Honors Gallery

Technology Transfer of Anti-Leukemia Product Candidates to Kurome Therapeutics

Award: Educational Institution and Federal Laboratory Partnership

Year: 2020

Award Type: Regional

Region: Mid-Atlantic

National Center for Advancing Translational Sciences (NCATS)

The National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (“NIH”), and Cincinnati Children’s Hospital Medical Center (CCHMC), have collaborated to develop small molecules that potently inhibit both the interleukin-1 receptor-associated kinase (IRAK) and FLT3 kinase enzymes, which play key roles in driving the progression of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). AML and MDS are blood cell cancers that urgently need improved treatments. Collectively, more than 30,000 new cases of MDS and AML are diagnosed in the United States each year. The median survival time for MDS is only 2.5 years after diagnosis, and the 5-year survival rate for AML is only 27%. Small molecule inhibitors of FLT3 have previously been advanced into the clinic and have shown initial promise in treating AML. However, FLT3 inhibitors have not provided long-lasting remission, since FLT3 inhibition results in increased compensatory signaling through IRAK1/4. The dual Inhibitors of IRAK and FLT3 (Inhibitor), co-developed by NCATS and CCHMC, will have potential to provide longterm treatments for MDS and AML.  

To advance the novel inhibitors as anti-leukemia drug candidates into clinic application (Project), Cincinnati Children’s Innovation Ventures (CCIV) and NCATS Office of Strategic Alliance (Offices) worked closely to explore pathways to support technology development. The Offices entered into an inter-institutional agreement (IIA), thereby allowing CCIV to take the lead in filing patent applications, and marketing and exclusively licensing their joint intellectual property (IP). CCIV filed and secured patents for the composition of matter and the methods of use for the Inhibitors.  

The project was in the late preclinical development phase (i.e. “Valley of Death”) after a lead product candidate is identified. This phase of product development often fails, because it is significantly more expensive than early-stage discovery, it involves lengthy process development, scale-up, and INDenabling toxicology testing and is less likely to receive federal funding.  

CCIV, in collaboration with NCATS, reached out to many biotech and big pharma. CCIV found that the conventional licensing approach did not work for this project. Established companies regarded the project as still early with big technical risks. Many of the companies shared feedback in that they would be willing to step in with a license or collaboration only after the project shows promise in preclinical development. CCIV aimed to establish a start-up whose sole focus is to develop the technologies. CCIV recruited an experienced entrepreneur-in-residence (EIR), Dr. Jan Rosenbaum, to manage the project operation and to coordinate product development by NCATS and CCHMC investigators. CCIV worked closely with Dr. Rosenbaum to develop a business plan and an investment pitch deck, with scientific input from CCHMC and NCATS investigators. CCIV presented the project to and secured commitment of equity investments from Cincinnati Children’s Investment Committee and angel/VC investment funds including CincyTech.  

In late January of 2020, CCIV facilitated to create a start-up, Kurome Therapeutics (Kurome), whose mission is to dedicate to pre-clinical and clinical development of the novel IRAK/FLT3 inhibitors. Dr. Rosenbaum became Kurome’s chief scientific officer and acting president/CEO. Kurome is raising series seed financing for $4 million to fully support drug lead optimization and other preclinical developments. Both CCHMC and CincyTech invested in the company.  

The Offices worked together to enable CCHMC to enter into an exclusive license with Kurome for the IP covering novel inhibitors and for the treatment and diagnostic applications for AML, MDS and solid tumors. CCHMC, Kurome, and NCATS also entered into a cooperative research and development agreement (CRADA), providing Kurome options to license future IP relevant to the inhibitors.  

The dual Inhibitors of IRAK and FLT3 (Inhibitor), co-developed by NCATS and CCHMC, will have potential to provide longterm treatments for MDS and AML.  

Since Kurome was founded in January of 2020, it has used the proceeds from the series seed investments to fund ongoing preclinical developments by the investigators at NCATS and CCHMC, dramatically accelerating the drug development. Significant progress has already been made, as optimized drug leads have been developed. 

NCATS, the newest of the 27 institutes and centers of the NIH, was established to transform the translation of scientific discoveries so that new treatments and cures for disease can be delivered to patients faster. Cincinnati Children’s is a world leader in pediatric healthcare, with a reputation for excellence in patient care, research & medical education.  

The principal investigators (PI) of the Project include Dr. Craig Thomas and Dr. Scott Hoyt at NCATS and Dr. Daniel Starczynowski at CCHMC. Dr. Thomas is a Leader of Chemistry Technologies at NCATS. Dr. Hoyt was a Principal Scientist in Discovery Chemistry at Merck Research Laboratories before he joined NCATS as a Chemistry Group Leader. Dr. Starczynowski is a Professor at Experimental Hematology and Cancer Biology of CCHMC.  

The PIs developed novel IRAK/FLT3 inhibitors with proof-of-efficacy in relevant molecular and cellular assays and animal models. At this stage, novel medical therapeutic development is at risk of languishing, often because of insufficient access to suitable funding or lack of expertise to develop ideas beyond the academic laboratory. To accelerate discoveries into clinical applications and market and thereby to improve the health of patients, CCIV worked closely with NCATS Office of Strategic Alliance to manage the technology development of the Project. Ami Gadhia, a Sr. Technology Transfer and Patenting Specialist at NCATS, and David Wang, a Senior Acceleration Manager at CCIV, were the Technology Transfer/Portfolio Managers. Lili Portilla, Director of the Office of Strategic Alliances at NCATS was instrumental in collaborating with Ami and David to help navigate the technology transfer pathway. Mayra Alvarez, the NCATS Program Specialist, worked to docket relevant IP information and agreements to meet NCATS/NIH requirements.  

CCIV filed and secured patents for the novel IRAK/FLT3 inhibitors, and is still managing the patent prosecution for the project even after Kurome is created.  

It is crucial to secure appropriate funding in order to move the Project forward, and it is challenging to obtain funding to support translation of cutting-edge but still immature technologies. CCIV facilitated series seed funding for Kurome from Cincinnati Children’s and angel/VC investment funds including CincyTech. Recruitment of experienced management is one of the most important endeavors for the success of a newco. CCIV engaged Dr. Jan Rosenbaum, who had a deep scientific background in the area of interest and translational expertise, to be EIR for the project before Kurome is created. Dr. Rosenbaum later became CSO and acting CEO of Kurome, and she works closely with the project PIs and effectively and efficiently manages the drug development.  

Technology transfer agreements are essential for Newcos. NCATS Office of Strategic Alliance and CCIV facilitated to have CCHMC enter into an exclusive license with Kurome for the IP covering novel IRAK/FLT3 inhibitors, and to have CCHMC and NCATS enter into a CRADA with Kurome. The CRADA provides Kurome an option to license future IP relevant to the optimized drug leads. The exclusive license agreement and the CRADA provide Kurome with a sustainable intellectual property portfolio.  

By making significant progresses in patent prosecution, management recruitment, fund raising, and technology transfer, the Offices laid a solid foundation for accelerated drug development of the Project and for the success of Kurome. 

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