VERVE-101

A Beam Therapeutics gene-editing therapy designed to fix a mutation at the root of a rare liver protein deficiency now has early signs of efficacy along with safety data that ease some concerns about this approach. The results also indicate Beam’s therapy could offer an edge over a therapy in development by a genetic medicines rival. The topline data announced Monday are for BEAM-302, which Cambridge, Massachusetts-based Beam is developing as a potential one-time treatment for alpha-1 antitrypsin deficiency (AATD), an inherited disorder that leads to lung and liver complications. Beam’s therapy employs base editing to perform an in vivo correction of the mutation at the root of the inherited disease. The Phase 1/2 test is designed with two parts: Part A is assessing the therapy’s effects on lungs while Part B will assess effects on the liver. The preliminary data announced Monday are for the first three doses in Part A. In nine patients (three for each dose level), results showed a single dose led to increases in levels of functional AAT protein measured at day 28. These increases were dose dependent and durable. Furthermore, the early results show up to 78% reduction in levels of the mutant protein that drives the inherited disease. Sponsored Post A Data-Driven Guide to Patient Access Success A new report from Relatient, A Data-Driven Guide to Patient Access Succes, highlights how focusing on data accuracy and relevance can enhance the performance of healthcare practices. By Relatient The best results were at 60 mg, the highest of the three doses tested. In this cohort, Beam reported AAT levels in study participants’ blood reached 12.4 micromolar, a measure of concentration. That tops the 11 micromolar mark set last fall by Wave Life Sciences, which is in Phase 1b/2a testing with its RNA-editing therapy for AATD, code-named WVE-006. Beam said all three doses of BEAM-302 were well tolerated with no adverse effects reported. That’s notable because Verve Therapeutics last April paused enrollment in a Phase 1b test of VERVE-101, an experimental treatment for an inherited form of high cholesterol, after high levels of liver enzymes and Grade 3 drug-induced thrombocytopenia were observed in a patient within four days of dosing. Verve developed this therapy with a license to Beam’s base-editing technology, so the safety signal raised concerns that there might be a problem with the Beam technology. Leerink Partners analyst Mani Foroohar wrote in a research note that the safety profile of BEAM-302 eases concerns about the safety of the lipid nanoparticle (LNP) used to ferry the therapy to liver cells. Beam management told Leerink that while the company obtains its LNPs from the same company as Verve, there are differences between them. With confidence from the strong safety profile so far, Beam aims to see if BEAM-302 can achieve even greater improvement in AATD levels. The company plans to continue the dose-escalation portion of its study by enrolling and dosing a fourth group. Beam expects to report additional data at a medical conference in the second half of this year. The biotech also plans to dose the first participant in the Part B portion of the study, which will enroll AATD patients with mild-to-moderate liver disease. presented by Artificial Intelligence Why Your Patients Are Leaving and How to Stop It Patient expectations continue to evolve, and healthcare practices that fail to adapt risk more than just revenue—they risk losing trust. By Bryan Sequeira, Director, Product Management Greenway Health Other biotech companies are developing potential AATD therapies. Arrowhead Pharmaceuticals is in Phase 3 testing with fazirsiran, an RNA-interference therapy that’s partnered with Takeda Pharmaceutical. Korro Bio recently began a Phase 1/2 test of KRRO-110, an RNA-editing therapy for AATD. Last summer, biotech startup AIRNA raised $60 million to advance to the clinic in 2025 with its experimental RNA-editing therapy for the disease. William Blair analyst Sami Corwin said in a research note that the increases in AAT and reductions in mutated versions of that protein achieved by BEAM-302 are comparable, if not better than Wave’s RNA editor, adding that the Beam therapy “has set the bar for efficacy in the space.” She also said the planned test to see if a higher dose leads to even better results could further differentiate the Beam therapy from competitors. Beam is capitalizing on the early positive clinical data with a $500 million stock offering priced at $28.48 per share. Despite the encouraging data, shares of the biotech still fell Monday, closing at $25.69, down 9.8% from Friday’s closing price. The broader stock market continued to slide amid business and investor uncertainty about tariffs as well as economic concerns after President Trump, in a Sunday television interview, declined to rule out the possibility of a recession this year. Image: by Sebastian Kaulitzki/Science Photo Library, Getty Images