EP Vantage Interview – Apitope seeking balance with new partners

Interviews

University of Bristol spin-out Apitope Technology is gearing up for its next phase of growth.

The British biotech generates therapeutic peptides designed to specifically suppress malfunctioning parts of the immune system and restore normality. The autoimmunity specialist is already working on one early-stage lead for MS with Merck KGaA which is in phase I trials, and is now on the hunt for new partners, chief executive Dr Keith Martin tells EP Vantage.

Important endorsements

Merck got on board Apitope’s MS programme in January 2009. The £154m ($203m) deal followed preliminary data for ATX-MS-1467, in six patients with secondary progressive MS, showing signs of efficacy with no safety issues.

“The collaboration is going really well,” says Dr Martin. “We’ve got one of the top three companies in MS as an immediate source of information and help. Having a partner on board early does give you that extra flexibility and a very strong stable platform to grow from.”

Merck will take over if positive proof of principle data is reported, from 40 relapsing MS patients being recruited over the next 12 months. On traditional deal terms this would mean a likely sizable milestone payment for Apitope, although Dr Martin would not confirm any details.

“[We] hope to have data by early 2012,” says Dr Martin. “It will drive the business forward, but will also be the first proof of principle in a large population, which will help prove the platform.”

Ideal partners

That Merck was willing to get involved before proof of principle is a sign of its optimism, while the deal also provided a third source of financing for Apitope. It was struck shortly after a $10m series B round led by European venture capital firms Versalius and LRM and a $1m injection from Fast Forward, the investment arm of the National Multiple Sclerosis Society in the US.

This has left the company with enough money to last until the end of 2012.

Apitope is now seeking new partners for its technology and is already out talking to people, although Dr Martin says it is too early to say when any deals may emerge. The ideal partner would be big pharma with a target antigen, and an interest in autoimmune conditions like rheumatoid arthritis or type 1 diabetes, he says: "It’s a chance to get in early on those areas."

The company's technology can deliver candidates as quickly as some small molecule platforms, Dr Martin says, adding it took only 12 months from receiving a target antigen to discovering potential products for its Factor VIII intolerance programme.

He adds the platform can also pursue obscure diseases where few therapeutic advances have been made, like its Graves' disease programme.

Restoring the immune balance

Apitope's platform synthesizes soluble epitopes – peptide fragments it calls apitopes – that activate regulatory T-cells. The company hopes to show these apitopes can be used therapeutically to redress imbalances in the immune system associated with autoimmune illnesses like MS.

Specifically, the normal balance of helper and regulatory T-cells, which respectively activate and deactivate immune responses, is disrupted in autoimmunity. Helper T-cells mistake body parts for pathogens; for example, in MS the myelin sheath protecting nerves becomes a target for the body's own immune system.

Apitopes approach seeks to restore normality in the immune system; “reinstating tolerance”, as Dr Martin puts it.

Rather than targeting the overactive helper T-cells - a technique used by Novartis' new oral agent Gilenya - Apitope is trying to trigger only the counteracting response, activating regulatory T-cells that suppress the helper T-cells.

Dr Martin says this approach has the potential to be truly disease modifying.

“Once you switch off the underlying cause of the pathology, you will not get further pathology. Even drugs that claim to be disease-modifiers suppress large parts of the immune system,” he says.

A safer bet?

This is certainly a logical approach to autoimmunity, but redressing the immune balance will be a mammoth task, an immunological holy grail not easily achievable.

ATX-MS-1467 is based on a fragment of myelin basic protein (MBP), involved in myelin sheath formation. This apitope represents Merck's most advanced MS pipeline programme behind Movectro, the oral candidate that is struggling to reach the market in Europe due to safety concerns (Negative EU vote on cladribine leaves Gilenya strolling to the finish line, September 24, 2010).

The recent US approval of Gilenya marked the age of oral therapy for MS, although the message from the gathering of experts in this field at the Ectrims conference earlier this month was that jury is still out on the long-term safety of this powerful immunosuppressant.

Apitope hopes it will also be able to “change the treatment paradigm”, and believes that ATX-MS-1467’s potential for once-fortnightly or once-monthly intradermal administration will also be attractive.

A lot more testing is still required and the next step is proving the platform in a bigger population, so Merck can confidently progress into more gruelling phase II trials.

Apitope has a long way to go to prove its therapeutic peptides can acheive the rebalancing they promise, and finding new partners will bring greater opportunity in more diverse settings.

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