Kymera Therapeutics Announces Positive Results from BroADen Phase 1b Clinical Trial of KT-621, a First-in-Class, Oral STAT6 Degrader, in Patients with Moderate to Severe Atopic Dermatitis KT-621 achieved deep STAT6 degra

Kymera Therapeutics Announces Positive Results from BroADen Phase 1b Clinical Trial of KT-621, a First-in-Class, Oral STAT6 Degrader, in Patients with Moderate to Severe Atopic Dermatitis

KT-621 achieved deep STAT6 degradation across both the 100 mg and 200 mg dose groups tested, with

median reductions of 94% and 98% in skin and blood, respectively, demonstrating strong translation from healthy volunteers to atopic dermatitis (AD) patients

KT-621 achieved strong reductions in disease-relevant Type 2 biomarkers in blood, including TARC

(median reduction of 74% in patients with baseline TARC levels comparable to dupilumab AD studies), Eotaxin-3, IL-31, IgE, and in core Type 2 inflammation and AD

disease-relevant gene sets in skin lesions

Robust clinical activity was observed across all disease endpoints measured including

mean 63% EASI reduction and mean 40% peak pruritus NRS reduction for all patients

Patients with comorbid asthma showed a median 56%

reduction in FeNO and meaningful improvements in asthma control, and those with comorbid allergic rhinitis experienced significant symptom and quality-of-life benefits

KT-621 was well-tolerated with no serious adverse events, no treatment related adverse

events, no reported cases of conjunctivitis and no clinically relevant changes in vital signs, lab tests or ECGs

KT-621 BROADEN2 Phase 2b trial in moderate to severe AD is ongoing, with data expected by mid-2027; Phase 2b BREADTH trial in moderate to severe asthma patients is on track to

Company to hold video conference call and webcast today at 8:00 a.m. ET

Watertown, Mass. (December 8, 2025) - Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing a new

class of oral small molecule degrader medicines for immunological diseases, today announced positive clinical results from the BroADen Phase 1b atopic dermatitis (AD) clinical trial of KT-621, its first-in-class, oral STAT6 degrader medicine.

"The BroADen study results

exceeded our highest expectations and provide a powerful additional validation of our industry-leading STAT6 degrader program," said Nello Mainolfi, PhD, Founder, President and CEO, Kymera Therapeutics.

"KT-621 demonstrated its potential to deliver a first-in-class once-a-day oral treatment for Type 2 inflammatory diseases across every measure we evaluated, including STAT6 degradation, biomarker modulation, clinical activity, impact on other comorbid Type 2 diseases and

safety. The results were in line with, or in some cases numerically exceeded, published data for dupilumab at week 4 and we believe further reinforce Kymera's pioneering expertise in developing transformative oral small molecules with the

potential for the activity and safety of injectable biologics."

"The most impressive outcome of our BroADen study is the consistency that KT-621 demonstrated in all measured endpoints: STAT6 degradation, reduction of blood Type 2 biomarkers, including the first known demonstration of impact of IL-4/13 pathway

blockade on IL-31 and FeNO in AD patients, and reduction of core Type 2 inflammation and AD disease-relevant gene sets in skin lesions. These results were further reinforced by activity across a broad range of

clinical endpoints that included objective measures as well as patient reported outcomes in patients with AD and those with comorbid asthma and allergic rhinitis," said Jared Gollob, MD, Chief Medical Officer, Kymera Therapeutics. "KT-621 achieved these results at doses that were well-tolerated, exhibiting a safety profile consistent with what we observed in the Phase 1a healthy volunteer study. We are excited to advance this innovative

program through the ongoing BROADEN2 Phase 2b study in AD patients and remain on track to initiate our BREADTH Phase 2b trial in asthma early next year. We are deeply grateful to the patients, investigators, and clinical teams whose collaboration

and commitment made this milestone possible."

"These results represent an innovative step forward in the treatment of atopic

dermatitis," said Eric Simpson, MD, MCR, Frances J. Storrs Medical Dermatology Professor and Director of CLEAR Eczema Center, Oregon Health & Science University. "There remains a clear need for new oral therapies that can

address the underlying biology of the disease while potentially offering patients greater convenience. KT-621's novel mechanism and encouraging early data showing impact on clinical endpoints and

biomarkers of Type 2 inflammation highlight the potential for this program to expand the options for people living with AD as well as other Type 2 allergic diseases."

KT-621 BroADen Phase 1b trial was an open-label, single-arm study that enrolled 22 patients with moderate to severe AD across two dose levels (enrolled in two sequential

cohorts) selected based on results from the KT-621 Phase 1a healthy volunteer study. Ten participants received 100 mg and twelve participants received 200 mg of KT-621

once daily for 28 days, followed by a 14-day follow-up period. Key objectives of the study were to evaluate KT-621 safety and

tolerability and to demonstrate that KT-621 could achieve robust STAT6 degradation in both blood and skin, resulting in dupilumab-like reductions in multiple Type 2 inflammatory biomarkers in circulation and

in the transcriptome of active AD lesions after 4-weeks of dosing. The study also explored effects on clinical activity and disease burden endpoints.

