THE FUTURE OF
ANTIBODY DRUG CONJUGATES FOR FIBROSIS & ONCOLOGY
IS HERE

An innovative approach improving efficacy while mitigating risks associated with systemic TGF-ß therapies

TGF-ß, a pleiotropic cytokine, has been clinically validated as a causal driver in cancer and multiple fibrotic diseases.

Systemic TGF-ß therapies, however, have limited clinical efficacy and cause significant host toxicity, especially to the heart.

At Synthis Therapeutics, we developed a first-in-class anti-fibrotic antibody drug conjugate (ADC) that selectively inhibits TGF-ß in disease driving cells.

SYNTHIS THERAPEUTICS

Developing Novel Therapies that Selectively Block TGF-ß for Cancer and Fibrotic Indications

In fibrotic diseases, excessive and unrelenting TGF-ß production is the main driver of tissue scarring and extracellular matrix deposition, leading to organ failure.

In cancer patients, TGF-ß is a dominant immunosuppressive cytokine that shuts down immune-mediated tumor clearance and drives resistance to cancer therapies (i.e., PD(L)1, CAR-T, radiation).

CURRENT DRUG STATUS

Despite long standing pharma interest in developing TGF-ß therapies for cancer and fibrotic indications,
there are no FDA-approved TGF-ß therapies yet.

A majority of cancer patients and patients with fibrotic diseases would benefit from selective TGF-ß therapies, such as the ones developed by Synthis Therapeutics.

APPROACH

How do we improve the safety and efficacy of TGF-ß therapies?

ADCs with a First-in-Class TGF-ß inhibitor payload

SYSTEMIC TGF-ß THERAPIES WITH LIMITATIONS

Systemic ALK5 inhibitors block TGF-ß signaling in all tissues, leading to toxicity, limited efficacy and a narrow therapeutic window. Synthis’ therapeutic modality and MOA solve this issue of toxicity and limited efficacy of systemic TGF-ß therapies.

Our cell-selective approach leads to improved efficacy, wider therapeutic window and no systemic toxicity.

SYNTHIS' CELL-SELECTIVE TGF-ß THERAPY

We developed a first-in-class ADC platform, built around our proprietary, linkable TGF-ß inhibitor payload. It can be conjugated to virtually any antibody to selectively block TGF-ß in disease driving cells, sparing host tissues.

We developed two distinct ADCs with the same TGF-ß payload.

SYN101 is an immune cell-targeted ADC. SYN303 is a myofibroblast targeted ADC. Both are effective and safe.

The efficacy of our two drugs has been demonstrated in the bleomycin lung fibrosis mouse model (SYN303) and in multiple tumor models in vivo (SYN101).

A DISTINCTIVE PAYLOAD

Most ADC payloads are cytotoxic.

Our first-in-class Synthis-003 payload is a novel kinase inhibitor selective for the TGF-ß receptor, ALK5. It is non-cytotoxic, highly potent, linkable and has broad utility across multiple disease areas and cell populations.

his unique payload can be conjugated to known or novel antibody targets to differentiate the MOAs and provide novel IP and composition of matter in other diseases. Synthis-003 is IP protected, with freedom to operate.

We are currently looking for partnerships to broaden our pipeline of targeted TGF-ß therapies in a variety of diseases, including cancer, IPF, myelofibrosis, scleroderma-ILD, fibrostenosing Crohn’s disease, kidney fibrosis, PAH, etc.