Nuformix gets cocrystal ball rolling

“You take a molecule and make a cocrystal of it and that gives us a new substance with new properties we can use in ways that weren’t previously possible.”

Dr Dan Gooding is enthused, as well he might be, about Nuformix’s ability to unlock new applications for existing drugs by reengineering their crystal form – and delivering IP under licence to other pharma firms at a fraction of the cost and time traditionally involved. Think Arm for pharma.

The reason I’m visiting Dan, the CEO, and CSO Jo Holland at their Science Park base is that the clinical studies for the company’s lead asset (NXP001) have just started. NXP001 is in development as a treatment for chemotherapy-induced nausea and vomiting (“CINV”), a large, under-exploited and growing market. First dosing of NXP001 took place successfully on March 20 last year, with results expected in June.

It’s significant progress and has been achieved by some nimble footwork, both financial and scientific. Formed in 2009, Nuformix recently went on the Standard List of the London Stock Exchange (NFX) after a reverse takeover of Levrett plc, created by a group of financiers looking for opportunities to invest in healthcare which “allowed us to move our products up the value chain independently”, says Dan.

Their scientific journey began with “moderate success” on the Science Park. Co-founded by some of the original founders of Pharmorphix (now owned by Johnson Matthey), cocrystal technology was just emerging.

“We started with what sounded like the Holy Grail of the pharma industry – finding novel forms of old drugs to create opportunities to maximise their value. This is what the technology offered. But as we reached critical mass, cost pressures meant standard life cycle management plays became less commercially attractive to pharma, so we had to switch track. This was in 2012/2013.”

At the same time, R&D costs for producing new drugs were spiralling. The failure rate was close to 19 in 20. It was unsustainable. But what if a new therapy could be made from an existing drug that already had regulatory approval? Bingo.

NXP001 is a new form of a known drug – Merck’s EMEND, which is marketed to reduce CINV.

“Merck originally developed the drug for depression but after failing, switched to CINV. However, patients were now in a fasted condition [standard for chemotherapy], so the drug was very hard to deliver,” says Dan. “In the early 2000s Merck worked out a way to improve delivery using nanotechnology.”

The drug was administered orally but not really dissolving: its absorption was limited, resulting in minimal therapeutic effect.

“For this drug, rapid dissolution in parts of the digestive tract is really important,” comments Dan. “It was peaking at 2 per cent when Merck first developed it, then it was improved to 6 per cent and came to market. With our cocrystal approach it’s up to 80 per cent in biologically relevant media.”

“Healthy volunteers were given NX001 alongside Merck’s drug in our study,” says Jo who, like Dan, had studied chemistry at Leeds, albeit in a different year. She had made her way to Cambridge via Millennium Pharma, where she met Dr Dave Tapolczay – currently Nuformix’s non-executive chairman – who was also a co-founder of Pharmorphix.

“Our molecule, when added to the chemotherapy drugs most patients are receiving, massively uplifts the efficacy treating CINV patients,” notes Dan. “Our goal is to help this drug to get to more patients. So we’ll prove the concept of easy and effective drug delivery, and hope to license our approach to other companies best positioned to rapidly commercialise.”

There’s the rub – the Arm model. Nuformix finds the molecule which will most benefit from cocrystal reengineering, get the trials sorted, then license it to pharma firms who put it out to the healthcare market. And the financial architecture to pipeline success has already been constructed. “If we can prove the product concept in the UK, that triggers a £2million milestone payment from our Chinese licensing firm, Shanghai Newsummit Biopharma, plus there’s a 10 per cent royalty payment on top – and that’s when we will see cocrystal technology and our business model working as we think it should.”

The study will also, of course, advance on-going discussions for licensing rest-of-world rights to NXP001 for CINV – a large, under-exploited and growing market, which in demographic terms comprises one third of global cancer patients. It will quickly provide clinical data in a cost-effective manner confirming NXP001’s applicability for rapid development as a treatment for CINV, but it doesn’t end there.

“It’s brilliant for us to reach this milestone of our getting our technology into the clinic but what we really want to do is reprofile further known drugs as new treatments for unmet needs. Reprofiling of old molecules has been happening for some time but the missing ingredients are how to protect the investment at a clinical trial – and how to make it so different that no one else can achieve anything similar.

“We have other cocrystals in our portfolio, five in total. Plus, there’s others in development. There’s three things we’re looking for in a drug:

 Drugs that are safe

 Drugs that are problematic so that we can improve them

 Drugs with a mechanism relating to unmet needs.”

Jo adds: “And we don’t just patent the technology. Each drug gets a whole new lease of life, and each drug gets its own study...”

There’s just five people working at Nuformix: Dan, Jo, Dave’s the chairman, Alex is head of chemistry and Maddy does general admin.

“We’ve been able to survive on a really moderate amount of money, with very low operating costs,” says Dan. “We don’t want to change from a cost-effective, lean business generating value to a behemoth.”

“There’s no need to do that,” says Jo.

“Where we’d like to go is to develop a selection of drug cocrystals from our portfolio to patient proof of concept. We believe our growing portfolio has value because our drugs can do something that other drugs can’t.”

The other diseases will probably include fibrosis.

“There are treatments on the market, but they cause terrible side effects, they’re expensive and they don’t prolong life.”

Jo adds: “The idea is to stop the fibrosis. Then there’s dermatology and respiratory diseases to look at too...”

There’s no stopping Nuformix now. With Andy Richards on the advisory board, the sky’s the limit, though Dan accepts that “the world of disease is so big we can’t ever expect to become an expert in all of it”.

You have to suspect that won’t stop him from trying.