Dantari's Novel High-Capacity Drug Conjugate DAN-222 Shows Promising Antitumor Activity in Patients with Metastatic HER2-Negative Breast Cancer

Data from Phase 1 clinical trial in heavily pretreated patients with metastatic breast cancer showed DAN-222 was safe and well tolerated and demonstrated clinical activity as monotherapy and in combination with a PARP inhibitor

DAN-222 is the first topoisomerase 1 inhibitor able to be combined with a PARP inhibitor at clinically relevant doses for extended time

Phase 1 data in metastatic HER2-negative breast cancer to be presented today at San Antonio Breast Cancer Symposium 

THOUSAND OAKS, Calif., Dec. 7, 2023 /PRNewswire/ -- Dantari, Inc. ("Dantari") today announced that data from the completed dose-escalation Phase 1 clinical trial showed that DAN-222 was safe, well tolerated, and demonstrated promising antitumor activity in patients with metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Results showed stable disease (SD) in 38% of participants receiving DAN-222 as monotherapy and SD in 67% of participants receiving DAN-222 in combination with a PARP inhibitor (niraparib) across all dose levels. These data will be presented today in a poster session at the 2023 San Antonio Breast Cancer Symposium (SABCS).

DAN-222 is a novel high-capacity drug conjugate with a topoisomerase 1 inhibitor (TOPO1) payload. The main risk of TOPO1 products in general is bone marrow toxicity. Because of its low bone marrow exposure in preclinical models and complementary mechanism of action with PARP inhibitors, DAN-222 has the potential for broad application and provide new utility as a combination therapy with PARP inhibitors and other agents. Importantly, the complementary enhanced efficacy is independent of BRCA status and broadly homologous repair deficiency status.

"These data on DAN-222 are encouraging as they show this novel platform with high chemotherapy capability was safe and well tolerated in heavily pretreated patients with advanced breast cancer," said Sara A. Hurvitz, M.D., FACP, senior vice president and director, Clinical Research Division, Fred Hutchinson Cancer Center, head, Division of Hematology and Oncology, University of Washington Department of Medicine, and clinical consultant and principal investigator of the study. "We believe these data support continued clinical development of DAN-222 and in combinations such as with PARP inhibitors."

"What is especially exciting about these results is that they show DAN-222 can be safely given as a monotherapy or in combination with a PARP inhibitor, a highly desired combination due to the known complementary mechanisms of action," said Richard A. Markus, M.D., Ph.D., president and CEO of Dantari. "We look forward to advancing the Phase 2 clinical trial of DAN-222 which will also help fulfill our vision to deliver groundbreaking next-generation targeted high-capacity drug conjugate therapeutics to a broad range of patients who are in need of new treatment options."

DAN-222 Phase 1 dose-escalation data at 2023 San Antonio Breast Cancer Symposium

This was an open-label, multicenter, Phase 1 dose-escalation clinical trial designed to assess the safety, tolerability, pharmacokinetics (PK), and initial clinical activity of intravenously (IV) administered DAN-222 as monotherapy or in combination with niraparib in patients with metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The initial clinical activity of DAN-222 is based on RECIST v1.1 criteria to determine the recommended Phase 2 dose.

Thirty adult women with metastatic HER2-negative breast cancer that progressed on standard therapies were enrolled, without restriction on BRCA or homologous repair deficiency status. The median age was 61.5 years old (range, 36-75) and the median number of prior treatment lines was six. All patients were PARP inhibitor naïve and BRCA wild type.

Results showed:

• DAN-222 was safe and well tolerated and did not require pre-medication with steroids, H1-blockers, or H2-blockers.
• Adverse events (AEs) were generally equivalent in frequency and severity for DAN-222 monotherapy and DAN-222 plus niraparib combination therapy. Grade 3-4 AEs observed were neutropenia (3/30; 10%), anemia (3/30; 10%), thrombocytopenia (1/30; 3%), and cystitis (1/30; 3%). All Grade 3-4 anemia were in the combination group and all Grade 3-4 neutropenia were at the highest monotherapy dose. No dose-limiting toxicities were observed in either the monotherapy or combination therapy cohorts. There were no Grade 5 events.
• Pharmacokinetics showed the designed control of DAN-222 payload was linear and dose-proportional. The mean half-life ranged from 25.2 to 33.5 hours across all cohorts.
• DAN-222 monotherapy and in combination with a PARP inhibitor showed encouraging clinical activity in highly pretreated patients that is consistent with Phase 1 results from other approved breast cancer products. Clinical activity during dose escalation was demonstrated with stable disease (SD) in 38% of patients receiving DAN-222 monotherapy and SD in 67% of patients receiving DAN-222 plus niraparib combination therapy across all dose levels.

About Dantari 
Dantari, Inc. is a clinical-stage biotechnology company developing best-in-class targeted therapeutics for the treatment of cancers and other diseases. Dantari is advancing a pipeline of T-HDC (Targeted High-capacity Drug Conjugate) chemotherapeutic agents and next-generation antibody-drug conjugate (ADC) therapeutics T-HDC technology originating from Caltech. Dantari's HDC and T-HDC platform technology uses chemically defined polymers with a high drug-antibody ratio (DAR), and a high degree of control and flexibility to optimize performance of targeted drug conjugates that can leverage validated targets across a broad range of therapeutic payload options. Visit us at www.dantari.com to learn more.

SOURCE Dantari