Sanofi will develop Principia Biopharma’s Phase I central nervous system (CNS) candidate PRN2246 as a treatment for multiple sclerosis (MS), through a collaboration that could generate up to $805 million for Principia, the companies said today.
PRN2246 is a low-dose, covalent Bruton's tyrosine kinase (BTK) inhibitor that can cross the blood–brain barrier to access the brain and spinal cord, enabling the drug to penetrate the CNS with the goal of effectively and safely modulating B-cell function without depleting B cells. According to Principia, the role of B cells in autoimmunity has been clinically validated with B-cell-depleting therapy in MS and other diseases that affect the nervous system.
Principia recently launched a Phase I trial of PRN2246 in healthy volunteers.
“Sanofi is an ideal partner for PRN2246,” Principia CEO Martin Babler said in a statement. “The agreement allows Principia to maximize the BTK opportunity in neurology with a strong partner for PRN2246 while focusing internal resources on our lead BTK inhibitor in another therapeutic area.”
Babler was referring to Principia’s lead candidate PRN1008, a BTK inhibitor in an ongoing Phase II trial development for pemphigus vulgaris, a rare orphan autoimmune disease associated with painful chronic blistering of the skin, and in Phase I for another undisclosed indication.
Principia agreed to grant Sanofi an exclusive, worldwide license to develop and commercialize PRN2246. In return, Sanofi agreed to pay Principia $40 million upfront, up to $765 million in payments tied to achieving milestones that could total $765 million, plus royalties on product sales.
The deal is expected to close in the fourth quarter, subject to customary regulatory approvals.
Principia also holds an option to co-fund Phase III development, in exchange for either increased royalties on worldwide product sales or a profit and loss sharing arrangement in the U.S.
Growing MS, Neurology Pipelines
Rita Balice-Gordon, Ph.D., Sanofi’s global head of MS/neuroscience therapeutic research area, added that the collaboration reflected the pharma giant’s strategic commitment to build its drug discovery and development pipeline in MS and neurological diseases.
MS is one of four areas of focus for Sanofi Genzyme; the other three are rare diseases, immunology, and oncology. In MS, Sanofi Genzyme markets Aubagio® (teriflunomide) and Lemtrada® (alemtuzumab), both indicated for relapsing forms of MS.
However, as of October 5, Sanofi Genzyme’s pipeline as indicated on its website listed a single MS candidate, GZ402668 (also called GLD52), a Phase I humanized monoclonal antibody designed to fight relapsing MS by targeting the human CD52 protein.
A study published in Neurology by Genzyme researchers in April 2017 showed that GZ402668 worked by binding to a different epitope on CD52 than Lemtrada—achieving similar levels of lymphocyte depletion as Lemtrada but with reduced cytokine release in vitro, suggesting a potentially improved infusion-associated reaction profile.
Sanofi Genzyme is recruiting patients for a long-term follow-up study of MS patients who participated in any of two past Phase I studies of GZ402668, TDU13475, or TDU14981 (NCT 02313285).
Principia’s collaboration with Sanofi is the South San Francisco biotech’s second with a biopharma giant launched in the past five months. On June 13, Principia joined AbbVie in announcing the start of an immunology collaboration designed to develop oral immunoproteasome inhibitors for an unspecified variety of immunological diseases. The value of that collaboration was not disclosed.