Selecta Biosciences, Inc. (NASDAQ:SELB) Q3 2022 Earnings Conference Call November 3, 2022 8:30 AM ET
Company Participants
Carsten Brunn – President and Chief Executive Officer
Kevin Tan – Chief Financial Officer
Peter Traber – Chief Medical Officer
Takashi Kishimoto – Chief Scientific Officer
Conference Call Participants
Elizabeth Scott – SVB Securities
Rick Miller – Cantor Fitzgerald
Yun Zhong – BTIG
John Newman – Canaccord
Tiffany Marchell – William Blair
Boobalan Pachaiyappan – H.C. Wainwright
Uy Ear – Mizuho
Operator
Good morning, and welcome to the Selecta Biosciences Third Quarter 2022 Financial Results and Business Update Conference Call. [Operator Instructions] This call is being webcast live on the Investor and Media section of Selecta’s website at www.selectabio.com and is being recorded.
For opening remarks, I would like to introduce you, Mr. Kevin Tan, Chief Financial Officer of Selecta. Please go ahead, sir.
Kevin Tan
Thank you, and good morning. Welcome to our third quarter 2022 financial results and business 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 September 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, and 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 and subsequent quarterly reports on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, November 3, 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 third quarter of 2022, we continued to make steady progress across the pipeline. And with an expected financial runway into mid-2024, we believe we’re well positioned to execute on our key priorities and reach multiple near-term value-driving events. In collaboration with our partner, Sobi, we expect to both complete the SEL-212 Phase III DISSOLVE trial and announce joint top line data in Q1 2023. We also remain on track to advance SEL-302, our proprietary gene therapy candidate in combination with ImmTOR to treat methylmalonic acidemia, or MMA, into a Phase I clinical trial in this quarter. Our key priority continues to be accelerating the development of our next-generation precision immune tolerance platform, ImmTOR-IL. We have made substantial progress in identifying a proprietary IL-2 candidate and continue to believe we’ll have a clinical lead candidate by year end. Additionally, our team continues to advance our preclinical pipeline, most notably the IND-enabling studies and manufacturing scale-up for our proprietary IgG protease, Xork, as a pre-treatment for AAV gene therapies, and IgA protease candidate selection with our partners for the treatment of IgA nephropathy.
On the cusp of these key milestones, we’d like to share details on how these programs, together with recent activities, align with our mission to solve the toughest challenges associated with autoimmunity and unwanted immunogenicity. Let us begin with the applications of our precision immune tolerance platform for autoimmune disease. Currently, over 24 million Americans suffer from autoimmune diseases. And while the current standards of care utilize immunosuppressive drugs or symptom-masking treatments, these treatments leave patients vulnerable to serious infection and malignancies and fail to adequately address the underlying cause of the disease, which is an imbalance of T regulatory cells versus T effector cells. By combining ImmTOR-IL with autoantigens, we hope to restore natural immune system balance by inducing and expanding antigen-specific regulatory T cells in vivo.
As we have highlighted before, we are very encouraged by our growing body of preclinical data in which we’ve observed the potential to amplify the magnitude and durability of antigen-specific immune tolerance by combining ImmTOR with an engineered Treg selective IL-2, an evolution of a platform we call ImmTOR-IL. By focusing on the induction and expansion of Tregs specific to the autoantigens responsible for the pathogenesis of autoimmune diseases, we believe ImmTOR-IL has the potential to be a truly differentiated first-in-class treatment for those suffering from autoimmune diseases. The first autoimmune indication in which we plan to evaluate ImmTOR-IL is primary biliary cholangitis, or PBC, a T-cell mediated liver disease driven by a well-defined antigen, PDC-E2. 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 work on identifying additional autoimmune indications to expand, and we expect to select an IL-2 candidate by year end. We also plan to provide an update on the broader strategic development path for ImmTOR-IL in the near future.
Moving on to our gene therapy vertical. In Q4 2022, we expect to initiate the Phase I/II trial of SEL-302. As a reminder, SEL-302 is a combination of ImmTOR with MMA-101, an AAV gene therapy being developed for the treatment of methylmalonic acidemia, a rare genetic metabolic disease. The Phase I/II trial will evaluate the safety and efficacy of SEL-302 in treating MMA and ImmTOR’s ability to mitigate antibodies against the MMA-101 AAV capsid. We believe this trial will build on the growing body of evidence pointing towards the potentially multifaceted benefits of ImmTOR in enhancing both the efficacy and safety of AAV gene therapies. By advancing SEL-302 into the clinic, we believe we can help all of our current and future gene therapy partners accelerate the use of ImmTOR in their gene therapy programs by providing a clear clinical and regulatory blueprint for them to follow.
