Nearly three years after moving its first agent into Phase I trials, Spirogen Ltd. is starting off 2007 with similar plans for a second compound.
The London-based company is focused on DNA-targeted therapies for cancer and infectious diseases, and hopes to introduce a second product to the clinic by late this year or early next.
After having spent its early years developing six products, Spirogen announced last month the appointments of a new chairman, J. Barrie Ward, as well as a U.S.-based chief business officer, Christopher Pugh.
The goal is to try to broaden our presence in the U.S.,' Pugh told BioWorld Today from his office in Philadelphia.
Spirogen was founded in August 2000 when entrepreneur Chris Martin, the current CEO, met with scientists David Thurston, John Hartley and Philip Howard, who had been working on DNA-interacting agents for more than 10 years.
Thurston serves as the company's chief scientific officer; Hartley is the director of research, biology; and Howard is the director of research, chemistry.
The company received its first round of funding in March 2001, and then a second round in May 2003. Investors have included Research Corporation Technologies and Paris-based Ipsen SA, the company's development and commercialization partner for its lead product SG2000.
The concept of the company is really based on targeting DNA sequences,' Pugh said, and developing small molecules that will penetrate through the cellular membrane and the nuclear membrane to target a specific DNA sequence and turn off that gene.'
In drug discovery, DNA is considered a superior target to RNA or proteins because large numbers of drug molecules are necessary to intercept all copies of RNA and proteins, while only two molecules of a DNA-targeted agent may be needed to stop production of a specific protein. That is because there are only two copies of any given gene per cell. As a result, therapeutic doses and, therefore, side effects, may be lower with DNA-targeted therapies than with RNA- or protein-targeted agents.
SG2000 is a dimeric pyrrolobenzodiazepine molecule that spans six base pairs in the minor groove of DNA and interacts with a Pu-GATC-Py sequence. It is based on the naturally occurring anthramycin family of anti-tumor antibiotics. It selectively crosslinks guanine residues located on opposite strands of DNA, exhibits potent in vitro cytotoxicity, and is unlike other covalent binding DNA-interactive antitumor agents because its adduct is non-distortive.
The product entered clinical development in April 2004, about a year after Ipsen licensed the product and participated in the second funding round. Ipsen and Spirogen also have a research agreement in the field of gene targeting.
The first Phase I trial of SG2000 began in the UK, and the first patient was dosed in a U.S. trial in February 2005. Currently, the agent is in four Phase I trials, three of which are in the U.S. and are being conducted by the National Cancer Institute. Cancer Research - UK is conducting the fourth trial in Europe.
The studies are evaluating SG2000 in patients with solid tumors and hematological malignancies.
Cancer Research reported in its Sept. 15, 2004, issue that early evidence suggests the compound's cytotoxicity is independent of p53 activation, which could turn out to be one of its most interesting attributes.' The mutation and expression of the p53 tumor contributes to treatment failure, as well as carcinogenesis and genomic instability.
I think it's fair enough to say we're encouraged by the results collectively,' Pugh said. About 53 patients have taken the drug through Phase I trials, and Spirogen expects SG2000 to enter Phase II development soon, but that is a decision that Ipsen will make, he added.
Two advantages to Spirogen's compounds is they have a natural ability to enter into the nuclear membrane,' and because they are small molecule agents, they should be easier to manufacture than other drugs, Pugh said.
Aside from SG2000, Spirogen is working preclinically on SG2285 and SG2057 (pyrrolobenzodiazepine dimer) for Methicillin-resistant Staphylococcus aureus infections. And in early research, it is working on targeted cancer therapies that protect healthy tissue.
Spirogen plans to partner all of its products once it's ready to file an investigational new drug application or once the products reach Phase II testing.
The company currently has 28 employees.