ProMIS Neurosciences Inc. (PMN) Q3 2026 Earnings Call Transcript

Good afternoon, and welcome to the Promise Neurosciences Third Quarter 2026 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. Following the prepared remarks, we will conduct a question and answer session. As a reminder, this call is being recorded. I would now like to turn the call over to Carrie Pierce, Vice President of Investor Relations and External Affairs. Please go ahead.

Thank you, operator, and good afternoon, everyone. Earlier today, Promise issued a press release announcing our financial results for the third quarter ended September 30, 2026, and provided a corporate update. The press release is available on the investor section of our website and on our quarterly report on Form 10-Q and has been filed with the SEC and on CEDAR+. Please join me on today's call are Neal Warma, our President and Chief Executive Officer, who will deliver our prepared remarks, and Dr. Larry Alsteel, our Chief Medical Officer, who will be available during the Q&A session. Before we begin, I would like to remind everyone that today's call will include forward-looking statements with the meaning of the Private Securities Litigation Reform Act of 1995 and applicable Canadian securities laws. These include, among others, statements regarding our clinical development plan and timelines for PMN 310 and other product candidates. The interpretation and significance of the blinded interim data from our precise AD trial, our expectations regarding future clinical results, including the timing of top-line data, our financial position and cash runway, and our overall business strategy. These statements are based on management's current expectations and are subject to risks and uncertainties that could differ from actual results materially, including the risk that early or interim results may not be indicative of final or top-line results. Please refer to the risk factor section in our most annual report on Form 10-K and our subsequent filings with the SEC, including our quarterly report on Form 10-Q and for the quarter ended September 30, 2026. These statements speak as of today, November 12, 2026, and we undertake no obligation to update them except as required by law. With that, I will turn the call over to Neal.

Thank you, Kerry.

Good afternoon, everybody, and thank you for joining.

