Briquilimab: A Breakthrough in Chronic Urticaria and Its Implications for Investors

Chronic urticaria, a condition characterized by persistent hives and itching, affects millions worldwide, yet existing treatments like antihistamines and omalizumab often fall short. Enter Jasper Therapeutics' briquilimab, a first-in-class monoclonal antibody targeting c-Kit, the receptor critical to mast cell survival. With compelling Phase 1b/2a trial data demonstrating rapid symptom relief, durable responses, and a favorable safety profile, briquilimab is positioned to redefine care for chronic urticaria patients—and offer investors an intriguing risk-reward opportunity.

The Case for Briquilimab: Clinical Data That Stands Out

Chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU) are refractory conditions marked by severe, unpredictable flare-ups. Current therapies address symptoms but do not address the root cause: mast cell overactivity. Briquilimab's mechanism—depleting mast cells via c-Kit inhibition—targets this underlying biology.

BEACON Trial: A Strong Showing in CSU

In the BEACON study, briquilimab demonstrated remarkable efficacy in CSU patients who had failed standard therapies:
- The 240mg single-dose cohort achieved 100% complete responses (UAS7 score = 0) at 8 weeks, with 66% maintaining “well-controlled” disease (UAS7 ≤6) at 12 weeks.
- At 12 weeks, the 120mg and 180mg dosing regimens showed mean UAS7 reductions of -27.2 and -13.2, respectively, far outperforming placebo.
- Serum tryptase, a mast cell-derived biomarker, dropped to undetectable levels in 100% of the 240mg cohort by week 1, reinforcing the drug's mechanism.

SPOTLIGHT Trial: Tackling Cold Urticaria and Dermographism

For CIndU subtypes like cold urticaria and symptomatic dermographism, the SPOTLIGHT trial reported:
- 83% complete responses (CR) in the 120mg cohort within 6 weeks, with significant improvements in provocation thresholds (e.g., TempTest®).
- 93% of all participants achieved clinical responses, a stark contrast to the limited efficacy of antihistamines in this patient population.

Both trials highlighted excellent safety, with no serious adverse events (SAEs) or grade 3+ toxicities beyond transient neutrophil decreases, which resolved without intervention.

Market Potential: A Large, Underserved Patient Population

Chronic urticaria affects approximately 1%–2% of the global population, with $2 billion in annual sales for existing treatments like omalizumab (Xolair). However, 20%–30% of patients fail to respond adequately, creating a $500 million addressable market for next-generation therapies.

Briquilimab's ability to deplete mast cells—a mechanism unmet by current options—positions it as a best-in-class therapy for severe cases. If approved, it could capture a significant share of this market, particularly in CIndU, where few alternatives exist.

Investment Considerations: A Catalyst-Driven Story

The upcoming Phase 2b registrational program for CSU, expected to begin in late 2025, is a critical catalyst. Positive results could fast-track regulatory submissions by late 2026, with potential FDA approval by early 2028.

Investors should monitor:
1. Data Readouts: Full results from the BEACON and SPOTLIGHT trials, including the 180mg/240mg cohorts, by mid-2025.
2. Competitor Landscape: While omalizumab and dupilumab (Dupixent) are mainstays, their mechanisms do not target mast cells, leaving room for briquilimab to carve a niche.
3. Commercial Viability: The drug's subcutaneous dosing and durable responses (up to 16 weeks) could reduce treatment burden, enhancing its appeal.

Risks and Challenges

• Small Trial Sizes: Early-phase data from small cohorts (e.g., N=3 in the 240mg single-dose group) may not fully predict outcomes in larger, diverse populations.
• Safety in Long-Term Use: While early data is reassuring, prolonged mast cell depletion could pose theoretical risks, though no such issues emerged in trials to date.
• Regulatory Hurdles: The FDA may require additional data on durability or biomarker endpoints before approval.

Conclusion: A Transformative Opportunity with Asymmetric Upside

Briquilimab's clinical profile—rapid symptom control, durable responses, and a clean safety profile—suggests it could become a cornerstone therapy for chronic urticaria. With a $2 billion+ market opportunity and a 2025–2026 catalyst timeline, Jasper Therapeutics offers investors asymmetric upside.

Investment Thesis:
- Buy: For investors seeking a high-risk, high-reward play in biotech, with catalysts in late 2025.
- Hold: For conservative investors awaiting Phase 2b data.

As the company progresses toward registrational trials, the risk-reward calculus for briquilimab continues to tilt favorable—a testament to its potential to transform a field where patients have waited too long for better options.