind of aspirin or really a bit of a kind of perfect situation, where we expect to have both.
Both phase III studies that are ongoing at IGN right now, we'll be wrapping up enrollment just as we're launching our phase III. So we anticipate that will be the only phase III trial out there enrolling during that timeframe. So that hopefully that will make for a fairly robust enrollment time lines for both tech and Springer study.
Got it that makes sense Super helpful. Thank you guys.
Gregory James Renza: Super helpful. Thank you, guys. Thank you, y'all. And we will take our next question from Gregory Renza with RBC Capital Markets. Your line is open.
Sure.
And we will take our next question from Gregory <unk> with RBC capital markets. Your line is open.
Gregory James Renza: Hi, congrats on the progress. This is support for great. I have a question about Ruby4.
Hi, Congrats on the progress. This is support on so great I have a question on Ruby folks could you remind us.
Stanford Peng: Could you remind us the rationale and if you have any preclinical evidence that BAP and Afro should work synergistically or additively in this indication and if they are better than the current standard of care? Thank you.
Rationale.
And if you have any preclinical evidence of Boston <unk> should work Synergistically adequately.
In this indication.
Better than the current standard of care. Thank you.
Oh at Stanford take that effort.
Stanford Peng: Yeah, there are several published studies demonstrating elevated levels of BASC-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 Movement model, which includes an autoimmune sequence leukemia manifestation, that treatment with Covitac Acept can be beneficial, and similarly, we have shown that in such models, inhibition of both BASC and APRIL, such as with Covitac Accept or other dual inhibitors, can be superior to either cytokine So that's why it's actually some of that preclinical data that tells 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 just want to remind you, those studies also did compare against some standard of care, therapeutics-like B-cell depletion, at least in translational or preclinical models. Go ahead.
Yes. There are there are several other studies demonstrating elevated levels of bad April yet.
Various sort of 10 years.
In many cases correlating with disease activity or superior security at the Cytopenia, we actually showed in some of our preclinical publications last year that.
And some preclinical models for example, and.
And any view on black quite lupus model, which includes the automated with UBS manifestations that treatment with open access can be beneficial.
Oh, you have shown that in such a model that.
Inhibition of both past April such as with <unk>, except for other dual inhibitors can be superior to either.
I'm sorry.
So that's that's what it's actually some of that preclinical data that told us to look at these.
And then of course, there is D J.
Our rationale that there is a heavy dependence on T cells.
Thanks, a lot for Bayou those studies also compare against some standard of care therapeutics like T cell depletion at least try at least toward all the preclinical models.
Alright, thank you.
Matt Beigler: Thank you. And we will take our next question from Matt Beigler with Oppenheimer. Your line is open. Oh, hey mission team.
We will take our next question from Matt Eichmann with Oppenheimer. Your line is open.
Okay merchant team good to hear from you.
Stanford Peng: 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. Yeah, you know, we have not seen any clinically significant ADA to date. That's something that we're obviously continuing to monitor, and as we have a more complete data set, we'll share that as we update you on what we've developed. 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? I think this is different than a lot of other recombinant proteins that are administered subcutaneously in the sense that the mechanism of the drug is almost designed to inhibit ADAs.
You guys plan to provide any analysis on an.
Anti drug antibody development or ideally lack thereof at that'd be seeing I guess, maybe to address some of the nagging questions on immune incident immunogenicity.
Yeah.
We have not seen any clinically significant 88 data is something that obviously, we're continuing to monitor it as we have a more complete data set we'll share that as the update on what we used to call. It.
Is it also possible maybe you know with a further follow up that ostensibly if the data matured nicely that we can kind of put that idea to arrest.
I think you know this is different than a lot of other recombinant proteins that are administered subcutaneously in a sense that the mechanism of the drug actually so much designed to inhibit 88, so in a certain sense.
Stanford Peng: So in a certain sense, you know, it's something that probably kind of sets itself up well for, but I think if you look at the data that we changed today, you'll see the nine-month data that we presented at WCN, and we're not seeing anything of clinical significance coming up. [inaudible] And we will take our next question from Joe Pantginis with HC Wainwright. Your line is open.
It's something that probably kind of sets us up well for them, but I think if you look at the data that we've seen to date and you will see the nine month data that we presented WCS.
We're not seeing anything of clinical significance to come out.
Great looking forward to it thanks.
Yeah.
And we will take our next question from Joe <unk> with each C. Wainwright Your line is open.
Joseph Pantginis: Everybody, thanks for taking the question. Good afternoon. So I was curious about 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 for the Pivotal Programs and Early Potential Commercialization. Thanks a lot. Thanks, John.
Hey, everybody. Thanks for taking the question good afternoon.
So was curious the extent of the translational data. That's also coming up that you alluded to earlier and then also now that youre going to be going pivotal. If you could just remind all of us sort of your capacity to address the manufacturing needs for.
For the pivotal programs in early potential commercialization. Thanks a lot.
Stanford Peng: I'll let Stanford take those, maybe deal with the translational data presented later this week, and then we can talk about manufacturing it for the top clinical spline. Yeah, we have some data at the European Lupus meeting later this week that will highlight some of the translational data. Expanding on some of the studies we showed at ACR last year, showing the rationale for April and BASC in lupus, but also preclinical studies looking at the distribution of the drug in different end organs, demonstrating that COVID-19 steps actually... a point about penetration and distribution and overall risk compared to wild-type tachy, which we think is part of why the drug at least frequently appears to look better than wild-type And then, Joe, just on the manufacturing questions related to clinical trials, we've, you know, been fortunate that we have had a very straightforward manufacturing process for COVID, and we have all the plants and supplies that we need to conduct our clinical trials. Method.
Thanks, Joe San Fran take those maybe deal with the translational data.
