AvidBiotics split forms CAR-T and antibiotic specialists

Bay area biotech AvidBiotics has decided that its two development programs in CAR-T and microbiome-driven antibiotics would do better as separate companies.

The company said it will split in two, creating one company called Xyphos to focus on cell-based therapies for cancer and another—Pylum Biosciences—taking forward its Avidocin antimicrobial protein portfolio for resistant infections.

The move promises to “unlock the value and accelerate the development of these two platforms,” according to AvidBiotics’ board member Kevin Cameron, co-founder of proxy advisory firm Glass Lewis. The two companies will now be free to seek independent financing and partnering opportunities.

Xyphos has its own spin on the CAR-T approach to cancer immunotherapy, which are targeted towards a single tumor-associated target. In contrast, the biotech’s platform combines the modified T cells used in this type of treatment with bispecific antibodies to direct them and—at least in theory—could create a single engineered T cell line to be directed at multiple tumor types by modifying the antibody component.

Using this approach, the company hopes it will be able to sidestep the need to develop different CAR-T cells for each target, and eventually for each patient, which would make CAR-T therapy “more easily designed, produced and delivered,” according to Xyphos’ CEO Jim Knighton.

"We have developed a CAR-T cell that is completely inert until it binds to a bispecific antibody, also developed by us, that we call a MicAbody," he tells FierceBiotech. The bispecific antibody activates the CAR-T cell to then kill the targeted cancer cell."

Importantly, by dosing more or less of the MicAbody, activity of the CAR-T therapy can be specifically controlled, potentially mitigating many of the risks associated with the current approved CAR-T therapies, he says. 

It could also avoid some problems associated with current approaches to CAR-T such as a lack of control, side effects on healthy cells and lack of efficacy caused by ‘tumor escape,' in which cancer cells evade being killed because they stop expressing the target antigens. Knighton said the company expects to begin clinical trials in early 2019 in liquid tumors, with an eye to moving toward solid tumors thereafter.

Pylum meanwhile—headed by David Martin, M.D.—is concentrating on another hot topic in biotech, targeting the microbiome—the complex bacterial ecosystem that populates our bodies that is thought to play a key role in health and disease.

The new company is focusing on a range of protein candidates that in early testing seem to have the potential to destroy bacterial cells with surgical precision—including problem pathogens like C. diff, E. coli and other resistant bacterial strains—without harming helpful, resident bacteria in the body. A spinoff from that is working on double-headed proteins that Pylum thinks could direct the immune system to seek out and destroy malignant or virus-infected cells.

Experimental results have revealed that in the rare cases in which C. diff bacteria develop resistance to the Avidocin agent, the bacteria lose the ability to cause disease in very sensitive experimental animals. The resistance does not seem to be able to spread to other C. diff but—even if it did—that might be a benefit as it could spread the loss of 'virulence'.

The new company’s lead program targets C. diff and is due to start clinical testing later this year, and needs to complete IND-enabling studies such as manufacturing downstream processing and GLP-Tox studies before it can move into phase I safety trials, according to Knighton, who says the first efficacy trial will likely be in elderly patients admitted to a hospital with a known bacterial infection that requires an antibiotic.

"We've gotten two very rich and exciting research platforms to the point of preclinical development, and we believe that by splitting the company into two entities, we will be able to offer investors a single play opportunity either in immuno-oncology or in the microbiome - two of the hottest areas of research today."