Exelixis Announces Promising Initial Dose-Escalation Results from the First-in-Human Phase 1 JEWEL-101 Trial Evaluating XB002 in Patients with Advanced Solid Tumors at ENA 2022

– XB002, a next-generation tissue factor-targeting antibody-drug conjugate, was well-tolerated at multiple dose levels –

– Pharmacokinetic analysis confirmed XB002 was stable with low levels of free payload –

ALAMEDA, Calif.--(BUSINESS WIRE)-- Exelixis, Inc. (Nasdaq: EXEL) today announced promising initial results from the ongoing dose-escalation stage of JEWEL-101, a phase 1 study evaluating XB002, Exelixis’ next-generation tissue factor-targeting antibody-drug conjugate. The data are being presented on Friday, October 28 during the Antibody-drug Conjugates Poster Session (abstract 256) at 10:00 a.m. CEST at the 34th Symposium on Molecular Targets and Cancer Therapeutics hosted by the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR).

“Following promising preclinical data, it is encouraging to see that XB002 was well-tolerated across multiple dose levels with a pharmacokinetic analysis supporting the ability of XB002 to remain stable after infusion and reach its target before releasing its cytotoxic payload,” said Susanna Ulahannan, M.D., M.Med., Assistant Professor of Medicine in the Section of Hematology/Oncology, University of Oklahoma College of Medicine and Associate Director of Oklahoma TSET Phase 1 Program, OU Health Stephenson Cancer Center at the OU Health Sciences Center. “As the dose-escalation phase progresses, and we initiate enrollment into tumor specific cohorts, I look forward to learning more about how XB002 may benefit people with advanced solid tumors, in particular in tumor types with high unmet need.”

JEWEL-101 is enrolling patients with advanced solid tumors for which therapies are unavailable, ineffective or intolerable. A total of 19 patients were enrolled across five initial escalating doses: 0.16 mg/kg (n=3), 0.5 mg/kg (n=3), 1.0 mg/kg (n=6), 1.5 mg/kg (n=3) and 2.0 mg/kg (n=4). The most common types of cancer for patients enrolled were pancreatic cancer, colorectal cancer, cervical cancer and prostate cancer. Median age was 63 years, and 63% of patients had an Eastern Cooperative Oncology Group score of 1. Seventy-nine percent of patients had at least three prior lines of therapy.

“We are pleased to present the first clinical profile of XB002 at ENA 2022, representing an important milestone for our first biologic in clinical development,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “We are eager to proceed to the expansion cohort stage of JEWEL-101 once the recommended dose is determined, as we aim to further understand the activity of this molecule as a potential new treatment for people who have difficult-to-treat tumors with limited treatment options.”

The recommended dose and maximum tolerated dose for XB002 have not yet been determined. As of the data cutoff, there were no dose-limiting toxicities. The primary reasons for treatment discontinuation included radiographic progression (47%), treatment-emergent adverse events (AEs; 11%), lack of clinical benefit (11%) and patient request other than AEs (16%).

A pharmacokinetic analysis demonstrated that XB002 exposure increased more than or proportionately to a dose increase from 0.16 mg/kg to 2.0 mg/kg. XB002 total antibody and intact antibody-drug conjugate pharmacokinetics were similar, suggesting XB002 is stable after infusion. Levels of free payload remained low (