PROMIS is entering probably the most important period in its history. Our Phase 1B study, PRECISE-AD, in Alzheimer's disease, is nearing completion. All patient visits are expected to conclude. This quarter, an unblinded 12-month top-line data remain on track for the first quarter of 2027. Today, I want to focus on four things. Why recent events in the field sharpen rather than weaken the case for PMN 310, the strength of the interim data from July that we have seen in our precise AD trial, how we will judge the top-line results coming shortly, and how we are positioned both strategically and financially to move efficiently once we have the data. First, I want to directly address the Phase 2 results reported two weeks ago by another company developing an antibody described as oligomer-selective. That trial did not meet its primary or secondary endpoints at 18 months. And we have looked closely at the limited data that were disclosed, and two key findings really stand out to us. Let's first... That the antibody produced statistically significant reductions in amyloid plaque on PET at both doses, and second, approximately 10% of treated patients developed RAE, or brain swelling. In our review, both of those findings indicate meaningful engagement of plaque and fibular amyloid, not selective targeting of oligomers. And that matters. A molecule that clears plaque and causes aria is behaving much like the existing plaque-directed drugs. So in our view, that trial did not test the oligomer hypothesis. Selectivity is not a label. It has to be demonstrated both at the bench and in patients. And this is precisely where we believe PMN 310 is different, and the data we have to date Support that view. The field still needs a clinical test of oligomer selective targeting. We believe precise AD will be that test. Let me explain a little what sets PMN310 apart. PMN310, our lead candidate, our lead antibody, was built around one hypothesis that toxic amyloid beta oligomers drive neurodegeneration in Alzheimer's disease, and that selective neutralizing, And clearing them can deliver benefit without the safety burden of plaque-directed therapies. Three key features set PMN310 apart. Number one, selectivity. In head-to-head preclinical studies, PMN310 was the only antibody tested that bound toxic oligomers, while avoiding monomers, avoiding fibrils, and avoiding plaque. Other antibodies, include those described as oligomer selective, consistently showed binding to plaque. And additionally, the interim results from our Phase I-B study presented last July, or this past July, have reaffirmed our confidence in PMN310's selective profile. Number two is design. Like the two approved antibodies, PMN 310 is built On an IgG1 backbone to engage microglia and actively clear toxic oligomers from the brain, we deliberately chose both neutralization and clearance. And number three is safety. By avoiding plaque, PMN 310 is designed to reduce the risk of aria, which is still the single greatest barrier to broader use. To the broader use of anti-amyloid therapy. At our six-month interim analysis, Precise AD showed no RAE, zero cases of RAE in any ApoE genotype. And that's meaningful because with the approved antibodies, most RAE occur within the first six months of treatment. So the interim read, to be clear, is not definitive. But it gives us real confidence going forward. The burden of aria goes beyond the brain swelling and bleeding it causes. To monitor for it, patients on the approved therapies must undergo as many as six MRI scans in their first year of treatment. And keep in mind, these are cognitively impaired patients, and every scan is a real physical and financial burden on them. Their caregivers and the healthcare system. So our goal with PMN 310 is to reduce the incidence of aria and, with it, dramatically reduce the need for repeated MRI monitoring. Should PMN 310 deliver aria rates at or near placebo with efficacy at least as comparable to existing therapies, we believe it could become a leading treatment for early Alzheimer's disease. And even open the door to preclinical asymptomatic patients where safety is absolutely paramount. And just as a reminder to the audience, the blinded six-month interim analysis of 136 patients, randomized three-to-one active to placebo that we reported July 28th of this year, gave us an encouraging early read. There were no RAE cases in any APOE genotype as of our cutoff date. ARIA-H, a rate of 4.4%, all mild and asymptomatic, very much in line with placebo rates. There were no drug-related discontinuations, no treatment-related serious adverse events. And on the target engagement potential drug effect side, we demonstrated pooled plasma PTAW-217, decreased... Approximately 15% from baseline, and CSF-MTBR-Tau243 decreased approximately 13% from baseline. And remember, these are blinded, schooled observations and not a determination of efficacy, but they are consistent with target engagement, and the safety profile is what we would expect from a true oligomer-selective antibody. Although no head-to-head studies have been conducted, Our Interim Safety Profile It really stands in clear contrast to the REE rates seen in the recent competitor trial and also with approved therapies. And let's turn for a minute, let me turn to what we would consider a win when the top-line data readout in Q1 next year. So every Alzheimer's therapy is ultimately judged on its balance of benefit and risk, as weighed by the FDA. By prescribing physicians, by patients, and their families. Today, that balance is a difficult one. The approved antibodies offer a modest slowing of decline at the cost of ARIA risk and an intensive MRI schedule. Our goal is to shift that balance decisively. PMN 310 is designed to do that by lowering the risk side of the balance. While preserving the benefit. Efficacy comparable to the approved therapies with a clear safety advantage would shift it meaningfully. Any efficacy above what we see with the market of drugs would shift it even further. At Topline, we will evaluate the totality of the data against that goal, really looking at four things. With respect to safety, We're looking for ARIA, drug-related adverse events, event rates approaching or comparable to placebo rates. Clinical efficacy, we want to see a directional slowing of decline on either the IADRIS or CDR semiboxes versus placebo, so similar to approved therapies at the 12-month Biomarkers. We'd like to see changes that align with PMN310's oligomer-targeted mechanism, so directional trends in line with our oligomer selectivity mechanism of action. And then with respect to mechanism of action, we would like to show direct changes in oligomer levels following treatment with PMN310. And if precise AD, if our clinical trial demonstrates a shift, a material shift in the benefit-risk profile, We believe it would be a significant value-creating event for PROMIS and a very meaningful step forward for patients.

So I want to take a minute now just to talk about how we are preparing for what comes next. We're not waiting.

We're not sitting and waiting for top-line data to come to plan the next phase. With fast-track designation already in hand, we intend to request a meeting with FDA after the full set of data is analyzed. And in parallel, we're developing a subcutaneous formulation of PMN 310 and preparing for potential registration study, which we could envision beginning towards the end of 2027. Subject to FDA feedback, of course. We have also strengthened the team for that next phase. As we reported on October 5th, Dr. Ivana Rubino has joined the Promise team as Chief Commercial Officer. Ivana brings more than 15 years of global neuroscience and Alzheimer's leadership from senior roles at Biogen and at Roche, and she will help shape our regulatory, late-stage development. And commercial strategy. And attracting someone of Ivana's caliber, I think, speaks volumes to the potential of PMN 310 and our overall platform. And while we, on that note, while we have a strong pipeline of selective antibodies for other serious neurodegenerative diseases with high medical need, and this includes ALS, Parkinson's disease, dementia with Lewy bodies, I have focused today's call On our commitment to the Alzheimer's patients and their caregivers, and really around the enthusiasm we have for PMN 310 and the upcoming data release.

