Eledon Pharmaceuticals, Inc.

Greetings. Welcome to the Elladon Pharmaceuticals report second quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. 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 Elladon Pharmaceuticals' second quarter 2021 financial results conference call. Joining me today is David Alexandra Groh, Chief Executive Officer, Steven Perrin, President and Chief Scientific Officer, and Jeff Bornstein, Chief Medical Officer. Earlier today, Elladon issued a press release announcing financial results for the second quarter ended June 30th, 2021. You may access the release under the investors tab on our company website, elladon.com. Before we begin, I would like to remind everyone that statements made today during this call related to Elladon'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 Elladon. Elladon expressly disclaims any duty to provide updates to its forward-looking statements, whether as a result of new information, future events, or otherwise. Participants directed to the risk factors set forth in Elladon's reports file 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 Alexandra Groh.

Thank you, Paul, and good afternoon, everyone. We continue to make significant progress during the second quarter advancing our lead molecule, AT1501. I'm excited by the promise offered to us by AT1501 as a potential therapeutic for organ or cellular transplantation, ALS, and serious immunological diseases where patients face limited treatment options. We plan to advance AT1501 in up to four clinical trials, 1, ALS, 2, the prevention of kidney allograft transplant rejection, 3, autoimmune nephritis starting with IgA nephropathy or IGAN, and 4, 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 four cohorts, and top-line data is expected in the first half of 2022. In renal transplantation, We previously communicated that the US FDA requested that we provide AT1501 specific renal transplant data in non-human 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 requirements 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 to conduct a preclinical renal transplant study evaluating AT1501 as monotherapy in four 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 XUS clinical trial, we received a no objection letter from Health Canada in response to our clinical trial application proposing to evaluate AT1501 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 IgA. 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 2 clinical trial of AT1501 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 remained 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're 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 AT1501 in non-human 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, AT5001, is an IgG1 anti-CD40 ligand antibody lacking 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 four targeted indications, ALS, kidney transplant, autoimmune nephritis, and IGAN in particular. And finally, islet cell transplant for the treatment of type 1 diabetes. Elidon'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 to 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'll 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 AT1501 with markers of B cell functions 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, MCP1, IL-6, and ENRAGED. 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 ALS-FRS, respiratory function, and the levels of neurofilament light chain and 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 AT5001 in six to 12 subjects undergoing renal transplant. This is an important study to demonstrate that AT5001 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's 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, and biomarkers of rejection, as well as safety and PKPD endpoints. In the terms of starting a trial in the United States, we announced in April that the FDA requested that we provide AT5001 drug-specific renal transplant data in non-human primates prior to potentially initiating a clinical trial in renal transplantation in the United States. We have now reached agreement with the US FDA that this study would consist of evaluating AT-1501 as monotherapy in four non-human 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 AT50-01 in over 60 non-human primates across multiple species, including preclinical efficacy data in a non-human primate model of islet cell transplant. Moreover, multiple historical anti-CD40 ligand molecules similar to AT50-01 have demonstrated preclinical safety and efficacy in hundreds of non-human primates, including specifically and a non-human primate model of renal transplantation. In autoimmunity, we will initially focus on IgA nephropathy, one of several autoimmune nephritis, which are autoimmune diseases of the kidney. There is a long history of preclinical and clinical data demonstrating that blocking CD40-Lignin 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, soluble CD40 ligand often correlates with disease flares in autoimmune diseases such as these. IgA nephropathy or IGAN is the leading cause of glomerular nephritis. Disease manifestation and clinical presentation involves renal dysfunction characterized by proteinuria 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. IgAIN 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 proteinuria levels greater than one gram per day. The formation of glycosylated IgA1 immune complexes in the kidney is hypothesized to be a multi-HIT pathogenic pathological process. HIT1 is the aberrant glycosylation of IgA due to errors in the enzymatic galactosylization of IgA1. HIT2 is the recognition by the immune system that