First Wave BioPharma, Inc. announced that the Company will initiate its planned Phase 2 clinical trial of an enhanced enteric microgranule delivery formulation for adrulipase for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF). The U.S. Food and Drug Administration (FDA) has reviewed the Investigational New Drug (IND) amendment and after requesting and receiving a modified protocol, has not provided any further comments in the 60 day period of review. The Phase 2 multi-center study is designed to investigate the safety, tolerability and efficacy of an enteric microgranule delivery formulation for adrulipase in a titrated dose-escalation study involving an estimated twelve (12) patients.

The primary efficacy endpoint is the coefficient of fat absorption (CFA), with secondary endpoints of stool weight, signs and symptoms of malabsorption and coefficient of nitrogen absorption (CNA). First Wave BioPharma expects to initiate patient screening in early February 2023, with topline data anticipated by mid-2023. Three clinical trial sites in the U.S. will be participating in the trial.

In vitro data suggest the microgranule drug delivery formulation offers improved protection against the acidic pH in the stomach followed by the rapid release of adrulipase in the small intestine where the drug is expected to mix with food and deliver its therapeutic benefit. Additionally, in vitro research indicates the enhanced formulation has the potential to significantly decrease the number of pills a patient would need to take to achieve the desired therapeutic effect. The pill burden for current commercial porcine pancreatic enzyme replacement therapy (PERT) can be as high as 40 capsules per day, creating a substantial challenge for EPI patients.

Phase 2 SPAN Trial Design The Phase 2 SPAN trial is designed to investigate the safety, tolerability and efficacy of a new enteric microgranule formulation of adrulipase. The SPAN trial is an open-label study that will be conducted at three sites in the U.S. A total of 12 cystic fibrosis patients, 18 years or older are expected to be enrolled. The trial design employs a dose titration strategy.

Patients will be screened at baseline to ensure that they have a coefficient of fat absorption (CFA) of at least 80%. Eligible patients will then be switched from their commercial enzyme product to adrulipase. Each patient will be started on a low dose of adrulipase.

If the patient is not clinically controlled, the patient will be switched to a medium dose, and if not controlled on this dose, the patient will be advanced to a high dose. The titrations will be carried out over a three week period, after which a CFA will be obtained. End of study CFAs will be compared to the baseline CFAs in a descriptive fashion.

A post-treatment safety visit will be conducted one week after completing the treatment period.