So before we kind of jump into a few questions and answers, I just want to turn briefly to our financial results for the quarter.

We ended Q3 with approximately $44.1 million in cash, which we expect to fund operations through 2027, well beyond the precise AD readout. And you can find full details of our financials in our press release and our Form 10-Q that was filed today. Research and development expenses were approximately $6.7 million, down 32% from the $9.8 million from a year ago. The decrease was really driven by a $3.6 million reduction in direct PMN 310 costs as the precise AD trial moved towards completion, and this is partially offset by more activity in our ALS and pipeline programs. G&A, general administrative expenses, were approximately $1.9 million, which was roughly flat with the $2 million from last year. Other income rose about $0.5 million from $0.2 million on higher interest income. Net loss overall for the quarter was $8.2 million, or $0.89 per share, and that's compared with $11.6 million, or $5.93 per share from a year ago. For the first nine months, net loss was roughly $28.1 million, or $339 per share, versus $29 million, or $19.58 per share in 2025. But just before we jump into the Q&A, just to summarize, recent events in the field had really made one thing more clear. Targeting oligomers is only as meaningful as the selectivity behind it. PMN 310 was designed for that selectivity, and our interim data to date, in the lab and in patients, fully support our hypothesis. We have encouraging interim safety and biomarker data, a strengthened leadership team, and a balance sheet that funds us through 2027. Our next catalyst is unblinded 12-month top-line data from the PRECISE-AD trial expected in the first quarter of 2027. And the question it will answer is whether PMN 310 shifts the benefit-risk balance in favor of patients with Alzheimer's disease. So, on that note, I'm now joined, many of you know our Chief Medical Officer, Dr. Larry Alsteel. I'm joined by Larry to answer questions coming through from the audience. So, operator, I'd like you to please open the line, and Larry and I will take questions from the group.

Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Thank you. Our first question comes from the line of Yatin Sunesha with Guggenheim. Please go ahead.

Thank you for taking my question. I'm going to the update. Sunil, I think you just started talking or recently have started talking about what constitutes a signal on the efficacy front. In fact, you have that also in the deck. So, you know, it would be great to maybe, you know, talk about that a little bit, also put in perspective the size of the study you are running relative to, you know, what we have seen in much larger study. I think it would be good for our investor to sort of understand that dynamic as well. Thanks.

Yeah, of course. Thanks, Jot, and thank you for the question. Yeah, it's interesting. We do obviously get questions around expectations around the trial. I kind of hinted that in the script here in talking through it, but what constitutes, you know, what's our target, you know, our target goal here with the Precise AD trial? And as I mentioned here, we're really focused on the benefit-risk profile. I don't mean to overemphasize that, but it really is important looking at both. The, you know, the risk side of the equation, so the safety versus the benefit side or the efficacy. And from our goal here, as we just went through, is to shift or alter meaningfully that benefit-risk profile. So our expectations in this trial, and as I think we said before, the best decision we made was in the design of this trial, and Dr. Alsteele sitting beside me is responsible for that in a good way, a very comprehensive Phase 1B study. So again, although it's comprehensive, it's 1B, we're looking at multiple endpoints. With respect to biomarkers, safety, clinical outcome measures, and even mechanism of action around the oligomer reductions, you know, we want to emphasize as well that this is a 140-patient study over 12 months, so direct comparisons with, you know, the larger 18-month study in 1,500 patients, we have to be careful putting that into context. But I think for us... For expectations coming out the other side of this trial in Q1, if we could see safety approaching or close to that background or placebo rate, especially around the ARIA, the burden of ARIA, as we mentioned, to patients and caregivers is significant. And that really, as we said, is the single most thing restricting the uptake of the marketed drugs. And we've heard this from prescribing physicians. We've heard this from pharma companies. If we, with PMS 310, can, you know, dramatically alter the safety profile, reduce ARIA levels at or close to placebo or background rates, that would be a significant win. And on the other side of the equation, with the benefit, the efficacy, if we could... You know, at least maintain similar efficacy. So, when kind of looking at some of those numbers, and again, we want to be careful here, but looking roughly at the efficacy numbers from the 18-month study, if you look at that 22 to 27 percent, if we kind of back that up to 12 months, and again, careful how we put this into context, if we saw an efficacy rate kind of in the range of You know, roughly 15 to 20 percent, so similar efficacy to what we're seeing with marketed drugs with a significant better safety profile. That, we feel, would be a significant win, and that's what we're hearing. And then any benefit kind of above that 20 percent would be total upside. So we're trying to look at similar-ish efficacy with a much improved safety profile, and I think that would be a significant win. If we saw that on the efficacy side as well, we would like to see directional trends in key biomarkers. So, I think the movement in the biomarkers, the trends we would see in some of these key biomarkers, would tell us why we're seeing the efficacy in the clinical outcome measures. And the clinical outcome measures that are important to us would be, you know, either or, the CDR semiboxes, or the IADRIS. So, these are the FDA, you know, approved endpoints. So, that, again, that range in that 15 to 20 percent either or, IADRIS or CDR semiboxes, supported by directional trends and key biomarkers, Which would really support the oligomer targeting thesis, together with a much improved safety profile with aria rates at or close to placebo.

