Unnatural Products Announces BridgeBio Exercises Option to License Macrocyclic Therapeutics for Rare Diseases and Oncology

Unnatural Products, Inc. a California-based biotech company specializing in AI-enabled massively parallel chemistry to develop orally bioavailable macrocyclic peptides, announced that BridgeBio Pharma, Inc. has exercised its option to license therapeutic candidates developed through their collaboration.

This follows a series of developments for Unnatural Products (UNP), including its January 2024 deal with Merck & Co., which committed up to $220 million to collaborate with UNP on developing macrocyclic peptide candidates for a challenging oncology target. Merck described macrocycles as the “next wave of drug discovery,” citing their unique ability to overcome the limitations of both small molecules and biologics.

The collaboration between UNP and BridgeBio began in 2021 and focuses on engineering macrocyclic peptides capable of targeting intracellular pathways associated with rare diseases and oncology. Macrocyclic peptides are known for their cyclic structures, which provide stability, specificity, and the ability to access intracellular targets previously deemed undruggable.

BridgeBio’s decision comes shortly after the FDA’s November 2024 approval of its drug Attruby (acoramidis) for transthyretin amyloid cardiomyopathy (ATTR-CM), a rare heart condition affecting over 120,000 U.S. adults. Attruby is the first new treatment in this space since Pfizer’s Vyndaqel, approved in 2019.

In this collaboration, UNP’s AI-driven platform is being used to address the complexities of medicinal chemistry in the macrocycle space, creating synthetic macrocycles with drug-like properties.

UNP’s proprietary platform integrates machine learning and parallel chemistry to develop cell-permeable and orally bioavailable macrocyclic peptides, expanding therapeutic possibilities for oncology and rare diseases. Under the terms of the BridgeBio agreement, UNP led discovery and preclinical development, while BridgeBio will now take responsibility for further preclinical and clinical development. UNP is eligible for milestone payments and tiered royalties upon commercialization.

Unnatural Products was founded in 2017 by Cameron Pye, Ph.D., and Joshua Schwochert, Ph.D., during their time as graduate students at the University of California, Santa Cruz. The company leverages technology originating from the lab of Scott Lokey, a pioneer in cyclic peptide research. The startup has focused on breaking the traditional constraints of medicinal chemistry, particularly the ‘rule of five’ that limits the development of bioavailable drugs. By developing methods like DNA-encoded libraries and phage display, UNP has rapidly advanced macrocyclic peptides as a therapeutic class.

Since its inception, UNP has garnered attention for its technology that combines AI with massively parallel chemistry. This includes early funding milestones, such as $6 million in seed funding in 2019 and a $23 million Series A round in 2023.

Cover image: Unnatural Products

Topics: Novel Therapeutics