• Data demonstrating favorable safety and tolerability profile; a maximum tolerated dose (MTD) was not determined
• Dose-dependent exposure and pathway engagement observed starting from lowest dose levels
• Preliminary signs of efficacy in multiple tumor types, including Renal Cell Carcinoma (RCC):
  1 partial response and multiple patients with stable disease in heavily pre-treated population

• Company seeking partners to advance HC-5404 in combination with standard of care VEGFR Tyrosine Kinase Inhibitors (TKIs)

NEW YORK, Nov. 27, 2023 (GLOBE NEWSWIRE) — HiberCell, a clinical-stage biotechnology company dedicated to addressing mechanisms of treatment resistance, cancer relapse, and metastasis, today announced the successful completion of its Phase 1 study of the novel PERK inhibitor, HC-5404, in solid tumors along with two pre-clinical publications in one of the leading journals of AACR, Clinical Cancer Research (CCR).

“We are excited to announce the successful completion of our Phase 1 monotherapy study of HC-5404 along with the two publications in Clinical Cancer Research,” said Jonathan Lanfear, President and CEO. “We are encouraged by the safety profile, dose-dependent exposure, and pathway engagement, as well as the preliminary signals of efficacy observed in our Phase 1 trial. This provides a forward path for Ph1b/Ph2 studies in multiple indications/combinations as outlined in our publications in Clinical Cancer Research. Our publications also highlight some of the promise of HC-5404, including the potential to resensitize tumors to TKI therapy, increase the overall response rate in combination with TKI as demonstrated in PDX models, as well as inhibiting metastasis by blocking survival of disseminated dormant cancer cells.”

The Phase 1 trial (NCT04834778) was designed to study the safety and tolerability, MTD, and pharmacokinetics (PK)/pharmacodynamics (PD) of HC-5404 in multiple solid tumor types. The study used a BOIN design to explore dose-levels ranging from 25 mg to 600 mg and demonstrated a favorable safety and tolerability profile. Notably, the MTD was not determined in the population evaluable for safety (N=23). The most common treatment-related adverse events observed included nausea, fatigue, diarrhea, and dry mouth. Furthermore, HC-5404 demonstrated dose-dependent exposure and pharmacodynamic responses consistent with pathway engagement even at the starting dose of 25 mg. Preliminary signs of efficacy included one patient who achieved a durable partial response (with a duration of response of greater than two years and ongoing), multiple patients demonstrating stable disease, and four patients (17.4%) remaining on therapy for >180 days.

Additionally, HiberCell announced the publication of “PERK inhibition by HC-5404 sensitizes renal cell carcinoma tumor models to antiangiogenic tyrosine kinase inhibitors,” illustrating significant anti-tumor activity when combined with standard of care VEGFR TKIs. HC-5404, by disrupting PERK-mediated adaptive stress response evoked by VEGFR-TKIs, presents a potential opportunity to address the acquired resistance mechanism of the TKIs. HiberCell is seeking partners to advance HC-5404 in combination with an antiangiogenic VEGFR TKI in the solid tumor metastatic setting. Link: https://doi.org/10.1158/1078-0432.CCR-23-1182

Albert Einstein College of Medicine also announced a second publication relating to HiberCell’s HC-5404 titled “A PERK specific inhibitor blocks metastatic progression by limiting integrated stress response-dependent survival of quiescent cancer cells.” This paper, developed in collaboration with HiberCell scientists speaks to the potential of HC-5404 in preventing metastasis and its potential use in earlier lines of treatment including dormant minimal residual disease . More information can be found in Albert Einstein College of Medicine’s press release and publication linked below. Press Release: https://www.einsteinmed.edu/news/12111/hope-for-eradicating-dormant-but-deadly-cancer-cells/; Publication: https://doi.org/10.1158/1078-0432.CCR-23-1427

About HC-5404

HC-5404 is a first-in-class, first-in-human selective and potent PKR-like endoplasmic reticulum kinase (PERK) inhibitor. PERK is a kinase of the Unfolded Protein Response (UPR), an adaptive cellular program used by cancer cells to survive by facilitating adaptation to harsh tumor microenvironments characterized by hypoxia, nutrient deprivation and oxidative stress. In preclinical studies, inhibition of PERK with HC-5404 has been shown to have anti-tumor and immunomodulatory activity. HC-5404 was investigated in a Phase 1 clinical trial for solid tumors (NCT04834778).

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.

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