Q&A: Understanding protein dysregulation key to preventing neurodegeneration

Key takeaways:

• A phase 1 clinical trial for the investigational therapeutic PRX019 is expected to commence later this year.
• Prothena is also conducting a trial of birtamimab for the treatment of AL amyloidosis.

Prothena Corp. recently announced it would receive $80 million from Bristol Myers Squibb for an exclusive global license to an investigational therapeutic developed to address protein dysregulation.

Healio spoke to Gene Kinney, PhD, president and CEO of Prothena, to find out what impact the potential therapy holds as well as the impact its new partnership may have on the future of neurodegenerative disease.

Healio: What factors led Prothena toward development of therapeutics specifically for conditions with elements of protein dysregulation?

Kinney: Every cell in our body makes proteins that are essential to life on a continuous basis. However, these proteins must properly fold in three dimensions to affect their intended biological functions.

When proteins misfold and deviate from this normal structure, it can lead to toxic confirmations that lead to diseases like Alzheimer’s disease, Parkinson’s disease and peripheral amyloid diseases. Understanding where, when, and how proteins dysregulate leads us to understand how to intervene in this process so that the resultant diseases can be prevented and treated.

The mission of Prothena has remained consistent: to develop novel and transformative medicines to create a better future for people in critical need of new treatment options.

Healio: Would it be fair to say PRX019 is your lead investigational candidate? What factors do you anticipate would determine its use with a specific neurodegenerative disease target?

Kinney: Birtamimab is our most advanced candidate and is currently being investigated in a confirmatory phase 3 clinical trial for AL amyloidosis, a rare, progressive, and often fatal disease. It occurs when misfolded proteins aggregate, causing damage in vital organs including the heart and kidneys. Birtamimab is the only investigational therapeutic that has shown a significant survival benefit in Mayo Stage IV patients with AL amyloidosis in a placebo-controlled study. We will initiate a phase 1 clinical trial for PRX019 by year end 2024. We look forward to sharing more information about the specific target for PRX019 at the appropriate time.

Healio: You have an IND in pocket from the FDA and Bristol Myers Squibb has chipped in $80 million. How will the funds be utilized towards research and development of PRX019 and other therapeutics?

Kinney: The $80 million development milestone payment we announced in late May was part of our collaboration with Bristol Myers Squibb, which has generated two clinical development programs.

Additionally, we are eligible to receive additional development, regulatory and sales milestone payments of up to $617.5 million. This receipt of this additional capital, when added to our existing cash position, will allow us to advance the PRX019 phase 1 clinical trial and continue to execute on our broad portfolio.

Healio: Should the pending phase 1 trial of PRX019 yield positive results, how soon do you anticipate commencing further studies?

Kinney: Following the results of the phase 1 clinical trial for PRX019, we will work with Bristol Myers Squibb to determine the appropriate path forward.

Healio: Can you discuss any other potential therapeutics currently in the pipeline?

Kinney: Prothena’s pipeline is composed of many exciting candidates, both wholly owned and partnered. Our wholly owned programs include a portfolio of candidates for the potential treatment of Alzheimer’s disease, specifically PRX012, a potentially best-in-class next-generation antibody delivered subcutaneously that targets amyloid beta and PRX123, our dual amyloid beta-tau vaccine.

Birtamimab is a wholly owned potential best-in-class anti-amyloid antibody for the treatment of AL amyloidosis designed to directly neutralize soluble toxic light chain aggregates and promote clearance of amyloid that causes organ dysfunction and failure.

In addition to PRX019 with BMS, our partnered programs include prasinezumab (Roche), a candidate for the treatment of Parkinson’s disease; coramitug/NNC6019 (Novo Nordisk), a candidate for the treatment for ATTR amyloidosis; and BMS-986446 (Bristol Myers Squibb), an Alzheimer’s disease candidate targeting tau.

Over the next 12 months, we look forward to sharing several updates on our pipeline, including a phase 3 topline readout of the AFFIRM-AL clinical trial evaluating birtamimab; an update on the ongoing phase 1 clinical trial for PRX012; a timeline update on the phase 1 clinical trial for PRX123, phase 2b topline PADOVA data for prasinezumab; and topline phase 2 data for coramitug/NNC6019.

Reference:

Prothena Announces Bristol Myers Squibb Opt-in for Exclusive Global License for PRX019, the Second Program from Global Neuroscience Research and Development Collaboration. https://ir.prothena.com/investors/press-releases/news-details/2024/Prothena-Announces-Bristol-Myers-Squibb-Opt-in-for-Exclusive-Global-License-for-PRX019-the-Second-Program-from-Global-Neuroscience-Research-and-Development-Collaboration/default.aspx. Published May 28, 2024. Accessed June 5, 2024.

For more information:

Gene Kinney, PhD, can be found on LinkedIn: https://www.linkedin.com/in/gene-kinney-05145925/.