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.

Leadership

Board of Directors

Investors

leadership

Alex Lugovskoy

Alex Lugovskoy

Chief Executive Officer

BIO

Patrick Andre

Patrick Andre

Chief Scientific Officer

BIO

Sandra Teixeira

Sandra Teixeira

Chief Development Officer

BIO

Eric Duhaime

Eric Duhaime

SVP, Finance and Corporate Development

BIO

Melissa Geddie

Melissa Geddie

VP, Drug Discovery

BIO

JC Hus

JC Hus

Sr. Director, Informatics

BIO

Board of Directors

Michael Gladstone (Board Chair)

Partner, Atlas Venture

Shelley Chu, MD, PhD

Partner, Lightspeed Venture Partners

James Topper, MD, PhD

Managing Partner, Frazier Life Sciences

Amol Punjabi

Principal, BVF Partners

Jernej Godec, PhD

Principal, Atlas Venture

Clayton Knox, MD

Managing Partner, Velosity Capital

Barbara Fox, PhD

Independent Director

Alex Lugovskoy, PhD

President & CEO, Diagonal Therapeutics

Investors

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.

Our Values: Trust, Transparency, Agility, Accountability, Respect, Inclusion, Integrity, Effectiveness

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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

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