TRx Biosciences presents classic Cambridge healthcare breakthrough

TRx Biosciences, an innovative biopharma start-up, was officially launched at Babraham Research Campus this week (October 12), with Cipla chairman Dr Yusuf Hamied the honorary guest.

TRx’s founders are CEO Dr Robin Bannister, CSO John Brew and CBO Dr Dan Gooding: together, in a small lab within Babraham’s accelerator building for the last six months, they have achieved a breakthrough in the development of a novel drug targeting technology, with the potential to disrupt how all small molecule drugs might be delivered.

The breakthrough is significant not just because it makes use of the lymphatic system – thus avoiding the liver to distribute drugs to the patient – but also because TRx has created a business model offering immense speed of product development for novel use of existing drugs, drugs stuck in development or new chemical entities.

At launch this week, four existing collaborative users of TRx’s approach were unveiled: Cambridge-based Monument Therapeutics, Canada-based Mandara Pharma, Oxford-based Oxilio, and Cancer Research UK (CRUK).

“Essentially, we’ve found a novel, safe and completely unexploited mechanism that uses natural human biology to transform the way we deliver small molecule drugs,” said Dr Gooding, who was founder and CEO of Nuformix until mid-2020. “It completely turns what scientists have thought about in terms of small molecule drug design and delivery for years on its head.

“We’ve built the company carefully, and have initially formed partnerships with a select few drug companies who face specific bio-distribution challenges in their R&D programmes. We’ve used these partnerships to better understand the possibilities of our technology and have demonstrated that we can solve a broad range of drug targeting and delivery challenges, including enhanced delivery to the brain, lung, tumours and immune system.

“We’re targeting the lymphatic absorption system in a very specific way, which avoids the liver – that’s good, because there can be huge drug loss via the liver due to metabolism. From there we can target the brain or other specific cells and tissues. TRx’s technology interacts with the lymphatic system in ways not previously possible. It’s a totally different approach.”

The only other company using the lymphatic system is PureTech Health in the US, which is collaborating with Boehringer Ingelheim to advance immuno-oncology product candidates using its proprietary platform. Otherwise, the only on-sale product is a lipid-formulated ibuprofen to relieve flaring joint pain and inflammation developed at Biocopea, where Robin was CEO and John head of biology.

Flarin, a patent-protected lipid formulated ibuprofen has, at a dose of 200 mg/day, been shown to be as effective as 400mg/day of standard liquid ibuprofen capsules in patients with acute joint pain. Flarin was the first commercialised product in this technology space. Through the development of Flarin, ibuprofen has been turned from a household name with problems to a wonder drug for inflammatory disease, marketed by Flarin Holdings.

“The drug is formulated in lipid and ingested orally,” John explains, “in the stomach, it’s released and interacts with gall-bladder juices. This process allows the formulation to interact with the small intestine, where it’s absorbed. From here, the body’s natural biology takes the formulation contents and forms chylomicrons, but now with drugs loaded inside.”

“Chylomicrons then transport to the lymphatic system, which has two functions – to allow lipids to go from the gut into the bloodstream, and to bring back tissue fluids from the extremities.”

The lymphatic system circulates lymph fluid and is the site of many key immune system functions.

“Therefore, the chylomicron allows the drug to go into the tissues utilising the body’s own systems,” concludes John.

“We’ve got the lymphatic system leveraged therapeutically,” adds Dan.

The time taken to get these applications into clinical studies is remarkably low.

“The pre-clinical formulations we use are not massively different from what patients will take and that is highly beneficial,” notes John. “It can take a year just to develop a formulation. We’re able to side-step that aspect.”

The Monument programme, MIT980, ‘the first potent centrally penetrant modulator of neuro-inflammation’, starts clinical trials in Q2 2022, with Mandara’s application for anxiety commencing later in 2022, followed by studies in traumatic brain injury and PTSD. But first up is Oxilio’s tumour-targeting drug.

“Oxilio is due to start a human clinical study in the first quarter of 2022 exploring an existing drug as a potential pan-cancer cure,” says John, “for people with untreatable cancers. But there are currently a series of issues to resolve, which we believe we can address with our technology.”

So this is a co-development? “It mirrors a co-development,” replies John. “It’s a long-lasting collaboration which will continue deep into clinical development.”

Dan adds: “As we were incubating the technology, we were aware that it would be relevant to a number of companies with projects re-developing known drugs – projects hoping to maximise the potential of new science in areas of unmet need.”

The business model for TRx partnerships involves both milestones and a profit-sharing mechanism. “We’ve already received multiple milestone payments from partners,” Dan says, “with more to come. There are many different routes to treating patients. For our Oxilio programme, it’s up to them on what path fits with their strategy and we’ll support them on that.

“The exciting aspect for us is that clinical trials are an opportunity to treat patients and it’s possible that we may be able to treat patients in late 2022 or early 2023. For a technology that’s so disruptive, that’s incredibly fast.”

Ultimately, of course, TRx Biosciences wants to initiate its own small molecule drug development programme, which it will do.

“We’re still in the technology validation phase,” Dan says. “Having closed our first investment round, we can formalise the management team and scientific advisory board.

“We can now consider the scientific and the commercial attributes of various opportunities under study, evaluate various molecules using our technology and focus on those most attractive. We’ll need to raise money for the second time later next year so that we can take our technology to clinic under our own steam.

“We’re at an exciting stage where our science has proven itself pre-clinically and to an extent in humans. As we deploy this initial investment, we’ll take both TRx and our technology through further inflection points and create confidence. This will better allow the business to raise the funds needed for its next stage of growth and deliver on its promise of creating a step-change in the biodistribution of small molecule drugs.”