Selecta Biosciences, Inc's (SELB) CEO Carsten Brunn on Q2 2022 Results - Earnings Call Transcript

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Selecta Biosciences, Inc. (NASDAQ:SELB) Q2 2022 Earnings Conference Call August 4, 2022 8:30 AM ET

Company Participants

Kevin Tan – Chief Financial Officer

Carsten Brunn – President and Chief Executive Officer

Peter Traber – Chief Medical Officer

Kei Kishimoto – Chief Scientific Officer

Conference Call Participants

Kristen Kluska – Cantor Fitzgerald

Yun Zhong – BTIG

Yatin Suneja – Guggenheim Partners

John Newman – Canaccord

Raju Prasad – William Blair

Boobalan Pachaiyappan – H.C. Wainwright

Operator

Good day, and welcome to the Selecta Bio Second Quarter 2022 Earnings Release Conference Call. All participants will be in listen-only mode. [Operator Instructions] After today's presentation, there will be an opportunity to ask questions. [Operator Instructions] Please note this event is being recorded.

I would now like to turn the conference over to Kevin Tan, Chief Financial Officer of Selecta Bio. Please go ahead.

Kevin Tan

Thank you, and good morning. Welcome to our second quarter 2022 financial results and corporate update conference call. The press release reporting our financial results is available in the Investors and Media section of Selecta's website, worldwide web selectabio.com, and our quarterly report on Form 10-Q for the quarter ended June 30, 2022, which we intend to file in the coming days with the Securities and Exchange Commission, or SEC. Joining me today are Carsten Brunn, President and Chief Executive Officer; Peter Traber, Chief Medical Officer; and Kei Kishimoto, Chief Scientific Officer.

During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, efficacy, regulatory and clinical progress of our product candidates, our financial projections and our future expectations, plans, partnerships and prospects. These statements are subject to various risks that are described in the filings made with the SEC including our most recent annual report on Form 10-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, August 4, 2022, and Selecta disclaims any obligation to update such statements except as required by law even if management's views change.

I would now like to turn the call over to Carsten Brunn. Carsten?

Carsten Brunn

Thank you, Kevin. Good morning. I appreciate everyone taking the time to join us today. In the second quarter of 2022, we made steady progress across our proprietary pipeline and achieved numerous key milestones. Most notably, on June 29, we completed the enrollment of the DISSOLVE II trial, triggering a $10 million milestone payment obligation from Sobi. Our partners continue to progress the ImmTOR platform in combination with their gene therapy candidates.

And in June, Sarepta extended their option and license agreement for Duchenne muscular dystrophy and certain limb-girdle muscular dystrophies subtypes by nine months and achieved certain preclinical milestones. These two events resulted in total payment obligations of $6 million from Sarepta that we anticipate receiving in Q3 2022.

Finally, on April 6, we priced an underwritten offering, raising approximately $38.7 million. We believe that our existing cash, cash equivalents, restricted cash and marketable securities as of June 30, 2022, will enable us to fund our operations into mid-2024. The second half of this year will be an important time for Selecta as we anticipate completing the Phase III DISSOLVE trial in collaboration with our partner Sobi. We expect to announce joint top line data from DISSOLVE in Q1 2023.

We also anticipate advancing SEL-302, our proprietary gene therapy candidate to treat methylmalonic acidemia, or MMA, into the clinic, and we remain on track to commence the Phase I clinical trials in the fourth quarter of this year. Our team continues to advance our preclinical pipeline, most notably IND-enabling studies and manufacturing scale-up, for our proprietary IgG protease, Xork, to help unlock the power of gene therapies.

IgA protease candidate selection with our partners Ginkgo Bioworks and IGAN Biosciences for the treatment of IgA nephropathy and accelerating the development of ImmTOR-IL, which is the evolution of our antigen-specific precision immune tolerance platform. With an expected financial runway into mid-2024, we believe we are well-positioned to re-imagine immunotherapy in autoimmune disease, unlock the potential of AAV gene therapy and amplify the efficacy of biologic therapies.

