Novel senolytic drugs for the treatment of lung and kidney fibrosis

SENFIB aims to deliver new drugs for the treatment of fibrotic diseases. Nearly one quarter of the global population will be over the age of 65 by 2050.

Populations over 65 suffer from multiple degenerative diseases including tissue fibrosis, estimated to account for upwards of 45% of all-cause mortality.

Animal models have demonstrated that senescent cells are causative in many fibrotic diseases including lung (i.e. idiopathic pulmonary fibrosis, IPF), and chronic kidney disease (CKD).

Senescent cells have experienced damage or stress and have permanently exited the cell cycle, yet remain viable and long-lived, generating a persistent, sterile inflammation.

Selective elimination of senescent cells in animal models of IPF, CKD, and aging demonstrated improved organ function and viability.

Senolytics, molecules that induce preferential killing of senescent cells while leaving healthy cells intact, have emerged as a promising approach for tackling age-associated diseases; this was named one of the “10 Breakthrough Technologies” of 2020 by the MIT Technology Review.

Thus far, few senolytics have been identified; their mode of action is often unknown, some present serious toxicities, and none has yet been demonstrated to have therapeutic activity in clinical trials.We propose to launch a drug discovery program based on a prioritized novel genetic target for senolysis, which we have already validated as senolytic using a tool compound in an in vivo model of IPF.

We will deliver a lead series of molecules with IPR that meet all typical drug requirements plus in vivo Proof-of-Concept data in different mouse models of IPF and CKD.

The ultimate goal of this project is to develop candidates for translation into clinical use to ameliorate fibrotic diseases via the selective elimination of senescent cells.