Therapies targeting the immune system – immuno-oncology candidates, in particular – are all the rage of late, but Bioniz Therapeutics Inc. is taking a different tack in its scientific approach to the immuno-inflammatory space. This week, the company closed a $13 million series A co-led by Takeda Ventures Inc. and David Pyott, former CEO of Allergan Inc., with participation from Joe Kiani, founder, chairman and CEO of med-tech company Masimo Corp., and Cota Capital.

Pyott was named chairman of the board at the Irvine, Calif.-based company, joined by Ilan Zipkin, senior investment director of Takeda Ventures, and Kiani.

According to SEC filings, the company previously raised approximately $4.9 million in several small rounds between 2013 and year-end 2015.

The company's lead compound, BNZ-1, is a selective inhibitor of the cytokines interleukin-2 (IL-2), IL-9 and IL-15 intended to treat the rare condition human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM), also known as tropical spastic paraparesis, and certain T-cell leukemias. The series A will enable Bioniz to advance its peptide platform technology into a phase I study in healthy volunteers, in partnership with the NIH.

HAM is a progressive neuroinflammatory and immune-mediated orphan disease that causes sensory and motor deficits, particularly in the legs, along with incontinence and impotence. As an orphan disease with no FDA-approved therapies, HAM has a certain development appeal, "but it's also a gateway to other neurological diseases, such as multiple sclerosis," said Nazli Azimi, the company's president and CEO. HAM, in fact, "is very similar to primary progressive multiple sclerosis," she said.

The FDA already accepted the company's investigational new drug application (IND) for BNZ-1.

In parallel, the company is advancing a second program, BNZ-2, a selective inhibitor of cytokines IL-15 and IL-21 that is in preclinical development to treat celiac disease and other immuno-inflammatory disorders of the gastrointestinal tract. The company's partnership on this asset with Takeda Pharmaceutical Co. Ltd. lured Takeda Ventures to the table in the first place, according to Azimi.

The technology developed by Bioniz – the company's name was derived by scrambling some letters in Azimi's name and adding "bio" – is designed to fill a fundamental gap that exists between the use of monoclonal antibodies (MAb) and JAK inhibitors for cytokine targeting and modulation.

Currently, MAbs are designed to inhibit a single cytokine, offering incomplete disease control, although a patient's immune function usually remains intact, Azimi pointed out. At the other end of the spectrum, JAK inhibitors block an entire family of cytokines, offering good coverage of the signal blockade but suppressing the immune function, as well.

"There's really nothing in between to address the inhibition of multiple cytokines," she told BioWorld Today. "We've positioned our technology right in the middle."

'SOME VERY INTERESTING CANDIDATES COMING UP'

Some monoclonal antibodies have proven effective at treating certain diseases, Azimi acknowledged, citing Humira (adalimumab, Abbvie Inc.) as one example. But much of the time they fail, she said, due to redundancy among cytokines in a majority of diseases. Some biopharmas have taken a cocktail approach to the use of MAbs to inhibit multiple cytokines simultaneously, but such an effort raises the degree of difficulty, she maintained.

JAK inhibitors, meanwhile, have their own set of challenges since they can't discriminate among different types of cytokines.

"For the sake of inhibiting a few cytokines that are disease drivers, you're knocking everything down, and that generates a lot of trouble in terms of serious long-term side effects, such as neutropenia, anemia and thrombocytopenia," Azimi pointed out.

Bioniz postulated that it could manipulate its therapeutic tool kit to inhibit only the cytokines that are active in a given disease, offering the prospect for improved efficacy with less toxicity. Thus, although the IL-2, or gamma-c, family of cytokines includes IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, BNZ-1 is engineered to selectively block signals only from IL-2, IL-9 and IL-15. The drug is designed to inhibit the assembly of the full receptor complexes for the cytokines that it targets without interfering with the assembly of the remaining complexes.

Azimi, who founded the company and co-developed its platform, and Yutaka Tagaya, the company's scientific co-founder, worked on the technological underpinnings while researchers at the NIH, but Bioniz holds full ownership to the technology.

Although the first trial of BNZ-1 will be conducted in the U.S., the company is steering development toward multiple regulatory filings, given that some of the targeted indications have orphan status in the U.S. "but are endemic in other parts of the world, such as Japan and South America," Azimi said.

In addition to completing the phase I of BNZ-1, funds from the A round will see the company through the IND filing for BNZ-2, bringing Bioniz to an inflection point "that will be a great time to raise our series B," she added.

Bioniz has a third, early stage asset, BNZ-3, that targets IL-4, IL-9 and IL-21, with the potential to address conditions such as chronic obstructive pulmonary disease, asthma, Sjögren's syndrome and systemic lupus erythematosus.

Thanks to its partnerships with the NIH and academic collaborators such as the University of Chicago and the University of Maryland, the company has remained lean, numbering only six full-time staff, although Azimi expects to hire a few additional scientists to round out the R&D team. Other C-suite officials include Fredrik Wiklund, chief operating officer, who previously served as vice president of corporate development and investor relations – and, briefly, as president and CEO – of Celladon Corp., where he managed last year's merger with Eiger Biopharmaceuticals Inc. following the futile phase IIb CUPID2 trial of heart failure candidate Mydicar. (See BioWorld Today, April 28, 2015.)

Pyott's former Allergan colleague, Eric Carter, a big pharma veteran who was senior vice president, chief medical officer and global head of clinical and non-clinical development at the time of Allergan's 2015 acquisition by Actavis Pharmaceuticals plc, chairs the Bioniz scientific advisory board.

Long term, "all options are open" for the company, Azimi insisted.

"The beauty of companies like ours that have a platform and not an asset is that we can entertain partnering deals, out-licensing or building out the company," she said. Takeda and other potential partners already have expressed interest in arrangements involving BNZ-2 or the application of other pipeline assets to additional indications.

"We are committed to continuing robust research and development internally," she pointed out. "We have some very interesting candidates coming up which could have maybe an even bigger impact in, for example, the cancer field. Because there's always opportunities for partnership or licensing, that will help determine which assets we bring forward."