Let me now walk you through some of the key highlights and recent activities across all three pillars of our pipeline. Over 24 million Americans suffer from autoimmune diseases. The current standards of care utilize immunosuppressive drugs, which often leave patients vulnerable to serious infections and malignancies or symptoms amassing treatments which fail to address the underlying cause of the disease.

Our approach re-imagines the treatment paradigm by addressing the underlying cause of autoimmune disease. Through our precision immune tolerance platform, we hope to restore immune system balance by inducing and expanding antigen-specific regular T-cells or Tregs in vivo. As we've highlighted before, we're very excited about a recent preclinical data we have generated, showing substantial synergistic activity when ImmTOR is combined with engineered IL-2 molecules that are selective for Tregs, and evolution of a platform we call ImmTOR-IL.

A top priority for Selecta in 2022 is accelerating the development of a proprietary engineered IL-2 to combine with ImmTOR. We have partnered with Cyrus Biotechnology, a world-leading protein engineering company spun out of David Baker's lab at the University of Washington, to facilitate development of our next-generation, highly differentiated IL-2 mutein to combine with ImmTOR. And like other programs in development using engineered Tregs selective IL-2 molecules that focus on generalized expansion of Tregs, ImmTOR and ImmTOR-IL when combined with antigen of interest is focused on induction and expansion of Tregs specific to those auto-antigens responsible for the pathogenesis of autoimmune diseases. We believe our technology has the potential to be a truly differentiated first-in-class antigen-specific treatment for autoimmune diseases. The first autoimmune indication in which we plan to evaluate our precision immune tolerance platform is in primary biliary cholangitis, or PBC, a T-cell mediated liver disease, driven by a well-defined antigen PDC-E2. In PBC, the immune system mistakenly attacks tissue in the liver and damage the small bile ducts.

While treatments to help slow the progression and prevent complications in PBC are available, approximately 30% to 40% of patients are intolerant to or do not respond to these treatments, leaving patients with limited alternative treatment options and a significant unmet need. Co-administering ImmTOR-IL with PDC-E2, the autoantigen implicated in PBC may result in the expansion of Tregs specific to PDC-E2 and restore immune system balance. We continue to work toward additional indication selection, and we plan to expand into other autoimmune indications. We expect to provide updates on our strategic development path for ImmTOR-IL in the near future.

Now moving on to our gene therapy pipeline. In Q4 2022, we anticipate starting a Phase I trial of SEL-302, a combination of ImmTOR with MMA-101 in AAV gene therapy being developed for the treatment of MMA. MMA is a rare metabolic disease in which the body cannot break down certain proteins and fats. The Phase I trial will evaluate the safety and efficacy of SEL-302 in treating MMA and ImmTOR's ability to mitigate neutralizing antibodies against the MMA-101 AAV capsid.

We hope this trial will build on our growing body of evidence pointing towards the potentially multifaceted benefits of ImmTOR, enhancing the efficacy and safety of AAV gene therapies. Additionally, development of SEL-302 could provide an important regulatory and clinical blueprint for our current and future gene therapy partners, potentially accelerating the development of safer and redoseable AAV gene therapies for patients suffering from rare genetic diseases.

This past May, at the American Society of Gene & Cell Therapy, Selecta showcased six presentations, including three from our partnership with AskBio. Our CSO, Kei Kishimoto, was awarded an Outstanding Poster Presentation Award for his abstract titled Combination of ImmTOR Tolerogenic Nanoparticles and IL-2 Mutein Synergistically Inhibits the Formation of Anti-AAV Antibodies. This poster showed ImmTOR-IL had the ability to induce durable immune tolerance to a co-administered AAV gene therapy vector in mice and demonstrated complete inhibition of anti-AAV antibody formation after multiple doses of gene therapy through 117 days.

Notably, this effect was observed and would be considered sub-therapeutic doses for ImmTOR alone. Building on this, today we are pleased to report new data from preclinical studies in mice using gene therapy vector doses of 5E13 vg/kg or 10x the dose of prior studies. This study demonstrated that a single dose of ImmTOR plus four monthly doses of IL-2 co-administered with AAV8-SEAP produced durable mitigation of anti-AAV antibodies over 131 days.

