INTERCEPT Blood System for Red Blood Cells TM
IN DEVELOPMENT Cerus is currently developing the INTERCEPT Blood System for Red Blood Cells to reduce the risk of transfusion-transmitted pathogens, as well as decrease the potential for adverse transfusion reactions.
Mechanism of Action The INTERCEPT Blood System for Red Blood Cells uses a proprietary compound, amustaline and a quencher glutathione (GSH), in a pH dependent reaction to crosslink nucleic acids to inactivate infectious pathogens and leukocytes in red blood cell components. When amustaline is added to RBCs, the compound rapidly passes through cell membranes, including viral envelopes, and intercalates into helical regions of the nucleic acids of pathogens and leukocytes as shown in Figure 1. Figure 1. Mechanism of Action
1
2
Targeting
3
Reaction
Degradation
LINKER EFFECTOR
ANCHOR
S-303
S-300 (UNREACTIVE)
AMUSTALINE
DOCKING
PERMANENT CROSSLINKING
(1) Amustaline rapidly passes through membranes to target nucleic acids and (2) intercalate or “dock” between nucleic acid base pairs. (3) Degradation yields unreactive by-products (S-300).
Inactivation of Bacteria and Viruses in Red Blood Cells1-3 The INTERCEPT Blood System for Red Blood Cells reduces a variety of pathogens including gramnegative/positive bacteria, enveloped/non-enveloped viruses, and parasites. Virus
(enveloped and non-enveloped)
Log Reductiona
Bacteria
(gram-negative, gram-positive)
Adenovirus type 5
>7.4
Escherichia colib
Bluetongue virus
≥5.0
Serratia marcescens
BVDVc (model for HCV)
>4.8
Staphylococcus aureusb
HIV-1, cell-associated
>5.9
Yersinia enterocolitica
DHBV (model for HBV)
>5.1
Log reduction is calculated as Log (untreated titer/post-treatment titer), when titer is expressed at 10x/mL. One replicate of E. coli and one replicate of S. aureus used blood that had not been leukoreduced. c Bovine Viral Diarrhea Virus a b
1. Henschler R, et al. 2011. Transfus Med Hemother 38:33-42. 2. Mufti N, et al. 2010. Biologicals 38(1):14-19. 3. D Hanson et al. 2015. Transfusion, 52:225A.
Log Reductiona ≥6.7 5.1 5.1 ≥6.8
IN DEVELOPMENT Clinical development program In 2016, the Biomedical Advanced Research and Development Authority (BARDA), awarded Cerus a 5-year contract entailing potential funding of up to ~$180M to support the development of the INTERCEPT Blood System for Red Blood Cells. Initial funding of ~$30M will include the support of a clinical trial to assess the safety and efficacy of INTERCEPT Blood System for Red Blood Cells in Puerto Rico, a region impacted by the current Zika virus epidemic. Subsequent option periods, if exercised by BARDA and completed, would extend the contract for up to 5 years with an additional $150M to cover activities related to possible US phase III clinical trials, manufacturing, and next generation INTERCEPT Blood System for Red Blood Cells. Cerus reported positive results of the INTERCEPT Blood System for Red Blood Cells from a European Phase III clinical trial in January 2015 and from a U.S. Phase II clinical trial in December 2014, as detailed below: Table 1. INTERCEPT Blood System for Red Blood Cells clinical trials
Figure 2. INTERCEPT Blood System for Red Blood Cells process
Study Description
Primary Endpoint
US Phase II Randomized, controlled, single-blind, 2-period crossover study to assess the recovery and lifespan of radiolabeled autologous S-303 treated red blood cells (n=26)
RBC Recovery ≼75% at 24-hours post-transfusion
European Phase III Randomized, controlled double-blind study to evaluate the safety and efficacy of S-303 RBC components in patients requiring transfusion support of acute anemia during or shortly after cardiac surgery (n=50)
Mean hemoglobin content per RBC unit
Treatment Process Filter Set
Integrated Processing SetSTEP
RBC (SCD) S-303
GSH
Š 2016 Cerus Corporation. MKT -EN 00254 v1.0.
SCD*
1
Mixing Bag Containing 140mL Processing Solution
2
3
Incubation Bag
4
Storage Bag Containing 90mL SAG-M
Step 1 Using the Reconstitution Set, collected RBC and reagents, GSH and Amustaline (S-303), are added to the Mixing Bag containing a diluent. Step 2 The RBC with reagents are transferred to the Incubation Bag for 18 - 24 hrs at room temperature. Step 3 Treatment solution is removed by centrifugation and expression from Incubation Bag. Step 4 RBC are transferred to Storage Bag containing SAG-M. * Sterile Connection Device
Global Headquarters Cerus Corporation | 2550 Stanwell Drive | Concord, CA US 94520 | +1 855 835 3523 www.cerus.com
European Headquarters Cerus Europe B.V. | Stationsstraat 79-D | 3811 MH Amersfoort | The Netherlands | +31 33 496 0600
The INTERCEPT Blood System for Red Blood Cells is in development and is not approved for sale.