:USA—Diagonal Therapeutics, a pioneering biotechnology startup specializing in the development of antibodies that activate, rather than block, their targets, has emerged from stealth mode with an impressive US$128 million in funding.

Founded by industry veteran Alex Lugovskoy and generously backed by leading biotech investors including Atlas Venture, Lightspeed Venture Partners, and Velosity Capital, Diagonal has garnered support from a diverse array of backers such as BVF Partners, RA Capital Management, and Viking Global Investors.

Headquartered in Cambridge, Massachusetts, the company has embarked on its journey with a focus on addressing the rare blood disease hereditary hemorrhagic telangiectasia and a pulmonary arterial hypertension, a condition affecting the lungs.

 The substantial funding secured will facilitate the advancement of its initial projects into early testing phases, according to BioPharma.

Traditionally, drugs fall into two categories: “antagonists,” which impede particular biochemical processes, and “agonists,” which stimulate them.

Commenting on thus development,  Lugovskoy noted crafting the agonist  is considerably more challenging, particularly in the realm of antibody therapeutics, which constitute an increasingly significant portion of the pharmaceutical landscape.

This complexity arises from the intricate task of identifying and structurally maintaining multiple binding sites for a drug.

 Lugovskoy emphasized that nature does not provide clear guidance on how these antibodies should bind, necessitating meticulous research efforts.

 Diagonal asserts that it has streamlined this process with a sophisticated computational platform, expediting the identification of potential antibody agonists. This accelerated discovery approach holds promise for unlocking novel treatment modalities.

Lugovskoy elaborated on the potential impact of their work, stating, “There are a lot of human diseases that require reactivation of signaling for a curative effect.”

The company’s initial focus lies on hereditary hemorrhagic telangiectasia (HHT), a genetic disorder affecting over 150,000 individuals, predominantly women, in the U.S. and Europe.

Diagonal aims to address a root cause of the disease by activating a protein complex impaired in individuals with HHT.

Additionally, Diagonal is pursuing a program targeting pulmonary arterial hypertension (PAH). Despite existing treatments, Lugovskoy believes their approach could complement current therapies, offering new avenues for patients.

Lugovskoy brings a wealth of experience to Diagonal, having previously held positions at Biogen, Merrimack Pharmaceuticals, and executive roles at biotech companies Morphic Therapeutic and Dragonfly Therapeutics.

The inception of Diagonal can be traced back to November 2021, when Lugovskoy, then an entrepreneur-in-residence at Atlas Venture, pitched the concept of a company focused on agonist antibodies to Michael Gladstone, a partner at the venture firm.

This initial pitch set the stage for a remarkable US$128 million Series A round, culminating less than three years later.

Reflecting on his motivation, Lugovskoy emphasized the transformative potential of drugs capable of activating malfunctioning cellular pathways, stating, “What drove me is understanding is there is a big void. Drugs that can activate malfunctioning cellular pathways ‘could transform a patient’s life.”

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