ADVANCING A GROUND-BREAKING APPROACH TO AGONIST ANTIBODY THERAPEUTICS
We are advancing medicines that reactivate critical biological pathways to treat the underlying cause of debilitating diseases.
Our Approach
Unlike most approved antibodies, which inhibit a cellular function, agonist antibodies activate a signaling cascade by binding two receptors and bringing them together in a highly specific conformation that enables their activation. Given the many potential binding sites between each receptor and an antibody, nearly infinite binding combinations exist, of which only a small subset will result in the desired agonistic activity. Historically, this has made identifying or rationally designing agonist antibodies difficult.
The DIAGONAL platform solves this challenge, combining proprietary computational and experimental techniques, enabling us to sift through billions of combinations at unprecedented speeds and find agonists with high fidelity.
Our Platform
Our platform enables us to rapidly discover agonist 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 multispecific 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 multi-specific antibody that is produced for experimental testing.
Optimizing molecular sequence characteristics
Once we identify a combination that elicits agonism, we can go back to its group and cluster to find additional binders that elicit agonism. 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 agonists 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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Our Pipeline
Our approach is effective and reliable. We have successfully demonstrated its utility across four structurally different receptor families. This versatility allows us to design agonist antibodies to treat multiple diseases. Further, antibodies are an established therapeutic modality with many advantages including high specificity, easy manufacturability, and straightforward patient administration.
PROGRAM
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Agonist Antibody for Hereditary Hemorrhagic Telangiectasia (HHT)
discovery
development
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HHT is a monogenic, orphan disease that affects more than 150,000 patients in the US and EU and for which there are currently no approved therapies. In HHT, mutations in the TGF-β receptor superfamily complex create two types of abnormal blood vessels - telangiectasias and arteriovenous malformations (AVMs)— that are fragile and susceptible to rupture and bleeding. These bleeding events lead to chronic anemia in patients necessitating iron infusions or red blood cell transfusions. AVMs, if left untreated, may result in lung and brain hemorrhage, stroke, heart failure, and death.
In preclinical models of HHT, our agonist antibodies reactivate an essential signaling cascade and address the root cause of HHT, reducing bleeding and reversing AVM formation.
Agonist Antibody for Pulmonary Arterial Hypertension (PAH)
discovery
development
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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. Diagonal's agonist antibody corrects signaling and restores vascular wall homeostasis.
Unnamed Target for Genetically Defined Vasculopathy
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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.
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Board of Directors
Investors
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Board of Directors
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Partner with Us
We have a big vision with an expansive opportunity.
Our platform can rapidly generate agonist 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
BD Opportunities: bd@diagonaltx.com
Media Inquiries: media@diagonaltx.com
200 Arsenal Yards Blvd, Suite 220
Watertown, MA 02472