Combination therapy of t-cell engager and chemotherapy for pancreatic cancer treatment - the american cancer society estimates that in 2025 approximately 67,440 new cases of pancreatic cancer will…

The National Institutes of Health National Cancer Institute awarded Oncotab, Inc. $1,130,587 on August 1, 2026, under the Cancer Treatment Research program (CFDA 93.395) to conduct Phase II SBIR research on a bispecific antibody T-cell engager (muCD3) combined with chemotherapy for pancreatic cancer treatment.

Oncotab will advance muCD3 through preclinical studies designed to de-risk its path toward first-in-human trials and commercialization. The work includes evaluating muCD3 structural stability in mouse serum, conducting pharmacokinetic studies in humanized mouse models to guide dosing, and assessing efficacy in four patient-derived xenograft orthotopic models across a range of MUC1 expression levels. In parallel, the recipient will perform cytokine release assays in human samples and establish the maximum tolerated dose of muCD3 in combination with nab-paclitaxel and gemcitabine through studies in non-human primates to define the safety margin of the combination approach.

Preclinical data demonstrated that muCD3 slowed tumor growth as monotherapy and significantly inhibited chemotherapy-resistant pancreatic tumors when combined with abraxane and gemcitabine, while reducing cytokine release—a common limitation of T-cell engagers. The project period runs through July 31, 2028, with place of performance in Charlotte, North Carolina.

Combination therapy of t-cell engager and chemotherapy for pancreatic cancer treatment - the american cancer society estimates that in 2025 approximately 67,440 new cases of pancreatic cancer will be diagnosed in the united states, with 51,980 deaths. Nearly 80% of patients present with locally unresectable or metastatic disease, where the 5-year survival rate is as low as 3%. Standard first-line regimens-folfirinox (5- FU, leucovorin, irinotecan, oxaliplatin) and gemcitabine plus NAB-paclitaxel (abraxane)-achieve median overall survival (MOS) of up to 21 months, yet outcomes remain dismal, underscoring the urgent need for novel therapeutic strategies. Advances in antibody engineering have enabled bispecific antibodies (bsabs) that engage t cells and redirect them toward tumors. In our prior phase i awards, we developed a panel of bsab t-cell engagers and identified MUCD3 as the lead candidate. Preclinical studies demonstrated that MUCD3 slowed tumor growth as monotherapy and, when combined with abraxane and gemcitabine, significantly inhibited chemotherapy-resistant pancreatic tumors. Importantly, the combination also reduced cytokine release, a common limitation of t-cell engagers. In this phase II sbir proposal, we will advance MUCD3 through key preclinical studies designed to DE-risk its path toward first-in-human (FIH) trials and eventual commercialization. MUCD3, produced from lonza-generated stable cell pools, will first be evaluated for structural stability in mouse serum at 37 °c, followed by pharmacokinetic studies in HUCD34-NSG and fcrn mice to guide dosing strategies. Efficacy will be assessed in four TMUC1- positive patient-derived xenograft (PDX) orthotopic models spanning a range of expression levels. In parallel, cytokine release assays in human samples and a maximum tolerated dose (MTD) study in non-human primates will establish the safety margin of MUCD3 in combination with NAB-PTX and gemcitabine. These animal models are essential to evaluate the in vivo pharmacokinetics, tumor-targeting efficacy, and safety of MUCD3 within an intact biological system, which cannot be fully replicated using in vitro approaches. We will collaborate with DR. TIM pardee (atrium health wake forest baptist), DR. Michael morse (duke health), and DR. Mohamed salem (levine cancer institute, atrium health), whose expertise in clinical oncology and trial design will guide execution of these studies and the design of the FIH trial. We anticipate that MUCD3, combined with abraxane and gemcitabine, will demonstrate enhanced efficacy with reduced toxicity compared to current chemotherapy, offering the potential to meaningfully improve survival and quality of life for pancreatic cancer patients