Kymera's Phase 2b Advancement: KT-621 Trial Launches for Eosinophilic Asthma

Kymera Therapeutics has commenced enrollment in its BREADTH Phase 2b study, marking a significant milestone for KT-621, an innovative oral therapeutic candidate targeting moderate to severe eosinophilic asthma. The first patient has received their initial dose, signaling the transition of the company’s lead program toward late-stage clinical evaluation. This Phase 2b trial represents a critical juncture in validating KT-621’s potential to address the persistent therapeutic gap in asthma management, where current options like inhalers and injectable biologics remain limited.

Eosinophilic asthma, a chronic inflammatory airway disease, continues to challenge clinicians and patients alike due to its complex immune mechanisms and heterogeneous patient populations. The underlying pathophysiology centers on Type 2 immune activation, where abnormal eosinophil accumulation and airway remodeling create chronic obstruction and breathing difficulties. Traditional treatment strategies, while effective for some patients, fail to achieve comprehensive disease control in others, underscoring the clinical need for mechanism-based therapeutics that target the root drivers of inflammation.

Clinical Trial Design: BREADTH Phase 2b Study Parameters

The BREADTH Phase 2b trial is structured as a global, randomized, double-blind, placebo-controlled, dose-ranging study designed to enroll approximately 264 adult patients over a 12-week evaluation period. Patient selection criteria reflect a focus on moderate to severe disease phenotypes, requiring participants to demonstrate an absolute blood eosinophil count of at least 300 cells/µL, a fractional exhaled nitric oxide (FeNO) reading of 25 ppb or higher, and pre-bronchodilator forced expiratory volume in one second (FEV1) between 40% and 80% of predicted values. These biomarker thresholds ensure enrichment for Type 2-driven inflammation and optimize the likelihood of detecting treatment benefit.

The primary endpoint centers on FEV1 change from baseline, a gold-standard measure of lung function improvement. Secondary endpoints comprehensively assess safety tolerability, additional efficacy markers, and patient-reported quality of life measures, providing a holistic evaluation framework for Phase 2b success criteria.

STAT6 Targeting: Mechanism and Type 2 Inflammation Control

KT-621 operates as a precision degrader of STAT6, a transcription factor central to Type 2 immune signaling. By targeting STAT6, the molecule effectively interrupts IL-4 and IL-13 signaling—the master regulators of eosinophilic inflammation, IgE production, and Th2 cell differentiation. This mechanism-first approach distinguishes KT-621 as the inaugural STAT6-directed therapeutic to advance into human clinical evaluation, representing a novel pharmacological strategy for Type 2-driven diseases.

Early Phase 1 data in atopic dermatitis patients demonstrated profound STAT6 degradation, substantial reductions in disease-relevant biomarkers, and clinically meaningful skin improvement coupled with a reassuring safety profile. These encouraging signals provide a mechanistic rationale for KT-621’s application across multiple Type 2 inflammatory indications, suggesting potential for broad therapeutic utility.

Concurrent Research: Parallel Phase 2b Trials Across Indications

Complementing the BREADTH asthma trial is the ongoing BROADEN2 Phase 2b study in moderate to severe atopic dermatitis patients, with efficacy readout anticipated by mid-2027. The parallel 2b-stage evaluation strategy across two genetically and clinically distinct Type 2 indications accelerates clinical development while simultaneously enabling dose optimization for subsequent Phase 3 registrational programs. This dual-pathway approach maximizes the probability of identifying optimal therapeutic dosing applicable to multiple disease settings, thereby de-risking later-stage development and improving path-to-market efficiency.

Path to Phase 3: Timeline and Financial Runway

BREADTH Phase 2b data is expected in 2027, providing a pivotal data readout to inform Phase 3 program design across asthma, dermatitis, and potentially additional Type 2-driven indications. Kymera’s balance sheet remains robust, with $1.6 billion in cash reserves as of end-2025, providing financial runway extending into 2029. This extended cash runway affords the company substantial flexibility to advance KT-621 through multiple Phase 2b programs and into Phase 3 registrational studies without near-term capital constraints.

The advancement of KT-621 through parallel Phase 2b trials underscores the company’s commitment to mechanism-driven drug development in the increasingly validated Type 2 inflammation space, positioning both BREADTH and BROADEN2 as potentially transformative clinical programs for patients with limited treatment alternatives.