Small Molecule Immunomodulators

We aim to develop the next generation of small molecule immunomodulators to fully access the potential of Toll-like Receptors for cancer patients

Small-molecule drugs are chemical compounds with a very low molecular weight that have been the therapeutic backbone in treating diseases for decades. Due to their small size, they can be highly efficient in penetrating tissues, and in modulating key targets both outside and inside the cell such as Toll-like Receptors or Kinases that play a critical role in the signaling processes that enable a strong immune response against cancer.

At BioNTech, we are focused on developing Small Molecule Immunomodulators (SMIMs) targeting Toll-Like Receptors (TLRs). TLRs play a critical role in the recognition of pathogens such as bacteria and viruses and internal danger signals that can be associated with the development of cancer. Upon activation, they trigger a strong immune response engaging both the innate and adaptive immune system. All TLRs are designed to monitor specific danger signals and the ones recognizing viral invasion have been shown to mount a very effective immune response. With our SMIMs, we are aiming to mimic the recognition sequence to activate these specific TLRs. Through this novel approach we aim to circumvent the immune evasion mechanisms cancer cells have established, providing a new avenue for cancer therapy. 

At a glance: Small molecules as a therapeutic drug class

  • Opportunity to be used synergistically in combination with other therapeutics such as mRNA, checkpoint inhibitors, radiation therapy and chemotherapy
  • Expand the realm of targets structures with ability to pass through cell membranes and reach intracellular protein targets
  • Easy administration route:  possibility to be given intravenously or orally as a tablet
  • Established manufacturing and cost-efficient production compared to larger compounds 

Our SMIMs aim to expand the therapeutic landscape for cancer patients by circumventing established tumor immune evasion mechanisms

Our small molecule immunomodulators (SMIMs) focus on a range of endosomal and intracellular targets that are known to stimulate the activity of a wide range of immune cells. We have developed a first SMIM product candidate that can mimic an activator of the TLR pathway, which triggers a broad immune system activation, including immature dendritic cells, cytotoxic T cells and Natural Killer (NK) cells, as well as stimulates the release of immune-activating signal molecules such as cytokines and chemokines, including IFN-α and IP-10. We plan to reactivate the immune response in the tumor microenvironment, which could have the therapeutic potential to be administered across various solid tumor indications. We are currently evaluating a first candidate in a clinical trial as a monotherapy as well as in a combination with other approved cancer therapies such as checkpoint inhibitors or chemotherapy. 

Read also