Kymera Therapeutics (KYMR) Q1 FY26 earnings call: guidance and Q&A

What is the basis for the 50%-80% modulation threshold for biomarker pathways in ex vivo stimulation assays for KT-579, and what does this translate to clinically?

The 50-80% modulation expectation is based on preclinical in vitro data, where at least 90% IRF5 degradation should lead to this range of blockade in TLR7/8/9 pathways. This range accounts for the multi-pathway nature of IRF5 biology. Clinical translation will be assessed in subsequent patient studies.

“So essentially, the way we came up with 50% to 80% is that our expectation based on our preclinical in vitro data is that if we're able to degrade IRF5 by at least 90%, we should be able to see that range of blockade of these particular pathways.”

asked by Jasmine Fels · answered by Jared Gollob

What level of IRF5 degradation is needed for clinical benefit in lupus patients, and how translatable is degradation from healthy volunteers to patients?

Preclinical data suggests 80% degradation is sufficient for efficacy, but the goal is to demonstrate >90% degradation for flexibility in dose-ranging studies. Historically, degradation levels have been consistent between healthy volunteers and patients for catalytic molecules like degraders, as performance depends on drug exposure, not target expression.

“So we expect that whatever we see in healthy volunteers will translate in patients. We've shown that with 621. We've shown it with IRAK4. We've shown it also in other programs in other disease areas.”

asked by Lut Ming Cheng · answered by Nello Mainolfi

What technology advances enabled the CDK2 molecular glue, and should we expect more molecular glues from the pipeline?

The CDK2 molecular glue addresses the challenge of high structural homology between CDK2 and CDK1, which causes dose-limiting toxicity with traditional inhibitors. Kymera achieved absolute CDK1 selectivity through a protein-protein interaction enabled molecular glue outside the ATP binding pocket. The company expects to see more programs using this concept across therapeutic areas.

“We did it through a protein-protein interaction enabled molecular glue that is outside of the ATP binding pocket. So this is the kind of the premise to my answer, which is, yes, I mean, you should expect Kymera to have other programs from our pipeline that will use this concept because this is just a continuation of protein degradation.”

asked by Brad Canino · answered by Nello Mainolfi

Why did the 100mg dose show higher BSA reduction than 200mg for KT-621 at AAD, and what does the difference between EASI and BSA suggest?

The observed differences between 100mg and 200mg doses for BSA reduction are not statistically significant due to overlapping error bars and small sample size; both doses achieved similar degradation. EASI captures both extent and severity, while BSA measures extent, but both showed comparable robust effects with KT-621.

“If you look at the error bars on those graphs, they're actually overlapping. And so the differences between 100 milligrams and 200 milligrams are really not significant differences, and it's probably a function of the small ends.”

asked by Nishant Shailesh Gandhi · answered by Jared Gollob

How will KT-621 maintain leadership against emerging STAT6 inhibitors, and what is the importance of oral vs less frequent injectable in AD and asthma?

Degraders are differentiated because they are catalytic, requiring low exposures for complete STAT6 removal, allowing for once-daily dosing with a wide therapeutic index. Inhibitors require high concentrations for stoichiometric blockade, posing safety and PK challenges. The oral aspect of KT-621 is crucial for mobilizing millions of untreated/undertreated patients who are not ready for injectable biologics, rather than competing solely on dosing frequency.

“Our answer is, yes, you need a degrader because inhibitor can't quite reach the level of pathway blockade that a catalytic degrader can.”

asked by Mayank Mamtani · answered by Nello Mainolfi

What are the implications of including adolescents and changing the chronic disease duration requirement for BROADEN2?

Including adolescents is part of a strategy to study KT-621 in younger populations, as AD often begins in childhood. The chronic disease duration requirement (3 years for adults, 1 year for adolescents) is to ensure patients truly have an AD diagnosis, aligning with Hanifin and Rajka criteria.

“So for adults, obviously, because they're older, the cutoff there is at least 3 years. With adolescents because they're younger, had the disease for a shorter period of time, there's a 1-year cutoff. And again, the reason for both of those is to give you increased certainty that these patients truly have a diagnosis of AD.”

asked by Biren Amin · answered by Jared Gollob

Can you quantify the population of patients on the sidelines due to needle aversion or other barriers to advanced therapies for AD?

The barrier is less about needle phobia and more about the perceived burden of advanced systemic injectable therapy for AD. There are approximately 40 million patients with moderate to severe AD, but less than 2 million are currently treated with advanced systemic therapies. This represents tens of millions of untreated/undertreated patients, a far greater opportunity than in mature markets like psoriasis.

“If you look about treated patients with this advanced systemic therapy, we're talking about less than 2 million. So that's the opportunity, and that's far greater than, for example, the opportunity in psoriasis these days.”

asked by Jeet Mukherjee · answered by Nello Mainolfi