We are a pharmaceutical company developing novel drugs for the treatment and diagnosis of cancer. Our three cancer-targeted compounds are selectively taken up and retained in cancer cells (including cancer stem cells) versus normal cells. Thus, our therapeutic compounds appear to directly kill cancer cells while minimizing harm to normal cells. This offers the potential for a paradigm shift in cancer therapy by providing efficacy versus all three major drivers of mortality in cancer: primary tumors, metastases and stem cell-based relapse. LIGHT is a small-molecule cancer-targeted PET imaging agent. We believe LIGHT has first-in-class potential and Phase 1-2 clinical trials are ongoing. HOT is a small-molecule, broad-spectrum, cancer-targeted molecular radiotherapeutic that delivers radiation directly and selectively to cancer cells and cancer stem cells. We believe HOT also has first-in-class potential. HOT Phase 1b dose-escalation trial is ongoing and we expect HOT to enter Phase 2 trials in the first quarter of 2013 as monotherapy for solid tumors with significant unmet medical need. COLD, a cancer-targeted non-radioactive chemotherapy, works primarily through Akt inhibition. We plan to file an IND for COLD in the first quarter of 2013. Together, we believe our compounds are able to “find, treat and follow”TM cancer anywhere in the body in a novel, effective and highly selective way.

Products

LIGHT is a small molecule imaging agent that we believe has first-in-class potential for selective detection of tumors and metastases in a broad range of cancers. LIGHT is comprised of a small, non-pharmacological quantity of CLR1404 (COLD, acting as a cancer-targeted delivery and retention vehicle) labeled with the short-lived radioisotope, iodine-124, a new positron emission tomography (PET) imaging isotope. PET imaging used in conjunction with CT scanning has now become the imaging method of choice in oncology. In studies to date, LIGHT selectively illuminated malignant tumors in 52 of 54 animal models of cancer, demonstrating evidence of broad-spectrum, cancer-selective uptake and retention. Investigator-sponsored Phase 1-2 trials of LIGHT as a PET imaging agent are ongoing. The trials include brain metastases, lung cancer and starting in the second quarter of 2012 other solid tumors. These human trials, if successful, will serve two important purposes. First, they would provide proof-of-concept for LIGHT itself as a PET imaging agent with the potential to supplant the current “gold standard” agent, 18-fluoro-deoxyglucose (FDG), due to what we believe to be LIGHT’s superior cancer-specificity and more favorable logistics of clinical use. Second, favorable results would accelerate clinical development of HOT by predicting efficacy and enabling calculation of efficacious doses of HOT for Phase 2 trials.

HOT (iodine-131 radiolabeled CLR1404) is a small-molecule, broad-spectrum, cancer-targeted molecular radiotherapeutic that we believe has first-in-class potential. HOT is comprised of a small, non-pharmacological quantity of CLR1404 (COLD) acting as a cancer-targeted delivery and retention vehicle and incorporating a cytotoxic dose of radiotherapy (in the form of iodine-131, a radioisotope that is already in common use to treat thyroid and other cancer types). It is this “intracellular radiation” mechanism of cancer cell killing, coupled with selective delivery to a wide range of malignant tumor types that imbues HOT with broad-spectrum anti-cancer activity. Selective uptake and retention has also been demonstrated in cancer stem cells compared with normal stem cells, offering the prospect of longer lasting cancer remission. In 2009 we filed an IND with the FDA to study HOT in humans. In early 2010 we successfully completed a Phase 1a dosimetry trial demonstrating initial safety, tumor imaging and pharmacokinetic consistency and establishing a starting dose for a Phase 1b dose-escalation trial. The ongoing Phase 1b dose-escalation trial is aimed at determining the Maximum Tolerated Dose of HOT. We expect to initiate HOT Phase 2 efficacy trials as a monotherapy for solid tumors with significant unmet medical need as soon as a minimal efficacious dose is established. We may determine such an effective dose upon seeing a tumor response in the Phase 1b trial or calculating it from ongoing PET imaging trials in cancer patients with LIGHT. Preclinical in vitro (in cell culture) and in vivo (in animals) experiments have demonstrated selective killing of cancer cells along with a benign safety profile. HOT’s anti-tumor / survival-prolonging activities have been demonstrated in more than a dozen xenograft models (human tumor cells implanted into animals) including breast, prostate, lung, glioma (brain), pancreatic, ovarian, uterine, renal and colorectal cancers and melanoma. In all but two models, a single administration of HOT was sufficient for efficacy. In view of HOT’s selective uptake and retention in a wide range of solid tumors and in cancer stem cells, its single-agent efficacy in xenograft models and its non-specific mechanism of cancer-killing (radiation), we expect first to develop HOT as a monotherapy, initially for solid tumors.