When combined with our human proof-of-concept study, where we observed ImmTOR's ability to inhibit the formation of neutralizing antibodies in healthy human volunteers out to 30 days, we believe these results suggest that ImmTOR-IL has the potential to solve the redosing problem associated with AAV gene therapies and transform the treatment paradigm from one and done to low and slow, whereby patients could receive multiple doses of gene therapy to titrate up to a therapeutic benefit and avoid the risks associated with higher vector doses of gene therapy needed in a onetime-only treatment model.

Another key challenge facing the gene therapy modality is one of accessibility. Currently, 30% to 70% of patient population for gene therapy trials are ineligible for inclusion due to preexisting neutralizing and anti-AAV antibodies, which are a result of natural infections. Thus many patients in need are unable to access potentially life-altering therapies for which there may be few or no treatment alternatives.

IgG proteases have shown promise as a pretreatment to transiently clear preexisting utilizing antibodies and create a window during which AAV gene therapies could be administered. However, IgG proteases are derived from bacteria and are themselves highly immunogenic. Additionally, some IgG proteases are derived from a common human pathogen. And consequently, the vast majority of individuals have pre-existing antibodies against these proteases.

Xork, our proprietary IgG protease candidate, has been optimized to specifically cleave human IgG, but is derived from a nonhuman pathogen, and we have observed low cross activity to preexisting anti-IgG protease antibodies. We believe that the combination of Xork with ImmTOR could enable repeat dosing of this enzyme therapy. We continue with IND-enabling studies and manufacturing scale-up.

I want to take a moment to discuss how important we believe Xork could be for the gene therapy modality. For many patients with rare genetic diseases, gene therapy could represent the most promising treatment option. Unfortunately, many patients are ineligible for gene therapy due to preexisting anti-AAV antibodies. By using Xork to open a therapeutic treatment window for these patients, we have the potential to bring hope to those who may not have any other effective treatment options. At the same time, by increasing the eligible patient population, we can help companies maximize the commercial potential of their gene therapy candidates. We're taking a multipronged approach protecting the immunogenicity challenges facing AAV gene therapies.

ImmTOR and ImmTOR-IL to mitigate the de novo formation of neutralizing antibodies and enable redosing and Xork to address those patients who, due to natural AAV infections, are ineligible for treatment by gene therapies. We continue to progress our gene therapy platform toward the goal of providing an industry-leading toolbox capable of unlocking the true promise of AAV gene therapies. We plan to maximize the value of our platform by actively pursuing business development and out-licensing opportunities for both ImmTOR and Xork.

Lastly, I want to provide an update on our biologics pipeline, starting with SEL-212, which we believe has served as clinical proof of concept for a precision immune tolerance platform with approximately 450 patients dosed to date. Many biologics can be highly immunogenic, resulting in suboptimal responses due to the development of antidrug antibodies after multiple treatments. Patients who develop an immune response may be forced to discontinue treatment or experience adverse reactions. We believe the use of ImmTOR as an adjunct to biologics offers a promising approach to reduce this immune response and improve patient outcomes.

SEL-212 is comprised of ImmTOR co-administered with a proprietary uricase, pegadricase for the treatment of chronic refractory gout and was licensed to Sobi in 2020. Our Phase III DISSOLVE clinical program picked up in the third quarter of 2020 and consists of two double-blind placebo-controlled trials of SEL-212. In both trials, SEL-212 is being evaluated at two dose levels of ImmTOR, 0.1 mg per kg and 0.15 mg per kg, with a single dose level of pegadricase of 0.2 mg per kg.

On December 1, 2021, we announced full enrollment for DISSOLVE I with 112 patients enrolled in the United States, and we recently closed enrollment at 153 subjects for DISSOLVE II, which is being conducted in four countries across Eastern Europe and the United States. As a reminder, we increased target enrollment of DISSOLVE II from 120 subjects to mitigate any subject discontinuations due to the ongoing geopolitical events in Russia and Ukraine.

