PGC-1α

PRAGUE & BASEL, Switzerland & BOSTON--( BUSINESS WIRE )-- SOTIO Biotech , a clinical-stage immuno-oncology company owned by PPF Group, today announced data supporting SOT201, its next-generation PD-1-targeting immunocytokine. The company also reported advancements in its BOXR cell therapy platform, introducing an innovative chimeric PGC-1α transgene to boost CAR T cell efficacy in patients with solid tumors. SOTIO will be presenting three posters highlighting these advancements at the 2024 Society for Immunotherapy of Cancer Meeting, taking place November 6–10 in Houston, TX, U.S. SOT201 is a PD-1-targeted and cis-acting attenuated IL-15 agonist designed to preferentially activate PD-1 + CD8 + T cells, inducing superior anti-tumor effects and reinvigorating exhausted CD8 + T cells in PD-1 sensitive and resistant tumors. The VICTORIA-01 study is a Phase 1, open-label, dose escalation trial that aims to assess the safety, tolerability, and preliminary efficacy of SOT201 as a monotherapy for adults with advanced unresectable or metastatic solid tumors ( NCT06163391 ). This trial is currently enrolling patients across six sites in the U.S., Belgium, Spain, and the Czech Republic. Four patients have been treated so far and the treatment was well tolerated. SOTIO Chief Scientific Officer Martin Steegmaier, Ph.D., noted, “ SOT201 demonstrates a superior ability to reinvigorate exhausted tumoral CD8 + T cells with a high cytotoxicity and minimal cellular exhaustion compared to the related cytokine PD1-IL2v. These data reinforce SOT201’s reduced off-target interactions and more durable anti-tumor efficacy in vivo , underscoring its potential to address current limitations in anti-PD-1 therapies, as we continue to enroll patients in the VICTORIA-01 study.” The third poster highlights a preclinical study of a chimeric PGC-1α transgene that enhances CAR T cell activity. Chimeric PGC-1α transduced cells displayed fewer dysfunctional mitochondria and improved glucose uptake compared to CAR T cell controls. “ Furthermore, the chimeric PGC-1α enhanced CAR T anti-tumor efficacy with no overt signs of toxicity, suggesting that co-expression of CAR and the chimeric PGC-1α is a promising approach to improving CAR T cell efficacy in solid tumors,” added Dr. Steegmaier. Presentation materials will be available here on Sunday, November 10, after the conference concludes. 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 www.sotio.com . SOTIO is a registered trademark of SOTIO Biotech a.s. in selected countries.

PRAGUE & BASEL, Switzerland & BOSTON--(BUSINESS WIRE)-- SOTIO Biotech , a clinical-stage immuno-oncology company owned by PPF Group, today announced it will present three posters at the 2024 Society for Immunotherapy of Cancer Meeting taking place November 6 - 10, 2024, in Houston, TX. Data to be presented include the investigation of a novel chimeric PGC-1α transgene to enhance CAR T cell efficacy in patients with solid tumors. The VICTORIA-01 study is currently evaluating the safety, tolerability and initial efficacy of SOT201 monotherapy for the treatment of advanced solid tumors, as well as data around SOT201, a next-generation clinical stage PD-1-targeting immunocytokine. Poster details are as follows: Title: “Chimeric PGC-1α expression in CAR-T cells improves metabolic function and anti-tumor efficacy in solid tumors” Abstract Number: 273 Date: Thursday, November 7 and Friday, November 8, 2024 Presenting Author: Amy Jensen-Smith Title: “VICTORIA-01: A multicenter, open-label, phase 1 study to evaluate the safety and preliminary efficacy of SOT201 in patients with advanced or metastatic solid tumors” Abstract Number: 675 Date: Friday, November 8, 2024 Presenting Author: Aung Naing Title: “SOT201, a novel cis-acting PD-1/IL-15 mutein-based immunocytokine that reinvigorates anti-tumor immunity qualitatively superior to PD-1/IL-2v-based IL-2/15Rβγ agonism” Abstract Number: 940 Date: Saturday, November 9, 2024 Presenting Author: Irena Adkins Presentation materials will be available after presentations conclude here . About SOTIO Biotech SOTIO Biotech (SOTIO) is shaping the future of targeted cancer therapies by translating compelling science into patient benefit. The SOTIO pipeline includes three clinical-stage programs: SOT102, a next-generation Claudin-18.2-targeted antibody-drug conjugate; BOXR1030, a metabolically-enhanced CAR-T cell therapy targeting GPC3-expressing tumors; and SOT201, a next-generation PD-1-targeting 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. 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

While GLP-1 receptor agonists continue to post impressive weight loss data – and attract a slew of high-priced deals – the drugs face several shortcomings in obesity, including the duration of effect after treatment ends. Resalis is aiming to fill those holes with a complementary therapy: an antisense oligonucleotide (ASO) that targets miR-22, which controls multiple pathways associated with the metabolic root of obesity.The company raised €10 million in a series A Thursday that will enable the start and finish of a Phase I trial of its miR-22 targeting ASO, RES-010. The round, which comes a year after Resalis’ initial €10 million seed funding, was led by Sunstone Life Science Ventures with participation from existing investors including Claris Ventures and angel investors. One target, many pathwaysResalis’ strategy for a disease-modifying obesity therapeutic hinges on one microRNA (miRNA). Riccardo Panella began investigating miR-22 as a postdoc at Harvard Medical School and discovered its importance in multiple metabolic pathways – and its potential as a therapeutic target for obesity. Soon after, he started collaborating with Sakari Kauppinen to further explore the biology of miR-22, thanks to a grant from the Novo Nordisk Foundation, and they designed ASOs that could inhibit the target. After settling on a lead compound and amassing pharmacological and animal model data, the pair founded Resalis in 2021. Panella serves as chief scientific officer; Kauppinen is the company’s chief technology officer. “Because they’re very short, one miRNA can interact with a lot of different targets, depending on what is expressed at that moment in a cell or tissue,” Panella told FirstWord. Some of the key targets of miR-22 the Resalis team has identified include FGF21, ACLY, PGC-1α, and SIRT1 – all which have key roles in metabolic pathways.The ability to affect multiple targets is especially attractive in obesity because it’s a complex, multi-tissue, multi-pathway disease. With RES-010, “We found a way to hit multiple birds with one stone,” Panella said. “By silencing miR-22, we can deregulate multiple players at the same time that are important for driving the obesity phenotype.”Getting at the metabolic rootThe end goal is to rewire our cellular metabolism – making it harder for the body to store fat, and promoting energy consumption, Resalis CEO Alessandro Toniolo said. Mice data hints at what the result of such rewiring could look like in humans. In a study published last year in the International Journal of Molecular Sciences, Panella and Kauppinen found that when two groups of mice were fed high-fat diets, those with a miR-22 knockout gained significantly less weight than those with the target intact. Plus, another mice study showed that miR-22 inhibition only triggered fat loss, not muscle – another drawback to GLP-1 receptor agonism. Toniolo said the team found that, unless the mice had an excess of fat, they did not lose body weight. Because GLP-1 receptor agonists are appetite suppressors, patients often lose both fat and muscle mass, which can be unhealthy for the elderly. Another shortcoming facing the modality is that when patients stop taking the drugs, they often regain weight.However, Toniology believes pairing a GLP-1 receptor agonist with RES-010 for a course of treatment could resolve these issues. He doesn’t see the ASO replacing GLP-1s, but rather as a complementary therapy. Resalis plans to start a Phase I dose-ascending study of RES-010 in Europe this half.