9/28/26 +5% since 7/1

Summary of Main Points (Daybreak Topline Discussion; Wet AMD and Implications)

Shift Toward More Personalized Wet AMD Treatment

• Speakers emphasized that wet AMD is heterogeneous, not a single uniform disease.
• IL-6 pathway inhibition (tarosemab / Zancuda) was framed as potentially useful for a broader set of patients.
• At the same time, speakers noted responses may vary depending on underlying biology, including whether an inflammatory component is present.

Trial Performance: “Drying” and Extended Dosing vs Fixed Monthly

• The program’s key value was presented as demonstrating non-inferiority/equivalence to aflibercept-type comparators during the loading phase.
• A major benefit highlighted was enabling many patients to extend dosing intervals.
• Speakers attributed the ability to extend treatment intervals to an expected extension of intraocular half-life, helping patients go longer between injections than with existing biologics.

Retreatment Approach Designed to Mirror Real-World Practice

• A differentiator was the retreatment algorithm:
  • Retreatment was triggered by presence of intraretinal/subretinal fluid.
  • Thresholds were described as close to real-world practice, rather than requiring major vision loss milestones.
• Unlike many trials that rely on vision acuity loss and/or large anatomic worsening thresholds, this study used fluid presence/absence.
• The approach was described as more aligned with how retina specialists manage patients, including treat-to-dry and extending intervals based on anatomic recurrence.

Who Might Benefit Most / Inflammatory Subgroup Uncertainty

• On whether “difficult-to-treat” wet AMD patients with inflammatory components could benefit from IL-6 inhibition:
  • Speakers acknowledged that such inflammatory patients likely exist.
  • However, the specific subgroup(s) and the magnitude of benefit remain to be determined through further analyses.
• Broad population benefit was considered plausible because the regimen is designed for durability/interval extension, not solely for inflammation-driven disease.

Real-World Expectations and Potential Mismatch

• Participants suggested clinicians may, in practice, treat with slightly less medication than trials permit, since routine care may differ from trial fluid-detection thresholds.
• Outcomes may also differ between:
  • Treatment-naïve patients, who may require less frequent dosing if durability holds
  • Previously treated patients, whose response patterns may not match naïve expectations

Interpretation of OCT/BCVA Statistics and Comparisons

• Questions were raised about whether OCT graph labeling versus table statistics drove apparent discrepancies.
• Clarifications included that differences relate to:
  • Observed mean change versus model-based estimates (e.g., least squares / MMR)
  • Baseline alignment differences across arms
  • The use of independent statistical models
• Speakers stated the statistical results were consistent with the predefined analysis plan.

Development Implications Beyond Wet AMD

• The discussion extended to expectations for DME (diabetic macular edema) and other inflammatory macular edema settings:
  • DME was characterized as more likely to include inflammatory components, making IL-6 inhibition potentially more compelling.
  • The panel expected DME outcomes may still be comparable in mean terms to standard therapy, but with possible subpopulation advantages.
• Data were positioned as reinforcing the development pathway.
• Subsequent readouts were noted as including KSI 101 and Messi, described as targeting related but distinct mechanisms/patient populations.

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Presenters / Contributors Mentioned

• Anupam Rama (JP Morgan; interviewer/questioner)
• Charles Woff(e) (presenter; addressed IL-6/inflammation and wet AMD questions)
• Dr. Brown (presenter; discussed “real-world criteria” and alignment with clinical practice)
• Dr. Wickoff (presenter; involved in treatment criteria/durability discussion)
• Dave (speaker; referenced retreatment algorithm, half-life, and AI/data unpacking — full name not provided in subtitles)
• Pablo Vasquez Martin (presenter; addressed mechanism/subgroup and program direction questions)
• Victor (presenter; provided a thank-you/positioning overview — full name not provided in subtitles)
• Mori Ray (questioner; Evercore ISI context)
• Michael Ye (questioner; UBS context)
• Omar Rafat (questioner; Evercore ISI context)
• Keith (mentioned casually at the end; “Shellyville” comment)
• Marl(i)n Faza (questioner/mentioned regarding OCT graph clarification — exact affiliation unclear from subtitles)