Briquilimab's Breakthrough in CSU Faces Manufacturing Hurdles: A Buy with Cautious Optimism?

The quest for effective therapies in chronic spontaneous urticaria (CSU)—a debilitating condition marked by chronic hives and itching—has taken a promising turn with Jasper Therapeutics' briquilimab. New data from its BEACON Phase 1b/2a trial and open-label extension studies reveal compelling efficacy, but manufacturing snags have cast a shadow over timelines and strategic priorities. For investors, the question is whether the drug's clinical potential in CSU outweighs execution risks tied to its production challenges. Here's why the stock (JSPR) could still be worth a cautious buy—if Jasper can navigate these hurdles.

The Clinical Case for Briquilimab

Briquilimab, an anti-KIT monoclonal antibody, has shown remarkable efficacy in early trials targeting mast cell-driven diseases. In CSU, the single-dose cohorts (240mg and 360mg) delivered striking results: 89% of participants achieved a complete response (UAS7=0) by week 2, with 78% maintaining well-controlled disease through week 8. The open-label extension at the 180mg dose—key for long-term management—also demonstrated 73% complete response rates at 12 weeks, underscoring durability.

The Urticaria Activity Score (UAS7) reductions were profound: mean drops of 28.3 points at 4 weeks in the 240mg cohort (vs. 22.9 in the 360mg group), far exceeding the 13-point threshold considered clinically meaningful. Crucially, briquilimab's safety profile appears favorable, with no grade 3+ treatment-related adverse events reported. Mild neutrophil count reductions were observed but did not correlate with infections or fever, a critical differentiator from other mast cell inhibitors.

These data position briquilimab as a potential best-in-class therapy for CSU, a market dominated by Xolair (omalizumab), which requires subcutaneous injections every 2–4 weeks. Briquilimab's subcutaneous dosing every 8 weeks could offer superior convenience, while its targeting of KIT—a mast cell-specific receptor—may reduce off-target effects.

The Manufacturing Hurdle: A Double-Edged Sword

The excitement around briquilimab is tempered by a critical manufacturing snag. A defective lot of the drug product affected 10 of 13 patients in the 240mg Q8W and 240/180mg cohorts, resulting in minimal tryptase level drops and no UAS7 improvements. Only two patients who received a “good” lot achieved complete responses, highlighting the issue's severity.

This defect has ripple effects:
- The Phase 2b CSU trial is delayed until mid-2026, pushing pivotal data further into the future.
- Development in asthma (ETESIAN trial) and severe combined immunodeficiency (SCID) has been halted indefinitely, narrowing Jasper's near-term catalysts.

The company is addressing the issue by replacing the faulty lots and re-enrolling 10–12 patients to bolster data for the CSU Phase 2b. However, the delay and halted trials raise concerns about cash burn and the timeline for regulatory approval.

(A graph showing JSPR's stock price, which may have dipped on the manufacturing news but could rebound with resolution.)

Balancing the Investment Thesis

The Bull Case:
- CSU Market Opportunity: With ~5 million diagnosed cases in major markets and unmet needs in treatment-refractory patients, briquilimab's efficacy could carve out a $500M+ annual revenue stream if approved.
- Safety Differentiation: No severe side effects reported to date, unlike some competitors, could position it as a preferred option.
- Strategic Pivot: Focusing solely on CSU (where efficacy is clear) while addressing manufacturing issues could streamline operations and preserve cash.

The Bear Case:
- Execution Risk: Manufacturing errors could recur, especially as production scales up.
- Competitor Pressure: Xolair remains entrenched, and potential rivals like AstraZeneca's fostamatinib are in late-stage trials.
- Cash Constraints: With halted trials in other indications, Jasper's burn rate must be tightly managed to avoid dilution.

Investment Recommendation

Jasper's stock presents a high-risk, high-reward opportunity. If the company can:
1. Resolve the manufacturing issue definitively,
2. Deliver robust Phase 2b data by late 2026, and
3. Extend its cash runway beyond 2025 via cost cuts and potential partnerships,

briquilimab's CSU profile could justify a buy rating. However, investors should demand cash visibility (e.g., ) and clarity on lot stability before committing.

For now, Jasper's shares are a hold until these uncertainties are addressed. But with CSU's unmet need and briquilimab's unique mechanism, this could be a stock to watch closely as the manufacturing cloud lifts.

Final Take: The CSU opportunity is too large to ignore, and briquilimab's data is compelling. But investors must weigh the risks of execution—manufacturing and otherwise—against the potential reward. Stay tuned for updates on the drug lot resolution and cash management.