Antibody agonism triggers $128M A round for Diagonal

03 Apr 2024
firstwordpharma.com
Drug ApprovalImmunotherapyADC
Rather than shutting down signalling pathways, Diagonal Therapeutics is developing antibodies to hit cellular “on” switches to treat rare, genetically linked diseases. The biotech raised a $128-million series A, co-led by BVF Partners and Atlas Venture, to take its lead candidate through proof-of-concept studies.
While most approved antibody therapies inhibit a cellular function, often to treat cancer, Diagonal is developing agonists that activate a signalling cascade, thus reactivating biological pathways to treat the underlying cause of certain diseases.
“The biopharmaceutical industry has a robust, growing toolkit of approaches to inhibit disease-associated pathways. However, we still lack systematic pharmacologic approaches to activate biological pathways to treat diseases caused by deficient signalling,” said Michael Gladstone, partner at Atlas and chair of Diagonal’s board. “Diagonal’s platform addresses this unmet need by rapidly identifying antibodies that activate key pathways.”
According to the company, developing antibody agonists has been historically bottlenecked due to the complexity of identifying or designing such treatments. With more than 10 billion possible binding configurations, and only a small subset that result in the desired therapeutic activity, it’s difficult and time-consuming to home in on the right combinations.
By combining computational and experimental technologies, Diagonal said its platform enables “scientists to sift through billions of combinations at unprecedented speeds and with high fidelity.”
The company’s lead agonist activates a receptor complex in the TGF-β superfamily that is genetically impaired in patients with hereditary hemorrhagic telangiectasia (HHT).
Wednesday’s round – which saw participation from Lightspeed Venture Partners, RA Capital Management, Frazier Life Sciences, Viking Global Investors, Velosity Capital, and Checkpoint Capital – will take the antibody through clinical proof-of-concept studies.
Diagonal’s second candidate is in preclinical development for pulmonary arterial hypertension (PAH). While the specific target is undisclosed, Diagonal said the agonist antibody corrects imbalanced signalling in the antiproliferative and hyperproliferative pathways to restore vascular wall homeostasis.
Last month, the FDA approved the first disease-modifying treatment for PAH: Merck & Co.’s  activin signalling inhibitor Winrevairactivin signalling inhibitor Winrevair (sotatercept-csrk).
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