AZD4241 / AstraZeneca, Pathos AI - LARVOL DELTA

Pathos AI…announced a collaboration and co-exclusive licensing agreement with AstraZeneca. (Businesswire) - "Under this agreement, the companies will advance AZD4241, a preclinical investigational therapy for patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer, with Pathos assuming responsibility for the early clinical development of the asset."

Licensing / partnership • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

AZD4241, an orally bioavailable ERα PROTAC, degrades wild-type and mutant ERα and delivers anti-tumour activity in preclinical breast cancer models (AACR 2026) - "Current ER‑pathway inhibitors include aromatase inhibitors (letrozole, anastrozole, exemestane), selective estrogen receptor modulators (SERMs; tamoxifen), and selective estrogen receptor degraders (SERDs; fulvestrant, elacestrant, imlunestrant)...In vivo, AZD4241 induced dose‑dependent anti‑tumour activity and, in some cases, tumour regressions across ESR1wt and ESR1m patient‑derived xenograft (PDX) models, including a palbociclib‑resistant model...Collectively, these data confirm that AZD4241 is a potent, orally bioavailable degrader of wt and mutant ERα, driving anti-tumour efficacy in ESR1wt, ESR1m, and CDK4/6 inhibitor‑resistant PDX models. These findings support the use of AZD4241 as a novel ER-PROTAC with potential to overcome key resistance mechanisms to current standards of care and deliver clinical benefit for patients with ER‑positive breast cancer."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CRBN • TFF1

Preclinical mechanistic PK/PD/Efficacy modeling for AZD4241, a novel oral estrogen receptor (ER) degrader (PROTAC), to support dose selection during early clinical development (AACR 2026) - "This work provides quantitative, mechanistic insight into how exposure drives biomarker modulation and antitumor responses, delineating the level of ERα degradation required for robust efficacy in endocrine‑sensitive PDX models. The framework supports interpretation of compound‑induced PD effects in patients under defined dosing regimens and supplies translational evidence to enable dose selection in early clinical development."

PK/PD data • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER