Q4 2022 Selecta Biosciences Inc Earnings Call

Speaker 2: Good morning and welcome to the Selecta Bio fourth quarter 2022 earnings release conference call.

Speaker 2: Our participants will be in listen only mode. Should you need assistance, please signify conference specialist by pressing the star key followed by zero.

Speaker 2: After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your telephone keypad.

Speaker 2: To withdraw your question, please press star and 2. Please note this event is being recorded. I would now like to turn the conference over to Blaine Davis, Chief Financial Officer. Please go ahead.

Speaker 3: Thank you and good morning everyone. Welcome to our fourth quarter and full year 2022 financial results and business update conference call.

Speaker 3: The press release reporting our financial results is available in the investors and media section of select his website at www.selectabio.com in our annual report on form 10k for the year and the December 31st 2022 which was filed earlier this morning with the Securities and Exchange Commission or the SEC joining me on today's call are Carson Brun President and Chief Executive Officer of the United States Department of Commerce

Speaker 3: projections and our future expectations, plans, partnerships, and prospects.

Speaker 3: These statements are subject to various risks that are described in the filings made with the SEC, including our most recent and report on Form 10K and subsequent quarterly reports on Form 10Q.

Speaker 3: Your caution not to place undue reliance on these forward-looking statements which speak only as of today March 2nd, 2023. We've selected this claim as any obligation to update such statements, except as required by law, even if management's views change.

Speaker 4: With that, I'd like to turn the call over to Carson. Thank you, Blaine. Good morning. I appreciate everyone taking the time to join us today. In the fourth quarter of 2022, and in the first month of 2023, we continue to make steady progress across the pipeline.

Speaker 4: and we believe we're well-positioned to execute in our key priorities and reach multiple milestones throughout this year. In collaboration with our partner Sylvie, we expect to announce top-9 data from the Phase 3 dissolved 1 and 2 clinical trials of SA-L212 later this quarter. Our remind line into the data facing the results from previous trials.

Speaker 4: in which we observe SEL212's differentiated profile and convening once-months-reducing regimen, we remain confident in its potential to improve the lives of patients suffering from chronic effectorigout.

Speaker 4: Further, we plan to continue to leverage our growing safety database to advance our Intuor Clinical Development Program for our ongoing reimagined Phase 1-2 clinical trial of SCL-302 for the treatment of methegalonic acidemia or MMA and propel our next generation programs forward. Notably, we recently identified an interleukin-2 or IL-2 candidate to be studied in combination with Intuor.

Speaker 4: in the broad set of potential autoimmune indications, as well as an ITA protease candidate for the treatment of ITA in the property. We also continue to accelerate our ITA protease called ZORP, following a deal with a cellar in early January , which involves the study of ZORP in combination with ATA for...

Speaker 4: value of our Intel platform and pipeline. On the cost of this pivotal moment in the company's growth trajectory, we'd like to provide an update on recent activities and share details on how these programs align with our mission to solve the toughest challenges associated with unwanted immunoscienticity. The current standards of care for autoimmune disease.

Speaker 4: utilize immunosuppressive drugs or symptom mask treatments. Unfortunately, these treatments often leave patients vulnerable to serious infections, malignancies, and fail to adequately address the underlying cause of the disease, which is an imbalance of regulatory T-cells versus effective T-cells.

Speaker 4: At selector, we're imagining immunotherapy. There are over 20 from in the Americans still suffering from autoimmune diseases. We believe in tour has potential to transform the treatment landscape by restoring national immune system balance through induction and expansion of regulatory itself in vivo.

Speaker 4: The combination of IMTOR and IL-2, which we call IMTOR-L, represents an evolution of selector's precision immune tolerance platform that has the potential to further enhance the magnitude and duration of immune tolerance in patients treated for autoimmune diseases.

