Unlocking the Potential of Immunotherapy
Tumors are classified as “T-cell inflamed” or “hot,” meaning that they contain many T cells, or “cold,” meaning they have a paucity of T cells or other immunosuppressive elements.
Many hot tumors are responsive to immunotherapy, which helps immune T cells attack cancerous cells. Cold tumors, however, make up the vast majority of cancers and affect 5 times as many patients as hot tumors. Because cold tumors lack activated T cells and have unique immunosuppressive characteristics, immunotherapy is minimally effective in treating these cancers.
By turning cold tumors hot, ImmunoGenesis seeks to unlock the potential of immunotherapy for the patients who present with cold tumors.
While traditional approaches and new combination treatments continue to disappoint, ImmunoGenesis is revolutionizing cold tumor treatment. With a deliberate drug development strategy based in cold tumor pathology, ImmunoGenesis is creating sophisticated therapies that target key mechanisms of immune resistance.
Key Mechanisms of Immune Resistance in Cold Tumors
- T cells excluded from the tumor microenvironment by immunosuppressive cells
- Immunosuppressive cells dominate the tumor microenvironment
- Tumor hypoxia limits T-cell access
- Lack of activated T cells
A platform based in cold-tumor pathology
The heart of our platform is a PD‑L1/PD‑L2 dual‑specific inhibitor, born out of Dr. Michael Curran’s realization that PD‑L2 is a critical regulator of human tumor immunity. Dr. Curran’s vision was to simultaneously target PD‑L1 and PD‑L2, the ligands of PD‑1, to create the same blocking function as PD‑1 inhibitors. And because the antibody targets the ligands, which are expressed on immunosuppressive and tumor cells (rather than T cells like PD‑1), cytotoxic effector function could be built in. He also had the foresight to see the potential for this antibody to be a tumor‑specific delivery vehicle and the base for dual-specifics capable of hitting additional targets.
To make this vision a reality, Dr. Curran worked closely with a novel antibody development company. Through trial and error, and multiple rounds of affinity maturation, a novel antibody was developed in which both arms bind with clinically relevant affinities to both PD‑L1 and PD‑L2.
With the development of this molecule, ImmunoGenesis will be the first company to target PD‑L2.
IMGS-001
Re-envision the treatment starting point
IMGS-001 re-envisions the starting point for cold tumor treatment with a novel, dual-specific PD‑L1/PD‑L2 antibody designed with effector function to kill the immunosuppressive cells in the tumor microenvironment. Rather than building on the fragile 5% response rate seen with PD‑L1 inhibition in cold tumors, we returned to the science to develop a superior foundation of a PD‑1 pathway blockade. Early readouts suggest that IMGS-001 may increase the cold tumor monotherapy response rate >5-fold and provides a strong therapeutic foundation for carefully designed add-on therapies to further optimize cold tumor outcomes.
IMGS-101
Reverse hypoxia in the tumor microenvironment
IMGS-101 (evofosfamide) is a chemotherapeutic prodrug (DNA-alkylating agent) that is activated in hypoxic (low-oxygen) environments. IMGS-101 is used to reverse immune resistance produced from a hypoxic tumor by utilizing a tissue-remodeling process that includes replacement of disrupted tumor vasculature with fully functional new vessels. This process is critical because approximately 50% to 60% of pancreatic, head and neck, and prostate tumors are hypoxic.
ImmunoGenesis is investigating the use of IMGS-101 in combination with checkpoint blockade (blocking immune inhibitory molecules PD-1 and CTLA-4) to make solid tumors more accessible to immune clearance. IMGS-101 has been studied extensively in clinical trials, with >1,600 patients being treated.
IMGS-501
Block checkpoint signals and attack the suppressive tumor microenvironment
STING as Immune Stimulating Antibody Conjugate (ISAC) builds on the novel PD‑L1/PD‑L2 inhibitor by conjugating a STING agonist to the antibody, combining an optimal PD‑1 pathway blockade with a powerful immune agonist. The team at ImmunoGenesis is developing this agent to effectively transport our intravenously delivered STING agonist to all tumor sites and targets within the microenvironment. This therapeutic advance pushes through an important barrier seen with traditional STING agonists, which consistently produce an effect only at the site of the intratumoral injection. Our STING agonist, delivered intravenously, can precisely target where it is most effective across tumor sites.
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Clinical ProgramsOur lead program, IMGS-001, entered clinical trials in 2023 with the first patient dosed in September. Our second clinical program, IMGS-101 (evofosfamide), will enter clinical trials in 2024. |
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Development ProgramsWe have several exciting candidates to extend our reach. Our platform presents opportunities to pair with additional programs, including
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Our Vision
By harnessing cutting-edge science, the ImmunoGenesis pipeline is designed to redefine the cold tumor treatment landscape, re-envision existing immunotherapy treatment approaches, and ultimately, provide necessary treatments for patients with cold tumors.
Fuel the science