Prothena Corp. Plc Q4 FY2021 earnings call

• 2021 was productive with progress in R&D portfolio, including three programs in mid-late clinical stages and six discovery candidates. - Organizational evolution with strengthened management team and Board, including appointment of new CMO and CSO. - Progress in specific programs: PRX012 expected to file IND this quarter, PRX005 Phase I data in 2022, dual vaccine showed robust immune response, prasinezumab data showed slowing clinical decline in Parkinson's subgroups, birtamimab Phase III AFFIRM-AL study enrolling, and Novo Nordisk planning Phase II trial for PRX004 in ATTR cardiomyopathy.

Prothena had various R&D programs in neurodegenerative and rare peripheral amyloid diseases. In 2021, they received $200 million in partner payments from collaborations with Bristol Myers Squibb, Novo Nordisk, and Roche. Key programs included PRX012 for Alzheimer's, PRX005 for Alzheimer's, a dual Abeta tau vaccine, prasinezumab for Parkinson's, birtamimab for AL amyloidosis, and PRX004 for ATTR amyloidosis.

• 2022 net cash used in operating and investing activities expected to be $120 million to $132 million, including $40 million clinical milestone from Novo. - Ending cash expected to be ~$454 million. - Net loss estimated $154 million to $170 million. - Milestones: PRX012 IND filing this quarter, PRX005 Phase I data this year, prasinezumab data at AD/PD in March, AFFIRM-AL top line data in 2024, Novo starting PRX004 Phase II trial in first half of 2022.

• Factors affecting forward-looking statements, including risks and uncertainties that could cause actual results to differ from forward-looking statements. - Uncertainties in clinical trial outcomes, regulatory approvals, and market reception of new therapies.

Q: Charles Duncan asked about PRX012's upcoming IND and clinical study start.

A: Gene Kinney said IND filing expected this quarter, Phase I trial to begin thereafter, and Prothena plans to develop PRX012 independently for proof-of-concept.

Q: Michael Yee asked about Alzheimer's scenarios and pharma interest.

A: Gene Kinney discussed upcoming data from donanemab, gantenerumab, lecanemab, and NCD determination by CMS, and Prothena plans to incorporate learnings into PRX012 program.

Q: Neena Bitritto-Garg asked about AFFIRM-AL study enrollment status.

A: Gene Kinney said top line data in 2024, sites are enthusiastic with investigator meetings well attended and sites being activated.

Q: Jay Olson asked about AL amyloidosis unmet need and Birtamimab's commercialization.

A: Wagner Zago explained Birtamimab's mechanism of removing resident amyloid vs standard therapies targeting production, and Prothena intends to commercialize Birtamimab independently.

Q: Kennen MacKay asked about IND gating for PRX012 and AFFIRM-AL site numbers.

A: Gene Kinney said IND filing for PRX012 on track for first quarter, and AFFIRM-AL enrollment has 117 sites for 150 patients, with new sites being added.

Q: Gobind Singh asked about DARZALEX traction in AL, OpEx guidance for PRX012, and dual vaccine pyroglutamate Abeta data.

A: Tran Nguyen discussed DARZALEX revenue breakdown, OpEx for Birtamimab, and Wagner Zago commented on dual vaccine's ability to clear pyroglutamate Abeta.

Q: Tazeen Ahmad asked about Roche milestones and ATTR efficacy endpoints.

A: Tran Nguyen said remaining milestone for prasinezumab is regulatory/commercial, and Gene Kinney discussed ATTR therapies' mechanisms and PRX004's differentiation in targeting advanced patient populations.