Speaker 4: If chosen I'll sue development candidate, that will be started in combination within Tor, to potentially further advance and expand our pipeline in autoimmune disease. To plan to initiate IND-Naping Studies in 2023, while also exploring multiple autoimmune indications that may be suitable for studying with INTRRL, with initial focus on diseases of the liver.

Speaker 4: We believe IntoroL has the potential to be a truly differentiated first-in-class treatment for those suffering from autoimmune diseases. We planned to initiate multiple treatment studies this year with this exciting combination.

Speaker 4: Moving on to our gene therapy vertical, which we believe has potential to enhance the efficacy and safety of AV gene therapy and broaden the elder patient population for such therapy. Immatures designed to enable patients to receive multiple lower doses of AV gene therapy, chitrate after a serbidic benefit and mitigate side effects associated with high-evector doses, thereby transforming the dose in paradigm from one and done to low and slow. In December 22, we initiated the phase 1, 2, clinical trial of SEO.

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Speaker 4: We believe our pre-natal data in non-human primates and mice indicate that two additional monthly doses of IMTOR have the potential to provide durable inhibition of NTAV maps if incorporated the stozing regimen in the rematch and trial.

Speaker 4: By advancing SEL302 into the clinic, we believe we can help our current and future gene therapy partners accelerate the use of IMTOR in their gene therapy programs by providing a clinical and regulatory blueprint to follow.

Speaker 4: In January 2023, we announced an exclusive licensing and development agreement for SOARC. We developed for the use with AT845, a stellar investigational AV-based treatment for late onset pump disease in adults. SOARC is a next-generation ITG protease.

Speaker 4: Most other ITG-proisting developments are derived from common human pathogens and as a result there is a high prevalence of tree-existing antibodies against these proteases that can restrict the utility. Zorch is differentiated by its low cross-sterectivity to improve existing antibodies in human serum and we believe it has the potential to deliver transformative gene therapy treatments to a broader range of patients living with the ability to do these diseases. Many patients are currently ineligible for clinical trials.

Speaker 4: with investigational AV gene therapies due to the presence of naturally occurring antibodies against AV capsules. Due to its selective product activity against NTAV NAPS, we believe STORC has the potential to expand access to life-changing gene therapies by addressing pre-existing immunity to AV. The objective of our gene therapy vertical is to bring hope to patients who may not have many other treatment options. Inable companies.

Speaker 4: to maximize the commercial potential of their gene therapy candidates and help to make otherwise un-economic gene therapy candidates viable targets for commercial development. We plan to continue to pursue business development and out-licensing opportunities to maximize the value of our platform. Now, turning to our Velocice pipeline.

Speaker 4: Many biologics can be highly immunogenic, resulting in suboptimal responses due to the development of antitrically antibodies after treatment. Patients who develop a new response may be forced to discontinue treatment or experience adverse reactions to continuous therapies. We believe the use of Intor as an adjunct to biologics offers a promising approach to reduce the unwanted immune responses and improve patient outcomes.

Speaker 4: We believe our most advanced program, SEL212, has served as clinical proof of concept for our Intel platform with over 500 patients' dose to date. As a reminder, SEL212 is comprised of Intel, co-administered with a proprietary Uricase for Gatricase for the treatment of chronic defector doubt and was licensed to SOVI in 2020. Our Phase III dissolved in the Gap Program, kicked off in the third quarter of 2020 and consists of two doublet blinds for the CEPA control trials.

Speaker 4: of SEL212. In both trials, SEL212 is being evaluated at two dose levels of Intor, 0.1 mixed per kick and 0.15 mixed per kick, with a single dose level of the gadget case at 0.2 mixed per kick. We continue to work closely with our partner, SOBI, our clinical trial providers, and regulatory authorities advance towards the successful completion of the Phase 3 program and we are on track to announce top-line data for dissolve one and two later this quarter. Based on the results from previous trials, in which we've observed SEL212's differentiated profile and, coming in once-monthed dose in regimen, we believe SEL212 is well positioned against the current Senate of Care and other drugs.

