Ocular Therapeutix – Piper Sandler Fireside Chat - OCULAR THERAPEUTIX INC

Explicit Guidance:

• NDA Filing: Submission of the New Drug Application (NDA) for Xpaxly in Q4 2024.
• Commercial Launch: Potential commercial launch of Xpaxly in the second half of 2025.
• Cash Runway: Guidance remains unchanged; approximately $600M in cash and cash equivalents sufficient to reach 2028 on a conservative basis.
• Regulatory Milestone: Two-year data readout for the SOL1 trial expected in Q1 2028.
• Future Guidance: Management intends to provide specific enrollment and data timing guidance for the HELIOS 3 trial (diabetic retinopathy) after the NDA filing and acceptance (post-2024).

Business-Segment Outlook:

• Xpaxly (AMD):
  • Label Expectations: Anticipates the first and only superiority label with flexible dosing ranging from 6 to 12 months and repeat dosing.
  • Safety Monitoring: Expects no specific post-market safety monitoring requirements on the label due to the robust safety profile.
  • Patient Population: Positioned as a maintenance drug (treating to dry), contrasting with bolus competitors; data shows two-thirds of patients in the difficult-to-treat population last 12 months without rescue.
  • Diagnostic Criteria: Utilization of a strict "dryness" definition (<10 nanoliters of fluid), with a 75% chance of an eye remaining dry for 9 months after a single injection post-loading.
• Diabetic Retinopathy (HELIOS 3):
  • Market Opportunity: Market size estimated at 3.5x larger than wet AMD; aims to treat both diabetic retinopathy and diabetic macular edema.
  • Treatment Paradigm: Anticipates a shift to once-yearly injection frequency (similar to dental cleanings) to address the "asymptomatic nature" of the disease and improve compliance.
  • Endpoint Strategy: Utilizes a validated ordinal endpoint where patients have "three shots on goal," aiming for a 0% rate of visual-threatening complications (vs. ~38% in controls).
• Xpaxly (Diabetic Retinopathy): The FDA has granted a Special Protocol Assessment (SPA) for the HELIOS 3 program.

Market and Competitive Outlook:

• Competitive Landscape (AMD):
  • Primary Competitor: iPoint (Lugatozan) is effectively removed from competition due to failed trials and lack of regulatory approval; Ocular has no direct competition in the maintenance drug space.
  • Bolus vs. Maintenance: Positions Xpaxly as a maintenance drug, whereas competitors like Kodiak (Tarkozyma) and others (Ilea, Vabistimo, Lucentis) are bolus injections.
  • Kodiak Assessment: Dismisses Kodiak's data as having an undefined "PRN regulatory path" (treat until well) and questions their definition of dryness and safety data transparency; expects Kodiak to compete against existing bolus drugs rather than Xpaxly.
• Future Pricing: Anticipates securing premium pricing due to the superiority label and unique maintenance positioning.
• Gene Therapy: Views gene therapy as a distant, high-bar competition; notes that irreversible genetic intervention requires "perfection" over the patient's lifetime (10-20 years), which is difficult to achieve when effective annual maintenance drugs exist.

Macro / Industry Outlook:

• FDA Leadership Change: Expects zero impact from the retirement of Dr. Bill Boyd and the appointment of Dr. Rhea Loy; confirms Dr. Lloyd is lockstep with previous FDA direction and has signed off on all prior milestones.
• Competitor Data Influence: States that external negative data from iPoint or positive data from Kodiak has no influence on the FDA's decision for Xpaxly, as the FDA evaluates raw submitted data, not press releases or market noise.
• Class Effect: Dismisses concerns regarding class effects for TKIs; notes that other anti-VEGF approvals have not been blocked by failures of other drugs in the class.

Strategic Initiatives:

• NDA Strategy: Pursuing a single-trial submission (SOL1) based on FDA collaboration; explicitly avoiding early readout of the SOLAR trial to prevent a major regulatory amendment and review restart.
• Inventory & Operations: Commercial preparation is complete with sufficient inventory and personnel (led by David Robinson) for a 2025 launch.
• Regulatory Protection: Preserving the integrity of the ongoing SOLAR trial specifically for non-U.S. regulatory agencies (O.U.S.), though it is not required for U.S. approval.
• Expansion: Scaling up for future launch of diabetic retinopathy indications; preparing for potential presentation at the OSN meeting in New York (November).

Risks and Headwinds to Outlook:

• SOLAR Trial Readout Risk: Disclosing SOLAR data prematurely during the FDA review of SOL1 could force a major amendment, resetting the regulatory clock and delaying approval.
• Regulatory Scrutiny: Risk of FDA requesting SOLAR data (considered "extraordinary unlikely" but mitigated by having the data ready).
• Patient Compliance (Diabetic): Potential headwind for HELIOS 3 is the asymptomatic nature of diabetic retinopathy; relies on the "rebound effect" risk and payer-driven enrollment to ensure adherence to once-yearly treatment.
• Enrollment Constraints: HELIOS 3 enrollment requires strict patient selection (windowing disease severity) to capture a treatment effect, which may slow enrollment speed despite high global interest.

Management Tone on the Future:

• Confidence Level: High confidence; repeated emphasis that "nothing has changed" internally despite external market volatility or FDA leadership transitions.
• Strategic Discipline: Firm commitment to single-trial submission to avoid regulatory delays; willing to delay data disclosure (e.g., HELIOS 3 details) to protect FDA relationships.
• Defensiveness: Strongly defensive against investor concerns regarding competitor failures (iPoint) and the TKI class history, attributing past failures to route of administration and poor patient selection, not the drug class itself.
• Clinical Focus: Emphasizes clinical data (patient-level safety, OCT control) over marketing narratives; notes that "nobody gives patient-level data" as a differentiator.

Miscellaneous:

• Data Disclosure Plans: No immediate commitment to release SOL1 Year 2 data in the near term to avoid jeopardizing the NDA review process.
• AAO Data: Highlights new retrospective analysis showing 75% chance of 9-month dryness with a single injection under strict criteria (<10 nl).
• Leadership Transition: Confirms Dr. Rhea Lloyd's involvement in all previous meetings and SPA approvals, ensuring regulatory continuity.
• Valuation Comment: CEO acknowledges current stock valuation does not reflect the diabetic retinopathy opportunity and plans to focus communication on this area post-2024.