Vera Therapeutics - October 22 Investor Webcast - VERA THERAPEUTICS INC

Explicit Guidance:

• Regulatory Submission: Supplemental BLA (sBLA) for Atacicept (TruTacna) to be submitted "this quarter" (Q4 2024) to support full approval.
• Approval Timeline: Anticipates FDA review of sBLA leading to full approval and an updated label in the "middle of 2027."
• Commercial Updates: Third-quarter financial results and first earnings call update scheduled for "November."
• Future Dosing Data: Results from a dose range/frequency study investigating monthly dosing of Atacicept expected to be generated "this quarter" and shared when appropriate.
• Data Release: Publication regarding preferred clinical trial design (52-week GFR endpoint) expected to be released in the near future following meetings with FDA/regulators.

Business-Segment Outlook:

• Commercial Inflection: Anticipates a "nice inflection point" in commercial uptake following the 2027 full approval, which will unlock the ability for the sales force to actively promote the comprehensive dataset and expanded indication.
• Current Commercial Mode: TruTacna is currently in "commercial mode" in the US with restricted detailing limited to the existing accelerated approval label (proteinuria reduction surrogate).
• Future Trials: Continued open-label data collection for ORIGIN-3 participants transitioning to active therapy through week 156, plus an additional open-label extension for Phase 2b/3 patients to monitor long-term efficacy and safety.
• Pipeline Expansion:
  • Adolescents: New data on Atacicept in adolescents with IgA nephropathy released at ASN; additional data presentation scheduled.
  • Membranous Nephropathy: First data for Atacicept in adjacent autoantibody-driven kidney disease (membranous nephropathy) presented at ASN with further results to follow.

Market and Competitive Outlook:

• Treatment Paradigm Shift: Market is moving toward "simultaneous therapy" (disease modification + supportive care) with an expected cessation of "watchful waiting" and no delay in initiating TruTacna for patients with proteinuria >0.5g/day.
• Competitive Validation: Two independent trials targeting BAF and APRIL inhibition (Vera's Atacicept and a competitor) validated treatment effects with "almost to the decimal point" consistency, confirming the dual-inhibition mechanism as a robust strategy.
• Steroid Displacement: Expected rapid decline in steroid usage for IgA nephropathy as TruTacna offers a safer, more effective alternative; steroids viewed as transitioning to the "history books."
• Diagnosis Rates: Anticipates a significant increase in kidney biopsies and earlier diagnosis of IgA nephropathy over the "next couple of years" driven by awareness campaigns regarding genetic risk and the existence of effective therapy.
• Endpoint Standardization: FDA and industry shifting toward 52-week GFR endpoints for approval; Vera's trial design is expected to "trailblaze" this new standard for future IgA nephropathy trials.

Macro / Industry Outlook:

• KDGO Guidelines: KDGO target for treatment success is defined as returning GFR loss to <1 mL/min/year (physiological rate of healthy individuals); current supportive care alone fails to meet this target.
• Regulatory Direction: FDA is adopting 52-week GFR endpoints for future approvals in IgA nephropathy, requiring drugs to demonstrate a "truly transformative" effect to be viable under this shorter timeline.
• Prevalence Awareness: Industry push to educate primary care and ER physicians to identify undiagnosed IgA nephropathy cases (estimated 160k+ biopsy-proven in US, potentially double the conservative estimate) earlier in disease progression.

Strategic Initiatives:

• sBLA Submission: Execution of supplemental BLA filing in Q4 2024 targeting full approval by mid-2027.
• Patient Transition: Immediate conversion of all ORIGIN-3 placebo patients to open-label Atacicept to preserve kidney function, a move agreed upon with the FDA to protect patient safety.
• Trial Design Innovation: Implementation of the 52-week GFR endpoint strategy in ORIGIN-3 to prevent placebo patients from suffering irreversible kidney loss, setting a precedent for future Phase 3 trials.
• Education: Ongoing industry-wide effort to shift treatment philosophy from steroid-based to precise immune modulation, leveraging the B-cell driven pathophysiology of IgA nephropathy.

Risks and Headwinds to Outlook:

• Regulatory Timeline: Full approval and label expansion are dependent on the 2027 sBLA review; delays in FDA review could postpone commercial inflection.
• Clinical Interpretation: Potential for market confusion regarding the interpretation of proteinuria vs. GFR protection; residual proteinuria does not correlate with continued decline in Atacicept-treated patients, which may challenge traditional efficacy metrics used by payers/prescribers.
• Long-term Safety: While no major signals found in 2 years, lifelong therapy (30–40 years) remains unproven; continued monitoring required for infection liability and anti-drug antibody (ADA) impact over extended periods.
• Diagnostic Delays: Current patient population is diagnosed late (avg. age 40, ~50% kidney function loss already), limiting the potential impact on lifetime kidney failure risk until earlier detection protocols mature.
• Trial Design Comparability: Difficulty in direct comparison with other Phase 3 trials (e.g., Semiprolimab) due to differences in population risk, endpoint definitions, and follow-up duration (52 weeks vs. 104 weeks).

Management Tone on the Future:

• Confidence: High confidence in the "transformative" nature of Atacicept, describing the data as "outstanding" and a "paradigm shift."
• Validation: Emphasis on the robustness of the safety and efficacy profile, noting the "placebo-like" safety profile and the achievement of physiological GFR loss rates.
• Strategic Optimism: View 2027 as a pivotal year for commercial growth; express strong belief that the new data will drive immediate uptake and change the standard of care from steroid reliance to disease-modifying therapy.
• Patient-Centricity: Repeated focus on patient protection (unblinding placebo early) and the potential to "free patients from a life of dialysis or transplant."

Miscellaneous:

• Safety Profile: No clinically relevant cases of hypogammaglobulinemia, opportunistic infections, or deaths in the Atacicept group; 97% resolution of hematuria at week 104.
• ADA Status: Anti-drug antibodies observed in ~50% of patients but deemed clinically irrelevant as they do not impact PK/PD or safety.
• Dosing: Current regimen is weekly subcutaneous injection (150mg); future monthly dosing data is pending.