HiberCell Maps Forward Path for Novel GCN2 Activator, HC-7366 in Acute Myeloid Leukemia (AML)

• In vitro and in vivo results demonstrated HC-7366 is a potent GCN2 activator with strong antitumor activity in AML as a single agent and in combination with venetoclax; data supports further clinical development of HC-7366 as a treatment for AML
• Company received FDA clearance of Investigational New Drug (IND) application for Phase 1b clinical trial of HC-7366 for the treatment of AML

BOSTON, February 22, 2023 – HiberCell, a clinical-stage biotechnology company developing novel therapeutics to address mechanisms of metastasis,  treatment resistance and cancer relapse, today announced data from a recent poster presentation at the American Association for Cancer Research (AACR) Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome, which took place from January 23-25, 2023 in Austin, Texas. The Company also announced the recently cleared Investigational New Drug (IND) application for the initiation of clinical studies of HC-7366, the Company’s GCN2 stress response protein kinase modulator for the treatment of AML.

“We are excited by the results of our encouraging preclinical data on HC-7366 in AML, and with the recent IND clearance from the U.S. Food and Drug and Administration (FDA),” said Jonathan Lanfear, President and Chief Executive Officer at HiberCell. “The series of study results indicate that HC-7366, our first-in-class, first-in-human GCN2 activator, which is currently completing the expansion phase of a Phase 1a clinical trial in solid tumors, demonstrated significant anti-tumor efficacy as monotherapy and in combination with venetoclax in pre-clinical models of AML. We now plan to initiate a Phase 1b clinical trial of HC-7366 monotherapy in the AML indication following the completion of the current study in advanced solid tumors. We intend to investigate safety and tolerability of HC-7366 in subjects with relapsed/refractory AML and high-risk myelodysplastic syndromes to determine the recommended phase 2 dose of HC-7366 for combination with venetoclax.”

Mr. Lanfear continued, “GCN2 plays a critical role in the Integrated Stress Response, or ISR, pathway in response to metabolic stressors, and we are demonstrating a novel anti-tumor mechanism by activating this signaling pathway. As the ISR is a known resistance mechanism of venetoclax, we are excited by our findings that HC-7366 could potentially reverse some of these mechanisms. These data further support our overarching aim at HiberCell to design therapeutics that overcome the limitations of current treatment paradigms by targeting adaptive stress response pathways such as the ISR.”

The poster highlighted the following:

• Expression of GCN2 and ISR markers has been shown to be higher in primitive or minimally differentiated AML cells, prompting the study of HC-7366 in this setting.
• In vivo efficacy studies in the minimally differentiated AML models, MOLM-16 and KG-1, showed 100% complete response and 100% tumor growth inhibition, respectively.
• Increased expression of the ISR markers confirmed HC-7366 functioned as a GCN2 activator in vivo. The viability and marker effects of HC-7366 were confirmed to be on-target through GCN2 using CRISPR knockout cells.
• The combination of HC-7366 and venetoclax resulted in 26% tumor regression in the MV4-11 model, a differentiated subtype of AML that shows limited response to venetoclax.
• HC-7366 treatment impacted some of the previously characterized venetoclax resistance mechanisms
• In a xenotransplantable model of patient-derived AML, HC-7366 significantly reduced myeloid restricted precursor (CD34+CD33+) AML cells in all tissues, especially bone marrow as compared to venetoclax

About HC-7366

HC-7366, a first-in-class, first-in-human GCN2 activator. In preclinical studies, HC-7366 was observed to have robust anti-tumor and immunomodulatory activity in a variety of models of solid tumors and hematological malignancies. HC-7366 is under investigation in a Phase 1a/b trial as monotherapy for treatment of advanced solid tumors including head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC), transitional cell carcinoma of the bladder, and other solid tumors.

About HiberCell

HiberCell is a clinical stage oncology company, dedicated to the advancement of first-in-class agents with the novel MOA of modulation of adaptive stress pathways and anti-tumor immunity. We believe that therapeutic modulation of these mechanisms allows us to address tumor metastasis, treatment resistance, and cancer relapse; all significant drivers of cancer-related deaths. Our product candidates HC-5404 and HC-7366, both completing Phase 1a clinical trials, target the stress response kinases PERK and GCN2, respectively, while our product candidate odetiglucan, currently in Phase 2 clinical development, modulates the anti-tumor innate immune response.

Contact:

Suzanne Messere

Stern Investor Relations Inc.

212.698.8801

suzanne.messere@sternir.com