Pfizer Strikes Over $1 Billion Deal with TRIANA Biomedicines for Molecular Glue Degraders

On October 15, the U.S. biotechnology company Triana Biomedicines (hereinafter referred to as "Triana") announced a strategic collaboration and licensing agreement with Pfizer to discover novel molecular glue degraders for multiple targets across several disease areas, including oncology.

According to the terms of the agreement, TRIANA will receive an upfront payment of $49 million (approximately 349 million yuan) and is eligible to receive over $1.5 billion (approximately 10.674 billion yuan) in potential future milestones, as well as tiered royalties. TRIANA will leverage its target-first and proximity-first molecular glue discovery platform to identify novel molecular glue degraders against multiple targets across various disease areas, including oncology.

At the same time, TRIANA will be responsible for leading the discovery and identification of potential development candidate pipelines, while Pfizer will have an exclusive licensing option to further advance preclinical and clinical development.

In recent years, Pfizer has actively invested in the incubation stage of innovative startups in the form of venture capital. This includes the collaboration with Flagship Pioneering reached in June this year to explore the preliminary incubation and investment cooperation for 10 new projects, as well as participation in the Series A financing round of the startup COUR Pharmaceutical. This cooperation with Triana Biomedicines marks Pfizer's first strategic partnership with a biotech company this year. Interestingly, two years ago, Pfizer also participated as a follow-up investor in Triana Biomedicines’ Series A financing round.

Why Does Triana Biomedicines Continue to Win Pfizer's Favor?

TRIANA Biomedicines, Inc. was co-founded in 2019 by investment firms RA Capital Management and Atlas Venture, and completed a $110 million Series A financing round in 2022, led by RA Capital Management and Atlas Venture with participation from Pfizer and others. In the press release at the time, Patrick Trojer, who joined in 2021 as President and CEO, stated that this funding should sustain the company’s operations until 2025. Now, just before 2025, TRIANA has successfully entered into a strategic partnership with Pfizer, securing additional funding to continue operations, which, if all goes well, will become a stable cash source for the company in the coming years.

In addition, TRIANA also announced at the time that the financing proceeds would be used to establish a potential "best-in-class" scalable technology platform for the discovery and development of molecular glues. The goal of its platform is to generate products that stabilize pre-existing interactions between two proteins or create new interactions, altering the function of disease targets.

From the limited available information, TRIANA’s strategy is to start with target proteins highly associated with diseases and then utilize AI and computational algorithms to identify the optimal E3 ligase for this target. Its "best-in-class" platform for systematically screening molecular glues incorporates a proprietary deep learning algorithm based on AI that identifies protein surface features potentially related to protein interactions. The platform validates and tests these features on existing protein interaction networks, using the algorithm to predict which target proteins have higher affinity, and then ranks the E3 ligases most likely to form complexes with the target proteins. According to previous reports from TRIANA, its platform can evaluate and prioritize over 600 known E3 ubiquitin ligases and their disease-related targets, while rapidly exploring and identifying the chemical space suitable for molecular glue degraders.

At the same time, Triana Biomedicines has established a "one-bead-one-compound DNA-encoded library" and introduced Lipinski's Rule of Five for drug screening — the chemical properties that orally administered small-molecule compounds should possess, such as no more than five hydrogen bonds and a molecular weight below 500 — to improve the in vivo absorption rate of the compounds.

Currently, Triana Biomedicines has not disclosed specific primary targets but has indicated that the company’s research focus is on oncology, with the goal of developing groundbreaking new cancer therapies.

Since researchers elucidated the mechanism of thalidomide analogs as molecular glue degraders in 2013, molecular glue has become a focal point for MNCs such as Pfizer, Eli Lilly, Sanofi, Novartis, Merck, and Bayer in recent years, with热度 comparable to ADC. Since 2023, MNCs including BMS, Roche, Merck, and Novo Nordisk have successively entered into molecular glue technology platform/project collaborations with overseas biotechs, with potential total transaction values exceeding tens of billions of dollars.

However, finding new molecular glue degraders is a huge challenge, and the discovery process is highly contingent, lacking a systematic approach for discovery and design. Currently, molecular glue technology platforms are being explored in three mainstream ways: blending and matching traditional drug development methods, utilizing mass spectrometry, and relying on artificial intelligence (AI) to predict and complete screening.

Among them, the continuous development of AI technology has brought new opportunities to the molecular glue field. In addition to Triana Biomedicines, which Pfizer has invested in and collaborated with this time, VantAI, despite having no product pipeline yet, has successively reached partnerships with BMS, Janssen, and Boehringer Ingelheim.

Under such热度, the overseas expansion story of Chinese biotech in molecular glue is unfolding. For instance, Jia Yue Pharmaceuticals reached an exclusive global licensing agreement with U.S.-based Erasca for Pan-RAS(ON) inhibitor JYP0015 worth $345 million; Dagge Biotech partnered with Takeda Pharmaceutical to leverage its GlueXplorer platform to discover, validate, and optimize molecular glue degraders targeting specific disease targets selected by Takeda, with a potential total transaction value of up to $1.2 billion.

However, the story of thalidomide cannot be "a one-hit wonder." The investment and cooperation of multinational corporations (MNCs) in the molecular glue field are still wavering between bold gambling and rationality. So far, there are not many molecular glue drugs on the global market with significant sales scale, and they still remain in the stage of the three major "domides." Although domestic and foreign enterprises are actively laying out their strategies, most of them are still in the clinical stage. Moreover, the clinical development of molecular glue has not been smooth. Previously, Celgene and Biotheryx’s GSPT1 degrader has ceased development; Novartis also stopped its IKZF2 degrader after Phase I trials.

In the field of molecular glues, we are still waiting for a new "myth."

Reference Article:

1. "The Pursued Molecule Glue Still Needs a Success Story" - Amino Observation

2. "Can 'Molecular Glue' Win the Nobel Prize?" VCBeat

3. "New Field Favored by Pfizer and Bayer, Start-up Triana Biomedicines Raises $110 Million with a Single Platform" VCBeat