Achievement of full enrollment in DISSOLVE II triggered a $10 million payment obligation from Sobi, and we remain on track to complete both studies in Q4 2022 with joint top line data anticipated in Q1 2023. We plan to work closely with our partner, Sobi, our clinical trial providers and regulatory authorities to advance towards successful completion of the DISSOLVE program.

With the extensive clinical data and SEL-212 currently in Phase III, we believe our biologics pipeline is mechanistically derisked and Selecta is well-positioned to leverage these learnings into our second biologics indications in IgA nephropathy, a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1 or IgA1 accumulate in the kidneys. Current treatments fail to address the IgA protein deposits, which is the underlying pathophysiology of the disease.

We believe our novel approach, which combines ImmTOR with an IgA1 protease, has the potential to move injurious IgA from the kidneys, improve markers of renal function and have a transformative impact on patients' lives. We are currently working with our external partners to identify an IgA protease candidate for this program and hope to finalize clinical candidate selection by year-end. We're extremely excited about the advancements across all three pillars of our pipeline and the value-driving milestones in the second half of 2022 and beyond.

With that, I'll turn the call over to Kevin to run through our financial results for the second quarter ended June 30, 2022. Kevin?

Kevin Tan

Thank you, Carsten. During the second quarter, we proactively took steps to bolster our balance sheet. Most notably, on April 6 we successfully priced an underwritten offering, raising gross proceeds of approximately $38.7 million and ended Q2 2022 with approximately $143.4 million in cash, cash equivalents, restricted cash and marketable securities. It is important to note that this cash balance does not include either the $10 million we have received in Q3 from Sobi or the $6 million from Sarepta that we anticipate receiving in Q3 2022. We believe that our existing cash, cash equivalents, restricted cash and marketable securities as of June 30, 2022 will enable us to fund our operating needs into mid-2024. We expect multiple clinical readouts within our anticipated cash runway, including the results from the Phase III DISSOLVE trials in Q1 2023 and initial results from our Phase I trial of SEL-302.

Turning to our financial results in the quarter ended June 30, 2022, net cash used in operating activities was $24.1 million for the six months ended June 30, 2022, as compared to $18.2 million of cash used in operating activities for the same period in 2021. Collaboration and license revenue recognized was $39.3 million for the second quarter of 2022 as compared to $19.7 million for the same period in 2021. Revenue was primarily driven by the shipment of clinical supply and the reimbursement of costs incurred for the Phase III DISSOLVE program pursuant to the license agreement with Sobi and a shipment of manufactured supply under the Sarepta agreement.

Research and development expenses for the second quarter of 2022 were $19.2 million as compared to $14.5 million for the same period in 2021. The increase in cost was primarily the result of expenses incurred for the SEL-212 clinical program, stock compensation and salaries. General and administrative expenses for the second quarter of 2022 were $6.2 million as compared to $4.7 million for the same period in 2021. The increase in cost was primarily the results of expenses incurred for issuance costs for the 2022 equity offering and stock compensation. For the second quarter of 2022, Selecta reported net income of $8.6 million or basic net income per share of $0.06 as compared to net income of $4.6 million or basic net income per share of $0.04 for the same period in 2021.

I will now turn it back to Carsten for closing remarks. Carsten?

Carsten Brunn

Thank you, Kevin. In summary, we are pleased with our progress in Q2 across all three pillars of our pipeline. We're excited about our plans to enter the clinic with SEL-302 in Q4 2022, the anticipated completion of the DISSOLVE program with our partner, Sobi, the advancement of IND-enabling studies across our wholly-owned pipeline supporting our numerous collaboration partners, and our plans to rapidly advance our next-generation precision immune-tolerant technology, ImmTOR-IL, into the clinic. We believe ImmTOR-IL could represent a generational leap forward for the ImmTOR platform, and we look forward to evaluating its full potential in PBC and beyond. We remain focused on our commitment dissolving the hardest challenges in autoimmune disease, and helping patients overcome autoimmunity and immunogenicity through evolving ImmTOR precision immune tolerance platform. Before we conclude today's call, I'd also like to thank the entire Selecta team, our investors and the many people who have been supportive along the way, including our patients and their families.

