A New Strategy For ImmunoCellular Therapeutics

I had the opportunity last week to discuss the updated strategy and expected milestones for ImmunoCellular Therapeutics (OTC: IMUC) in 2010 and beyond with CEO, Manish Singh, following the conclusion of the OneMed, JP Morgan, and other healthcare conferences in San Francisco. IMUC is an emerging cancer immunotherapy company that is developing therapeutic and diagnostic product candidates taking aim at the root cause of the disease, cancer stem cells, based on two technology platforms that include active (therapeutic cancer vaccines) and passive (monoclonal antibodies) approaches.

IMUC has adopted a new strategy for 2010, including plans to conduct a Phase 2b trial of ICT-107 as the best way to increase shareholder value based on the impressive Phase I survival data in brain cancer patients that was updated last fall. Previously, IMUC planned to seek a licensing deal for further development of ICT-107 while retaining ICT-121 for in-house development as an off-the-shelf therapeutic cancer vaccine that has not yet entered clinical trials.

ICT‐107 is an autologous (patient-derived) dendritic cell (DC) therapeutic cancer vaccine that has been evaluated in a Phase I clinical trial initiated in May 2007 with a goal of determining the safety and immune response of patients with glioblastoma multiforme (GBM is the most aggressive and common form of primary brain cancer). ICT-107 targets six cancer-specific peptide antigens (a multi-epitope cancer vaccine targeting the following: HER2, TRP-2, gp100, MAGE-1, IL13R alpha, and AIM-3), including targets that are highly expressed on cancer stem cells.

ICT-107 will be evaluated in a randomized, controlled Phase 2b study (there is no need for a dose-ranging Phase 2a component in this study since dosing of ICT-107 is already established) that is structured to compare treatment groups receiving the standard of care (SOC) for GBM (radiation therapy plus temozolomide / Temodar) versus patients receiving SOC + ICT-107. This study is expected to begin during 2H10 with similar inclusion / exclusion criteria to the previous Phase I open-label study in patients with GBM.

In addition, IMUC has recently initiated the process to obtain Orphan Drug status in the U.S. and Europe for ICT-107 for GBM and expects to file and obtain this designation during 1H10. Last October, IMUC presented new data for its therapeutic cancer vaccine product candidate ICT-107 that included a median PFS survival time in the 16 newly diagnosed patients enrolled in the trial of 19 months, which is over 12 months longer than the historical PFS of just 6.9 months.

According to NCI/NIH statistics, approximately 19,000 people in the U.S. (plus a similar estimated incidence in Europe) are diagnosed with primary brain cancers each year, representing an unmet medical need that afflicts less than 200,000 people annually, which is the cut-off for Orphan Drug designation.

If later stage clinical trials confirm the impressive Phase 1 brain cancer survival data, ICT-107 has the potential to emerge as a leading, next-generation DC-based therapeutic cancer vaccine because of an excellent safety profile and several unique features that are outlined below, which differentiate IMUC’s approach to cancer immunotherapy from that of Dendreon (NASDAQ: DNDN) and other companies in the space.

  1. Multi-epitope (targeting epitopes / specific peptide regions of six tumor-associated antigens) rather than targeting a single cancer-related antigen that results in ICT-107 targeting BOTH cancer cells that comprise the bulk of tumors (daughter cells) AND the much less prevalent / residual cancer stem cell population thought to be responsible for the recurrence and spread of the disease;
  2. Highly expressed cancer stem cell antigen components of ICT-107 are also present in other forms of the disease such as ovarian, pancreatic, and breast cancers plus melanoma (with a possible Phase I/II trial in ovarian cancer patients being initiated in 2011 since this would likely result in the shortest time frame to generate data);
  3. Impressive early-stage, Phase 1 survival results for GBM that provides the rationale for the upcoming Phase 2b randomized / controlled study; and
  4. Manufacturing benefits include the ability to produce 5-10 doses of ICT-107 from a single production run at an estimated cost of goods sold (COGS) of $15,000;
  5. Favorable economics / business model based on a low COGS and a projected dosing regimen that includes an initial dose, followed by maintenance doses administered every 3-6 months for estimated revenue of $100,000 per patient treated each year; and
  6. R&D / formulation activities are underway to develop an off-the-shelf product based on the six cancer-specific peptide antigens present in ICT-107 combined with an immune system adjuvant (e.g. GM-CSF) with the goal of developing a sustained-release depot that is administered by subcutaneous injection and packaged in a single ready-to-use vial (with a Phase 1 study for this formulation possible by late 2010).

IMUC is also developing an off-the-shelf (i.e. does not require obtaining cells from the patient as part of the manufacturing process) peptide-based, therapeutic cancer vaccine (ICT-121) which targets a protein marker called CD133 that is over-expressed on cancer stem cells. An IND filing / clearance with the FDA would be required prior to initiation of clinical studies, but IMUC is now shifting its focusing on the clinical stage development (Phase 2b) of ICT-107 rather than starting the entire clinical testing process over for ICT-121.

In addition, IMUC previously acquired a platform technology to create cancer monoclonal antibodies (mAbs) based on a differential immune response (DIAAD) methodology. IMUC is developing cancer‐specific mAb candidates targeting small cell lung cancer, pancreatic, ovarian, colon cancers and multiple myelomas. ICT‐69 is being developed for multiple myeloma / ovarian cancer with a previously announced option license agreement with Roche (OTC: OTCQX:RHHBY) that includes up to $32 million in payments and royalties.

Last September, IMUC announced promising results from a pilot study evaluating the ability of the mAb (ICT-109) to distinguish between inflammatory conditions, cancerous, and non-cancerous tissue among pancreatic and lung cancer samples in the blood. ICT-109 was able to detect the pancreatic and lung cancer samples by binding to specific regions (glycosylated epitopes) of two common, over-expressed markers (CEA-CAM6 and CEA-CAM5) in a wide range of cancers.

In addition, glycosylated CEA is over-expressed in patients with pancreatic / lung cancers and can be used to detect these cancers using a direct blood test. IMUC has guided for a potential partnering of ICT-109 during 2010 and will also continue to develop additional mAbs targeting cancer stem cells (CSCs).

The combination of existing cash / equivalents ($1.4 million at year-end), a low cash burn rate (approximately $600,000 per quarter), and the previously announced $10 million financing commitment provides IMUC with adequate resources to fund operations / development over the next 2.5–3 years, including the new strategy to conduct a randomized / controlled Phase 2b trial of ICT-107 as the best way to increase shareholder value based on the impressive open-label Phase I survival data in brain cancer patients.

IMUC is currently trading at 90 cents with a three-month average daily trading volume of 40,000 shares, which represent significant percentage increases for both metrics since I first wrote about the company in early April 2009 while it was trading at 25 cents per share with an average daily trading volume below 5,000 shares. Despite these impressive gains, IMUC currently trades at a market cap of approximately $15 million with no debt – leaving plenty of room for upside gains if the company successfully executes on its new strategy for advancing ICT-107 through Phase 2b clinical trials, with additional catalysts and news flow also expected from its monoclonal antibody technology platform and ICT-121.

Disclosure: Author holds a long position in IMUC.OB