Really helpful context. Thank you so much.

Thank you, Yadon.

Your next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Please go ahead.

Hey, good afternoon, Neil and Larry, and thank you for taking my question. You know, first question, you know, part of it is sort of theoretical, but it would be great to hear your perspective. You do have these oligomers. They vary in molecular weight and size, consisting of the same fragments. Does binding them necessarily mean neutralization? And can you speculate if antibody-bound oligomer could still have neurotoxic effects? And then sort of tying that back to the question of how much of an impact can the FC isotype make, especially IgG1 versus IgG2? Thanks.

Okay, thanks, Pete. It's a really interesting question. Does binding necessarily mean neutralization? I think that we have some hint from this from some of our preclinical studies in transgenic mice where treatment with PMN310 actually preserved memory acquisition and memory retrieval and also reduced the amount of inflammatory cytokines that were produced in the brain compared to placebo. So that does tell us, gives us at least a hint, that neutralizing the antibodies does have some effect in terms of... Now, in terms of activity. Now, can the antibody— And I think that the antibody can stabilize the toxic oligomers and render them less toxic. However, if there's some ambiguity there, that really does speak to the importance of the IgG1 background, because even if there is residual toxicity of the antigen-antibody complex, That removal ablates that effect, so that really does speak to the importance of what we've done here of having a very highly specific antibody that has a really, really, you know, low KD. That means that it really binds to it, hangs on to that oligomer, doesn't let go, and then it's bound and removed by microglia. So, I think that they both work in concert that way.

All right. Thank you very much.

Your next question comes from the line of Key Nakay with Chardon. Please go ahead.

Yeah, thank you. Yeah, appreciating that your data is going to be at 12 months and there's some interpolation there. So, does the shape of the curve at 12 and the degree of separation, how much does that also impact your go, no-go decisions?

Yeah, I think it needs to be looked at kind of collectively, Kay.

Thanks for the question. You know, again, we're looking at it across the various, you know, the various kind of baskets of endpoints, if you will. And if we see, again, it's 140 patients, three to one randomized. I keep referencing that. I think if we see, you know, if we see that benefit coming in that range that we're saying, you know, the separation we see between active and placebo. Combined with directional trends and those key biomarkers, I think that will be kind of a really important signal. Again, we've also got, you know, safety is going to drive a lot of this as well. And then I think we sit with the FDA. Again, we plan with our interface to meeting once we collect all the data and we sit with them and we, you know, we work with the FDA to demonstrate the benefit risk profile that we're taking forward. The rationale around reducing significantly, we feel, the number of MRIs that would be required. We've also got our mechanism of action data. Again, for the first time, we've got the assay that allows us to measure and detect levels of oligomers and their reduction with PMN310. And I think if you put those data points together and really showcase that benefit-risk change, then FDA should be in favor of allowing us to move forward with that next, you know, ideally registrational study.

Okay, and if I could ask for a follow-up on the sub-Q, how confident are you, based on any PK data you have, that you'll be able to formulate something equivalent, and how soon might that be ready? Will that be what you use in the pivotal?