With that, we're happy to take questions.

Question-and-Answer Session

Operator

Thank you, Carsten. We will now begin the question-and-answer session. [Operator Instructions] Our first question today comes from Joe Schwartz of SVB Securities. Please go ahead.

Unidentified Analyst

Hi. This is Beth on for Joe. Thank you for taking our question today. So Horizon Therapeutics noted during their first quarter update this year that KRYSTEXXA had achieved less than 5% penetration in the refractory gout market. We were wondering what you think could be driving this low uptake. And if you and your partner, Sobi, have discussed any opportunities that you could pursue to enhance SEL-212's uptake is proved. Thank you.

Carsten Brunn

Yes. Hi, Beth. That's a great question. Obviously, we're not giving commercial guidance since Sobi has commercial rights, but we remain extremely excited about the commercial opportunity in general. I think Horizon has done a lot of the heavy-lifting actually creating physician awareness, patient awareness, setting a fairly high price point. But as you can tell, with the very low penetration at this point, there remains a tremendous commercial opportunity. And we believe one of the key differentiators, of course, is always efficacy. And we're extremely excited by the Phase II results that we saw.

But one of the key drivers in this patient population is also compliance. And as you know, KRYSTEXXA has to be used twice a month with the new approval with methotrexate, even a more complex treatment measurement with daily folic acid and weekly methotrexate, whereas SEL-212, if approved, would be a monthly treatment, which would be tremendous differentiation for those patients who have to come into an infusion center, which is usually longer drives. Somebody has to take them and it makes a huge difference whether this is once or twice a month.

Operator

Our next question comes from Kristen Kluska of Cantor Fitzgerald. Please go ahead.

Kristen Kluska

Hi, good morning everybody. For the Sobi partnership, what is the total amount of milestone payments that you remain eligible for at this time? And I know that you've guided your cash runway doesn't necessarily include any potential for any of these milestones. But I would imagine that some of these might be tied in with the top line readout and a potential filing. And then has Sobi guided anything in terms of if the data does read out positively about sales force and steps they're taking to prepare for a potential commercialization?

Carsten Brunn

Yes. Hi, Kristen. Great question. So we have overall guidance that we're eligible to receive $630 million in milestones, which is breaking down in $80 million in regulatory and development milestones, and $550 million in commercial milestones. And as we just announced, we're eligible to receive $10 million for the full enrollment. So there are some payments milestones left in the current development vector phase. But maybe, Kevin, if you have the numbers on top of mind, would you...

Kevin Tan

Yes, so we [Technical Difficulty] we received...

Kristen Kluska

Sorry, Kevin – sorry, Kevin I wasn't able to hear you. I don't know if it's my line or...

Carsten Brunn

Sorry, to be clear, we've already received $15 million in regulatory and development milestones, and we're eligible for the balance of $65 million.

Kristen Kluska

Got it. And then just on this new data you had for ImmTOR-IL and gene therapies, wondering if you might look to share some of these additional findings at an upcoming conference or when we could expect to see the specific details.

Carsten Brunn

Yes. We'll definitely share such data at an upcoming conference. We'll also include it into our corporate deck, which you actually can see on our website. So the data actually is on there already.

Kristen Kluska

Perfect. Thanks.

Carsten Brunn

Thank you.

Operator

The next question is from Yun Zhong of BTIG. Please go ahead.

Yun Zhong

Great. Thank you very much for taking the question. My question is on the ImmTOR-IL. And I believe you indicated in the past that you were now going to use IL in the MMA study. And is that because either engineered IL-2 will not be ready by the time you initiate the study, given that you – the new data that you just talked about, ImmTOR-IL in gene therapy. Does it make sense to maybe try to introduce IL into the planned MMA study? And do you have a plan to look for additional – sorry, in terms of gene therapy indication to potentially include IL-2?

Carsten Brunn

Yes, that's a great question, Yun. So you're right, we don't anticipate to include ImmTOR-IL, at least initially in the MMA trial. And we're really encouraged by the human proof-of-concept study that we read out last year with an anti AAV anti-capsid where we saw good control to the antibodies. But we can – once we have an IL-2 available and went through the appropriate safety studies, we could potentially always add in into IL. But at least for this Phase I, it is not planned to include an IL-2.

