BioWorld International Correspondent

Billing the investment as the largest venture capital round in German biotechnology since 2001, Immatics Biotechnologies GmbH raised €40 million (US$52.1 million) in a second funding round to further its pipeline of cancer vaccines based on peptides derived from tumor-associated antigens.

Immatics, which was spun out of the department of immunology at the University of Tübingen in 2000 to commercialize the work of Hans-Georg Rammensee and colleagues, raised more than €14 million in its Series A round. The company, also based in Tübingen, will use the bulk of the proceeds from the current round to progress its two most advanced programs.

It plans to move its lead vaccine, IMA901, into a Phase II clinical trial in renal cell carcinoma in the second quarter of this year. IMA910, a preclinical vaccine candidate in development for colorectal carcinoma, is next in line. "I expect it to get to the clinic by the end of the year," Immatics chief medical officer Juergen Frish told BioWorld International. Two other programs are at an earlier stage of preclinical development.

Each of Immactics' vaccines contains multiple peptides - called Tumaps - that are highly conserved in tumor antigens identified from patient samples. IMA901, for example, contains 10 such peptides, which were identified from a population of about 50 patients with renal cell carcinoma.

To be included in the preparation, each individual peptide has to be highly conserved, to be highly immunogenic and to be part of an expressed protein that has an important functional role in the tumor cell. The presence of multiple epitopes derived from different antigens ensures that the targeted malignant cells do not have an obvious escape route.

Each vaccine preparation contains peptides that correspond to Class I and Class II HLA antigens, to ensure a cytotoxic T-lymphocyte response and a T-helper cell response to the vaccine, respectively.

The company conducted a Phase I clinical trial of IMA901 directly, without first performing animal experiments, because of the species specificity of HLA repertoires. "Things that are happening in a mouse are not easily translated into a human," Frisch said. The current version of IMA901 targets tumors in individuals who are HLA-A2 restricted, a phenotype strongly represented in U.S. and European populations. If successful, additional versions will be generated to cover other populations, Frisch said.

The first-in-man study did provide grounds for optimism, although it only was powered to demonstrate safety and tolerability. "We found very promising indications there might be early signs of efficacy in this trial," he said. "I know it's very hard to interpret Phase I data in terms of efficacy."

The peptides are administered, along with an adjuvant such as Granulocyte Macrophage Colony-Stimulating Factor, via injection into the skin. Dendritic cells take up and present the antigens on their cell surface and then migrate to the lymph nodes where they activate T cells via the HLA-peptide complex expressed on their cell surface and via specific co-stimulatory molecules found on their surface.

The first trial involved a course of eight injections administered over about 10 weeks. The upcoming Phase II trial, which will recruit more than 70 patients, will involve up to 17 injections delivered over nine months. The data should become available by late 2008, Frisch said, by which time Immatics would be ready to partner the program.

Although patients with renal cell carcinoma recently have gained new chemotherapy options, namely Sutent (sutinib) and Nexavar (sorafenib), which are marketed by New York-based Pfizer Inc. and by Emeryville, Calif.-based Onyx Pharmaceuticals Inc. and its partner Leverkusen, Germany-based Bayer AG, respectively. Some may relapse after therapy or no longer derive benefit as efficacy declines. Immatics therefore is positioning IMA901 initially as third-line therapy, after surgery and chemotherapy. But if it can demonstrate efficacy with minimal side effects, it may be able to address a broader patient population.

The financing round was led by DH Capital GmbH & Co. KG and OH Beteiligungen GmbH & Co. KG, which represent the interests of software entrepreneur Dietmar Hopp, an active investor in several German biotechnology companies. Other new investors included Kuwait-based National Technology Enterprises Company and Frankfurt, Germany-based KfW Bankengruppe. Existing backers London-based 3i plc and Munich, Germany-based Wellington Partners also participated. Immatics has sufficient funding for the next three and a half years, Frisch said.