This past October at the 29th Annual European Society of Gene and Cell Therapy, or ESGCT conference, Selecta showcased 3 presentations, including 1 joint presentation with our partner, AskBio. These presentations highlighted the immunogenic nature of empty capsids in healthy volunteers and the potential of ImmTOR and ImmTOR-IL in addressing key efficacy and safety challenges in gene therapy. Our evolving precision immune tolerance platform is designed to enable AAV vector redosing by amplifying the magnitude and duration of effectively inhibiting the formation of anti-AAV antibodies, while simultaneously mitigating adverse responses associated with high AAV doses. In our human proof-of-concept study, we evaluated ImmTOR’s ability to inhibit the formation of neutralizing antibodies in healthy human volunteers, and observed that with a single dose of ImmTOR, all subjects treated with 0.3 mg/kg of ImmTOR maintained NAb titers of below 1:25 at Day 30, and 2/3 of the subjects at this level of ImmTOR maintained NAb titers below 1:5 at Day 30. Our preclinical data in non-human primates and mice indicate that 2 additional monthly doses of ImmTOR has the potential to provide durable inhibition of anti-AAV antibodies. We plan to use this dosing regimen in our upcoming Phase I/II trial in MMA.
We’re also excited by our preclinical data, which indicates that ImmTOR or ImmTOR-IL may potentially transform the treatment paradigm for AAV gene therapy from a one-and-done to a low-and-slow, whereby patients could receive multiple lower doses of gene therapy, titrate up to a therapeutic benefit, and avoid the risk associated with high rate of doses of AAV gene therapy needed in a one-time only treatment model. The area of precision genetic medicine is here, and AAV-mediated gene therapies have the potential to be transformational for those who can access them. However, 30% to 70% of the patient population are not eligible for treatment or trial inclusion due to pre-existing anti-AAV antibodies from natural AAV infections. This prevents them from gaining access to potentially life-altering therapies for which there may be a few or no treatment alternatives.
We’re developing Xork, our proprietary IgG protease candidate that is designed to specifically cleave human IgG with the goal of expanding access to gene therapies, to those patients who are currently excluded due to preexisting anti-AAV antibodies. Xork is derived from a non-human pathogen and has low cross reactivity to pre-existing anti-IgG protease antibodies. In addition to potentially enabling dosing of patients with pre-existing AAV antibodies, we believe that the combination of Xork with ImmTOR could open a therapeutic treatment window and enable repeat dosing of this enzyme therapy. At the same time, by increasing the eligible prevalent patient population, we aim to bring hope to those who may not have any other effective treatment options, enable companies to maximize the commercial potential of their gene therapy candidates, and help to make otherwise uneconomic gene therapy candidates viable targets for commercial development.
Finally, we continue to work with Ginkgo Bioworks to design novel AAV capsids with a goal of improving transduction efficiency, liver tropism and immunogenicity profile. Selecta will conduct all nonclinical and clinical studies with Ginkgo’s uniquely designed engineered capsids. By combining ImmTOR with more efficient capsids, we could potentially further reduce the doses of AAV gene therapy needed to see therapeutic benefit. As you can see, we’re taking a multidimensional approach to tackling immunogenicity challenges facing AAV gene therapies. ImmTOR and ImmTOR-IL to mitigate the de novo formation of neutralizing antibodies and able redosing. Xork to address those patients who, due to natural AAV infections, are ineligible for treatment by gene therapies. And next-generation AAV capsids to improve both organ tropism and transduction efficiency of gene therapies. We’re actively pursuing business development and out licensing opportunities for Xork, ImmTOR and our next-generation AAV capsids in gene therapy applications. And our goal is to maximize the value of our gene therapy vertical by becoming the leading provider of solutions to manage immunogenicity to AAV gene therapy developers.
