Our Technology

ONCOLOGY

THE OPPORTUNITY AND NEED
THE PROMISE OF SYNTHETIC VECTOR IMMUNOTHERAPIES
ENABLING A UNIQUE THERAPEUTIC APPROACH
OUR SYNTHETIC VECTOR PLATFORM
PUBLICATIONS & PRESENTATIONS

THE OPPORTUNITY AND NEED

While available therapies for cancer patients continue to improve outcome for some patients, a significant need exist to improve outcomes for a much larger percentage of patients. New, more recent advancements in immunotherapies that target a patient’s own immune system are emerging, but unfortunately, the reality is that most patients still do not respond to many of the most recent therapeutic advancements.

While these therapies have brought improved treatment options for some patients, a much larger percentage of patients still have significant, unmet medical needs. DevaCell’s is addressing these challenges by focusing on the discovery and development of high impact therapeutics and bringing to patients in need, new, transformative therapies with the potential to dramatically improve outcomes in a true bench-to-bedside manner.

Harnessing the Power of The Human Immune System

Viral immunotherapies are uniquely suited to activate both innate and adaptive immunity.

The Innate Immune System

The human innate immune system is our first line attack from foreign invaders and upon recognition is responsible for producing the first attack, identifying and directly killing cancer cells.

A diverse set of cell types are part of our innate immune system and include natural killer (NK) cells, macrophages and dendritic cells that, in a synergic matter, generate a rapid response to these foreign invaders, including cancer cells.

The Adaptive Immune System

The human adaptive immune system is our second line of defense, enabling a long-lasting protective response

The adaptive immune system includes two parts, a cell-mediated component (T cells) and a humoral component (B cells), which act in a synergistic fashion and can establish more durable memory, enabling a more rapid response when a foreign invader such as a cancer cell reappears.

THE PROMISE OF SYNTHETIC VECTOR IMMUNOTHERAPIES

The objective in cancer immunotherapy is to activate and enhance a patient’s own immune system, harnessing the power of the human immune system to identify, attack and kill tumor cells, while potentially establishing durable, long-term immunologic memory protecting against recurrence.

To significantly improve outcomes for cancer patients, we are developing an emerging therapeutic approach that not only activates and enhances a patient’s T cell response, which is the mechanism of action for the use of checkpoint inhibitors, but to also activate and enhance in a synergistic manner, additional key immune cells within the innate and adaptive immune systems.To accomplish that objective, we are developing a synthetic vector-based platform of novel product candidates that we believe represents one of the most attractive approaches to activate and enhance the immune system in a highly synergistic fashion in order to achieve improved outcomes for cancer patients.

ENABLING A UNIQUE THERAPEUTIC APPROACH

The objective in cancer immunotherapy is to activate and enhance a patient’s own immune system, harnessing the power of the human immune system to identify, attack and kill tumor cells, while potentially establishing durable, long-term immunologic memory protecting against recurrence.

To significantly improve outcomes for cancer patients, we are developing an emerging therapeutic approach that not only activates and enhances a patient’s T cell response, which is the mechanism of action for the use of checkpoint inhibitors, but to also activate and enhance in a synergistic manner, additional key immune cells within the innate and adaptive immune systems.To accomplish that objective, we are developing a synthetic vector-based platform of novel product candidates that we believe represents one of the most attractive approaches to activate and enhance the immune system in a highly synergistic fashion in order to achieve improved outcomes for cancer patients.

TRANSFORMATIVE AND UNIQUE THERAPEUTIC APPROACH

Synthetic vector-based immunotherapies have several unique properties that distinctly differentiate our therapeutics from other therapeutics, representing a new and transformative approach to cancer care.

1. Target and selectively kill tumor cells by immunogenic cell death mechanism

DevaCell’s synthetic vector-based immunotherapies are designed to selectively target and kill cancer cells while sparing healthy cells. Using novel targeting approaches, cancer cells can often be selectively targeted, reducing potential side effects.

2. Establish an induced, inflammatory state that can turn cold tumors hot

DevaCell’s synthetic vector includes an engineered adenovirus subtype 5 (Ad5). After invading cancer cells, the virus replicates and following multiple cycles of viral replication, the cancer cells die and release antigens that are patient-specific, triggering an activation of the patient’s innate immune system and generating an increase in inflammation within the tumor microenvironment. In a cascade of events, recognizing this inflammation, innate and adaptive immune cells are then attracted to the tumor microenvironment. In preclinical studies, DevaCell’s synthetic vector-based immunotherapies have been shown to convert tumors with a “cold tumor” phenotype, typically defined as a tumor that has few tumor-infiltrating immune cells, into “hot tumors”, defined as tumors with high numbers of tumor-infiltrating immune cells, which is a tumor type that has been shown to respond to immunotherapeutics.

