Pfizer collaborates with Triana in $49M deal

Pfizer is expanding its commitment to the development of protein degraders by partnering with Triana Biomedicines, a startup specializing in the emerging field of molecular glues. This collaboration aims to target multiple diseases, including cancer, through various drug targets selected by Pfizer. Triana will initially receive $49 million and could potentially earn over $1.5 billion in milestone payments, as revealed by both companies on Tuesday.

Pfizer has maintained a leading position in the protein degrader arena, especially through its substantial partnership with Arvinas, a company known for creating PROTACs. These complex molecules work by binding a problematic protein with one side and attaching an enzyme known as E3 ligase with the other. This enzyme then marks the protein for elimination by the cell's waste disposal system.

PROTACs have challenged traditional drug design conventions due to their large structures. Despite advancements in the field, developing drugs using PROTACs has proven difficult. Molecular glues present an alternative, offering a more compact structure that could potentially result in more effective drugs, though designing them remains challenging. "No one has systematically figured out how to create molecular glue degraders," said Triana CEO Patrick Trojer in an interview. "This partnership with Pfizer will allow us to enhance our understanding and development in this area."

Triana will concentrate on the initial stages of drug discovery and design, while Pfizer has the option to license the drug candidates and further develop them through preclinical and clinical phases, according to Trojer. Unlike PROTACs, which can be pieced together by designing the two ends separately, molecular glues are more complex to create because their functional components are closely integrated. Additionally, well-known molecular glues were mostly discovered by chance and target a very small subset of the numerous E3 ligases.

Triana was established to address these challenges, combining insights from two venture capital firms to improve molecular glue discovery. RA Capital developed a machine learning algorithm to pinpoint optimal E3 ligase and target protein pairings, while Atlas Venture created a method to screen numerous potential molecular glue structures using a DNA-encoded library of macrocycles.

Since its inception and emergence from stealth mode with $110 million in April 2022, Triana has built on these methods, as noted by Trojer. Pfizer has been aware of Triana for some time, partly because Pfizer Ventures is an investor in the startup.

Triana is currently working on three drug programs, all focusing on protein degraders targeting specific cancer genes, which Trojer believes can be developed independently. However, he has not disclosed specific targets or indications. The company is nearing the selection of its first development candidate and may file its first Investigational New Drug (IND) application within the next 18 to 24 months, potentially leading to its first clinical trial by 2026 or early 2027.

One significant advantage of protein degraders is their potential to address traditionally undruggable targets, and they may also help overcome resistance that tumors develop against existing enzyme-targeting drugs. "The advantage of a molecular glue is that it doesn't have to bind to the active site; it can attach anywhere on the protein," Trojer explained. "This allows binding to a part of the protein that doesn't mutate,” which is an approach being taken in one of Triana's programs.

Trojer previously mentioned that the initial funding would sustain the company until 2025, and the payment from Pfizer extends this timeline to 2026. However, Triana will likely need to raise a Series B round to obtain early clinical data from its lead program and advance its second candidate into clinical trials, probably in the latter part of next year.