SPONSORS

Sponsored by

KAEL-GemVax

Jay Sangjae Kim

With its Phase III therapeutic cancer vaccine, GV1001, currently being studied in the largest clinical trial for pancreatic cancer worldwide, potential for further development of its lead candidate in other indications, and a stable financial situation, South Korea-based KAELGemVax could be one of the most exciting new companies in the oncology space.

The firm was formed in 2008 when KAEL acquired GemVax, a Norwegian subsidiary of Denmark’s Pharmexa, leading to the establishment of KAEL-GemVax as a subsidiary of the newly merged (and renamed) GemVax & KAEL. According to the company, “The founding concept was to develop a universal immunotherapy platform for cancer and other indications.”

Pancreatic Cancer
Through this acquisition and spin-out process, KAEL-GemVax acquired all rights to GV1001, one of 22 cancer vaccines currently in Phase III trials worldwide, and one of only three cancer vaccines in Phase III for pancreatic cancer, a disease with a particularly poor prognosis. The other pancreatic cancer vaccines in Phase III are: OncoTherapy Science’s OTS102, NewLink Genetics’ HyperAcute-Pancreas Immunotherapy and Cancer Advances polyclonal antibody stimulator.

The 53-site Phase III TeloVac trial of GV1001, which is being overseen by the University of Liverpool in the UK in 1,110 patients, is aiming to assess the primary endpoint of overall survival in patients with inoperable pancreatic cancer, with results expected in late 2012. The trial has been funded in part by Cancer Research UK.

GV1001 targets telomerase, an enzyme over-expressed in around 90% of all cancer types that helps maintain telomere length in dividing cells and is required for tumour growth. The oncovaccine is a 16-amino acid peptide fragment of the human reverse transcriptase (hTERT) catalytic subunit of telomerase, and generates a T-helper lymphocyte response against cells expressing hTERT.

KAEL-GemVax notes that it differs from NewLink Genetics’ vaccine in particular, as “HyperAcute-Pancreas is a personalised cell vaccine, which involves the harvesting and processing of pancreatic cell lines from patients, whereas GV1001 is a standardised peptide vaccine”.

Current therapies for pancreatic cancer include Lilly’s nucleoside analogue Gemzar (gemcitibine) and Roche’s EGFR inhibitor Tarceva (erlotinib).

Other Indications
However, it is not just in pancreatic cancer that GV1001 has potential. In October 2011 the company released results from a Norwegian Phase II trial of the vaccine in non-small cell lung cancer (NSCLC), which showed improved progression-free survival in patients with an immune response.

KAEL-GemVax has since revealed plans to initiate a multinational, multicentre NSCLC Phase III trial, which includes the US, Russia, Italy, Norway, Sweden, Hungary, Poland and South Korea. Recruitment for this trial will begin in the first quarter of 2012.

GV1001 is also in a Phase II trial for chronic lymphocytic leukaemia, and the company plans to continue further development with the vaccine for melanoma as its next priority (most likely in combination with Merck & Co’s Phase III melanoma candidate Temodar (temozolomide)).

Malaria In addition, the company is working on another promising project, VaxOnco’s (KAEL-GemVax holds 75% of VaxOnco) ex-Epimmune malaria vaccine EP1300, which entered Phase I in September 2010 and completed enrollment in November 2011. EP1300 is a polyepitopebased DNA vaccine for the prevention of malaria caused by Plamodium falciparum, the most serious form of the infection. KAELGemVax has a licensing agreement with Ichor Medical Systems to combine the vaccine with Ichor’s TriGrid electroportation delivery system, which provides improved intracellular delivery and is expected to enhance potency.

Funding

KAEL-GemVax has been relatively free from the fundraising pressures faced by most similar stage bioventures, thanks to its position as part of a large listed group. In addition to wholly owning GemVax, it also holds 75% of VaxOnco, a company specialising in vaccines, and acquired the US firm Epimmune in 2009. In July 2011, the firm raised approximately $30 million from Susquehanna International Group in the form of a convertible bond through GemVax & KAEL.

