Myricx Bio is bringing new therapeutic possibilities to the highly promising area of antibody-drug conjugates for treating cancer.

Myricx Bio, a cancer therapy spinout based on research carried out at Imperial and the Francis Crick Institute, has raised £90 million ($114 million) in investment to move its novel treatments for a range of different tumour types, including breast, lung and gastric cancer, into clinical development. The investment is among the largest Series A rounds ever raised by a European academic biotech spinout.

The enthusiastic response from investors reflects both the attraction of Myricx’s proprietary platform and the pharmaceutical industry’s current intense interest in antibody-drug conjugates (ADCs) for cancer therapy. This approach involves using antibodies that bind to the surface of specific tumour types to deliver a drug to its target.

Initially set up to develop a pipeline of small-molecule drugs to fight treatment-resistant cancers, Myricx pivoted in 2021 to adapt its drugs for delivery as ADCs.

“The ADC landscape has evolved rapidly in recent years, and we recognised the opportunity to apply our uniquely potent small molecule drugs as a class of powerful ADC payloads with a completely novel mode of action, an innovation the field has been seeking for some time,” says Professor Ed Tate, GSK Chair in Chemical Biology in the Department of Chemistry at Imperial and a Satellite Group Leader at the Francis Crick Institute, a specialist biomedicine research institute in London.

“It’s fantastic to see this record-breaking investment in the therapeutic potential of an idea seeded in an Imperial chemistry lab." Dr Simon Hepworth Director of Commercialisation, Imperial

Professor Tate co-founded Myricx in 2019 with Dr Roberto Solari, then a visiting professor at the National Heart & Lung Institute at Imperial, and Dr Andrew Bell, a PhD alumnus of the Department of Chemistry. All three remain closely involved with the company as advisers.

“It’s fantastic to see this record-breaking investment in the therapeutic potential of an idea seeded from discoveries in an Imperial chemistry lab,” said Dr Simon Hepworth, Director of Commercialisation at Imperial. “The combination of academic talent and industry experience that came together in the founding team is a hallmark of Imperial’s scientific and translational capabilities.”

Joined-up thinking

The idea that drugs could be targeted as ‘magic bullets’ in this way dates back more than a century, but it wasn’t until the 1980s that ADCs started to show promise in clinical trials. The US Food and Drug Administration began to approve them in 2000, yet only a dozen or so are currently in use due to challenges in matching the right payload to the right antibody.

In recent years, however, significant advances have been made in the techniques needed to produce ADCs. “Antibodies have become a mature therapeutic modality,” says Professor Tate. “The linkers used to attach molecules to antibodies have also matured, but people have been using similar variations on a theme of two or three types of payload molecule, so this is an area with wide scope for innovation.”

The drugs developed by Myricx offer just the kind of novel approach the sector is looking for. They selectively inhibit an enzyme called N-myristoyltransferase (NMT), which modifies proteins and is vital for multiple specific processes cancer cells use to stay alive.

“It hits one specific point in cell biology that links into dozens of different pathways, many of which are critical for cancer cells compared to normal cells,” says Professor Tate. This means the drug can more selectively affect cancer cells, without the same kind of toxic effects seen with drugs that damage DNA, for example.

The NMT inhibitor also works over an extended period compared to other drugs. “Where most ADC payloads have an immediate effect, our drug takes up to several days before it starts to kill cancer cells, giving normal tissues ample time to recover,” Professor Tate says. “An antibody is the perfect way of keeping an NMT inhibitor where it needs to be for long enough to get the full benefit of the mechanism.”

A further key advantage is that NMT inhibitors are not dependent on cells dividing to have their effect, unlike drugs that interfere with DNA replication or cell division. This means they will also attack cancer cells that have become dormant or ‘senescent’. “If you want long-term remissions, you also need to clear out these senescent cells,” Professor Tate says.

Looking good

Initial results for Myricx’s ADCs have been encouraging, with complete and durable tumour regressions, at well-tolerated doses, in many animal models of solid cancers. Positive results have also been obtained in patient-derived organoid models.

The investment announced this week will allow Myricx’s potential therapies to move into clinical testing. The two antibody targets being given priority are against clinically validated targets for large solid tumour indications.

The funding also means that Myricx will now evolve from a largely virtual operation into a fully-fledged company, with its own laboratories and in-house R&D team in central London.

The Series A financing round was led jointly by investment firms Novo Holdings and Abingworth, together with British Patient Capital, Cancer Research Horizons, Eli Lilly, Brandon Capital and Sofinnova Partners.

From malaria to cancer

The involvement of Cancer Research Horizons, the innovation arm of Cancer Research UK, represents a continuation of the long-term support that the medical research charity has given to Professor Tate’s group. This journey began more than a decade ago, when his lab was working on NMT inhibitors as a possible treatment for malaria.

“Although we were targeting the malaria version of this enzyme, we also found molecules that were very good against the human version, and it was clear to us that this had potential as a cancer treatment,” he recalls.

"CRUK shared our vision and have stuck by us. Without their support and the support of their donors, we would not have made it to this exciting turning point." Professor Ed Tate Imperial

Cancer Research UK stepped in with Programme funding to support work on how this might function as a therapy, and to help develop drug-like molecules good enough to take into the clinic. 

“We work in a chemistry department, and it was quite unusual for Cancer Research UK to fund groups like ours,” Professor Tate says. “But they shared our vision on the potential of our research and have stuck by us. Without their support and the support of CRUK’s donors, we would not have made it to this exciting turning point.”

Cancer Research UK is now supporting Professor Tate’s group as it turns its attention to another group of enzymes that are also involved in post-translational protein modification. “They work in a more diverse and more complex way, and there is a lot of emerging evidence that they are going to be interesting in cancer and many other diseases,” he says. “So, what we have learned working on NMT we can apply in future to this much broader spectrum of cancer biology.”

Photos: Imperial College/Jason Alden