In an interview with PharmaShots, Andrew Hall, CEO at IMV share his views on the data of  DPX delivery platform in the bladder and ovarian cancer, presented in two e-posters at the AACR-NCI-EORTC virtual conference

Shots:

• The company has reported additional data to support the immunotherapeutic capabilities of its DPX technology. In pre-clinical/clinical data, DPX technology generates peptide-specific, T cell-based immune responses that are more persistent than conventional water-based formulations
• IMV’s maveropepimut-S is currently being evaluated for advanced and recurrent ovarian cancer & induced a robust, and persistent, survivin-specific T cell response, well-tolerated in multiple clinical trials
• DPX-SurMAGE was well tolerated for bladder cancer and elicits robust and targeted T cell responses against both survivin and MAGE-A9 peptides along with a good safety profile in preclinical models

Tuba: Highlight the key features & its capabilities of the DPX Delivery Platform

Andrew Hall: Our DPX technology is a unique, versatile, and patented delivery platform that incorporates a range of bioactive molecules into our lipid-based formulations to produce targeted, long-lasting immune responses in many potential therapeutic areas. The DPX platform can be used for the delivery of single or multiple bioactive molecules, including peptides, small molecules, nucleic acids, and virus-like particles. When formulated with peptide antigens, DPX and its cargo are actively transported by antigen-presenting cells to the lymph nodes for T-cell and/or B-cell activation. This results in rapid, persistent, and robust antigen-specific immune responses against tumor cells or infectious agents.

Tuba: Discuss the key benefits of a powerful, versatile platform & advantages over other immunotherapies.

Andrew Hall: The DPX platform is a lipid-based delivery technology that maintains antigens at the injection site upon injection compared to standard aqueous formulations that diffuse into surrounding tissues. As it does not release components at the injection site, this allows for longer interaction with antigen-presenting cells to elicit a robust and sustained immune response that can be maintained over an extended period with limited side effects. The DPX platform is able to elicit specific T cell-based immune responses that are not achievable with conventional water-based emulsion delivery. The DPX platform has shown a more robust antigen-specific response than conventional emulsion delivery both in preclinical and clinical studies.

In addition, the DPX platform has other important advantages such as excellent safety profile, ease and low cost of manufacturing, the ability to incorporate both hydrophilic and hydrophobic molecules, no cold-chain requirements for shipping and storage, extended shelf stability, and subcutaneous injection for simple administration in a doctor’s office.

Tuba: Discuss the pre-clinical/clinical data of this platform presented at the AACR-NCI-EORTC conference on molecular targets and cancer therapeutics for ovarian cancer patients.

Andrew Hall: Two posters were presented at the AACR-NCI-EORTC conference this year supporting the DPX technology as a versatile delivery platform. The first poster showcased additional data demonstrating the ability of the DPX platform to generate peptide-specific, T cell-based immune responses that are more robust and more persistent than conventional emulsion formulations.

Our second asset featured in another poster presentation, DPX-SurMAGE, is a dual antigen targeted immunotherapy that targets survivin and MAGE-A9, two tumor-associated antigens that are correlated with a poorer prognosis in bladder cancer. Preclinical data showed that DPX-SurMAGE was well tolerated and generated robust and targeted T cell responses against both survivin and MAGE-A9 peptides in animal bladder cancer models. DPX-SurMAGE with and without intermittent low dose CPA induced robust T cell responses, supporting the impending Phase 1 clinical trial in high-risk early-stage bladder cancer patients. These data demonstrate that the DPX delivery platform can be leveraged to develop novel multi-targeted antigen T cell activating immunotherapies.

Overall, these results support the versatility of the DPX delivery platform to instruct a targeted and persistent immune response and its potential application in many different therapeutic areas.