Baseline Characteristics

The two dose groups were

generally well-balanced for gender, age, race, and measures of disease severity including vIGA-AD, EASI and peak pruritus NRS. The mean baseline EASI score across the two groups was approximately 25. Approximately 46% of patients had comorbid asthma

or allergic rhinitis and approximately 23% had prior biologics treatment with either dupilumab and/or tralokinumab.

Pharmacokinetics and STAT6

KT-621 exhibited a plasma PK profile across the 100 mg and 200 mg dose groups consistent with

the Phase 1a healthy volunteer trial results. KT-621 demonstrated deep and consistent STAT6 degradation in both blood and skin across the 100 mg and 200 mg dose groups, translating strongly from the Phase 1a

healthy volunteer study. At Day 29, median STAT6 degradation in blood as measured by flow cytometry was 98% at both the 100 mg and 200 mg doses. In skin lesions, where STAT6 levels were 2-fold higher compared

to healthy volunteers, KT-621 achieved median STAT6 degradation of 94% by mass spectrometry at both the 100 mg and 200 mg doses with multiple subjects' STAT6 level dropping below the lower limit of

quantification (LLOQ).

Thymus and Activation-Regulated Chemokine (TARC): A validated biomarker of Type 2 inflammation, TARC reductions with

KT-621 were robust and highly associated with baseline levels of TARC in treated patients, consistent with reported dupilumab studies across multiple diseases. In patients with baseline TARC in line with

dupilumab AD studies, defined as 1,600 pg/mL (which is the lower bound of the 95% confidence interval for median baseline TARC levels from the dupilumab SOLO1-2 AD studies), the median TARC reduction at

Day 29 was 74%, in line with published dupilumab results at week 4. Across all patients, TARC was reduced by a median 48% and 55% for the 100 mg and 200 mg dose groups, respectively.

Eotaxin-3: At Day 29, KT-621 achieved a median reduction in Eotaxin-3 of 62% and 73% for the 100 mg and 200 mg dose groups, respectively. Eotaxin-3 is a highly specific downstream cytokine of the IL-4/IL-13 pathway. These results numerically exceeded what has been reported with dupilumab in asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) patients even at 52 weeks.

Immunoglobulin E (IgE): At Day 29, KT-621 achieved a median IgE reduction of 5% and 14% for the 100 mg and 200

mg dose groups, respectively, which were comparable to the reported dupilumab data at week 4. As expected for a Type 2 biomarker with a long half-life, reductions emerged gradually and aligned with kinetics observed in studies for representative

IL-31: KT-621 achieved robust reductions in serum IL-31, a validated Type 2 biomarker linked to pruritus in AD. At Day 29, median IL-31 levels were reduced by 56% and 54% in the 100 mg and 200 mg dose groups, respectively,

demonstrating potent suppression of this pruritogenic cytokine through STAT6 degradation. This is the first known demonstration in AD patients of reduction in blood levels of IL-31 with IL-4/13 pathway blockade.

Fractional Exhaled Nitric Oxide (FeNO): A validated biomarker of Type 2 lung

inflammation shown to be modulated by biologics like dupilumab targeting the IL-4/13 pathway in asthma, KT-621 achieved median FeNO reductions at Day 29 of 25% and 33%

among all patients within the 100 mg and 200 mg dose groups, respectively. This is the first known demonstration of FeNO reduction in AD patients, providing initial proof of concept for KT-621 inhibition of

Type 2 inflammation in lungs.

Skin Transcriptomics: Across all patients and doses, KT-621 led to decreases

in core Type 2 inflammation and AD disease-relevant gene sets in skin lesions after 4-weeks of dosing, including genes such as TARC, PARC, Eotaxin-3, periostin, keratin

16 and TSLP, with results comparable to dupilumab at week 4.

Eczema Area and Severity Index (EASI): Mean EASI score reductions at Day 29 were 62% and 63% in the 100 mg and 200 mg dose groups, respectively, and 63%

across all patients. KT-621 demonstrated rapid onset of action with measurable EASI impact by Day 8, the earliest timepoint reported. Comparable reductions were observed in patients with low or high baseline

TARC levels and patients with low or high baseline EASI. EASI-50 (³50% improvement from baseline) was 67% and 83% in the 100 mg and 200 mg dose groups, respectively, and 76% across all patients. EASI-75 (³75% improvement from baseline) was 33% and 25% in the 100 mg and 200 mg dose groups, respectively, and 29% across all patients.

For EASI and all other clinical endpoints measured, KT-621 achieved improvements that were in line with or in some

cases numerically exceeded published data for dupilumab at week 4. In addition, results were generally comparable across patients with or without prior biologics use.

Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): At Day 29, the proportion of vIGA-AD responders (patients achieving a score

of 0 or 1 with at least a 2-point improvement) was 22% and 17% in the 100 mg and 200 mg dose groups, respectively, and 19% across all patients.

Peak Pruritus (Itch): Mean Peak Pruritus Numerical Rating Scale (NRS) reductions at Day 29 were 47% and 35% in the 100 mg and 200 mg dose groups,

respectively, and 40% across all patients. KT-621 demonstrated rapid onset of action with measurable impact on pruritus as soon as Day 8, the earliest timepoint reported.

SCORing Atopic Dermatitis Index (SCORAD): KT-621 demonstrated improvements across all SCORAD domains, including

itch and sleeplessness, reflecting both lesion improvement and symptom relief. At Day 29, total SCORAD scores decreased substantially with 52% and 46% mean reductions in the 100 mg and 200 mg dose groups, respectively, and 48% across all patients.

For sleeplessness, at Day 29 mean reductions were 72% and 78% in the 100 mg and 200 mg dose groups, respectively, and 76% across all patients. For itch, at Day 29 the mean reductions were 40% and 47% in the 100 mg and 200 mg dose groups,

respectively, and 44% across all patients.

DLQI and POEM: KT-621 produced meaningful improvements in

patient-reported quality of life, as measured by the Dermatology Life Quality Index (DLQI) and Patient-Oriented Eczema Measure (POEM). Both scores declined steadily over the 4-week treatment period across both

dose levels. These outcomes underscore KT-621's rapid, patient-perceived impact on daily functioning and well-being, complementing the objective clinical improvements observed across other endpoints.

Impact on Comorbid Type 2 Diseases

Asthma: In those AD patients with comorbid asthma (n=4), at Day 29, KT-621 achieved a median FeNO reduction of

56%, which numerically exceeded published data for dupilumab at week 4 in asthma patients, and clinically meaningful ACQ-5 mean change of -1.2 points which corresponded

to a 100% responder rate ( 0.5-point improvement). These results support systemic STAT6 degradation and modulation of Type 2 inflammation in the lungs and validate

KT-621's mechanistic breadth and potential to benefit patients across Type 2-driven diseases, including asthma, where FeNO serves as a key biomarker of disease activity and therapeutic response.

Allergic Rhinitis: In evaluable patients with comorbid allergic rhinitis, KT-621 demonstrated activity

with meaningful improvements in both Total Nasal Symptom Score (TNSS, n=7) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, n=6) measures, with notable responder rates ( 0.5-point

improvement) in both endpoints. These findings demonstrate KT-621's broader potential across immuno-inflammatory diseases, reflecting systemic Type 2 pathway engagement.

Safety and Tolerability

KT-621 was well-tolerated with a favorable safety profile consistent with the Phase 1a healthy volunteer trial results.

There were no serious adverse events (SAEs), no severe AEs, no related treatment-emergent-adverse events (TEAEs) or TEAEs leading to discontinuation, no AEs of conjunctivitis, herpes infections or arthralgias, and no clinically relevant changes in

vital signs, laboratory tests or electrocardiograms.

The Company's KT-621 BROADEN2 Phase 2b trial in moderate to severe AD patients is ongoing, and patient dosing has

commenced. Data is expected to be reported by mid-2027. The BREADTH Phase 2b trial in asthma is planned to start in the first quarter of 2026. These studies are intended to accelerate KT-621 development and enable dose selection for subsequent parallel Phase 3 registration studies across multiple Type 2 dermatology, gastroenterology and respiratory indications.

Kymera will host a video conference

call today, December 8, 2025, at 8:00 a.m. ET. To join the video call or view the livestreamed webcast please register via this link or visit "News and Events" in the Investors section of

Kymera's website at www.kymeratx.com. A replay of the webcast and the presentation will be available following the event.

KT-621 is an investigational, first-in-class, once daily, oral degrader of STAT6, the specific transcription factor responsible for IL-4/IL-13 signaling and

the central driver of Type 2 inflammation, and currently in Phase 2 clinical testing. In the Phase 1 clinical study in atopic dermatitis patients, KT-621 demonstrated deep STAT6 degradation in blood and skin,

robust reductions in disease-relevant Type 2 inflammatory biomarkers, meaningful improvements on clinical endpoints and patient-reported outcomes in AD and comorbid asthma and allergic rhinitis, and was well tolerated with a favorable safety

profile. KT-621, the first STAT6-directed drug to enter clinical evaluation, has the potential to transform treatment paradigms for more than 140 million patients around the world, including children and

adults, suffering from Type 2 diseases such as atopic dermatitis (AD), asthma, bullous pemphigoid (BP), chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic esophagitis (EoE), chronic

spontaneous urticaria (CSU), and prurigo nodularis (PN), among others.