Acrivon Therapeutics (ACRV) KOL event summary

Strategic fit and acquisition

• Acquisition added rights to ACR-525 and the preclinical PKCθ program, including IP, data, filings, and drug supply, for undisclosed cash consideration with no future royalties or milestones.

• Immunology and inflammation became a strategic pillar alongside oncology; AP3 is intended to guide disease and patient selection, dose optimization, and biomarker-based endpoints.

• PKCθ, a kinase central to T-cell activation, adds pipeline depth; AP3 may support its optimization and combination development.

EoE market and treatment

• U.S. EoE incidence was estimated at 120,000 patients annually and prevalence at over 500,000; prevalence rose from 28 per 100,000 in 2009 to 163 in 2022.

• Care includes diet elimination, PPIs, swallowed topical steroids, dilation, and dupilumab; disease often recurs after treatment cessation and requires long-term therapy.

• At least 50% may not respond to initial therapies; adherence, restrictive diets, side effects, loss of response, and frequent dupilumab injections are challenges.

• EoE involves type 2 inflammation and JAK-STAT signaling, including IL-4, IL-5, IL-13 and TSLP; TGF-beta contributes to fibrosis.

ACR-525 rationale and evidence

• AP3 uses phosphoproteomic data and drug-centric pathway analysis for responder prediction, indication selection, and combination hypotheses, without relying on genetic alterations or clinical information.

• Cellular assays showed ~120x JAK1/JAK2 selectivity versus ~20x cited for filgotinib; profiling against six approved JAK inhibitors and dupilumab found high selectivity and minimal off-target effects.

• ACR-525 showed broader anti-inflammatory effects than IL-4/IL-13 blockade alone and suppressed non-SMAD TGF-beta signaling; in an EoE epithelial model it reversed IL-13- and oncostatin M-induced changes.

• Two Phase 1 studies showed dose-dependent CXCL10 reduction, predictable dose-proportional PK, a 12-hour half-life, no serious adverse events, and no significant reticulocyte effect.

• Phase 2-ready ACR-525 is an oral, once-daily option; capsule, tablet, and esophagus-flowing formulations were discussed, including one for patients with difficulty swallowing.