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.
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
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. 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 as 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.
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 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.
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.
While not our lead programs, we have several exciting candidates to extend our reach.
Our platform presents opportunities to pair with additional programs, including
A tri-targeting dual-specific inhibitor PD‑L1/PD‑L2 plus a 4-1BB agonist
A tri-targeting dual-specific inhibitor PD‑L1/PD‑L2 plus a CTLA-4
Evofosfamide (Evo), a hypoxia-reversal agent and primer for enhanced checkpoint inhibition in cold tumor treatment. By reoxygenating immune T cells in the tumor microenvironment, Evo frees T cells to traffic to the tumor and attack cancerous cells
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