The cancer vaccine space might still be waiting for a real phase III success story, but this has not stopped Roche moving in on a couple of early-stage projects. The potential to combine these immune targeting therapies with emerging immuno-oncology molecules has prompted the Swiss pharma’s interest.
In September Roche licensed Inovio’s DNA-based vaccine INO-5150, targeting prostate cancer, and this month it signed a collaboration with Immatics to develop products targeting three cancer types, using the German company’s technology, which identifies tumour-associated peptides. After years of disappointments, another path is emerging for cancer vaccines.
Targeting the T-cells
Utilising the immune system to fight tumours is a research area still in its infancy, and potential drug candidates are few and far between. The Roche deals were struck after the company undertook a broad review of the field – it is entirely possible that more are on the way.
“We started talking to them in April 2012. Then we had to wait for them to complete their review of the space,” Paul Higham, chief executive of Immatics, says. “They were looking to find the best approach to cancer immunology; in the end, they liked our concept and our platform.”
Immatics' technology not only identifies relevant tumour-associated peptides, according to Mr Higham, it also pinpoints those that are highly immunogenic.
As well as buying rights to a phase I-ready gastric cancer candidate, IMA942, Roche is funding the company’s research into other cancer peptide antigens in gastric, prostate and non-small cell lung cancer. The work will take a couple of years, and the peptide complexes delivered to Roche could then be developed into cancer vaccines or other types of therapies, based on antibodies or T-cell receptors, for example.
Potential milestones possible under the deal could reach $1bn, while Roche has already paid $17m up front.
The pharma giant paid $10m up front to Inovio, meanwhile; as well as the prostate cancer candidate it also bought rights to the company’s hepatitis B project, INO-1800, and an option over other vaccines opportunities that might emerge from an oncology research collaboration.
INO-5150 is a dual-antigen synthetic DNA vaccine targeting two key antigens associated with prostate tumours; animal studies have shown that the agent generates strong T-cell immune responses.
Combination approach
In announcing both deals, Roche made no secret of its desire to combine the products it has accessed with other immuno-modulatory molecules in its pipeline. Its lead asset is the anti-PD-L1 antibody RG7446, which it expects to put into phase III in non-small cell lung cancer early next year.
However, a combination approach is considered to be the future in immuno-oncology, and Roche’s strategy appears to be no different (Immunotherapy steps up a gear with lung cancer and combo focus, October 3, 2013).
Mr Higham says Roche is planning to run a large phase I study with IMA942 that is likely to recruit hundreds of patients and test the vaccine with RG7446 and other molecules against immune-stimulating targets, such as CD40.
Bristol-Myers Squibb, arguably the leader in this field, is employing a similar approach with its anti-PD1 antibody, nivolumab, which is in at least eight phase I studies of 100+ patients, in combination with various other immune targeting or boosting therapies.
There is certainly a logic to combining the Inovio and Immatics know-how – which direct a T-cell response towards specific antigens – with an immune checkpoint inhibitor like nivolumab. PD-L1 is a ligand found on tumours that binds to PD-1, the so-called programmed death protein expressed on the surface of T-cells. The interaction is thought to allow tumour cells to evade a normal T-cell killing mechanism, and blocking either PD-1 or PD-L1 should effectively uncloak a tumour.
Drugs like the anti-PD-L1s should be the ideal combination for Immatics’ products, My Higham believes, in terms of boosting efficacy and limiting off-target effects. Considering the huge and wide-ranging studies that Roche is planning, data confirming this hunch are probably not too far away.
And if they are successful, cancer vaccines, long possessing potential but still plagued by disappointment, could be given a new lease of life.
To contact the writer of this story email Amy Brown in London at [email protected] or follow @AmyEPVantage on Twitter.
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