Prothena Corp. Plc Q4 FY2023 earnings call

• Mission: Prothena aims to create transformational therapies for diseases caused by protein dysregulation. • Portfolio: Robust portfolio with four wholly-owned and five partnered programs targeting neurodegenerative and rare peripheral amyloid diseases. • Clinical progress: PRX12 in Phase 1 with preclinical data showing high avidity for amyloid plaques; Birtamimab in Phase 3 AFFIRM AL trial with top-line results expected in late 2024 to early 2025; Prasinezumab in Phase 2b PADOVA trial with enrollment completed and top-line data expected later in 2024; NNC6019 in Phase 2 signal detection trial with top-line results expected in first half of 2025. • Pre-commercial efforts: Building commercial leadership for Birtamimab, including market research on patient populations with MAYO Stage IV AL Amyloidosis and collaboration with KOLs and guideline publishers. • 2023 financials: Net cash used in operating and investing activities was $136.7 million, net loss was $147 million, and cash position was $621 million as of December 31, 2023.

No detailed product segment revenue contribution breakdown provided. The focus is on clinical programs and overall financials, with key clinical programs like PRX12, Birtamimab, Prasinezumab, and NNC6019 being highlighted in terms of their development progress.

• 2024 net cash used in operating and investing activities expected to be between $208 million and $225 million. • End of 2024 cash, cash equivalents, and restricted cash expected to be approximately $405 million (midpoint of range). • Estimated 2024 net loss: $229 million to $255 million, including an estimated $51 million of non-cash share-based compensation expense.

• Forward-looking statements are subject to risks, uncertainties, and other factors that could cause actual results to differ materially from those in forward-looking statements. Details can be found in the press release issued today and the most recent filings with the SEC. • No specific operational failures discussed in detail during the call, but general risks associated with clinical trial outcomes, regulatory approvals, and market adoption were acknowledged.

Q: Charles Duncan asked about patient enrollment in PRX12 and update timing for PRX12.

A: Gene Kinney referred to Hideki Garren who discussed strong enrollment in the PRX12 trial and ongoing study progress, with updates on PRX12 to be determined later in the year.

Q: Jay Olson inquired about the PRX012 MAD study's six-month open-label extension.

A: Gene Kinney and Hideki Garren explained the open-label extension is for safety, tolerability, pharmacokinetics, and pharmacodynamic measurements, with patients in the placebo-controlled phase potentially transitioning to open-label PRX12.

Q: Michael DiFiore asked about ARIA rates in PRX12 and reconciliation with other antibodies.

A: Gene Kinney and Hideki Garren discussed molecule-dependent Aria rates and the exposure response relationship of PRX12, noting Aria rates in the 70 mg cohort were consistent with placebo.

Q: Neena Bitritto-Garg asked about Aria in PRX12 cohorts and dose selection.

A: Gene Kinney and Hideki Garren addressed Aria consistency with placebo across cohorts and the rationale for dose level selection in the study.

Q: Yasmeen Rahimi asked about Aria rates in APOε4 populations and efficacy expectations.

A: Gene Kinney and Hideki Garren talked about APOε4 homozygosity impact on Aria and trial design considerations for optimizing doses across the population.

Q: Michael Yi asked about Aria consistency with placebo and dose confidence for PRX12.

A: Gene Kinney discussed the double-blind placebo-controlled study and therapeutic index, indicating confidence in exploring higher dose ranges based on current data.

Q: Jason Butler asked about Prasinezumab's benefit magnitude and clinical incorporation.

A: Gene Kinney and Hideki Garren spoke about Roche's data from prior trials, the Phase 2b PADOVA trial, and the clinical meaningfulness of the trial's endpoints, with anticipation for top-line results later in 2024.

Q: Ananda Ghosh asked about PUC, C-Max, and fractional occupancy in PRX12.

A: Gene Kinney discussed the exposure response relationship of PRX12 and its relevance to plaque clearance and Aria rates, similar to anti-beta antibodies like lecanemab.