Speaker 4: the first when immune complexes of an antibody called immunoglobulin A1 or IGA1 accumulate in the kidneys.

Speaker 4: In December 2022, we selected the next generation IGA approach from IGA and biosciences for the treatment of IGA and planned to initiate I&D vaping studies in 2023. By combining in-tour with an IGA approach, we believe our novel approach has potential to address the underlying pathophysiology of the disease by removing injures IGA from the kidneys and improve markers of renal function.

Speaker 4: We're extremely excited about the advancements across our pipeline and the growing body of clinical data showcasing the promise of our Intel platform in a number of applications. We look forward to continuing our momentum in the coming year. With that, I'll turn the call over to our newly appointed chief financial officer, Blaine Davis, to run through our financial results for the fourth quarter and full year. Blaine brings more than 25 years of experience, investor relations, business development, corporate affairs, and sales and marketing at life science companies with a particular focus on rare diseases. Blaine's impressive track record makes him an ideal fit for selector at his critical inflection point and we're truly delighted to have him on board. Blaine. Thank you, Garsten. I'm thrilled to join the select team and look forward to working closely.

Speaker 3: with everyone as we deliver our mission to improve the lives of our patients. I would like to briefly run through our financial results for the fourth quarter and full year 2022. Revenue for the fourth quarter and full year 2022 was $16.8 million and $110.8 million respectively as compared to $29.9 million and $85.1 million for the same periods in 2021. Revenue was primarily driven by the License Agreement with SOBI, resulting from the shipment of clinical supply and the reimbursement of cost incurred for the Phase 3 dissolved clinical program.

Speaker 3: Research and development expenses for the fourth quarter and full year 2022 were $19 million and $72.4 million respectively as compared to $20.3 million and $68.7 million for the same periods in 2021. The quarterly decrease was primarily driven by a decrease in expenses incurred for the ESEL-212 clinical program.

Speaker 3: The annual increase was primarily driven by expenses incurred for preclinical programs, increased personnel expense, and stock compensation expense. General and administrative expenses for the force quarter and full year 2022 were $6.3 million and $23.9 million respectively as compared to $5.5 million and $20.9 million for the same periods in 2021. The quarterly and annual increases were primarily driven by increases in stock compensation and personnel related expenses.

Speaker 3: But the fourth quarter and full year 2022, selected reported net income of $5.9 million, or basic net income per share, of four cents.

Speaker 3: A net income of $35.4 million or basic net income per share of 24 cents respectively. For the fourth quarter and full year 2021.

Speaker 3: Select a reported net income of $12.2 million or $0.10 per share and a net loss of $25.7 million or $22 cents per share respectively.

Speaker 3: Select ahead 136.2 million in cash equivalence marketable securities in the restricted cash as a December 31, 2022, as compared to $129.4 million as of December 31, 2021. We believe our available cash cash equivalence restricted cash and marketable securities.

Speaker 4: of data's inter-platform. We continue to advance our diversified clinical pipeline and we establish the strategic collaborations that we believe can propel our next generation programs toward multiple IND filings.

Speaker 4: We look forward to building on the momentum of our recently announced deal with the Stela Spazork and Pompid Disease, the initiation of the Phase 1, 2 trial and MMA, the identification of an IL-2 candidate and selection of an IG-approviate candidate, and we remain on track to report top-line data from the Phase 3 dissolve and 1 and 2 clinical trials, investigating SCL-212 in chronic infected gout later this quarter. We remain blind to the data, but as previously stated, our confident in SCL-212's competitive profile

Speaker 4: Before we conclude today's call, I would once again like to thank the entire selected 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.

Speaker 2: momentarily to assemble our roster. And our first question will come from Joseph Schwartz of SVBC.

