(ELDN) 2021 Q2 法說會逐字稿

Greetings. Welcome to the Eledon Pharmaceuticals Report Second Quarter 2021 Financial Results Conference Call. (Operator Instructions) Please note that this conference is being recorded. I will now turn the conference over to your host, Paul Little, Chief Financial Officer. You may begin.

Good afternoon, and thank you for joining Eledon Pharmaceuticals' Second Quarter 2021 Financial Results Conference Call. Joining me today is David-Alexander Gros, Chief Executive Officer; Steven Perrin, President and Chief Scientific Officer; and Jeff Bornstein, Chief Medical Officer. Earlier today, Eledon issued a press release announcing financial results for the second quarter ended June 30, 2021. You may access the release under the Investors tab on our company website, eledon.com.

Before we begin, I would like to remind everyone that statements made today during this call related to Eledon's expected future performance, future business prospects or future events or plans may include forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. All such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act. Actual outcomes and results could differ materially from these forecasts due to the impact of many factors beyond the control of Eledon. Eledon expressly disclaims any duty to provide updates to its forward-looking statements, whether as a result of information, future events or otherwise.

Participants directed to the risk factors set forth in Eledon's reports filed with the SEC on our website under the Investor tab. We encourage you to review these documents carefully. It is now my pleasure to pass the call over to our CEO, Dr. David-Alexander Gros. DA?

Thank you, Paul, and good afternoon, everyone. We continue to make significant progress during the second quarter, advancing our lead molecule, AT-1501. I'm excited by the promise offered to us by AT-1501 as a potential therapeutic for organ or cellular transplantation, ALS, and serious immunological diseases, where patients face limited treatment options. We plan to advance AT-1501 in up to 4 clinical trials: one, ALS; two, the prevention of kidney allograft transplant rejection; three, autoimmune nephritis starting with IgA nephropathy or IgAN; and four, the prevention of islet cell allograft transplant rejection for the treatment of type 1 diabetes.

We selected these indications based on preclinical data that was generated with both our molecule as well as historical anti-CD40 ligand molecules. Steve will give more details about each of these, but at a high level, our recent progress is as follows.

In the ALS Phase II biomarker study, our trial is progressing according to plan. We are completing enrollment of our third of 4 cohorts, and top line data is expected in the first half of 2022.

In renal transplantation, we previously communicated that the U.S. FDA requested that we provide AT-1501 specific renal transplant data in nonhuman primates prior to initiating a clinical trial in renal transplantation in the United States. And that as a result, we would both look to complete the FDA requirement as quickly as possible as well as look to initiate a clinical trial outside of the United States.

In terms of our U.S. regulatory requirements, we reached alignment with the FDA and to conduct a preclinical renal transplant study evaluating AT-1501 as monotherapy in 4 nonhuman primates. We anticipate initiating this nonhuman primate study in collaboration with an academic collaborator with vast transplant experience next quarter with completion of the study in mid-2022.

With regards to our ex-U.S. clinical trial. We received a No Objection Letter from Health Canada in response to our clinical trial application proposing to evaluate AT-1501, replacing tacrolimus as an immunosuppressive regimen component in patients undergoing kidney transplantation. The trial is expected to be initiated in the last quarter of 2021, with interim data readouts expected to begin in late 2022.

In autoimmune nephritis, we will be targeting IgA nephropathy. There is a long history of preclinical and clinical data demonstrating that blocking CD40 ligand signaling ameliorates disease progression, modifies biomarkers of disease and improves renal function in autoimmune diseases of the kidney, such as IgAN. We selected IgAN because of the unique approach that an anti-CD40 ligand brings in going after both the cellular and the antibody-mediated portions of disease pathophysiology.

In islet transplantation for type 1 diabetes earlier this year, we initiated a Phase II clinical trial of AT-1501 as a replacement for tacrolimus.

As we announced previously, we learned in early January that our study site in Canada voluntarily stopped performing islet cell transplants on a temporary basis because of COVID-19 before allowing for the resumption of these procedures. Unfortunately, until late June, vaccination rates in Canada remains far behind those in the United States, and the number of islet cell transplant procedures performed remained much lower than pre-COVID.

As a result, we are still waiting for our first patient to be enrolled. Steve will discuss the steps we are taking to address the pace of this study, including making it easier for patients to enroll and looking at additional geographies, where islet cell transplants are performed. Steve will also provide an update on AT-1501 in nonhuman primate islet cell data that was presented at the American Transplant Congress in June.

