Amryt announces that The Lancet Diabetes & Endocrinology has published the full results of the global Phase 3 MPOWERED clinical trial that compared Mycapssa® (oral octreotide capsules) to long-acting injectable Somatostatin Receptor Ligands (iSRLs) for maintenance of biochemical response in patients with acromegaly. The MPOWERED trial was designed to support the marketing authorization application for Mycapssa® to the EMA which is currently under evaluation. The MPOWERED trial adds to the evidence base built with two previous Phase 3 trials, CH-ACM-01 and CHIASMA OPTIMAL, both of which supported the US FDA approval of Mycapssa® for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with injectable octreotide or lanreotide.

Key outcomes of the MPOWEREDPhase 3Trial are listed below: Mycapssa® was non-inferior to long-acting injectable octreotide or lanreotide in maintenance of biochemical control,in patients previously responding to both treatments On the primary endpoint of the proportion of patients maintaining biochemical response throughout the 9-month Randomized Control Treatment (RCT) phase, 91% of patients on Mycapssa® maintained response compared to 100% on iSRLs. Response was defined as the time-weighted average of IGF-1 <1.3 x upper limit of normal (ULN) throughout the phase. Mean IGF-1 was the same at the start and end of the RCT phase in both groups and was maintained within normal limits All sensitivity analyses supported the results of the primary endpoint using both time-weighted average and more traditional landmark methods of analyzing IGF-1 data Oral octreotide results for breakthrough and active acromegaly symptoms At the end of the RCT phase, 15% of patients in the oral octreotide group reported breakthrough symptoms of acromegaly, compared with 31% in the iSRL group.

The overall number of individual active acromegaly symptoms was similar between treatment groups. A significant reduction in the number of certain active acromegaly symptoms was reported in patients responding to Mycapssa® at the end of the run-in phase. Specifically, significant reductions were shown in the proportions of participants with swelling of extremities (p=0.01) and fatigue (p=0.03).

Patient reported outcomes with oral octreotide capsules A significant improvement was reported from baseline while treated with iSRLs to the end of the run-in phase in patients responding to Mycapssa® in three of the five Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) scales (emotional reaction, treatment convenience, and treatment satisfaction), with improving trends in the other two scales (gastrointestinal interference and symptom interference) Change from start of the RCT phase for each of the five Acro-TSQ scales was generally similar between treatment groups Oral octreotide capsules showed comparable safety profile to iSRLs The incidence of adverse events (AEs) during the RCT was similar between groups with 39 (71%) of 55 participants in the oral octreotide group and 26 (70%) of 37 participants in the iSRL group reporting at least one AE. In both treatment groups, most treatment-related AEs were gastrointestinal. 17 (47%) of 36 participants randomly assigned to iSRL reported injection site reactions via the Acro-TSQ scales at the end of the RCT, and 13 (81%) of 16 reported that injection site reactions interfered with daily activities About the MPOWERED Phase 3 Trial The MPOWERED trial was a global, randomized, open-label and active-controlled, 15-month trial intended to support approval of Mycapssa® in the European Union.

Chiasma/Amryt completed enrollment of 146 adult acromegaly patients into the trial in June 2019, of which 92 patients who were deemed responders to octreotide capsules per the protocol following a six-month run-in were randomized to either octreotide capsules (n=55) or iSRLs (octreotide long-acting release or lanreotide autogel) (n=37). These patients were then followed for an additional nine months in the RCT phase. At the end of the RCT phase patients were provided the option to continue into an open label phase and receive Mycapssa®.

FDA APPROVED INDICATION AND USAGE Mycapssa® (oral octreotide) delayed-release capsules, for oral use, is a somatostatin analog indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide.