Index bets heavy on novel ‘blood of the gods’ clotting antibody

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The $11m in series A funding provided by Index Ventures for a preclinical project today could either be one of the obvious signs of the overheating biotech market or a very shrewd investment if the excitement around what is a unique anti-clotting drug lives up to its promise.  

XO1, a newly formed Cambridge company, is the recipient of the funds and owner of what David Grainger, venture partner at Index, described as “the most amazing thing” he has seen in 20 years. Ichorcumab, an antibody targeting the clotting enzyme thrombin, certainly must be special to make Index offer its largest life science investment at such an early stage, but observers should remember that the project still has many years to go and hurdles to cross before it starts to save the “millions of lives” some are already talking about.

Admittedly ichorcumab, named after Ichor, the ethereal fluid in the blood of Greek gods that granted them immortality, could be the holy grail of anticoagulation if it does indeed manage to tread the fine line between clot prevention and dangerous bleeding.

However, it is a feat that many, including the new generation of oral anticoagulants, have struggled with, and in the case of treating acute coronary syndrome (ACS) they have almost to a man failed (FDA’s no means no for new blood thinners in acute coronary syndrome, March 5, 2013). Indeed so high is the physiological and regulatory hurdle that both Bristol-Myers Squibb and Boehringer Ingelheim have not continued to pursue the indication with Eliquis and Pradaxa. Xarelto has so far been the only one to secure approval in ACS, and only in Europe.

Even the old stalwarts of Plavix and warfarin are riddled with issues over dosing and bleeding risks, so if ichorcumab can indeed work with no added bleeding risk in this indication and the lucrative area of atrial fibrillation the rewards would be enormous.

Very long odds

What is also enormous about the project is the chance of it actually ever having been discovered, were it not for a combination of chance and opportunity.

In 2008 a patient presented at an emergency room at Addenbrooke’s Hospital Cambridge with a head injury, and despite having the clotting ability associated with severe haemophilia managed to recover after what should have been a fatal bleed.

This was noticed by Dr Trevor Baglin, who called in researcher Professor Jim Huntington at the university’s Institute of Medical Research, who narrowed the phenomenon down to the patient’s unique paraproteins. Paraproteins are the equivalent of a benign tumour of the immune system and occur in a few percent of people as they get older.

“It’s very common to have these high-level antibodies in your blood. Typically they don’t react against anything, so go unnoticed,” said Mr Grainger. “This antibody is a random clone that has been expanding and happens to have this particular reactive pattern. It’s a million to one chance that it happened.”

Dr Huntington subsequently went on to design a synthetic version of the antibody by copying the binding site, and used animal models to confirm the antibody.

Next steps

With the money from Index now in the bank XO1 is expecting to take 18 months to get ichorcumab into the clinic, roughly the time required to establish good manufacturing practices for an antibody. Hopes are, however, high that the drug will ace phase I.

“What’s unique is that in albeit just one person we have a clinical trial of what this antibody can do at very high doses for long periods of time, and that is unique. Mostly when you have a preclinical asset, it’s precisely that, preclinical, and you therefore don’t know what will happen when you get it into humans. Usually things tend to turn out to be rather less exciting than you thought they were when you make that transition, but not here,” said Mr Grainger.

It is this profile, albeit in a rather risky-looking single patient, that gave Index the confidence to make its early investment. But the group believes that the promise of ichorcumab is compelling. “It took me about 20 seconds to see this as something we should do,” Mr Grainger said.

Lean operation

True to its investing style Index is running the single-asset company virtually. The sole full-time employee will be a chief executive, a role that Mr Grainger has on an interim basis until a new CEO is appointed in the next couple of months.

Other “staff” will be consultants who will come and go as their particular skillset and expertise is required in the development process. Even with the lean, virtual model the aim will be to complete the first in-man study with the current funding and then raise a series B, which should take the company to proof of clinical concept and Index’s usual exit point.

If over the next few years and numerous trials ichorcumab does live up to its promise, it would be easy to see the dollar signs of a future blockbuster, but this is a field where numerous drugs have failed to find the balance of perfect blood coagulation. The antibody approach has also never been tested in blood thinning, so while it might be the stuff of gods, ichorcumab needs to spend a few more years in humble labs proving its divinity.

To contact the writer of this story email Lisa Urquhart in London at lisau@epvantage.com or follow @LisaEPVantage on Twitter

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