Now turning to our biologics pipeline. Many biologics can be highly immunogenic as well, resulting in suboptimal responses due to the development of anti-drug antibodies after treatment. Patients who develop an immune response may be forced to discontinue treatment or experience adverse reactions to continued therapy. We believe the use of ImmTOR as an adjunct to biologics offers a promising approach to reduce the unwanted immune response and improve patient outcomes. Our most advanced program, SEL-212 has served as clinic proof-of-concept for a precision immune tolerance platform with over 400 patients dosed to date. As a reminder, 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 kicked off in the third quarter of 2020 and consists of 2 double-blind, placebo-controlled trials of SEL-212. In both trials, SEL-212 is being evaluated at 2 dose levels of ImmTOR 0.1 mg/kg and 0.15 mg/kg with a single dose level of pegadricase at 0.2 mg/kg.
We believe SEL-212 represents a potentially clinically differentiated asset for people with chronic refractory gout. In our Phase II trial, we observed a numerically higher percentage of patients responding to therapy on SEL-212 versus Krystexxa. The higher percentage of responders in patients with visible uric acid crystal tissue deposits, or tophi, as well as statistically significant lower serum uric acid levels in treatment periods 3 and 6 versus Krystexxa. These responses were achieved with no need for oral immunosuppressive or weekly methotrexate and less frequent dosing of an I infusion with monthly dosing of SEL-212 versus biweekly infusions with Krystexxa.
Accordingly, with its tolerability profile, simplified dosing and avoidance of immunosuppression or methotrexate, we believe SEL-212 is well positioned against the current standard of care and other drugs in the class to target this patient segment. We continue to work closely with our partner, Sobi, our clinical trial providers and regulatory authorities to advance towards the successful completion of the DISSOLVE program. And we are on track to both complete DISSOLVE I and II and announce joint top line data in Q1 2023. With extensive treatment data in SEL-212 currently in Phase III, we believe Selecta is well positioned to leverage these learnings into our second biologics indication in IgA nephropathy, which is a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1, or IgA1, accumulate in the kidneys. By combining ImmTOR with an IgA protease to remove injurious IgA from the kidneys and improve markers of renal dysfunction, we believe our novel approach has the potential to address the underlying pathophysiology of the disease. We are currently working with our external partners to identify an IgA protease candidate for this program and plan to finalize clinical candidate selection by year end.
We’re extremely excited about the advancements across our pipeline and the growing body of evidence showcasing the promise of our pioneering ImmTOR precision immune tolerance platform in a number of applications. We look forward to continuing our momentum and executing towards upcoming value-driving events. With that, I’ll turn the call over to Kevin to run through our financial results for the third quarter. Kevin?
Kevin Tan
Thank you, Carsten. During the third quarter, our balance sheet was strengthened the $10 million milestone payment from Sobi for enrollment completion of DISSOLVE II. Additionally, we received a $2 million payment for extending Sarepta’s option periods under our research license and option agreement for ImmTOR to Q1 2023, and an additional $4 million payment for achievement of certain preclinical milestones. We ended the third quarter with cash, cash equivalents, marketable securities and restricted cash of $148 million as of September 30, 2022, compared to $129.4 million as of December 31, 2021. We believe these funds will enable us to fund our operating needs into mid-2024.
Turning to our financial results in the quarter ended September 30, 2022. Net cash used in operating activities was $19.8 million for the 9 months ended September 30, 2022, as compared to $28.9 million of cash used in operating activities for the same period in 2021. Collaboration and license revenue recognized was $20.7 million for the third quarter of 2022 as compared to $24.4 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 in the license agreement with Sobi. Research and development expenses for the third quarter of 2022 were $16.5 million as compared to $21 million for the same period in 2021. The decrease in cost is primarily the result of expenses incurred for the SEL-212 clinical program, preclinical programs and the AskBio collaboration.
General and administrative expenses for the third quarter of 2022 were $5.8 million as compared to $5.4 million for the same period in 2021. The increase in cost was primarily the result of expenses incurred for stock compensation and personnel expenses. For the third quarter of 2022, Selecta reported a net loss of $7.9 million, or basic net loss per share of $0.05, as compared to a net loss of $17.9 million, or basic net loss per share of $0.16 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’ve had yet another quarter of great progress here at Selecta. And 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, and supporting our numerous collaboration partners and our plans to move ImmTOR-IL into the clinic. We remain deeply committed to solving the hardest challenges in autoimmune disease and helping patients overcome autoimmunity and immunogenicity through an evolving ImmTOR precision immune tolerance platform. We believe ImmTOR-IL could represent a generational leap forward for the ImmTOR platform and for patients in need of alternative treatment options. And we look forward to evaluating its full potential across a wide range of autoimmune diseases of the liver and beyond. In parallel, we will continue to seek opportunities to strategically partner in our gene therapy vertical to maximize the value of our platform.
