What are the key takeaways from this Beyond Biotech episode?

Key insights include: **Clustering antibody mechanism:** Unlike conventional antibodies that bind a single receptor, clustering antibodies force co-association of four receptors — two ALK1 and two BMPR2 — into a functional tetramer, replicating the signaling complex that nature requires for endothelial integrity. This distinction means the therapy restores normal biology rather than modulating a downstream compensatory pathway.; **HHT disease burden and unmet need:** Approximately 330,000 patients across the US and EU have HHT, yet zero drugs are approved specifically for the disease. Nearly 100% of patients experience recurrent nosebleeds, over 60% develop anemia requiring iron infusion or transfusion, and 20–70% develop arteriovenous malformations in the brain, liver, or lungs.; **AI-accelerated antibody discovery:** Diagonal's platform uses a computational algorithm developed at the University of Texas at Austin to screen billions of epitope combinations across four receptor domains. This narrows wet-lab testing to 200–400 representative antibodies, with roughly 30% demonstrating the desired signaling activity, compressing the discovery cycle to approximately six months.

What did Patrick Andre discuss on Beyond Biotech?

Patrick Andre, CSO of Diagonal Therapeutics, explains how the company's clustering antibody platform targets the root cause of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension. Lead program DIAG-723 holds FDA and EMA orphan drug designation and is entering clinical trials mid-2026, backed by a $125M Series B. Key topics include: **Clustering antibody mechanism:** Unlike conventional antibodies that bind a single receptor, clustering antibodies force co-association of four receptors — two ALK1 and two BMPR2 — into a functional tetramer, replicating the signaling complex that nature requires for endothelial integrity. This distinction means the therapy restores normal biology rather than modulating a downstream compensatory pathway.; **HHT disease burden and unmet need:** Approximately 330,000 patients across the US and EU have HHT, yet zero drugs are approved specifically for the disease. Nearly 100% of patients experience recurrent nosebleeds, over 60% develop anemia requiring iron infusion or transfusion, and 20–70% develop arteriovenous malformations in the brain, liver, or lungs..

How long is this episode of Beyond Biotech?

This episode is 31 minutes long. SignalCast provides an AI-generated summary so you can get the key insights in about 3 minutes.

Beyond Biotech

Diagonal Therapeutics’ innovative clustering antibodies for vascular diseases

April 24, 2026

31 min episode · 2 min read

Patrick Andre

Episode

31 min

Read time

2 min

Topics

Fundraising & VC, Design & UX, Artificial Intelligence

AI-Generated Summary

Published Apr 24, 2026

Key Takeaways

✓Clustering antibody mechanism: Unlike conventional antibodies that bind a single receptor, clustering antibodies force co-association of four receptors — two ALK1 and two BMPR2 — into a functional tetramer, replicating the signaling complex that nature requires for endothelial integrity. This distinction means the therapy restores normal biology rather than modulating a downstream compensatory pathway.
✓HHT disease burden and unmet need: Approximately 330,000 patients across the US and EU have HHT, yet zero drugs are approved specifically for the disease. Nearly 100% of patients experience recurrent nosebleeds, over 60% develop anemia requiring iron infusion or transfusion, and 20–70% develop arteriovenous malformations in the brain, liver, or lungs.
✓AI-accelerated antibody discovery: Diagonal's platform uses a computational algorithm developed at the University of Texas at Austin to screen billions of epitope combinations across four receptor domains. This narrows wet-lab testing to 200–400 representative antibodies, with roughly 30% demonstrating the desired signaling activity, compressing the discovery cycle to approximately six months.
✓Preclinical proof of disease reversal: In mouse and rat HHT models developed with the Finchten Institute, DIAG-723 both prevented and reversed arteriovenous malformation formation. It also reversed anemia and reduced mortality from blood loss. Human patient-derived cells with loss-of-function mutations confirmed the antibody restores receptor clustering and normal downstream signaling.
✓Clinical and pipeline milestones funded by Series B: The $125M round led by Sanofi and Janice Anderson funds a single ascending dose trial in HHT patients starting mid-2026, with proof-of-concept data expected by end of 2027. Proceeds also advance four early-discovery programs toward drug candidate nomination in 2026 and at least one IND filing by 2027.

What It Covers

Patrick Andre, CSO of Diagonal Therapeutics, explains how the company's clustering antibody platform targets the root cause of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension. Lead program DIAG-723 holds FDA and EMA orphan drug designation and is entering clinical trials mid-2026, backed by a $125M Series B.