3. Trigger the release, spread and presentation of patient-specific tumor antigens

Tumor cell killing by synthetic vector-based immunotherapeutics produce a diverse range of tumor-specific antigens, which result from direct tumor cell killing (direct oncolysis), that are then presented to the immune system. We believe this “display” of tumor antigens results in a more complete presentation of tumor antigens versus other therapeutic approaches, offering the potentially to produce a patient-specific immune response that is more potent and effective. Through this novel mechanism of action, we believe we can activate and enhance not only the innate immune response, but also synergistically activate and enhance an adaptive immune response, including both a T cell response and antibody response that selective targets, attacks and kills tumor cells throughout the body, while also establishing immunologic memory, which may protect against potential recurrence. 

4. Engineered synthetic vectors expressing transgenes localized to the tumor microenvironment

DevaCell’s synthetic vectors have been engineered with multiple transgenes that code for a range of therapeutic agents including immune checkpoint antibodies, immunostimulatory cytokines, and other therapeutic proteins that have been shown in human clinical trials, when delivered as recombinant protein therapy, to improve immune responses. The ability of our synthetic vector-based immunotherapies to deliver to the tumor microenvironment, highly potent immunostimulatory factors, creates a highly synergistic effect, reducing the suppressive tumor microenvironment, activating and enhancing the improve immune response, while simultaneously reducing toxic side effects, together offering the potential for improved outcomes.

DevaCell synthetic vector-based immunotherapeutic platform is designed to target a wide range of tumor types, with a focus on bringing the transformative potential of our novel therapies to patient’s as quickly as possible.

OUR SYNTHETIC VECTOR PLATFORM

Systemic Delivery with Potential for Repeat Administration

DevaCell’s synthetic vector platform represents a unique and potentially transformative, next-generation immunotherapy. Build upon an engineered, adenoviral, subtype 5 (Ad5) viral vector, our synthetic vector platform has been designed to optimally activate and enhance a patient’s own immune response, which historically has been a challenge using conventional immunotherapy approaches.

Based on our novel and proprietary ONCoat encapsulation technology, our synthetic vector-based immunotherapies offer several unique advantages. First, we believe for the first time, our synthetic vectors enable the systemic delivery of a highly potent immunotherapy, while also offering targeted delivery, resulting in high localized delivery of therapeutic agents, which we believe will also result in lower toxicities. Second, also for the first time, we believe our synthetic vector enable repeat administration, which is typically going to be required to maximize efficacy in most cancer indications.

Our strategic focus is to develop and advance multiple product candidates with different transgene compositions, in order to effective target the widest range of tumor types. Our lead product candidate, DEVA-OV1, is a systemically-delivered synthetic vector immunotherapy targeting multiple solid tumor cancers. Additional product candidates, with different transgene configurations, are advancing through preclinical development. In addition, in preclinical development outside of oncology is an infectious disease product candidate, DEVA-COVID19, targeting the SarsCov19 virus, as well as gene therapy/gene editing product candidates in discovery research. 

Engineered to Maximize Effectiveness and Safety

We believe our ONCoat synthetic vector platform represents a transformative, next-generation immunotherapeutic approach that offers the potential to significantly impact patent care based on three unique characteristics of our product platform.

Capacity for multiple transgenes that synergistically maximize immune response

Using our proprietary ONCoat technology, our synthetic vector-based product candidates have been engineered with a synergistic combination of transgenes that offer the potential for improved immune response, which include the following:

Activates and enhances a more potent, systemic immune response

The synergistic combination of multiple immunostimulatory agents that can be targeted to the tumor microenvironment offers the potential in enhance response rates while reducing to systemic toxicity.

Full replication competency to enable maximum tumor-killing potency

Using our proprietary synthetic vector Platform, we are developing product candidates that retain their full ability to selectively replicate in tumor cells.

By comparison, traditional viral-based immunotherapies are engineered to attenuate their replication competency in both normal and tumor tissues to reduce toxicity. We believe this reduces the potential effectiveness.

Optimized safety strategies to limit viral activity to tumor cells

Our synthetic vector platform incorporates multiple unique and transformative approaches to allow for tumor-specific replication in order to focus viral activity to tumor cells.

We insert genetic regulatory elements within the genomes of our synthetic vectors. These genetic elements are designed to preferentially target viral replication to tumor cells and not normal healthy cells.