I will now turn over the call to Steve Perrin, our President and Chief Scientific Officer, to discuss our clinical programs. Afterwards, Paul Little will provide a financial update. Steve, please go ahead.

Thank you, DA. As a brief reminder, our lead asset, AT-1501, is an IgG1 anti-CD40 ligand antibody blocking Fc effector function. Physiologically, the interaction of CD40 ligand and CD40 results in clonal expansion, antibody production and secretion of pro-inflammatory cytokines that amplify an immune response. The CD40, CD40 ligand pathway is an attractive drug development target because the engagement of these receptors plays a pivotal role in immune system activation by mediating both antibody and cellular immune responses. We are focusing our efforts on the development of an antagonist antibody targeting the ligand rather than the receptor since targeting the ligand has been shown to be more efficacious in preclinical models of autoimmunity and as well as in the prevention of acute and long-term allograft transplant rejection.

I'll now dive into 4 targeted indications: ALS, kidney transplant, autoimmune nephritis and IgAN, in particular; and finally, islet cell transplant for the treatment of type 1 diabetes.

Eledon's ALS trial is a 12-week open-label dose-escalating study enrolling at 13 sites in the United States and Canada. Our enrollment continues to be on track, and we have now enrolled 17 of 18 patients in the third cohort, with the last patient in this cohort currently completing the screening assessments. We expect to complete enrollment of the fourth and final cohort by the end of the year, enabling the reporting of top line data in the first half of 2022. This data will consist of safety and tolerability data as well as multiple categories of biomarker endpoints with each subject serving as their own control by comparing changes from baseline.

In the first category of biomarkers, we will assess biomarker to CD40 ligand target engagement. Mechanistically, blocking CD40 ligand has profound effects on B cell maturation, antibody production and antibody class switching. We anticipate that we'll be able to assess CD40 ligand target engagement by AT-1501 with markers of B cell function such as CXCL13.

The second category of biomarkers are changes in pro-inflammatory chemokines and cytokines upregulated in people living with ALS. There is a long history of ALS data describing increases of pro-inflammatory signals in circulation, including TNF alpha, MCP-1, IL-6 and ENRAGE. We anticipate blocking of CD40 ligand will result in an overall decrease of these ALS-related pro-inflammatory markers.

Finally, we will also assess other exploratory endpoints, including changes in ALS Functional Rating Scale, or ALSFRS, respiratory function and the levels of neurofilament light chain in circulation. We consider these exploratory since the short duration of the study of 12 weeks may not provide sufficient time to see changes in clinical endpoints or changes in neurofilament light chain.

Moving on to renal transplant. We recently announced that we received a No Objection Letter from Health Canada to proceed with our first safety pharmacokinetics and efficacy study of AT-1501 in 6 to 12 subjects undergoing renal transplant. This is an important study to demonstrate that AT-1501 can safely be utilized to replace calcineurin inhibitors as part of first-line immunosuppressive therapy in solid organ transplantation and prevent acute and long-term solid organ transplant rejection. We expect that replacing calcineurin inhibitors will result in a measurable improvement in the quality of life for people undergoing organ transplant and eliminate the nephrotoxicity, cardiotoxicity, neurotoxicity, induction of type 1 diabetes that associated with chronic exposure to CNIs.

The study will be an open-label multiple site study, which we anticipate initiating by the end of the year, with initial interim data expected in late 2022. Endpoints will include biopsy-proven acute rejection, antibody mediated rejection in biomarkers of rejection as well as safety and PK/PD endpoints. In the terms of starting a trial in the United States, we announced in April that the FDA requested that we provide AT-1501 drug-specific renal transplant data in nonhuman primates prior to potentially initiating a clinical trial in renal transplantation in the United States. We have now reached agreement with the U.S. FDA that the study would consist of evaluating AT-1501 as monotherapy in 4 nonhuman primates.

To do this, we will be collaborating with a world-renowned expert in the development of new treatments and protocols for the prevention of allograft transplant rejection. We anticipate starting this study in the fourth quarter with the completion in mid-2022. These data will continue to build on the strong foundation that has already been established for AT-1501 in over 60 nonhuman primates across multiple species, including preclinical efficacy data in a nonhuman primate model of islet cell transplant. Moreover, multiple historical anti-CD40 ligand molecule similar to AT-1501 have demonstrated preclinical safety and efficacy in hundreds of nonhuman primates, including specifically in a nonhuman primate model of renal transplantation.

