# Third line treatment of drug resistant FLT3-positive acute myeloid leukemia with a novel FLT3 kinase inhibitor

> **NIH NIH R44** · KINARX, LLC · 2021 · $999,998

## Abstract

Project Summary
Acute myeloid leukemia (AML) is one of the most challenging malignancies with the 5-year survival for younger
and medically fit patients hovering around the 30% mark for over 3 decades. About 30% of AML patients harbor
activating mutations in FLT3 kinase that are associated with very poor prognosis. The non-specific tyrosine
kinase inhibitor (TKI) Midostaurin was approved in 2017 for combination treatment with standard chemotherapy.
However, remission achieved with this treatment, if any, is short-lived. FLT3-AML patients that relapse or are
refractory to this treatment are treated with newly developed, more specific, FLT3 inhibitors Quizartinib and
Crenolanib that are in clinical development or Gilteritinib that was recently approved. However, this treatment
also eventually fails due to emergence of secondary FLT3 mutations within the tyrosine kinase domain and/or
upregulation of compensatory resistance pathways. For these patients the time to death is around 3 months with
no 3rd line treatment option available. KinaRx has developed a novel class of orally bioavailable 5-substituted
aminonapthyridine TKIs that are active against secondary mutated FLT3 resistant to the 1st and 2nd generation
FLT3 inhibitors. Extensive in vitro and in vivo data, including protection in orthotopic mouse models of drug
resistant FLT3-AML presented in this proposal, establish our lead compound KRX-101 as the best-in-class FLT3
inhibitor and a strong candidate as 3rd line treatment option for FLT3 mutated relapsed or refractory patients that
do not respond to gilteritinib, crenolanib or quizartinib. In this multiple PI, Direct to Phase II SBIR, we propose to
advance KRX-101 through completion of IND-enabling studies. In Aim 1 we will technology transfer the synthesis
procedure and analytical methods to CMO for process scale up, analytical development, and production of a 100
g demonstration lot. In Aim 2, we will complete efficacy data package including activity toward primary AML cells
and efficacy in patient-derived xenograft models and conduct preliminary safety studies. Aim 3 will focus on
developing a regulatory strategy and holding a Pre-IND meeting with FDA. A GLP toxicology lot (5 kg) will be
produced in Aim 4 and used to conduct a full battery of IND-enabling GLP safety-pharmacology studies in Aim
5. The project brings together a strong team of investigators with decades of experience in drug discovery and
development: Dr. Holtsberg, VP of Operations at KinaRx with 25 years of experience in pharma and biotech, Dr.
Sintim, Professor of Chemistry at Purdue University an expert in anti-cancer drug discovery and the inventor of
KRX compound series, Dr. Emadi, Professor of Hematology and Oncology at University of Maryland (UMB), a
highly experienced clinician, former regulatory officer at FDA, and a recognized expert in hematological
malignancies with a focus on clinical research and management of AML, Dr. Lapidus, Associate Professor at
UMB, an ex...

## Key facts

- **NIH application ID:** 10169389
- **Project number:** 5R44CA247134-02
- **Recipient organization:** KINARX, LLC
- **Principal Investigator:** Frederick Wayne Holtsberg
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $999,998
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169389

## Citation

> US National Institutes of Health, RePORTER application 10169389, Third line treatment of drug resistant FLT3-positive acute myeloid leukemia with a novel FLT3 kinase inhibitor (5R44CA247134-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10169389. Licensed CC0.

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