FDA Orphan Drug Designation Granted to HT-KIT for Mastocytosis Treatment

A new molecular entity HT-KIT, has been granted orphan drug designation by the FDA for the treatment of mastocytosis, according to Hoth Therapeutics, Inc.¹

HT-KIT is designed to specifically target the receptor tyrosine kinase, KIT, which is required for proliferation, survival and differentiation of bone marrow-derived hematopoietic stem cells. Data from preclinical studies have shown that HT-KIT induces apoptosis of neoplastic mast cells and reduces metastasis associated with aggressive mastocytosis.

"This designation is an important milestone for HT-KIT, paving the drug development pathway to reach patients in need of new therapies for treatment of mastocytosis," said Stefanie Johns, PhD, chief scientific officer of Hoth. "It is an honor to develop a novel therapeutic like HT-KIT, which provides a new mechanism of action to tackle serious conditions such as aggressive systemic mastocytosis, mast cell leukemia, and systemic mastocytosis with associated hematologic neoplasm, acute myeloid leukemia, gastrointestinal stromal tumors, and other cKIT-driven diseases. Hoth will leverage provisions under the Orphan Drug Act to efficiently advance the HT-KIT therapeutic into the clinic."

HT-KIT shares the same molecular class as Hoth's current HT-004 drug which is currently in the late preclinical stage of development and is currently under investigation for treatment of asthma using inhalation administration.

In June 2021, positive results from a preclinical trial were presented and announced by Hoth discussing the potential of HT-KIT, an antisense oligonucleotide which works to target the proto-oncogene cKIT by inducing mRNA frameshifting.²

The preclinical trials were conducted using humanized mast cell neoplasm models. They were representative in vitro and in vivo models for aggressive, mast cell-derived cancers, including mast cell leukemia and mast cell sarcoma. Findings from the mouse models demonstrated that HT-KIT reduces KIT expression and induces apoptosis of neoplastic human mast cells and inhibits tumor growth in humanized xenograft mast cell neoplasia models.

Additionally, investigators found HT-KIT to reduce liver infiltration of neoplastic mast cells, reduce tumor growth in isograft models of mast cell neoplasia, and even reduce signs of mast cell leukemia in an isograft model of mutant mast cell neoplasia.

The positive results from the HT-KIT preclinical trial further reinforce the company’s belief that being able to target mutations in the KIT pathway could impact the way patients living with mast cell-derived cancers and related conditions are treated.

Hoth intends to pursue the anaphylaxis indication for HT-KIT in parallel to cancer treatment and HT-004 development.

References:

1. Hoth Therapeutics Announces orphan drug designation granted to cancer therapeutic HT-KIT to treat mastocytosis. News Release. Hoth Therapeutics, Inc. March 11, 2022. Accessed March 11, 2022. https://bit.ly/3t3Ol86

2. Hoth Therapeutics shares positive preclinical results of novel HT-KIT therapeutic. News Release. Hoth Therapeutics, Inc. June 03, 2021. Accessed March 11, 2022. https://prn.to/3i1Ew49