In autoimmunity, we will initially focus on IgA nephropathy, one of several autoimmune nephritises, which are autoimmune diseases of the kidney. There is a long history of preclinical and clinical data demonstrating that blocking CD40 ligand signaling ameliorates disease progression, modifies biomarkers of disease and improves renal function in diseases such as focal segmental glomerulosclerosis, lupus nephritis and IgA nephropathy. Moreover, a soluble CD40 ligand often correlates with disease flares in autoimmune diseases such as these. IgA nephropathy, or IgAN, is the leading cause of glomerulonephritis. Disease manifestation and clinical presentation involves renal dysfunction characterized by protein urea with a slow relentless course with approximately 30% to 40% of patients ultimately reaching end-stage renal disease.

The standard of care for end-stage renal disease is dialysis or kidney transplant, which represents a significant economic burden as well as a major impact on a patient's quality of life. IgAN is diagnosed via renal biopsy and the presence of IgA containing immune complex deposition in the kidney. At time of diagnosis, renal dysfunction is highly variable with protein urea levels greater than 1 gram per day. The formation of glycosylated IgA1 immune complexes in the kidney is hypothesized to be a multi-hit pathogenic pathological process.

Hit 1 is the aberrant glycosylation of IgA due to errors in the enzymatic galactosylation of IgA1. Hit 2 is the recognition by the immune system that this aberrant form of IgA1 called Gd-IgA1 is foreign and autoantibodies are generated against circulating Gd-IgA1. Hit 3 is the formation of Gd-IgA1 immune complexes in circulation. And Hit 4 is the deposition of these immune complexes in the mesenterial cells of the kidney, resulting in immune cell infiltration, cytokine production, complement activation leaded to chronic loss of kidney function, kidney damage, proteinuria and end-stage renal disease.

There is no FDA-approved therapies for IgAN. Guidelines for current standard of care for people with IgAN suggest the use of certain classes of anti-hypertension medications to modulate hemodynamic stresses on the kidney, resulting in an improved glomerular filtration rate and reduced protein urea. Treatment with either angiotensin converting enzymes or ACEs, or angiotensin receptor blockade (sic) [blockers], ARBs, a standard of care of proteinuria is greater than 1 gram per day and suggested if is greater than 0.5 grams per day.

The treatment with ACEs and ARBs as well as several molecules in clinical development are focusing on Hit 4, the downstream pathological mechanism of the disease after immune complex formation in the kidney and decreased kidney function. The exciting opportunity for AT-1501 in IgA nephropathy is that AT-1501 has the potential ability to ameliorate pathologies associated with Hits 2, 3 and 4. AT-1501 can prevent the production of auto antibody towards Gd-IgA1 referred to as Hit 2. This is due to the ability of AT-1501 to inhibit B cell maturation, thus decreasing antibody production and preventing antibody class switching. The inhibition of antibody class switching at the IgM stage will not only decrease the amount of IgA synthesized that will be available for improper galactosialization (sic) [galactosylation] but it also prevents the production of high-affinity IgG1 antibodies that form the immune complexes. Blocking CD40 ligand has the ability to decrease immune complex formation, has been shown in multiple animal models of autoimmunity as well as in the clinic, thus, AT-1501 has the potential to reduce pathogenesis associated with Hit 3 immune complex formation.

Finally, blocking CD40 ligand inhibits pro-inflammatory polarization of T cells and macrophages and has been shown to decrease immune cell infiltrate and infiltration inflammation in the kidney, Hit 4.

In conclusion, when IgAN's pathophysiology is taken as a whole, AT-1501 has the potential to ameliorate immune cell infiltration subsequent complement activation in the kidney and improve kidney function. We plan to launch an international Phase II study by the end of this year and will provide more details, including trial design, when we enroll the first patient.

Finally, in diabetes. We are focusing on people living with high-risk type 1 diabetes who are on chronic treatment with exogenous insulin and experience severe swings in blood glucose levels, hypoglycemic unawareness and associated comorbidities. Clinical trials conducted by the Clinical Islet Transplantation Consortium as well as islet cell transplants in other countries have demonstrated a islet cell transplantation in patients with difficult to control type 1 diabetes maintains glycemic balance, reinstates metabolic control and in some cases, even eliminates the need for exogenous insulin.