Speaker 4: the study that you're commencing. I know you previously said that you'd expect to release data on a patient by patient basis, but since the first patient I think is being dose without Intor, I was wondering if you'd expect to wait until you have the first Intor dose patient as well to present the initial data set. Yeah, so that's a great question. Yeah, as we previously guided, we will report

Speaker 4: interim data, so three months data, looking, obviously this is primarily a safety study, but also, biomarkers of the disease, and then specifically we are interested in Intor and the NAP response. So we've sector released data towards the end of this year, as you rightly said, the first patient only receives the gene therapy, the second patient and will receive Intor. So, likely release data towards the end of the year. Okay, thanks. And then on Intor IEL, I was wondering if we could get your thoughts on the recent IEL2.

Speaker 4: trial failure in SLE. And why do you think your PBC program is perhaps better suited for success? And do you plan to report any new preclinical data across your early stage pipeline this year? That's not a great question. Obviously we haven't looked at the data in a lot of detail, but obviously where we think we are highly differentiated is the combination of Intour with an engineer's ILQ. We actually are really a first in class by inducing and expanding.

Speaker 4: QX selective, you know, cell. So I think that approach, the end of the specific approach, is really unique and you have a much better chance at addressing the underlying disease. We are going into audiences of the liver and we think it's really low-hinged in the food also because of, you know, intor accumulates in the liver and actually we've shown in a couple of models that intor alone actually ready is, it's about to protect it. So we're pretty confident in the liver approach and yes, we will release, you know, after everybody has the eyes on the calizes

Speaker 5: out and in some cases, even before the MDCAPS of data, wanted to know how you believe that some of the MMA data and of course your discussions with the respective regulatory agencies could further help with your conversations with current partners, but then also how it could potentially open the door for others that are interested.

Speaker 4: Yeah, Chris, that's a great question. I think the fact that we signed two deals with Takeda and Sirapha ahead of the NCAPS just shows the unmet medical need in this field. I mean, there's tremendous unmet needs to prevent the formation of NAPS and give patients a chance to receive a second dose. We definitely believe that, you know, it's just the fact that we have NCAPS data available. It's an important data point. And most importantly, we have a clear regulatory path. I think that's really important. That's the reason we're actually running the MMA program. We can give clear guidance to our partners on how to develop.

Speaker 4: in tour and in this case with three monthly doses of in tour. And obviously we believe that the data from the MMA study you know will also be helpful along the way as well. Thanks for that. Then the second part on gene therapy is how would you say that you know general awareness of the platform potential here has increased. Given you've had more data over time, there have been safety and durability hiccups from others in the space as well as...

Speaker 5: Of course, just seeing the number of deals you've been able to execute as well. We just repeat the question you were breaking up here on my end, sorry. Yes, sorry about that. The question was just on understanding the awareness of the platform potential. Given you've had more data, you know, there have been some safety and durability hiccups in the space, as well as, you know, just seeing the execution you've had through striking deals with others. God, yeah, thank you so much. Yeah, I mean, there's obviously there is increased.

Speaker 4: awareness and you know they have been a number of setbacks to last two years in the gene therapy field Toxicity's associated with AV so I think there's acute awareness around Intor and the potential of Intor But also, you know, we really position ourselves as a solution provider Address it from the key challenges in gene therapy which number one is the ability to potentially read those within Tor

Speaker 4: But also, secondly, with our ITG Protei Zorch, to increase the number of patients eligible to gene therapy as well. And I think our deal with Estela is testimony and so that. There's a lot of awareness and interest in the platform in gene therapy. And we've been pretty outspoken. This is really a vertical we want to pursue from a partnering perspective. Great. And then of the last question I have for you is just, you know, how many roughly liver diseases you believe into our IL could be evaluated in. And then, you know, what are some of the criteria on your wish list essentially when choosing which indication you might start.

Speaker 6: diseases for IEL. But to your specific question about liver diseases, there are a number of clearly autoimmune liver diseases.

Speaker 6: which are T cell mediated and affect the liver. PVC is a quintessential one, but there are others that are even more clinically important have more unmet medical needs, such as autoimmune hepatitis. There are a couple types of that disorder, primary biliary colon, colon gytus, which is associated with...

