Good morning, and welcome to the Selecta Biosciences third quarter 2022 financial results and business update conference call. Currently, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Selecta's website at www.selectabio.com and is being recorded. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touch-tone phone, and to withdraw your question, please press star then two . For opening remarks, I would like to introduce you to Mr. Kevin Tan, Chief Financial Officer of Selecta. Please go ahead, sir.
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, www.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.
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 pre-clinical pipeline, most notably the IND-enabling studies and manufacturing scale-up for our proprietary IgG protease, Xork, as a pretreatment 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're 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 neutralizing 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 three presentations, including one joint presentation with our partner, AskBio. These presentations highlighted the immunogenic nature of empty AAV 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 per kg of ImmTOR maintained NAb titers below one to 25 at day 30, and two-thirds of the subjects at this level of ImmTOR maintained NAb titers below one to five at day 30. Our preclinical data in non-human primates and mice indicate that two 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/III 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 higher doses of AAV gene therapy needed in a one-time-only treatment model. The era 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%-70% of the patient population are not eligible for treatment or trial inclusion due to preexisting anti-AAV antibodies from natural AAV infections. This prevents them from gaining access to potential life-altering therapies for which there may be 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 preexisting anti-IgG protease antibodies. In addition to potentially enabling dosing of patients with preexisting 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 the goal of improving transduction efficiency, liver tropism, and immunogenicity profile. Selecta will conduct all non-clinical 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 the immunogenicity challenges facing AAV gene therapies. ImmTOR and ImmTOR-IL to mitigate the de novo formation of neutralizing antibodies and enable redosing. Xork to address those patients who, due to natural AAV infections, are ineligible for treatment by gene therapies. 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.
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 clinical 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 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/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.
A 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 three and six versus Krystexxa. These responses were achieved with no need for oral immunosuppressive or weekly methotrexate and less frequent dosing of an IV 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 that 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 one and two and announce joint top-line data in Q1 2023.
With extensive clinical data and 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?
Thank you, Carsten. During the third quarter, our balance sheet was strengthened with the $10 million milestone payment from Sobi for enrollment completion of DISSOLVE 2. 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 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 ending September 30, 2022, net cash used in operating activities was $19.8 million for the nine 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 under 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, pre-clinical 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 Brunn for closing remarks. 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 our evolving ImmTOR immune tolerance platform. We believe ImmTOR-IL could represent a generation 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'll continue to seek opportunities to strategically partner in our routine 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.
We will now begin the question-and-answer session. To ask a question, you may press star then one on your touch tone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we'll pause momentarily to assemble our roster. The first question will come from Joseph Schwartz with SVB Securities. Please go ahead.
Hi, this is Beth on for Joe. Congrats on the progress and thanks for taking our question today. 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.
Yeah, that's a great question. Obviously we're quite confident about this trial. We're in a unique position that we've run two phase II trials prior, one even head to head versus Krystexxa. We had response rate in the mid-60% range. Just to remind everyone, the actual phase III is placebo-controlled, and we know from Krystexxa there's no placebo effect. You know, 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 that we've seen in the phase II, and the fact that the treatment frequency is a key differentiator as well, that you know we only need monthly dosing versus every two weeks, and this is a pretty you know noncompliant patient population. That's kinda what we're kinda looking for. We're not looking at ADAs as a primary endpoint, so we're basically looking at SUA levels at month six for the top line readout in Q1 next year.
Great. Thanks. 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.
Yeah. 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.
Great. Thank you.
Thank you.
The next question will come from Kristen Kluska with Cantor Fitzgerald. Please go ahead.
Hi. Good morning. This is Rick on for Kristen. Thank you for taking our questions. To start out with one, at ESGCT Select presented some data out today, 131, showing IL-2 mutein plus ImmTOR-inhibited anti-AAV antibodies in a pre-clinical model. Could you talk about any promising signals you've seen in these pre-clinical models with increased length of follow-up post-dosing? Thanks.
Yeah. I'll let Kristen see, so answer the question. I see you presented the data. Kei?
Thanks, Carsten. 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 this field. We went up to vector doses of 5 × 10^13 vg per kg. 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. To remind you, we've shown that three monthly doses of ImmTOR can provide durable inhibition, both in mice and non-human primates. That's the regimen we're taking forward in our methylmalonic acidemia clinical trial. That's starting later this year.
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-BAFF antibody. Both showed the ability to mitigate immune responses out to around day 131, as you indicated.
Okay. Thank you. 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 autoantigen is a must-have, but are there any other key factors for the IL-2 approach in your view?
Yeah, that's a great question. Yeah, we're definitely initially focused on diseases like PBC where we clearly know the autoantigen, PDC-E2 in this case. We obviously see very broad applicability with this approach, which is, I think important. 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. You know, there's no reason why this wouldn't work in other, systemic diseases such as MS, for example. I think as a company, we wanna focus initially on liver-directed diseases and adjacency also kidney as well, potentially.
Okay. Thank you very much for taking our questions.
Thank you.
The next question will come from Yun Zhong with BTIG. Please go ahead.
Hi. Good morning. Thank you very much for taking the question. A question on the IL-2. What would you like to achieve with your identification of the engineered IL-2 and as compared to currently available candidates? By any chance, is that gonna be one that you maybe have used in preclinical studies and have shown data?
That's a good question. I'll start and then I'll hand over to Kei. We see the key differentiation in our approach combining an engineered IL-2 with ImmTOR. If you just use an IL-2, you just expand all pre-existing T regulatory cells, and you basically hope for a bystander effect, nonspecific. Whereas you can combine it with ImmTOR, we're aiming for an antigen-specific approach where we induce and expand antigen-specific Tregs. We obviously want to have a differentiated IL-2 to begin with. Ideally have a best-in-class IL-2 that is competitive with the IL-2s that are out there right now. 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.
