Haplomers™
The Haplomers technology platform applies to a large class of compounds capable of triggered activation reactions. Activation occurs only in the presence of a triggering genetic sequence found in a specific type of living cell—for example a tumor cell. Activated Haplomers thus serve as a unique, targetable marker for cells harboring a specific genetic signal. Haplomers provide a crucial molecular bridge between genetic information in a cell and immunotherapy intervention.
The Challenge:
Powerful therapies cannot be directed against tumor cells, due to lack of specific markers.
Immunotherapy relies on the presence of targetable markers on the tumor cell surface. Unfortunately, accessible markers have not been found for most tumor types. Even when acceptable tumor surface markers are discovered, they often are also present on some normal cells, resulting in significant side-effects. There is an urgent need to establish more effective strategies to treat currently “un-targetable” tumors.
The Solution: Haplomers produce new markers specifically on tumor cells, with genetic precision.
The rapid advance of genetic sequencing technology has discovered an abundance of tumor-specific RNA targets for many cancer indications. Haplomers are designed to be activated in the presence of tumor-specific RNA triggers, producing a targetable immunotherapy marker upon activation. The Haplomers technology platform combines the strength of three major recent advances in medicine: immunotherapy, genetic diagnostics, and RNA-targeted therapy.
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Features
Haplomers are administered as a pair of compounds, and corresponding members of a pair must be brought together on a tumor-specific triggering RNA sequence for the Haplomers pair to be activated. Each member of a pair has a nucleic acid component, designed so that the Haplomer pair will bind adjacent to each other on the triggering RNA. Each member of a pair also carries a chemical “payload”, which is inactive by itself. Upon binding of both Haplomers to the triggering RNA, the payloads react, generating the activated marker product (typically a short peptide). It is this activated marker that engages a therapeutic antibody or T-Cell receptor to mediate tumor cell destruction.
In cells lacking the tumor-specific triggering RNA, Haplomer pairs do not bind together in close proximity. The activation reaction thus does not occur, so normal cells are not marked for destruction by the immunotherapy agent.
Benefits
The Haplomers platform provides several key benefits for development of anti-cancer therapies:
• Well-Established Proof of Mechanism: Haplomers therapies leverage immunotherapy mechanisms of action that have been proven clinically effective.
• Specificity = safety: Avoids toxicity against normal cells-- Haplomers are inert in absence of genetic trigger.
• Flexible and Modular: Can be readily designed to target any genetic target of interest; opens vast new array of previously un-druggable targets.
• Highly Versatile Targeting: Unlike other RNA-targeted approaches, therapy does not depend on the function of the RNA target. Non-coding RNAs can thus be targets.
• Efficient: Immunotherapy element may be reused for any new target; no need to develop new antibodies, T cell receptors, or chimeric antigen receptors for new indications.