CalciMedica Inc. announced positive topline data from CARPO, the Company's randomized, double-blind, placebo-controlled Phase 2b trial evaluating Auxora? for the treatment of acute pancreatitis (AP) with accompanying systemic inflammatory response syndrome (SIRS). The trial established a dose response for Auxora across multiple endpoints, identified both the target patient population and the likely drug dose for a pivotal trial, and re-affirmed Auxora's safety profile and tolerability as seen in prior clinical trials.

The Phase 2b CARPO trial was an international, randomized, double-blind, placebo-controlled, dose-ranging trial intended to establish Auxora's dose-response and efficacy in AP with accompanying SIRS. The trial reached its target enrollment of 216. Patients were randomized into four groups to receive either high 2.0 mg/kg dose (n=53), medium 1.0 mg/kg dose (n=56) or low 0.5 mg/kg dose (n=52) of Auxora or a matched dose of placebo (n=53) intravenously every 24 hours for a total of three doses.

Treatment and observation of patients continued for 30 days. Patients were stratified by baseline hematocrit, a biomarker for inflammation severity, so that efficacy in a pre-specified hyper-inflamed sub-group of patients could be evaluated. These patients represented approximately 43% of the patients enrolled (2.0 mg/kg, n=23; 1.0 mg/kg, n=25; 0.5 mg/kg, n=24; and placebo, n=20).

Patients were well-matched for all baseline characteristics with the exception that the placebo group had approximately 12% lower proportion of hyper-inflamed patients than the study overall. CARPO met its study objective by showing a dose response for time to solid food tolerance as well as other clinical endpoints. The primary endpoint of median time to solid food tolerance in the pre-specified subgroup of patients with hyper-inflammatory acute pancreatitis showed a statistically significant dose response with placebo patients requiring 4.7 days to tolerate solid food and patients in the high dose group showing a 1.9 day improvement (41.0% relative risk reduction) when compared to placebo, the medium dose group a 2.1 day improvement (43.6% relative risk reduction) and the low dose group a 1.5 day improvement (31.0% relative risk reduction).

In patients without hyper-inflammatory AP, Auxora did not show a measurable benefit due to the patients tolerating solid food relatively quickly in all treatment groups. Additionally, Auxora demonstrated a statistically significant dose response in reduction of severe organ failure which was defined as respiratory failure requiring invasive mechanical ventilation or 48 hours or more of high-flow nasal canula therapy, renal failure requiring renal replacement therapy, or cardiovascular failure requiring the use of vasopressor or inotropic support for greater than 48 hours. Severe organ failure occurred in 3.8% of high dose patients, 3.6% of medium dose patients, 9.6% of low dose patients, and 9.4% of placebo patients, representing a 59.6% relative risk reduction for the high dose patients when compared to placebo and 61.7% risk reduction for the medium dose patients when compared to placebo.

The median length of hospital stay was 5.0 days for the placebo group while the high dose group showed a reduction in the length of stay of 1.0 day. The mean length of stay showed a greater benefit: the placebo patients had a mean stay of 7.1 days and both the high dose and medium dose patients had a reduction of 1.2 days. In the patients with hyperinflammatory acute pancreatitis, the reduction was even greater, 1.5 days for the hyper-inflamed high dose patients and 1.9 days for the hyper-inflamed medium dose patients.

The proportion of patients who remained in the hospital for longer than 21 days was 0% for high dose patients, 1.8% for medium dose patients, 5.8% for low dose patients, and 5.7% for placebo patients. Comparing the combined placebo and low dose patients to the combined high and medium dose patients, this represents a 84.3% relative risk for a prolonged hospital stay. Auxora was well-tolerated with 20 treatment-emergent serious adverse events (TESAEs) reported in the placebo group, 14 in the high dose group, 21 in the medium dose group, and 23 in the low dose group.

None of the TESAEs in the high and medium dose groups and only 1 in the low dose group were deemed to be drug-related. There were no related TESAEs in the placebo group. Treatment-emergent adverse events (TEAEs) led to drug discontinuation in 3 patients in the placebo group, 2 in the high dose group, 2 in the medium dose group, and 2 in the low dose group.

TEAEs led to death in 1 patient in the placebo group and 1 in the medium dose group. There were no deaths in the high dose or low dose group.