Inside Interius' Global Regulatory Strategy

By Matthew Pillar, Editor, Bioprocess Online

Back in July, Bioprocess Online editor Tyler Menichiello spent some time with Interius BioTherapeutics CEO Phil Johnson, M.D., their conversation yielding this column on the company’s first-of-its kind approach to manufacturing chimeric antigen receptor (CAR) therapy in-vivo.

More recently, that lentiviral gene therapy (dubbed INT2104), which creates CAR T and CAR NK cells inside patients’ bodies, headed to clinical trials and dosed a first patient with a B-cell malignancy. On the heels of that early milestone in the company’s INVISE (INjectable Vectors for In Situ Engineering) trial, I caught up with Dr. Johnson to learn about the company’s regulatory strategy.

A MULTINATIONAL REGULATORY ADVENTURE

As the trend toward seeking efficient and expeditious clinical progress goes, Interius has orchestrated a global regulatory strategy that’s centered in Australia. That strategy, says Johnson, is nuanced due to varying regional requirements. True “regulatory harmonization in the developed world,” he says, is a pipe dream. “It’s difficult to envision how you could bring people together to create global harmonization,” he says. “While the EU is generally harmonized, each country brings additional layers above and below its stringent review and data protection standard, so even there you’re dealing with each country in the EU independently, and experts in each country have their own opinions.”

Johnson says the questions regulators ask in Australia, versus the EU, versus the U.S. are all very different in their level of detail and, he says, basic scientific understanding of Interius’ therapeutic approach. “Germany was very sophisticated. They knew exactly what we were doing. Australia was right behind them. Others can be a mixed bag,” he says. “To put my head around how we would harmonize those fundamentals, I think it would be almost impossible.”

Australia’s advanced understanding of Interius’ therapeutic approach, coupled with the substantial savings in trial expenses compared to the U.S., made Johnson and company’s decision easy. The country’s Commonwealth Government offers generous incentives, including R&D tax rebates, for companies conducting clinical trials there, which significantly reduces development costs. Australia’s TGA (Therapeutic Goods Agency) also approved a trial of INT2104 quickly, allowing Interius to commence in-human clinical studies sooner than it would have elsewhere. That yields faster access to clinical data, the all-important factor in funding future milestone efforts. Johnson says the country also boasts world-class facilities like Peter MacCallum Cancer Centre, staffed by renowned investigators who excel in pioneering studies. The presence of one such clinical investigator, Dr. Michael Dickinson, played a key role in the decision.

“We put together a group of key opinion leaders, our Clinical Advisory Board, to map out our strategy. From that effort emerged a champion for our product in the physician, scientist, and investigator Michael Dickinson,” says Johnson. “When we began to discuss the entirety of the process, including going to the FDA, the EMA, and the costs associated, Dr. Dickinson stepped up and said, ‘you know, we do this kind of thing very well in Australia.’ His colleagues on the advisory board, many of which were familiar with Dr. Dickinson’s work, agreed.

MANAGING THE LOGISTICS OF GLOBAL REGULATORY ACTIVITY

Today, Interius has clinical investigation sites in Melbourne and Sydney. Johnson acknowledges that the geographic and time zone disparity create logistical challenges, but they’re trivial when weighed against the advantages. “It's more complicated when you do something ex-U.S., simply because you have to deal with customs, border issues, storage, providence, and time zone differences, but these are standard considerations,” he says. Interius hired a storage facility in Australia that handles the distribution of its drug product. “Working at a premier institution like Peter McCallum makes things easier. They’re used to dealing with products coming into Australia that are not of Australian origin. A lot of things are tested there that did not originate there.”

Interius’ staff conducted site initiation visits, whereby its internal staff and the company’s CRO spent a full week auditing and aligning on the studies (and let’s be honest, there are worse places to spend a week). Interius’ U.S. team also provides 24/7 web and phone support to cover the time zone difference. “Our development and drug product leads are on call to receive phone calls if something needs to be answered, or if we need to be notified that a patient has been enrolled and dosed in in the study,” he says. “If the pharmacy has a question about formulation, they call our drug product lead, and that could be at 2 AM.”

Beyond the logistics of people and product, Johnson says global clinical efforts require just a bit of extra attention paid to the logistics of data. “The Europeans have pretty rigorous data protection regulations, which require training of your entire staff, and that’s not the case in the U.S.,” he says. “Training on those regulations is ongoing, because if you’re audited, they’ll ask for records,” he warns. Much of the data logistics responsibility, he says, falls to the CRO. “We’re not Merck, Bristol Myers, or J&J,” he says. “We hire a lot of this out to our CRO.”

Ensuring that CRO was up for a global exercise came down to an RFP process that ensured Interius’ chosen partner could execute in Australia, Europe, and the U.S. “You’re paying somebody to do this work for you, but you also have to be familiar with it yourself. That's where our regulatory consultant comes in.”

Conducting clinical trials overseas creates a long checklist of to-dos, but Johnson says none of them are cutting new ground. “It’s all following a regulatory pathway that's well worn. It’s just a different set of boxes you check from one agency to the next.”

AUSTRALIA PAVES THE WAY TOWARD GLOBAL TRIALS

Australian trials are often designed to align with the requirements of the FDA and EMA, ensuring that data collected can support multi-region submissions. Clinical trial data generated in Australia is therefore recognized and often directly applicable to submissions in the EU and the U.S., creating a seamless bridge across major regulatory territories.

That’s precisely the path Johnson and Interius intend to take. In November, the company submitted regulatory documents to the European Union, and Johnson says it’s got champions in Germany and Spain there. “We had a Pre-IND meeting with the FDA as well, and we will be back to the United States,” he says, “but we'll come back with folders of data that support the IND development here in the U.S.”

As biopharma companies increasingly adopt global regulatory strategies, Australia's position as a cost-effective, high-quality clinical research hub is likely to strengthen. Its ability to facilitate rapid, reliable, and globally relevant trial data offers a compelling value proposition for U.S. and multinational biotechs.