Inhibiting latent TGFβ

WIKIMEDIA: European Bioinformatics Institute

Selective inhibitors of TGFβ1

While TGFβ is at the apex of the fibrotic signaling cascade, there are safety concerns linked to off-target effects of neighboring growth factors by non-selective approaches.

Scholar Rock identified potent and selective inhibitors of TGFβ1 signaling at the source of disease in the tissue microenvironment. Preclinical studies show that these highly specific inhibitors can prevent the activation of the growth factor in the fibrotic matrix and may offer a powerful new approach to suppressing pro-fibrotic signaling in multiple organs.

Scholar Rock is collaborating with Gilead with the aim of selecting molecules to be developed as new medicines for patients with fibrotic diseases.

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Scholar Rock

Targeting growth factors

Cells produce protein growth factors in the precursor, or latent, form. For the mature growth factor to carry out its function, it must be activated (through molecular events) and separated from the prodomain.

Scholar Rock monoclonal antibodies target the prodomain of the precursor, or latent form of growth factors, and block the cage’s lock to inhibit activation. Given the much greater structural differences of the prodomain, we leverage this variance to achieve extraordinary selectivity.

With greater selectivity, we aim to minimize toxicity that have challenged approaches that target the mature form of growth factors.

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Targeting ‘zombie cells’

Excerpt

Lewis Gruber, who’s turning 70 this year, says he has no plans on dying.

Well, that’s not entirely true. The biotech entrepreneur has prepared a will. And when pressed on exactly how long he expects to live, he replied calmly, “Something on the order of 120 I wouldn’t think would be out of the realm of possibility.”

Gruber is the co-founder and chief scientific officer of SIWA Therapeutics, a Chicago biotech startup focused on “anti-aging.” The company is developing a drug that aims to cure a variety of aging-related diseases by targeting senescent cells. Senescent cells, sometimes referred to as “zombie cells,” stop dividing and repairing tissue. They can accumulate in the body and feed tumor growth and interfere with the body’s natural ability to repair itself.

SIWA says it has discovered a monoclonal antibody, called SIWA 318H, that selectively binds to and removes both senescent cells and cancer cells. The startup will initially focus its therapy on cancer, specifically pancreatic cancer to start, and believes it has the potential to become the first comprehensive cancer therapy to reduce cancer cells as well as the senescent cells that feed tumor growth.

SIWA, which is currently in the pre-clinical stage, hopes to tackle a range of different cancers and other aging-related diseases, like breast cancer, Alzheimer’s disease, Parkinson’s and ALS.

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