Tuba: Discuss in detail the IMV’s maveropepimut-S & its MoA. Highlight its importance for ovarian cancer patients

Andrew Hall: Maveropepimut-S (MVP-S) is DPX-based immunotherapy that targets survivin-expressing cells for elimination by educated, cytotoxic T cells. Survivin is overexpressed in about 50% of stage I/II and up to 100% of stage III/IV ovarian cancers but is not expressed in normal ovarian tissue. Survivin positivity increases with histological Grade (Grade 1/2, 50% vs Grade 3, 76%) and is associated with reduced overall survival. MVP-S combines the DPX platform with Survivac, an antigen preparation that combines 5 survivin-derived, immunogenic peptides designed to target common human leukocyte antigen (HLA) haplotypes. MVP-S drives antigen presentation of these immunogenic survivin peptides to induce a persistent tumor-specific T cell response.

In our DeCidE1 Phase 2 clinical trial, MVP-S was administered with intermittent, low-dose cyclophosphamide (CPA) and led to robust polyfunctional, antigen-specific T-cell generation in patients with advanced, recurrent ovarian cancer. We saw that MVP-S treatment increased survivin-specific T cell tumor infiltration. This higher baseline T cell infiltration in tumor tissue was evident in patients with clinical benefit (defined as >10% on-treatment tumor regression).

Recent translational findings further suggest that immunogenic or inflamed tumors are more susceptible to the MVP-S treatment with potential mechanisms of primary resistance identified. Together, these results provide insight for possible predictors of response to treatment with MVP-S and will inform the design of the next IVM-sponsored clinical trial in patients with advanced, recurrent ovarian cancer, expected to be initiated in 2022. The study will evaluate MVP-S with intermittent low-dose CPA.

Ovarian cancer has the highest mortality rate of all gynecologic cancers. MVP-S is an immunotherapy that specifically activates the immune system rather than suppressing it and aims to reduce negative treatment side effects, such as hair loss, skin damage and gastrointestinal issues that are common with chemotherapy.

Tuba: Are you planning to evaluate the maveropepimut-S in other indications?

Andrew Hall: Survivin is one of the most promising targets for cancer immunotherapy due to its overexpression in many tumor types, immunogenicity, and important roles in tumor growth and survival. In addition to ovarian cancer, our ongoing clinical development program is evaluating MVP-S alone and in combination with immune modulators and anti-cancer drugs in patients with advanced diffuse large B-cell lymphoma (DLBCL), breast cancer, and other solid tumors where survivin is expressed.

We are investigating MVP-S in a Phase 2 basket trial that is underway in combination with Keytruda® in patients with advanced or recurrent solid tumors in the bladder, liver (hepatocellular carcinoma), ovarian, or non-small-cell lung (NSCLC) cancers, as well as tumors positive for the microsatellite instability-high

(MSI-H) biomarker. The trial has the potential to identify new target indications that we may advance into disease-specific Phase 2 testing.

Also with MVP-S, we recently initiated a Phase 1b study in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer.

Tuba: Share IMV’s broader efforts to advance research and development of next-generation therapies

Andrew Hall: The DPX platform is the current focus of our research and the backbone for all our immunotherapies in development. Our primary focus is on developing effective cancer therapies that bolster patients’ quality of life. We believe recent data on our DPX platform supports the expansion of our clinical oncology pipeline across a wider range of tumor antigens. We look forward to exploring other immunomodulating molecules that may be leveraged using the DPX platform, beyond our current research in peptides. This may include mRNA, small molecules, or VLPs.

Tuba: Are you open to collaboration to develop a clinical asset pipeline outside of oncology?

Andrew Hall: Given the immense capacity of the DPX technology to produce potential therapies across indications, we do consider other applications in collaboration with other companies. Part of our strategy is to actively monetize our non-immuno-oncology programs such that the broad potential impact of DPX’s approach can be leveraged in other areas, while we remain focused on oncology. We are actively working to partner with non-immuno-oncology programs in areas such as a respiratory syncytial virus (RSV) where we have validated DPX as a useful tool in an infectious disease setting. In RSV, we investigated the potential of a DPX-based product in a Phase 1 trial and saw a significant increase of antibody protection as well as a favorable safety profile, even in aged adults.

Image Source: Medical News Today

About Author: Andrew Hall is the CEO at IMV. Andrew brings more than 20 years of executive experience in biopharmaceuticals and life sciences. Andrew Hall holds a Master of Science from RMIT University and a Bachelor of Medical Science with Honors from Melbourne University.

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