In terms of other indications, as you know, we have paused our OTC deficiency indication just to preserve cash. And we really see the gene therapy modality as a partner in play. We're very committed to MMA. We want to own the regulatory pathway. So I think we set a clear precedent for our strategic partners on how to use ImmTOR into the clinic. I don't want to rule out we're going to pursue this program in the future, but for now, we're focused on MMA.

Yun Zhong

Okay. Then on the autoimmune indications, I think that's going to be the major direction going forward. And in terms of indication selection, do you have any specific criteria in terms of the autoantigens that you would like to develop? Thank you.

Carsten Brunn

Yes. That's a great question. And as you know, we've just released the exciting ImmTOR-IL data beginning of this year. We're working through indication selection. We have guided to PBC, which we like as an initial indication since it has a clearly identified autoantigen, PDC-E2. It's also a liver-directed disease as well. As you know, ImmTOR accumulates in the liver. So we think liver-based autoimmune diseases are a focus. So – and we'll give more guidance around this, but definitely we have a clear focus on autoimmune disease of the liver.

Yun Zhong

Great. Thank you very much.

Operator

The next question comes from Yatin Suneja of Guggenheim Partners. Please go ahead.

Yatin Suneja

Hi, guys. Thank you for taking my question. Just a couple for me. With regard to the chronic refractory gout data coming up, could you maybe just help us understand the expectation from that study? And then also if you can just touch on how do these data maybe serve as a proof of concept for the GI program that you have? So that's the first question. I do have two more, which I'll ask after this.

Carsten Brunn

Yes. Absolutely. So as you know, the Phase III study is a placebo-controlled study. We know from the KRYSTEXXA trials, there's no placebo effect. So we're very confident here that we'll have technical success. We have run two Phase II studies where we saw efficacy in the 50% range pretty consistently. And I said, I think, in the main call, over 450 patients dosed. So I'm kind of looking at this data kind of as a baseline in terms of expectations. I mentioned earlier that we think the monthly dosing will be a key differentiator. So I think that's the expectations around efficacy. So we're – and we've done, in the past, extensive market research and feel this is an attractive and differentiated profile.

In terms of proof-of-concept, I mean we actually believe just based on the Phase II data, we think we have very clear proof-of-concept. In the Phase I study actually, we dosed 19 patients with the enzyme alone pegadricase. Only three made it to week four, which shows you it's a highly immunogenic enzyme here. You add ImmTOR, if you look at the Phase II studies, you get a response rate, the 50% at months five and six. So you can clearly see that you induce tolerance and prevent the formation of ADAs. So we definitely feel very strongly that we already have technical proof-of-concept, which we're obviously planning to use for our second enzyme program, which is an IgA protease. But of course, the Phase III will be additional validation. We'll have additional safety data. So – but overall, we're quite excited about this upcoming readout in Q1 next year.

Yatin Suneja

And then with regard to the ImmTOR program, now first, on the PBC side, are there good biomarker to find who could respond to your ImmTOR versus not. So that's the first part. And then where are you with your own IL-2 mutein, what are the time lines there? Are there particular characteristics of an ideal IL-2 mutein to be combined with ImmTOR? If you can just comment there. Thanks.

Carsten Brunn

Yes. Great question. I'll let Peter answer the first question around biomarkers and PBC. Peter?

Peter Traber

Yes. Thanks, Carsten. In PBC, there are very good and validated well-established biomarkers of disease. The one that's been used most frequently is alkaline phosphatase levels. And in fact, these are regulatory endpoints, which have been used for approval of other drugs such as obeticholic acid. So a reduction in alkaline phosphatase levels is an extremely good biomarker and one that can be easily monitored and has a relatively rapid response rate. So that's what we would be utilizing primarily.

