Dantari emerges with a new way to make cancer drug conjugates

ADCDrug Approval
Dive Brief:
Dantari, a cancer drug startup built on California Institute of Technology research into targeted drug conjugates, launched Thursday with $47 million in venture funding.
The Thousand Oaks, Calif.-based company’s lead drug candidate, named DAN-222, is currently in a Phase 1/2 trial for HER2-negative breast cancer. Another drug candidate for other forms of breast cancer, DAN-311, is expected to enter human testing in 2023.
Dantari’s Series A round was led by Westlake Village BioPartners, along with investors from Corner Ventures, Alexandria Venture Investments and Caltech.
Antibody-drug conjugates, or ADCs, have featured in pharmaceutical company pipelines for years. Recently, though, they’ve drawn increased investment on the back of high-profile clinical trial successes.
ADCs work by linking a toxic compound to an antibody capable of targeting tumor cells. The technology underpinning all three components — the antibody, the payload and the linking molecule — has steadily improved over the years, leading to new drugs. Still, the potent treatments can lead to serious side effects.
In 2019, the Food and Drug Administration approved three ADCs, the most ever in a single year at that point. Merck & Co., AstraZeneca and Gilead Sciences spent billions of dollars in the months following to buy into targeted cancer drugs and the companies that make them.
2019 was also the year Dantari was born. The company, named after the Hindu god of health and medicine Dhanvantari, claims its technology could yield drug candidates that can deliver larger therapeutic payloads with fewer adverse effects.
Dantari’s lead program, DAN-222, is what the company calls a high-capacity drug conjugate and features a toxin called camptothecin linked to a nanoparticle. It was designed to evade the immune system and avoid the bone marrow, said Richard Markus, the company’s CEO.
Dantari is studying it for HER2-negative metastatic breast cancer in combination with the PARP inhibitor ZejulaPARP inhibitor Zejula. Many targeted breast cancer drugs, most notably Roche’s Herceptin and Perjeta, home in on tumors expressing the protein HER2. But such options are more limited for patients whose tumors have low or no levels of HER2.
Earlier this year, AstraZeneca and Daiichi Sankyo won FDA approval for their ADC Enhertu to treat aggressive breast cancer in patients with low levels of HER2. DAN-222 looks to be part of a growing pipeline of drugs also aimed at adding new treatment options for these patients.
Data from an ongoing trial of DAN-222, set to be presented Thursday at the San Antonio Breast Cancer Symposium, show the drug conjugate was well-tolerated among study participants. The trial is ongoing, and Dantari aims to enroll 30 volunteers, according to a federal database.
“This is key for the performance of the therapeutic and for the translation of the technology into patients, which substantially de-risks the platform technology for the rest of the pipeline,” said Markus, a former Amgen executive who left to lead the startup.
Dantari’s pipeline beyond DAN-222 consists of “next-generation” ADCs that the company says support a higher ratio of drug to antibody. Along with DAN-311, Dantari has a third research program focused on prostate cancer that is in preclinical development.
The startup is also eyeing central nervous system diseases, with the possibility that its platform “can target the blood-brain barrier similar to how we add targeting agents for cancer,” Markus said.
“This broader therapeutic index (greater efficacy and better safety) should enable this technology to surpass today’s ADCs with broad applicability,” said Sean Harper, a partner at Westlake Village BioPartners and former head of R&D at Amgen.
Editor’s note: This story has been updated to clarify Dantari hasn’t yet treated 30 patients in the DAN-222 study.
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