TMAb™ (Tumor Microenvironment Activated Biologics) Platform

Our TMAb platform has the potential to unlock previously undruggable immune targets. Many immune targets are found within the tumor and in healthy tissue compartments, which limit the therapeutic range and potential safety of traditional monoclonal antibodies. TMAb antibodies bypass tissue compartments other than the low-pH tumor microenvironment. This avoids a pharmacological ‘sink’ and creates the potential for higher target engagement and improved safety.

We have conducted preclinical studies using TMAb antibodies that bind only in the naturally occurring, low pH tumor microenvironment of pH~6, with greater than 600-fold specificity compared to their binding at normal physiologic pH of 7.4.

Sensei Bio discovers and develops TMAb antibodies using a proprietary screening methodology without the use of molecular switches or masks that are cleaved at low pH. This can free antibodies to bind outside the tumor and create potential on-target / off-tumor toxicity. Conversely, TMAb antibodies bind their targets selectively within the tumor.

The Tumor Microenvironment of pH~6 is Lower than Physiological pH of 7.4

ImmunoPhage™ Platform

Sensei has built a pioneering vaccine platform named ImmunoPhage™, dedicated to training the immune system to react to specific antigens and deliver a strong, coordinated immune response. We engineer non-infectious lambda bacteriophage viruses to display target antigens on the capsid surface. This approach simulates the equivalent of a natural viral infection, resulting in strong immune responses via innate immune activation and downstream adaptive immunity (e.g. B cells, antibodies, and T cells).

ImmunoPhage™

Sensei’s next generation of vaccines are supercharged by features that enable direct targeting to – and selective activation of – “professional” antigen presenting cells (APCs) and modulation of the tumor microenvironment. The key features are comprised of alpaca-derived nanobodies, which have several superior properties compared to standard full-length human antibodies. In acquiring Alvaxa Biosciences, Sensei has direct access to expertise in nanobody generation, screening and optimization to facilitate the generation of supercharged phage-based vaccines and standalone nanobody-based immunotherapy assets.

Nanobodies are small molecular weight antigen-binding domains (VHHs) with the potential for very high-affinity binding and demonstrate robust “drug-like” characteristics such as stability, manufacturability, and high sequence homology to human IgGs that may obviate need for humanization. The nanobody capabilities acquired from Alvaxa Biosciences have already been leveraged against multiple key immuno-modulatory targets to kickstart our pipeline of supercharged phage-based vaccines.

ImmunoPhage™ possesses a number of key features that differentiates itself from other platforms in the field of oncology vaccine development

null

Vaccine editing“on the fly”

Antigen selection is optimized throughout clinical development using a dynamic cocktail approach.

null

Large payload capacity

The phage can accommodate multiple proteins and domains. We can blend multiple phage per cocktail for virtually unlimited capacity.

null

Well tolerated

Positive clinical results.

null

“Complete”
immune response

Self-adjuvanted through intrinsic PAMPs (pathogen-associated molecular patterns) including phage-encoded CpG motifs and icosahedral geometry; Intrinsic APC-targeting. B- and T-cell activation.

null

Cost effective, fast and scalable manufacturing in-house

Manufacturing at small 10L scale in GMP conditions yields 5,000-10,000 doses. From concept to GMP bulk drug in 4 weeks. Easy tech transfer and scale up to commercial volumes.

null

Broadly applicable

Can be easily applied to multiple oncology indications.

Personalized vaccine cocktails with off-the-shelf ImmunoPhage™ phage “ingredients”

The high speed and low cost-of-goods of Sensei’s ImmunoPhage™ platform enable our unique approach to personalized immune-therapy. Most cancers overexpress a variety of tumor-associated antigens (TAAs), that are shared by many patients across a variety of tumor types. Sensei is developing a library of pre-made, clinical-grade bacteriophage vaccines, covering this shared cancer-antigen landscape. We envision a future clinical paradigm, where a tumor is biopsied, diagnosed and analyzed for expression of hundreds of potential TAAs. Based on that profile, Sensei Biotherapeutics mixes an ImmunoPhage™ cocktail, customized to the patient, to be delivered within weeks of diagnosis. We believe that these advantages, along with the long-term stability of ImmunoPhage™, make personalized ImmunoPhage™ cocktails a commercially viable solution to the current challenges facing fully personalized patient-specific immunotherapy.

Our proprietary ImmunoPhage™ platform and Phortress™ library

We believe our ImmunoPhage™ platform has the potential to deliver personalized, off-the-shelf product candidates tailored to a patient’s specific tumor. The versatility of our ImmunoPhage™ platform allows us to design product candidates in a modular fashion, based on a cocktail of common and patient antigens built from our proprietary library of ImmunoPhages, which we refer to as Phortress™.

Nanobody Capabilities and Incorporation into ImmunoPhage™

Sensei’s next generation of vaccines are supercharged by features that enable direct targeting to – and selective activation of – “professional” antigen presenting cells (APCs) and modulation of the tumor microenvironment. The key features are comprised of alpaca-derived nanobodies, which have several superior properties compared to standard full-length human antibodies. In acquiring Alvaxa Biosciences, Sensei has direct access to expertise in nanobody generation, screening and optimization to facilitate the generation of supercharged phage-based vaccines and standalone nanobody-based immunotherapy assets.

Nanobodies are small molecular weight antigen-binding domains (VHHs) with the potential for very high-affinity binding and demonstrate robust “drug-like” characteristics such as stability, manufacturability, and high sequence homology to human IgGs that may obviate need for humanization. The nanobody capabilities acquired from Alvaxa Biosciences have already been leveraged against multiple key immuno-modulatory targets to kickstart our pipeline of supercharged phage-based vaccines.

Publications