-ARIUS report new data and program updates on cancer stem cell targeting
TORONTO, April 15 /PRNewswire-FirstCall/ - ARIUS Research Inc., (TSX: ARI), a biotechnology company discovering and developing the next wave of antibody therapeutics, today announced that it will be presenting new findings and program updates related to its CD44, TROP-2, CD59, and CD9 antibody programs at the American Association for Cancer Research (AACR) Annual Meeting held from April 12-16, 2008 in San Diego, California.
"Our five presentations at AACR shows the tremendous progress we made over the last year with our lead programs. The new findings from our cancer stem cell programs targeting CD44 and CD9 are of particular interest to the scientific community as this is a promising new area of cancer research," said Dr. David Young, President and CEO of ARIUS. "Specifically, we have been able to demonstrate that our CD44 program has the potential for wide therapeutic application in solid tumors, as well as blood cancers. Our cancer stem cell antibody targeting CD9 differentially recognizes AML cancer stem cells compared to normal stem cells. Furthermore, treatment with this antibody can functionally reduce cancer stem cell self-renewal which has very important therapeutic implications."
CD44 Cancer Stem Cell Program
Preclinical development of huARH460-16-2, a humanized antibody to the CD44 cancer stem cell target. Abstract Number 3975. Experimental and Molecular Therapeutics 32, Tuesday, April 15, 2008, 8:00 AM
ARIUS' ARH460-16-2, a functional antibody that targets CD44, has a new potential cancer indication for pancreatic cancer. The new findings show anti-tumor effects in an established BxPC3 human pancreatic cancer model (78.7% tumor growth inhibition at 2 mg/kg compared to control group). This antibody has broad effects in solid tumors since it have been shown to be effective in pancreatic, breast, liver, prostate cancer as well as AML. The results of the toxicology study support the ongoing development of the of the ARH460-16-2 antibody.
Anti-CD44 antibody, ARH460-16-2, binds to human AML CD34+CD38- cancer stem cells and demonstrates anti-tumor activity in an AML xenograft model. Abstract Number 3976. Experimental and Molecular Therapeutics 32, Tuesday, April 15, 2008, 8:00 AM
This presentation highlights the effects of ARIUS' CD44 targeting antibody, ARH460-16-2, on tumor cells from patients with various hematological cancers, including acute myeloid leukemia (AML). This antibody shows very potent anti-tumor effects in an AML tumor model (57% tumor growth inhibition at a 10 mg/kg compared to control group). In addition the antibody lead to an increase in the median survival to 62 days compared to 49 days in the control group. These results demonstrate that the ARH460-16-2 antibody has the potential for wide therapeutic application in hematological malignancies in addition to its application to the therapy of solid tumors.
ARIUS' ARH460-16-2 antibody is currently being manufactured for human clinical studies. It targets CD44 which is a marker of cancer stem cells in a broad range of solid cancers and AML. The first toxicology studies have been completed for this antibody, and a U.S. FDA pre-IND meeting has been held earlier in the year. This antibody is unique among CD44 antibodies in that it has the capacity to cause tumor regression in established solid tumors. It can directly act on cancer cells to induce apoptosis, or programmed cell death. The antibody may be broadly applicable to solid tumors as well as hematologic cancers.
CD9 Cancer Stem Cell Program
Anti-CD9 antibody, AR40A746.2.3, inhibits tumor growth in pancreatic and breast cancer models and recognizes CD9 on CD34+CD38- leukemic cancer stem cells. Abstract Number 3993. Experimental and Molecular Therapeutics 32, Tuesday, April 15, 2008, 8:00 AM
ARIUS has demonstrated that treatment with ARIUS' CD9 targeting antibody, AR40A746.2.3, induced apoptosis in BxPC-3 pancreatic cancer cell as a monotherapy. Moreover, apoptosis is achieved through inhibition of the AKT pathway, commonly believed to be an important pathway for cancer cell survival.
New immunohistochemistry (IHC) studies using this antibody showed that CD9 is expressed in a variety of human tumor samples, resulting in moderate to high levels of staining in 61/82 (73.5%) of tumor cells from various organs including pancreas, prostate, stomach and liver. The antibody demonstrated potent anti-tumor efficacy in in vivo models of pancreatic, breast and AML cancers and treatment led to a decrease in phosphorylation of several receptor tyrosine kinases.