COLD is a cancer-targeted chemotherapy that in pre-clinical experiments inhibits the phosphatidylinosotol 3-kinase (PI3K)/Akt survival pathway, which is overexpressed in many types of cancer. As a result, COLD selectively inhibits Akt activity, induces caspase-mediated apoptosis and inhibits cell proliferation in cancer cells versus normal cells. COLD also exhibits significant in vivo efficacy in mouse xenograft tumor models, including non-small cell lung cancer and triple-negative breast cancers, producing long-lasting tumor growth suppression and significantly increased survival. We believe COLD has the potential to be best-in-class versus other Akt inhibitors in development due to a) cancer cell/cancer stem cell targeting, resulting in cancer-selective inhibition of Akt and cell proliferation or b) suitability for intravenous administration that we believe offers the prospect of greater systemic exposure and hence Akt inhibition in cancer cells, which we believe would result in superior efficacy. We expect to submit an Investigational New Drug (IND) application to the United States Food and Drug Administration (FDA) in the first quarter of 2013.

Technology

COLD, HOT and LIGHT are alkylphospholipids (“APLs”) that interact with lipid rafts, which are specialized microdomains within cell membranes. Importantly, the core chemical structure shared across all three products provides selective targeting of cancer cells in preference to normal cells (due to enrichment of lipid rafts in the former). COLD was deliberately designed to contain iodine (in the form of the stable, non-radioactive isotope, 127I), thus enabling additional, distinct products differing only with respect to the form of iodine they contain – HOT contains short-lived radioactive 131I and LIGHT contains even more short-lived 124I. As a result, three cancer-targeted product profiles have been generated from a single chemical structure – a chemo-therapeutic agent (COLD), a molecular radiotherapeutic agent (HOT) and a diagnostic/imaging agent (LIGHT).

Using a fluorescent-labeled analog of COLD (CLR1501 or “GLOW1″), selective uptake and retention has been demonstrated in cancer cells in vitro. Twenty-four hours after treatment, a variety of human tumor cell types (melanoma, colorectal, uterine, pancreatic, ovarian, glioblastoma) show six to ten-fold more staining with GLOW1 relative to normal cells (e.g., skin fibroblasts) do not. Significantly, uptake/retention was also seen in cancer stem cells which are known to be relatively resistant to both chemotherapy and radiation and may therefore contribute to eventual relapse of disease following conventional chemotherapy.

Malignant tumor targeting, including targeting of cancer stem cells, has also been demonstrated in vivo. For example, mice without intact immune systems, and inoculated with Panc-1 (pancreatic carcinoma), were injected with CLR1502 (“GLOW2″, a fluorescent-labeled analog of COLD that is active in the near-infrared range) 24 and 96 hours prior to imaging. In vivo optical imaging showed pronounced accumulation of GLOW2 in tumors versus non-target organs and tissues. Similarly, PET imaging of tumor-bearing animals (colon, glioma, triple negative breast and pancreatic tumor xenograft models) administered the imaging agent LIGHT clearly shows selective uptake and retention by both primary tumors and metastases, including cancer stem cells. Furthermore, PET/CT analysis following co-injection of HOT (for therapy) and LIGHT (for imaging) revealed time-dependent tumor shrinkage and disappearance (over 9 days) in a cancer xenograft model. Finally, we believe that the capability of our technology in targeting cancer stem cells in vivo was demonstrated by treating tumor-bearing mice with GLOW1 and then removing the tumor and isolating cancer stem cells, which continued to display GLOW1 labeling even after three weeks in cell culture.

The basis for selective tumor targeting of our compounds lies in differences between the plasma membranes of cancer cells as compared to those of most normal cells. Specifically, cancer cell membranes are highly enriched in “lipid rafts”. Lipid rafts are specialized regions of the membrane phospholipid bilayer that contain high concentrations of cholesterol and sphingolipids and serve to organize cell surface and intracellular signaling molecules (e.g. growth factor and cytokine receptors, the phophatidylinosotol 3-kinase (P13K)/Akt survival pathway. Lipid rafts are central to the activity of our compounds in two ways:

1. Lipid rafts are portals of entry for APLs such as COLD, HOT and LIGHT. The marked selectivity of our compounds for cancer cells versus non-cancer cells is due to the fact that cancer cells have far more lipid rafts. In addition to accumulating in lipid rafts, COLD, HOT and LIGHT are transported into the cytoplasm, where they distribute to organelle membranes (mitochondria, ER, lysosomes) but not the nucleus.