Speaker 6: represent a significant number of affected individuals and significant unmet medical need. While there's therapy and PBC available, as you know, there's only a single approach to AI autoimmune hepatitis and no successful therapies in...

Speaker 6: primary sclerosis and colon gyrus PFC. So we think that there's an area there to make an impact which will be one of our focuses. Not the only focus we'll have in autoimmune disease, but a key one.

Speaker 5: Great. Thank you. Looking forward to seeing the data next couple of weeks here. Thanks, Kristen. So are we?

Speaker 4: The next question comes from John Newman of Canacord Genuity. Please go ahead. Good morning. Thank you for taking my question. Regarding the top line data for SCL212, I'm just curious as to how much information you might be able to share regarding the safety, specifically the gout flares. I know that...

Speaker 6: Some of the early development suggested that in addition to good efficacy, you may actually be able to improve the incidence of gut players, maybe lower that a bit. Just curious if you'll be able to talk about that at all, excuse me, on the top line Yeah, that's a great question, John . And obviously, what's important to note that we've been completely blinded to the data? Since we haven't seen the data, but I'll let Peter address what we expect in terms of showing the top line perspective. Yeah, John , I'll tell you what we expect, but I'll just clarify a little bit kind of some of the historical data from our program. So first of all, it's well established that gut players increase with uricase therapy. That's been established by all of the pegloadicase trials that have been done. So you do get an increase in gut players.

Speaker 6: as you start to dissolve and reduce the urate deposits in the body. In phase one and early phase two, it did appear that there was some reduction in gap flare incidents with SEL212. But in the compare trial, which as you know was a large comparison trial with 83 patients receiving SEL212, we didn't see a real reduction in gap flares. Now in...

Speaker 6: In dissolve, we'll be comparing the best comparison because we'll be comparing Gaupflares versus placebo. And we'll be able to look at the number of Gaupflares in different periods of time of the therapy versus placebo. So we will have those data and we'll be able to report on that. Okay, great. Thank you.

Speaker 4: The next question comes from Yeon-Zong of BTIG. Please go ahead. Hi, good morning. And thank you very much for taking the question. So the first one is a kind of follow-up question on the indication selection for M2 or IO2. I don't see the press release specifically mentioned PBC. I just wanted to confirm that PBC is still likely the first indication to choose or I do believe that you mentioned that multiple pre-clinical IND Nibbally studies will be initiated in 2023. So I assume those studies are for different indications. Yeah, it's a great question. Very observant. And a great question. As Peter said, I mean, PBC definitely is still part of the question. The next question comes from the next question.

So we want to open the front a little bit and look broader at autoimmune diseases off the liver, as there are multiple indications of high interest indications that are well-suited for M2L, like PVC, where we know the auto-anogen impacting the disease, PVC2.

but also there's other indications with high on the feed as Peter mentioned like auto-meant hepatitis. So definitely, PVC is still part of the mix but we want to open up the funnel and we'll give more detailed guidance after the dissolve readout. Okay, then the second question on the collaboration was a staleist. It's a very exciting one. But I believe the gene therapy program uses AAD-8 and which happens to be the capsid used in the empty capsid study. So just curious, did athletes show any interest in Intor? And I just wanted to confirm also that Intor and also Zorke, both of them are agnostic to the capsid used in the study. So the effect is not affected by which capsid to choose.

Is that correct? Yeah, that's a good question. And yeah, so Estella's exclusive license, the use of Zork for the use in their Pompeii program. And you also write that both approaches, as far as you know, are agnostic. We've shown with different AV subtypes that, you know, interprevent the formation of the end of the bodies. And we assume the same for Zork as a pre-treatment, the same that's agnostic actually to the AV exposure that patients had. Great, thank you very much. The next question comes from...

interesting area. As Peter mentioned, we think it's low-hing fruit because Intuo accumulates in the liver, there are indications that we can execute on as a company, all the way through commercial actually. I mean, it's all attractive, but still kind of orphan-type indications that we can execute on. At the same time, there are larger indications which are of interest. We might potentially do an initial proof of concept study, but then you would look for partnerships to see this through for sure.

given the complexity that is specific disease expertise but also the cost of the programs. Excellent. And maybe just to organize things for us here. What sort of milestones are you expecting on a positive readout from the pivotal studies for SOPE here? Thank you. Yeah, good question as well. So, and I think we've gotten the past. So.