Yeah, it's a good question. I mean, our goal is, I think, as we've said over the past few months now, we really initiated that sub-Q development program around the time of the interim analysis. I think we were certainly given confidence by the interim data enough to pull the trigger to get the formulation around sub-Q going forward. It is our goal. To bring the product to market as a sub-Q product, we're looking to where the market's evolving to and where it will have evolved in the next few years. Sub-Q is going to be important if we come to the market with You know, that benefit-risk much improved. We want to be there with a very patient-compliant product as well. So, the early studies we've been working on are encouraging. Obviously, a lot's going to depend on the results from the study around dose, but the kind of the PK that we're looking at early studies, the viscosity, the volumes required for sub-Q and making it manageable and painless for the patient are all going well. Our goal, then, is to, once we get into that next. Ideally, the registration study, we would see ourselves running a sub-Q arm within that larger study. So this would be, you know, we're not going to slow down IV to let sub-Q catch up. So, no, Larry, it'll be kind of a combined.

Yeah, I think, you know, when you talk about PK, one of the things we'd like to get from the phase 1b study is a dose and exposure that gives us a maximum effect with respect to efficacy, safety, and biomarkers. And so that would be an initial benchmark. And by running the... The sub-Q formulation equivalency studies alongside Phase III, we've got a comparator arm so that we know what we have to hit with the sub-Q. And so we're not slowing down the IB formulation, no far from it, but I think the sub-Q formulation will be able to catch up, especially because we have these normative data from the Phase III study. Yeah, so it's looking good, and it is, as I said, it is our goal to get to market with a sub-Q, for sure.

Great, thank you.

Thanks, Kay.

Your next question comes from the line of Fazia Ahmed with Brookline Capital Markets. Please go ahead.

Hi, team. Thank you for taking my question. My first question is with the upcoming CTAT presentation focused on the six-month interim safety and biomarkets finding, could you give us some sense whether there'll be additional insights from the data or it will just be the similar what we know that was disclosed in July?

Hey, Fazia. Yeah, thanks for joining. Thanks for the question. It will be, yeah, no additional information at CTAD. I mean, our goal at CTAD, as you rightfully say, is coming next week. When we're all there, we're presenting a poster which represents the interim analysis from last July. I think our goal there is just to continue to remind people of the differentiation of PMN 310, remind them of the data that's been generated to date, including the interim analysis from a couple of months ago, remind them of the data that's coming up in a few months. So it's really to kind of increase our exposure. You know, we're reaching out very much a clinical KOL-driven event. We've got a number of interactions with KOLs, a number of interactions with strategics and pharma companies. So it really is a way just to kind of, you know, reinforce our differentiation as a, you know, I won't say the only, but certainly in our view, one of the more exciting next generation anti-amyloid therapies company, anti-amyloid drugs coming along. So, it's very much kind of getting out in front of some of the KOLs and clinicians and pharma companies, but again, no new data will be presented on our part.

I think there will be probably some contextual interest here given the results with ACU-193, and so we'll be able to kind of reemphasize what we have had accomplished at the interim.

Thank you. And then I have one follow-up. So, given that toxic oligomers are, like, structurally heterogeneous and, you know, they, like, keep changing conformation, can you share some thoughts on how PM310, we know it recognizes a very specific conformation or specific epitope on that conformation. So, as these oligomers are changing, how accessible that epitope is to PM310?

Yeah, I think when the epitope is exposed, that's kind of a definition, in fact, of the toxic oligomers. As you point out, they are very plastic, poorly structured, and the epitope does appear on these, but as they become more structured and less toxic, that epitope is buried inside fibrillar structures, high-order fibrils, and ultimately in plaque. So, really, it's almost definitional that the... The aggregates of A-beta peptide that display this epitope do represent probably the bulk of the toxic oligomers that we're trying to eliminate. And they are consistent across kind of all brains.

In Alzheimer's brains, we've tested hundreds. And that binding, that conformational epitope is consistent across all Alzheimer's brains.

Yeah, and of course, it's not just one patient or a handful of patients. And also, too, you know, looking at low molecular weight fragments of brain homogenous, enhanced in oligomers, PMN310 removes the bulk of the oligomeric material there.

Perfect. Thank you so much.

Thanks, all of you. Thanks, all of you.

Your next question comes from the line of Bubalon Pachayapan with Ross. Please go ahead.

