Powering Possibility Through Oral Medicines with Biologics-like Profiles
Last week, on June 2nd, we announced the highly anticipated first-in-human data of our first-in-class, oral STAT6 degrader, KT-621.
In a past blog I shared why and how we began our pioneering STAT6 work, but today I want to reflect on the significance of the data we have generated and what they mean for Kymera, our KOL’s, clinicians and more importantly, for patients with Th2 diseases.
First, I want to take the opportunity to reinforce a few principles about Kymera that are fundamental to our strategy and led to this monumental milestone:
– We are purposeful in how we approach science. Kymera has always focused on marrying the right target with the power of technology, in our case targeted protein degradation. But we don’t degrade proteins just because we can. In biotech, resources, both people and capital are precious, and most science platforms fail because they have pursued the wrong target/biology. At Kymera, we pursue a strict target selection strategy focused on undrugged or poorly drugged disease-causing proteins with proven biology. They also must address an unmet need and have a clear path to commercialization. With that in mind, it’s not hard to see why, within immunology, STAT6 is emblematic of our target selection strategy.
– We tackle the most challenging problems with a sense of urgency. A sense of urgency doesn’t mean rushing blindly. It means relentlessly pursuing answers to critical problems, being nimble in our research and innovation, and empowering our cross-disciplinary teams to respond with precision and purpose. We treat every challenge, not as an obstacle, but as a call to act boldly to advance the industry and patient care.
– We are committed to long term value creation. There are no shortcuts to making impactful medicines. While bootstrapping and pushing programs to an inflection point for an eventual return on investment can work, it is not a strategy for long-term success. From an early stage, we decided that we were going to build capabilities to be one of the best and most innovative biopharma companies in the world. It takes time to build the team and capabilities to be able to credibly state that goal, let alone to achieve it. It took us years to establish screening, structural biology, chemistry, biology, translational, and development competencies to target STAT6 and develop a molecule like KT-621. We were able to accomplish this because our goal has never been to simply advance the company to an inflection point. Rather, our goal has always been to build a fully integrated biopharma company.
Going back to STAT6, we initiated our Phase 1 healthy volunteer trial in October of 2024 with confidence in STAT6’s promise that was well-supported by human genetics, pathway biology, our own preclinical dataset and market data.
– IL-4 and IL-13 targeting is the most powerful mechanism to treat Th2 inflammatory diseases that affect more than 100 million people around the world.
– Dupilumab, an injectable monoclonal antibody targeting IL-4Rα, is the only approved drug that blocks both IL-4 and IL-13. Dupilumab has been approved in multiple indications including atopic dermatitis (AD), asthma, chronic obstructive pulmonary disease (COPD), prurigo nodularis (PN), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic esophagitis (EoE), and chronic spontaneous urticaria (CSU), and is projected to be a $25 billion/year drug by the end of this decade.
– However, dupilumab has low penetration in most of these approved indications for several reasons such as access, price, inconvenience, needle phobia, among others.
– STAT6 is the selective transcription factor that binds directly to IL-4Rα and is responsible for translating IL-4 and IL-13 signaling, suggesting targeting STAT6 should phenocopy IL-4Rα targeting.
– Leveraging the natural protein recycling mechanism to degrade STAT6 is the only small molecule approach to block the pathway as effectively as a saturating dose of dupilumab with a once-a-day oral pill.
– We designed and characterized the first, once-a-day oral STAT6 degrader KT-621, which was shown in in vitro and in vivo studies to be equal or more potent than dupilumab at blocking the IL-4 and IL-13 pathway with a pristine safety profile.
In preclinical efficacy studies, 90%+ degradation (Wang et al. American Thoracic Society, 2025) was able to achieve impact on both Th2 biomarkers and efficacy endpoints in line or superior to dupilumab. As a result, our goal for the first-in-human study was to demonstrate that 90%+ degradation could be achieved in blood and skin in humans and that drugging STAT6 would be well tolerated.
We have spent the past few months (actually, the past few years!) building to this important event to demonstrate that STAT6 could be targeted safely and that an oral STAT6 degrader, like KT-621, has the potential to disrupt the whole Th2 space by delivering an oral drug with a biologics-like profile.
In fact, the Phase 1 healthy volunteer data surpassed our target product profile with compelling translation from preclinical studies to humans. We observed >90% STAT6 degradation in blood in all doses above 1.5 mg and complete STAT6 degradation in both blood and skin in all doses ≥50 mg. Additionally, the impact on Th2 biomarkers was comparable and, in some cases, superior to dupilumab in healthy volunteers. And, importantly, we saw placebo-like safety with no serious adverse events (SAEs) and no treatment related AEs reported in more than one subject.
Source: KT-621 Phase 1 Healthy Volunteer Trial Results Presentation, June 2025
This therapeutic level target/pathway engagement continues to support KT-621’s dupilumab-like profile. These data represent a powerful validation of Kymera’s approach to this high value drug target. Importantly, the data further derisks our path forward and highlights the possibility of KT-621’s “dupilumab in a pill” profile which offers great promise to be a first-line oral option for many dermatologic and respiratory diseases like AD, asthma, COPD, among others.
I’ve shared this before, but it bears repeating: I keep an empty pill bottle on my desk as a constant reminder of the unmet needs in our industry—and of the urgency we face. In the mission to serve patients, every week, every day, and every hour matters. Today’s immunology treatment landscape still leaves millions without adequate options, forcing difficult trade-offs between efficacy, safety, cost, and convenience.
With KT-621, the first STAT6-targeted therapy to enter clinical development, we have a chance to reshape that landscape. Our goal is to deliver a transformative oral medicine that matches the power and precision of complex injectable biologics, yet is far more accessible and convenient. The data shared last week marks a significant step toward that vision.
There’s still a lot of work ahead. Drug development is never straightforward—but with KT-621, we are forging an entirely new path. It’s one of the most compelling immunology programs in the field today, and I’m truly excited, honored, and humbled to be part of this journey.