Just to remind you of the overall bill term, so we licensed the asset to SOBE in 2020, received $100 million upfront. We're also to receive $630 million in milestones that's broken down, $80 million in regulatory and development, and $550 million in commercial. Out of the $80 million, we've received $15 million so far. So we were so out of the receipt, $65 million. We haven't broken out to which event this is tied to. And then also we're out of the receipt royalties in the double digits as well. Thank you. Very helpful.

The next question comes from Tiffany Marshall of William Blair. Please go ahead. Hi, this is Tiffany. I'm for Ron. Thanks for kicking in question. For the IDG proteasort, can you maybe discuss a bit how you and a cell have planned to use ZARC prophylactically for preexisting antibodies? And do you imagine this still a certain cutoff in the level of preexisting antibodies that might be effective for, or really just how much do you imagine ZARC could be?

expand the tree will population here. Yeah, that's a good question. And obviously, I can't comment how as they're planned to develop this, but I can just comment on how we view the approach. And so there's interesting data from ITG proteators that basically cleave free existing antibodies, which prevent dosing. And specifically, we're looking here patients had a natural AV in section.

So, not necessarily patients that were exposed to an AV gene therapy get very high titers in the thousands. We're looking here more at natural AV infections. And that inflicted about, between 30 to 70 percent of all patients had a natural AV infection, not elsewhere to receive gene therapy. So, we think it's very attractive both from a patient perspective, but also a commercial perspective. You potentially double the number of patients eligible, and that definitely played them in part of YSLS license or.

Great, that makes sense. And I guess for Zork, do you also plan to share any additional pre-clinical data this year on that? So we haven't guided to that. I think we've shared some of the initial data, but at this point, we have not guided specifically to share additional data. All right, thanks.

Great, that makes sense. And I guess for ZORC, do you also plan to share any additional pre-clinical data this year on that? So we haven't guided to that. I think we've shared some of the initial data, but at this point, we have not guided specifically to share additional data. So. All right, thanks. Thank you.

The next question comes from Boba Long, Patia Nyappen of HC Wainwright. Please go ahead. Hi, this is Boba Long. Can you hear me okay? Yes, Boba, we can hear you. Thank you. All right. Great. A few questions from our end. So, firstly, with respect to IGN property, obviously you might have your own area of the FBA pool of this very Spartan Sun. So I'm curious how this FBA pool might alter the dynamics of your IGN program, especially in light of the fact that the agent that was approved, the increase of the scope of liver injury on birth defects. Yeah, so maybe I let Peter just talk a little bit about our approach here and why we think it's a truly novel approach.

And really see this complementary to some of the other products in development, Peter. Yeah, Ruben, happy to answer that question. I think that what you're referring to is that there were some warnings on the latest approval based on age group. We don't anticipate age group issues, but of course we will be starting our development program in adults.

Now, with regard to the specific approach, all the approaches that have either been approved or are in development are either looking at a type of steroid which affects the upstream production of IgA or downstream effects of the deposits in the kidney. We're the only approach which is targeting the IgA viewing complexes in the kidney to try to clear those to see whether that will improve the disease. So our approach is complimentary to...

the two drugs that have been recently approved, as well as all of those in the development pipeline. Now, approval of additional drugs will certainly affect the development program from the standpoint of exclusions and inclusions and standard of care and so forth, but we'll have to wait to see how that evolves with the recent approvals. But by and large, ours is a novel approach that no one else at this point is utilizing. Thanks for the color. As you're thinking deeply about your IGN program, this is curious. Are there specific biomarkers that you will be paying close attention, maybe in the next few quarters, to gain confidence in the program in addition to say UPC ratio? Yeah, so biomarkers, you're talking about of effect in IGN.

the target, the field or agent or for general or all, again, patients? Well, I think that we are looking at that carefully. We haven't decided exactly which patient population or segment that we will focus our development program on.

