From S-3
We have developed a platform technology, DCVax®, which uses activated dendritic cells to mobilize a patient's own immune system to attack their cancer. The DCVax technology is expected to be applicable to all types of solid tumor cancers, and is embodied in several distinct product lines. One of the product lines (DCVax®-L) is designed to cover all solid tumor cancers in which the tumors can be surgically removed. Another product line (DCVax®-Direct) is designed for all solid tumor cancers which are considered inoperable and cannot be surgically removed. We believe the broad applicability of DCVax to many cancers provides multiple opportunities for commercialization and partnering.
Our DCVax platform technology involves dendritic cells, the master cells of the immune system, and is designed to reinvigorate and educate the immune system to attack cancers. The dendritic cells are able to mobilize the overall immune system, which includes T cells, B cells and antibodies, natural killer cells and many others. Such mobilization of the overall immune system provides a broader attack on the cancer than mobilizing just a particular component, such as T cells alone, or a particular antibody alone. Likewise, our DCVax technology is designed to attack the full set of biomarkers, or antigens, on a patient’s cancer, rather than just a particular selected target or several targets. Clinical experience indicates that when just one or a few biomarkers on a cancer are targeted by a drug or other treatment, sooner or later the cancer usually develops a way around that drug, and the drug stops working. We believe that mobilizing all agents of the immune system, and targeting all biomarkers on the patient’s cancer, contributes to the effectiveness of DCVax.
The DCVax Technology
Our platform technology, DCVax®, is a personalized immune therapy which consists of a therapeutic vaccine that uses a patient’s own dendritic cells, or DCs, the master cells of the immune system, as the therapeutic agent. The patient’s DCs are obtained through a blood draw, or leukapheresis. The DCs are then activated and loaded with biomarkers (“antigens”) from the patient’s own tumor. The loading of biomarkers into the DCs “educates” the DCs about what to attack. The activated, educated DCs are then isolated with very high purity and constitute the DCVax personalized vaccine.
We believe that injection of DCVax-L into the patient, through a simple intra-dermal injection in the upper arm, can initiate a potent immune response against cancer cells, mobilizing the overall immune system and doing so in the way nature intended, with the numerous immune agents acting in their normal roles and in combination with each other.
Importantly, each activated, educated dendritic cell has a large multiplier effect, mobilizing hundreds of T cells and other immune cells. As a result, small doses of such dendritic cells can mobilize large and sustained immune responses. Also very importantly, dendritic cells activate diverse populations of T cells (i.e., T cells targeted at a variety of different biomarker targets on the patient’s cancer). In contrast, T cell based therapies employ T cells aimed at just one biomarker target on the cancer, similar to targeted drugs.
DCVax Product Lines
We have developed several different product lines based on the DCVax technology, to address multiple different cancers and different patient situations. There are two main components to each DCVax product: the immune cells (dendritic cells) and the cancer biomarker targets (antigens).
All of our DCVax product lines are made from the patient’s own dendritic cells. The dendritic cells are freshly isolated, and newly matured and activated. We believe that the existing dendritic cells in a cancer patient have already been compromised by the cancer, and we believe that is one of the reasons other vaccines aimed at the existing dendritic cells in patients have largely failed. However, the patient’s body continues to produce new precursors of dendritic cells, and these precursors (monocytes) circulate in the patient’s blood stream. For all DCVax products, these precursors are obtained through a blood draw, and then (through our proprietary manufacturing processes), the precursors are matured into a fresh batch of new dendritic cells.
DCVax-L - is designed for operable solid tumors. It is made with cancer antigens from tumor lysate (a protein extract from processed tumor cells) from the patient’s own tumor tissue. As such, DCVax-L incorporates the full set of tumor antigens, making it difficult for tumors to find detours around it (“escape variants”), as described above. This is the DCVax product that has been used in our brain cancer and ovarian cancer clinical trials, and is currently being studied in our 348-patient Phase III brain cancer trial. DCVax-L is expected to be applicable for any types of solid tumor cancers in situations in which the patient has their tumor surgically removed as part of the standard of care.
DCVax-Direct - is designed for inoperable solid tumors – situations in which it is not feasible or not desirable for patients to have their tumors surgically removed, either due to multiple metastases or for other reasons. Like DCVax-L, DCVax-Direct also incorporates the full set of tumor antigens - but it does so in situ in the patient’s body rather than at the manufacturing facility. With DCVax Direct, the fresh, new dendritic cells are partially matured in a special proprietary way so as to be ready to pick up antigens directly from tumor tissue in the patient’s body, and also communicate the information about those antigens to other agents of the immune system, such as T cells. The partially matured dendritic cells are then injected directly into the patient’s tumor(s). There, the dendritic cells pick up the antigens in situ rather than picking up the antigens from lysate in a lab dish at the manufacturing facility, as is done with DCVax-L. DCVax-Direct is anticipated to be applicable to any type of inoperable solid tumors.
Phase III Clinical Trial of DCVax®-L
Our DCVax®-L product is currently in a 348-patient Phase III trial for newly diagnosed Glioblastoma multiforme brain cancer, which is on a partial clinical hold in regard to recruitment of new patients. The trial is a double-blind, randomized, placebo controlled trial with two treatment arms (standard of care plus DCVax-L vs. standard of care plus a placebo). The trial also includes a crossover option for any patients to receive DCVax-L treatment after progression (tumor recurrence). The primary endpoint is progression free survival, or PFS, and the secondary endpoints include overall survival, or OS, and a number of other measures.
The trial is being conducted in the U.S., the U.K., Germany and Canada. Over 300 of the total 348 planned patients have been recruited into the Phase III trial and these patients are continuing to be treated in accordance with the trial protocol. New screening of patient candidates for additional recruitment has been suspended pursuant to the partial hold. The Company is in ongoing dialog with regulators about the partial hold and the Trial.
Phase I/II Trial of DCVax®-Direct
Our DCVax®-Direct product is in a Phase I/II trial program for inoperable solid tumor cancers. The Phase I portion has been completed, and involved 40 patients with 13 different types of cancers. The patients had multiple metastases, had failed other treatments and had poor prognoses. Following treatment with DCVax-Direct, twenty percent of these patients are still alive at survival timesexceeding two years. The longest survivor has reached nearly three years.
For the Phase II portion of this trial, we plan to conduct several studies in parallel, applying DCVax-Direct in different cancers. We also plan to use an enhanced treatment regimen with more treatments, closer spacing of the treatments, and injections of DCVax-Direct into more tumors in the patient. (In Phase I, only one of the patient’s tumors was injected with the treatment).
Target Markets for DCVax Products
Since our DCVax-L product is potentially applicable to all types of operable solid tumors, and our DCVax-Direct product is potentially applicable to all types of inoperable solid tumors, we believe the potential markets for DCVax products are quite large. According to the American Cancer Society, 1 in 2 men, and 1 in 3 women in the U.S. will develop some form of cancer in their lifetime. There are nearly 1.5 million new cases of cancer per year in the U.S., and nearly 600,000 deaths from cancer. The statistics are similar in Europe and in much of the rest of the world.
