Our Technology

Tiltbio’s patented TILT® technology, based on oncolytic viral therapies, works by modifying the tumor microenvironment and eliminating its ability to suppress immune responses to cancer, thereby enhancing checkpoint inhibitors and T-cell therapies such as TIL and CAR T therapies.

Or, put simply, TILT® technology works by modifying the tumor microenvironment to help “light up” the immune system to fight cancer. Tiltbio scientists develop oncolytic viruses that encode for immunostimulatory payloads like cytokines.

1. The viruses are delivered intravenously.  Intratumoral or intraperitoneal injections can also be used. When a virus encounters a cell, it uses its outer fiber structures to enter the cell.
2. The oncolytic virus replicates in cancer cells and uses the cells’ machinery to produce immunostimulatory payloads like cytokines. The virus has double selectivity for replication only in cancer cells. Viral replication causes cancer cells to burst (lysis) resulting in generation of new viruses. At the end of the viral replication, the cell breaks down and newly created virions (particles) and immunostimulatory payloads are released into the tumor microenvironment.
3. Viral replication, combined with the produced cytokines, attracts T cells into the infected tumor, turning immunological cold tumors hot and enhancing T-cell therapies. Attracted T cells can originate from the patient’s own immune system or, for example, from tumor infiltrating lymphocyte therapy.
4. The arrival of antitumor immune cell populations in a tumor, whose microenvironment has been transformed by the oncolytic viral therapy into an immunostimulatory one, triggers the killing of cancer cells.

TILT-123’s Potential in Ovarian Cancer

Ovarian cancer is generally highly resistant to immunotherapy, with immune checkpoint inhibitors only working in less than 1 in 10 patients. This is primarily because of ovarian cancer’s immunosuppressive tumor microenvironment. Tiltbio is focused on increasing a positive immunotherapy response for patients with ovarian cancer.

TILT-123, Tiltbio’s lead investigational asset, has the potential to help improve the prognosis for patients diagnosed with platinum-resistant or refractory ovarian cancer. This asset:

• Is an investigational, engineered oncolytic virus armed with two immunostimulatory cytokines: tumor necrosis factor (TNF) and interleukin-2 (IL-2). Tiltbio is the only company using these two human cytokines in its lead product candidate.
• Is designed for intravenous administration to integrate seamlessly with other cancer immune therapies, including immune checkpoint inhibitors.
• May help increase the antitumor efficacy of other immunotherapies without adding serious side effects.
• Is now in Phase II clinical development in ovarian cancer, following the successful completion of Phase I trials investigating TILT-123 both as a monotherapy and in combination with cancer immunotherapies in various solid tumor indications worldwide.

TILT-123 Potential with TILs in Melanoma Patients Refractory to Immune Checkpoint Inhibitors

Treatment of melanoma with TIL transfer, incorporating pre- and post-conditioning regimens,  can yield to durable and significant clinical outcomes in more than 1 in 3 patients.  However, time required for TIL manufacturing results in treatment hiatus and the conditioning regimens encompassed in the therapy can lead to severe side-effects. These limitations restrict the applicability of TIL therapy to a wider range of patients. Tiltbio is developing a companion therapy to TIL treatment for refractory melanoma patients, with the potential to provide continuous therapeutic care, eliminate treatment gaps, and enhance tolerability by removing the need for high-dose post-conditioning IL-2.

TILT-123 has the potential to help improve the prognosis for patients diagnosed with unresected metastatic melanoma receiving TIL therapy while improving its reach to more patients. This asset:

• Allows for intravenous and intratumoral administration in melanoma enabling integration in melanoma clinical practice.
• Allows for patient treatment with TILT-123 while TILs are being manufactured.
• May help increase the antitumor efficacy and tolerability of TIL therapy without post-conditioning IL-2.
• Is now in Phase Ib clinical development in melanoma, following the successful completion of a Phase I trial investigating TILT-123 in combination with TIL therapy without conditioning regimens.