ProMIS Neurosciences Inc. Common Shares (ON) 2026 Q2 Earnings Call

Please go ahead. Thank you, operator, and good afternoon, everyone.

Thank you for joining ProMIS Neurosciences second quarter 2026 financial results and business update conference call. Presenting on our call today are Neil Warma, our President and Chief Executive Officer, and Dr. Larry Altstiel, our Chief Medical Officer. Earlier today, we filed our quarterly report on Form 10-Q with the SEC for the quarter ended June 30, 2026, and issued a press release with our financial results. Both are available in the investor relations section of our website at promisneurosciences.com. Before we begin, I would like to remind everyone that statements made on this call include forward-looking statements with the meaning of the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These include, among others, statements regarding our clinical development plans and timelines for PMN310, PMN267, and PMN442, and our other product candidates.

The interpretation of the significance of the blinded interim data from our PRECISE-AD trial, our expectations regarding future clinical results, and our financial position and cash runway, and our overall business strategy. These forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied. We encourage you to review the risk factors described in our most recent annual report on Form 10-K, our Form 10-Q filed today, and other filings with the SEC. We undertake no obligation to update or revise any forward-looking statements as a result of new information, future events, or otherwise, except as required by law. With that, I would like to turn the call over to Neil.

Thank you, Carie. Welcome to all those who are joining us today to discuss ProMIS Neurosciences results for the second quarter of 2026, and also to review the recent progress across our pipeline. As Carie said, joining on the call today is Dr. Larry Altstiel, our Chief Medical Officer, who will walk us through the encouraging interim data we recently reported from our phase I-B PRECISE-AD clinical trial. I'll then provide a financial update before we open the line up for a few questions. As many of you know, ProMIS is a clinical stage biotechnology company applying our patented technology platform to build a portfolio of antibody therapies and therapeutic vaccines for neurodegenerative diseases, with a focus on Alzheimer's disease, dementia with Lewy bodies, ALS, and Parkinson's. We believe these diseases share a common biological cause. Normal proteins that misfold become toxic and kill neurons.

Our platform is designed to combine protein biology, physics, and supercomputing to selectively target these toxic misfolded proteins while sparing their healthy, properly folded counterparts. Our lead product candidate is PMN310, which is a monoclonal antibody designed to treat Alzheimer's disease by selectively targeting toxic misfolded oligomers of amyloid beta. Behind PMN310, we are advancing PMN267 for ALS, which targets misfolded TDP-43, and PMN442 for synucleinopathies such as dementia with Lewy bodies and Parkinson's disease, which target pathogenic alpha-synuclein. Both PMN267 and 442 have been humanized in a human IgG1 framework and are advancing toward IND-enabling studies. We are also progressing a set of vaccine programs in Alzheimer's and Parkinson's and ALS. As we have recently discussed, the second quarter was a defining period for ProMIS. In late July, we reported positive, blinded six-month interim safety and biomarker results from our ongoing phase I-B PRECISE-AD clinical study of PMN310.

Data we believe reinforce the core thesis behind our oligomer-selective approach. Larry will walk us through the details in a moment, but at a high level, the blinded interim analysis yielded a favorable safety profile across all participants and genotypes, showing no cases of ARIA-E and early directionally consistent movement in two complementary biomarkers, plasma p-tau217 and CSF MTBR-tau243, which is consistent with target engagement. We believe these data reinforce the central thesis behind PMN310, that by selectively targeting toxic amyloid beta oligomers rather than plaque, we have the potential to deliver the benefits of amyloid-directed therapy without the ARIA burden that has constrained this class of medicines. We actually hosted a live webinar back on July 28 with two independent key opinion leaders, Dr. Thomas Montine, University of Minnesota, and Dr. Michael W. Weiner of UCSF, who shared their perspective on the data and its clinical relevance.

For those of you who missed it, the presentation and recording of the webinar are available archived on our website. This, we believe, is truly the most meaningful clinical milestone in the company's history to date. I would now like to ask Dr. Altstiel to walk through the PRECISE-AD summary of the interim data in a little bit more detail. Larry, if you would please.

