TTI-101 Receives FDA’s Orphan Drug Status for IPF

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by Patricia Inácio, PhD |

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The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Tvardi Therapeutics’ TTI-101 for the treatment of idiopathic pulmonary fibrosis (IPF).

TTI-101 is a small molecule, given orally, that acts as a direct inhibitor of STAT3, an inflammatory protein that plays a role in the development and progression of fibrosis, or tissue scarring.

Pulmonary fibrosis (PF) is characterized by the abnormal activation and excessive growth of fibroblasts — the cells responsible for making collagen and other molecules that, when present in excessive amounts, can lead to tissue scarring. Blocking STAT3 may reduce fibroblast activation and proliferation and thereby lessen or reverse signs of fibrosis.

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Orphan drug status is awarded by the FDA to encourage the development of therapies for rare and serious diseases — those affecting fewer than 200,000 people in the U.S. — through several incentives. These include seven years of market exclusivity upon approval and exemption from regulatory application fees.

“We are pleased to receive Orphan Drug Designation from the FDA for TTI-101 for the treatment of IPF,” Imran Alibhai, PhD, CEO of Tvardi, said in a press release. “This designation provides further support for the development of TTI-101, which has shown promise in treating diseases in which STAT3 plays a critical role.”

In preclinical studies, STAT3 inhibition with TTI-101 reversed scarring and restored lung function in animal models of IPF.

STAT3 is overly active in several tumors, and preclinical data in mice showed that TTI-101 impaired the growth of several solid tumors, including those in the breast, head and neck, lung, and liver. The therapy was deemed safe when administered at high doses to mice, rats, and dogs.

This has prompted the launch of a Phase 1 trial (NCT03195699), currently recruiting participants, to assess the maximum tolerated dose, as well as the therapy’s pharmacokinetics profile in patients with advanced solid tumors. Pharmacokinetics refers to the movement of a medicine into, through, and out of the body.

A Phase 1/2 trial (NCT05384119) is also testing the combination of TTI-101 with targeted therapies in those with hard-to-treat breast cancer. According to Tvardi, Phase 2 trials are planned for this year to test TTI-101 in patients with IPF and cancer.

“Tvardi is dedicated to pursuing treatment of STAT3-driven diseases with TTI-101, beginning with a Phase 1 trial in oncology and now advancing to Phase 2 clinical trials in both IPF and oncology,” Alibhai said.