Calando Pharmaceuticals, a majority-owned subsidiary of Arrowhead Research Corporation based in California, US, has announced plans to advance its lead candidate, CALAA-01, into Phase I clinical trials this year. The drug is a nanoparticle that contains small interfering RNA (siRNA) that targets the M2 subunit of ribonucleotide reductase, a well-established cancer target.
Small interfering RNA (siRNA) therapies are short strands of RNA that interfere with a particular gene, preventing it from producing its protein product - the more conventional drug target. Since its discovery, many companies have started to develop therapies based on the Nobel Prize winning RNAi technology. However, so far there are only five therapies in clinical trials and none of these were for cancer.
"This will be the first targeted, formulated siRNA therapeutic to be used in humans," said John Petrovich, Calando's CEO.
"Others are taking a non-targeted approach to cancer, but based upon our work and those that are published in the open literature, we believe that some form of targeting to cancer cells that provides for efficient intracellular uptake is essential for good efficacy."
The company is currently conducting toxicity studies in rats and monkeys and is scaling up the therapeutic manufacturing process for the trial. This will enable them to submit an investigational new drug (IND) application to the US Food and Drug Administration (FDA) shortly.
As well as the siRNA, CALAA-01 also contains a transferrin protein targeting agent on the surface of its nanoparticle delivery system. This protein is found in a variety of tumours, according to Calando, and by binding to transferrin, the nanoparticle will be taken up by the cancer cells before releasing its payload.
Its nearest competitor in the field of cancer therapies based on RNAi is Silence Therapeutics. Formerly known as SR Pharma, the UK company expects to file an IND for its cancer drug next year.
A subsidiary of Silence, called Atugen, along with partners Quark Biotech and Pfizer is currently investigating a siRNA therapy for wet Age-related Macular Degeneration (AMD). RTP-801i is currently in Phase I clinical trials.
There are several other companies utilising RNAi for its potential therapeutic benefits. Among them is Alnylam Pharmaceuticals, which was founded by the leading scientists who pioneered the discovery of RNAi. It currently has one product in clinical development - ALN-RSV01 - in Phase I trials for Respiratory Syncytial Virus.
Sirna Therapeutics was the first company to take a siRNA drug into trials. It had two drug candidates in clinical development - one for AMD and one for hepatitis C - when Merck & Co bought it this year, in a deal worth $1.1bn (€850m).
Opko was formed when Acuity Pharmaceuticals an Froptix Corporation merged in March of this year. The company has the most advanced siRNA therapy, this time to treat AMD and diabetic macular edema (DME) -bevasiranib has completed Phase II trials.
Biotech company Nucleonics has recently been cleared by the FDA to begin a Phase I trial of its RNAi based therapy for hepatitis B. Slightly different to the others, this therapy uses strands of DNA which, once in the body, produce siRNA. Dubbed expressed interfering RNA (eiRNA), the company plan to start dosing patients in June.
An Australian company celled Benitec also have a RNAi therapy, this time designed to target HIV/AIDS, in Phase I clinical development.
Although there is one therapy in Phase II trials and five in, or about to start Phase I trials, with the exception of Benitec's HIV/AIDS drug, the diseases targeted do not carry the weight of a potential cancer therapy and the industry will be eagerly awaiting the results of Calando's and Silence Therapeutics' upcoming clinical trials.