HiberCell Announces Presentation at ASH, Highlighting Preclinical Data for HC-7366 with Standard of Care Agents in Acute Myeloid Leukemia (AML)

2023-12-18

AACR会议临床2期

HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics to address cancer relapse, metastasis, and resistance, today announced data from a poster presentation at the 65th ASH Annual Meeting and Exposition, which took place from December 9-12th, 2023 in San Diego, California.

“Our presentation at ASH builds on our poster presentation earlier this year at the AACR Special Conference in AML and showed the potential of HC-7366, an activator of integrated stress response (ISR) kinase GCN2, in addressing various resistance mechanisms of SOC agents, venetoclax and azacitidine,” said Jonathan Lanfear, President and Chief Executive Officer at HiberCell. “Our data also demonstrated that HC-7366 has monotherapy activity in TP53-mutant preclinical models as well as tumor regressions in models of AML as part of a triplet combination with venetoclax and azacitidine. Both the TP53-mutant and relapsed/refractory, to venetoclax and azacitidine, are settings with poor prognoses for patients and represent major unmet clinical needs. We look forward to providing additional information on our clinical development plans for HC-7366 in AML in 2024.”

Presentation Title: Activation of GCN2 by HC-7366 Results in Significant Anti-Tumor Efficacy As Monotherapy and Overcomes Resistance Mechanisms When Combined with Venetoclax in AML

Abstract Number, Link: 2943, https://ash.confex.com/ash/2023/webprogram/Paper181245.html

The poster presentation highlighted the following:

HC-7366 potently activates integrated stress response (ISR) signaling via GCN2 and shows single-agent antitumor activity in vivo in TP53-mutant AML CDX models.

Genome-wide CRISPR screen demonstrates that HC-7366-treated cells are sensitive to BCL2 inhibition.

The combination of HC-7366 and venetoclax shows combination benefit, characterized by enhanced activation of ISR by the doublet and inhibition of several modes of venetoclax resistance.

The triplet combination of low-dose HC-7366, venetoclax, and azacitidine is significantly more efficacious than the venetoclax/azacitidine doublet.

Importantly, the triplet combination also significantly inhibits the resistance mechanisms, including the anti-apoptotic MCL1 protein, a known mechanism of resistance to venetoclax.

Together, these data support the treatment of AML patients with HC-7366 in combination with venetoclax and azacitidine.

About HC-7366

HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have anti-tumor and immunomodulatory activity as a monotherapy and in combination with SOC agents in models of both solid and liquid tumors. HC-7366 is currently under investigation as monotherapy in Ph1a/1b studies in advanced solid tumors (NCT05121948).

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 advancing towards Phase 2 clinical development, modulates the anti-tumor innate immune response. For more information about HiberCell, please visit hibercell.com.

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