Thank you, Neil, and good afternoon, everyone. I will walk through the six-month blinded interim data from PRECISE-AD that we announced on July 28. Starting with the trial design, then safety, then biomarkers, and close with what to expect as we move toward the 12-month top-line readout. PRECISE-AD is an ongoing phase I-B trial of PMN310 in patients with mild cognitive impairment due to early Alzheimer's disease. It is a randomized, double-blind, placebo-controlled, multiple ascending dose study. We completed enrollment in December 2025, with 144 subjects across 21 active sites in the U.S., randomized three-to-one active drug versus placebo across three dose cohorts of 5, 10, and 20 milligrams per kilogram, dosed monthly by IV infusion over 12 months. Of the 144 enrolled subjects, 136 were included in this interim safety analysis. This is a genetically and demographically representative population.

Mean age was 73.3 years, 58% of patients were female, and importantly, 61% of patients carried at least one ApoE4 allele, with 11% being ApoE4 homozygotes. That is the proportion of the very highest risk of ARIA with plaque-binding antibodies and one that is often underserved by approved amyloid-directed therapies today. As of the July 22nd data cutoff date, all 136 safety evaluable patients had been dosed for at least six months. 78% had passed nine months, and 49% had already completed the full 12 months of dosing. Safety was the primary focus of this interim look, given that PMN310 was designed as a non-plaque binding antibody with the goal of significantly reducing the ARIA risk. The results were encouraging. We observed zero cases of ARIA-E, which is the more serious symptomatic form of ARIA involving brain swelling.

This result was noted across all genotypes, including in the ApoE4 homozygote population. Total ARIA, which includes the milder ARIA-H microhemorrhage finding, was 4.4%, and every case was mild and asymptomatic. We saw no treatment-related serious events and no drug-related discontinuations through the interim cutoff, and only one single non-serious infusion reaction, a rate notably lower than the infusion reaction rates reported for approved anti-amyloid therapies in their pivotal trials. These are descriptive comparisons against published data and not head-to-head studies. Directionally, this is a differentiated safety profile, particularly in the ApoE4 carrier population, where approved therapies today carry their most significant warnings. Now with biomarkers, I want to frame this next part carefully because PRECISE-AD remains a blinded ongoing trial, and these are early exploratory signals and are not efficacy readouts. We looked at two complementary biomarkers chosen to bracket different points in the Alzheimer's cascade.

Plasma p-tau217, one of the earliest and best-validated biomarkers of amyloid-driven tau pathology, and CSF-mtVR tau243, a more downstream tangle-specific marker that correlates closely with tau PET imaging and cognitive decline. In untreated placebo arm patients from published natural history data, both markers are expected to rise over time as disease progresses. In our blinded pooled analysis, meaning this combines both drug and placebo-treated patients under the 3-to-1 randomization, we saw the opposite. Plasma p-tau217 declined approximately 15% from baseline. p-tau243 declined by approximately 13.3%, with about 62.5% of patients showing a decline. Both the direction and the proportion of patients showing a favorable response are broadly consistent with the trial's 75% active drug allocation. We think it's notable that both an upstream and amyloid-linked biomarker and a downstream tangle-specific biomarker moved in the same favorable direction at the same time point.

That consistency is encouraging, although again, this remains a blinded interim look, and it is not a determination of clinical efficacy. The trial is ongoing and remains blinded. We anticipate all patients to complete their 12-month dosing by the fourth quarter of this year, and following database lock and statistical analysis, we expect to report unblinded 12-month top-line data in the first quarter of 2027. That readout will include the full safety data set, a more detailed biomarker panel, and for the first time, we will also report on clinical cognitive outcome measures, which will let us assess PMN310's efficacy in a controlled and unblinded setting. With that, I'll hand it back to Neil.

Thanks very much, Larry. Again, a very encouraging set of interim data. Thanks for the presentation. Beyond PMN310, as I touched on earlier, our broader pipeline continues to advance. PMN267, our program targeting misfolded TDP-43 in ALS, has been humanized in an IgG1 framework and is progressing towards IND-enabling studies. PMN442, our lead candidate for dementia with Lewy bodies and Parkinson's disease, potentially other synucleinopathies, has also been humanized and is advancing towards IND-enabling studies based on its selective binding to pathogenic alpha-synuclein. Behind those, we continue to advance our vaccine program in Alzheimer's disease, ALS, and Parkinson's, and are further developing our EpiSelect discovery platform, in which we are incorporating machine learning to accelerate identification of new disease-specific epitopes. Just turning to the financial results briefly.