GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - OCULIS HOLDING AG

Explicit Guidance:

• Cash Runway: As of end of September, the company holds $252 million in cash (excluding a $100 million Swiss debt facility with BlackRock), providing a runway through the second half of 2029.
• Financial Efficiency: Anticipated Phase 3 costs for the Licaminimab program (four trials: two symptom, two sign) are projected to be under $10 million per trial due to biomarker-enriched patient selection, targeting a total patient pool of ~650 versus the typical 2,000 patients required for standard dry eye trials.
• Pricing Assumptions: Management assumes a pricing range of $900 to $1,000 per month (annualized $10,800–$12,000) for Licaminimab, comparable to current market leaders (Mibefradil, Restasis, Xyris) which range from $132 to $1,004 per month annually.

Business-Segment Outlook:

• Licaminimab (Dry Eye Disease):
  • Timeline: Top-line results expected in "a matter of weeks" following the completion of the PREDICT-1 study enrollment (176 patients, ~160 randomized); further execution details to be unveiled at the R&D day on December 8.
  • Target Population: Focuses on 1.5 million patients in the US (13–19% of the 40 million dry eye patients) who are TNFR1 genotype-positive, moderate-to-severe (score >60), and unresponsive to artificial tears.
  • Efficacy Targets: Expects the primary efficacy endpoint (discomfort scale improvement) to double or increase by 50% compared to Phase 2 "all-comers" data (where drug-placebo difference was 4.3 points), targeting a responder rate (gain >20 points) of >25% (vs. 18% in Phase 2) in the TNFR1 cohort.
  • Strategic Shift: Aims to transition the market from "trial and error" to "test and treat" via a rapid saliva/sweat test for TNFR1, predicting higher adherence and revenue potential (2x–3x value per patient) compared to current competitors due to superior efficacy.
• Pivomec (Neuroprotection):
  • Indication Expansion: Three primary programs: Optic Neuritis (Orphan, no current treatment), NAION (Orphan, increasing due to therapy complications), and Acute MS Relapse.
  • PIONEER Program:
    • PIONEER 1 (Optic Neuritis): Enrollment tracking on plan; goal to activate 30 of 60 sites by year-end to align with seasonal relapse surges in December and May. Requires two studies (PIONEER 1 and PIONEER 2) for Optic Neuritis approval.
    • PIONEER 2 (MS-specific Optic Neuritis): Supports MS population labeling.
    • PIONEER 3 (Acute MS Relapse): IND submission for acute MS relapse expected in the fourth quarter (next month); study design to be a 3-month endpoint using the same regimen/dose as PIONEER 1, requiring one study for approval (supported by PIONEER 2 and PIONEER 3 data).
  • Biomarkers: Utilization of OCT (2-micron precision) and neurofilament/GFAPs to demonstrate structural and functional neuroprotection; FDA has accepted 3-month endpoint for Phase 3 in acute MS relapse.

Market and Competitive Outlook:

• Dry Eye Market: Seeks to displace market leaders (Restasis, Xyris, Mibefradil) by offering a precision medicine approach; anticipates that current competitor attrition rates (only 10–15% of patients remain on therapy after 6 months) will be reversed by Licaminimab's higher responder rates, driving superior long-term revenue capture.
• Orphan Indications: Optic Neuritis and NAION are identified as high-value, untreated markets targeting young adults and specific MS complications, offering potential for premium pricing and rapid market penetration due to lack of competition.

Macro / Industry Outlook:

• Regulatory Pathways: Management notes high confidence in accelerated pathways, citing FDA acceptance of 3-month endpoints for acute MS relapse and the ability to conduct smaller, more efficient Phase 3 trials due to biomarker stratification.
• Reimbursement Strategy: Anticipates that payers will favor the "test and treat" model, as genotyping ensures a higher likelihood of response, improving cost-effectiveness compared to empiric treatment of the broader dry eye population.

Strategic Initiatives:

• R&D Day: Scheduled for December 8 to provide updates on PIONEER 1 execution, timing adjustments for PREDICT 1, and a comprehensive blueprint for multiple neuro-ophthalmology indications.
• Trial Efficiency: Implementation of a two-week artificial tear run-in period and baseline symptom thresholds (>60 points) to filter placebo responders and enrich the patient pool with TNFR1-positive subjects (2/3 of PREDICT 1 cohort), reducing trial size and cost.
• Labeling Strategy: Aiming for dual labels in Optic Neuritis (via PIONEER 1 for all-comers and PIONEER 2 for MS patients) and Acute MS Relapse (via PIONEER 3), supported by the same molecular entity.

Risks and Headwinds to Outlook:

• Regulatory Negotiation: The exact number of required studies for Dry Eye approval (base case is 2 symptom + 1 sign; potential expansion to 2+2) remains subject to FDA negotiation following the PREDICT 1 results.
• Placebo Effect: Acknowledges the high placebo response rate in dry eye disease; the efficacy of the biomarker-enrichment strategy to overcome this is a key variable in the December data readout.
• Seasonality: Optic Neuritis relapses are seasonal (peaking Dec/May); delays in site activation or enrollment could hinder meeting the critical mass needed to capture the December/May wave.
• Execution Risk: Dependence on the rapid rollout of the TNFR1 saliva/sweat test for patient identification and the timely confirmation of the IND for the MS indication.

Management Tone on the Future:

• Confidence: High confidence in the biological data and operational execution, describing the PREDICT 1 enrollment as "extremely fast" and the Phase 2 efficacy data as "meaningful" and "exceptional."
• Optimism: Management expresses strong belief that Licaminimab's value story is "much stronger" than competitors due to precision medicine mechanics, predicting significantly higher adherence and revenue potential.
• Clarity: Tone shifts from general pipeline updates to specific quantitative targets (e.g., doubling efficacy, under $10M/trial cost, specific site activation goals), indicating a clear, near-term catalyst-driven outlook.

Miscellaneous:

• Investment Thesis: The company positions itself as a mid-term value driver driven by the Licaminimab readout and the multi-indication potential of the Pivomec portfolio, with a clear path to commercialization by 2029.
• Competitive Landscape: Management explicitly contrasts their 650-patient trial requirement against the industry standard of 2,000 patients, highlighting capital efficiency as a competitive advantage.