STIFEL 2026 HEALTHCARE CONFERENCE - 4D MOLECULAR THERAPEUTICS INC

Explicit Guidance:

• No financial guidance (revenue, earnings, margins, capex, etc.) provided.
• Cash Runway: Expected to extend into the second half of 2028.
• Clinical Milestones: Top-line readouts for both Phase 3 trials (Forefront 1 and Forefront 2) expected in 2027; Forefront 1 results in Q2 2027, Forefront 2 in H2 2027.

Business-Segment Outlook:

• Lead Program (4D150): Positioning as a "backbone therapy" for wet age-related macular degeneration (wet AMD) with potential for "lifelong continuous disease control" from a single intravitreal dose.
• Target Product Profile: Aims to allow some patients to be injection-free for life; addresses unmet need of preserving vision and reducing treatment burden compared to current episodic bolus injections.
• Phase 2 Data Reference: Out to two years, recent diagnoses showed 1.6 supplemental injections on average, representing an 87% treatment burden reduction vs. standard of care (q8 weeks Ilea), with 66% injection-free.
• Phase 3 Enrollment: Trials (Forefront 1 & 2) fully enrolled; Majority of patients are treatment-naive (first interventional gene therapy in this population).
• Reimbursement Model: Anticipated to utilize a "buy and bill" model familiar to retina clinics, with pricing expected to be significantly higher than a single bolus anti-VEGF dose.

Market and Competitive Outlook:

• Market Size: Wet AMD described as a $16 billion category driven by an aging population and new innovative therapies.
• Competitive Landscape:
  • Regenexx: Expects data later this year; differentiates via subretinal surgery (OR-based) vs. 4DMT's intravitreal (clinic-based) delivery.
  • Adverum/Lilly: Intravitreal approach noted but distinguished by a high-dose strategy vs. 4DMT's low-dose; concerns raised regarding potential inflammatory events compared to 4DMT's R100 capsid profile.
• Therapeutic Paradigm Shift: Moving from "incremental durability gain" (weeks/months) to "continuous disease control" (24-7 backbone therapy).
• Physician Adoption: Anticipates broad adoption due to reduced clinic capacity strain; 40% of retina docs currently report clinics are at capacity.
• Long-term Patient Retention: Notes that in current paradigms, up to 60% of patients stop therapy within 5 years; 4D150 aims to capture this value loss through a single-dose solution.

Macro / Industry Outlook:

• Regulatory Environment: Supportive interactions with FDA (RMAT designation), EMA (PRIME designation), and PMDA; trials powered for non-inferiority of vision at Week 52.
• Industry Dynamics: Busy marketplace due to significant unmet needs; focus on aligning therapy duration with the chronic, variable nature of wet AMD.

Strategic Initiatives:

• R100 Capsid Development: Proprietary vector enabling low-dose, targeted retinal delivery with minimal toxicity/inflammation potential.
• Trial Design Optimization:
  • Enrolling treatment-naive patients (aligns with FDA requirements for vision benefit).
  • Anatomical entry caps at 500 microns; requires 15% CST reduction or fluid resolution for randomization to reduce variability.
  • Rescue criteria designed to protect primary vision endpoint (5-letter loss + 50-micron anatomy increase OR 10-letter loss / 100-micron anatomy increase).
• Safety Protocol: Implementation of a 20-week prophylactic Durazol (steroid) regimen; early phase data showed no serious adverse events post-treatment period.
• Commercialization Strategy: Single in-office intravitreal injection designed to fit seamlessly into busy retina clinic workflows.

Risks and Headwinds to Outlook:

• Safety/Inflammation: Acknowledges historical issues with gene therapy (e.g., inflammatory events); potential for safety profile deviations despite low-dose R100 capsid and prophylactic steroids.
• High-Dose Competitor Risks: Concerns regarding safety profiles of high-dose competitors (Adverum/Lilly).
• Physician Adoption Barriers: Potential hesitancy regarding the 20-week prophylactic steroid regimen, though management notes current patient/physician receptivity is high.
• Economic Uncertainty: Final pricing not yet determined; need to establish value proposition vs. current buy-and-bill models.
• Trial Outcome Binary: Phase 3 non-inferiority result is a binary pass/fail scenario for vision endpoints; retreatment rates in trial (targeting 80-90% burden reduction) are not guaranteed.

Management Tone on the Future:

• High Confidence: Describes 4D150 as having the "potential to establish a new treatment paradigm" and "completely change" clinical practice.
• Optimism on Adoption: Believes the therapy could become the "backbone, basal type of approach for the majority of patients" with wet AMD.
• Differentiation Emphasis: Stresses that unlike competitors focusing on incremental durability, 4DMT offers a fundamental shift to continuous control.
• Caution on Specifics: Hesitates to provide specific retreatment rate numbers for Phase 3 to avoid "binary conversation," but references Phase 2 data suggesting high 80s% burden reduction for recent diagnoses.

Miscellaneous:

• Investor Timeline: Key investor focus expected over the next 6-12 months leading up to the 2027 readouts.
• Clinical Evidence: Phase 2 "PRISM" study highlighted as proof of concept for the "continuous control gap" solution.