Beam’s Base Editor Advances to Pivotal Development on Back of ‘Impressive’ AATD Data

 

Beam is now in the strongest position of all companies advancing a genetic therapy for alpha-1 antitrypsin deficiency, according to analysts at William Blair.

Beam Therapeutics’ investigational base editor increases the functional levels of a key enzyme that is otherwise deficient in patients with alpha-1 antitrypsin deficiency, opening a path to pivotal development later this year.

Alpha-1 antitrypsin deficiency, also known as AATD, is a heritable disorder caused by mutations to the SERPINA1 gene that result in a deficient AAT enzyme. Patients with AATD can suffer from progressive damage to the lungs, cirrhosis and sometimes liver failure. Beam’s asset, BEAM-302, is designed to correct the underlying genetic alteration in AATD and increase the production of functional AAT.

Phase 1/2 data presented on Wednesday support this mechanism. After a single administration of 60 mg BEAM-302, 94% of circulating AAT was correctly folded, while the concentration of the faulty enzyme dropped by 84%. The average circulating level of AAT reached 16.1 uM.

“This is the highest mean serum AAT level we have clinically seen to date from SERPINA1 correction approaches,” William Blair analysts told investors in a note on Wednesday, calling the data “impressive.”

Initial safety findings for BEAM-302 indicate that adverse events were mostly mild to moderate, with no dose-limiting toxicities. The biotech detected one case of grade 4 liver enzyme elevation—a signal that, according to William Blair, was “muting upside potential”—though this was asymptomatic and did not require medical intervention.

“Overall, today’s results reinforce BEAM-302’s best-in-class profile and place Beam in the strongest position among emerging genetic approaches to AATD,” the firm said.

With these data, along with feedback from the FDA, Beam on Wednesday also announced that it will seek the regulator’s accelerated pathway for approval. A pivotal expansion portion of the ongoing Phase 1/2 study will form the basis of this application and is slated to start in the back half of this year.

Analysts from H.C. Wainwright expressed confidence in the asset, writing in a Wednesday note that Beam’s readout not only de-risks its pivotal plans but also “reinforces our conviction in BEAM-302’s best- and first-in-class potential.”

If approved, the firm projects annual peak revenues of approximately $4 billion for BEAM-302.

https://www.biospace.com/drug-development/beams-base-editor-advances-to-pivotal-development-on-back-of-impressive-aatd-data