However, the current use of calcineurin inhibitors, or CNIs, for the prevention of islet cell transplant rejection poses 2 issues. First, CNIs are toxic towards transplanted islets, potentially resulting in significant islet cell loss post transplant and may lead to the requirement for multiple islet cell transplants. Indeed, in published trials, islet cell transplant recipients typically require multiple transplants with the need for a second transplant often apparent within approximately 90 days after the first transplant.

At the American Transplant Congress in June this year, Dr. Norma Kenyon, Director of the Diabetes Research Institute at the University of Miami, presented data comparing an aggregated group analysis of animals receiving AT-1501 as either monotherapy or in conduction with induction therapy to animals on tacrolimus in conduction with induction therapy in a nonhuman primate model of islet cell transplant. Her findings indicated that animals on AT-1501 had significantly longer rejection-free survival, significantly longer overall islet cell graft survival and maintain greater body weight compared to animals on tacrolimus.

In addition, C-peptide levels were 4x higher for animals treated with AT-1501 compared to animals treated with tacrolimus. In one group of animals receiving AT-1501 monotherapy at 10 mg per kg every 14 days, she decreased the dosing frequency by half starting on day 224, and one of these animals [continue] with graft function well over 400 days, which according to her, represented a functional cure of type 1 diabetes in this animal. Finally, she reported that animals on tacrolimus were more susceptible to life-threatening CMV infections, a common toxicity associated with CNIs.

As a result of data such as this, we believe that replacing CNIs with AT-1501 may improve islet cell survival and clinical outcomes associated with islet cell transplant, thus potentially allowing for islet cell transplant to become a viable treatment option and even a potential functional cure for persons living with high-risk type 1 diabetes. We currently have an active clinical site in Alberta, Canada seeking to enroll a single arm open-label study. Primary endpoints include safety and tolerability, glucose control, insulin independence, reduction of HbA1c, graft survival and function. We will also be assessing hypoglycemic awareness events as well as renal function.

Unfortunately, Canada and the province of Alberta were significantly impacted by COVID in the first half of this year, and the rollout of vaccinations in Canada was until recently far behind the U.S. This significantly impacted the ability of the staff to work on site and maintain a normal process of patient screening enrollment for islet cell transplant procedures. Moreover, travel between provinces in Canada was seriously impacted as well as the willingness of patients to take the immunosuppressants necessary for an elective transplant procedure.

Taken together, the effect has been to very significantly reduce the number of islet cell transplant procedures being performed so far this year compared to pre-COVID. We are working with the site to facilitate patient recruitment into the study included by reaching out to more endocrinologists across the province in Canada as well as by beginning to work on ways to allow patients to receive drug closer to home, thus decreasing their need to travel.

Separately, we have assessed the ability to expand the study to sites in Europe but have found that to date, they have experienced similar issues with COVID-19 as Canada. As the COVID situation continues to evolve, we will reassess the potential for international expansion. We are still targeting to enroll this trial as soon as possible, which would allow us to meet our goal of generating interim data in islet cell transplant in the first half of 2022. This is based on the timing to assess graft function and acute transplant rejection is 90 days post transplant on a patient-by-patient basis.

With that, I'll turn the call over to Paul for our financial update.

Thank you, Steve. In addition to the financial results summarized in our press release, you can find additional information in our Form 10-Q, which we will file later today.

The company reported a net loss of $7.4 million or $0.50 per share for the 3 months ended June 30, 2021 compared to a net loss of $2.6 million or $2.74 per share for the same period in 2020. Research and development expenses were $4.2 million for the 3 months ended June 30, 2021 compared to $800,000 for the same period in 2020. The increase in R&D costs primarily reflects clinical and CMC activities as we advance our AT-1501 programs. G&A expenses were $3.7 million for the 3 months ended June 30, 2021 compared to $1.3 million for the same period in 2020. The increase in G&A spend primarily reflects increased personnel and stock-based compensation costs, legal and other professional fees.

Now turning to a few key financial metrics for the full year to date. The company reported a net loss of $15.9 million or $1.07 per share for the 6 months ended June 30, 2021 compared to a net loss of $10.8 million or $11.31 per share for the same period in 2020. R&D expenses were $9.9 million for the 6 months ended June 30, 2021 compared to $2.5 million for the same period of 2020. The increase in R&D costs primarily reflects clinical and CMC activities as we advance our AT-1501 programs. G&A expenses were $7.1 million for the 6 months ended June 30, 2021 compared to $3 million for the same period last year. The increase in G&A spend primarily reflects increased personnel and stock-based compensation costs, legal and other professional fees.

The company had $101.1 million in cash and cash equivalents as of June 30 compared to $108.6 million in cash and cash equivalents as of March 31, 2021. We expect our financial resources to be sufficient to fund operations as currently planned well into 2023.

Finally, subsequent to our acquisition of Anelixis in 2020, we undertook a strategic review of the Novus Pharmaceuticals (sic) [Novus Therapeutics] legacy assets for otitis media. We recently concluded this review and determined that the best path forward was to terminate license agreements associated with these assets and return the rights to the original license holders. We did this in July. There was no financial impact with the return of these assets.

With that financial update, let me turn the call back over to DA.

Thank you, Paul. We made significant progress during the second quarter advancing our lead molecule, AT-1501 and look forward to multiple potential upcoming milestones. This year, we expect to present AT-1501 nonhuman primate data at the International Pancreas and Islet Cell Transplantation World Congress Annual Meeting in October to initiate clinical trials -- a clinical trial in the prevention of kidney transplant rejection and a trial in IgAN and to initiate a nonhuman primate kidney transplant study. We then expect to begin reporting data readouts from these trials starting in the first half of 2022 with ALS and islet cell transplantation for type 1 diabetes as well as the nonhuman primate kidney transplant study.

With that, I will now ask the operator to begin our Q&A session. Operator?

(Operator Instructions) Our first question comes from Alethia Young with Cantor Fitzgerald.

This is [Nina] on for Alethia. We were wondering for the islet cell transplantation program if you had any idea or leads on when the first patient might be enrolled and if you think that will be in Canada or also in Europe. And how quickly do you think you can line up patients? And also, if you can just remind us how many patients you plan on recruiting?

Sure. [Nina], thank you for the question. We are looking to enroll the first patients as soon as possible. Currently, the trial is only open in Canada. And so that's where we are focused. But as you heard and as we discussed, we will look, especially as COVID progresses, to see whether there are ways to add additional countries to the trial as well. What's nice here is that we can begin to get data quickly since patients often need second transplant procedures within 90 days after the first transplant, when they receive current standard of care, which could allow us to quickly see the effect that AT-1501 is having.

What's nice here is that we can get significant learnings with just a few patients. And so we plan on reporting the data that we have on the totality of patients that we'll be able to have enrolled in the first half of next year. Steve, let me see if you have anything you'd like to add.

Yes. No -- yes, again, I mean, we're working hard with the site to get back up and running. They've had challenges with COVID-19 as has everybody. The important thing about the islet cell transplant procedures, as DA mentioned, is the ability to fairly rapidly assess graft function on a subject-by-subject basis, which could still yield exciting data next year.

Our next question comes from Matt Kaplan with Ladenburg Thalmann.

I wanted to just dig in a little bit more to the renal transplant program. I guess, given the readouts that you expect for the nonhuman primates in middle of next year and clinical data late next year, when do you think you'll be able to start a U.S.-focused study in renal transplant?

Thanks, Matt. Why don't I turn that over to Steve to go through the plan?

So I think that there were 2 questions here, Matt. One was about the nonhuman primate study, and the other was about anticipation on moving into the U.S., correct?

Correct. Yes.

So for the nonhuman primate study, as we indicated, we had very specific guidance from the agency on what they wanted there, which was monotherapy AT-1501 in a nonhuman primate renal transplant model. Because of that guidance, we can reach out and start to work with an excellent collaborator in that regard. We know based on lots of historical data that we've mentioned, hundreds and hundreds of animals have undergone renal transplant studies with monotherapy for various anti-CD40 ligand antibodies. In the absence of any treatment, animals reject very, very quickly, within a few days to a week.

Even on monotherapy, there's some variability in the durability of preventing rejection. But typically, average survival times would suggest that we can conduct this experiment fairly quickly. Monotherapy treatment, standardly depending upon the types of primates and the types of treatments, can go anywhere from 14 days to 30 days with some standard deviations with animals surviving longer than that. But a fairly straightforward study given that they're looking for just to demonstrate that AT-1501 can move out the time frame from acute rejection in untreated animals.

