STIFEL 2026 HEALTHCARE CONFERENCE - PROMIS NEUROSCIENCES INC

Financial Performance:

• No specific quarterly revenue, earnings, or cash flow figures disclosed; company is well-funded beyond the end of next year following a recent financing round.
• Financing secured from top-tier investors including Ally Bridge, Janus, Wellington, and DeepTrack.
• Company is publicly listed under the ticker PMN (Promise Neuroscience).

Guidance and Future Outlook:

• Primary catalyst: Top-line data from the Phase 1b Alzheimer's clinical trial expected in Q1 of the following year (final data readout in Q2).
• Long-term goal: Materially improve the risk-benefit profile compared to current market leaders (lecanemab, donanemab) by drastically reducing ARIA (amyloid-related imaging abnormalities) side effects.
• Future target population expansion: Potential to expand from Mild Cognitive Impairment (MCI)/Early AD to preclinical/asymptomatic populations if safety profile is superior.
• Strategic priority: Achieve speed to market by planning Phase 3 registration trials concurrently with the current Phase 1b study.

Business Segments and Product Lines:

• Core Technology: "EpiSelect" platform designed to selectively target misfolded protein species (toxic oligomers) rather than amyloid plaques.
• Lead Asset: PMN310, an IgG1 antibody designed to bind toxic oligomers and recruit microglia for clearance, distinct from the IgG2 backbone of competitor Acumen (ACU193).
• Differentiation: PMN310 binds selectively to oligomers without binding to plaques or monomers, theoretically eliminating the specific ARIA risks associated with plaque targeting.
• Pipeline Development: Concurrently developing a subcutaneous (Sub-Q) formulation to improve patient administration; Chief Commercial Officer Dr. Rubino (former Biogen/Roche executive) has been hired to lead commercialization and Phase 3 design.

Market and Competitive Landscape:

• Market Context: Current Alzheimer's drugs suffer from poor risk-benefit profiles (20-30% ARIA incidence) and moderate efficacy, limiting patient uptake to ~5% of the addressable population.
• Competitive Set: Competitors including Acumen (ACU193), Eisai, Biogen, and Eli Lilly are developing amyloid-targeting agents.
• Differentiation Strategy: Promise Neuroscience positions PMN310 as the only drug selectively targeting toxic oligomers while avoiding plaque binding, aiming to eliminate ARIA liability (specifically edema/REE) that plagues competitors.

Risks and Challenges:

• Clinical Risk: The success of the Phase 1b trial is critical; if efficacy signals (15-20% slowing of cognition) or safety targets (ARIA rates near placebo) are not met, further development could be jeopardized.
• Trial Limitations: The Phase 1b study is smaller (144 patients) than typical Phase 3 trials (~1,500 patients) and is not statistically powered to demonstrate definitive efficacy (p<0.05) but rather to detect trends and ARIA incidence.
• Safety Concerns: While interim data shows zero cases of brain edema (ARIA-E), the full 12-month data is required to confirm the absence of hemorrhage (ARIA-H) and long-term safety.
• Biomarker Assay Complexity: Historically, there have been no assays to measure oligomer levels in humans; Promise has developed a proprietary assay to validate mechanism of action within the trial.

Management Commentary and Tone:

• CEO Neil Wormer and CMO Dr. Larry Alsteele displayed high confidence in the platform's ability to solve the selectivity and safety issues of the field.
• Management expressed strong enthusiasm regarding interim data (July 2023), specifically the zero cases of ARIA-E and favorable biomarker trends at the 6-month mark.
• Tone was defensive yet assertive regarding competitor failures (specifically Acumen), attributing their lack of efficacy to non-selective binding and IgG2 backbones that fail to clear oligomers.
• Emphasis placed on the "risk-benefit" rebalancing as the primary driver of regulatory and market success.

Analyst Questions and Answers:

• Q: Differentiation from Acumen given their recent disappointing data?
  • A: Acumen's antibody is not purely selective (binds plaque/multiple species) and uses an IgG2 backbone that does not elicit an immune clearance response; Promise's IgG1 backbone recruits microglia to clear oligomers.
• Q: Can PMN310 prove it binds oligomers in humans?
  • A: Yes; the company developed a proprietary assay to measure circulating oligomers pre- and post-treatment, which will be utilized in the Phase 1b study.
• Q: What efficacy results are needed to move forward?
  • A: A base case of 15-20% slowing of cognition (vs. placebo) and ARIA rates reduced to near placebo levels; anything above 20% separation is upside.
• Q: Will PET scans be used to measure plaque changes?
  • A: Yes, but minimal changes are expected since the drug does not target plaque; PET is used to confirm target engagement and rule out off-target effects.
• Q: What are the next steps if data is positive?
  • A: Initiate Phase 3 registration trial design immediately, submit data to FDA, and utilize the Sub-Q formulation for market launch.

Other Key Points:

• The Phase 1b study was fully enrolled (144 subjects, 3:1 active:placebo) ahead of target due to high physician interest in a safer alternative.
• Interim analysis at 6 months showed zero cases of ARIA-E (edema) and zero discontinuations due to treatment-related adverse events.
• Biomarkers P-tau 217 and neurofilament light chain (NfL, referred to as MTBR in transcript) showed a decrease from baseline, contrary to the typical increase seen in untreated patients.
• The study includes APOE4 heterozygotes and homozygotes, the population most at risk for ARIA.
• Management emphasized that current market drugs require ~6 MRIs in the first year; the goal for PMN310 is to reduce this to 1-2 MRIs due to the absence of ARIA.