EP Vantage Interview - F-Star to push forward with bispecific antibody pipeline


With interest in bispecific antibodies booming, F-Star has picked an opportune moment to accelerate its search for an internal pipeline of therapeutic candidates. The last few years has seen several research and product specific deals struck between various players, culminating in Amgen’s $1.2bn takeout of Micromet earlier this year, suggesting real progress is being made in attempts to boost the potency and expand the scope of traditional monoclonal antibodies.

F-Star, which today announced a series of new senior appointments and an expansion of its research operations, is hoping to ride that wave by moving beyond a platform technology play to a company with products. Incoming chief executive John Haurum, previously of Imclone Systems and a co-founder of Danish biotech Symphogen, tells EP Vantage he hopes to have a lead candidate selected for pre-clinical development by the end of the year and to follow that up with a third collaboration with a larger player; existing research deals with Boehringer Ingelheim and Merck Serono are also progressing well, he says.

Specific progress

The potential of bispecific antibodies, which can bind two separate targets on an antigen concurrently, has been long appreciated but their development hobbled by complex manufacturing process and issues such as short half lives and immunogenicity. The last few years has seen notable progress, however, including the first such agent to make it to market – Removab or catumaxomab, a treatment for the rare condition malignant ascites originally developed by Trion Pharma and sold by Fresenius, received European approval in 2009.

Through its swoops on Micromet Amgen now owns probably the most advanced bispecific antibody in development, blinatumomab, which is in phase II development for acute lymphoblastic leukaemia, although the acquisition would also have been struck for the company’s BiTE platform (Amgen BiTEs at the chance to buy Micromet, January 26, 2012).

By eliciting a T-cell response – which traditional therapeutic antibodies cannot do - as well as binding to tumour-associated antigens, Micromet’s antibodies have a dual mechanism of action. Others working with bispecifics are attempting to create antibodies that bind to different regions of the same antigen, thereby more effectively blocking growth and proliferation pathways.

Through its technology, Austria-based F-star can produce antibodies that can bind with both the variable region, employed by traditional antibodies, and the constant or Fc region. What the company has termed Fcabs, F-star has developed a library of engineered Fc-antibodies that can then be combined with the variable region of a traditional antibody, to generate a bispecific.

“So Avastin for example, would bind VEGF in the variable region. We could take a constant region from our library that might bind with another anti-angiogenesis receptor or another receptor tyrosine kinase, and that would replace the normal constant region of Avastin,” Dr Haurum says.

In this way, full length antibodies can be created from existing, validated antibodies and F-star’s library of Fcabs.

Overcoming hurdles

F-Star believes it has managed to overcome many of the challenges that have held back progress with some bispecifics, that have required new domains or scaffolding structures that complicated manufacturing and created pharmacokinetic and stability issues. The manufacturing process will be very similar to normal monoclonal antibodies, and relatively simple for bispecifcs, which sets the company apart from others in the field, Dr Haurum says.

They also look very similar to traditional products, which overcomes issues of pharmacokinetics and stability.

“From the body or immune system’s perspective, there is not much difference between ours and conventional monoclonal antibodies,” he says.

The two deals struck in 2010 and 2011 with Boehringer and Merck Serono shows the company is already generating interest in its technology. Both multi-target deals, F-Star is still in the process of feeding candidates into the companies’ pipelines, although none have entered the clinic at this stage.

Mr Haurum would like to strike one more similar deal in the next 12 to 18 months, although he says the search for interested parties has only just begun.

“We would like something that provides strategic value for the company, although its shape has not been specifically designated. It could be something similar, or it could be a more strategic collaboration,” he says.

Pushing forward

The main focus in the coming months will be selecting a lead candidate for pre-clinical development that F-Star can progress internally.

“It is likely to be in cancer, although we are not disclosing the target at this stage. Hopefully within 2012 we will be able to select a lead candidate,” Mr Haurum says.

Having raised €34m in venture capital over the last five years, the company has sufficient funds to get any candidate into the clinic. That is likely to take a couple of years, and at that stage further funds will be required."

We have two very good collaborations which were the first step in leveraging the value of the technology platform, but to capture full value we want to invest internally, with capital and our own efforts, to generate our own compounds. We and our investors see this as a natural evolution of the company," Mr Haurum says.

With venture capital investors increasingly keen to create exit opportunities, an internal pipeline should certainly help in this regard.

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