Meeting Report: the buzz was about gene therapy

The buzz at the Phacilitate Cell & Gene Therapy Forum in Washington DC on 26 to 28 January was that gene therapy will become a mainstream activity in the global pharmaceutical industry over the next five years, driven in part by the new gene-modified cell therapies and genome editing.

The buzz at the Phacilitate Cell & Gene Therapy Forum in Washington DC on 26 to 28 January was that gene therapy will become a mainstream activity in the global pharmaceutical industry over the next five years, driven in part by the new gene-modified cell therapies and genome editing.

Not so long ago the experimental gene therapy technologies focused on the use of viral vectors encoding DNA to deliver a functional gene into a cell to replace a mutated one. The preponderance of research today is still in this modality. But recently, the gene-based technologies have come to include some of the innovative cancer therapies such as the chimeric antigen receptor (CAR) T cell therapies being developed by Novartis and the University of Pennsylvania.

The Washington DC-based Alliance for Regenerative Medicine (ARM) now describes gene and gene-modified cell therapies as comprising gene replacement technologies (viral and non-viral delivery); immunotherapies such as CAR T cells, T cell receptors and tumour-infiltrating lymphocytes (TILs); and genome editing.

A representative of the ARM told the meeting that $3 billion was raised last year for companies operating in the gene and gene-modified cell therapy space, more than five times the amount in 2013. This figure was significantly affected by a follow-on financing for Bluebird Bio Inc, which is developing gene therapies for orphan diseases, and by initial public offerings (IPO) for Kite Pharma Inc and Juno Therapeutics Inc. Both Kite and Juno are developing T cell immunotherapies. Meanwhile, UniQure NV of the Netherlands whose Glybera gene therapy was the first gene medicine to be approved in the western world, raised $91.8 million in a US IPO.

The Glybera approval was a “watershed” for the industry, Joshua Schimmer of Piper Jaffray told the meeting. The approval, issued by the European Commission in 2012, showed that it is possible for a sector which previously had a high-risk profile, to deliver a safe and effective product. Investors are now looking at gene therapy’s potential as a treatment for haemophilia, he commented.

Howard Liang of Leerink Partners LLC highlighted the cancer immunotherapy space pointing out that the experimental CAR T cell medicines have shown good activity targeting CD19, a protein expressed on B cells and on B-cell malignancies. The question now is whether the technology can be directed against different antigens in order to work in solid tumours.

This point has not been lost on Novartis whose representatives at the conference confirmed that work is ongoing on several fronts to advance its own CAR T cell technology which targets CD19. This includes reducing the cost of goods and improving the yield of vectors. It too is investigating solid tumours which would involve different vectors and antigens. In addition, the company is looking at how genome editing can be applied to metabolic disorders.

The scope of the new gene-modified cell therapies was illustrated by presentations from Lion Biotechnologies Inc and Adaptimmune Ltd.

California-based Lion has developed TIL technology which describes the use of tumour infiltrating lymphocytes to migrate to a tumour and launch an attack. The lymphocytes are isolated from a patient’s tumour, expanded, and then infused back into the patient.

Laszlo Radvanyi, Lion’s chief scientific officer, told the meeting that the technology has already shown efficacy in a Phase 2 study in metastatic melanoma.

UK-based Adaptimmue is developing T cell receptor technology which is being clinically tested in multiple myeloma, melanoma, sarcoma and ovarian cancer. Helen Tayton-Martin, the chief operating officer, told the meeting that Adaptimmune has identified more than 30 intracellular targets that are not tractable to antibodies or CAR therapies. Moreover the targets are not expressed on normal tissue.

Adaptimmune is currently in an oncology collaboration with GlaxoSmithKline Plc and in September last year raised $104 million in a Series A financing round.

In the area of somatic stem cell therapy, the creation of insulin-producing pancreatic beta cells at the Harvard University laboratory of Douglas Melton was listed as one of the most important developments in 2014. Dr Melton reported that when transplanted into mice, the cells secreted human insulin in a glucose-regulated manner raising the possibility that they might eventually be used to treat Type 1 diabetes.

Brock Reeve, executive director of the Harvard Stem Cell Institute, told conference participants that talks are underway with investors and pharmaceutical companies to commercialise the product. “Now is the time to move it out of the lab,” Mr Reeve said.

– By Victoria English and William Ellington

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