GOT2

PRAGUE & BASEL, Switzerland & BOSTON--(BUSINESS WIRE)-- SOTIO Biotech, a clinical-stage immuno-oncology company owned by PPF Group, today announced it will present a Trial-in-Progress poster on the DUET-01 Phase 1/2 study of BOXR1030 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 31 – June 4, 2024, in Chicago, IL. BOXR1030 is a next-generation GPC3-targeted CAR T-cell therapy enhanced with a transgene encoding GOT2, a critical enzyme involved in cellular metabolism. Preclinical studies of BOXR1030 have demonstrated its superior activity compared to standard CAR T-cell therapies. It is the most advanced therapeutic candidate from SOTIO’s BOXR platform of enhanced cell therapies for the treatment of solid tumors. The DUET-01 clinical trial is a first-in-human, open-label, multicenter, dose escalation study to assess and determine the recommended Phase 2 dose of BOXR1030 in patients with GPC3 positive advanced solid tumors. The trial will enroll up to 98 patients with advanced, unresectable hepatocellular carcinoma, squamous cell lung cancer, myxoid/round cell liposarcoma, and Merkel cell carcinoma. Poster details are as follows: Title: “DUET-01: A first-in-human, phase 1/2 study of BOXR1030 in patients with advanced glypican-3-positive solid tumors” Abstract Number: TPS2681 Session: Developmental Therapeutics — Immunotherapy Date & Time: June 1, 2024, 9:00 a.m. – 12:00 p.m. CDT Presentation materials will be available after presentations conclude here. About SOTIO Biotech SOTIO Biotech (SOTIO) is shaping the future of cancer immunotherapies by translating compelling science into patient benefit. The SOTIO pipeline includes SOT102, a next-generation Claudin-18.2-targeted antibody-drug conjugate which entered the clinic in 2022; BOXR1030, a metabolically-enhanced CAR-T cell therapy targeting GPC3-expressing tumors as well as other molecules approaching clinical stage such as SOT201, our next-generation PD-1-inhibiting immunocytokine. SOTIO is a member of the PPF Group. For more information, please visit the company’s website at . SOTIO is a registered trademark of SOTIO Biotech a.s. in selected countries. View source version on businesswire.com: Contacts Company contact: Richard Kapsa Head of Communication T: (+420) 224 174 448 M: (+420) 603 280 971 kapsa@sotio.com Media contact: Lisa Raffensperger Ten Bridge Communications M: +1 (617) 903-8783 lisa@tenbridgecommunications.com Source: SOTIO Biotech View this news release online at:

PRAGUE & BOSTON--(BUSINESS WIRE)-- SOTIO Biotech, a clinical-stage immuno-oncology company owned by PPF Group, today announced it will present new preclinical data at the American Association for Cancer Research (AACR) Annual Meeting taking place April 5-10, 2024, in San Diego, California. In a poster at the conference, SOTIO will present data from the company’s BOXR platform of enhanced T cell therapies. SOTIO leveraged the BOXR technology to design CAR T cells enhanced with transgenes encoding GOT2 (glutamine oxaloacetate transaminase) and TIGAR (TP53-induced glycolysis and apoptosis regulator), both of which are believed to play a role in T cell fitness in the hostile solid tumor microenvironment. Compared to unmodified CAR T cells and CAR T cells enhanced with GOT2 solely, CAR T cells enhanced with GOT2 and TIGAR showed better tumor infiltration, lower levels of exhaustion, and superior anti-tumor activity in a mouse model of solid tumors. SOTIO’s lead candidate from the BOXR platform, BOXR1030 — a GOT2-enhanced CAR T-cell therapy — is currently being evaluated in a Phase 1/2 study for patients with solid tumors. A second study to be presented at the meeting investigated the immunostimulatory effects of PARP inhibitors in models of epithelial ovarian cancer, determining their activity on molecular and cellular pathways to inform better combination therapy strategies with cancer immunotherapies. Poster details are as follows: Title: “Dual expression of exogenous glutamine oxaloacetate transaminase (GOT2) and TP53-induced glycolysis and apoptosis regulator (TIGAR) enhance CAR T cell activity in preclinical solid tumor models” Presenting Author: Amy Jensen-Smith Abstract Number: 4012 Date & Time: April 9, 2024, 9:00 a.m. – 12:30 p.m. PT Title: “Immunological control by PARP inhibitors for successful immunotherapy in metastatic ovarian carcinoma” Presenting Author: Peter Holicek Abstract Number: 5278 Date & Time: April 9, 2024, 1:30 p.m. – 5:00 p.m. PT Presentation materials will be available after presentations conclude here. About SOTIO Biotech SOTIO Biotech (SOTIO) is shaping the future of cancer immunotherapies by translating compelling science into patient benefit. The SOTIO pipeline includes SOT102, a next-generation Claudin-18.2-targeted antibody-drug conjugate which entered the clinic in 2022; BOXR1030, a metabolically-enhanced CAR-T cell therapy targeting GPC3-expressing tumors as well as other molecules approaching clinical stage such as SOT201, our next-generation PD-1-inhibiting immunocytokine. SOTIO is a member of the PPF Group. For more information, please visit the company’s website at . SOTIO is a registered trademark of SOTIO Biotech a.s. in selected countries.

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 monthsPhase 2 AURELIO-04 combination study of SOT101 and KEYTRUDA® is enrolling patients across multiple solid tumor indications BASEL and CAMBRIDGE, Mass., Nov. 10, 2022 (GLOBE NEWSWIRE) -- SOTIO Biotech, a clinical stage immuno-oncology company owned by PPF Group, presented preclinical data evaluating 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) 37th 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 (TSCM) 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 (NCT05256381) 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 α 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. Company contact:Media contact:Richard KapsaMichael TattoryHead of CommunicationLifeSci CommunicationsT: (+420) 224 174 448T: (+1) 609-802-6265M: (+420) 603 280 971mtattory@lifescicomms.comkapsa@sotio.com 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 (ADC) has recently entered the clinical phase. BOXR1030, a GPC3-targeted CAR-T based on proprietary technology designed to improve on the efficacy of CAR-T therapies in the tumor microenvironment, will enter the clinical phase in coming months. SOTIO is a member of the PPF Group. For more information, please visit the company’s website at www.sotio.com. SOTIO is a registered trademark of SOTIO Biotech a.s. in selected countries.