Before we conclude today’s call, I would once again 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
[Operator Instructions]
And the first question will come from Joe Schwartz with SVB Securities.
Elizabeth Scott
Hi, this is Beth on for Joe. Congrats on the progress. So heading into the SEL-212 joint Phase III readout, it would be helpful to understand what you guys are hoping to see in terms of the serum uric acid response rate as well as the anti-drug antibody mitigation rate.
Carsten Brunn
Yes, that’s a great question. Obviously, we have — we’re quite confident about this trial. We’re in a unique position that we run 2 Phase II trials prior, one even head-to-head versus Krystexxa. And we had response rate in the mid-60% range. And just to remind everyone, the actual Phase III is placebo-controlled. And we know from Krystexxa, there’s no placebo effect. So we think from a technical perspective, the study is actually very low risk. We also believe that the profile, as we understand it right now, is quite competitive with the response rate we’ve seen in the Phase II. And the fact that the treatment frequency is a key differentiator as well, that we only need monthly dosing versus every 2 weeks, and this is a pretty uncompliant patient population. So that’s kind of what we’re kind of looking for. We’re not looking at ADAs as a primary endpoint. So we’re basically looking at SUA levels at Month 6 for the top line readout in Q1 next year.
Elizabeth Scott
Great. And if I could squeeze in a quick follow-up. I was also wondering if you’re able to provide any color on the Phase III discontinuation rates so far and comment on any read-through this might have into real-world duration of use.
Carsten Brunn
Yes. So we haven’t guided any discontinuation rates. We’re obviously blinded in this Phase III, and we’ll report the top line in Q1 next year.
Operator
The next question will come from Kristen Kluska with Cantor Fitzgerald.
Rick Miller
Hi, good morning. This is Rick on for Kristen. To start out with one. At ESGCT, Selecta presented some data out to Day 131 showing IL-2 mutein plus ImmTOR inhibited anti-AAV antibodies in a preclinical model. Could you talk about any promising signals you’ve seen in these preclinical models with increased length of follow-up post dosing?
Carsten Brunn
Yes. I’ll let Kei, our CSO, answer that question as he presented the data. Kei?
Takashi Kishimoto
Yes. Thanks, Carsten. Yes. So in that study, we were specifically looking for the ability to mitigate immune responses to high vector doses because that’s been an issue for the field. So we went up to vector doses of 5E13 vg/kg. And what we were looking for is that durability of response that you referred to, as we have seen breakthrough in some studies both preclinically and in our empty capsid study. So to remind you, we’ve shown that 3 monthly doses of ImmTOR can provide durable inhibition both in mice and non-human primates. And that’s the regimen we’re taking forward in our methylmalonic acidemia clinical trial that’s starting later this year. And then at ESGCT, we presented data on the combination of ImmTOR plus an engineered IL-2 molecule as well as ImmTOR plus Benlysta or an anti-BAb antibody. And both showed the ability to mitigate immune responses out to around Day 131, as you indicated.
Rick Miller
Okay. Maybe just one more then, also kind of staying in the same lane. As you’re looking at other potential autoimmune indications, what criteria are you weighing? We understand that a well-characterized auto-antigen as a must have. But are there any other key factors for the IL-2 approach, in your view?
Carsten Brunn
Yes, that’s a great question. Yes, we’re definitely initially focused on diseases like PBC, where we clearly know the autoantigen, PDC-E2 in this case. And we obviously see very broad applicability with this approach, which is I think important. So we’re not limited there. But initially, we will focus on liver-directed autoimmune diseases such as PBC. As you know, ImmTOR accumulates in the liver, so we think that’s kind of low-hanging fruit and as an initial approach. But there’s no reason why this wouldn’t work in other systemic diseases such MS, for example. But I think as a company, you want to focus initially on liver-directed diseases and adjacency also kidney as well potentially.