this aberrant form of IgA1 called GD IgA1 is foreign and autoantibodies are generated and 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 mesangial cells of the kidney, resulting in immune cell infiltration, cytokine production, complement activation, leading to chronic loss of kidney function, kidney damage, proteinuria, and end-stage renal disease. There is no FDA-approved therapies for IgA1. Guidelines for current standard of care for people with IGAN suggest the use of certain classes of antihypertension medications to modulate hemodynamic stresses on the kidney, resulting in improved glomerular filtration rate and reduced proteinuria. Treatment with either angiotensin-converting enzymes or ACEs or angiotensin receptor blockade ARBs, the standard of care of proteinuria is greater than 1 gram per day and suggested if as great as 0.5 grams per day. The treatment with ACEs and ARBs, as well as several molecules in clinical development, are focusing on HIT4, the downstream pathological mechanism of the disease after immune complex formation in the kidney and decreased kidney function. The exciting opportunity for AT50-01 and IgA nephropathy is that AT50-01 has the potential ability to ameliorate pathologies associated with HITs 2, 3, and 4. AT50-01 can prevent the production of autoantibody, towards GDA IgA1 referred to as HIT2. This is due to the ability of AT50-01 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 would be available for improper galactosylization, 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 as has been shown in multiple animal models of autoimmunity as well as in the clinic. Thus, AT50-01 has the potential to reduce pathogenesis associated with HIT3, 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 inflammation in the kidney, HIT4. In conclusion, when IGAN's pathophysiology is taken as a whole, AT50-01 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 two study by the end of this year, and we'll 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 that 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 two 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 AT1501 as either monotherapy or in conduction with induction therapy to animals on tacrolimus in conduction with induction therapy in a non-human primate model of islet cell transplant. Her findings indicated that animals on AT5001 had significantly longer rejection-free survival, significantly longer overall islet cell graft survival, and maintained greater body weight compared to animals on tacrolimus. In addition, C-peptide levels were four times higher for animals treated with AT5001 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 continued 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 who 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 AT5091 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 and enrollment for ILSL transplant procedures. Moreover, travel between provinces in Canada was seriously impacted, as well as the willingness of patients to take the in-person presence necessary for an elective transplant procedure. Taken together, the effect has been to very significantly reduce the number of ILSL 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 and I would sell transplant in the first half of 2022. This is based on the timing to assess graph 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 follow later today. The company reported a net loss of $7.4 million, or $0.50 per share, for the three months into 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 three months into 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 AT1501 programs. G&A expenses were 3.7 million for the three months into June 30th, 2021, compared to 1.3 million for the same period of 2020. The increase in G&A spend primarily reflects increased personnel and stock-based compensation costs, legal and other professional fees. I'll turn 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 six months ended June 30, 2021, compared to a net loss of $10.8 million, or $11.31 per share, for the same period of 2020. R&D expenses were $9.9 million for the six 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 AT1501 programs. G&A expenses were $7.1 million for the six months ended June 30th, 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 cash and cash equivalents as of June 30th, compared to $108.6 million in cash and cash equivalents as of March 31st, 2021. We expect our financial resources to be sufficient to fund operations as currently planned well into 2023. Finally, subsequent to our acquisition of Adalexis in 2020, we undertook a strategic review of the Novus Pharmaceuticals legacy assets for Otis 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, AT1501, and look forward to multiple potential upcoming milestones. This year, we expect to present AT1501 non-human 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 IGAM, and to initiate a non-human 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 non-human primate kidney transplant study. With that, I will now ask the operator to begin our Q&A session. Operator?

Thank you. At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may remove your question by pressing star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment while we poll for questions. Our first question comes from Alethea Young with Cantor Fitzgerald. You may proceed with your question.

Hi, this is Nina. I'm for Alethea. Thanks for taking your questions. We are 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 they'll be in Canada or elsewhere 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. Thanks.

