Dantari

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 to learn more. SOURCE Dantari

Dantari’s drug conjugate asset has produced positive data as both a monotherapy and in combination with a PARP inhibitor in an early-stage breast cancer trial, paving the way for a Phase II test. The biotech’s Phase I dose escalation trial studied DAN-222 as a single agent and in combination with GSK’s Zejula in 30 metastatic HER2-negative breast cancer patients with a median of six prior lines of therapy. Results from the trial come one year after Dantari raised $47 million in a Series A round. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Dive Brief:Eli Lilly has reached a deal to acquire Emergence Therapeutics, a German biotechnology startup focused on antibody-drug conjugates, or ADCs, the company confirmed to BioPharma Dive on Thursday.In a short statement, European cancer drug developer and founding Emergence investor Heidelberg Pharma said Lilly is acquiring all of the startups shares. Deal terms werent disclosed, but Heidelberg will receive $7 million for its stake in the company. Lilly, in an email, declined to provide more details. Emergence's lead candidate, called ETx-22, focuses on a target called Nectin-4, thats overexpressed in most bladder cancers. The protein is the focus of other experimental drugs in clinical development, as well as Seagens marketed medicine Padcev.Dive Insight:Though Eli Lilly is best known for its diabetes treatments, its spent significant resources of late bulking up its cancer drug business, starting with its 2019 acquisition of Loxo Oncology.That pursuit has included a focus on targeted cancer medicines, which are meant to hone in on tumors more specifically while sparing healthy tissue. And as of late, its begun to show renewed interest in ADCs, which link a targeting antibody to a tumor-killing toxin. Last year, it rekindled a relationship with ImmunoGen. Now its buying Emergence.In an email, Lilly declined to specify what other ADCs the company is working on. A spokesperson said the companys research involves internal expertise and external relationships.Lilly isnt alone, however. Drugmakers have invested heavily in ADC research in recent years, leading to multiple large acquisitions and the approvals of drugs like Daiichi Sankyo and AstraZenecas Enhertu.A growing group of startups are focusing on ADCs too, including recently launched biotechs Tagworks Pharmaceuticals and Dantari.Emergence is among them. The startup raised a 87 million Series A round in 2021 from a syndicate of U.S. and European investors, aiming to develop ADCs for solid tumors. Its lead program, currently in preclinical studies, is being developed for bladder and triple negative breast cancer. Emergence has claimed ETx-22 may be more selective than Seagens drug, which is associated with certain skin-related side effects. It plans to study the drug in other malignancies as well.The deal is the third by Lilly in June. The company on Thursday announced plans to acquire cell therapy developer Sigilon Therapeutics for up to $310 million, and previously announced a $2.4 billion deal to buy inflammatory disease drugmaker Dice Therapeutics.In addition to Heidelberg, Emergence is backed by Pontifax Venture Capital, RA Capital Management and OrbiMed. In 2022, the company struck an ADC-focused deal worth up to $360 million with a Dutch biotech called Synaffix. '