BlossomHill Therapeutics (BLSM) 3rd Annual Guggenheim Healthcare Innovation Conference summary

BH-30643 design and profile

• Macrocyclic design aims for precise ATP-site binding, high potency against primary and resistance mutations, and selectivity over wild-type EGFR.

• BH-30643 showed sub-nanomolar activity against EGFR exon 19 deletion and L858R, with 10-fold greater potency than TAGRISSO; activity was also reported against compound-resistant, atypical, and exon 20 insertion mutations.

C797S clinical results and development

• C797S was estimated at 13% of patients after TAGRISSO resistance, representing 300–3,200 U.S. patients annually and 16,000 worldwide; prior approaches produced responses lasting only 3–4 months.

• In 40 C797S patients, BH-30643 had a 45% response rate, with responses lasting beyond 15 months; dose reductions occurred in 8%–9% and toxicity-related discontinuations in 3%.

• FDA discussions aligned on 50 mg BID as the RP2D; exposure exceeded osimertinib, and the FDA agreed the clinical package could support single-arm registrational development, subject to efficacy benchmarks.

• Phase II is planned to start in H1 2027; the ongoing trial spans 40 sites in 10 countries, with China to be added to support enrollment.

• A C797S update with more than 40 patients, including durability, is expected in H1 2027; Foundation Medicine CDx collaboration is intended to support a validated assay for a future NDA.

EGFR strategy and upcoming data

• First-line development is assessing classical, atypical, and exon 20 mutations; classical-mutation response rates are expected to be similar to TAGRISSO, while durability remains to be established.

• Chemo combination dose escalation is underway; initial safety and activity data and first-line TKI-naive cohort efficacy and durability are expected in H2 2027.

• The team expects to clarify over the coming year which indication offers the most efficient, highest-return path to Phase III; the strategy includes monotherapy and combinations for EGFR-resistant disease.