Mode of action

Nerve Growth Factor (NGF) and its high affinity receptor TrkA appear to play a crucial role in the generation of pain and hyperalgesia in several acute and chronic pain states. TrkA antagonism is therefore expected to be a highly effective therapeutic approach in many pain states, and to be free of the adverse effects of traditional analgesic drugs.

BXL1H5 (formerly MNAC13), a humanized antibody against TrkA, binds to TrkA receptors expressed on the surface of living cells, thereby antagonizing the action of NGF. Promising data demonstrate efficacy and long-lasting effects of BXL1H5 in several preclinical models of both chronic and acute pain.

Among BXL1H5’s potential advantages over current treatments may be an improved safety profile and higher specificity, which could translate into improved efficacy and enhanced patient compliance. Antibodies have a long half-life and also do not penetrate the blood-brain barrier, thereby avoiding effects on the central nervous system. BXL1H5 also has potential advantages over an antibody against NGF itself, including the possibility of a lower effective dose due to the reduced number of molecules that need to be targeted.

In February 2006, BioXell signed an exclusive license agreement with Lay Line Genomics S.p.A. (LLG) for the development and potential commercialization of BXL1H5 by BioXell.

BXL1H5 for the treatment of pain

TrkA, the high affinity receptor for NGF represents an interesting candidate as a target molecule for a new approach to treating chronic pain. The NGF/TrkA system appears to be a master control system in the spread of inflammation and pain, functionally placed upstream of several molecular pathways involved in the inflammatory process.

BXL1H5 is an anti-TrkA antibody with a strong therapeutic potential in the field of pain, representing a promising potential alternative to current treatments such as morphine or Cox-2 inhibitors. The BXL1H5 antibody binds to TrkA receptors expressed on the surface of living cells, antagonizing the action of NGF, TrkA’s natural ligand.

There is strong preclinical data demonstrating efficacy and long-lasting effects in several preclinical models of both chronic and acute pain. To date, various animal models have shown that anti-NGF neutralizing antibodies have a stronger analgesic effect than morphine.

About pain (Therapeutic Area)

Pain is the most common symptom for which patients seek medical assistance. Chronic pain in particular presents a huge economic and social burden, with existing treatments largely unable to satisfy medical needs. More than $24 billion in revenues were generated with pain medications in the seven major markets.

Current treatments for pain mainly include non-steroidal anti-inflammatory drugs (NSAIDs) for mild to moderate pain, and opioids such as morphine for moderate to severe and chronic pain. The opioids are notoriously associated with tolerance and dependence, while safety issues with Cox-2 inhibitors, an important class of NSAIDs, have led to market withdrawals, leaving a void in the pharmacological treatment of pain.

Development status

In 2009, the Company will complete the pharmacological package in animals and enter into the GMP manufacturing of BXL1H5. Toxicology studies are planned for 2010. An IND is scheduled for H1 2011.