Carsten Brunn

Thank you, Peter. In regards to IL-2, so we haven't guided an exact timing. But as you know, yes, it's a tough topic for us. And we're working with our partner, Cyrus and we'll definitely give an update in the very near future. It's a top priority. But I'll let Kei talk a little bit about what we're trying to achieve here in terms of differentiation with this Treg-selective IL-2. Kei?

Kei Kishimoto

Yes. It's Kei. So if you're familiar with the IL-2 space, one of the goals is to expand total Tregs. And our approach is more antigen-specific because we believe antigen-specific Tregs are going to be really the key to autoimmune disease where you have a large pool of antigen-specific refractory T-cell. So the fact that we see this profound synergy of IL-2 with ImmTOR indicates that we're getting both expansion of total Tregs, which can provide by standard suppression. But more importantly, we feel we're getting this huge increase in antigen-specific Tregs.

Yatin Suneja

Thanks, Kei.

Operator

The next question comes from Gil Blum from Needham. Please go ahead.

Unidentified Analyst

Hi. This is Chen for Gil. Thank you for taking our questions. So our first question is about ImmTOR for MMA study. It seems that ImmTOR-IL more doses can give very good inhibition of the antibodies. So are you planning to include more doses of ImmTOR in the MMA study? The second one is about, is there any time line for the combination of ImmTOR and Xork? So it is now in the IND-enabling study. Are you planning to hopefully start a trial next year? Thank you.

Carsten Brunn

Yes. Great question. I'll give the first one to Peter, around the MMA setup.

Peter Traber

Yes, this is an excellent question. And in the MMA trial, because of our results in the empty capsid trial as well as the preclinical results in nonhuman primates and mice, we have decided to treat with three monthly doses of ImmTOR following the single dose of the AAV vector. And this has been approved by the FDA, and it's going to be part of our clinical trial. So subjects will receive the AAV gene therapy plus ImmTOR. And then 56 – excuse me, one month and two months later, they will receive a second and third dose of ImmTOR. And this is a direct result of the findings in nonhuman primates that we're able to continue to suppress antibody levels with that regimen.

Carsten Brunn

Thank you, Peter. On the question on Xork, we have not guided to an IND filing date, but I think your assumption is not far off. It's not a top priority that we are pursuing.

Unidentified Analyst

Thank you.

Operator

The next question comes from John Newman from Canaccord. Please go ahead.

John Newman

Hi, guys. Thanks for taking my question. For your proprietary IL-2 that you're developing in conjunction with Cyrus, just curious about the initial indication there. I think the initial work with IL-2 will be PBC, but I believe that would be with a different IL-2. Curious as to what you're thinking for the proprietary version that you're working on.

Carsten Brunn

Yes. Good question, John. We actually plan on for now use the proprietary out we were developing with Cyrus for the PBC indication, actually. I think we have stated in the past that we are open to partnerships with existing IL-2 players as we believe we have quite a unique value-add here by differentiating by inducing antigen-specific immune tolerance actually. So – but the first indication would be with a proprietary IL-2 in PBC.

John Newman

Okay, great. Thank you.

Operator

The next question comes from Raju Prasad from William Blair. Please go ahead.

Raju Prasad

Hi. Thanks for taking the question. Maybe just a little bit more color, if you can, on the gating events needed to start the Phase I MMA trial. And then just a quick follow-up. Thinking about the IgG protease and the potential development of that, how would you think to kind of initiate the clinical program for that asset? Could you kind of put it into the Phase I trial? Or do you have to kind of study it separately? Thanks.

Carsten Brunn

Yes. I'll let Peter comment on the gating for the MMA trial. As you know, it's a single-center study at the NIH, and we're currently going through motions to get it started. But I'll let Peter elaborate in more detail.

Peter Traber

Yes. Thank you, Carsten. The gating for starting the trial at the NIH are really just some administrative approvals at the NIH, which are well underway and the setup of all the administrative and operational issues in collaboration with our CRO, which is helping to support the trial, the NIH. So there's nothing regulatory or CMC or any other issues that are gating through the initiation of that trial. So it's on track for a subject treated in the fourth quarter of this year.

