LONDON - The U.K.'s latest start-up, Enzacta Ltd., raised £2 million for the discovery and development of targeted chemotherapies for cancer.

The company said it has an integrated technology base, or “toolkit,“ for targeting agents, enzymes, clearance agents and drugs. Its lead program is expected to enter clinical trials later this year.

Jon Dickens, Enzacta CEO, told BioWorld International, “Our focus is on the discovery and development of therapies which have site-specific effects. We will achieve this by combining prodrugs with targeting agents. Conventional tumor targeting with antibodies has been around for years. The problem is that this approach is limited by the toxicity of the cytotoxic agent.“

Enzacta's treatment will consist of four components: a targeting agent, a prodrug, an enzyme and a clearance system. Following administration of the prodrug, the enzyme is delivered to the tumor site by the targeting agent. The enzyme then converts the prodrug to an active cytotoxic drug, while the clearance system removes any of the prodrug that is not localized to the tumor.

“As a result, far higher levels of cytotoxic are delivered to the tumor, with fewer side effects,“ Dickens said.

The company is based on the work of Kenneth Bagshawe, a U.K. oncologist and the originator of antibody-directed enzyme prodrug therapy. However, Enzacta also is filing for patents on a broad-spectrum targeting agent, a macromolecule that Dickens said can locate and lock on to all solid tumors.

“The patent is about to be published so I don't want to discuss the details, but the physical characteristics of tumors allow certain molecules to lock on,“ Dickens explained. “Animal work suggests ours is a pan-tumor molecule. It will be used to deliver the enzyme, which activates the prodrug, and should localize to primary and secondary tumors.“

Dickens, a former technical director of Chiroscience plc and one of the founders of British Biotech plc, said the toolbox approach gives Enzacta a particular strength.

“Three of the four elements have already been tested in humans, and a fourth [the macromolecule targeting agent] has been tested in animals,“ he observed. “We can mix and match the components. We can choose to apply the targeting technology to cytotoxic drugs that are already on the market to improve existing therapies. We plan to work with pharmaceutical companies to make prodrugs from existing chemotherapy agents and to improve the therapeutic window of drugs in the late stages of development. And we have novel cytotoxic compounds which we have licensed from an academic group in the U.S.“

In fact, Enzacta is planning to use a slightly different approach in its first clinical trial, a Phase II in 10 patients with either lung or breast cancer. The company will administer an established cytotoxic drug with a rescue agent, which is given to alleviate the side effects of the drug. This will be combined with an antimetabolite that deactivates the effect of the rescue agent at the tumor site.

“All these elements have been in patients before, but not in this combination,“ Dickens said.

Enzacta's initial £2 million funding has come from the venture capital company 3i plc. Dickens said, “We expect to rapidly bring in more money through deals. Ken Bagshawe and the team have been in this area for a decade or so, and he is extremely well known. We have already started to get approaches, and aim to do a range of deals. Most cancer therapies would be improved if you could widen the therapeutic window.“

Bagshawe will be a full-time employee of the company.

The company currently has 18 staff members, and expects to double that number in the next two to three years.

Enzacta is the first tenant of a new science park set up at the U.K. government's chemical and biological weapons research institute at Porton Down, near Salisbury.

“We have got a nice building and access to 350 scientists, and facilities such as libraries and instrumentation,“ Dickens said. *