Immatics' cancer vaccine platform receives €54m vote of confidence

The late-stage cancer vaccine pipeline is set to gain a new contender late this year, when Immatics Biotechnologies is due to fire the starting gun on a large pivotal trial of its renal cell carcinoma therapy, IMA901. The private German company announced a healthy €54m ($71m) Series C fundraising today, a large proportion of which will go towards paying for the study.

Working on the principle that when it comes to defeating tumours, more is more, IMA901 targets ten novel antigens; other cancer vaccines in late-stage development such as Merck KGaA’s Stimuvax target only one. Results will not be due until late 2013 but Paul Higham, chief executive of Immatics, says the aim is to show that the vaccine can extend the life of advanced kidney cancer patients by several months over treatment with Sutent, a readout that would represent a big win in this patient population.

Multiple targets

Because tumours are so efficient at downregulating peptides, Immatics believes that by hitting multiple targets cancer vaccines will give have a greater chance of having an impact.

The company packs its cancer vaccines with anything from 10 to 15 tumour-associated peptides, which are identified by screening tumour samples using its platform technology, called Xpresident. Thousands of peptides are screened to identify those which are specific to a certain cancer type and, importantly, highly immunogenic. Therefore different off the shelf vaccines could be created for different tumour types.

“We only put in the peptides that we know definitely stimulate a very strong immune response. A lot of companies have assumed (a peptide) would create an immune response and created a product from that. We don’t take that risk,” Mr Higham says.

Throughout trials of its products the company has taken regular samples from patients to check the immune response occurring; a difficult, costly and time consuming process that other cancer vaccines companies have skipped, to their detriment, Mr Higham says.

“So we’re able to show a clear link in our product between those [patients] that respond immunologically and those that respond clinically, and that’s a really important point. As time moves on in cancer vaccines and people come to understand how critically important that is, the regulators if not demanding it are certainly going to expect to see immune response data. Otherwise you can’t prove your mode of action,” he says.

Straddling approaches

With failures still more notable than successes in the cancer vaccine space, the cash raised by Immatics today is certainly a vote of confidence in its approach. Pfizer’s exit from the space last month and the underwhelming deal terms Transgene managed to extract from Novartis all suggest considerable scepticism remains (Celldex reeling from Pfizer break up, September 6, 2010).

This is not to say that sentiment is not improving, buoyed by Dendreon’s success with Provenge and growing belief that immunotherapy will eventually play a central role in fighting cancer, alongside the targeted agents. In fact, Immatics’ phase III trial straddles the two worlds of targeted therapies and immunotherapy. IMA901 will be tested in combination with the tyrosine kinase inhibitor Sutent, considered standard of care for kidney cancer, and against Sutent alone.

Whilst Sutent has managed to delay progression free survival in kidney cancer, the agent has struggled to demonstrate any real prolongation in overall survival. In cancer vaccines the opposite has often been seen to be true, thought to be because it takes a while for the immune system to become primed by the vaccine. Small molecules get to work much quicker.

As such, a combination of the two approaches appears to hold potential. Patients with advanced renal cell carcinoma treated with Sutent are expected to live 22-23 months.

“We are looking for a survival gain of a number of months beyond that,” Mr Higham says.

Strong phase II data bode well, although the trial was conducted in a different setting, in second-line patients and in combination with an immune boosting agent, cyclophosphamide. Mr Higham says at 18 months 70-80% of patients in the trial were alive. At 18 months on Sutent, 40-50% of patients would be expected to be alive, he says.

Independent future

Immatics now has the funds to complete this trial independently. Half the cash in this series C round were raised from existing investors, including dievini Hopp Biotech and Wellington Partners.

A number of projects further behind will also be funded, including a phase II colorectal cancer vaccine on which data is due at the end of 2011 and a phase I glioblastoma candidate, which should generate data in 2012. Partners will be sought for IMA901 once the phase III data reads out, although the colorectal cancer candidate could be up for grabs after phase II data has been generated.

Still, Transgene’s experience shows that very strong data will be needed to attract decent deal terms (Transgene settles down for the long haul but did they miss an opportunity?, May 10, 2010). And not much pivotal data from the cancer vaccine space generally is due until Immatics is ready to reveal its own results (Data from late-stage cancer vaccine pipeline on distant horizon, May 12, 2010).

So while it seems real validation of Immatic's peptide-packed approach is still a few years way, the company has enough cash for the long haul.

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