Lycera's double-action immuno-oncology drug starts trials

Says RORgamma agonist 'removes the brake and pushes on the accelerator' of immune system.

Lycera has pushed the first of its RORgamma agonist immuno-oncology drugspartnered with Celgeneinto early-stage clinical testing.

Current immuno-oncology drugs are often described as "removing the brake" on a cancer patient's immune system, re-arming the body's own defenses against tumors. But Lycera claims its drugs go one step further, applying the accelerator to the immune system to rev up that response.

The promise of that double activity prompted Celgene to hand over $82.5 million upfront to claim rights to Lycera's entire RORgamma agonist portfolio in 2015, pledging another $22.5 million in near-term payments and taking an option to buy the entire company.

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The University of Michigan spinout has started recruiting patients into a phase 1/2a trial of lead RORgamma agonist candidate LYC-55716 in patients with advanced, relapsed or refractory solid tumors. The study will be used to determine the best dosing for the drug and assess its safety, as well as to look for preliminary signs of efficacy including response rates.

According to Lycera, RORgamma agonists boost the production of cytokines and amp up the cell-killing activity of T cells, while also keeping some T-cell subtypes active and alive for longer, says chief executive Paul Sekhri.

That process of reprogramming immune cells is "unique" and separates the company's candidates from other cancer immunotherapies that either stimulate the immune system or reduce immune suppression, he suggests.

LYC-55716 is also orally bioavailable, while the new generation of immuno-oncology drugs—including PD-1/PD-L1 inhibitors like Bristol-Myers Squibb's Opdivo, Merck & Co.'s Keytruda and Roche's Tecentriq—are delivered by injection.

John Nemunaitis, a specialist in targeted cancer therapies based at the Mary Crowley Medical Research Centre in Dallas, will lead the clinical trial. He reckons the profile of the drug could mean it demonstrates "single agent activity, as well as show synergy in combination with other immunotherapies."

It is estimated that about three dozen drugmakers have active RORgamma programs, but many of these are focusing on inverse agonists for inflammatory diseases such as psoriasis, drawing on data showing that the drugs can reduce levels of the inflammation-boosting cytokine interleukin-17 (IL-17).  

Along with smaller biotechs like Lycera, Nuevolution and Innovimmune Biotherapeutics, big pharma companies such as AstraZeneca, Roche, Merck and Pfizer also have R&D projects in this area. At the moment, any cancer-targeting programs are in preclinical development.