Hey, Ryan This week and then we can talk about manufacturing clinical supply yeah, we have some data.
The European Lupus meeting later this week or are they just saw the translational data like extending some of the studies we showed at ACR last year, showing the rationale April and Baskin.
But also.
Preclinical studies looking at the distribution of the drug in different and more again, demonstrating the pokertek, except actually is pretty.
Quite good penetration and distribution ended.
Andrew I guess compared to well attacking which we think is part of why the drug in these preclinical me up here, so look better than Balkan techies.
Great.
And then Joe just on the manufacturing questions relate to the clinical trials, we've been fortunate that we've had a very straightforward manufacturing process.
A lot of the supply that we need to conduct a trust.
Fantastic Thanks for the info.
Yes.
Yeah.
Stanford Peng: And we will take our next question from Robert Driscoll with Wedbush Securities. 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 IgANs, what we call ketosis sets? I think you've mentioned that nine months is kind of the important endpoint here for regular treatment. You know, how long are you looking at Ruby3 patients for as follow-up? Well, I think, like most therapies in this pathway, I think we're looking right now at a definite 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 is not necessarily a need to limit treatment due to potential side effects.
We will take our next question from Robert Driscoll with Wedbush Securities. Your line is open.
Hey, good afternoon, guys and thanks for taking the questions maybe a little premature at this point, but how are you guys thinking about deals with kind of length of treatment to see Nikon Coca Cola.
At least we've mentioned nine months is kind of important endpoint for regulatory.
How long are you looking at really three patients bonds Colo.
Yeah.
Well I think right post therapy.
<unk> therapy in this pathway, we're looking right now.
Feedback scores of these initial treatment.
Don't know yet what the optimal duration is.
The drugs appear to be quite so.
So there's not necessarily a need to limit treatment.
Robert Driscoll: 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.
Judith.
Potential side effects that being said of course, we're very interested in the mechanism of disease modifying therapy that may be a huge long term remission. So perhaps as a subsequent live investigation. We would then think about exploring a different class of treatment.
May result in long term responses are hopefully cure.
Yeah.
Stanford Peng: Thanks, guys. And we will take our final questions from Andy Chen with Wolf Research, your line in your line in your line in your line in your line in your line in your line in your line in your, Hey, thank you for taking the question. So regarding RUBI3 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?
Got it thanks guys.
And we will take our final question is from Andy Chien with Wolfe Research. Your line is open.
Hey, Thank you for taking the question. So regarding Ruby three enrollment can you remind us if enrollment is staggered by indication. So we've seen a few patients and igen, we've seen one patient and a man we havent seen L. N data are we going to see progressively higher ends in newer indications. So are we going to see more.
More patients in that men and then a few months later, we're going to see another wave of data in L. N.
And then agco vasculitis like how does that work.
Andy Chen: Yeah, I mean, it wasn't because of protocol, but in the way we operationalized the study, we focused almost exclusively on IgG nephrosophy initially, given part of the prior rationale of the pathway in that disease. And then, you know, ANGLA has actually only recently been formally added to the study, so that's the only maybe protocol-related restriction in timing. But it was after we saw the encouraging initial data at ASM that we really started pushing on the other indications, and of course, that eventually added pancovasculitis to the study, so that's, Like I said, not so much a protocol-restricted timing, but more operational focus in terms of the different indicators. And 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.
Yeah I mean.
Not for protocol, but I think the way we offer each study we focus.
It's almost exclusively on Iga nephropathy initially given part of the prior rationale of the pathway.
That disease.
And then I.
And I was actually only recently been formally added to the study. So that's the only maybe protocol related.
Restriction that tightening but with after we.
So the encouraging initial data and then when you start pushing on other indications and of course that is actually.
Got it.
Vasculitis in the studies so that's.
Like I said, not so much a protocol restricted I think a bit more operational.
Our focus in terms of the different indications.
Anyway.
You will see a continuous flow of updates coming out about the Rubicon ran room before and I think that's one of the benefits we get out of that obviously will get longer term follow up from <unk> 40 dose levels.
Stanford Peng: Obviously, we'll get longer-term follow-up from Igannin, both the 80 and 240 dose levels. But, you know, we'll continue to get data in TN-9 and in LN. We'll see the initial anti-vasculitis data come out, so it will be a trial that continues to support, you know, a robust data flow coming out of those baskets. We did enroll in 80mg. It is a multiple ascending dose study, so 80mg was enrolled first. That's why that was the first data set that we announced last fall, and the 240 is behind that. This is an ascending dose study.
We will continue to get data in P M and L. Analysts see the initial Endovascular ahead, it's got to come out.
There will be a trial that continues to support.
It's a robust data flow coming out of those studies.
Yes.
We did that.
We did enroll 80 milligrams is a multiple ascending dose studies, so 80 milligrams wherever else Paris, that's why.
That was the first dataset that we announced last fall.
And the true 40th lagging behind that.
This is the SME.
Ascending dose design and that's per indication.
Stanford Peng: And that's per indication. Thank you. That's helpful. Thank you. And there are no further questions. The end of our time.
Thank you that's helpful. Thank you.
And there are no further questions. So this brings us to the end of our time for questions. Dr. Ralph I'll turn the call back over to you for closing remarks.
Mitchell H. Gold: This is Dr. Gold turning the call back over to you. Thanks, Operator. I'd like to thank everyone that participated today in the call, and we look forward to seeing many of you at upcoming investor and veterinary 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. Thank you again, and Levi's Injections.
Thanks, operator, I'd like to thank everyone that participated today to call and we look forward to seeing many of you at upcoming investors investor at 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.
Yeah.
Thank you.
Hmm.
Yeah.
Thank you again.
And ladies and gentlemen.