The company told Scrip last year that it is actively exploring the possibility of an IPO on Nasdaq in the US once the TeloVac trial had completed, though the plans were not firm. KAEL-GemVax believes that with the TeloVac trial having been recommended to continue three times by an independent panel, the planned initiation of a Phase III trial of GV1001 in NSCLC and the further potential of GV1001 in other indications, it has the potential to be an attractive investment interest.

Sponsored by

PCI Biotech

Per Walday

PCI Biotech, named for its lead technology, a light-directed drug delivery system called Photochemical Internalisation (PCI), has based its research and strategy on its patented photosensitiser, Amphinex, which has huge potential in many targets and has put the company in a strong research position. PCI Biotech was originally founded in 2000 as a subsidiary of the Norwegian pharmaceutical company Photocure, which has been one of the pioneers of photodynamic therapy. Identifying a major opportunity to commercialise PCI, the drug delivery technology that PCI Biotech had developed, the company was demerged and listed on Oslo Stock Exchange, the Axess list, in June 2008 – one of just three successful biotech listings in Europe that year.

Since then, the company has gone from strength to strength, seeing rapid progress with its lead programme, securing itself in a stable funding position and gaining recognition from organisations such as the Norwegian Research Council.

PCI Biotech completed its first Phase I/II study in 2011, where Amphinex was used in combination with the cancer drug bleomycin for the treatment of head and neck cancer, breast cancer and osteosarcoma. The trial was conducted in the UK in 19 patients with local recurrence or metastatic, cutaneous or subcutaneous malignancies. The primary objective was to assess the maximum tolerated dose. Amphinex was well tolerated across several dose levels. A strong tumour response was observed in all patients, and complete clinical regression of the treated target lesions in a majority of the patients that completed two efficacy assessments. The majority of patients in the trial were suffering from squamous cell carcinoma of the head and neck.

PCI technology
PCI is a technology for light-directed drug delivery which enables therapeutic molecules to be introduced in a biologically active form specifically into diseased cells. The basis of the PCI technology is a light-induced rupture of endocytic vesicles pre-treated with proprietary photosensitisers, releasing endocytosed molecules into the cell cytosol.

The key advantage of PCI Biotech’s technology is that it can enhance the delivery of all molecules taken into the cell by endocytosis. This includes most types of macromolecules, drugs carried by antibodies or nanoparticles, as well as some small molecule drugs. Other advantages of the technology include:

• It can be administered systemically
• It can, in many cases, give effect preferentially in diseased tissues (eg, tumours)
• It generally has low toxicity in nonilluminated areas
• It can be applied to molecules already in clinical use for cancer It has the potential to improve the efficacy both of existing drugs and of emerging treatments.

PCI Biotech is researching the technology’s potential to enhance the effects of other cancer drugs, such as docetaxel, gemcitabine and erlotinib, as well as the use of Amphinex with vaccines.

The unique attraction of the company and its technology is that it is applicable within many areas, such as gene therapy, protein therapy, oligonucleotide therapy, chemotherapy and nanomedicine. In all of these areas, it can be used to enhance and target drug delivery, make macromolecule delivery more efficient and make possible the therapeutic use of molecules that it has previously not been possible to use, perhaps because of too low delivery efficiency, or too high toxicity in non-target tissues.

In oncology in particular, where the emphasis is increasingly on targeted therapy with reduced side effects and treatment times, PCI’s recently completed Phase I/II study has shown it can meet these criteria. The company plans to initiate a Phase II trial of Amphinex in combination with bleomycin in 2011/2012.

Sucesful IPO
The completion of an IPO in 2008 was the company’s first financial highlight, when it raised NOK60 million ($11.9 million) with its initial public offering and listed on the Oslo Stock Exchange, the Axess list. Though this was NOK40 million off the firm’s target of NOK100 million, it was nonetheless a big achievement in a year when only three European biotech companies managed to float. Since then, PCI Biotech has raised a further NOK90 million in an oversubscribed rights issue in 2010.

In May 2011, the company was awarded a NOK10.85 million grant from the Research Council of Norway for the project, ‘Immunological effects of photochemical internalisation – local treatment of cancer with metastasis’. The project goal is to document that PCI Biotech’s PCI technology induces immunological mechanisms in cancer treatment, and to develop a treatment regime for optimal use of this mechanism. It was initiated in Q3 2011 and will run for three years, with the grant covering 35% of the project costs.