Epstein-Barr virus vaccine(MedImmune LLC)

Merck & Co – known as MSD outside the US and Canada – has signed a worldwide licensing deal worth up to $922.5m with Opko Health’s ModeX Therapeutics unit for its experimental Epstein-Barr virus (EBV) vaccine. The partnership will see both companies advance MDX-2201 to an Investigational New Drug application filing, after which Merck will be responsible for clinical and regulatory activities, as well as product commercialisation. In exchange, Opko will receive an upfront payment of $50m and will be eligible for milestone payments of up to $872.5m plus royalties on global sales. There are currently no FDA approved vaccines or treatments for EBV, a common virus which infects most people at some point during their lives. Most can recover in a few weeks without treatment, and the virus usually does not cause health issues other than infectious mononucleosis, also called mono. After infection however, the virus becomes latent in the body and can be a cause for some specific types of cancer and multiple sclerosis. Based on ModeX’s ferritin nanoparticle vaccine platform, MDX-2201 presents antigens from four viral proteins involved in viral entry into host cells. These include a recombinant antigen designed from the proteins gH, gL and gp42, as well as an antigen derived from gp350. By using ModeX’s multi-targeted approach, this combination inhibits infection in two cell types, B cells and epithelial cells, which contrasts from efforts that previously focused on gp350 alone. Tarit Mukhopadhyay, vice president, infectious diseases and vaccine discovery, Merck Research Laboratories, said: “We look forward to working with the ModeX Therapeutics team to apply our experience and expertise to evaluate the potential of MDX-2201 to help protect against EBV infection and other, potentially related, conditions.” The agreement follows Opko’s recent acquisition of ModeX, a biopharma and diagnostics company founded by former Sanofi veterans Elias Zerhouni and Gary Nabel, for $300m in common stock. Zerhouni, president and vice chairman of Opko, said: “We founded ModeX to develop innovative multi specific biologics for cancer and infectious diseases that target multifactorial pathways that cause illness. “This first collaboration leverages our scientific excellence and innovative platforms along with Merck’s discovery and clinical development expertise with the goal of benefiting patients around the world.”

Epstein-Barr is among the most common viruses, but no vaccines are available to prevent its infection. Merck is joining the pursuit for a vaccine by striking a deal with Opko Health, paying $50 million for global rights to a preclinical program whose multi-pronged approach could overcome failures encountered by earlier efforts to neutralize the pathogen. Under the deal announced Wednesday, Merck receives global rights to MDX-2201, an Epstein-Barr virus candidate from Opko subsidiary ModeX. The two companies will work together to advance the molecule to the submission of an FDA investigational new drug application, after which Merck will be responsible for further development. Beyond the $50 million upfront payment, Opko could receive milestone payments reaching up to $872.5 million, plus royalties from sales if the vaccine reaches the market. Epstein-Barr virus is part of the herpes virus family. Spread through bodily fluids such as saliva, the virus can lead to infectious mononucleosis, which is sometimes referred to as “the kissing disease.” Symptoms include severe fatigue, fever, an inflamed throat, and swollen lymph nodes. Treatment is mainly supportive care to address the symptoms. Epstein-Barr virus is also associated with the development of certain forms of cancer. Much Epstein-Barr virus vaccine research has focused on gp350, a protein abundant on the virus’s surface and key to the pathogen’s ability to enter and infect cells. Opko’s MDX-2201 addresses that protein and others involved in viral entry into host cells. It was developed with ModeX’s nanoparticle vaccine platform, which can express as many as 24 copies of an engineered antigen on the molecule’s surface to spark an immune response. For Epstein-Barr, the vaccine candidate presents antigens for the proteins gH, gL, gp42, and an antigen derived from gp350. Opko says its multi-targeted approach distinguishes it from research efforts focused solely on gp350. GSK reached as far as mid-stage clinical development with a gp350-targeting vaccine. Results published in 2007 showed a 78% reduction in the incidence of infectious mononucleosis, but no efficacy in preventing asymptomatic Epstein-Barr viral infection. So far, ModeX has tested its Epstein-Barr vaccine in animals. Results from the preclinical research showed that the vaccine elicited neutralizing antibodies in mice, ferrets, and monkeys. Those antibodies blocked the virus’s entry into both B cells and epithelial cells. Science Translational Medicine published the study results last May, just prior to Opko announcing its acquisition of ModeX in a $300 million stock deal. ModeX has more in its pipeline beyond Epstein-Barr virus. The company is also developing a tri-specific monoclonal antibody as a potential treatment for HIV infection in adults and children whose disease has developed drug resistance. This molecule, licensed from Sanofi, is currently in a Phase 1 clinical trial sponsored by the National Institute of Allergy and Infectious Disease, according to Opko’s annual report. The company’s new Merck alliance lends additional validation to the ModeX platform technology. “Through the acquisition of ModeX, we broadened our technology foundation and expanded our product pipeline into new therapeutic areas,” Opko Chairman and CEO Phillip Frost said in a prepared statement. “Merck represents the ideal partner to develop and commercialize a new vaccine candidate, and we are particularly proud to enter into this high-potential agreement so soon after completing the ModeX transaction last May.” Merck joins a small but competitive group of vaccine candidates for Epstein-Barr. The National Institutes of Health last year began a Phase 1 study testing a gp350-targeting vaccine. Moderna has two messenger RNA-based Epstein-Barr vaccines in development. The most advanced of the two, mRNA-1189, addresses the viral proteins gp220, gp42, and the gH/gL protein complex. That vaccine candidate, which carries four mRNAs that encode for those proteins, is in Phase 1 testing. Meanwhile, Valneva aims to prevent infection of both B cells and epithelial cells with its preclinical contender, VLA2112, which is designed to address the proteins gp350, gH/gl, and gB. Public domain image by the CDC