Paying the TLR Toll

Some much needed good news for the Toll-Like Receptor (TLR) space today. Merck-Serono, a division of Merck KGaA, announced it was licensing Idera Pharmaceuticals' two lead TLR9 agonists, IMO-2055 and IMO-2125.

Under the agreement, Merck-Serono agreed to pay $40 million up-front, plus downstream milestones worth approximately $380 million for the two therapeutics. IMO-2055 is in Phase I clinical trials for non-small cell lung cancer and in Phase II trials for renal-cell carcinoma. IMO-2125, meanwhile, is in Phase I clinical trials in patients infected with the Hepatitis C virus who have not responded to standard treatments such as interferon-alpha. This indication is not included in the agreement with Merck, which is centered purely around oncology applications.

To date, scientists know of 10 different TLRs in the human immune system that enable the body to detect pathogenic threats--viruses or bacteria that cause disease. Both Idera's IMO-2055 and IMO-2125 are novel activators of the TLR9 protein, a molecule found in certain innate immune cells such as B cells and dendritic cells. Along with TLR7, TLR9 activation has been the focus of much research--and hype--in recent years.

It's also been the subject of some high-profile failures. In January, Coley Pharmaceuticals and its partner Pfizer announced they were suspending development of their TLR9 agonist, Actilon, after disappointing results in two clinical trials of the molecule to treat Hepatitis C. In July, Anadys also suspended development of its TLR, ANA975, yet another anti-HCV drug partnered with Novartis, because of disappointing toxicology data in animals.

But despite the disappointing results in HCV, many believe TLRs have an important role to play in cancer treatments. Certainly Pfizer remains a believer: in November the company agreed to pay $164 million to acquire its partner to gain complete access to the technology, including a non-small cell lung cancer drug in Phase III clinical trials.

Depending on the sucess of the Merck-Serono/ Idera partnership, other pharmas may become converts too.