Enlaza Therapeutics Grabs $61 Million to Industrialize Covalent Biologics

Enlaza Therapeutics, the first covalent biologic platform company, officially launched today with $61 million in seed funding. The money will be used to advance Enlaza’s unique covalent biologic platform, called War-Lock, and to set up a pipeline of cancer treatments with improved safety and efficacy.

“[Covalent biologics] is something that no one has done before,” Sergio Duron, PhD, CEO of Enlaza, told GEN Edge. “It’s ‘white space’ for drug discovery, and we think there’s a monumental opportunity here to improve [drug] safety and efficacy. We want covalency to become a standard part of the toolbox in this field of biologics and protein drug discovery.”

In its first year, Enlaza has grown to about 30 staff and assembled a leadership team that also includes Sanford (Sandy) Madigan, PhD, president and chief business officer; Analeah Heidt, PhD, chief scientific officer; and Lei Wang PhD, scientific advisor and professor at the University of California, San Francisco (UCSF).

The financing for Enlaza—derived from the Spanish word enlazar, which means to link or to connect, and describes the War-Lock technology to covalently bind proteins—was spearheaded by Avalon Ventures with assistance from Lightspeed Venture Partners, Frazier Life Sciences, and Samsara BioCapital.

The wizardry of War-Lock

Most drugs work via weak, reversible bonding. A few attempts have been made over the past decade to develop small-molecule drugs that work through covalent binding (examples include Avila and Principia—eventually bought out by Celgene and Sanofi, respectively, for their work on developing BTK targeted covalent inhibitors in a race for FDA approval and commercialization—as well as Terremotto, which launched in 2022). But these small molecules are typically inhibitors and carry an electrophile that reacts non-selectively. Duron says that there’s been significant progress in the covalent and biologic spaces, and he believes that coupling covalency with biologics, such as antibody-drug conjugates (ADCs) and radioligand therapies (RLTs), opens up a brand new field.

Enlaza’s technology uses “unnatural” amino acids that are essentially non-reactive until the biologic binds the molecular target and forces proximity between the unnatural amino acid and a nucleophile on the target, resulting in cross-linking. The War-Lock technology can be applied to any protein drug that can incorporate unnatural amino acid with the aim to improve safety and efficacy. Duron says that the nature of the War-Lock platform can enable a variety of biological or drug discovery strategies with a very diverse set of potential partners.

“We can mediate toxicity by leveraging high clearance but also have long-term pharmacodynamics and efficacy without exposure to the drug,” said Duron. “We can improve efficacy for targets that have low copy number or receptor density. This is something that is challenging in today’s drug discovery. If you have a target that has a low copy number or receptor density, covalency can impact the fidelity of the payload we’re trying to attach.”

Culling cancer with covalency

Where biologics have failed as cancer treatments because of issues with safety and efficacy, Duron thinks covalent biologics could make improvements. Enlaza intends to expand the covalent biologic platform to multiple oncology treatment strategies using antibody-drug ADCs and RLTs.

The Enlaza CEO also envisions small-format protein biologics that can have very good penetration and high clearance of solid tumors without having to use half-life extension strategies. According to Duron, Enlaza has produced preclinical data for its oncology drug candidates that demonstrate rapid tumor penetration along with high systemic clearance, high tumor retention, and low off-target toxicity.

The seed funding will help advance several of these programs and support IND enablement, including CMC (chemistry, manufacturing, and controls) activities. It will also enable Enlaza to continue the proof-of-concept work and industrialization of the War-Lock technology, which is built on technologies that have been exclusively licensed from UCSF and The Scripps Research Institute.