As far as the clinical plans in the U.S. I think that that's just very dependent on what the data looks like from Canada. I mean we're really excited for the study to initiate in Canada by the end of the year. As we know, transplant studies are a little bit more complicated in humans than they are in animals. But really, I think the decision to get back to the agency with not only their request for the nonhuman primate data but with also some human data from that Canadian study is key. So I think we need to wait until we see what that Canadian data looks like.

So we'll look -- we'll look as when we begin to have human data as well as complete the study to return and reinitiate discussions with the FDA, which could be obviously as soon as this -- in the second half of next year.

Okay. Makes sense. And then a second question. Thanks for all the detail on IgA nephropathy and potential kind of nodes of impact that 1501 can have. Can you give us a little bit more color on the study that you plan, the Phase II that you plan to start? And also, what kind of read-through do you think this study will give to potential other etiologies of autoimmune nephropathy? Or nephritis, I should say.

So in terms of specific color on trial design, we'll give more color as we begin to initiate the trial and enroll patients. As you can understand, we'd like to finish our discussions with the various regulatory bodies and have our CTAs approved before we go to -- before we go into full detail. With regards to the potential read-through in autoimmune nephritis overall and the overlap between [various] autoimmune nephritis, let me turn that over to Steve.

Yes, it's a great question, Matt, about read-through because as you know, one of the common themes, even though these diseases are different, I mean, I'm thinking of lupus nephritis, FSGS, IgAN and others, I mean, there's differences within each of these indications. But a common theme here is kidney dysfunction protein urea, ultimately eGFR improving all of the above. So there is some crossover, if you will, once you get some data points in one of these indications that if you're improving downstream kidney function by ameliorating immune infiltration, complement activation or a host of other pathophysiologies, that could easily read through to other indications. So the data in IgAN, I think, is very important to help us understand mechanistically how the drug is working, but also if we're improving kidney function.

Our next question comes from Thomas Smith with SVB Leerink.

Just on the autoimmune nephritis. I mean you previously talked about FSGS and lupus nephritis as potential initial indications. Can you just walk us through how you thought about IgAN relative to those other 2 indications and how you ended up settling on IgAN?

Yes. So we've historically spoken about autoimmune nephritis as covering the 3, so FSGS, lupus nephritis and IgAN. We ultimately selected IgAN because as we thought about both our understanding of the disease as well as the way of using an anti-CD40 ligand could impact the disease, that's where we felt that we had the greatest chance of success. Let me turn it over to Steve to just provide some more color on the use of -- potential use of CD40 ligand in igAN.

Yes. I mean DA certainly hit the highlights there. I mean we think that there's opportunities on unmet need in FSGS, lupus nephritis and even other autoimmune nephritises. But really, the disease mechanisms for some of these indications are still a little unclear. There is significant heterogeneity and patient stratification can be a problem. In the context of FSGS, in particular, I'm thinking about all of the above. I mean, mechanistically, we're still trying to elucidate what are the real mechanisms leading to kidney dysfunction and FSGS.

And when we compare and contrast that to the pathophysiology of what we know about IgAN, we just understand more of what causes disease in IgAN and the fact that blocking CD40 ligand can play a very significant role in multiple parts of that process really makes it an exciting opportunity to really understand if blocking immune complex formation downstream, if moving upstream and actually eliminating immune complex formation by eliminating antibody production and moving even further upstream from that is really modulating ultimately the production of IgA by knocking down B cell production of antibodies and blocking class switching. AT-1501 has the potential to do all of those things. So it really is an exciting opportunity to look and see if blocking CD40 ligand function can have a dramatic impact on the upstream processes of kidney dysfunction and IgAN.

Got it. Okay. That's helpful. And then just a follow-up on an earlier question. I understand you're still working through the details of the study design, and you're waiting to hear feedback from some of the regulators. But I guess, do you have any initial sense of when we could see a first look at data from this program?

Yes. So we'll look to construct the trial to be able to begin to get some data readouts next year.

Okay. That's helpful. And then maybe just one last question. Just on islet cell and the presentation at the Islet Transplant World Congress coming up here in October. What should we be looking for in terms of new data sets in that presentation?