Hi, this is Aaron on for Bubalon. I just wanted to ask a question about Acumen's reported TSF antibody oligomer engagement was assayed before by your company, and I wanted to know what kind of oligomer binding differences, oligomer species binding differences you detected that may explain some of the clinical differences that have been observed, and if you will be reporting on any of these readouts in In the oligomer species, and free oligomers are antibody-bound complexes in the readout later in 2027.

I think that the Acumen binding assay really represented an antibody saturation assay, and the antibody being saturated with whatever PMR8-ACU-193 binds, oligomers and a lot of other stuff as well. Now, our assay is quite a bit different in that it measures the absolute concentrations of A-beta oligomers themselves. It is not inferential with respect to antibody saturation, but rather it measures the absolute concentration of oligomers in the cerebral spinal fluid. We demonstrated this. It was disclosed in a poster earlier this year at AAIC, and it's, to the best of our knowledge, The first time that anybody's ever been able to do this with this sort of sub-pecomolar kind of sensitivity that's required. They detect not only the oligomers, but also, in our particular case, a dose response in a single, you know, phase one, a single dose phase one study. So that's what we'll be reporting is the absolute decrement or change in oligomers as opposed to an antibody saturation.

Yeah, that's why it kind of takes the question there. And it's exciting for us, as Larry said, for the first time, we'll be able to kind of show, you know, hopefully to prove our mechanism of action or our hypothesis that we've got an antibody that binds and clears oligomers. And up until now, we've never had an assay. No one's had an assay that was sensitive enough to measure these, this low-concentration of maligomers. So, again, importantly, if we can show the safety biomarker movement, clinical outcome measures, and we can show precisely that it's due to the... Thank you. To the mechanism that we have proposed, that will be very, very interesting, not only for FDA, but also for us and pharma companies going forward, if we can connect the mechanism of action. So we're excited to be able to present those data. And that assay, as Larry said, is being implemented into the Phase 1B trial. So we'll look at pre and post treatment of oligomer levels with PMM 310.

Great. Thank you, guys.

Thanks.

Your next question comes in the line of Ragaram Savarahu with HC Wainwright. Please go ahead.

Hi, Larry. This is Jade on Varam. Thanks for taking our question.

Hi, Jade. Hi, Jade.

Okay. So, you've, you know, previously discussed the potential for substantially less frequent MRI monitoring. Really, the question is, like, how and when would you evaluate whether this was reduced schedules appropriate, particularly in the ApoE4 homozygote?

Well, right now, to date, we have seen, or at least not to date, but in the six months of analysis, we haven't seen any RAE. And we have a normal distribution that one would expect with ApoE genotypes. You know, in an Alzheimer's population, so there were a number of ApoE4 homozygotes, you know, a high degree of ApoE4 heterozygotes, and again, we saw no ARIA-E in this population, and an ARIA-H rate that was consistent with what one would expect to see in an untreated patient population, just the natural history. Now, with respect to, you know, how many Many MRI scans will be required as per the label. That's a discussion that we have to have with the agency, and we can't really predict that, you know, that they will say no more MRIs. We will just simply present the evidence as we have it to date, and then as it accrues in subsequent studies. And I think if we see the same sort of trend, I think that we'll be able to get rid of much of the MRI surveillance early on in the study.

And importantly, too, Jay, I believe that when you look at trontinumab that's using a shuttle here, and... You know, they've reduced their ARIA incidents. They're significantly with a shuttle. Of course, shuttles bring their own complications. But interestingly, I believe in their phase three design, the agency has reduced the number of MRIs that they're allowed from five or six down to three. So there's precedence coming, you know, from the FDA that if you can reduce, you know, so I think it's important. We've been asked, is this a class effect? And as an anti-amyloid targeting agent, regardless of RE, you're going to be given the same, you know, whack on the wrist that lecanumab, denanumab found. And I don't think that's the case. And I think trontinumab shows that it's not a class effect. And if we can come with an even cleaner safety profile, then there's a good chance that the MRI burden will be significantly reduced, ideally in the next registration study that we want to run. And if we can consistently show low levels of RA going forward, we would expect that come launch time, it's not going to be on the label, which is important. So I think there's good signs that we can dramatically reduce the MRI, because as I said in the piece earlier, it really is so... Well, cumbersome, burdensome for these patients and their caregivers to go multiple times a year for an MRI. You can imagine putting, you know, some of these patients who are not feeling too well into an MRI machine multiple times a year is horrible. So, ideally, that's one of our goals, and I think that, you know, in addition to saving on, you know, costs and healthcare costs, you know, the burden for the patient will be significantly reduced.