CD9 is highly and differentially expressed in AML versus normal CD34+CD38- stem cells. Experiments strongly suggest that ARIUS' CD9 targeting antibody inhibits human AML outgrowth in pre-clinical studies. In secondary transplantation experiments, treatment with ARIUS' CD9 targeting antibody dramatically reduced the self-renewal capacity of AML cancer stem cells. CD9 is the first description of a marker that is differentially expressed on cancer versus normal stem cells.
Trop-2 Signal Transduction Program
AR47A6.4.2, a naked monoclonal antibody targeting Trop-2, exhibits anti-tumor efficacy in multiple human cancer models as a monotherapeutic agent and demonstrates efficacy in combination therapy. Abstract Number 3990. Experimental and Molecular Therapeutics 32, Tuesday, April 15, 2008, 8:00 AM
ARIUS shows its Trop-2 targeting antibody, AR47A6.4.2, is involved in the MAPK pathway. This antibody demonstrated potent anti-tumor efficacy in human pancreatic, breast, colon and prostate cancer models. In combination with Gemcitabine, this antibody also inhibited tumor growth by 93% in a human pancreatic cancer model. ARIUS' Trop-2 targeting antibody is the only naked therapeutic antibody targeting Trop-2.
A humanized version of this antibody has greater higher affinity than the murine version and will be used in a pre-clinical toxicology study. A cell line has been developed for the Trop-2 targeting antibody and it is currently in manufacturing to generate material for Phase I clinical studies.
CD59 Complement Inhibitor Program
A monoclonal antibody targeting CD59 (AR36A36.11.1), enhances complement activity and exhibits potent in vivo efficacy in multiple human cancer models. Abstract Number 3995. Experimental and Molecular Therapeutics 32, Tuesday, April 15, 2008, 8:00 AM
ARIUS has expanded its expression profiling and has characterized the affinity for its CD59 targeting antibody, AR36A36.11.1. This antibody has demonstrated significant in vivo anti-tumor activity towards a broad range of high incidence cancers and is highly potent at low dose concentrations in tumor xenografts, comparing favorably to standard of care in breast and prostate cancer.
The effectiveness of this very potent antibody may be attributed to its ability to block CD59 function, representing a novel approach to cancer treatment. Currently, there are no other reported naked therapeutic antibodies targeting CD59 in clinical development.
A humanized version of ARIUS' CD59 targeting antibody demonstrated equivalent affinity and potency to the murine version, and a CHO cell line producing humanized AR36A36.11.1 has been generated to manufacture material for future clinical studies.
ARIUS is a biotechnology company discovering and developing the next wave of antibody therapeutics. Established in 1999, ARIUS has built a proprietary technology platform, FunctionFIRST(TM), that rapidly identifies and selects antibodies based on their functional ability to affect disease. This antibody generation engine has enabled ARIUS to assemble a portfolio of more than 500 antibody candidates. In addition to the antibodies it is developing in-house, ARIUS has ongoing partnerships with key biotechnology and drug development companies. ARIUS is listed on the TSX under the symbol "ARI". For further information, visit http://www.ariusmabs.com
Certain statements in this news release constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, which involve known and unknown risks, uncertainties and other factors that may cause our actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Forward-looking statements in this release include, but are not limited to, ARIUS successfully advancing its new product programs as well as licensing opportunities. These statements are only predictions and actual events or results may differ materially. Factors that could cause such actual events or results expressed or implied by such forward-looking statements to differ materially from any future results expressed or implied by such statements include, but are not limited to: early stage of development; technology and product development; dependence on and management of current and future corporate collaborations; future capital needs; uncertainty of additional funding; no assurance of market acceptance; dependence on proprietary technology and uncertainty of patent protection; intense competition; manufacturing and market uncertainties; and government regulation. These and other factors are described in detail in ARIUS' Annual Report, forthcoming news releases and other filings with Canadian securities regulatory authorities available at http://www.sedar.com. Forward-looking statements are based on our current expectations and ARIUS is not obligated to update such information to reflect later events or developments.
|SOURCE ARIUS Research Inc.|
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