Biogen is paying $125 million upfront to work on InnoCare’s orelabrutinib, an oral, small-molecule Bruton’s tyrosine kinase inhibitor (BTKi) that the pair hopes can cut it in multiple sclerosis.
Biogen, much in need of some new innovation in MS given what analysts see as a lack of preparation for a patent cliff for its three key MS drugs—Tysabri, Tecfidera and Vumerity—is turning to Beijing-based InnoCare Pharma to help.
Orelabrutinib is a covalent BTKi with high selectivity and it's currently being studied in a phase 2 test for relapsing-remitting MS (RRMS).
InnoCare nabs $125 million upfront but is also in line for biobucks worth $812.5 million as well as a percentage of sales, should the therapy gain approval.
With the ability to cross the blood-brain barrier, orelabrutinib could stop B-cell and myeloid-cell effector functions in the central nervous system and, the pair hopes, demonstrate the “possibility to slow disease progression.”
“Given the complex and chronic nature of MS, we believe the unique characteristics of orelabrutinib, combining high selectivity and CNS penetrance, may translate to potential clinical advantages relative to other BTKi programs,” said Alfred Sandrock Jr., M.D., Ph.D., head of R&D at Biogen.
MS can affect the brain and spinal cord, causing a wide range of potential symptoms, including problems with vision, arm or leg movement, sensation or balance. And, while it's a lifelong condition, it can hit patients in waves, sometimes being mild and manageable and other times severe and causing considerable disability.
RRMS is the most common form of the disease, with more than eight out of every 10 people with MS diagnosed with the relapsing-remitting type, which causes episodes of new or worsening symptoms known as relapses.
These typically worsen over a few days, last for days to weeks to months, then slowly improve over a similar time period. The idea of treatment is to dampen these relapses or stop them altogether. The disease is, however, poorly understood, and many drugs can also come with unwanted side effects.
BTK inhibitors' mechanism of action is not without its baggage, as earlier drugs in the class were linked to numerous safety woes including liver toxicity, abnormal heart rhythms and low platelets. Newer versions are looking to bypass these safety concerns, and BTKs have seen growing attention of late after Sanofi picked up a new one last year in the $3.7 billion acquisition of Principia Biopharma.
Principia's team develops small molecules that bind to two proteins, ensuring that the medicine only binds to the BTK protein and not others, which they hope will lead to fewer side effects. The new biotech unit under Sanofi is testing the drug in a range of autoimmune diseases, including MS.
The data so far were a mixed bag: Last April, Sanofi posted data for SAR442168 (tolebrutinib), the drug it now owns, in a phase 2 that linked the BTK inhibitor to relative reductions in new lesions of 85% or more, but criticism of the study design means doubt remained high as the program entered the pivotal stage.
Biogen, which has put most of its eggs in the Alzheimer’s disease basket after a series of pipeline flops in recent years, will hope for once to have an easier R&D journey. The company will also hope to have better luck than it had with opicinumab, which was culled last fall in MS after failing a phase 2, the final nail in the coffin for the program. This came four years after a previous trial fail for the antibody. Biogen does have its own BTK for MS in BIIB091, though this is in phase 1.
Analysts at RBC Capital were cautious about the InnoCare deal and its prospects, in a note to clients published early Tuesday morning. “It is still […] unknown about what BTKi characteristics might optimize clinical efficacy,” the firm said.
"Our sense is that [blood-brain barrier] penetration may be necessary to drive better efficacy … However, none of these theories have been yet validated in the clinic and though many large pharma competitors have late [phase 3] programs underway, these programs are potentially still at least several years from data.”
RBC also noted that the need for the deal “suggests Biogen may still be experiencing issues such as with formulation/bioavailability with '091.”
BTKs have also notched up success in cancer: InnoCare, in fact, already has several approvals in China for orelabrutinib in blood cancers.