Reposted from Bioworld
www.bioworld.com/articles/717209-biomissiles-multispecific-antibodies-harness-nk-cell-engagers
By Tamra Sami, Bioworld , Feb. 12, 2025
Biomissile Pharmaceuticals Co. Ltd. is developing multispecific antibodies that overcome resistance associated with antibody-drug conjugates (ADCs) via its next-generation natural killer (NK) cell engagers.
"ADCs are very efficacious, but they do have a drawback with side effects and resistance, because ultimately ADCs are similar to chemotherapy because you bring toxins to the tumor site," Biomissile co-founder and CEO Chao Tu told BioWorld.
"Some solid tumors don't respond at all, and so solving that dilemma is what drives our company,” he said.
Shanghai and Boston-based Biomissile is focusing on a different mechanism to treat solid tumors by bringing immune cells, especially NK cell engagers, to the tumor site rather than toxins.
Using its fully human domain antibody display (UDAB) library, Biomissile can screen out fully human nanobodies quickly to discover lead candidates in as little as four weeks, Tu said, and because nanobodies are so small, they can find unique epitopes on NK cells or T cells.
"What differentiates our molecules from our competitors is that we not only activate NK cells, we also activate T cells indirectly on the tumor sites. That's important, because T cells dominate the immune system” He stressed the importance of activating T cells indirectly, because if they're activated directly it results in a cytokine storm and severe side effects. By activating T cells indirectly within the tumor microenvironment, side effects can be reduced.
"Because we use nanobodies to activate those immune cells, we can retain the original monoclonal antibody's function to shut down the tumor antigen associated TAA signaling pathway."
The strategy consists of three pillars: NK cell engagers elicit an innate immune response; engaging the T cells indirectly elicits an adaptive immune response; and then the TAA pathway can be shut down.
"Before bispecifics became popular, people only focused on the TAA pathway, but we have added to that by activating NK cells and T cells."
Lead product BM-230 is an NK cell engager and in phase I trials in Australia. The pan-cancer basket trial includes breast cancer, lung cancer, colon cancer, gastric cancer and ovarian cancer. The company anticipates filing an IND with the U.S. FDA soon.
Biomissile has a pipeline of more than 10 biologics that include several potentially first-in-class fully human domain antibodies and multispecific antibodies.
"For autoimmune diseases we can also attack pathogenic B cells for B-cell depletion,” Tu said. “Right now, T- cell engagers are hot to deplete B cells, but NK cells can also deplete B cells, and we have data showing our NK cell engager BM-366 can deplete B cells even faster and more robustly than T-cell engagers. And, because it's an NK cell engager, it is safer because it doesn't release cytokines.”
Autoimmune disease is different from cancer because it tends to be a chronic condition, and patients stay on medication for a long time so safety data need to be more stringent.
Also in phase I is BM-012, (HT-102), which was jointly developed by Biomissile and Suzhou Hepa Thera Biotech for the functional cure of hepatitis B virus (HBV). Preclinical studies show that BM-012 rapidly cleared HBsAq and HBV DNA from systemic circulation.
BM-219, a bispecific, broad-spectrum, inhalable anti-COVID-19 molecule is in phase I/ll testing for both the treatment and post-exposure prophylaxis of COVID-19 infection.
Founded in 2020, Biomissile has raised $55 million to date - $25 million in a series A round and $30 million in a series B round. Tu said he hopes to raise another $30 million to $40 million in a series B+ round to advance BM-230 from phase I to phase II and to explore potential combinations with NK cells. The funds will also bring the autoimmune project to the clinic.
Biomissile won the first-place award at the 2024 ChinaBio Partnering Forum’s “Startup Spotlight Pitch Competition" that included a cash prize of ¥ 500,000 (US$68,000).
Tu splits his time between Shanghai and Boston. The company's main R&D team is in Shanghai, while business development and regulatory activities are conducted in Boston. All of the company's functional heads have more than 20 years of pharma experience.
Tu founded two U.S.-based biotechs before co-foundinq Biomissile. He was also a senior researcher and team leader at Pfizer Inc. for five years. Prior to that, he was a postdoc fellow at the U.S. National Cancer Institute and the NIH.