This lipid-based system is able to tightly target antigen-presenting cells and thus trigger a rapid, persistent and robust T cell response against various cancers.
IMV CSO Jeremy Graff, Ph.D./Courtesy of IMV
Cambridge, Mass.-based pharmaceutical company, IMV, has developed a lipid-based drug delivery platform to deliver immunotherapies for aggressive cancers. Unlike aqueous formulations, this lipid-based system does not release its cargo at the injection site. It is able to tightly target antigen-presenting cells and thus trigger a rapid, persistent and robust T cell response against various cancers.
After detailing the technology recently in two e-posters at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, IMV CSO Jeremy Graff, Ph.D. sat down with BioSpace to discuss this breakthrough.
BioSpace (BSp): You call this technology DPX™. What is that and why is it novel?
Jeremy Graff (JG): The DPX technology is a delivery platform for immune instruction. It provides specific information to specific immune cells to foster robust immune reactivity.
Standard delivery technologies involve lipids in water that, once injected, diffuse slowly from the injection site into surrounding tissues. Our delivery system, in contrast, has no water in its final formulations and doesn’t allow the cargo to dilute into other tissues. Therefore, the cargo in DPX remains concentrated and is consumed over time by specific immune cells. This enables DPX to persistently stimulate the immune system and thus elicit a more robust, sustained response to specific disease targets (such as novel tumor antigens).
BSp: What are the benefits of this approach?
JG: The benefit is that DPX technology essentially spoon-feeds the instructions to the immune system, over time, in a way that no other technology can. That’s the distinguishing feature of the DPX technology and is at the heart of why DPX can elicit an effective, robust immune response while so many other cancer vaccines have not. Other technologies don’t allow the cells to consume the information appropriately. But, by slowing the release and delivery directly to antigen-presenting cells, DPX can create a specific, persistent immune response.
DPX is very versatile. We can pack all sorts of cargo – including other immunotherapies – into the DPX technology. It’s also very safe. We have experience from 350 patients.
BSp: Tell me about your lead program. The data presented at AACR-NCI-EORTC indicated it elicited specific T cell-based immune responses that water-based emulsion delivery systems failed to achieve.
JG: That’s right. We’re currently evaluating maveropepimut-S (MVP-S; formerly DPX-Survivac) in patients with advanced and recurrent ovarian cancer. MVP-S inspires a T cell response to the protein survivin, which is a cancer antigen that is highly expressed in rapidly progressing cancers. When we delivered the same survivin peptides (originally from Merck KGaA) in a standard emulsion, it didn’t elicit those benefits. Yet, when we administered them using DPX, we got a much more robust immune response. This shows that the DPX™ platform can do things that standard emulsions cannot do.
We also have a Phase II diffuse large B-cell lymphoma (DLBCL) trial underway, and we expect results from a basket trial for bladder, liver and microsatellite instability-high (MSI-H) tumors to be released before the end of the year.
BSp: Where does this fit in the grand scheme of cancer therapies?
JG: DPX is our delivery vehicle for immunotherapies, and so can be complementary to Keytruda® (pembrolizumab) and other checkpoint inhibitors. We are exploring the combination of Keytruda and MVP-S in a Phase II trial for DLBCL. It has broad applicability because the survivin antigen, which MVP-S targets, is broadly overexpressed in aggressive cancers, including ovarian cancer, DLBCL and others. We can administer it to very advanced patients who may not tolerate conventional chemotherapy.
We also have a second therapeutic product in the bladder cancer space. Called DPX-SurMAGE, it targets the MAGE-A9 protein, which is overexpressed and drives progression in bladder cancer, as well as survivin. Both are associated with poor prognosis in bladder cancer. In preclinical models, DPX-SurMAGE generated a robust, targeted T cell response against both peptides. So, by combining cargo to two distinct cancer antigens in one product, we expect we can generate a response to multiple tumor antigens simultaneously.
Data suggest that DPX technology can be used beyond immuno-oncology, too. We have a lot of data showing it could be leveraged to protect against infectious diseases, such as malaria, anthrax, RSV and other viruses.
BSp: What’s the next milestone for IMV?
JG: By the end of 2021 or early 2022, we are aiming to receive FDA approval to extend a Phase II trial for advanced ovarian cancer as well as to provide data from our basket trial. We’re hoping that next summer we’ll be able to release data on the first stage of our DLBCL trial with Keytruda.
