As the biotech class of 2021 looks to outscore the deeply impressive turn it had last year, Bolt Biotherapeutics has raked in $230 million from its upsized IPO.
One of the first immune-stimulating cancer drugs, prostate cancer vaccine Provenge, never quite lived up to expectations, but the scientist whose work led to the development of the product remains committed to immuno-oncology.
He’s Edgar Engleman, M.D., professor of medicine and pathology at Stanford University. His creation, Bolt Biotherapeutics, founded in 2015, recently launched its first clinical trial of its lead compound, which is part of a new class of cancer drugs called immune-stimulating antibody conjugates (ISACs). The drug is a tumor-targeting antibody that’s connected to an agent that stimulates the immune system.
In animal studies, the drug, which targets the tumor marker HER2, eradicated large tumors, according to a presentation at the Society for Immunotherapy of Cancer annual meeting in Maryland back in 2019. The drug also protected the animals from the development of new tumors, the company said.
That candidate, known as BDC-1001, is now in the clinic as a treatment of patients with HER2-expressing solid tumors, including those with HER2-low tumors. Bolt’s approach is different from a typical antibody-drug conjugate method of action, because its ISAC technology is based around the idea of connecting antibodies to agents that stimulate the immune system to attack the cancer rather than to compounds that directly poison cancer cells. And it’s designed to be able to be used as a solo therapy.
“We have designed BDC-1001 as a Boltbody ISAC comprised of a HER2-targeting biosimilar trastuzumab conjugated to one of our proprietary TLR7/8 agonists to maximize the potential anti-tumor response,” the biotech said in its recent SEC-1 filing.
It started a phase 1/2 trial of BDC-1001 around a year ago and is currently in the dose-escalation portion of the trial; it expects to advance into phase 2 dose expansions in 2021 in “four clinically important and commercially compelling indications,” it said.
“As of January 12, 2021, we have treated 19 patients and BDC-1001 appears to be well tolerated with mild to moderate adverse events and no dose-limiting toxicities, or DLTs, or drug-related serious adverse events observed to date. We have seen clinical activity in the form of stable disease, reductions in tumor volume and increases in pharmacodynamic markers that we believe are consistent with our proposed mechanism of action.”
Bolt also has other, earlier preclinical programs, including one that focuses on CEA, a well-known tumor antigen that is overexpressed in various solid tumors with significant unmet medical need including, but not limited to, colorectal cancer, non-small cell lung cancer, pancreatic cancer and breast cancer. That could be in the clinic by next year.
It’s also at work on another early program for a PD-L1 Boltbody ISAC, which is targeting patients with tumors that are nonresponsive or become refractory to immune checkpoint blockade.
The biotech will trade on the Nasdaq under the ticker “BOLT.” The company previously filed for a $150 million IPO but, like so many in the past year, went well past this.