Well, as Neil pointed out, there is the FDA precedent that we've seen. That when you have the appropriate data, FDA will make a data-driven decision and say, you know, the data suggests that you don't need all these scans. We think that we'll come in with a safety data package that we'll present to the FDA. I'm not going to presume what they will say, but we do have the precedent that they are, you know, flexible about, you know, eliminating this apparent class effect and having a data-driven outcome.

Great. Thank you so much. And just quickly, just I was trying to find the participant number for the plasma PTAO 217 and the CSF MTBR TAO 243 charts in the presentation, and I wasn't able to find them. Could you tell me?

Yeah, we didn't provide, I mean, these are kind of when all. When all patients, you know, the total number of patients enrolled was 144. The safety valuable number was 136. So when all those patients had reached the six-month level, that's when we did our safety and biomarker analysis. We didn't give specific numbers on MTBR or P-tau as far as how many numbers of samples were collected from the patients, but so we didn't break that in kind of finite detail. We'll do all this kind of at the end of the study. We'll put all the patients and all the unblinded data, but we didn't communicate that at the interim level.

Okay, great. Thanks so much. Looking forward to it.

Yeah, thanks. Thank you.

Your next question comes from the line of Pete Stavaropoulos with Cantor Fitzgerald. Please go ahead.

Yeah, thank you for taking my follow-up. You know, assuming a positive outcome for the Phase 1B, and, you know, I understand that you need to, you need regulatory interactions, but, you know, how are you sort of currently thinking about next steps? Are you leading towards a Phase 2B or a Phase 3 or perhaps a Phase 2-3 adaptive design, and, you know, what will drive that decision? Thank you.

Yeah, thanks, Pete. That's a good question. I mean, we're doing a lot of that discussion now, and obviously bringing somebody like Ivana Rubino onto the team allows us to think a little bit more, you know, deeply comprehensively around those questions. I think for us, you know, it could be, you know, our thinking is kind of a registrational type study, whether that's a phase three or two, three adaptive. You know, we'll see what kind of, you know, the data will dictate some of that. We're doing those kind of design elements now, kind of including a sub-Q arm, as we talked about earlier. I think, you know, for us, we're being pretty bullish on, you know, single registration study, the exact size and shape and cost we're working on now. We haven't really given any guidance. I think we'll use, you know, Ivana's expertise, Larry's expertise to continue to, you know, think through various, um, You know, various approaches, what we are doing, you know, taking advantage of this wave and enthusiasm around AI, and we're careful how we do that, but there's a lot of input we're getting from AI, or we will get from AI. So, there's a number of elements we're building into the design perspective, and I think as we go forward, get the data, sit down with the agency, you know, and get their feedback, that will kind of shape our final decision.

Yeah, I think, Pete, I wouldn't dwell too much on whether we call it a Phase 2B, Phase 3, or 2-3, but rather focus on a clinical trial that's going to stand as a registration-quality study. Now, there's a lot of different ways to get there, and as Neil pointed out, we're exploring them as we speak, but that's our goal.

Yeah, and again, keep in mind, the reason, you know, we designed such a comprehensive One B study was to, you know, to be able to step into a registrational type study. As I said, we were pretty aggressive in numbers and length of treatment in order to kind of, you know, speed time to market and ideally get in front of the agency and propose a registration study that gets us, you know, that gets us to commercial stage quicker than if we had done, you know, a smaller one B study. So we're pleased with the design and ideally, you know, the outcome will dictate a lot of things in a few months.

Great.

Thank you for that, and I'm looking forward to the data in OneQ. Very good. Thank you so much, Pete.

This now concludes our question-and-answer session. I would like to turn the floor back over to Neil for closing comments.

Yeah, thanks, Kate, very much for your support. And thank you, everybody, for your time and your questions today. As I said, our focus really remains on patients and their families, And we are looking forward to showing in a few months. That PMN 310 could change the benefit-risk balance in Alzheimer's disease and really help the patients who so urgently need it. So thank you so much for your attention and your support. We'll update again soon.

Ladies and gentlemen, thank you for your participation. This does conclude today's teleconference. You may disconnect your lines and have a wonderful day.