Obviously, there are different ways to segment the patients in terms of when they were diagnosed, whether they have failed other therapies, what their baseline renal function is, whether they have evidence of progressive, rapidly progressive disease or slowly progressive disease. We'll be looking at all of that to take into account how to focus our program.

And we haven't really made those decisions yet. We do think that patient segmentation will be an important part of the program. Wait, and maybe one final question. Would your future ask this gene therapy collaboration? Um.

This is more like a classification. Is there a requirement of the agent or the gene therapy agent plus your zerg? It should get to skeletal and cardiac muscles.

If I understand the question correctly, this is around Intor or Zork. Intor works to deliver, but we have partnerships and all the data we've generated is in liver.

directed vectors, but obviously we do have a partnership with Seraptor, the look at neuromuscular disease, where we also believe that there's a good rationale why we could use Intor as T-Rex migrate, obviously, as well systemically that hopefully addressed the question.

So the question was not about in terms of a ZORC, but yeah, thanks for the color. I can comment on the ZORC. So the ZORC works through a clearance of systemic IGG, so the neutralizing antibodies included. So regardless of where the caps did.

The target is, as long as it's systemically delivered, it's going to be intercepted by the neutralizing antibodies, so the ZORC and I should be active in that situation.

Thanks for the caller. Thanks so much for taking our questions. The next question comes from Oyir of Mizzouha. Please go ahead. Hey guys, thanks for taking my question. So I guess the first question is. Thanks for the question.

on the MMA study that you guys are ongoing. Just curious to sort of get a better sense of what you're seeing in terms of patient's interest in the gene therapy. And my second question is, given the completion of the dissolved wine and dissolved two studies, just curious to curious to see if you can help us.

understand how to think about R&D for 2023. It looks like the consensus is projecting kind of flat R&D versus 2022. And yeah, that's essentially it. Yes, I'll give the first question to Peter who is obviously ultimately intimately involved in the rematch in trial, which we're running at a single center at the NIH. Peter.

Yeah, happy to answer that. In terms of the patient interest, we have done a good deal of promotion of the trial through the Organic Acidemia Society, the website for the trial. Then we have gotten a lot of interest, both in the U.S. and international. But of course, this is a trial where we are sequentially...

in rolling subjects over time. So it's not like the trial success is going to be dependent on a very large group of patients interested right at the beginning because we're going to enroll them sequentially over the course of two years. We have, as you know, the trial is active. It has been since the end of last year. We have enrolled a subject, a first subject, and that subject is going through the extensive screening process leading up to...

Let me give a little bit of context. So as you could expect, we continue to have clinical trial expenses associated with the SEL-212 program that will be continuing in 2023. And then we'll also start to have obviously a decent amount of ramp up activity associated with the earlier state pipeline around preclinical activities as well as kind of a number of other R&D-related expenses. So...

There will start to be a shift in kind of where those R&D expenses are associated on a go-forward basis. You know, we do have a number of kind of early stage activities and programs as well as the ongoing MMA study that will start to have a shift overall. But I don't want to provide kind of specific guidance at this particular juncture on how to think about overall expenses. But hopefully that gives a little bit of context in some of the moving parts as we think about 2023.

Okay, thank you. This concludes our question and answer session. I would like to turn the conference back over to Kirsten, Bruin for any closing remarks. Thank you, operator, and thank you to everyone who joined us this morning. They say it's unhealthy. This concludes today's call. Thanks. The conference is now concluded. Thank you for attending today's presentation. Goodbye. And you may now disconnect. This concludes today's call.