Eleven Biotherapeutics: Taking on ADCs with targeted protein therapeutics

By Dan Stanton contact

- Last updated on GMT

TPTs, like ADCs, are 'smart missiles' which can deliver cytotoxic payloads to tumour cells. Image: iStock/jojje9999
TPTs, like ADCs, are 'smart missiles' which can deliver cytotoxic payloads to tumour cells. Image: iStock/jojje9999
A two-step manufacturing process makes antibody-drug conjugate production expensive and causes stability issues, says Eleven Biotherapeutics which is fusing antibody fragments to cytotoxic proteins.

Cambridge, Massachusetts-based Eleven Biotherapeutics spent 2016 focusing on its targeted protein therapeutic (TPT) portfolio, selling off its recombinant albumin technology to Albumedix​, acquiring Viventia Bio​ and its TPT pipeline, and striking a licensing deal with Swiss Pharma giant Roche​.

TPTs are fully biologic single protein molecules built by genetically fusing a tumour targeting antibody fragment to a very potent cytotoxic protein. These front-end navigating molecules selectively bind to antigens or receptors that are over expressed on cancer cells.

While this “smart missile”​ concept is the same idea behind antibody-drug conjugates (ADCs), Eleven CEO Stephen Hurly said TPTs offers a number of efficacy and manufacturing advantages.

“One of the challenges ADCs face is their stability: their structure relies on a two-step more expensive manufacturing system,”​ he told stakeholders during a conference call to discuss end-of-year results, Friday.

For an ADC, both an antibody and small molecule drug payload must be made and conjugated together causing “significant challenges with some of these products falling apart in circulation,”​ he continued, resulting in the premature release of a payload that is no longer targeted.

“Our TPTs are engineered as single protein molecules that are produced in the single, one step manufacturing system and employ stable, genetically engineered linkers, which allow them to remain intact until they internalise by the cancer cells.”

He added there are significant cost advantages over ADCs as TPTs are engineered as single protein molecules produced in a single, one step manufacturing system.

Antibody fragments

By using antibody fragments, Hurly believes his firm can “deliver significantly more drug to improve the tumour bed. Antibody fragments have shown the ability to travel two tumour beds and much more effectively than full-length antibodies that of the basis of most ADCs.”

There are also cost advantages of using antibody fragments rather than full antibodies, something Crescendo Biologics​ has been able to benefit from through their Humabody-drug conjugate (HBD) development.

But TPTs use protein toxins – not small molecules – for payloads which according to Hurly “kill a broader array of cancer cells and not be affected by multi-drug resistance pumps that cancer cells use to eliminate the small molecule payloads that are commonly used by ADCs.”

He added: “These toxins shut down protein production; this can mediate the killing of both rapidly proliferating but also slower growing cancer cells, potentially including cancer stem cells. In contrast, most ADCs are only effective at killing rapidly proliferating cells.”

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