Carsten Brunn

And Peter, since you're on the role, maybe as you know, we haven't fully guided on the clinical development plan for Xork. And obviously, we would like to take this into an indication, if possible, but maybe you can talk a little bit of our thinking around kind of starting this in a Phase I study in healthy volunteers.

Peter Traber

Yes, sure. Happy to do that, Carsten. The issue with Xork is that we're trying to reduce existing AAV antibodies in patients in order to be able to give them the gene therapy. Well, for that purpose, we can use healthy volunteers who have existing titers of anti-AAV vectors. And as Carsten said, that can be anywhere from 40% to 70% of patients in the general population. So that's the relevant group. So our phase – first Phase I study will be looking at both the safety and tolerability of Xork alone and in combination with ImmTOR and with the efficacy, looking at the reduction of anti – naturally occurring anti-AAV antibodies. So that's the first trial, and that really serves as a proof-of-concept for gene therapy trials. And so then following that, we would be looking to include that as a pretreatment before an actual gene therapy.

Raju Prasad

Thanks, Peter.

Operator

[Operator Instructions] The next question comes from Boobalan Pachaiyappan of H.C. Wainwright. Please go ahead.

Boobalan Pachaiyappan

Hi. Can you hear me okay?

Carsten Brunn

Yes, we can.

Boobalan Pachaiyappan

All right. Great. So a few questions on PBC. So you guided to us that PBC is a primary indication in the autoimmune disease space. So can you comment on the market opportunity and how you are differentiated from competitors in this space?

Carsten Brunn

Yes. And since we have a resident expert, Peter, I'm going to give that question as well. But maybe just kind of to frame it up, obviously, we believe they're really addressing the underlying autoantigens that's driving the disease pathology actually, to really addressing the root cause of the disease mechanistically. But I'll let Peter give it more detail.

Peter Traber

Yes. Carsten, thanks. That's correct. I mean all of the drugs that are currently being used in PBC don't get at the root immunologic cause of the disease. And that's what we're trying to do. Now the number of patients that respond to the current therapies is – about 35% to 40% respond to ursodeoxycholic acid, and then another half of those may respond to obeticholic acid, but that's restricted to people without severe liver disease. So people are still even with the therapies today progressing to cirrhosis and requiring liver transplant, and there are approximately 10% to 12% of people who receive liver transplants in the United States for PBC. So I think that there is still an unmet medical need to address the underlying root cause of the immunologic damage. And that's what our precision immune tolerance platform is aimed at.

Boobalan Pachaiyappan

Great. Thanks for the color. So it appears PBC mostly affects women than men. So do you have a reason why that's the case? And would you consider enrolling more female patients in your future clinical studies?

Peter Traber

Yes. You're correct that as many as 90% to 95% of individuals who have PBC are women. And this – it is the case for many autoimmune diseases that there is a higher percentage of women in other autoimmune indications in the liver like autoimmune hepatitis, there's 70% of individuals that are women. So that is a common theme in autoimmune disease. So in our trials of PBC, we anticipate that the vast majority will be women that are enrolled in the trial. In terms of the underlying – in terms of your question about the underlying reason why women are more affected, I don't think that, that's been clearly worked out, although the animal models that are used for PBC are also much more prevalent and severe in female animals. So it does seem to be something that's replicated in the animal models of PBC.

Boobalan Pachaiyappan

Okay. Thanks for the color. And one final question from me. It appears ImmTOR-IL is a versatile molecule with a broad therapeutic potential. Obviously, your first indication is a rare disease. Are there plans to pursue mass market indications within the realm of autoimmune disease space using ImmTOR-IL?

Carsten Brunn

Yes, that's a great question. And obviously, we've just guided one indication at this point, PBC. We'll give more guidance. And we definitely have – absolutely. Whether you take all those indications into Phase III is a different discussion, but we don't want to limit ourselves to rare diseases only.

Boobalan Pachaiyappan

Thanks so much for taking my questions.

Operator

This concludes our question-and-answer session. I would like to turn the conference back over to Carsten Brunn for closing remarks.

Carsten Brunn

Thank you, operator, and thank you, everyone, for joining us this morning. Stay safe and healthy. This concludes today's call. Thank you.

Operator

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

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