Prothena recently reported fourth quarter and full year 2024 financial results, another successful year of progress in our effort to address unmet needs for the millions of patients and their loved ones that are affected by devastating, life-threatening diseases caused by protein dysregulation. With many of our clinical programs nearing significant inflection points in 2025, we are looking forward to the transformational year ahead. Read on to hear from President and CEO Dr. Gene Kinney on what to expect from Prothena in 2025.

Q: Looking back, what are you most proud of the Prothena team accomplishing in 2024?

A: I am incredibly proud of all that Prothena accomplished in 2024, laying the foundation for an exciting year ahead. As a result of our commitment to our mission, we have created a robust portfolio of therapeutic drug candidates targeting both neurodegenerative and rare peripheral amyloid diseases. In 2024, we remained focused on advancing our clinical programs as we strive to become a fully integrated commercial biotechnology company. I’d like to thank our talented Prothenians for their ongoing commitment to advancing protein dysregulation science to make a real impact for the patients and families we serve. I’d also like to acknowledge and thank the patients, their families, physicians, and study site staff who participate in all our clinical trials. Without their support, we Prothenians could not elucidate the potential impact of the new medicines we’re developing.

Q: What are you most excited about in 2025 for Prothena?

A: 2025 will be a transformational year for Prothena with significant clinical read-outs from our wholly-owned programs and continued clinical advancement of our strategically partnered programs. Looking ahead, we are excited to announce topline results from our confirmatory Phase 3 AFFIRM-AL trial evaluating birtamimab* in patients with Mayo Stage 4 AL amyloidosis, clinical data from our Phase 1 ASCENT clinical trials evaluating PRX012* as a potential best-in-class treatment in early Alzheimer’s disease, completion and topline results from Novo Nordisk’s Phase 2 signal-detection trial evaluating coramitug* for the treatment of ATTR-CM, and lastly sharing further clinical development updates for PRX123*, prasinezumab*, BMS-986446* and PRX019*. It’s going to be a very busy year for us.

Q: Tell us more about the anticipated next steps for Birtamimab?

A: We are particularly excited about birtamimab, currently the only potential treatment for AL amyloidosis that has demonstrated an early survival benefit in a randomized clinical trial. The survival data from our prior Phase 3 VITAL trial enabled us to receive a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA) for the confirmatory Phase 3 AFFIRM-AL clinical trial with a primary endpoint of all-cause mortality (time-to-event) at a statistical significance level of 0.10. We hope to confirm these results in our ongoing Phase 3 AFFIRM-AL trial and expect to announce topline results in the second quarter of this year.

We look forward to the opportunity to potentially bring a new therapy to people living with this devastating disease, and for our company, the opportunity to become a fully-integrated commercial biotechnology company.

Q: Bringing birtamimab to this stage of development took determination and persistence. What does this tell us about Prothena’s commitment to rare disease patients?

AL amyloidosis is a rare, progressive, and difficult to diagnose disease. If left untreated, it can lead to organ failure and eventually death. When data from our earlier VITAL study showed a robust survival benefit for some of the sickest AL amyloidosis patients, we initiated the AFFIRM-AL Phase 3 trial for patients with Mayo Stage IV AL amyloidosis under a Special Protocol Assessment (SPA). And that has led us to where we are today. The path for this program didn’t follow a perfectly straight line, but we never lost sight of the destination: a new therapy to potentially provide a survival benefit for patients suffering from this deadly disease.

Q: What developments do we expect in Alzheimer’s disease in 2025?

A: Beginning around mid-year and continuing through the second half of 2025, we expect to share results from our ongoing Phase 1 ASCENT clinical trials evaluating PRX012 in early Alzheimer’s patients. PRX012 is our anti-amyloid beta (Aβ) antibody program designed to be a single-injection, once-monthly, subcutaneous treatment.

Q: What makes Prothena’s Alzheimer’s disease portfolio unique?

A: Our Alzheimer’s disease portfolio includes unique programs designed to address the unmet needs of the millions of patients with Alzheimer’s disease and their families.

PRX012 is unique in that it is designed to be a once-monthly subcutaneous treatment, which we believe will ease the treatment burden for patients and their caregivers. PRX123 is designed for the treatment and prevention of Alzheimer’s disease that targets both Aβ and tau, two proteins implicated in the causal biology of Alzheimer’s disease. And with our partner Bristol Meyers Squibb, we continue to advance BMS-986446, a potentially best-in-class antibody that targets a key part of the tau protein. Together, these programs may enable us to address a very large and underserved market, comprised of millions of patients and their families whose needs are not fully addressed with today’s treatment options

Q: What can we expect from Prothena’s partnered pipeline programs in 2025?

A: Our partnered research programs enable us to leverage external resources and expertise to advance potentially transformative medicines to patients. It’s a successful strategy for us, which explains why half of our pipeline programs are partnered. And 2025 looks to be eventful for our partnered programs.

With Novo Nordisk, we expect results this year from the Phase 2 trial evaluating coramitug, an anti-amyloid antibody for the potential treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). Our partner Roche announced topline results from the Phase 2b PADOVA study in December of 2024, investigating prasinezumab for the potential treatment of early Parkinson’s disease and look forward to updates from discussions with regulators about the data. Additionally, we made significant progress last year with our two partnered clinical programs with Bristol Myers Squibb: BMS-986446, the partnered Alzheimer’s disease program I mentioned, initiated its Phase 2 trial last year and PRX019, a second partnered program with Bristol Myers Squibb in neurodegenerative disease, initiated its Phase 1 study. In short, 2025 looks to be a year with significant continued momentum in our partnered programs.

Learn more about our pipeline here.

*Birtamimab is an investigational therapy for the potential treatment of Mayo Stage IV AL amyloidosis; PRX012 and PRX123 are investigational therapies for the potential treatment of Alzheimer’s disease; coramitug is an investigational therapy for the potential treatment of ATTR amyloidosis with cardiomyopathy; prasinezumab is an investigational therapy for the potential treatment of Parkinson’s disease.