ABOUT DEVA-OV1

Our lead synthetic vector-based product candidate, DEVA-OV1, currently in IND-enabling studies and expected to enter human clinical trials in 2021, is engineered to activate and enhance a potent immune response, designed to synergistically harness the power of a patient’s own immune system to product a comprehensive anti-tumor response. This targeted, anti-tumor response is designed to directly kill cancer cells (direct oncolysis), the direct tumor cell killing produces tumor-cell-specific antigens that activate and enhance a patient’s own innate and adaptive immune response through a mechanism know as immunogenic cell death. This immune system response produces a more durable, longer-lasting response that establishes anti-tumor memory, to reduce the risk of recurrence. In addition to the unique oncolytic activity of our synthetic vectors, DEVA-OV1 has been engineered to include multiple transgenes to further activate and enhance the immune response.

In addition to DEVA-OV1, we have in development a product portfolio that include multiple transgene combinations that are specifically engineered to the unique needs of multiple tumor types.

Key Product Characteristics of DevaCell’s Product Pipeline

  • Combines multiple transgenes, each intended to activate and enhance a patient’s immune response.
  • Well known immunotherapy agent with established biological pathways and efficacy data from human clinical trials: IL-12, IL-15, PD-1, PD-L1, CTLA-4, TGF-b, OX40, CD40, 4-1BB, and other signaling pathway targets.
  • Synthetic vector based on the adenovirus, subtype 5 (Ad5), produces potent tumor cell killing, tumor-antigen spread, and activation and enhancement of innate and adaptive immune response (immunogenic cell death), enabling a more durable, long-lasting response and protection against tumor recurrence.
  • Synergistic use of multiple transgenes activates and enhances multiples arms of the immune system
  • Tumor cell targeted and localized transgene expression designed to reduce systemic toxicity
  • Fully replication-competent synthetic vector designed to maximize tumor cell killing
  • Systemic delivery, with repeat administration enables multiple therapeutic interventions that may be necessary to eradicate metastatic cancers.

OUR ONCOATTM SYNTHETIC VECTOR PLATFORM

Systemic, Repeat Administration of Synthetic Vector-Based Immunotherapies

The opportunity to systemically deliver via intravenous (IV) administration of our synthetic vector-based immunotherapies is a unique and highly attractive option that enables the treatment of tumors, even metastatic tumors, providing a unique, next-generation approach that offer the potential to improve patient outcomes for a wide range of tumor types.

In addition, by enabling the repeat administration of difficult to treat tumors, our synthetic vector-based immunotherapeutics offer the potential to improve outcomes for a significantly larger number of cancer patients.

We believe our unique and proprietary ONCoatTM synthetic vector platform, by enabling systemic delivery and repeat administration, will revolutionize cancer care and we are laser focus on bringing this advancement to cancer patients as rapidly as possible.

ONCOATTM – A NOVEL NANOPARTICLE-BASED SYNTHETIC VECTOR PLATFORM

We have developed a novel nanoparticle-based synthetic vector platform that includes an engineered adenoviral subtype 5 (Ad5) synthetic vector, encapsulated with our novel and proprietary ONCoatTM nanoparticle-based encapsulation technology, that creates a synthetic vector that is stealth to the immune system, while allowing for retargeting to the appropriate tissue type. 

Our ONCoatTM synthetic vector platform is designed to overcome multiple challenges associate with unmodified “naked” virus-based delivery, which typically results in the production of neutralizing antibodies that limit efficacy with systemically delivered viral vectors.

With the use of ONCoatTM-enabled, synthetic vectors that have been redirected to the tumor microenvironment, the synthetic vector can target cancer cells and replicate selectively in cancer cells, killing the cancer cells (direct oncolysis), spreading tumor-specific antigens and virus particles that can continue to infect and kill adjacent tumor cells, while priming the immune system through the mechanism of immunogenic cell death, recruiting an innate and adaptive immune response, activating an even more potent anti-tumor immune response (indirect oncolysis).

In addition to our lead synthetic vector-based product candidate, DEVA-OV1, our ONCoatTM synthetic vector immunotherapy product candidates are built upon our ONCoatTM synthetic vector platform and will continue to  utilize novel and proprietary formulations, preclinical, clinical and manufacturing strategies, which will allow us to maintain a high level of efficiency in the development of subsequent product candidates in oncology, as well as other indications outside of oncology, including our infectious disease vaccine for SarsCoV19, DEVA-COVID19, as well as our gene therapy/gene editing applications currently in discovery research.

Our ONCoatTM synthetic vector platform product candidates offer the potential to:

  • Enable systemic delivery and repeat administration
  • Simultaneously treat localized, as well as metastatic tumors through intravenous delivery
  • Treat cancer that have been difficult or impossible to treat with direct, intratumoral injection

DEVACELL PUBLICATIONS & PRESENTATIONS

BIO Investor Conference 2020
Slide Deck and One-Page Summary, October 2020

Encapsulation of adenovirus serotype 5 in anionic lecithin liposomes using a bead-based immunoprecipitation technique enhances transfection efficiency
Biomaterials (2014)