ADVANCING A GROUND-BREAKING APPROACH TO DISEASE-MODIFYING CLUSTERING ANTIBODY THERAPEUTICS
Our Approach
Dysregulated cellular signaling pathways lie at the heart of many chronic illnesses, yet treatments for these diseases often focus on symptom management rather than addressing the root cause of the disease. Clustering antibodies can regulate a signaling cascade by binding two or more receptors and bringing them together in a highly specific conformation that enables activation or inhibition of downstream signaling. These antibodies promote complex assembly of receptors to either stimulate or inhibit pathogenically altered signaling pathways, paving the way for treatments that bring disease modification within reach.
Given the many potential binding sites between each receptor and an antibody, nearly infinite binding combinations exist, of which only a small subset will induce cell signaling. Historically, this has made identifying or rationally designing clustering antibodies difficult. The DIAGONAL Product Engine solves this challenge, combining proprietary computational and experimental techniques, enabling us to sift through billions of combinations at unprecedented speeds and identify clustering antibodies with high fidelity.
Our Pipeline
Our approach is effective and reliable. We have successfully demonstrated its utility across five structurally different receptor families.This versatility allows us to design multi-specific clustering antibodies to treat multiple diseases.Further, antibodies are an established therapeutic modality with many advantages, including high specificity, easy manufacturability, and straightforward patient administration.
HHT is a rare disease that affects more than 150,000 people in the US and EU, and for which there are currently no approved therapies. In HHT, loss of function point mutations in members of the TGF-β receptor superfamily complex create abnormal blood vessels that are fragile and susceptible to rupture and bleeding. These bleeding events lead to chronic anemia, necessitating frequent iron infusions or red blood cell transfusions. Internal arteriovenous malformations, if left untreated, are at risk of rupturing, resulting in lung and brain hemorrhage, stroke, heart failure, and death.
The study is a first-of-its-kind non-interventional, observational, longitudinal evaluation characterizing the variability of HHT patient-reported outcomes, including nosebleeds, hematologic support, and quality of life. To learn more about the HHT Impact study in partnership with Cure HHT, please visit: https://curehht.org/hhtimpact/.
PAH is an orphan disease that results in high blood pressure that affects the arteries in the lungs and the right side of the heart. In patients with PAH, narrowing of the vasculature is caused by an imbalance in the antiproliferative and hyperproliferative pathways. DIAG723 corrects signaling and restores vascular wall homeostasis.
Our Platform
Our platform enables us to rapidly discover clustering antibodies against any receptor complex of interest in a timeframe unimaginable using legacy approaches.
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Generation of deep immune repertoires of sequences to each target
We generate immune repertoires containing ~200,000 distinct antibody sequences that cover all possible binding sites on each receptor. Because we build multi-specific antibodies, there are >10 billion possible combinations.
Clustering by shape of antibodies
Shapes of antibodies predicted by computational methods are clustered to eliminate redundancies.
Binning by complementarity to the receptor
Distinctly shaped sequences are then grouped by their unique binding spots on the receptors.
Generation of antibodies based on possible bin combinations
One representative binder from each group is then combined into a multispecific antibody that is produced for experimental testing.
Optimizing molecular sequence characteristics
Once we identify a combination that induces signaling, we can go back to its group and cluster tofind additional binders that elicit the desired effect. This step allows us to pick molecules with the best characteristics.
Characterize in in vitro and in vivo models
These molecules are optimized using proprietary technologies to derive optimal antibodies to test in vitro and in vivo. This process leads us to clinical candidate selection.
Lead candidate progresses to human clinical trials
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About Us
At Diagonal Therapeutics, we have assembled a team of scientific and business leaders with extensive experience in building companies and developing innovative antibody therapies.
Leadership
Board of Directors
Investors
leadership
Alex Lugovskoy
Chief Executive Officer
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John Lee
Chief Medical Officer
Patrick Andre
Chief Scientific Officer
Sandra Teixeira
Chief Development Officer
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Eric Duhaime
SVP, Finance and Corporate Development
Board of Directors
Investors
Partner With Us
We have a big vision and an expansive opportunity.
Our platform can rapidly generate clustering antibody therapeutics against any target. We understand the value of collaborating with industry partners to explore more therapeutic ideas and deliver more drug candidates to patients in need.
If you are interested in working with us to expand the reach of our transformative approach, please contact us.
Our Team
Our success comes from discovering medicines that positively impact patients’ lives. To reach our goals, we believe it takes a nimble, cohesive team of experts capable of diligently reducing our ideas into practice. At Diagonal Therapeutics, we value agility, inclusion, effectiveness, and accountability in our work and operate with trust, respect, transparency, and integrity
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Get in Touch
General Contact: info@diagonaltx.com
Media Inquiries: media@diagonaltx.com
Clinical Trial Information: clinicalinfo@diagonaltx.com
200 Arsenal Yards Blvd, Suite 220
Watertown, MA 02472