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Science & Pipeline

HERVS & DISEASES OF AGING

Illuminating dark genome targets for novel immune therapies

With just 2 percent of our DNA responsible for all cellular function, the remaining 98 percent comprises repetitive elements long considered extraneous, non-functional “junk DNA.” Recent insights into the biological impact of these highly repetitive elements have renewed interest in what is now called the “dark genome” as a source of new disease targets.

Circular chart showing that 2% of human DNA encodes for proteins and the remaining 98% is the dark genomeCircular chart showing that 2% of human DNA encodes for proteins and the remaining 98% is the dark genome

Human endogenous retroviruses (HERVs), a class of well-characterized dark genome antigens, are the genetic remnants of ancient viral infections that integrated into the human genome millions of years ago

HERV genes are methylated and lie dormant when we are healthy and young but are reactivated as we age or develop certain diseases. Upon expression, HERVs can promote dysregulated cell division and suppress the immune system, contributing to the onset and progression of chronic age-related conditions. Despite their known impact on multiple diseases, HERV targeting approaches have remained elusive because the immune system views them as self-antigens.

OUR APPROACH

Rationally designed HERVs to treat diseases of aging

At HERVolution, we have broken human immune tolerance to HERVs, enabling therapeutic HERV targeting for the first time. We are revolutionizing treatment of complex age-related diseases with proprietary engineering approaches that allow us to make these once-invisible antigens visible to the immune system.

Our rationally redesigned HERV antigens induce potent and durable anti-HERV immune responses and can be expressed using adenoviral, virus-like particle, and mRNA vectors, providing opportunities for expanding our disease targets and dosing range to improve outcomes for the world’s increasingly aging population.

Graph showing increased human white blood cell activation with an engineered HERV-K antigen versus a native HERV-K antigen
Engineered HERV enables breaking of tolerance and activation of Human White Blood Cells

HERV Engineering

With a deep understanding of HERV biology, we rationally modify HERVs to deactivate their inherent immune suppression and yield highly immunogenic antigens for immune-system engagement.

Simplified representations of native versus engineered HERV genes with engineered region highlighted in white

    The HERV opportunity: Functional targeting of previously undruggable elements

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    Proprietary breakthrough

    Rational redesign of HERVs deactivates immunosuppression while maintaining immunogenicity

    Icon of two horizontal parallel lines each with a line of three green circles on top

    Off-the-shelf applications

    Ready-made HERV-targeted immunotherapies with pipeline-in-a-product potential

    Icon of a stylized DNA strand inside a circle with rays pointing outward, denoting expanding potential

    Revolutionary impact

    Robust data support potential to expand the landscape of targetable HERVs, targeting modalities, and disease indications

    OUR PIPELINE

    Empowering the immune system to address age-related disease

    Our platform fuels a pipeline of off-the-shelf assets that target HERVs implicated in age-related diseases, with a focus on cancer, type 2 diabetes, and eventually, neurodegenerative diseases and longevity.

    PROGRAM
    INDICATION
    DISCOVERY
    LEAD OPTIMIZATION
    IND ENABLING
    PHASE 1

    Oncology

    IPT-001HERV-K cancer immune therapy
    Prostate, Pancreatic
    IND ENABLING
    IPT-001 + IPT-002 mRNA boosterHERV-K cancer immune therapy
    Prostate, Pancreatic
    IND ENABLING

    Metabolic disease

    IPT-001HERV-K T2D immune therapy
    Type 2 diabetes (T2D)
    Discovery

    Aging

    HERV senolytic immune therapy
    Senescence
    Discovery
    AAv background imageAAv background image
    Simplified representation of an redesigned HERV gene atop a stylized AAV vector

    IPT-001

    IPT-001, our lead candidate, is a dual adenoviral (Ad) vector immune therapy that offers potential to address a range of diseases as monotherapy or in combination with other agents by delivering a redesigned HERV-K antigen.

    IPT-001 utilizes two unique, proprietary Ad-vectors with low pre-existing immunity and excellent antigen expression. These vectors enable simultaneous induction of potent HERV-specific T and B cell responses following a single treatment.

    IPT-001 is supported by a robust suite of preclinical data that demonstrate its ability to stimulate powerful immune responses in relevant models. We anticipate initiating clinical evaluation in patients with prostate or pancreatic cancer in 2025.

    Lipid Nanoparticle background imageLipid Nanoparticle background image
    Simplified representation of an redesigned HERV gene atop a stylized lipid nanoparticle

    IPT-002

    IPT-002 is an immune therapy that leverages mRNA vectors to deliver a redesigned HERV-K antigen and stimulate strong immune responses when used alone or when combined with another therapy.

    The use of mRNA vectors allows for repeat dosing in humans as well as maintenance and amplification of adenovirus-initiated immune responses when administered in a prime-boost treatment strategy with IPT-001.

    THERAPEUTIC AREAS

    Envisioning a future with expanded options for diseases of aging

    HERVs have been implicated as contributors to the onset and progression of many well-known diseases of aging. We are advancing rationally redesigned HERVs as a new avenue through which we can address these complex and challenging diseases.

    • CANCER
    • METABOLIC DISEASES
    • SENESCENCE
    Abstract helix shape overlaid upon an image of a bright yellow immune cell attacking a faded blue HERV presenting cancer cell

    CancerOur objective: Harness an off-the-shelf neoantigen that is resistant to immune escape, enabling durable, broad anti-tumor immunity.

    HERVs are an untapped source of tumor-specific antigens that may enable selective cancer targeting and immune engagement of previously cold tumors. HERV proteins are expressed across several cancer types, including pancreatic, prostate, colorectal, breast, and ovarian cancers.

    Immunity to HERV-K has been correlated with improved patient responses to existing immune checkpoint inhibitor therapies (eg, anti-PD-1) in lung cancer and renal cell carcinoma.

    Our unique immunotherapies contain a viral vector and an RNA vector that stimulate strong antibody and T cell immune responses against HERVs, offering potential for cancer elimination when administered as monotherapy or in combination with approved immunotherapies.

    Publications & Presentations

    Explore the science behind HERVs

    • PUBLICATIONS & PRESENTATIONS
    • SUPPORTING LITERATURE
    April 6, 2023

    An Endogenous Retrovirus Vaccine Encoding an Envelope with a Mutated Immunosuppressive Domain in Combination with Anti-PD1 Treatment Eradicates Established Tumours in Mice

    View Publication
    JANUARY 25, 2022

    A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches

    View Publication
    JANUARY 19, 2020

    The Potential of Adenoviral Vaccine Vectors with Altered Antigen Presentation Capabilities

    View Publication