Galera Therapeutics, Inc. announced the first patient has been dosed in a Phase 2a clinical trial of lead product candidate avasopasem manganese (GC4419) to evaluate its ability to reduce the incidence of radiation-induced esophagitis in patients with lung cancer. The open-label, multi-center trial will evaluate the efficacy of avasopasem manganese, a highly selective small molecule superoxide dismutase (SOD) mimetic, in reducing the incidence of severe (Grade 2 or worse on the NCI Common Terminology Criteria for Adverse Events scale) acute radiation-induced esophagitis in patients with lung cancer receiving chemoradiotherapy. Approximately 60 adult patients with pathologically confirmed unresectable Stage 3A/3B or post-operative Stage 2B non-small cell (NSCLC) or limited-stage small cell (SCLC) lung cancers will be enrolled at approximately 10 sites. Patients in the trial will receive 90 mg of avasopasem manganese by infusion on the days they receive their radiation therapy. There are approximately 230,000 new lung cancer patients diagnosed annually in the United States, and approximately 50,000 of those are treated with radiation therapy. Esophagitis, or mucositis of the esophagus, is a common and painful complication of radiation therapy for lung cancer. Symptoms can be life-threatening and include an inability to swallow, severe pain, ulceration, infection, bleeding and weight loss, and may require hospitalization. Galera’s lead product candidate, avasopasem manganese (GC4419), is a highly selective small molecule superoxide dismutase (SOD) mimetic that is initially being developed for the reduction of radiation-induced severe oral mucositis (SOM). Avasopasem manganese is designed to rapidly and selectively convert superoxide to hydrogen peroxide and oxygen, protecting normal tissue from damage associated with radiation therapy. Left untreated, elevated superoxide can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis (OM), which can limit the anti-tumor efficacy of radiation therapy. GC4419 is currently being studied in the ROMAN trial, a randomized, double blind, placebo-controlled Phase 3 trial with 365 patients (NCT03689712 available at clinicaltrials.gov) to determine the efficacy and safety of avasopasem manganese in patients with locally advanced head and neck cancer and radiation-induced OM. In Galera’s 223-patient, double-blind, randomized, placebo-controlled Phase 2b clinical trial in patients with locally advanced head and neck cancer receiving concurrent radiation therapy, avasopasem manganese significantly reduced the duration of SOM by 92% (from 19 days to 1.5 days in the 90 mg treatment arm). The incidence of SOM and the incidence of Grade 4 OM were also significantly reduced (by 34% and 47%, respectively, in the 90 mg treatment arm) in patients treated with avasopasem manganese. No significant safety signals were observed demonstrating avasopasem manganese is well tolerated when added to a standard radiotherapy regimen. The two-year tumor outcomes follow up of patients enrolled in the trial were consistent with expectations for intensity-modulated radiation therapy (IMRT)/cisplatin alone suggesting that radiation efficacy was maintained. Avasopasem manganese is also currently being studied in a Phase 2a trial for its ability to reduce the incidence of radiation-induced esophagitis in patients with lung cancer, as well as in a pilot Phase 1/2 trial (NCT03340974 available at clinicaltrials.gov) in combination with stereotactic body radiation therapy (SBRT) in patients with locally advanced pancreatic cancer. The U.S. Food and Drug Administration granted Fast Track and Breakthrough Therapy designations to avas opasem manganese for the reduction of the duration, incidence and severity of SOM induced by radiotherapy.