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Programs

Opportunity

It’s time we recognize cancer as a chronic disease and focus on developing therapies that address the most common cause of cancer mortality: relapse and metastasis.

Cancers usually start localized within a single tissue and then cells from the primary tumor spread to other organs. So even when primary tumors are surgically removed or seem to have been successfully cleared, treatment-resistant cancer cells have often already disseminated elsewhere in the body and lie dormant, waiting to reawaken as relapse and metastatic disease.

The immunosuppressive tumor microenvironment and adaptive stress biology allow these cells to persist. We believe treatments focused on modulating these foundational barriers will meaningfully impact patient outcomes.

Science

We have leveraged the scientific insight of the HiberCell team and experts in the field to define the key barriers of the tumor microenvironment and adaptive stress response that our therapeutic programs need to address.

As such, our programs are focused on delivering:

Single agent/standard-of-care combinations to modulate stress biology in primary tumors
Therapeutic modulation of stress-mediated adaptivity and tumor survival
Strategies that address the multifaceted nature of relapse and metastasis

the journey of a cancer cell

View the following animation to follow the journey of a cancer cell from undetectable to cancer diagnosis, and then into a dormant phase, before a transition to relapse and metastatic disease.

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Undetected

1. Undetected

Cancers can exist for years in premalignant forms. In the preinvasive stage, cancer is undetected and minimally or not proliferating.

Diagnosis / First-line treatment

2. Diagnosis / First-line treatment

In the invasive stage, a malignant lesion grows and is detected.
Primary tumors are treated in this stage via therapeutics, radiation, and/or resection.

Foundational BarriersAdaptive stress biology / Tumor microenvironment

Pipeline MoleculesImprime / PERK Inhibitor / ISR Modulator

Clinical Dormancy

3. Clinical Dormancy

Successful treatment or resection of a primary tumor leads to a period of minimal residual disease. Current standard of care involves ongoing monitoring for cancer relapse or metastasis.

Foundational BarriersTumor microenvironment / Adaptive stress biology / Non-proliferating, treatment-resistant cells

Pipeline MoleculesPERK Inhibitor / ISR Modulator

Detectable Metastatic Disease

4. Detectable Metastatic Disease

Malignant lesions reemerge, either at the same site as the primary tumor or in new locations. There are few effective therapeutic options in this setting.

Foundational BarriersTumor microenvironment / Adaptive stress biology / Non-proliferating, treatment-resistant cells

Pipeline MoleculesImprime / PERK Inhibitor / ISR Modulator

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Foundational Barriers

Explore the following graphics to understand how the tumor microenvironment and stress biology interfere with cancer treatment response, and the therapeutic opportunities found within HiberCell’s pipeline to overcome these barriers.

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Tumor Microenvironment

Stress Biology

Ineffective anti-cancer immune responses may result from limited T-cell based anti-cancer immunity, insufficient antigen presentation, or a suppressive tumor microenvironment.

Strategies aimed at overcoming these barriers will provide patients with an opportunity for robust and durable clinical responses.

As a systemically-administered innate immune activator, Imprime PGG has the potential to significantly increase the number of patients who benefit from combinatorial approaches with immuno-oncology therapies such as checkpoint inhibitors.

Imprime PGG primes the innate immune system and reprograms the immunosuppressive tumor microenvironment to drive enhanced antigen presentation, triggering T-cell activation and ultimately enhancing the immune response against tumors.

Cancer cells are exposed to a wide range of stressors including the accumulation of reactive oxygen species, hypoxia, nutrient deprivation, and ER dysfunction leading to accumulation of unfolded proteins, among others.

Stress biology is a foundational barrier, which contributes to tumor cell dormancy, malignancy and drug resistance.

The adaptive stress response provides a key survival advantage to cancer cells.

Inhibiting the kinases known to mediate the unfolded protein response (UPR) and integrated stress response (ISR) represent a unique context-dependent therapeutic approach. Addressing stress biology is a differentiated opportunity to provide both direct anti-tumor activity and reprogram the tumor micro-environment.

HiberCell is developing a PERK inhibitor to address UPR-driven ER Stress and a ISR- modulator. These first-in-human programs will have applications for solid and hematologic cancers and be tested in the primary tumor and relapse/metastasis settings.

