GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - OCULIS HOLDING AG

Financial Performance:

• Maintained $252 million in cash on hand as of late September, excluding a separate $100 million debt facility with BlackRock.
• Current liquidity runway extends into the second half of 2029.
• Cash reserves are sufficient to fund the full execution of the PREDICT-1, Pioneer 1, Pioneer 2, and Pioneer 3 trials.
• Anticipated clinical trial costs are significantly lower than industry standards (approx. $10 million per trial) due to biomarker-enriched patient selection.

Guidance and Future Outlook:

• Top-line results for the PREDICT-1 trial are expected in a matter of weeks.
• Full regulatory submission confirmation for the Neuro-indication (Acute MS relapse) IND is anticipated within upcoming days/weeks.
• R&D Day scheduled for December 8th will provide updates on Pioneer One execution, timing for PREDICT-1, and the multi-indication blueprint for Prevom.
• Strategic goal to transition from "trial and error" to "test and treat" in dry eye disease to improve payer access and patient adherence.
• Aims to finish the current fiscal year with 50% site activation for Pioneer One (targeting 30 out of 60 total sites).

Business Segments and Product Lines:

• Likaminimab (Anti-TNF): Precision medicine ophthalmic product targeting TNFR1-positive patients; 176 patients enrolled in PREDICT-1 trial (2/3 are TNFR1 genotype).
  • Phase 2 data indicated TNFR1 patients had 5-6x better response in signs compared to all-comers.
  • Target market of 1.5 million moderate-to-severe dry eye patients in the US.
  • Potential peak revenue estimated higher than current market leaders (e.g., Mibo, Restasis) due to superior efficacy and adherence, assuming comparable pricing (~$900–$1,000/month).
• Prevom (Neuro-protection): Late-stage asset focused on three orphan indications: Optic Neuritis, NAON, and Acute MS relapse.
  • Pioneer 1 (Optic Neuritis): Tracking on plan; Phase 2 "ACQUITY" data showed 18-letter LCVA improvement, structural preservation (GCIPL/RNFL), and reduced biomarkers (neurofilament/GFAP).
  • Pioneer 2 & 3: Required for NDA approval; Pioneer 3 will also support the Acute MS Relapse indication.
  • Acute MS relapse IND expected Q4 or next month, leveraging existing Phase 2 data in MS populations.

Market and Competitive Landscape:

• Targeting a $900 average monthly price point for dry eye treatments, though potential for higher pricing exists given superior efficacy.
• Current market leaders (Restasis, Mibo) face low patient adherence (10-15% retention at 6 months); Likaminimab aims to double or triple value per patient through higher responder rates.
• Prevom addresses the "oldest" unmet need in Neuro-Ophthalmology: the first neuroprotective drug for Optic Neuritis.
• Utilizes OCT imaging (2-micron precision) for clinical endpoints, offering faster data generation (4 weeks vs. 4 years for MRI) compared to traditional neurology endpoints.

Risks and Challenges:

• High placebo response rates in dry eye disease, necessitating strict screening (run-in period with artificial tears) and threshold-based randomization (discomfort score > 60).
• Regulatory uncertainty regarding the exact number of studies required for approval (base case scenario is 2 symptom + 2 sign trials, though FDA negotiation is pending).
• Market adoption risk dependent on successful payer acceptance of precision medicine testing (TNFR1 genotyping).
• Seasonal variability in Optic Neuritis and MS relapse rates affecting enrollment pacing in Pioneer 1.

Management Commentary and Tone:

• Tone is highly confident and optimistic, emphasizing the efficiency of their precision medicine approach and the "unmet need" in orphan indications.
• CEO Riyadh Sharif highlighted the "two shots on goal" for Prevom (treatment + measurement model) and the transformative potential of moving from trial-and-error to test-and-treat in dry eye.
• Management emphasized the rapid patient screening and enrollment speeds achieved in recent studies.
• Expressed strong conviction that the TNFR1 biomarker allows for significantly smaller, faster, and cheaper Phase 3 trials compared to the industry standard of 2,000 patients per trial.

Analyst Questions and Answers:

• Q: Phase 2 data perspective? A: TNFR1 patients showed 5-6x improvement in signs vs. all-comers; PREDICT-1 expects similar or higher efficacy in this enriched population.
• Q: Study design and placebo? A: Addressed via 2-week run-in, symptom thresholds, and TNFR1 enrichment; 2/3 of PREDICT-1 cohort is TNFR1 positive.
• Q: Success criteria? A: Aim to double the Phase 2 effect size (approx. 4.3 points) in TNFR1 patients; responder rate target >25% (50% more than current competition).
• Q: Regulatory path for Prevom? A: FDA accepts month-3 endpoint; requires 300 patients exposed (2 studies needed); Pioneer 3 will serve dual purpose for Optic Neuritis and Acute MS Relapse.
• Q: Financial runway? A: Cash on hand + debt facility covers operations through H2 2029, securing funding for all planned trials.

Other Key Points:

• Likaminimab is a fragment antibody with high ocular tissue penetration.
• The 1.5 million patient addressable market represents 15% of the total dry eye population (30-40 million), specifically those who are moderate-to-severe and TNFR1 positive.
• The Acute MS relapse indication is directly supported by data showing Prevom efficacy in the MS subset of the Optic Neuritis trial.
• Clinical trial efficiency is a key competitive advantage, reducing total patient exposure from ~2,000 to ~650 for the full program.