Novel oncology therapies presented at Genesis 2010

18 Jan 2011

The prestigious biotechnology conference, Genesis, has taken place in London each December since 2001. This tenth anniversary meeting was the first such conference following the merger of the London Biotechnology Network with ERBI, its partner organisation for the East of England, to form One Nucleus; the programme was again put together by the indefatigable Tony Jones, now director of business development at One Nucleus.

Genesis 2010 took place in the Queen Elizabeth II conference centre in Westminster on Thursday 9 December. It thus coincided with the controversial vote in the UK parliament on the raising of tuition fees, an event that many delegates followed closely, concerned for the effect of these developments on the country's vital higher education and academic research sectors. Outside the political sphere, however – and, hopefully, much less controversially – the importance of cancer for the biotech sector was highlighted by the inclusion on the programme of a themed session on the development of novel oncology therapies.

This well attended session was chaired by Philip Oliver, Executive Director for Global External R&D for Eli Lilly in Europe. Oliver began the session by introducing Lilly's innovative, decentralised model for drug development. Lilly, the tenth largest pharma company worldwide has since 2004 decentralised much of its pre-clinical development portfolio via its Chorus development engine, designed to take drug development candidates to clinical proof of concept as quickly and cheaply as possible. Thirty drug development projects have been initiated through the Chorus engine since it was set up, covering most of Lilly's therapeutic areas, including oncology. "This approach fills a gap in the development pipeline between lean, specialist biotech companies and large pharma", said Oliver. "It can suit candidate molecules for oncology very well". He went on to introduce briefly the three biotech companies represented in the session and the technologies that they were to present: immuno-therapeutics, small molecule gene silencing, and fusion proteins.

The first speaker was Satu Vainikka, CEO of ValiRx, a London-based company that specialises in the development of therapeutic and diagnostic products for cancer. The company's flagship technology is the GeneICE™ platform which was developed by Imperial College, London and Cancer Research Technology, the technology development arm of Cancer Research UK. Imperial spun out the company Cronos Therapeutics to exploit this development; Cronos was bought by ValiRx in 2006 and runs it as the independent unit ValiPharma. This technology exploits the fact that gene expression is controlled by small chemical changes to DNA sequences and to the proteins that associate with them. In particular, acetylation of basic lysine residues in histones – the proteins that DNA binds to form the compact structure of chromatin and, thus, chromosomes – causes the DNA to "unwind" enough to allow gene expression, whereas histone deacetylation causes the chromatin to condense and prevents expression.

Cancer is caused by aberrant gene expression. GeneICE™ technology "turns off" genes that are over-expressed in cancer by mimicking the natural process of histone deacetylation. This involves a class of enzymes known as histone deacetylases (HDAC). GeneICE™ consists of a combination of a peptide that binds selectively to the target gene and another that recruits the patient's HDAC enzymes to the gene, silencing it by histone deacetylation. The company's first candidate molecule, VAL 201, is likely to enter clinical trials for androgen independent prostate cancer in 2011.

James Noble, CEO of Oxford-based Immunocore, presented his company's T-cell receptor based technology for targeting and killing cancer cells. "Antibody based therapies have dominated oncology since the development of Herceptin, but there is still a shortage of cancer-specific antibody targets", said Noble. "Our solution is to use T-cell receptors, which can target any protein." There are many challenges to developing these proteins into therapeutic agents, however; they become highly unstable when solubilised, their affinity is low, and they have no intrinsic effector function. Immunocore's scientists developed methods for stabilising T-cell receptors by introducing a novel disulphide bond and for increasing their affinity from micromolar to picomolar levels. These modified targeting receptors were lastly linked to anti-CD3 antibody fragments to make therapeutic agents that Immunocore calls ImmTACs, which, when bound to the surface of their target cells, recruit passing T cells to destroy them. "As our antibodies and T-cell receptors are human-specific, we cannot run the traditional animal-based toxicity tests, and we had difficulty persuading regulatory agencies to allow us to start clinical trials without these", said Noble. Nevertheless, the first ImmTAC in Immunocore's pipeline, IMCgp100, entered Phase I/II clinical trials for malignant melanoma in 2010.

The third and final speaker was Hans Menssen, chief medical officer of the Swiss-Italian biotech company Philogen, founded in 1996 by the Neri brothers and still privately owned. Philogen's core technology is the fusion of antibody fragments that target solid tumours and lymphomas with proteins or small molecule drugs known to target angiogenesis. This can be applied to any disease where angiogenesis is important, including inflammatory conditions such as arthritis as well as cancer. Radioactive elements such as iodine 124 or iodine 131 can also be bound to antibodies, with applications in both diagnostic imaging and targeted radiotherapy. "We have modified antibodies in all stages of clinical development for both diagnostic and therapeutic applications", said Menssen. One of the most advanced product series is based on the antibody L19, which binds to a form of the glycoprotein fibronectin that is expressed in newly formed blood vessels in solid tumours but not in normal tissue. A fusion of L19 with the cytokine TNFa is in Phase II clinical trials for the treatment of malignant melanoma, and darleukin, an L19 - interleukin 2 fusion protein, , is being tested as a combination therapy in melanoma, pancreatic cancer, and some other solid tumours.