Operator
The next question will come from Yun Zhong with BTIG.
Yun Zhong
Hi, good morning. Thank you very much for taking questions. So a question on the IL-2. So what would you like to achieve with your identification of the engineered IL-2 as compared to currently available candidates? And by any chance, is that going to be one that maybe you have used in clinical study — sorry, not clinical, but preclinical studies and have shown data?
Carsten Brunn
That’s a good question. Maybe I’ll start and then I’ll hand over to Kei. Obviously, we see the key differentiation in our approach, combining an engineered IL-2 with ImmTOR. So if you just use an IL-2, you just expand all pre-existing T regulatory cells, and you basically hope for bystander effect non-specific. Versus you combine it within ImmTOR, we’re aiming for an antigen-specific approach where we induce and expand antigen-specific Tregs. But we obviously want to have a differentiated IL-2 to begin with. So ideally have a best-in-class IL-2 that is competitive with the IL-2s that are out there right now. But I think the ultimate differentiation that we’re aiming to be a first-in-class around antigen-specific approach where we really target Tregs specific to an antigen. But Kei, do you want to add something to that?
Takashi Kishimoto
Yes. I think that’s absolutely right, Carsten. With regard to the ones that we’ve used in the studies that we’ve presented, that’s actually been with a mouse-specific IL-2 mutein. So it’s just a model for our preclinical studies. But obviously, we’ve been working very diligently on identifying a proprietary molecule, and we think we’re very close to being able to announce that to you.
Yun Zhong
Okay. Maybe a similar question then on the IgA protease. And once the final candidate is identified, do you expect Selecta to have 100% rights to that molecule? And is Selecta going to be mainly driving the clinical studies going forward? And also, does it make sense to add IL-2 as well to IgA nephropathy indication, or maybe not necessarily?
Carsten Brunn
Good question, Yun. So, yes. So once we’ve selected an enzyme candidate, an IgA protease, we will own this asset, and we’ll drive it forward ourselves 100%. So we’ll be responsible for all preclinical, for manufacturing and also for clinical development as well. As the IL-2, it’s theoretically possible, I would say. But I think we’ve seen — this program, what’s important, this program is really building on the experience we have with SEL-212, where we are basically combining another enzyme, highly immunogenic fungal origin, with ImmTOR, we’re able to re-dose with ImmTOR. So I think the initial approach will be with ImmTOR alone.
Operator
The next question will come from John Newman with Canaccord.
John Newman
Hi, guys. Good morning. Thanks for taking my question. Just wondered if you could remind us of the dosing strategy for ImmTOR in the upcoming gene therapy study that you’ll be starting in the fourth quarter. I believe you’ll be giving a higher number of doses of ImmTOR in combination with the gene therapy, but just wanted to review that.
Carsten Brunn
I’ll hand that question to Peter who can kind of walk you through the design and some of the data leading us to the protocol we’re moving into the clinic, Peter?
Peter Traber
Yes. Thank you, Carsten. Hi, John. Based on our data in the empty capsid study, we are starting with a dose level of 0.5 mg/kg. And also based on the non-human primate studies, we’re giving 3 monthly doses at that dose. So it’ll be 3 monthly doses following the AAV at 0.15 mg/kg. In the protocol, depending on the activity of neutralizing antibodies in the first several subjects, we do have the option of increasing the dose of ImmTOR, should that be necessary.
Operator
The next question will come from Raju Prasad with William Blair.
Tiffany Marchell
Hi, this is Tiffany on for Raj. Thanks very much for taking our questions. I was just wondering if you guys’ plan to share any data on the selection process for the IL-2 or the IgA protease development candidate? And I guess any color or details on what the next update we can expect to see from either of these programs might look like.
Carsten Brunn
Yes. Hi, Tiffany. Good question. So the key is that we gave guidance that we’ll select clinical candidates by the end of the year for both the IL-2 and the IgA protease. And I think there’s a good chance that we’ll, throughout next year at conferences, we’ll highlight these molecules in more detail, and we’ll also share some on how we got to the selection of those. And as you know, we have various different approaches for each of those. For the IL-2, we’re working with Cyrus, a protein engineering company out of the Baker Lab in Seattle. And for the IgA protease, we’re kind of a dual approach. We have an option for an IgA protease from a small company called IGAN, and we’re also working with Ginkgo Bioworks as well. So we’ll definitely, once we have selected the lead candidate, share also a bit about the selection process.
