T-win® Technology platform
Our T-win platform is a novel approach to cancer immunotherapy designed to activate naturally occurring T cells to target immunosuppressive mechanisms. Our T-win product candidates are designed to employ a dual mechanism of action:
(1) direct killing of immunosuppressive cells, including both tumor cells and genetically stable cells in the tumor microenvironment (TME), that express key immunosuppressive proteins such as IDO and PD-L1, and (2) modulation of the TME into a more pro-inflammatory, anti-tumor environment.
Our T-win technology is built upon our team’s deep understanding of both the TME and a tumor’s ability to evade surveillance and destruction by the immune system. Our approach is in contrast to previous methods that have sought to either block single immunosuppressive pathways or to direct the immune system against specific identified antigens expressed by tumor cells.
We are developing a pipeline of product candidates that leverage our T-win technology platform to address targets within the TME. In addition to a potentially registrational Phase 3 trial in melanoma, we are planning two Phase 2 basket trials in additional solid tumors and treatment settings.
We are also developing earlier stage product candidates that target additional immunosuppression-related targets that are expressed in a broad range of solid tumors. We expect to use these earlier stage product candidates in combination with our existing pipeline candidates. Our pipeline of product candidates is summarized in the table below.
1. In combination with pembrolizumab
2. In combination with an anti-PD-1 monoclonal antibody therapy
3. Expected to be developed in combination with third party drugs or biologics
4. NSCLC = non-small cell lung cancer, UBC = urothelial bladder cancer, SCCHN = squamous cell carcinoma of the head and neck
Our product candidates are designed to induce the immune system to simultaneously target and disrupt multiple pathways that regulate tumor-induced immunosuppression.
IO102-IO103IO102-103, our lead immuno-oncology candidate, targeting IDO and PD-L1
Our lead product candidate, IO102-IO103, combines our two fully-owned, novel immunotherapeutics, IO102 and IO103, which are designed to target IDO and PD-L1 expressing cells, respectively. IDO and PD-L1 are often dysregulated and over-expressed in a wide range of solid tumors, and result in the inhibition of the body’s natural pro-inflammatory anti-tumor response within the TME. IO102-IO103 is designed to employ our novel dual mechanism of action approach, leading to killing of cells expressing IDO and PD-L1 and modulation of the TME into an enhanced pro-inflammatory environment. This is in contrast to previous approaches which have sought to block single immunosuppressive pathways or to direct the immune system against specific identified antigens expressed by tumor cells. By combining IO102 and IO103 in a single treatment regimen, we also aim to provide a synergistic effect on tumors.
BTD granted for IO102-103 by FDA
On December 14, 2020, the FDA granted us BTD for IO102-IO103 in combination with an anti-programmed cell-death protein 1 (PD-1) monoclonal antibody for the treatment of patients with unresectable or metastatic melanoma based on data from the MM1636 Phase 1/2 clinical trial.
BTD enables us to solicit guidance from the FDA as to how to conduct an efficient development program for IO102-IO103. The MM1636 trial was an investigator initiated, single-arm Phase 1/2 trial of 30 anti PD-1/PD-L1 naïve patients with metastatic melanoma receiving IO102-IO103 and nivolumab, an anti-PD-1 monoclonal antibody.
In this trial, investigators initially observed an ORR of 80% (24 out of 30 patients); however, two of 24 patients in which a response was observed progressed before subsequent radiological confirmation, which resulted in a confirmed ORR of 73%. In addition, 47% of patients achieved a CR, or complete elimination of their tumors.
Data from this trial suggests a manageable tolerability profile for patients. In addition, we observed treatment-induced infiltration of CD3/CD8 T cells into the tumor site in responding patients and detected IO102+IO103-specific T cells in tumors after treatment in correlative biomarker data where this was analyzed.
IO112O112, our second immuno-oncology candidate, targeting Arginase-1
IO112 is our fully-owned, novel product candidate containing a single Arginase 1-derived peptide designed to engage and activate Arginase 1-specific human T cells. IO112 is designed to target T cells that recognize epitopes derived from Arginase 1, an immunoregulatory enzyme highly expressed in difficult-to-treat tumors associated with high levels of myeloid-derived suppressor cells (MDSCs) including colorectal, breast, prostate and pancreatic and ovarian cancers. Arginase overexpression is a well-documented tumor escape mechanism.