The 60 mg dose of Beam’s therapy led functional protein levels to rise above the accepted threshold for a therapeutic effect in Alpha-1 antitrypsin deficiency.\n Boston biotech Beam Therapeutics has announced initial data from a phase 1/2 trial of its gene therapy for a genetic lung and liver disease, with no serious adverse events reported among the nine patients dosed so far.“We see the initial proof-of-concept data from BEAM-302 positively as it validates the safety and efficacy of BEAM’s LNP and in vivo base editing platforms,\" analysts from William Blair wrote on March 10. \"We are inclined to say BEAM-302 has set the bar for efficacy in the space.\"The one-time therapy appears to correct the mutation that causes the disease, known as Alpha-1 antitrypsin deficiency (AATD), with a higher dose leading to more functional molecules of the protein made by the gene, Beam said in a March 10 release.The data come from the first part of an early-stage trial that is expected to enroll about 106 adult patients with AATD, a genetic disease caused by a mutation in the SERPINA1 gene. This gene makes Alpha-1 antitrypsin (AAT), a protein made in the liver that then migrates to the lungs and helps regulate enzyme activity.Without enough functional AAT, patients can develop lung symptoms like chronic cough and shortness of breath, as well as liver symptoms like throwing up blood and yellow skin.The trial\'s first part includes patients with AATD and lung disease, while the second part will include patients with AATD, plus patients with AATD that also have mild to moderate liver disease. Beam plans to begin dosing for the second part of the trial later this year, according to the release.The nine patients included in the newly dropped data received a single intravenous infusion of the BEAM-302 gene therapy. The participants were evenly distributed across cohorts and received either 15, 30 or 60 milligram doses.All adverse events were mild to moderate, with no dose-limiting toxicities reported as of the data cutoff. Some patients saw asymptomatic grade 1 elevations of alanine transaminase and aspartate aminotransferase and grade 1 infusion-related reactions, which didn’t require treatment, Beam said. The three patients given the lowest dose, 15 mg, saw their functional AAT increase 1.6-fold at day 28. The three patients given 30 mg had 1.9-fold increases, while the final three given 60 mg had a 2.8-fold increase. “This landmark result in medicine represents the first clinical evidence of precise correction of a disease-causing mutation by rewriting the genetic code,” Beam CEO John Evans said in the release. “With a simple intravenous infusion, promising safety profile, sustainable increase of total AAT above the therapeutic threshold and rapid reduction in toxic mutant Z-AAT, we believe BEAM-302 has the potential to be a transformative therapy.”BEAM-302 targets the liver and is designed to use CRISPR to precisely cut and fix the single errant letter of DNA that causes the majority of AATD cases, a mutation called PiZ. Patients with the PiZ mutation make a mutant form of the AAT protein known as Z-AAT. BEAM-302\'s reparative technique separates it from many other CRISPR trials, which often try instead to completely knock out a dysfunctional gene. For example, Wave’s GSK-partnered therapy, WVE-006, doesn’t fix the mutation in the SERPINA1 gene but instead is designed to use an oligonucleotide to edit and correct the mutation in the mRNA encoded by the gene. This approach requires patients to be continually dosed with the therapy, rather than the one-time fix Beam is aiming for.“We believe the increases in serum total AAT and decreases in Z-AAT are comparable, if not better, than what have been reported with Wave’s RNA editor,” analysts from William Blair noted on March 10.Wave presented data from two patients given a single dose of its RNA editor in October 2024, showing the treatment increased their levels of functional AAT.The 60 mg dose of Beam’s therapy led AAT levels to rise above the accepted threshold for a therapeutic effect in AATD, the William Blair analysts added. Analysts from Mizuho, however, wrote in a March 10 note to clients that the Beam data \"do not seem necessarily better than WVE-006\'s.\" WVE-006\'s continual dosing could enable it to reach higher levels of AAT than Beam\'s single-dose genetic fix, the analysts said, and Beam\'s upcoming safety data in liver patients could prove important \"especially as it relates to potential liver enzyme elevations (seen in today\'s lung cohort).\"The Mizuho analysts also highlighted the potential for Beam\'s therapy to cause off-target edits to DNA, a feature seen in preclinical results but one that Beam hasn’t addressed yet in its phase 1/2 data.Given BEAM-302\'s clean safety profile so far, \"we believe it is prudent the company evaluate an additional dose level to see if higher levels of AAT correction and lower mutant AAT levels can be achieved, which could further differentiate BEAM-302 from competitors,\" the William Blair analysts wrote.Beam plans on enrolling a fourth dose cohort in the trial, the company said in the release, and intends to present more data at a medical conference in the second half of the year.After a brief spike to $36.82 per share at market open, Beam\'s stock dropped 14% from $28.5 at market close last Friday to $24.5 today as of 12 p.m. ET.Editor\'s note: This story was updated at 2 p.m. on March 10 to add comments from Mizuho analysts.
