Synthekine Presents Positive Initial Results from Phase 1a/1b Clinical Trial of ?/? Biased IL-2, STK-012, for Treatment of Advanced Solid Tumors

Synthekine Inc., an engineered cytokine therapeutics company, today announced positive initial results from a Phase 1a/1b clinical trial of its ?/? biased IL-2 partial agonist, STK-012, for the treatment of advanced solid tumors. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego. STK-012 is a first-in-class ?/?-IL-2R biased partial agonist engineered to selectively stimulate CD25+ antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid broad stimulation of other lymphocytes, such as natural killer (NK) cells, which are associated with IL-2 toxicity. In the results presented, which included 47 patients treated in Phase 1a dose escalation, STK-012 monotherapy demonstrated a favorable safety, efficacy, pharmacokinetic and pharmacodynamic profile.

"The promise of IL-2 in the treatment of solid tumors has yet to be realized as IL-2 analogues developed to date have had limited efficacy and an unacceptable toxicity profile," said Naiyer Rizvi, M.D., chief medical officer of Synthekine. "We are excited to report multiple objective responses with STK-012 monotherapy, driven by robust induction of interferon?gamma (IFN?) and selective expansion of antigen activated T cells. At the same time, we do not see the severe toxicities typically associated with IL-2 treatments, such as hypotension, capillary leak syndrome (CLS), or transaminitis. We look forward to completing the dose expansion portion of this study to further evaluate its potential for patients."

Synthekine initiated the Phase 1b portion of its study in September 2023 after successfully completing the Phase 1a dose-escalation portion. The Phase 1b portion of the study includes dose expansion cohorts to evaluate STK-012 as monotherapy at the candidate recommended phase 2 dose (RP2D) in selected solid tumor types, including renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). Along with the Phase 1a results, Synthekine presented a case study on a subject with Stage IV ccRCC treated with STK-012 monotherapy in the ongoing Phase 1b portion of the study. The subject had 2 prior lines of therapy, including immune checkpoint inhibitor, before starting on STK-012 and went on to achieve a confirmed partial response with 85% reduction in target lesion size as best overall response.

The poster, titled "Initial results from a Phase 1a/1b study of STK-012, a first-in-class ?/? IL-2 receptor biased partial agonist in advanced solid tumors (NCT05098132)," will be presented today at AACR from 9 am to 12:30 pm PT. The poster will be on poster board 11 in the session "First-in-Human Phase I Clinical Trials 2." Following presentation at the meeting, the poster will be available on Synthekine's website. For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT05098132.

STK-012 Initial Phase 1a Monotherapy Dose Escalation Data

• As of February 26^th, 2024, 47 subjects were treated with STK-012 monotherapy at 7 dose levels across the 2 dosing schedules (QW and Q3W) in the Phase 1a
• Majority of patients (60%) had three or more prior lines of therapy in the advanced setting and 79% had received prior immune checkpoint inhibitor (ICI)
• Treatment-related adverse events (TRAEs) were reversible with standard management and mostly Grade 1 or 2 in severity
• Most common TRAEs (?10% of subjects) were maculopapular rash, fatigue, injection site reaction, nausea, diarrhea, pruritis, vomiting, and arthralgia
• Based on observed PK (half-life of ~4 days), only the Q3W schedule was advanced beyond the 0.75 mg dose during the STK-012 monotherapy dose escalation
• STK-012 demonstrated selectivity (pSTAT5 induction) for T cells that express IL-2R? (CD25)
• STK-012 demonstrated dose proportional increase in IFN? and activated proliferating CD8 T cells
• STK-012 showed limited expansion of NK cells and Tregs
• Of 40 efficacy evaluable subjects, partial response (PR) was observed in 3 (RCC, NSCLC and HNSCC) and 12 had stable disease (SD) as their best overall response (BOR) by RECIST V1.1
• In the subset of 15 subjects who were ICI refractory and minimally pretreated (? 2 prior lines), 3 had BOR of PR and 6 had BOR of SD
• Durability of response was observed in multiple subjects

About Synthekine

Synthekine is harnessing the potential of cytokine therapeutics to develop selective immunotherapies designed to improve the treatment paradigm of cancer and inflammatory disease. Using insights on cytokine structure and function, the company engineers therapeutics designed to unlock the full efficacy potential of cytokines while avoiding their associated toxicities. Synthekine is applying principles of cytokine partial agonism and immunological specificity across multiple protein engineering platforms to create a broad and deep pipeline of product candidates. These novel immunotherapies include modified cytokines, cytokine-enhanced cell therapies and surrogate cytokine agonists. For more information, visit www.synthekine.com, and follow us on X @synthekine and LinkedIn.