On December 8, 2022 Dantari, Inc. ("Dantari"), a clinical-stage biotechnology company developing best-in-class targeted therapeutics for the treatment of cancers and other diseases, reported that its emergence from stealth mode with $47 million Series A financing (Press release, Dantari, DEC 8, 2022, View Source [SID1234624938]). The Series A financing was led by Westlake Village BioPartners ("Westlake") and included participation from Corner Ventures, Alexandria Venture Investments, and Caltech. The Company also announced the appointment of Richard A. Markus, M.D., Ph.D., as president and chief executive officer (CEO), and its board of directors, chaired by Sean Harper, M.D., a co-founding managing director at Westlake.
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Proceeds from the financing support the advancement of Dantari’s differentiated antibody-drug conjugate (ADC) and chemotherapeutic platforms. Dantari’s platform of T-HDC (Targeted High-capacity Drug Conjugate) technology enables a significantly higher drug-antibody ratio (DAR) and tunable-release of chemotherapy compared to today’s ADCs. The Company’s next-generation targeted therapeutics can deliver larger payloads with a DAR of 60 for greater efficacy, and their biodistribution reduces bone marrow exposure, providing broad therapeutic potential.
The Company’s lead clinical investigational product is DAN-222, a novel HDC chemotherapeutic agent with a topoisomerase 1 inhibitor (topo1) payload. The use of topo1 products is often limited due to bone marrow toxicity. Because of its low bone marrow exposure in preclinical models, DAN-222 has the potential to broaden indications and provide new utility as a combination therapy with PARP inhibitors and other agents. DAN-222 is being evaluated in a Phase 1/2 clinical trial for the treatment of metastatic human epidermal growth factor receptor (HER) 2-negative breast cancer. Early results from the dose-escalation portion of the study will be presented today in a poster session at the 2022 San Antonio Breast Cancer Symposium (SABCS). The study is ongoing and full results will be presented in a future scientific forum.
Dantari’s pipeline also includes several next-generation ADC programs leveraging the T-HDC platform. The Company’s next program, DAN-311 for HER2-positive and HER2-low breast cancer, is planned to enter the clinic in the second half of 2023. Dantari’s other T-HDC product candidates combining validated targets and payloads for a variety of solid tumors including prostate cancer are progressing through preclinical development.
"We are excited to announce Dantari’s launch and initial clinical data. Our vision is to deliver groundbreaking next-generation targeted high-capacity therapeutics with enhanced efficacy and safety," said Dr. Markus. "DAN-222, our lead program in HER2-negative breast cancer, has significant commercial potential while also substantially de-risking our T-HDC platform technology. We look forward to sharing our dose-escalation data today at SABCS which demonstrate excellent translation from preclinical species into patients. We will continue to progress our pipeline as rapidly as possible, including advancing our lead T-HDC candidate DAN-311 in HER2-positive and HER2-low breast cancer into the clinic in 2023. We look forward to bringing much-needed new options to patients who have failed current therapies including traditional ADCs."
Dantari’s HDC and T-HDC platform technology originated at the California Institute of Technology (Caltech) with more than 20 years of research and uses standard organic chemistry manufacturing. Dantari’s T-HDC platform uses chemically defined polymers with a high degree of control and flexibility to optimize performance of targeted drug conjugates and leverages validated targets across a broad range of therapeutic payload options. Payload conjugation enables tunable-controlled release, with no ‘burst release’ and the high drug load enables more payload for greater bystander effect killing of tumor cells including in heterogenous tumors.
Dr. Harper commented, "The Dantari team has made great progress in building a world-class platform for oncology drug innovation. Dantari’s proprietary T-HDC platform provides significantly enhanced capabilities for targeted delivery of therapeutics, which I believe will usher in a step-change in the treatment of solid tumors. With Richard at the helm and this outstanding team, we look forward to the exciting future for this company and the medicines it will advance for patients."
As part of the Series A financing, Mark Davis, Ph.D., Warren and Katherine Schlinger Professor of Chemical Engineering at Caltech, and Pascal Touchon, president and CEO of Atara Biotherapeutics, join Drs. Harper and Markus on the Company’s board of directors.
DAN-222 Phase 1 dose-escalation data at San Antonio Breast Cancer Symposium
Poster Title: A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects with Metastatic Breast Cancer (NCT05261269)
Presenter: Tim Hagerty, Ph.D., vice president of translational sciences, Dantari
Poster ID: OT3-28-01
Session: Ongoing Trials Poster Session 3
Date/Time/Location: Thursday, December 8, 2022; 5:00-6:15 PM CT, Henry B. Gonzalez Convention Center
DAN-222, a novel clinical investigational product, has complementary mechanism of action with PARP inhibitors and can be used in combination since it has demonstrated reduced bone marrow risk in preclinical models. Importantly, the complementary enhanced efficacy is independent of tumor homologous repair deficiency (HRD) status, including BRCA status.
This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics (PK) of intravenously (IV) administered DAN-222 and includes a dose-escalation of DAN-222 in combination with niraparib in patients with HER2-negative metastatic breast cancer.
Results from the first three cohorts showed that the PK profiles of DAN-222 are linear and dose proportional, and that DAN-222 is stable and releasing the payload with consistent kinetics with very low variability between patients (CV% = 7.1 – 20.5). The PK profile of DAN-222 is consistent with and without niraparib.
"These early data on DAN-222 are encouraging as they show this novel platform with high chemotherapy capability appears to be delivering as expected and is well tolerated by patients," said Sara A. Hurvitz, M.D., associate professor at the David Geffen School of Medicine at University of California, Los Angeles (UCLA), medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa Monica-UCLA Outpatient Oncology Practices, director of the Breast Cancer Clinical Trials Program at UCLA, and clinical consultant and principal investigator of the study.