ADX 097

After a mid-stage failure in atopic dermatitis, Q32 Bio plans to take bempikibart forward in alopecia instead, despite a trial in that indication also coming apart due to an error in patient enrollment. Q32 Bio’s update on the TSLP and IL-7Rα inhibitor disappointed investors, dropping its stock $QTTB by as much as 67% premarket. In part B of the Phase 2a SIGNAL-AD study, which enrolled 100 moderate-to-severe atopic dermatitis patients, subcutaneous bempikibart for 12 weeks offered a 74% improvement in the average Eczema Area and Severity Index — also known as EASI — at 14 weeks, compared with 76% for the placebo group. Meanwhile, part A randomized 15 adults to placebo or two different doses of bempikibart every two weeks for 12 weeks. At week 14, improvement in the EASI score was 58% in patients with the low dose, 84% in the high dose and 38% among placebo patients. Q32 Bio said it will investigate the notable discrepancy in the placebo response in the two parts. As for the SIGNAL-AA Phase 2a trial of bempikibart in alopecia areata, Q32 aimed to show the drug’s benefit over placebo on SALT, a scale evaluating scalp hair loss. After the trial database was locked, Q32 had to exclude one trial site from the efficacy analysis based on “marked protocol violations of entry criteria.” The subsequent removal of three placebo patients rendered the statistical analyses for the primary endpoint “inappropriate” due to the reduced sample size, the company said. The only data available are from a post-hoc analysis of the remaining 27 per-protocol patients. Bempikibart recipients showed a mean reduction in SALT score of 16% compared with 2% with placebo. Post-hoc analyses have little scientific value, and in any case, the alopecia market is tiny compared with atopic dermatitis. Q32 will delay the start of a planned Phase 2 trial of its complement inhibitor ADX-097 in ANCA-associated vasculitis, previously planned for 2025, to focus on bempikibart in alopecia and a mid-stage basket trial of ADX-097 in several renal disorders.

Dive Brief:Shares of Q32 Bio lost two-thirds of their value Wednesday after the company reported disappointing study results for an experimental medicine in two indications.The drug, bempikibart, is an antibody designed to interfere with two cytokines that play a role in immune function. In the two trials Q32 Bio reported late Tuesday, researchers tested their effects in eczema and a condition called alopecia areata that causes patchy hair loss.The drug failed to meet the primary endpoint in the second part of a trial for eczema, also known as atopic dermatitis, Q32 Bio said. In the other study, researchers observed what the company called promising signals of efficacy, but the results were marred by protocol violations.Dive Insight:The data readouts can only be characterized as messy, Piper Sandler analyst Christopher Raymond wrote in a note to clients. Though Q32 Bio plans to keep developing bempikibart for alopecia, Raymond and his team took potential sales out of their model, considering the work too risky. That leaves another experimental drug, ADX-097, as the sole value driver for the company, Raymond said.Shares of Q32 Bio traded below $8 Wednesday morning, after closing at $24.41 on Tuesday. Raymonds team cut its price target for the stock to $20 from $85, though stuck with an overweight rating. Leerink Partners was less optimistic about the companys future, slashing its price target to $9 from $68 and downgrading the stock to market perform from outperform.We are moving to the sidelines, pending further analyses of study results and more clarity on the path forward for bempikibart in alopecia and ADX-097 in renal diseases, Leerink Partners analyst Thomas J. Smith wrote to clients. Analysts expect the company to report data on ADX-097 in a renal basket study in the first half of next year.Q32 Bio also said it will defer enrollment for a planned Phase 2 trial of ADX-097 in ANCA-associated vasculitis which had been planned for next year. Instead, the company will focus its resources on the Phase 2 renal basket research for ADX-097 as well as an expanded study for bempikibart in alopecia areata.Results from the alopecia study, dubbed SIGNAL-AA, were muddied by the exclusion of one site because of protocol violations, leaving three placebo patients out of the planned analysis. Now, Q32 Bio plans to expand the trial with about 20 additional patients.The drug was safe and well tolerated in both the alopecia and eczema studies and demonstrated potent effects against the two cytokines known as interleukin-7 and thymic stromal lymphopoietin, the company said. '