How Recce Is Delivering 5,000 Doses Per Week For Its Clinical Trials
A conversation with James Graham, CEO, Recce Pharmaceuticals
Successfully manufacturing copious doses of any drug for clinical trials requires a few key conditions, and Recce Pharmaceuticals seems to have met most of them.
Using an in-house, automated system, the antibiotic developer produces all its clinical supply for an ongoing Phase 2 trial and an anticipated Phase 3 trial ahead. It boasts of producing 5,000 doses of its R327 intravenous and topical broad-spectrum anti-infective per week under GMP, which is a stunning number by any measure.
Beyond its Phase 2 and anticipated registrational Phase 3 trial, the company provides investigational medicine for the Australian Therapeutic Goods Administration Special Access Scheme.
Recce CEO James Graham tells us that the company has applied to begin a Phase 3 trial in Indonesia to treat diabetic foot infections (DFI). Type II diabetes is a major health issue in Indonesia, with a prevalence of more than 9% by recent estimates, according to research published in Nature. In addition, Recce is conducting a topical burn wound trial with the U.S. Department of Defense following a grant of $2 million in recognition of R327 as a gel formulation for topical treatment.
Graham’s grandfather, Graham Melrose, Ph.D., founded the company and invented R327 along with its unique mechanism of action. He’s a former executive director and head of research for Johnson & Johnson in Australia and Asia.
We had some questions for Graham, the CEO, about Recce’s approach to manufacturing and distribution at such a scale and about doing business in Australia, where Recce is headquartered. Answers have been edited for clarity and brevity. Here’s what he told us.
Five thousand doses per week is just a tremendous number. What did it take to bring your production and distribution network up to speed to manage that demand?
Graham: It has been challenging. It started as a very manual process, and I think a lot of technologies really do start that way, but we wanted to automate that process.
And the obvious question is: why do you do that? One is for quality control purposes, so you’re producing the same product every time. But you also do it to start to scale up or to see the commerciality of what can be done when you automate in a reaction vessel and when you increase the size of the reaction vessel and the feed components.
So, is it challenging to do? Most definitely.
But is it a commonly trodden path to go from a manual process to an automated process and then to increase the feedstocks and reaction vessel sizes with that? It's pretty commonly done.
It's taken some time, but we achieved it, and we are, in fact, working on increasing that scale in the background.
It’s probably more than just the capability of scaling. It takes confidence in your product, too. If you're investing in that scale-up, in that automation, you should be pretty certain that it's going to be effective.
Graham: It really runs in parallel to the development process.
So, the manual process — that was just in vitro, a little in vivo. When you step into first-in-human, that's where you really want that fingerprint approach.
Does this fingerprint of what you want it to be represent what you've actually made?
And then that gives you, the regulators, clinicians, patients, and all involved the confidence they're receiving the desired compound.
We didn't start on the day of invention producing 5,000 doses with automated, scaled manufacturing. That happened on quite a different day. And as we're now stepping into that Phase 3 study, we're looking to increase the size some tenfold to meet what we believe to be a strong demand for the product.
Does that additional demand put extra strain on your suppliers? Is it difficult to get raw materials as you scale?
Graham: No. We're lucky. Raw materials are plentiful. Our raw materials, if I go through them briefly, are water. Well, that's easy. PEG or polyethylene glycol — 50% of pharmaceuticals use that, so that's pretty easy.
The one that's a little sporty is the material that's called acrolein. Acrolein is a derivative of propene. It's a hyperreactive material, and it's, for generations, been known for its antibacterial properties, but it's also known for its hyper-combustible status.
So, we take that hyperreactive material, and we polymerize it all together to a stable state whilst retaining the antibacterial properties.
People can, in a controlled circumstance, get hold of acrolein. It is technically plentiful, but it's difficult to access because it's very volatile. For us, it’s easy enough and inexpensive because of its limited commercial value in any other area of industry. For us, it's very valuable and very useful.
Does sepsis present any unique logistical challenges? For example, patients with acute conditions could require immediate treatment. What challenges come with making sure medicine is available to patients when they need it?
Graham: The advantage that we have is clinicians can administer quickly and with confidence that you will kill any type of bacteria in the patient's blood. It will work with repeated use, meaning it doesn't matter what type of bacteria or mutation stage, and it includes the evolution of superbugs.
We are positioning for first-line therapy, whether it be the early underlying UTI infection — because 30% of septic cases are caused by an underlying UTI, whether patients realize it or not — through to the all-out septic state.
The compound is stable currently in a non-refrigerated environment for six months, and we're extending that out. In a refrigerated environment, it's at least one year. So, having clinically available supply from a shelf-life perspective is easy.
From a distribution perspective, patients generally present to hospitals. Hospitals are easy to identify and make a product available. It's a fairly optimal sepsis candidate from all the pain points of existing therapies. It's just literally straight into the IV line and off you go.
Can you talk about any advantages and incentives for producing drugs for global clinical trials from Australia?
Graham: Look, Australia is a fantastic place to start any new R&D initiative.
So, as many may know, we have what's called the Australian Research and Development Tax Incentive. For any company in Australia undertaking activities in Australia, the government will fund up to 43½ cents of every dollar you expend.
When I say fund, they'll give you a rebate, non-dilutionary, caveat-free. So, if you raise — I'm just making up numbers here — you raise $10 million for your activities, you've really got about $14.5 million dollars of true cash runway, broadly speaking. So that's good for the inventive side, that's good from a non-dilutionary side, and it's good from a de-risking side.
Now, in our company's unique instance — we're one of maybe five companies in Australia that has this — the government approved extending that R&D rebate to anywhere around the world.
So, for our activities in the U.S., our activities in Indonesia and Europe, and so on, our 43½ cents R&D rebate is extended all around the world, and the government guarantees up to about $55 million over three years.
So, that really extends your footprint globally. It does it in an incredibly incentivized manner.
And then, of course, when we look locally to what we have in Australia — the Australian clinical trial landscape — I saw a statistic the other day that there are more Phase 1 trials from Australia submitted to the FDA than any other part of the world at this time. So, globally, companies are coming in to do their Phase 1 trials here in Australia.
It's a great landscape to do your Phase 1 safety and Phase 2 preliminary efficacy trials. In our case, we’re going to do our Phase 3s internationally, in places where we want to do business.
So, maybe I'm a little patriotic, but I would highly recommend Australia as a fantastic landscape to start a company and grow from there.
About The Expert:
James Graham is the chief executive officer of Recce Pharmaceuticals and formerly served as executive director. He has extensive experience in marketing, business development, and commercialization of early-stage technologies. He also serves on Recce’s board of directors and is an investor in the company.