Kymera Therapeutics (NASDAQ:KYMR) used its fourth-quarter 2025 update call to highlight what management described as a “breakout year” driven by clinical progress for its oral STAT6 degrader KT-621, the launch of a new IRF5 degrader program with KT-579 entering the clinic, and strengthened finances following significant capital raising.
KT-621: Phase IIb programs underway in atopic dermatitis and asthma
Founder, President and CEO Nello Mainolfi said Kymera’s 2025 progress was led by KT-621, which the company positions as a first- and best-in-class oral STAT6 degrader intended to replicate the efficacy and safety of IL-4/IL-13 pathway biologics while offering daily oral dosing. The company previously reported results from both a phase I healthy volunteer study and a phase Ib study in atopic dermatitis (AD), which management characterized as showing robust STAT6 degradation, good tolerability, and encouraging efficacy signals.
Gollob said clinical endpoints improved across multiple AD measures including EASI, Pruritus NRS, IGA, SCORAD, and patient-reported outcomes. He added that results were “in line with or numerically exceeded” published dupilumab data at four weeks, while emphasizing KT-621 was well tolerated.
Kymera is now running two parallel phase IIb dose-ranging, placebo-controlled trials:
- BROADEN2 (atopic dermatitis): Approximately 200 adult and adolescent patients with moderate-to-severe AD; primary endpoint is percent change from baseline in EASI at 16 weeks. Enrollment is expected to complete by the end of 2026, with top-line results targeted for mid-2027.
- BREADTH (asthma): Approximately 264 adults with moderate-to-severe eosinophilic asthma; primary endpoint is change from baseline in pre-bronchodilator FEV1 at 12 weeks. Kymera dosed the first patient last month and expects data in late 2027.
Gollob said the company expects to generate phase IIb data in close to 500 patients from both trials and will also build longer-term safety experience in AD via a 52-week open-label extension. He said the trials are designed to support future phase III development not only in AD and asthma but also in other type 2 dermatologic, respiratory, and gastrointestinal diseases.
Company frames large type 2 market opportunity for an oral STAT6 degrader
Mainolfi spent a portion of his prepared remarks outlining what he said is a large, underpenetrated market for advanced systemic therapies in type 2 inflammatory diseases. He estimated about 140 million diagnosed type 2 patients across the U.S., five major European markets, and Japan, with roughly 50 million in the moderate-to-severe category. Despite that, he said only about 2 million patients are treated with advanced systemic therapies, mostly injectable biologics and “overwhelmingly” dupilumab.
He attributed the treatment gap to limitations in existing options, including the limitations of local therapies, safety and monitoring requirements for some oral systemic therapies (he cited JAK boxed warnings and blood monitoring), and the burden of injectable biologics, including loading regimens, cold chain storage, and patient drop-off over time. Mainolfi said the current advanced systemic therapy segment represents an approximately $20 billion annual market and argued it could expand materially if an oral option can maintain biologic-like safety and efficacy.
KT-579: IRF5 degrader begins human dosing after IND clearance
Kymera also highlighted progress in its IRF5 program. Mainolfi said the company completed IND-enabling studies and, following FDA IND clearance, recently initiated dosing in a phase I healthy volunteer study of KT-579.
Gollob described IRF5 as a genetically validated transcription factor and “central amplifier” of immune responses. He said KT-579 is designed to selectively degrade IRF5 to modulate multiple interconnected pathways—type I interferons, pro-inflammatory cytokines, and autoantibody-related pathways—through targeting a single regulator, with the goal of avoiding infectious adverse events associated with broad immunosuppression.
In phase I, Kymera is running single-ascending dose and multiple-ascending dose cohorts with once-daily oral dosing. Gollob said the company’s translational objective is approximately 90% or greater IRF5 degradation in blood at safe and well-tolerated dose levels. Because IRF5 pathways are not activated in healthy volunteers, Kymera plans to use whole blood ex vivo stimulation assays to evaluate functional impact after stimulation of TLR7, TLR8, and TLR9. Management said it would look for 50% to 80% reductions in biomarkers across these pathways as supportive evidence of effective IRF5 engagement. The company said it expects to share first-in-human data in the second half of 2026 and anticipates moving into a patient proof-of-concept study in lupus thereafter.
Collaborations and financial update: $1.6B cash and runway into 2029
Chief Financial Officer Bruce Jacobs reported fourth-quarter 2025 collaboration revenue of $2.9 million attributable to the company’s partnership with Gilead. He said Kymera previously received a $40 million upfront payment under the CDK2 molecular glue licensing and option agreement, and that the company is eligible for up to $750 million in total milestones, including a $45 million payment if and when Gilead exercises its option upon declaration of a mutually agreed-upon development candidate.
Jacobs also said partner Sanofi is advancing KT-485, an oral IRAK4 degrader, and plans to initiate phase I testing this year. Kymera expects additional updates in coming months, including receipt of a milestone upon dosing of the first healthy volunteer. Jacobs reminded listeners the Sanofi agreement includes the potential for nearly $1 billion in total milestones, and said potential near-term milestones from both collaborations are not included in Kymera’s cash guidance and are not expected to materially impact its runway.
For the quarter, Kymera reported R&D expense of $83.8 million, including $7.6 million in non-cash stock-based compensation, and G&A expense of $16.9 million, including $6.9 million in non-cash stock-based compensation. On an adjusted cash basis excluding stock-based compensation, Jacobs said R&D spending was $76.2 million, up 16% from the comparable third-quarter 2025 amount, while adjusted cash G&A spending was $10.0 million, up 1% from the comparable period.
Management said the company ended December with $1.6 billion in cash after raising “almost $1 billion” during 2025, extending its runway into 2029. Jacobs said this capital is expected to support completion of the KT-621 phase IIb trials and fund a large part of the first phase III trial for KT-621, while also advancing KT-579 through initial proof-of-concept testing and continuing to expand the research pipeline.
Leadership addition and upcoming milestones
Mainolfi also announced Neil Graham joined as Chief Development Officer, noting Graham’s experience across early and late-stage drug development and his work on the development of dupilumab at Regeneron. Looking ahead, management reiterated expectations for KT-621 enrollment completion in AD by the end of 2026, KT-579 phase I data in the second half of 2026, and the goal of announcing at least one new development candidate program annually, with the next program targeted for the second half of the year.
About Kymera Therapeutics (NASDAQ:KYMR)
Kymera Therapeutics, Inc is a clinical‐stage biopharmaceutical company headquartered in Watertown, Massachusetts, focused on the discovery, development and commercialization of small‐molecule therapies that harness the body’s natural protein homeostasis pathways. Since its founding in 2016, Kymera has pursued a targeted protein degradation platform designed to identify and selectively eliminate disease‐causing proteins. The company’s proprietary Pegasus™ platform integrates insights from ubiquitin biology and medicinal chemistry to advance novel degrader candidates across a range of therapeutic areas.
The company’s pipeline emphasizes immunology and oncology.
