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Driving Drug Discovery Using Patients’ Immune Response

Driving Drug Discovery Using Patients’ Immune Response

Dec 06, 2019PAP-Q4-19-CL-019

Rather than picking targets based on conventional approaches, Immunome is letting a patient‘s ability to fight the disease guide target selection and therapy identification.

Leveraging Human Immune Responses

Most drug discovery today follows a similar path: study of disease biology in animal models, selection of a target based on a proposed mechanism of action and the development of a potential means of engaging the target. Immunome has taken the opposite approach, leveraging technologies developed at MIT’s Whitehead Institute and Thomas Jefferson University. Our technology both captures and interrogates patient immune responses to uncover novel antigens, and antibodies associated with them, that can have significant therapeutic potential. We are currently developing first-in-class cancer therapies by unlocking the tumor-educated B cell responses in patients. In many cases, the identified antibody–target pairs are enabling Immunome to develop novel therapies, including targeting untapped areas of cancer biology.

Focused on a Sophisticated Part of the Immune System

Highly tumor-educated B cells isolated from patients are immortalized by combining them with fusion partners using Immunome’s proprietary hybridoma technologies. By interrogating B cell response at unprecedented breadth, depth and speed, we are able to identify novel and unique antibody–target pairs against various cancers. Our proprietary technology enables us to conduct 20,000 assays on a single slide at breaking speed, providing the ability to scan a wide array of cancer antigen sources. The antibodies we identify exhibit high specificity and selectivity and are typically directed at first-in-class targets.

We then conduct various mechanistic studies to determine whether engaging the target can underwrite an efficacy hypothesis. Once confirmed, the antibody against the target is advanced into preclinical development.

Industrializing the Approach

Immunome has recently expanded its technical expertise and industrialized this approach. We have developed more than 150 hybridoma libraries containing over 200,000 human antibodies. Our extensive assessment so far led to over 1000+ hits and 50+ novel antigen/antibody pairs. We uncover approximately 10 potential targets per month on average —which is an unprecedented success rate.

Our approach is unique in being unbiased and agnostic with respect to target identification. This approach yields novel targets, which are noncanonical. We let patient responses dictate where we should look, through the lens of a human B cell.

Four Preclinical Candidates

We are currently evaluating four antibodies in preclinical development. Each of these candidates has unique mechanisms of action involving immuno-oncology, signaling pathways and angiogenesis in cancer cells. We would like to advance one or more of these into clinics after successful preclinical evaluation.

Expanding into ADCs

Many of the antibodies we identify have high specificity and selectivity and may be uniquely suited to combine with other targeting technologies, such as antibody–drug conjugates (ADCs), bi-specific antibodies or CAR-T therapies. We recently announced our first collaboration with pH Pharma Co. Ltd., where we plan to combine our unique antibodies with pH Pharma’s mammalian spliceosome modulators to develop novel ADC candidates.

pH Pharma will have the right to develop and commercialize the first candidate generated in the collaboration. Either company can then develop and commercialize subsequent candidates, and they will pay the other partner certain development, regulatory and commercial milestones worth up to $100 million per product. This unique approach allows both firms to build value with limited upfront investment.

Our technology both captures and interrogates patient immune responses to uncover novel tumor antigens and fully human antibodies with therapeutic potential against those targets.

Looking to Bispecifics, CAR-T Cell Therapies and Beyond

Immunome is interested in pursuing other partnerships, such as bispecifics and chimeric antigen receptor (CAR)-T cell therapies with both big pharma and smaller biotechs possessing proprietary and complementary technologies.

Furthermore, as we identify novel targets at an unprecedented rate, we are gaining unique insights into how the targets seem to cluster around novel cancer pathways. This clustering phenomena was not anticipated and has highlighted areas of biology that have not been historically the focus of significant cancer research. Interestingly, this insight is enabled by antibodies isolated from multiple patients with different cancers and immune responses, showing that these target-rich areas are shared across many different patients.