Leading the Fight

Against Solid Tumors

Tumor infiltrating lymphocytes (TILs) are a type of cell therapy that harness the patient’s own immune cells to target their own tumors. TIL therapy involves the isolation of lymphocytes from the patient’s tumor, expansion of the isolated cells outside the body, and then infusion of the cells back into the patient. TILs have the ability to penetrate, recognize, and kill cancer cells and offer potential to treat or cure solid tumors.

Turnstone’s next-generation Selected TILs have the potential for treatment of multiple solid tumors. Our innovative Selected TIL approach focuses on selecting and expanding the most potent tumor-reactive T cells to overcome the limitations of bulk TILs. This approach is grounded in work conducted in academia that demonstrated improved clinical responses for Selected TILs in solid tumors. We are leveraging this work to establish a standardized manufacturing process for large scale production of our Selected TILs.

Our Selected TIL approach employs the following foundational principles with the goal of yielding the greatest number and proportion of tumor-reactive T cells in our TIL products:

• Unbiased identification of patient-specific tumor antigens.

  We seek to identify the most comprehensive set of patient-specific tumor antigens. We use an unbiased identification process that aims to find and capture the greatest diversity of antigens with the potential to drive the most robust T cell response. Our proprietary approach is unlike other TIL products that are biased toward a specific subset or class of antigen(s), which may miss relevant tumor antigens or focus on the wrong targets.

• Selection of greatest breadth of tumor-reactive T cells from patient extracted TILs.

  Our goal is to capture and isolate the greatest number and proportion of a patient’s tumor-reactive T cells that have the potential to attack and destroy heterogeneous solid tumors.  We aim to select the greatest diversity of T cells by using a function-based screening process that confirms reactivity to the identified patient-specific tumor antigens rather than relying on a bioinformatics-based prediction algorithm that may not be truly predictive.

• Expansion of tumor-reactive T cells and removal of non-tumor-reactive bystander cells.

  We expand our selected tumor-reactive TIL population to magnitudes consistent with bulk TIL products and actively remove unnecessary bystander cells. This selective expansion resulted in a substantially higher proportion of tumor-reactive T cells in the final product, which we believe will result in targeted tumor killing.

Our Superior Killing Virus, or SKV Vaccinia, is derived from the Copenhagen strain of vaccinia that exhibits powerful oncolytic activity in human tumors and we have engineered the viral backbone to develop a highly potent viral immunotherapy. The SKV Vaccinia backbone modifications were specifically designed and selected to support:

• Enhanced immune activation through removal of immunosuppressive genes
• Highly selective tumor targeting for increased potency and safety
• Delivery of multiple transgenes to encode for specific functions
• Optimized viral spread and infection in the tumor
• Systemic and intra-tumoral (IT) administration

We believe that Turnstone is strongly positioned to be a leader in leveraging viral immunotherapy to further increase the activity of our TIL therapies, if approved.

Viral immunotherapy is a therapeutic modality with widespread potential to drive and modulate immune responses to solid tumors. Many viruses have inherent oncolytic activity that can be modulated through genetic engineering. These viruses preferentially infect, replicate within, and kill malignant tumor cells, and can induce broad immune responses. Viral immunotherapies are designed to convert immunologically unresponsive “cold” tumor microenvironments to more reactive “hot” tumor microenvironments and thereby enhance the activity of other immunotherapies.

We are initially evaluating viral immunotherapies in combination with our lead Selected TIL product candidate, TIDAL-01, via two approaches:

• Administration of virus prior to TIL extraction to optimize TIL harvest and broaden applicability to additional tumor types with low immune cell infiltration, and
• Administration of virus following treatment with TIDAL-01 to optimize TIL trafficking and infiltration into solid tumors and to support the anti-tumor functions of infiltrating immune cells.