Results of Preclinical Animal Studies
Conducted with CEL-1000

Animal Studies of CEL-1000 in Disease Models: Studies in murine models established that CEL-1000 acts as a vaccine adjuvant for diverse antigens from: HIV, HSV, Hep-17 from P. yoelli, melanoma cells, and more recently another malaria peptide antigen (Charoenvit unpublished observations). In addition, as expected for adjuvants that act via the innate immune system, CEL-1000 can also confer protection against multiple diverse infectious agents, including two very different viruses (RNA and DNA) and two parasites. Other studies have also shown that CEL-1000 activates similar responses in human cells (in culture). Accordingly, CEL-1000 may have the potential to provide broad-spectrum protection prior to exposure to unknown infectious hazards in a new environment. CEL-1000 treatment would be especially useful when immunization may not be possible or CEL-1000 could facilitate immune protection until post-vaccination immunity may be established. Such a therapy would be especially useful in very high risk situations where there may be possible exposure to these infectious agents.

Studies of CEL-1000 to Determine Safety / Toxicity Profile: No toxicity has been reported with CEL-1000 following sub-cutaneous administration at the base of tail or nape of neck in several hundred mice (mainly A/J, but also C57/BL6 and some C3H and BALB/c). Mice have also been treated with multiple injections of the CEL-1000 peptide and have shown no measurable adverse effects.

CEL-1000 Structure: CEL-1000 is a modified analogue of the peptide ‘G’ TCBL which is obtained from within the human MHC II beta chain second domain (aa 135-149). It differs from peptide G because the N-terminal asparagine is replaced by aspartic acid. This alteration was incorporated to enhance the stability of the peptide. Based on site directed mutagenesis studies of MHC II-chain and/or peptide competition studies, peptide G and CEL-1000 should bind to CD4, a T-cell co-stimulator molecule.

Formulation: Presently CEL-1000 has been prepared by two companies that are experienced in making peptide in accordance with GMP requirements. CEL-1000 is formulated in a salt/sugar solution, micro-filtered, aseptically vialed in sterile vials and then lyophilized. The preparation is then ready for re-constitution and administration. HPLC studies of lyophilized material stored for up to 1 year at various temperatures were performed to evaluate the stability of these preparations.

Mechanism of action: CEL-1000 as a peptide conjugate has been shown to accelerate the humoral antibody immune responses (as measured by the formation of antigen-specific antibodies in the sera of injected animals and by culture of immune cells obtained from immunized animals) and as a free peptide to increase the protective efficacy of cellular immune response and sustain the immunity for a longer time against malaria and melanoma cancer. Mice immunized with malaria antigen in the presence of CEL-1000 developed a much higher level of protection (from Malaria challenge) than mice immunized with malaria peptide without CEL-1000. High levels of gamma interferon (IFN-g) in serum and elevated frequencies of splenic CD4+ IFN-g positive T-cells were detected in the immunized protected mice 24 hours after an additional boosting dose of CEL-1000. The protected mice displayed Th1-type antibody profiles. In a melanoma cancer model, mice immunized with radiation-attenuated melanoma cells plus CEL-1000 had 40 -50 % higher survival levels and lived longer than mice immunized with irradiated melanoma cells only. CEL-1000 has also been shown to enhance antibody production in a conjugate with another peptide, HIV or HSV using CEL-SCI’s ligand epitope antigen presentation system (L.E.A.P.S.(TM))* technology.

In addition to the ability to enhance antigen-specific protective immune responses, CEL-1000 has also been shown to be capable of promoting protective-innate immunity against malaria, and other pathogens including Herpes Simplex type 1 virus, Leishmania major and Arbo-encephalitis virus AR 86 in animal models of disease (Zimmerman, Rosenthal and Goel, Personal communication). These animal test findings demonstrate that CEL-1000 has bi-functional effects, which include a) the ability to elicit innate immune response that can then provide prophylaxis against initial exposure to unknown pathogens and b) the ability to stimulate an acquired immunity following immunization.

No L.E.A.P.S. product has been approved for sale, barter or exchange by the FDA or any other regulatory agency for any use to treat disease in animals or humans. The safety or efficacy of these products has not been established for any use. Lastly, no definitive conclusions can be drawn from these early-phase, preclinical-trials data involving these investigational products.

* L.E.A.P.S. is the trademark of CEL-SCI for this investigational platform technology, and this proprietary name is subject to FDA review.