Sure. Hey, Nina, thank you for the question. We are looking to enroll a first patient 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, you know, 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 fact that AT1501 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.

Yeah, again, 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 procedure, 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.

Okay, thank you.

Our next question comes from Matt Kaplan with Ladenburg-Thalmann. You may proceed with your question.

Hey, guys. Thanks for taking the questions. I apologize if there's some background noise. We're just getting hit with a thunderstorm right now. We're going 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 the 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 was two questions here, Matt. One was about the non-human primate study, and the other was about anticipation on moving into the U.S., correct?

Correct, yes.

So for the non-human primate study, as we indicated, you know, we had very specific guidance from the agency on what they wanted there, which was monotherapy AT1501 in a non-human primate renal transplant model. Because of that guidance, we can reach out and start to work with an excellent collaborator in that regard and 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. And in the absence of any treatment, you know, 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, you know, average survival times would suggest that we can conduct the sperment fairly quickly. Monotherapy treatment, you know, 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 AT5001 can move out the timeframe from acute rejection in untreated animals. As far as the clinical plans in the US, 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 non-human 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 at 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 in the second half of next year. Okay, makes sense. Thanks.

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 two 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 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.

Yeah, 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, proteinuria, 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 and IGN, I think, is very important to help us understand mechanistically how the drug is working, but also if we're improving kidney function.

Great. Thanks, Stephen. D.A.? ?

Our next question comes from Thomas Smith with SVB Liernick. You may proceed with your question.

Hey, guys. Good afternoon. Thanks for the updates, and thanks for taking the questions. 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 two indications and how you ended up settling on IGAN?

Yeah, so we've historically spoken about autoimmune nephritis as covering the three, 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 the way 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 potential use of CD40 ligand in IGAM.

Yeah, I mean, DA certainly hit the highlights there. I mean, we think that there's opportunities and 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's significant heterogeneity, and patient stratification can be a problem in the context of FSGS in particular. You know, I'm thinking about all of the above. I mean, mechanistically, we 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, 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. AT51 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 ligand.

Got it. Okay. That's helpful. And then just to 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?

Yeah, 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?

Yeah, 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 her non-human primates in AT1501. Steve? Okay, got it.

Yeah, 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 non-human primate model. 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 rejection and even induce tolerance and a functional cure in some animals. So we're really excited to be working with Norma and her team.

Okay, got it. Got it. Thanks, guys. Looking forward to the presentation, and thanks for taking the questions.

Thank you. As a reminder, if you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the queue. Our next question comes from Rami Kakuta from LifeSci Capital. You may proceed with your question.

Hey, guys. Congrats on all the updates, and thanks again for taking my questions. I know Steve touched upon this briefly, but can you guys provide a little more insight on the differentiation between AC1501 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.

Yeah, so you're probably specifically talking about April BAF BCMA inhibitors?

Yep, exactly.

Yeah, 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 two 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 BAF and APRIL inhibitors may not specifically do is modulating immune cell infiltrate into the kidney post-immune 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 BAF.

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

Said another way, you know, it goes, I think, back to what Steve had described, which is when you think about the four-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 non-human 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 AT1501 in kidney transplantation?

Sounds great. Thank you, guys.

Our next question comes from Vernon Bernardino. You may proceed with your question.

Hi, I'm DA Steve and Paul. Thanks for the update. Thanks for taking my question. Most of my questions were related to the choice of IGAND and therefore asked and answered and then what to expect at the conference in October. And then you briefly mentioned it's private work, but will some of that work also be related to the IGAND 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 Norma's 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 or impact autoimmune nephritis indications. Now, the animals that we're talking about doing for monotherapy for the renal transplant study in non-human 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 IGANT study, I just wanted to confirm, is that going to be a Phase II study, and are you going to look at 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. Okay.

Just wanting to get ahead. Thanks for taking my question. Everything else was already asked and answered, so appreciate the update and all the answers. Thank you.

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.