Sonnet BioTherapeutics Shares Decline Following SB221 Clinical Trial Expansion

Overview of Clinical Trial Expansion and Market Response

Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) shares experienced a decline of 6.86% on October 10, 2025, closing at $4.41. This movement followed the company's announcement regarding the expansion of its SB221 clinical study, which evaluates SON-1010 in combination with atezolizumab for patients with platinum-resistant ovarian cancer (PROC). The stock's performance reflects immediate investor reaction to the news, occurring amidst broader market scrutiny of clinical-stage biotechnology firms.

The SB221 Study: Progression and Key Data

The SB221 trial is a Phase 1b/2a dose-escalation and proof-of-concept study. It investigates SON-1010 (IL12-FHAB®) in combination with Genentech's atezolizumab (Tecentriq®) for advanced solid tumors or PROC. Sonnet reported positive safety outcomes from the trial's dose escalation phase.

Enrollment for the E6 dose expansion group (1200 ng/kg) has been completed, with two out of three patients in this cohort demonstrating confirmed partial responses (PRs). Encouraged by the strong safety profile observed at the top dose, the Safety Review Committee (SRC) recommended the addition of an E7 cohort at a maintenance dose of 1500 ng/kg. This expansion aims to further assess the combination's safety and effectiveness at a higher dosage.

Richard Kenney, M.D., Sonnet's Chief Medical Officer, stated, > "We are very pleased with the progress of the SB221 study and look forward to investigating the effect of a higher dose of SON-1010, with the hope that it could maximize efficacy without inducing cytokine toxicity."

Analysis of Market Reaction and Technical Indicators

Despite the clinical progress, Sonnet BioTherapeutics stock recorded a 6.86% decrease on the last trading day, falling from $4.74 to $4.41. Over the past ten days, the stock has declined in seven sessions, resulting in a 17.26% loss for the period. Trading activity for SONN on October 10, 2025, saw approximately 523,000 shares traded, valued at about $2.30 million. The stock experienced significant intraday volatility, fluctuating 15.23% between a low of $4.33 and a high of $4.99.

Technical analysis by StockInvest.us indicated a shift in sentiment, downgrading the stock from a "Buy" to a "Sell candidate." The stock currently holds sell signals from both short-term and long-term Moving Averages, suggesting a negative forecast. Resistance levels are identified at $5.20 and $4.71, while support is found near $3.96. The stock's "very high risk" classification is further underscored by its wide and falling trend channel.

Broader Context and Implications for Clinical-Stage Biotech

The biotechnology sector, particularly clinical-stage companies like Sonnet BioTherapeutics, often experiences heightened volatility tied to trial outcomes and regulatory milestones. SONN's current price of $4.41 stands in stark contrast to its 52-week high of $18.86 and its 52-week low of $1.08, reflecting the significant fluctuations inherent in drug development.

The market's immediate negative reaction, despite seemingly positive clinical updates, highlights investor cautiousness regarding the long development timelines and capital intensity associated with bringing new therapies to market.

Looking Ahead: Milestones and Market Watchpoints

Investors will be closely monitoring Sonnet BioTherapeutics for upcoming data readouts. Preliminary efficacy results for the expanded SB221 study, specifically from the E6 cohort, are anticipated later this year. Following this, Phase 2a randomization is planned for next year, which will be a critical step in further evaluating the therapy against standard care. From a technical perspective, the stock will need to establish a new bottom pivot to reverse its current negative trend. The ability of SONN to sustain upward momentum will depend on continued positive clinical data and investor confidence in its development pipeline.