BASEL, Switzerland—Global pharmaceutical giant Roche is in the process of acquiring Adheron Therapeutics, a privately held biotechnology company that has developed a method of disrupting immune cell adhesion through a cell surface protein called Cadherin-11. The objective, according to Berkeley, Calif.-based Adheron, is to develop potential treatments for a variety of inflammatory and autoimmune diseases such as rheumatoid arthritis and fibrotic diseases.
Adheron’s SDP051, a humanized monoclonal antibody that targets Cadherin-11 (Cad-11) in rheumatoid arthritis (RA), has completed Phase 1 of clinical development that confirmed safety and tolerability in healthy volunteers. The antibody could provide a complement to existing therapies, said Adheron CEO Hari Kumar, which is why Roche is paying $105 million up front and as much as $475 million in milestone payments to take over the company, as toxicity studies continue ahead of Phase 2 trials with SPD051, according to BioWorld Today.
Kumar expects that Roche will build on work done at Brigham and Women’s Hospital and Harvard Medical School that shows that Cad-11 causes RA and other fibrotic conditions. Cad-11, a surface protein that acts as an “adhesive” between cells, is expressed on fibroblasts in the skin and lungs, and fibroblast-like synoviocytes (FLS) in the joints. It is a key mediator of joint destruction in rheumatoid arthritis, and is also an important contributor to fibrotic pathology, he added.
Cad-11 is expressed at high levels at injury sites in RA, resulting in further joint damage. By blocking Cad-11, cells can be kept from aggregating. RA, an autoimmune disease that affects about 40 million people worldwide, causes joints to become chronically inflamed, painful and swollen—patients can become increasingly disabled as cartilage and bone are damaged. RA patients are often treated with a number of medicines, combining protein-based biologic therapies with methotrexate (MTX). Kumar believes that as many as half of the patients are not responding properly to available drugs.
A paper published in November 2013 in Oncotarget has linked Cad-11 to cancer, especially tumors derived from epithelium. Cad-11 can also cause cancer cells to migrate to other cells, according to the paper. Kumar described Cad-11 as a “unique identifier for a type of cells called myofibroblasts,” that are “not normally present in normal, healthy individuals,” but manifest as a result of the body’s inflammatory signal. Researchers at Georgetown University have been examining Cad-11’s role in cancer, especially pancreatic and triple-negative breast cancer. Kumar believes that Adheron’s research could end up targeting “a whole bunch of interesting indications in the future” for Roche.
John Burt, chief executive of Abzena, said that Roche’s $580 million acquisition of Adheron boosts the potential for future royalties and license fee payments to Adheron. Roche CEO Severin Schwan told Reuters that the arrangement meshes with Roche’s strategy of acquiring small companies when Roche says that prices for “medium-sized biotech companies with experimental drugs in late-stage development have soared out of reach,” and it is continuing “to look at smaller acquisitions of firms with early-stage compounds several years from reaching the market,” according to an article by Michael Shields.
Formerly called Synovex Corp. when it was launched in 2006, Adheron was founded by Michael Brenner and David Lee of Brigham and Women’s Hospital and Harvard Medical School around discoveries into the function of Cad-11 as an adhesive control part of cell-cell interaction—the company relaunched as Adheron in 2013. CEO Hari Kumar joined the company in September 2013, along with Chairman Robert Baltera, both of whom had been on the executive team of San Diego-based Amira Pharmaceuticals Inc. Adheron, which operates largely as a virtual company, has investors that include Health Care Ventures, MedImmune Ventures, Partners Innovation Fund, Amgen Ventures and SROne.
Kumar concluded, “We are very excited about this acquisition, as it is an important step towards the development of breakthrough medicines in the area of inflammation and fibrosis. This deal brings together Adheron’s deep understanding of the underlying science of Cadherin-11 with Roche’s vast experience in researching and developing next-generation medicines. We are proud to move our promising investigational medicine to the next level and into a new home at Roche.”
In other recent Roche news in the autoimmune arena (at least for those who hold to the prevailing theory that multiple sclerosis is an autoimmune disease), the company announced in early October data from three positive, pivotal Phase 3 studies of ocrelizumab in people with relapsing multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS). Data from two identical studies (called OPERA I and OPERA II) in people with relapsing MS, which affects approximately 85 percent of people with MS at the time of diagnosis, showed ocrelizumab was superior to interferon beta-1a (Rebif), a well-established MS therapy, in reducing the three major markers of disease activity over the two-year controlled treatment period, according to Roche.
In a separate study (called ORATORIO) in people with PPMS, a form of the disease marked by steadily worsening symptoms and typically without distinct relapses or periods of remission, ocrelizumab significantly reduced the progression of clinical disability sustained for at least 12 weeks (the primary endpoint) and 24 weeks (a secondary endpoint) compared with placebo. Additionally, the study met other secondary endpoints of reducing the time required to walk 25 feet, the volume of chronic inflammatory brain lesions and brain volume loss.