2. Lipid rafts also regulate signaling-based cell functions including apoptosis and cell proliferation, and COLD disrupts this regulation. For example, one key signaling pathway that is regulated by interactions with lipid rafts and phospholipids is the phosphatidylinosotol 3-kinase (PI3K)/Akt pathway. Akt (a serine/threonine protein kinase) is activated in lipid raft regions via phosphorylation by PI-dependent kinases and goes on to phosphorylate anti-apoptotic proteins (e.g., Bcl-xL and FLIP) resulting in their inactivation and, thus, promotion of tumor cell survival. COLD pharmacologically inhibits the activation of Akt. In cancer cells, Akt inhibition is associated with induction of apoptosis and decreased cell proliferation/survival.

The pivotal role played by lipid rafts is underscored by the fact that disruption of lipid raft architecture suppresses uptake of GLOW1 and radiolabeled COLD into cancer cells.

ImmunoCellular Therapeutics, Ltd. is a clinical-stage biotechnology company that is focused on developing new immune-based products to treat and diagnose cancer. Designed to harness both arms of the native immune system, our pipeline includes both active immunotherapies and patented monoclonal antibodies. Our active immunotherapies target not only regular tumor cells, but also the cancer stem cells believed to cause cancer growth and recurrence. Our strategy is to become the first company focused primarily on the development of cancer stem cell therapeutics, while working with partners to develop and commercialize our broadly applicable monoclonal antibodies. We believe our promising clinical programs, strong intellectual property, proprietary discovery technology, high-profile partnerships, and experienced leadership will allow us to continue building value for our shareholders.

Our mission is to improve cancer treatment and diagnosis through the discovery and development of new immune-based products. Designed to harness both arms of the native immune system, our pipeline includes both active immunotherapies and patented monoclonal antibodies (mABs). Our active immunotherapies target not only regular tumor cells, but also the cancer stem cells believed to cause cancer growth and recurrence. Our most advanced clinical programs are in glioblastoma multiforme (GBM), but our technologies have potential applications in many cancers with high unmet medical need, including pancreatic, ovarian, colon, small-cell lung, and multiple myeloma.

Our lead product candidate is ICT-107, a personalized, dendritic cell-based vaccine for the treatment of GBM. We intend to initiate a Phase II study of ICT-107 later this year following the strong results of a Phase I study in which it significantly prolonged survival with minimal side effects. We also intend to file an IND for ICT-121, our peptide-based “off-the-shelf” vaccine for the treatment of GBM.

Our strategy is to become the first company focused primarily on the development of cancer stem cell therapeutics, while working with partners to develop and commercialize our broadly applicable monoclonal antibodies. We have strong intellectual property surrounding our monoclonal antibodies, which were designed with our proprietary discovery technology. We also have an exclusive worldwide licensing agreement with Cedars-Sinai Medical Center for our immunotherapy and cancer stem-cell technologies.

Immunotherapy

Every day, our immune systems protect us from countless foreign invaders, including bacteria, viruses, and allergens. However, it typically does not target cancer because tumors arise within the body, not outside it. The purpose of immunotherapy is to trick the immune system into recognizing cancer as a foreign invader, thereby activating its sophisticated weaponry against a dreaded killer.

Immunotherapy presents a number of potential advantages over approved oral cancer treatments. Many immunotherapies are designed to precisely target tumor cells without damaging healthy tissue, and they generally produce fewer toxic side effects.

Our Approach

The immune system consists of two different arms:

• The cellular (T-cell based) immune system deploys special killer cells to target and destroy foreign invaders
• The humoral (B-cell based) immune system produces antibodies and carries them through bodily fluids to foreign invaders for destruction

Our product development strategy is to utilize both of these mechanisms to maximize the powerful synergies between them. While cellular immunotherapies have the potential to provide long-term protection against cancer and prevent its recurrence, monoclonal antibodies can confer an immediate shield against the disease. This is especially important when the patient’s immune system is compromised due to treatment, which can initially prevent an adequate cellular response.