Synthekine Presents Updated Clinical and Translational Data Demonstrating Strong Activity for STK‑012 in First‑Line Non‑Squamous NSCLC in Oral Presentation at AACR 2026

STK-012 + pembrolizumab + chemotherapy in first‑line non‑squamous NSCLC demonstrated a 50% ORR in predominantly PD‑L1-negative patients

61% ORR with the regimen in patients with at least one mutation in the STK11, KEAP1, or SMARCA4 tumor suppressor genes

50% ORR, PFS 5.5 months, and 88% 6-month OS with the regimen in patients with STK11/KEAP1 co‑mutated tumors

MENLO PARK, Calif.--(BUSINESS WIRE)--Synthekine, Inc., a clinical‑stage biotechnology company developing precision cytokine therapeutics, today reported updated clinical and translational data for STK‑012 in combination with pembrolizumab, pemetrexed, and carboplatin (PCT) in first‑line PD‑L1-negative, non‑squamous (NSQ) non‑small cell lung cancer (NSCLC). The data were presented by Salman Punekar, M.D. (NYU Langone Health), in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego, CA.

STK‑012 is a first‑in‑class α/β IL‑2 receptor‑biased partial agonist designed to selectively stimulate antigen‑activated T cells, which are linked to anti‑tumor activity, while minimizing broad activation of other lymphocytes, such as natural killer cells, which are associated with IL‑2‑related toxicities. These updated results, from 36 efficacy‑evaluable patients, build on clinical data first presented at SITC 2025 and include longer follow‑up, new translational analyses, and the first detailed look at durability in the STK11/KEAP1 co‑mutated subgroup.

“These data underscore the potential for STK-012 to improve outcomes for some of the hardest-to-treat patients with lung cancer,” said Naiyer A. Rizvi, M.D., Chief Medical Officer of Synthekine. “Chemoimmunotherapy remains the first‑line standard of care in non‑squamous NSCLC, but many patients derive limited benefit. These tumors are often PD‑L1-negative and/or enriched for STK11, KEAP1, and SMARCA4 loss-of-function alterations, all of which contribute to an immune-cold tumor microenvironment. The response rates and early durability signals we are seeing, together with compelling translational evidence of targeted T‑cell activation, establish a strong case that STK-012 can overcome the immune resistance that has historically limited outcomes in this population.”

Efficacy and Safety in Immune Resistant Biology

STK-012 plus pembrolizumab and chemotherapy (PCT) demonstrated robust activity in patient subsets typically associated with resistance to chemoimmunotherapy:

• Nearly all patients in the study were PD‑L1-negative (n=32/36), a population in which standard-of-care chemoimmunotherapy has historically produced objective response rates of 23% to 32%. In contrast, STK-012 plus PCT achieved a 50% objective response rate and 97% disease control rate in the overall efficacy-evaluable population.
• In patients with STK11, KEAP1, and/or SMARCA4 loss-of-function alterations (n=18/36)—where standard-of-care response rates have been reported in the 7% to 33% range—STK-012 plus PCT delivered a 61% objective response rate and 100% disease control rate.
• In the STK11/KEAP1 co‑mutated subgroup (n=8/36), STK-012 plus PCT achieved a 50% objective response rate. Median progression-free survival was 5.5 months, with two patients still on treatment, and median overall survival was not reached at a median follow-up of 6.8 months (6-month OS rate 88%). These results compare favorably to published standard-of-care benchmarks of 7%–15% ORR, ~3 months median PFS, and 5.4–7.0 months median OS in this subgroup. STK11/KEAP1 co‑mutated patients represent approximately 10% of first-line NSQ NSCLC.

Across 39 safety-evaluable patients, STK-012 plus PCT was generally well tolerated, with no dose-limiting toxicities and no STK-012–related discontinuations. The most common treatment-related adverse events were rash/dermatitis (51%), nausea (51%), and fatigue (46%), which were manageable and reversible.

Translational Data Show Selective and Durable Immune Activation

New translational data presented at AACR provide strong biological support for the clinical findings:

• Sustained exposure: STK‑012 half‑life of 5.7 days supports continuous pharmacodynamic activity across the 3‑week dosing cycle
• Targeted cytokine induction: robust IFN‑γ and IP‑10 induction with minimal IL‑6 and TNF‑α, consistent with selective T‑cell‑driven activity rather than broad immune activation
• Robust expansion of activated T cells: strong proliferation of 4‑1BB+ CD8+ T cells, with limited expansion of NK cells or regulatory T cells
• Clonal T cell expansion: 3.5% of circulating T cells were derived from newly expanded clonotypes after a single cycle, and greater clonal expansion was associated with clinical response
• Immune reactivation in STK11/KEAP1 co‑mutated subgroup: STK‑012 restored proliferation of the activated T‑cell population (4‑1BB+ CD8+), reinvigorated exhausted T cells (PD‑1+ CD8+ T cells), and drove robust clonal T cell expansion—even in tumors with the most suppressive microenvironment

“Although STK11/KEAP1 co-mutated tumors have a high neoantigen burden, the immunologically dysfunctional tumor microenvironment renders immune checkpoint inhibitors largely ineffective in this setting,” said Martin Oft, M.D., Chief Scientific Officer of Synthekine. “Our translational data suggest that STK-012 can work synergistically with immune checkpoint inhibitors to help re-engage antitumor immunity and enable functional T-cell responses in these tumors.”

The AACR presentation is available on Synthekine’s website.

About the SYNERGY-101 Randomized Phase 2 Clinical Trial

Development of STK-012 is ongoing in SYNERGY-101, a global, randomized Phase 2 study evaluating STK-012 plus pembrolizumab and chemotherapy versus pembrolizumab and chemotherapy alone in first‑line, PD‑L1-negative non‑squamous NSCLC. The study is currently enrolling with the first patient dosed in November 2025. Synthekine has entered into a clinical trial collaboration and supply agreement with Merck, under which Merck provides Keytruda® (pembrolizumab) for use in the trial. Synthekine retains all commercial rights to STK-012.

For additional information about the SYNERGY-101 trial, please visit www.clinicaltrials.gov and use the identifier NCT05098132.

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 therapeutic areas to create a broad and deep pipeline of product candidates. These novel immunotherapies include modified cytokines and surrogate cytokine agonists. For more information, visit www.synthekine.com, and follow us on X @synthekine and LinkedIn.