Discovery and Development

 

Antibody Discovery and Development

In-house capabilities from early discovery to GMP manufacturing

At Agenus, we believe vertical integration is critically important. We have taken aggressive steps to accomplish this, facilitating rapid and efficient advancement of our antibody programs and minimizing reliance on external vendors. Through innovation and strategic acquisitions, we have developed an unparalleled suite of internal technologies and capabilities. These, combined with our fully integrated approach, enable us to precisely control and design the properties of our antibodies so that we can generate products with the desired properties to enhance their efficacy.

Our antibody discovery and development capabilities are driven by innovative technology and guided by our deep expertise in immunology, structural biology and computational biology. Aided by two unique antibody display platforms (Mammalian Retrocyte Display and Phage Display) and with an automated high throughput screening platform, Agenus UK can discover novel antibodies and deliver high quality producer cell banks at extraordinary speeds.

Our in-house Cell Line Development group uses state-of-the-art technologies to deliver cell lines that are monoclonal, stable and have commercial grade yields. These cells lines are used to provide material for conducting preclinical (PK/PD and toxicity) and clinical studies, as well as efficient technology transfer for commercial supply. Bringing CLD in-house has provided assurance of quality, flexibility with production schedules, reduced timelines and reduced cost of development. At our CLD facility in Cambridge, UK, we have established an efficient system starting with high throughput screening and selection of clones, to developing robust and reproducible cell lines that are viable for commercial scale production. These capabilities culminate in faster INDs with a seamless supply of product which is essential for clinical and commercial success. The ability to rapidly deliver high expressing, stable cell lines is critical to shortening timelines from candidate molecule nomination to IND filing and treating patients.

The integration of our discovery, development and manufacturing capabilities provides Agenus with unique advantages in an era when quality, efficiencies and speed of development and commercialization are paramount to successfully developing a new generation of I-O biopharmaceutical therapeutics.

 

Vaccine Technology

Innovative and highly differentiated “personalized” and “off-the-shelf” vaccines

Cancer vaccines are designed to train the immune system to attack cancer cells. To create a cancer vaccine candidate, antigens specific to cancer cells (cancer neo-antigens) are combined with a delivery vehicle. The presence of a cancer antigen in the context of this “delivery vehicle” alerts the immune system that the antigen is detrimental and should be eliminated from the body.

At Agenus, we are developing “personalized” vaccines (ProphageTM & AutoSynVaxTM) containing cancer neo-antigens that are specific to a given patient and “off-the-shelf” vaccines (PhosphoSynVaxTM) containing cancer neo-antigens we believe to be widely expressed across tumors. Our neoantigen vaccines are designed with unique features, each conferring important advantages:

  • Proprietary methods to develop an effective and relevant “blueprint” of immunogenic neoantigens for each patient
  • Heat shock proteins (HSPs) to efficiently deliver neoantigens to the right immune cells to activate an anti-cancer immune response. Our proprietary linker technology enables efficient neoantigen loading for a robust cancer specific immune response with 10X less peptide
  • QS-21 Stimulon®, a potent immune stimulator now in GSK’s approved and highly efficacious shingles vaccine, SHINGRIX® (up to 97% effective).

Selecting Tumor targets for our Vaccines:

Our proprietary algorithms help us select Neoantigen Tumor Targets for our vaccines. Using Next Generation Sequencing (NGS) technologies, cloud computing and our cutting-edge proprietary bioinformatics capabilities, we rapidly profile each patient’s tumor to accurately identify the exact DNA mutations that are in the tumor cells but not in healthy cells. Next, our proprietary Agenus Immunogenic Mutation (AIM™) algorithms sift through the terabytes of DNA data to find mutations that are present throughout the tumor and predicted to be seen by the patient’s own immune system for effective vaccine design.

 

VISION

Integrated R&D Platform for Target Discovery,
Drug Development and Intelligent Clinical Trial Design

Agenus is driving the discovery and development of novel human therapeutics using functional genomics and computational approaches. Our Virtual Systems for Immuno-Oncology (VISION) platform interrogates how cells and molecules interact in response to physiological challenges that occur in the tumor microenvironment. We then mine massive amounts of data using proprietary algorithms to answer fundamental questions in cancer immunobiology, discover novel therapeutic targets, optimize therapeutic candidates to achieve desired biologic function, and inform intelligent clinical trial design. Designed for maximum impact, our VISION Platform is:

  • Versatile
    Interrogates multiple aspects of antitumor immunity, including T cell dysfunction, innate immune regulation, stromal interactions and other therapeutic resistance pathways
  • Trackable over time
    Monitors the natural history of an antitumor immune response across an extended time course
  • Comprehensive
    Collects molecular, ‘omic and functional data for deep characterization of cellular interactions
  • Scalable
    Performs mid-to-high throughput screens with antibodies, small molecules or gene editing libraries
  • Integrative
    Combines with Agenus’ innovation and therapeutic development engines for rapid path to clinic

Agenus is leveraging the power of VISION to fuel a new wave of innovative I-O therapies that address resistance pathways and have the potential to significantly improve treatment of patients with cancer. Agenus is leveraging this platform for novel target discovery with partnership opportunities.

 

Agenus’ Artificial Intelligence (AI) Based R&D Platform Drives New Molecular Targets for Cancer Therapy

In addition to novel therapeutic development, our VISION platform generates vast amounts of data showing how T cells interact with tumor cells in the TME. These data are fed into our Adaptive Learning Platform Systems (ALPS) for further analysis.

ALPS is our proprietary artificial intelligence-based R&D platform to identify optimal molecular targets for cancer therapy. ALPS leverages advanced gene editing, sequencing, and single cell technologies to provide deep insights into the biology of antitumor immunity. This information is used by our proprietary algorithms that model complex phenotypes of T cells in the tumor microenvironment. The models help us predict potential responses to new treatments and define biomarker signatures, which we expect to lead to smaller and quicker clinical trials with higher impact for patient benefit. Ultimately, the data we collect from clinical trials will be fed back into our proprietary algorithms, strengthening our predictive models and optimizing patient outcomes over time.

 

Cell Line Development Facility (Cambridge, UK)

Key to execute rapid drug development

Cell line development (CLD) is a critical first step towards drug development. Agenus has established a cutting-edge in-house CLD facility that assures quality and flexibility with production schedules while reducing timelines and costs. Our CLD facility in Cambridge, UK (Agenus UK) has established an efficient system starting with high throughput screening and selection of clones and ending with the development of robust and reproducible cell lines with commercial grade yields. Agenus UK can efficiently deliver high-yielding, stable monoclonal cell lines to our in-house GMP manufacturing facility (Agenus West) for commercial scale production within ~ 4 months. Through close collaboration and parallel workflows, Agenus UK and Agenus West facilitate faster INDs and a seamless supply of clinical product, which is essential for clinical and, ultimately, commercial success. Current efforts by our team at Agenus UK to automate the CLD process is expected to shrink timelines even further.