Tiffany Marchell
Okay. Great. And just one more. I know you’re still on track to initiate the main gene therapy study by year end. Can you just detail any additional sort of activities you guys are working through in order to get that off the ground?
Carsten Brunn
Yes. I can let Peter speak to this, but I think there’s not a whole lot new to report. It’s going to be a single center study at the NIH. Chuck Venditti will be the PI there. And we are on track to kick the study off this quarter, unless there’s any additional color, Peter, you can share?
Peter Traber
Yes. That’s correct, Carsten. And we have all the requisite approvals that we need to initiate the study. So that will be initiated soon with enrolling the first subject with consent and screening.
Operator
The next question will come from Boobalan Pachaiyappan with H.C. Wainwright.
Boobalan Pachaiyappan
Hi, can you hear me, okay? Okay. So following up on the MMA Phase I study. So you indicated earlier that you plan to assess initial efficacy and safety at 3 months for each patient before progressing to the next patient. So maybe can you remind us how many patients you want to enroll and what would be the approximate time to data?
Carsten Brunn
I’ll have Peter address that question as well in terms of the high-level design and how many patients and what kind of data will be available next year. I can see that Peter has technical issues. So yes, so I can take the question, of course. So the primary endpoint is at 1 year, but we’ll have an initial readout at Month 3 where we’re looking at a couple things. One, obviously primarily safety, but we’re also looking at biomarkers of the disease such as serum UA. We have a unique breath test that looks at propionate acid. And of course we’re looking at variation as well at the level of neutralizing antibodies. And there is a safety data monitoring board that will assess after each patient whether we can move forward or not. So it’s going to be a sequential approach. And we haven’t guided exactly when we’ll have data, but we’ll release data throughout next year.
Operator
The next question will come from Uy Ear with Mizuho.
Uy Ear
Hey, guys. Thanks for taking my question. So on the DISSOLVE I/DISSOLVE II, as you indicated, you expect to joint top line the data next year. Just wondering, like how should we sort of think about your study versus Horizon’s MIRROR study? What are the differences in terms of patients and in terms of the efficacy that will read out? At least numerically, should it be similar or different?
Carsten Brunn
Yes. That’s a great question that we do get a lot. And obviously we’re — these are very different patients we’re looking at. So if you look at the MIRROR study patients, there’s a lot of exclusion criteria, actually. So patients are excluded that don’t tolerate methotrexate. You have to — or they exclude patients that have chronic kidney disease, which is defined as an eGFR below 40. Patients that have more than three drinks per week. So it’s kind of starting out kind of the 100 patients, about 20 patients actually are eligible for that combination. So it’s a more limited patient population you’re looking at.
And then it’s quite — you have to have a very motivated patient population as well since you’re starting out the first month with daily folic acid, weekly methotrexate where you don’t really treat the underlying disease. You have to ensure compliance, and then after that two week of methotrexate, versus 212 is six monthly infusions. What the studies do have in common is the endpoint, which is defined as SUA levels below six at Month six. So you basically, in short, you’re looking at a different subset of patients. I think what’s great for patients is to have potentially another treatment option available. The current penetration is below 5%. There are over 100,000 patients available. So there’s a huge unmet medical need and obviously also a large commercial opportunity as well.
Uy Ear
And for Kevin, as you indicated, the R&D is down — is lower at least sequentially this quarter and year-over-year as well because some studies were winding down. Just wondering how should we think about, I guess, R&D in the fourth quarter and going forward, given all the push and pulls.
Kevin Tan
Yes. That’s a good question. The period-to-period kind of comparison, it went down, obviously, because we were enrolling DISSOLVE last year. And as you know, we completed enrollment in Q2 of this year. So obviously it’s down year-on-year for the quarter comparison. But going forward, I would expect it to start to creep up as we start to enroll patients in the MMA trial, and then continue to increase into 2024 as we start to ramp up other things. So not significantly, but it will directionally be going up.
Operator
This concludes our question-and-answer session. I would like to turn the call back over to Selecta’s CEO, Mr. Carsten Brunn, for any closing remarks. Please go ahead, sir.
Carsten Brunn
Thank you, operator, and thank you to everyone who joined 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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