Kei, do you wanna add something to that?
Yeah, 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. It's just a model for us for our pre-clinical studies. 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.
Maybe a similar question on the IgA protease. Once the final candidate is identified, do you expect Selecta to have 100% rights to that molecule? Is Selecta going to be mainly driving the clinical studies going forward? Does it make sense to add IL-2 as well to IgA nephropathy indication, or maybe not necessarily?
Good question, Yung. Yeah. Once we've selected an enzyme candidate, an IgA protease, we will own this asset, and we'll drive it forward ourselves 100%. We'll be responsible for all pre-clinical, 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 of fungal origin, with ImmTOR, and we're able to redose with ImmTOR. I think the initial approach will be with ImmTOR alone.
Okay, great. Thank you very much.
The next question will come from John Newman with Canaccord Genuity. Please go ahead.
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. Thanks.
Yeah. I'll hand that question to Peter, who can kinda walk you through the design, and some of the data leading us to the protocol we're moving into the clinic. Peter?
Yeah. 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 per kg. Also based on the non-human primate studies, we're giving three monthly doses at that dose. It'll be three monthly doses following the AAV at 0.15 mg per 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.
Great. Thank you.
The next question will come from Raju Prasad with William Blair. Please go ahead.
Hi, this is Tiffany. I'm for Raj. Thanks so much for taking our question. 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, you know, details on what the next update we can expect to see from either of these programs, might look like. Thanks.
Yeah. Hey, Tiffany. Good question. The key is that we give guidance that we'll select clinical candidates by the end of the year for both the IL-2 and the IgA protease. I think there's a good chance that we'll you know, throughout next year, at conferences, you know, we'll highlight those molecules in more detail and also share some on how we got to the selection of those. As you know, we have various different approaches for each of those. For the IL-2, we're working with Cyrus Biotechnology, a protein engineering company, out of Dave Baker's lab in Seattle. For the IgA protease, we've kind of a dual approach.
We have an option for an IgA protease from a small company called Igen, and we're also working with Ginkgo Bioworks as well. We'll definitely, once we have selected the lead candidates, share also a bit about the selection process.
Okay, great. Thanks. Just one more. I know you're still on track to initiate the MMA 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?
Yeah. I can let Peter speak to this, but I think there's not a whole lot new to report. It's gonna be a single center study at the NIH. Chuck Venditti will be the PI there. You know, we are on track to kick the study off this quarter, unless there's any additional color, Peter, you can share.
Yeah. That's correct, Carsten. We have all the requisite approvals that we need to initiate the study. That will be initiated soon with enrolling the first subject with consent and screening.
All right. Great. Thanks. That's it for me.
The next question will come from Boobalan Pachaiyappan with H.C. Wainwright. Please go ahead.
Hi. Can you hear me okay?
Yes.
Okay. Following up on the MMA phase one study. You indicated earlier that you plan to assess initial efficacy and safety at three months for each patient before progressing to the next patient. Maybe can you remind us how many patients you want to enroll and what would be the approximate time to data?
Yeah. 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 just see that Peter has technical issues. Yeah. I can take the question, of course. The primary endpoint is at one year, but we'll have an initial readout at month three 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 MMA. We have a unique breath test that looks at propionic acid.
Of course, we're looking at what Raj mentioned as well, at the level of neutralizing antibodies. There is a safety data monitoring board that will assess after each patient whether we can move forward or not. It's gonna be a sequential approach. We haven't guided exactly when we'll have data, but we'll release data throughout next year.
Thank you. That's it from me.
The next question will come from Uy Ear with Mizuho. Please go ahead.
Hey, guys. Thanks for taking my question. On the DISSOLVE I, DISSOLVE II, you know, as you indicated, you expect topline 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, you know, in terms of the efficacy that will read out at least numerically? Should it be similar or comparable or different? Thanks.
Yeah, that's a great question that we do get a lot. Obviously these are, you know, very different patients we're looking at. If you look at the MIRROR study patients, there's a lot of exclusion criteria actually. Patients are excluded that don't tolerate methotrexate. Or they'll exclude patients that have chronic kidney disease, which is defined as an eGFR below 40. Patients that have more than 3 drinks per week. It's kind of starting out kind of the 100 patients, probably about 20 patients actually are, you know, eligible for that combination. It's a more limited patient population you're looking at.
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 weeks of methotrexate versus SEL-212 is, you know, six monthly infusions. What the studies do have in common is the endpoint, which is defined as SUA levels below 6 at month 6. So you basically in short, you're looking at a different subset of patients. I think what's great for patients is to have, you know, potentially another treatment option available. The current penetration is below 5%. You know, there are over 100,000 patients available.
there's a huge unmet medical need and obviously also a large commercial opportunity as well.
Thanks. For Kevin, I know as you indicated, the R&D is down, is low at least sequentially this quarter and year-over-year as well, because some studies was 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? Thanks.
Yeah, that's a good question. The period-to-period comparison it went down obviously because we were enrolling DISSOLVE last year. As you know, we completed enrollment in Q2 of this year, so obviously it's down year-on-year for the quarter comparison. 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. Not significantly, it will directionally be going up.
Okay. Thank you.
Again, if you have a question, please press star then one. This concludes our question and answer session. I would like to turn the call back over to Carsten CEO, Mr. Carsten Brunn, for any closing remarks. Please go ahead, sir.
Thank you, operator, and thank you to everyone who joined us this morning. Stay safe and healthy. This concludes today's call. Thank you.
The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.