SOTIO Biotech: SOTIO Presents Preclinical Data from BOXR CAR-T Program and Trial Design of Phase 2 AURELIO-04 Study at SITC Annual Meeting

• Findings on the mechanism of action from the BOXR CAR-T platform indicate improved metabolic function and preservation of early memory subsets of T cells
• SOTIO anticipates initiating first-in-human DUET-01 trial for lead CAR-T cell therapy candidate, BOXR1030, in coming months
• Phase 2 AURELIO-04 combination study of SOT101 and KEYTRUDA is enrolling patients across multiple solid tumor indications
  

BASEL and CAMBRIDGE, Mass., Nov. 10, 2022, a clinical stage immuno-oncology companyowned by PPF Group,presented preclinical dataevaluating the mechanism of action and metabolic function of its BOXR T cell platform in a poster presentation at the Society for Immunotherapy of Cancer (SITC) 37^th Annual Meeting, taking place in Boston, Massachusetts from November 8-12, 2022. An additional poster was presented on the trial design of AURELIO-04, an ongoing Phase 2 study evaluating the efficacy and safety of SOT101 in combination with pembrolizumab in patients with advanced solid tumors.

"Preclinical results from the study of our BOXR T cell therapy platform indicate a strong clinical path for our first transgene-expressing CAR-T cell, BOXR1030, as a potential clinical treatment for the 90% of adult cancer patients with solid tumors," said Radek Spisek, M.D., Ph.D., chief executive officer of SOTIO. "The GOT2 infused CAR-T cell therapy improved metabolic fitness, increased cell survival and proliferative capacity of CAR-T cells when exposed to suppressive tumor microenvironments, indicating potentially improved access to solid tumors; a long-standing challenge for CAR-T and other cancer therapies to date. We look forward to initiating first-in-human safety studies of BOXR1030 in the coming months."

Pratirodh Koirala, Ph.D., presenting author from SOTIO Biotech Inc. (U.S.) commented: "CAR-T cell therapy has made significant strides in the treatment of hematological malignancies, yet solid tumors remain resistant to current CAR-T strategies due to suppression by the tumor microenvironment. The preclinical data presented at this year's SITC annual meeting demonstrate a promising mechanism of action for SOTIO's BOXR1030 and underscore the potential that GOT2-expressing CAR-T cells have for enhanced metabolic fitness or more durable early memory phenotypes - benefits which could improve clinical outcomes against solid tumors despite a suppressive tumor microenvironment."

An analysis of the BOXR1030 T cell data show that the BOXR CAR-T cells co-expressing the metabolic gene GOT2 have a higher frequency of less differentiated stem cell memory T cell (T_SCM) populations and more CD27⁺ cells in all memory T cell subsets, suggesting fewer terminally differentiated cells compared to control CAR-T cells lacking the GOT2 transgene. When BOXR1030 T cells were exposed to stressful conditions characteristic of difficult-to-penetrate tumor microenvironments such as low glucose and chronic stimulation, the cells exhibited improved metabolic fitness, increased cell survival and proliferative capacity, multiple characteristics of less differentiated or early memory T cell populations, and retention of effector functions relative to control CAR-T cells.

Dr. Spisek added: "Additionally, progressing our lead clinical asset, SOT101 into the Phase 2 AURELIO-04 study has been a significant clinical milestone for SOTIO. The trial size of 320 patients, all of whom are facing a variety of metastatic cancers that present high unmet needs, will enable us to significantly increase our data pool as SOT101 continues to advance through the clinic."

The design of the Phase 2 AURELIO-04 study, launched by SOTIO in July of 2022, was presented by Aurélien Marabelle, M.D., Ph.D., immuno-oncologist from the Drug Development Department at Gustave Roussy Cancer Center.

The AURELIO-04 study) is a Phase 2, open-label, single-arm, multicentered study of SOT101 in combination with pembrolizumab to evaluate the efficacy and safety in patients with multiple advanced solid tumor indications. The solid tumor selection was based on previous pembrolizumab studies and/or data from other checkpoint inhibitors (CPI) and includes both CPI-relapsed and/or CPI-naïve tumors. The study will enroll up to a total of approximately 320 patients with a maximum of 50 to 57 per indication in Europe and the United States. SOTIO entered into a clinical trial collaboration and supply agreement with MSD (a tradename of Merck & Co., Inc., Rahway, NJ, USA). MSD supplies KEYTRUDA for the study. In a Phase 1 study, SOT101 in combination with pembrolizumab has reported clinical benefit in 15 out of 19 patients with at least one post-baseline tumor assessment.

Poster presentations from SITC are available on the SOTIO Biotech website.

About the BOXR Technology:

SOTIO's BOXR cell therapy platform is designed to improve the functionality of immune cells such as CAR-T cells by identifying novel "bolt-on" transgenes that can be co-expressed with tumor-targeting receptors to overcome resistance and improve the function of respective immune cells in the solid tumor microenvironment. BOXR-discovered transgenes are selected to address T cell metabolism and overcome multiple mechanisms of immunosuppression, including competition for metabolites, exhaustion due to chronic stimulation, and resistance to immunosuppressive cells.

About SOT101:

SOT101 is a subcutaneously administered IL-15R superagonist based on IL-15 fused to the sushi+ domain of the IL-15 receptor a chain. SOT101 has demonstrated strong preclinical in vivo efficacy in various tumor models showing increased long-term survival and tumor regression, as well as a favorable toxicology profile. SOT101 has been shown in pre-clinical models to synergize with checkpoint inhibitors and antibody therapies exerting ADCC.

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About SOTIO Biotech

SOTIO Biotech is shaping the future of cancer immunotherapies by translating compelling science into patient benefit. The robust SOTIO clinical pipeline includes a differentiated superagonist of the attractive immuno-oncology target IL-15, SOT101, currently being tested in phase II clinical trials. SOT102, a next generation Claudin18.2-targeted antibody-drug conjugate.

SOTIO is a registered trademark of SOTIO Biotech a.s. in selected countries.