Armed with library of molecular glues, Degron launches out of a Shanghai lab
A transpacific biotech focused on molecular glues now has more funds to play with as it works to vie for Big Pharma’s attention.
Degron Therapeutics announced a Series A worth $22 million Thursday, with Chinese VC Med-Fine Capital as lead investor and other investors such as Dyee Capital and Baidu Venture tagging along. Seed investors CO-WIN Ventures and Yuanbio Venture Capital also participated, Degron said in a statement.
The biotech was founded just last year out of the lab of Yong Cang, a professor at ShanghaiTech University, branching out with $10 million from a seed round in April 2021. Using an array of different types of screening, from phenotypes to proteomics and AI, Degron researchers seek to predict ways that different protein targets can be degraded via molecular glue.
So far, the biotech’s library of potential molecular glues is around 6,000, with the majority of them binding to a ubiquitin E3 ligase known as Cereblon.
While molecular glues and proteolysis targeting chimeras, aka PROTACs, both take advantage of the human body’s protein destruction system, their methods of action are a bit different. Molecular glues, a type of monovalent degrader, seek to “program” a ubiquitin E3 ligase to attach to target cell surface proteins and break them down. PROTACs, on the other hand, are bifunctional small molecules that tether a protein of interest at one end, and at the other end bind to an E3 ligase to degrade and ultimately dispose of that protein.
CEO Lily Zou told Endpoints News that what sets Degron apart from other protein degradation biotechs — in a field that is still relatively new alongside Nurix, Plexium and Kymera — is the “scaffolding” it uses.
“The structure of the small molecule decides — determines what kind of target you can recruit. And we have a different starting point. Our initial scaffold was discovered in a screening that’s different from most, as far as I know,” the CEO said.
Zou added that most other companies look for derivatives from two of the main approved molecular glue drugs: Celgene’s lenalidomide (Revlimid) and pomalidomide (Pomalyst).
“So they are derivatives of that, but there is one chemical space. Imagine that we are in a different chemical space. So because we’ve discovered this new scaffold, we’ve built our library around that and expanded, because of that we can find different targets,” Zou further elaborated.
Zou added that the biotech currently has 20 programs in different stages of preclinical development in a variety of targets that Zou said were once deemed untargetable. So far, the indications range from mostly oncology to some focus in inflammation, metabolic disease and rare disease.
Three of its programs are in the IND-optimization stage, and Zou hopes to have those three programs in humans in the next 18 months. In the course of the next year or two, target optimization and validation will narrow the number of preclinical programs down.
Zou said among the most advanced programs is a WEE1 kinase degrader. Degron has two choices for that target: either a single-target degrader or a dual-target degrader, but the final decision has not been made yet. Another target remains undisclosed, but the CEO just called it “protein A” for name’s sake.
“The most exciting thing about protein A: It’s undruggable because it’s not an enzyme or something you can inhibit the function of. It’s a structural protein of a kind,” Zou said. “So, traditional small molecule inhibitors cannot target it. And also, it’s inside the cell, so it’s not targeted by antibodies or other things.”
As of right now, Degron has space in the Johnson & Johnson-sponsored JLABS space in Shanghai. Zou also elaborated that the company has been talking with J&J, and that the company is moving to Roche Accelerator, which is Roche’s attempt at building an “innovation hub” in China. In the meantime, Med-Fine Capital partner Jing Yu is joining Degron’s board of directors.
