The art of the cell

ImmunoCellular Therapeutics enters into option agreement with the M.D. Anderson for a novel cancer stem cell therapy

LOS ANGELES—ImmunoCellular Therapeutics, a clinical-stagecompany that is developing immune-based therapies for the treatment of brainand other cancer, has entered an option agreement with the University of TexasM.D. Anderson Cancer Center relating to an immunotherapy targeting cancer stemcells (CSCs).

The agreement bolsters ImmunoCellular's portfolio oftechnologies targeting CSCs. This portfolio already features several promisingtherapies, including ICT-107, a dendritic cell based immunotherapy thatrecently completed a Phase I study, and ICT-121, an off-the-shelf peptidevaccine that targets a protein marker called CD133 that is overexpressed oncancer stem cells. IND filings for FDA approval to begin human clinical trialsfor ICT-121 are expected for brain cancer during the first quarter of 2010 andfor pancreatic cancer during the third quarter of the year.

According to Manish Singh, president and CEO ofImmunoCellular, the deal gives the company worldwide, exclusive rights to thetechnologies when the option agreement ends. No financial terms have beendisclosed due to confidentiality requirements from both sides, Singh adds.

The technology being optioned from M.D. Anderson is animmunotherapy targeting cancer stem cells using abnormal Notch and Numbpathways, two mechanisms implicated in many common solid tumors includingbreast, colon and ovarian cancers. The therapy was developed at M.D. Andersonby Dr. Constantin G. Ioannides and Satoko Matsueda. Ioannides is also credited,along with others, with the development of the E75 peptide targeting Her-2/neu,which has been tested in a Phase II study to prevent breast cancer recurrence.

Malfunctioning of the notch pathway is a common phenomenonon several cancers marked by an overexpression of notch protein on cancer stemcells. The notch pathway is a signaling mechanism that regulates stem cells andin cases of cancer it acts as an oncogene that promotes the growth of tumors.

A number of cancers such as leukemia, lymphoma, breastcancer, lung cancer and brain cancer are known to have aberrant notch signalingleading to cells with greater migratory facilities which promotes metastasis.Research indicates that cytotoxic T cells induced by these peptidespreferentially target cancer stem cells derived from breast cancer, ovariancancer and pancreatic cancer; expression of these peptides has beendemonstrated on clinical samples from ovarian cancer patients.

"We plan to use this to develop novel immunotherapy productsto target breast cancer and ovarian cancer initially. These may also beapplicable to other cancers due to shared commonalities between variouscancers," Singh says. "We plan to conduct preclinical work for the next twelvemonths to demonstrate utility of these peptides in several cancer models."

According to Singh, smlecting the M.D. Anderson CancerCenter as a partner wasn't a difficult decision.

"They have unique technologies developed to target notch andnumb pathways, which we had earlier identified as one of the major pathways forour product development efforts," Singh says. "This latest addition to our portfolioof CSC targeting therapies should serve to further increase our ability tospecifically identify and destroy these important tumor building blocks bytargeting additional pathways that were not addressed by our current portfolio.By acquiring rights to this previously unaddressed pathway, we are now wellpositioned to continue development of a therapy that will enhance our abilityto target these important cells, which we believe may lead to more effectiveand better tolerated treatments that are capable of targeting a number ofdifferent tumor types."

Singh says a successful IND in 2011 will be the main goal ofthe collaboration.

ImmunoCellular also has a research and license option dealwith Roche for one of its mAbs for the diagnosis and treatment of ovariancancer and multiple myeloma. The company stands to earn up to $32 million inlicensing and milestone payments plus royalties if Roche exercises its optionand commercializes the technology for multiple indications.

ImmunoCellular is also in preclinical development of anothermonoclonal antibody product candidate for the treatment of small-cell lungcancer and pancreatic cancer, and is also evaluating its platform technologyfor monoclonal antibody discovery using differential immunization fordiagnosing and treating multiple types of cancer.

While Roche and Merck develop early clinical-stagegamma-secretase inhibitors that block notch signaling, ImmunoCellular istargeting cancer stem cells that express aberrant notch peptides by educating theimmune system to recognize and attack these cells.

They aren't the only companies working in this area. OncoMedand GlaxoSmithKline formed a strategic alliance in late 2007 that included acancer stem cell monoclonal antibody, OMP-21M18, that is currently in Phase Iclinical development and works by blocking a notch receptor signalingcomponent.



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