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Targeting glioblastoma with CM93, a novel EGFR inhibitor with exceptional brain penetration

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA281586-01
Agency Tracking Number: R41CA281586
Amount: $400,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NCI
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-05-15
Award End Date (Contract End Date): 2024-04-30
Small Business Information
Brookline, MA 02446
United States
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: Yes
Principal Investigator
 (617) 632-2932
Business Contact
Phone: (617) 823-3851
Research Institution
BOSTON, MA 02215-5450
United States

 Domestic Nonprofit Research Organization

The epidermal growth factor receptor (EGFR) gene is mutated and/or amplified in majority of
primary glioblastoma (GBM). While EGFR-mutant GBM cancer cells are dependent on EGFR
signaling for survival, numerous small molecule EGFR tyrosine kinase inhibitors (TKIs) have failed
to show efficacy in this disease. There are two main reasons for these failures: i) Many of these
EGFR-TKIs fail to cross the blood-brain barrier (BBB); ii) These EGFR-TKIs were developed to
specifically target mutant EGFRs with mutations in the kinase domain found in non-small cell lung
cancer (NSCLC), but they have poor activity (low binding affinity) against GBM EGFR variants
with a wild-type tyrosine kinase domain. CM93 has been developed at Crimson Biopharm as a
novel therapeutic agent to specifically tackle these challenges in treating GBM. CM93 has distinct
features that set it apart from all other EGFR-TKIs, including osimertinib. CM93 is highly enriched
in the brain, with an exceedingly low blood concentration (rt2,000% brain penetration). This
extraordinary property of CM93, in conjunction with its high potency against EGFR with wild-type
tyrosine kinase domain, offers a powerful and unique opportunity for CM93 to effectively inhibit
GBM with EGFR variants without significant systemic toxicity. Notably, CM93 has received IND
approval for the first-in-human phase 1 clinical trial in GBM patients and is currently part of
NIH/NCI’s “Glioblastoma Therapeutics Network (GTN)” to conduct phase 1 and surgical window
studies led by Dr. Patrick Wen, Director of Neuro-Oncology at Dana-Farber Cancer Institute
(DFCI). The overall objective of this STTR application is to evaluate the combination of CM93 with
abemaciclib (an approved CDK4/6 inhibitor with notable CNS activity as proposed in Aim1 and
biomarker analyses in Aim 2 in patient-derived GBM models to provide important pre-clinical proof
of concept to better support CM93’s first-in-human phase 1 and window-of-opportunity surgical

* Information listed above is at the time of submission. *

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