Genocea Biosciences, Inc. presented clinical, preclinical, and manufacturing data at the American Association for Cancer Research (AACR) Annual Meeting 2022 beginning April 8, 2022 in New Orleans and virtually. The presentations include promising initial data from the TiTAN™ clinical trial for the neoantigen-targeted peripheral T cell (NPT) therapy product candidate GEN-011, results demonstrating successful production of GEN-011 using Genocea's PLANET™ manufacturing process, and new preclinical data on Inhibigens™, antigens of suppressive immune responses uniquely identifiable by Genocea's ATLAS™ platform. The Phase 1/2a TiTAN trial investigates the safety, tolerability, T cell persistence and proliferation, and clinical activity of GEN-011 in patients with refractory solid tumors.

The study includes two dosing cohorts. Cohort A patients (n=2) received a lower intensity regimen without lymphodepletion with fractional GEN-011 doses monthly, and with post-infusion intermediate dose interleukin-2 (IL-2) (125K IU/kg daily s.c.). In Cohort B, patients (n=3) received GEN-011 as a single infusion after lymphodepletion, followed by IL-2. This Cohort includes one of three escalating lymphodepletion and IL-2 dose regimens, and patients have not yet been dosed at the high regimen.

The early results presented at AACR show anti-tumor activity despite the lower intensity regimens and heavily pretreated tumors. Stable disease was seen at the initial Day 57 scan in four of the five patients. While all patients had progressive disease (PD) at their Day 113 scan, three of the five experienced clear biologic changes after infusion.

These included palpable improvement in peripheral nodal disease and resolution of severe neuropathy causing arm paralysis and pain in patients with refractory SCCHN. A patient with metastatic non-small cell lung cancer (NSCLC) experienced a 10% reduction in tumor diameters (approx. 30% reduction in volume), also with resolution of tumor associated cough.

The potential for drug product proliferation and persistence for months is supported by translational assays, and clinical activity is associated with declines in detectable circulating tumor DNA (ctDNA) after treatment in some patients. Genocea has had a 100% success rate in manufacturing GEN-011 through its PLANET process to date. Of the 17 patient samples entering PLANET, 100% have either successfully yielded a released drug product (14) or are continuing in process (3).

Significantly, as a result of continuous process improvements, the next six patients will be dosed with drug products that have a median two-fold increase in cell dose and greater neoantigen specificity and potency. Additional data presented at AACR highlights ongoing work characterizing inhibitory antigens, or Inhibigens - putatively pro-tumor antigens that are uniquely identifiable by ATLAS and present in nearly every cancer patient profiled by Genocea. With the benefit of ATLAS, Genocea excludes T cells to Inhibigens from GEN-011.

A preclinical poster presented at the meeting demonstrates how detrimental these Inhibigens are to the efficacy of cancer therapeutics in mouse models of melanoma and pancreatic cancer.