Kymera Therapeutics (NASDAQ:KYMR) used a fireside chat at the Guggenheim Conference to outline its focus on targeted protein degradation in immunology, with CEO Nello Mainolfi emphasizing the company’s goal of delivering “biologics-like activity” in a once-daily oral drug.
Positioning Kymera around oral “biologics-like” immunology drugs
Mainolfi described Kymera as founded on the promise of targeted protein degradation, which he said can enable the company to pursue targets that have not been successfully drugged before. He said Kymera has chosen to focus on immunology and believes it can show that “if you go after the right target in the right pathway,” an oral medicine can deliver activity comparable to injectable biologics.
Market opportunity and the company’s view of valuation questions
He cited a broad patient population, saying there are more than 100 million Type 2 disease patients, and estimated 40 million to 50 million moderate-to-severe patients as the initial development population. Mainolfi characterized several of the markets as “very immature,” noting that many have one or two drugs and often lack an effective oral option. He said penetration of advanced systemic therapy is roughly 1 million to 2 million patients relative to the broader moderate-to-severe population he described.
Mainolfi said current annual sales of drugs in these spaces are around $20 billion to $25 billion and argued the market could expand “dramatically,” potentially by 5x to 10x, across areas such as AD, asthma, COPD, and eosinophilic esophagitis (EoE). He said oral drugs with biologics-like efficacy could drive significant market expansion and added that STAT6 sits in what he called the “most validated pathway” in Type 2 diseases for both efficacy and safety.
Why Kymera believes an oral option could expand uptake
Discussing what patients and prescribers want from new therapies, Mainolfi said feedback from investigators and key opinion leaders consistently points to demand for oral drugs. He described a psychological barrier associated with injections and suggested convenience can influence adherence over time.
He also said that a meaningful portion of patients discontinue biologics after a couple of years, attributing that to the ongoing burden of injections and planning. Mainolfi highlighted pediatric patients as an underserved group and said earlier intervention could potentially alter disease progression, referencing the “atopic march.” He argued that only an oral drug could be used early enough for very young children.
KT-621: safety disclosure, biomarkers, and early efficacy signals
Mainolfi addressed questions about the company’s characterization of KT-621’s safety profile as “clean” without presenting granular adverse event tables in the update. He said Kymera’s practice has been to share treatment-related adverse events tables, but in the referenced study there were no treatment-related adverse events to tabulate. He said the company is preparing a publication and may provide additional detail, including non-treatment-related adverse events, which he described as benign.
On chronic toxicology studies, Mainolfi said the company expects to provide an update “soon,” adding that Kymera has recently said it is in the completion phase of that process.
Turning to efficacy, Mainolfi emphasized the breadth of the Phase Ib dataset and Kymera’s focus on linking target degradation to biomarker changes and then to clinical endpoints. He said deep degradation of the target was associated with changes across multiple biomarkers measured in AD patients, including:
- TARC
- Eotaxin
- IgE
- IL-31 (blood)
- FeNO (to assess Type 2 inflammation in the lungs)
He said those biomarker shifts corresponded with changes in clinical and patient-reported outcomes, including itch, EASI, SCORAD, sleeplessness, and other measures. He also referenced asthma-related measures collected in comorbid patients, including FeNO and the ACQ-5 questionnaire.
Mainolfi said the results were consistent with Kymera’s initial guidance, which he described as being in the “dupilumab range” at day 28, while adding that the numbers were numerically better than dupilumab data in the early study but should not be interpreted as proving superiority. He also said the internal consistency across endpoints made it, in his view, “completely shocking” if the drug failed to show a strong effect in a Phase IIb study.
On duration of effect, Mainolfi said he does not believe KT-621’s AD effect had plateaued at four weeks, pointing to the shape of the improvement curves from day 7 through day 28 and noting that drugs targeting IL-4/IL-13 pathways generally do not plateau by day 28. Asked how much better it could get, he said he expects it to be better than dupilumab-like efficacy at day 28.
Interpreting upcoming Phase II data and asthma read-through
Mainolfi said cross-trial comparisons in AD are challenging due to differences in baseline severity and other factors. He noted that baseline EASI in historical dupilumab studies was around 30, while more recent trials often fall in the mid-20s, which he said can be associated with higher placebo responses. He suggested treatment effect remains important to evaluate, and said categorical endpoints such as vIGA 0/1 and EASI-75 may be more useful for looking across trials because placebo rates tend to be lower.
He emphasized that the primary goal of Kymera’s Phase II study is dose selection for Phase III, assuming efficacy and safety are established.
On asthma, Mainolfi described FeNO as an established biomarker of Type 2 inflammation used in some settings to guide therapy. He said reductions in FeNO indicate reduced Type 2 lung inflammation, and framed the Phase Ib FeNO changes as evidence the drug is reaching the lungs and degrading STAT6 locally. He said the combination of FeNO and ACQ-5 results increased his confidence that KT-621 should be active in asthma, and added that preclinical studies show strong performance in asthma models and that the drug distributes well in lungs.
In addition to STAT6, Mainolfi discussed Kymera’s IRF5 program KT-579, saying IRF5 has genetic validation through functional variants in disease patients. He said IRF5 expression is limited to certain cell types—such as NK cells, macrophages, monocytes, and B cells—and that healthy volunteer studies can help establish whether KT-579 achieves the level of degradation Kymera is targeting and whether that translates into expected biological effects in ex vivo stimulation assays, including impacts on cytokines, Type 1 interferon, and IgG.
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.
