Also In the Pipeline
Relatively small companies are also seeing investor interest in OTS therapeutic cancer vaccines. Immatics Biotechnologies recently raised €53.8 million (about $68.5 million) in a Series C financing to advance its therapeutic cancer vaccine pipeline. Lead product IMA901 consists of peptides derived from a medley of synthetically produced tumor-associated peptides (TUMAPS) frequently over-expressed in most patients suffering from renal cell carcinoma.
Later this year the firm hopes to start a Phase III renal cancer trial with primary endpoint as overall survival. Initial results are expected toward the end of 2013.
Additionally, enthusiasm for cancer therapeutic vaccines spiked after Celldex reported positive Phase IIb results with rindopepimut (CDX-110), a glioblastoma multiforme (GBM) vaccine that was partnered with Pfizer until this September. In 2008, Pfizer paid $40 million up front plus $10 million in equity investments and assumed responsibility for the Phase IIb trial. Celldex stood to receive about $390 million in milestones plus double-digit royalties if the product reached commercialization.
Pfizer said that it returned rights to Celldex because the cancer vaccine no longer fit with its strategic plans despite the impressive interim data presented at the 2010 American Society of Clinical Oncology meeting. With regard to Pfizer returning rights to rindopepimut, Celldex’ svp and CMO, Thomas Davis, M.D., told GEN, “Our current resources are sufficient to complete our ongoing clinical study. There is a lot of interest in rindopepimut, there are multiple routes to achieving our goal, and we don’t see it as a major hurdle.”
Rindopepimut was studied in three open-label clinical studies that evaluated the vaccine in combination with temozolomide. The company reported that the treatment produced a 70% progression-free survival rate, corresponding to the 8.5-month rate seen in the company’s other two GBM trials.
Based on historic controls from Duke University and The University of Texas MD Anderson Cancer Center, median progression-free survival for patients with EGFRvIII-positive GBM was 6.3 months. Celldex anticipates reporting further results at a meeting being held by the Society of Neuro-Oncology next month.
Rindopepimut comprises a peptide based on amino acid regions flanking the extracellular portion of EGFRvIII. “In EGFRvIII the most common mutation of the normal receptor protein, the extracellular portion of the peptide, is spliced out, and you are left with a new sequence of amino acids on the cell surface,” Dr. Davis explained to GEN.
“The external sequence resulting from the splice makes a perfect cancer target because it is not found in normal tissues, and it is highly immunogenic.” The peptide vaccine is administered to patients along with granulocyte-macrophage colony-stimulating factor and keyhole limpet hemocyanin as a carrier protein and adjuvant.
Celldex believes that its next-generation vaccines will be based on its antigen-presenting cell (APC) targeting technology consisting of antibodies that are specific for APC receptors known to be “entry portals” for antigen-processing pathways. APCs can internalize these targeted antigens into cellular compartments, process them, and then present them on the cell surface to initiate the desired immune response that could, potentially, avoid isolation of autologous patient cells.
“Beyond rindopepimut we may combine EGFRvIII with other brain-tumor targets,” Dr. Davis told GEN. “Long term we would like to attack tumors by using more antigens that appear on brain tumor cell surfaces.”
An article published in the January 2009 issue of Expert Reviews stated that scientists and clinical cancer vaccine developers “cannot be anything other than troubled by the sheer number of Phase III clinical trial failures.” But the review also noted that these failures have yielded significant knowledge and improved understanding of how the immune system interacts with cancer.
OTS cancer vaccines indeed have their own manufacturing complications and have yet to establish their efficacy in the clinic. Yet they offer the most compelling choice for pharma companies and investor interest.