Yes. So the presentation will be again done by Norma Kenyon from the University of Miami. And so she'll continue to give more details on all of the work that she has done to date with our nonhuman primates in AT-1501. Steve?

Yes. I mean Norma continues to be really excited about the data that she's generated thus far. And given her long history going back over 20 years, I mean, Norma has had her fingers on a lot of different potential treatments to prevent transplant rejection in her nonhuman primate model. So she continues to look at the data and will continue to build on her story of mechanistically how blocking the ligand has the potential to prevent short-, long-term reduction and even induce tolerance and a functional cure in some animals. So we're really excited to be working with Norma and her team.

(Operator Instructions) Our next question comes from Rami Katkhuda from LifeSci Capital.

Congrats on all the updates. I know Steve touched upon this briefly, but can you guys provide a little more insight on the differentiation between AT-1501 and some of these B cell modulating therapies in development for IgA nephropathy, specifically?

Sure. Rami, thanks for the question. Let me turn that over to Steve.

Yes. So you're probably specifically talking about APRIL, BAFF, BCMA inhibitors?

Yes, exactly.

Yes. So the very targeted therapy is much like CD40 ligand. They're targeting the upstream processes of antibody formation and production. So the second and third hits, if you will, that I was talking about. And the strategies there are probably fairly similar to how we think CD40 ligand would inhibit those 2 processes. You're modulating B cell function, B cell maturation, antibody production, class switching downstream of IgM, which is critical.

I think one of the potential differentiation points is more in the downstream process. The one thing that blocking CD40 ligand does that the BAFF and APRIL inhibitors may not specifically do is modulating immune cell infiltrate into the kidney post a mean complex deposition. And that's one of the things that blocking the ligand may do that's a little bit mechanistically different than blocking APRIL or BAFF.

Got it. That makes a lot of sense. And then I guess switching gears a little...

So said another way, it goes, I think, back to what Steve had described versus if you think about the 4-hit hypothesis. What this allows us to do is to potentially have an impact on more hits than other approaches.

Got it. And then looking at the open-label kidney transplant trial. I know this is somewhat hypothetical, but is there potential for positive data from that program to kind of expedite the development pathway with regards to the FDA?

So that's what we're looking to do, is to see how quickly we can move the program forward, and we'll do it in a way that's as expeditious as possible, while also, of course, respecting our regulatory requirements and making sure we do what's right for patients. But the idea is to meet the FDA's requests in terms of the nonhuman primate study and then use the data that we are looking to generate in patients to see what is the -- assuming that data is positive, what is the fastest next step in terms of the development of AT-1501 in kidney transplantation.

Our next question comes from Vernon Bernardino.

Most of my questions were related to the choice of IgAN and therefore, asked and answered and then the -- what to expect at the conference in October. And then you briefly mentioned it's primate work. But will some of that work also be related to the IgAN research?

So the work in -- first, thank you very much, Vernon, for the question. The work that we'll present is going to be primarily focused on enormous work in islet cell transplant. But let me turn that over to Steve to talk about how that work could impact or could read through other immune conditions as well.

I mean the work that we're doing with Norma is fairly focused on islet cell transplant. I mean, mechanistically, there's probably not a lot of read-through there for understanding mechanistically how it could work out or impact autoimmune nephritis indications. Now the animals that we're talking about doing for monotherapy for the renal transplant study in nonhuman primates, we will be looking, obviously, at not only rejection but also immune cell infiltrate and other downstream parameters associated with transplant rejection and function that could be informative in the context of autoimmune nephritis.

So that could provide -- that study could provide some information on mechanistically how blocking CD40 ligand modulates the immune system and may mitigate improvements in renal function in the context of transplant. So that one could have some read-through downstream.

Okay. That's perfect. And then, therefore, with the IgAN study, I just want to confirm. Is that going to be a Phase II study? And are you going to look at -- on different doses?

So it's going to be -- to your point, this will be a human clinical trial, so we'll look to do a Phase II. The specific trial design and the potential to use multiple doses will give more color on further down the line.

At this time, we have reached the end of the question-and-answer session. I will now turn the call over back to management for closing remarks.

Thank you, operator. And thank you, everyone, for joining us today on the call. We are pleased you could join to hear our progress during the second quarter, and we look forward to keeping you updated on our company and programs.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. .