Key Questions Answered

•Clustering antibody mechanism: Unlike conventional antibodies that bind a single receptor, clustering antibodies force co-association of four receptors — two ALK1 and two BMPR2 — into a functional tetramer, replicating the signaling complex that nature requires for endothelial integrity. This distinction means the therapy restores normal biology rather than modulating a downstream compensatory pathway.
•HHT disease burden and unmet need: Approximately 330,000 patients across the US and EU have HHT, yet zero drugs are approved specifically for the disease. Nearly 100% of patients experience recurrent nosebleeds, over 60% develop anemia requiring iron infusion or transfusion, and 20–70% develop arteriovenous malformations in the brain, liver, or lungs.
•AI-accelerated antibody discovery: Diagonal's platform uses a computational algorithm developed at the University of Texas at Austin to screen billions of epitope combinations across four receptor domains. This narrows wet-lab testing to 200–400 representative antibodies, with roughly 30% demonstrating the desired signaling activity, compressing the discovery cycle to approximately six months.
•Preclinical proof of disease reversal: In mouse and rat HHT models developed with the Finchten Institute, DIAG-723 both prevented and reversed arteriovenous malformation formation. It also reversed anemia and reduced mortality from blood loss. Human patient-derived cells with loss-of-function mutations confirmed the antibody restores receptor clustering and normal downstream signaling.
•Clinical and pipeline milestones funded by Series B: The $125M round led by Sanofi and Janice Anderson funds a single ascending dose trial in HHT patients starting mid-2026, with proof-of-concept data expected by end of 2027. Proceeds also advance four early-discovery programs toward drug candidate nomination in 2026 and at least one IND filing by 2027.

Notable Moment

Patrick Andre describes how a 50% reduction in a single receptor — caused by one loss-of-function mutation — is sufficient to collapse the entire signaling pathway and produce severe vascular disease, illustrating why only an approach that physically reconstructs the receptor complex can fully correct the defect.

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Episode Transcript

Hello, and welcome to Beyond Biotech, the weekly podcast from La BioTech. I'm Dylan Kysain, and this is episode 194 for the podcast. Today, we're joined by Patrick Andre, chief scientific officer at Diagonal Therapeutics. A trained vascular biologist, Patrick's career spans groundbreaking work at Pfizer, Acceleron, Pliant Therapeutics, and earlier companies where he focused on TGF beta superfamily signaling and receptor pathways that keep blood vessels healthy. Now at Diagonal, he's leading a bold mission, developing clustering antibodies that correct the root cause of serious genetic vascular pathies rather than just managing symptoms. In this episode, Patrick walks us through his personal journey into science, the company's diagonal platform, and their lead program, Diag seven two three, which recently received orphan drug designation for the rare disease HHT and is advancing towards the clinic. We also discussed Diagonal's oversubscribed a 125,000,000 series b financing round that closed in January 2026, and what clustering antibodies could mean for patients with HHT, pulmonary arterial hypertension, and more. Patrick, welcome to Beyond Biotech. Thanks, Dylan. Thanks for having me, and it's true pleasure to be here. To kick things off, maybe you could share a little bit about what first sparked your interest in science. Really interesting question. I think there there were probably two decisive moments. One actually that happened long time ago, like, forty years ago. It was really painful and one more recently that was really pleasant. So I'll go through the painful one, and that relate to broken ribs. When I grew up, I was, you know, a kid really into comics, books, science fiction, reading the title, Marvel novels, and all those things. And I was one of the kids thinking that if you concentrate enough, you can achieve fantastic things. So one day, I was waking up. I tried to fly, and I jumped out of the bed. And, the landing was landing was really pretty hard, and I broke two ribs. And, that was the first time I really realized that things happens for a reason, and that science fiction actually was written with two words and not just one. So that was my first eye opening moment that I actually, things are rules by some laws, basically. The second moment came later when I was doing my postdoc at the Center for Blood Research, that was at HMS. And my my PI was really fantastic, was Teresa Wagner. And, this was the heat moment for me for for science. So it all came from a experiment I did in a dark room where we were doing a trivetal microscope here. It consists in isolating cells that circulate in blood. And, you wash them and you label them with a fluorescent dye, and you reinfuse the cells into a living animal. And, when you use inverted intravital microscopy, it allows you to track interaction of circulating cells with the vessel wall. And, it also allow you to, at that time, understand that, cellular biology interaction …

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