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Pipeline

Tumor Microenvironment Modulator

Therapy

Imprime PGG (+ Immune Checkpoint Inhibitor)

Indication

Treatment-Naïve, Resectable, Stage III Melanoma

Preclinical

Phase 1

Phase 2

Phase 3

Treatment-Naïve, Resectable, Stage III Melanoma

Rationale: ICI monotherapy can induce pathological responses in ~ 30% stage III, resectable, melanoma patients and extend the time to progression (TTP). The addition of Imprime PGG to ICI therapy may enhance complete pathologic response rates and further extend the TTP, “vaccinating” these patients against disease recurrence.

Key endpoints: Pathologic Complete Response (pCR), Pathologic Partial Response

Design: Imprime + ICI (n=60) vs ICI alone (n=20)

Therapy

Imprime PGG (+ Immune Checkpoint Inhibitor)

Indication

Metastatic Breast Cancer Post HR Failure

Preclinical

Phase 1

Phase 2

Phase 3

Metastatic Breast Cancer Post HR Failure

Rationale: In combination with ICI therapy, Imprime has demonstrated clinical benefit for mBC patients who have progressed through hormone +/- CDK4/6 inhibitor therapy and have “converted” to ER/PR- status. The combination of Imprime + ICI therapy may provide novel clinical benefit after progression through hormonal therapy +/- CDK4/6 inhibitors for these ER/PR- patients as well as for patients who remain ER/PR+ at progression.

Key endpoints: ORR by RECISTv1.1, PFS, OS

Design: Imprime + ICI (n =70) in ABA+, metastatic breast cancer patients immediately after progression through hormonal therapy +/- CDK4/6 inhibitors

Adaptive Stress Modulators

Therapy

PERK Inhibitor

Indication

Renal Cell Carcinoma (CC and VHLm), Breast (HER2+), Gastric and Small Cell Lung Cancer

Preclinical

Phase 1

Phase 2

Phase 3

Renal Cell Carcinoma (CC and VHLm), Breast (HER2+), Gastric and Small Cell Lung Cancer

Description: An orally bioavailable protein kinase R–like endoplasmic reticulum kinase (PERK) inhibitor providing anti-tumor monotherapy & combinatorial activity in several stress mediated tumor types.

Rationale: A basket trial evaluating the tumor types that are endowed with an inherently stressful microenvironment or are driven by mutations that trigger this ‘context’ of stress.

Key endpoints: Safety, ORR, PFS, OS, Disease Control and Stabilization, Biomarker Endpoints

Design: Monotherapy and/or SOC combination

Therapy

ISR Modulator

Indication

Solid/Liquid Tumors

Preclinical

Phase 1

Phase 2

Phase 3

Solid/Liquid Tumors

Description: An orally bioavailable ISR (integrated stress response) modulator providing both anti-tumor monotherapy & combinatorial activity in a range of tumor types.

Rationale: The ISR pathway is a key metabolic stress sensor in cells. The ISR signaling pathway is upregulated in the ‘context’ of nutrient (amino acid and glucose) deprivation or starvation. HiberCell has an extensive portfolio of ISR modulators aimed at abating this context-dependent biology in cancer.

Tumor Microenvironment

Tumors disrupt the structure and function of surrounding normal tissues, creating a wound healing response that is largely governed by local immune cells. This wound-healing response actively shields the tumor from immune detection and attack, fostering tumor survival and growth. Overcoming this immune suppressive microenvironment is key to successful cancer treatment. Imprime PGG binds unique receptors (Dectin, CR3, FcɣR) on these altered immune cells, reprogramming the local tumor environment and enabling tumor detection and destruction.

Tumor Microenvironment

Stress Biology

The Integrated Stress Response (ISR) is activated by various cellular stressors such as hypoxia, amino acid deprivation, glucose deprivation, viral infection, and accumulation of misfolded proteins. Activation of the ISR within tumor cells directly promotes tumor cell survival while also facilitating avoidance of immune surveillance. Modulation of key ISR pathways disrupts this adaptive stress response, directly blocking tumor cell survival while also promoting immune mediated tumor cell destruction.

Stress Biology

Expanded Access

HiberCell is committed to developing novel therapeutics that address the most common cause of cancer mortality: relapse and metastasis. The use of investigational treatments not yet approved by the FDA, to treat patients with serious or life-threatening diseases or conditions, who have exhausted other treatment options and who cannot participate in a clinical trial, is referred to as Expanded Access.

View Expanded Access Policy