LONDON – Varmx BV is poised to demonstrate its modified recombinant factor X acts a universal antidote to reverse the effects of direct oral anticoagulants in patients suffering severe spontaneous bleeding or needing emergency surgery, after closing a €32 million (US$36.1 million) series B round.

The funding enables the Leiden, the Netherlands-based company to carry out a phase I proof-of-concept volunteer trial in 2021 and to progress to later-stage studies in both severe bleeding and emergency surgery indications.

Millions of patients in the U.S. routinely take direct oral anticoagulants (DOACs), such as Eliquis (apixaban, Bristol Myers Squibb Co.), Lixiana (edoxaban, Daiichi-Sankyo Co. Ltd), Pradaxa (dabigatran, Boehringer Ingelheim GmbH), or Bayer AG's Xarelto (rivaroxaban), to prevent spontaneous stroke or deep vein thrombosis.

In the event of internal bleeding, or if emergency surgery is required, there are specific antidotes to reverse the effects of those products, such as Praxbind (idarucizumab), for reversing the effects of Pradaxa, or Andexxa (factor Xa recombinant) for blocking Xarelto and Eliquis.

However, physicians treating in an emergency situation need to know which anticoagulant a patient is on, and to titrate the dose of the antidote according to the amount of anticoagulant drug in the blood.

VMX-C001 draws inspiration from the factor Xa in one of the most poisonous snakes in the world, the Australian brown snake Pseudonaja textilis, whose venom causes human blood to clot even in the presence of factor Xa inhibitors. The scientists behind Varmx identified the specific protein behind that effect and applied it to modify recombinant human factor Xa.

The product, injected as an inactive pro-enzyme, immediately restores hemostasis via the natural coagulation cascade. Unlike the other antidotes, it does not interact with DOACs.

In preclinical studies in nonhuman primates, VMX-C001 has been shown to reverse the effects of a number of DOACs.

“We are now in execution mode, moving to the first-in-human trial, which we hope to start in 2021,” said Alexander Vos, CEO of Varmx. The phase I dose-escalation study aims to show VMX-C001 blocks anticoagulation in healthy volunteers and to inform a decision on whether to pursue severe bleeding or emergency surgery as the initial indication.

When Varmx began development of VMX-C001 there were no approved drugs for reversing the effects of any DOAC. Despite their arrival on the market, Vos said there remains significant advantages of the company’s approach.

Currently, an emergency physician needs to know not only what DOAC a patient is taking, but also when the last dose was administered, in order to avoid giving an overdose of the antidote and triggering a thrombotic event.

“Our market research says there is a regular flow of patients with this form of bleeding, or needing emergency surgery. With [VMX-C001], physicians will be confident they can safely treat these patients. There [will be] no safety issue and no risk of overdose,” Vos told BioWorld.

Varmx has canvassed the opinions of 150 physicians in the U.S. and 150 in Europe. Their response is that if the expected properties of VMX-C001 play out in clinical trials, it will represent an advance over existing products.

Vos said that over and above restoring coagulation during an emergency bleed, there will be further advantages afterward, because VMX-C001 will work in concert with intravenous heparin that typically is administered as an anticoagulant until a patient is safe to revert to a DOAC drug.

“The fact that a patient is taken off a DOAC is a risk factor in itself,” Vos noted. In one clinical study, there was a risk of thrombotic events as few as three days after administration of Andexxa.

Because VMX-C001 directly activates the coagulation cascade, it should work in tandem with heparin. “We think [VMX-C001] will work with a heparin bridge,” Vos said. “You can then put a patient back on a DOAC at any time.”

Despite COVID-19-related restrictions on travel and physical meetings, Varmx attracted multiple new investors to the series B. “We were positively surprised by the leaning forward of investors, even in this difficult time,” Vos said. “Any type of serious financing requires a lot of travel and face-to-face contact, and of course that was not possible.”

The round was co-led by Ysios Capital and Inkef Capital with Lundbeckfonden Venture and LSP. Existing investors Biogeneration Ventures and Innovationquarter followed on.

Vos said the round will fund the company through to the end of 2022 or early 2023, by which time the first-in-human trial will be completed and manufacturing in place.

“We will then decide on the strategy going forward, in terms of the indication, and financing or partnering in the future,” said Vos.

Should the properties of VMX-C001 pan out as expected, it would be a valuable asset. In May, Andexxa’s owner, Portola Pharmaceuticals Inc., was acquired by Alexion Pharmaceuticals Inc. for $1.4 billion.

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