Johnson & Johnson (J&J) placed its trust in the future of Centyrin technology into familiar hands at Aro Biotherapeutics Co., a startup co-founded by two former J&J executives, including the co-inventor on the Centyrin patents.

The Philadelphia-based company, formed a year ago, raised $13 million and hired a team to advance the first two programs of the next-generation protein therapeutics through lead optimization and preclinical testing as they continue their march toward the clinic.

The concept for Aro – the Maori word for "focus" – emerged when Sue Dillon, the company's president and CEO, and Karyn O'Neil, chief scientific officer, were still in their former roles. For Dillon, that was global therapeutic area head for immunology at J&J unit Janssen R&D, where she moved blockbusters like Remicade (infliximab), Simponi (golimumab), Stelara (ustekinumab) and Tremfya (guselkumab) through development and to market. O'Neil, the Centyrin co-inventor, was director of antibody discovery and venture leader for Centyrex, a J&J venture, where she focused on designer protein platform technologies and led the team advancing the Centyrin platform.

"We were both excited about the possibility of being able to apply this protein drug platform for a variety of applications that we think could be disruptive in the biologics space," Dillon told BioWorld.

The duo's street cred convinced J&J, of New Brunswick, N.J., to provide Aro with an exclusive global license for the research, development, manufacturing and commercialization of Centyrin protein therapeutics. Initial funding came from Johnson & Johnson Innovation – JJDC Inc. and Biomotiv LLC, the Cleveland-based drug development accelerator.

Centyrins are small, structurally simple, ultra-stable, highly soluble proteins, O'Neil explained.

"Centyrins were designed and conceived from the start with properties that were differentiated from antibodies so that we could address targets in a way that has not been done previously," she told BioWorld. "We can link Centyrins together and modulate cell surface receptors in unique ways for more complex disease targets."

Centyrins can be readily expressed in mono-, bi-, tri- or multispecific formats with flexible architecture, enabling recognition and modulation of multiple target antigens on tumors or immune cells to achieve a desired therapeutic effect. Such flexibility makes them ideal for precise delivery of complex drug payloads, including oligonucleotide therapeutics and nanoparticles, O'Neil pointed out, enabling tissue-specific delivery of medicines to previously undruggable intracellular targets.

Thanks to their relatively small size, Centyrins penetrate and disseminate through solid tissues, and their inherently short in vivo half-life enables clearance by the kidneys. Rapid screening of multiple libraries with different antigen binding surfaces allowed Aro scientists to discover Centyrins that bind to a variety of epitopes on target proteins. The researchers then tweaked the Centyrins to extend exposure and tune pharmacokinetics to a desired in vivo profile.

Aro's lead program, a bispecific Centyrin that targets the cMET receptor and EGFR, is in late-stage lead optimization for advanced non-small-cell lung cancer. The second program, a Centyrin-siRNA conjugate for undisclosed cancer targets, is a first-of-its-kind combination designed to deploy payloads in high concentration to the disease site while lowering off-target toxicity.

'Opportunity to do something completely new'

The range of potential payloads that may be delivered using Centyrins represents one of the platform's most compelling features, according to Dillon. She cited the opportunity to overcome "historic limitations in the field" by, for example, delivering nucleic acid-based and other genetic therapies to "tissues involved in a whole host of serious diseases" without harming normal tissues at the same time. "That opportunity to do something completely new that takes advantage of the properties of our platform is very exciting to us," she added.

Aro is not the first or only company plying the technology. Janssen previously provided basic licenses for the use of Centyrins to Poseida Therapeutics Inc. for use with CAR T-cell therapy and to the not-for-profit Centre for Probe Development and Commercialization to develop nuclear imaging probes for cancer. (See BioWorld Today, Aug. 12, 2015.)

"The rest of the universe of applications for Centyrins is licensed to Aro," Dillon said.

The company intends to take full advantage of that range of possibilities, advancing oncology and immunology assets internally while assessing partnerships in other indications. Those conversations, already underway, also factor into the long-term business strategy.

"We're building a whole pipeline of drug candidates that were discovered by Aro and will be developed and commercialized by Aro," Dillon said. "It's too early to say what types of partnerships we may develop around the internal portfolio, but suffice to say that our business plan anticipates that we will hire a team to bring the programs we develop to approval."

Aro's 11 employees include Derek Miller, an alum of Celator Pharmaceuticals Inc. and Genentech, as chief business officer and head of corporate strategy; J&J veteran Mark Laurenzi as vice president of finance and operations; and Steven Nadler, former executive director and head of immunoscience, immuno-oncology and oncology discovery translational research at Bristol-Myers Squibb Co., as vice president of discovery and translational research. The remainder of the team, for now, is focused on advancing the company's science, but Dillon expects to build preclinical and clinical capability over the next 18 to 24 months.

To that end, the company is "actively in discussions regarding series A financing, and we're excited about the interest that we've seen," Dillon said, without divulging a goal or timetable for the round.

"Because the Centyrin platform has many applications and, being a small company, we've chosen where we will focus, there are still quite a number of other possibilities," she pointed out. "We're working with leaders in the industry to leverage the Centyrins for delivery of a variety of types of drug payloads that interest other companies. Ultimately, this approach will also allow us to explore different sets of diseases."

The company isn't married to certain categories of disease, rare or otherwise, O'Neil added.

"We'll take development where the science leads us," she said. "We're trying to capitalize on the properties of our molecules, and we'll apply them in the disease areas where they seem most relevant."