STIFEL 2026 HEALTHCARE CONFERENCE - PROMIS NEUROSCIENCES INC

Explicit Guidance:

• Data Readout: Top-line data from the Phase 1b trial (PMN310) expected in Q1 of next year, following completion of patient dosing and final visits in Q2 of the current year.
• Financial Runway: Company is well-funded, with financing from Ally Bridge, Janus, Wellington, and DeepTrack sufficient to extend operations well beyond the end of next year.
• Future Study Design: Planning ongoing for a Phase 3 registration study, to be designed following Q1 data readout and subsequent FDA feedback meetings in the coming year.
• Commercial Launch: Targeting a launch with a subcutaneous (Sub-Q) formulation; Phase 3 initiation expected immediately following positive Q1 data.

Business-Segment Outlook:

• Therapeutic Focus: Continued focus on neurodegenerative diseases, specifically Alzheimer's disease, targeting toxic amyloid beta oligomers.
• Pipeline Inflection Points: Immediate catalyst is the Q1 Phase 1b readout; success is defined by meeting specific safety (ARIA reduction) and efficacy (15–20% slowing of cognition vs. placebo) criteria to proceed to registration.
• Formulation Strategy: Active development of a Sub-Q formulation to enable a market launch with improved administration; this is prioritized alongside the IV trial success.
• Patient Population Strategy: Initial commercial focus on Mild Cognitive Impairment (MCI) due to Alzheimer's (early AD); long-term expansion planned into preclinical/asymptomatic populations if the safety profile holds.
• Clinical Trial Metrics: Study powered 95%+ to detect even a single case of ARIA; expected efficacy signal in the range of 15–20% slowing of cognition compared to placebo at 12 months.

Market and Competitive Outlook:

• Competitive Differentiation: Claims to be the only antibody selectively binding toxic oligomers without binding plaques or monomers, differentiating from Acumen (ACU193), Lecanemab, and Donanemab which bind multiple species.
• Safety Landscape: Anticipates material improvement over current market leaders by significantly reducing the incidence of Amyloid-Related Imaging Abnormalities (ARIA), specifically ARIA-E (edema) and ARIA-H (hemorrhage), which currently limit adoption of existing therapies to ~5% of the addressable population.
• Adoption Drivers: Success hinges on rebalancing the risk-benefit profile; specifically, reducing the need for six annual MRIs (required with current drugs) to one or two annually, and eliminating serious safety events like ARIA-E.
• Market Expansion: Seeks to capture the preclinical/asymptomatic segment (currently pursued by Lilly, Acumen, and Roche) where current high ARIA rates deter patient participation.

Macro / Industry Outlook:

• Regulatory Strategy: Plans to engage with the FDA in the coming year post-Q1 data to align on Phase 3 design and registration pathways.
• Industry Trends: Acknowledges a shift in the field toward upstream oligomer targeting rather than plaque clearance, though notes industry-wide failure to achieve true selectivity so far.
• Clinical Trial Standards: Indicates a move toward more rigorous safety monitoring in early-stage trials to definitively rule out ARIA liability before scaling.

Strategic Initiatives:

• Leadership Expansion: Recently hired Dr. Rubino as Chief Commercial Officer to lead Phase 3 design, pricing, reimbursement, and global launch strategy; she brings 11 years of Biogen experience (Lecanemab launch) and prior CNS leadership at Roche.
• Platform Validation: Utilization of the proprietary "EpiSelect" platform to design antibodies against conformational epitopes specific to misfolded proteins; ongoing validation of a new biomarker assay to measure circulating oligomers in clinical settings.
• Trial Execution: Completed enrollment of 144 subjects (exceeding target of 128) in a placebo-controlled, double-blind, randomized, 12-month, IV dosing study across the U.S.
• Interim Analysis: Completed blinded interim analysis at 6 months showing zero cases of ARIA-E, zero serious adverse events related to treatment, and zero discontinuations.

Risks and Headwinds to Outlook:

• Clinical Failure Risk: The Q1 top-line data is a binary catalyst; failure to demonstrate efficacy (slowing cognition) or if safety signals (ARIA) emerge above placebo levels would halt progression.
• Statistical Power Limitations: The Phase 1b study (140 patients) is not powered to achieve statistical significance (p-value 0.05) for efficacy; the outcome relies on favorable trends and biomarker movement.
• Regulatory Uncertainty: Success is contingent on FDA acceptance of the Phase 1b data as sufficient to trigger a registration study; the agency may request further data or different trial parameters.
• Competitive Pressure: High ARIA rates in the broader market (Lilly, Roche, Acumen) create a high bar for patient enrollment in the potential preclinical segment.

Management Tone on the Future:

• Confidence Level: Highly confident and enthusiastic, describing the interim safety data as "absolutely superb" and the drug's selectivity as a "huge win" that materially changes the risk-benefit ratio.
• Caveats/Hedges: Management emphasizes the need to keep the "12-month, 140-patient" context in perspective against the 18-month, 1,500-patient studies of competitors; explicitly states they are not expecting p-value 0.05 on efficacy.
• Strategic Focus: Tone is heavily weighted on "speed to market" and "unmet medical need," with a clear emphasis on solving the ARIA problem as the primary value driver over marginal efficacy improvements.
• Prior Guidance: No changes to prior financial guidance mentioned (as none was explicitly provided), but the strategic narrative has reinforced the focus on the Q1 readout as the critical near-term event.

Miscellaneous:

• Assay Development: Development of a novel assay to measure circulating oligomers is complete and will be integrated into the clinical study to prove mechanism of action.
• Biomarker Focus: Tracking of P-tau 217 and MTBR biomarkers showing downward trends (reduction) from baseline at 6 months, contrasting with the expected increase in untreated patients.
• ARIA Context: Notes that 95% of ARIA cases in prior drugs (Lecanemab/Donanemab) occur in the first six months; current trial data at 6 months shows zero ARIA-E cases.