Interview – UK’s Cell Medica looks to confirm T-cell therapy hopes

The UK’s Cell Medica this week became the latest company to tap investors’ growing enthusiasm for all things immuno-oncology, raising £50m ($79m) in a series B round. The cash will be used to run confirmatory trials of an autologous T-cell-based product that is being tested in a rare form of lymphoma.

Data could start to emerge in around 18 months, and the company hopes to replicate the highly encouraging results generated by the Baylor College of Medicine with a similar technology. “For patients with advanced disease there are no treatments available, so we hope this will help us take an accelerated approach to approval,” Gregg Sando, chief executive, tells EP Vantage.

Cell Medica licensed the technology in 2010 from Baylor College in Houston, Texas, where the T-cell immunotherapy has been in development for over 15 years. The work showed responses in lymphoma patients who had failed multiple rounds of chemo and radiotherapies and bone marrow transplants, with some of them going into long-term remission.

Since bringing the technology in, Cell Medica has made changes to the manufacturing process to lower costs, and now needs to run confirmatory studies with its project, called CMD-003.

The Citadel trial will run in the US, Europe and South Korea, and seek to recruit 30 patients with advanced NK/T-cell lymphoma. This tumour type was chosen because all patients will express the Epstein Barr virus (EBV) antigen – the target for CMD-003.

“This is a logical first target for us. We will move into the larger lymphoma subtypes, where the percentage of patients with malignant cells expressing EBV antigens can be as low as 20%, but we will demonstrate the concept here first,” says Mr Sando.

Prevalent target

The EBV is well studied for its oncogenesis, and the majority of lymphoma patients will receive EBV screening because it is associated with different patterns of disease progression. Most people are latently and harmlessly infected with the virus, and carry T-cells against it. However in many cancers the malignant cells express the viral antigen, suggesting that T-cells have been deactivated.

“We take these T-cells and essentially rescue them. We take them out the body, teach them to recognise the antigen again, make them highly functional and expand them a thousandfold, and put them back in the patient,” Mr Sando says.

Five treatments can be created from one extraction of blood, and “vein to vein” takes about 40 days.

In its study, Baylor reported 11 complete responses out of 21 patients with relapsed or resistant disease. And 28 of 29 high-risk or multiple-relapse patients remained in remission at a median of 3.1 years. The results were published in the Journal of Clinical Oncology earlier this year.

In advanced NK/T-cell lymphoma median survival is six months. If the results from Citadel are close to these findings, talks with regulators about the pathway to approval will begin in 2016, Mr Sando says.

Pushing forward

Citadel will cost about $25m, Mr Sando estimates, while a second confirmatory trial is also planned. The new financing will also fund the pipeline: Cell Medica has other T-cell therapies in development, and an announcement on a second candidate should be made early next year.

Impressive results with similar technologies from the likes of Juno Therapeutics, Kite Pharma and Novartis have raised huge hopes for this field, and similarly spectacular amounts of money. Kite this week unveiled a $138m follow-on offering, a mere five months after banking $147m from an IPO.

Cell Medica’s more modest sum probably reflects, in part, a simpler approach. The group is focusing on cancers associated with oncogenic viruses using naturally occurring T-cells, as opposed to genetically modifying T-cells to target cancers that express human tumour-associated antigens.

A potential downside is that Cell Medica has to rely on the patents protecting its manufacturing process, although the complexity of this undoubtedly raises substantial barriers. Mr Sando does not believe that the company has any direct competitors at this stage.

While Cell Medica might not have amassed the war chest of its US rivals, £50m represents the third-biggest venture financing raised by a UK-based drug developer in the past five years, EvaluatePharma data reveal. Considering that this month also saw the collapse of Dendreon, which notoriously failed to make a commercial success from the first US cell therapy approval, it is clear that for investors this field has lost much of its toxicity (Lessons from Dendreon’s slow-motion car crash, November 10, 2014).

Huge expectations are being built on hopes that regulators will allow these therapies on the market in the near future, fuelled by the response rates being generated in previously untreatable cancers.

Of course these technologies still have some way to travel, on safety as well as efficacy. Cytokine release and off-site toxicities remain issues for the T-cell engineering approaches, for example; encouragingly, Baylor did not report any infusional issues and only minimal toxicities from the 50 patients it treated.

With T-cell therapies likely to be a main focus at the ASH conference next month, updates on the field will be followed with interest.

To contact the writer of this story email Amy Brown in London at [email protected] or follow @AmyEPVantage on Twitter