Dive Brief:

• Diagonal Therapeutics, a biotechnology startup focused on creating antibodies that activate, rather than block, their targets, emerged from stealth Wednesday with $128 million in funding.
• Created by industry veteran Alex Lugovskoy and seeded by biotech investors Atlas Venture, Lightspeed Venture Partners, and Velosity Capital, Diagonal drew the support of a wide range of backers including BVF Partners, RA Capital Management and Viking Global Investors.
• The Cambridge, Massachusetts-based company is starting out with programs for the rare blood disease hereditary hemorrhagic telangiectasia and a lung condition known as pulmonary arterial hypertension. The funding will help it bring its first projects into early testing.

Dive Insight:

Drugs can be grouped into two categories: “antagonists” that block a particular cascade of events, and “agonists” that trigger them. According to Lugovskoy, designing the former is a lot easier than the latter, especially when it comes to the antibody medicines that make up more and more of the pharmaceutical business.

The reason, he said, is that designing an antibody agonist is more complex, involving finding multiple binding sites for a drug and holding them together in a specific way. That’s no small task, given there are a nearly infinite number of options for drugmakers to choose from and only a small fraction that are helpful.

“Nature doesn’t teach you how these antibodies need to bind,” Lugovskoy said, meaning scientists have to figure it out through painstaking research.

Diagonal claims it has made this work easier with a computational platform that can helps its scientists sift through potential combinations more quickly. The result, the company says, is a faster way of discovering antibody agonists, which could open up new ways to treat disease.

“There are a lot of human diseases that require reactivation of signaling for a curative effect,” Lugovskoy said.

Diagonal is starting with hereditary hemorrhagic telangiectasia, or HHT, a genetic disorder that affects more than 150,000 people, mostly women, in the U.S. and Europe, according to the company. Abnormal blood vessels in people with HHT can rupture and cause chronic anemia. While there are treatments for the disease’s symptoms, Diagonal says its antibody may address a root cause by activating a protein complex that’s impaired in people with the condition.

Diagonal’s other named program targets PAH. Though multiple treatments exist — including Merck & Co.’s Winrevair, which U.S. regulators approved last week — Lugovskoy said Diagonal’s approach could be complementary.

Lugovskoy previously worked at Biogen and Merrimack Pharmaceuticals before landing executive roles at biotechs Morphic Therapeutic and Dragonfly Therapeutics. In November 2021, while an entrepreneur-in-residence at Atlas, he pitched Michael Gladstone, a partner at the venture firm, on the concept of building a company focused on agonist antibodies.

That set the wheels in motion for a $128 million Series A round that closed less than three years later.

“What drove me is understanding is there is a big void,” he said. Drugs that can activate malfunctioning cellular pathways “could transform a patient’s life.”