Amotosalen: Allogeneic Cellular Immunotherapies system, INTERCEPT Plasma System, INTERCEPT Platelet System, S 59

Adis CommentsCerus Corporation is developing a variety of pathogen-inactivation systems, based on its Helinx technology. Three of the systems include amotosalen [S 59] as the inactivation compound. Amotosalen is a light-activated, DNA-, RNA-crosslinking psoralen compound, which is used to neutralise pathogens. The systems that utilise amotosalen are called the INTERCEPT Platelet System, the INTERCEPT Plasma System and the Allogeneic Cellular Immunotherapies (ACIT) system. The INTERCEPT Platelet System and INTERCEPT Plasma System are two of the systems that make up Cerus' INTERCEPT Blood Systems. The other system is the INTERCEPT Red Blood Cell System, which contains S 303 as the inactivation compound rather than amotosalen. Cerus' Helinx technology is able to prevent replication of DNA or RNA that is present in pathogens but not in the blood components being treated (e.g. platelets and plasma). When added to the blood components, the inactivation agent (in this case amotosalen) crosses the membrane or cell wall of the pathogen. When activated by LIGHT, amotosalen binds to the nucleic acid of the pathogen and prevents replication. This process prevents Infection. INTERCEPT Platelet System: Cerus developed its INTERCEPT Platelet System, in collaboration with Baxter Healthcare, for use in blood centres. Platelets are an essential component of the coagulation process and may be required by patients undergoing surgery, Cancer chemotherapy, transplantation or with bleeding disorders. The system is made up of an illuminator device, a compound absorption device and a processing kit containing amotosalen. In October 2002, the two companies announced that CE Mark approval had been received for the illuminator device for the INTERCEPT trade mark Blood System. Application of this technology to platelets is the first to be approved. As it is a new technology, the system is currently undergoing process validation in accordance with European Blood Bank GMP requirements. This validation process is currently being conducted in Denmark, France, Germany, Sweden and the UK. Marketing approval applications for the INTERCEPT Platelet System have also been submitted in Australia and Canada. In addition, the regulatory submission process has begun in the US. A phase III trial (EuroSPRITE) has been conducted in 103 patients in Europe with pooled random donor platelets. The platelets were collected using the buffy coat process. Another two 20-patient clinical trials have also been conducted in Europe, as well as a 40-patient trial using platelets collected by an apheresis collection system. Cerus has also conducted a phase III trial (SPRINT) in the US. The trial was conducted in 671 patients and used platelets collected by Baxter's apheresis collection system. INTERCEPT Plasma System: Cerus is also developing the INTERCEPT Plasma System in collaboration with Baxter Healthcare. The system also combines amotosalen, an illumination device and a compound absorption device. The two companies are currently preparing regulatory applications for the INTERCEPT Plasma System for the US. This application will be followed by a submission for CE Mark designation in Europe. Patients undergoing surgery, or transplantation, or with bleeding disorders, may require transfusions of plasma, often to control bleeding. The type of plasma is stored in frozen form and is called fresh frozen plasma (FFP). The INTERCEPT Plasma System is currently in phase IIIc development in the US. Patient enrolment in the trial is still ongoing. The trial is comparing INTERCEPT trade mark Plasma System treated versus untreated FFP in 30 patients with thrombotic thrombocytopenic purpura. Allogeneic Cellular Immunotherapies system: Cerus is also investigating the potential of its Helinx technology to improve the outcome of bone marrow transplantation procedures (used to treat leukaemia and lymphoma) through the treatmatment for many forms of leukaemia and is most effective when the donor is very closely matched to the patient for the major human leucocyte antigen (HLA) groups. As part of the transplant procedure, patients receive donor T cells to improve engraftment of the bone marrow transplant and strengthen the patient's immune system. However, donor T cells expose the patient to a high risk of contracting graft-versus-host disease (GVHD) caused by the proliferation of donor T cells, which attack the patient's healthy tissue. GVHD has a high mortality rate. Cerus' ACIT system has been developed to decrease the stringency of matching donors to patients and to inhibit the ability of donor T cells to cause GVHD. Light-activated amotosalen binds and permanently crosslinks DNA, preventing replication and thus stopping proliferation of donor T cells. Phase I development is currently being conducted in this area in the US using amotosalen as the neutralising agent. Cerus completed a phase I study investigating the safety and tolerability of its ACIT system in 2001. The study was conducted in patients receiving closely matched allogeneic bone marrow transplants for leukaemia. The company is currently collaborating with the National Marrow Donor Program in order to conduct further clinical studies in patients receiving bone marrow transplants from unmatched donors. Cerus has development, manufacturing and marketing agreements with Baxter covering the INTERCEPT Blood Systems, which includes the INTERCEPT Platelet system, the INTERCEPT Plasma System, and the INTERCEPT Red Blood Cell System. Under the terms of the agreements the two companies usually share the very early development activities. Cerus then conducts preclinical and clinical trials, while Baxter is responsible for the development of the systems disposables and devices. Following commercialisation Cerus will supply amotosalen and Baxter will supply the other components of the system and market, sell and distribute the system In January 2001, Cereus announced that it has entered into a collaborative agreement with the Pharmaceutical Division of Kirin Brewery in Japan to develop and market products for stem cell transplantation based on Cerus' proprietary Helinx technology. Under terms of the agreement, Cerus and Kirin will jointly develop the products. Cerus has received an initial license fee of US dollar 1 million. In addition it may receive up to US dollar 11 million in future payments upon achievement of development milestones. Kirin will also fund all development expenses for the Asia-Pacific region and a portion of Cerus' development activities aimed at obtaining product approval in the US. Kirin will market the products in the Asia-Pacific region, including Japan, China, Korea and Australia, and Cerus will receive a specified share of product revenues. Cerus will retain marketing rights in the rest of the world, including the US and Europe.