Our targeted approach
Current antibody-drug conjugate (ADC) shortcomings
ADCs combine a highly selective tumor-specific monoclonal antibody with a potent toxin delivered directly to the targeted cancer cells. The multifaceted design and complex manufacturing process of ADCs represent major challenges for developing safe and effective treatment options. To date, only a limited number have reached the market.
ADCs consist of 3 key components: an antibody, a toxic payload, and a linker. Bringing these 3 components together in a safe and effective drug is a challenge for ADC development.
Antibodies need to differentially target molecules that the tumor expresses in high levels and that are absent or expressed at low levels in healthy tissues. The antibody must bind to a distinct antigen preferentially expressed on to tumor cells or to other cells in the tumor microenvironment and deliver its toxic payload effectively. To ensure delivery of the toxic payload only to tumors, the linker is engineered to release the payload only when it is cleaved by tumor-specific enzymes. Additionally, the conjugation strategy used to join the antibody to the linker and payload is equally as important. Traditional, nonspecific conjugation techniques have led to varying amounts of payloads attached to random regions of the antibody, which can negatively impact stability and activity.
Ultimately, an expansive opportunity exists to develop more effective ADCs that lead to improved clinical outcomes for patients with difficult-to-treat cancers.
Our approach to ADCs
ADCs deliver potent cancer-killing agents directly to tumor cells. Our technology platform is designed to enable us to develop safer and more effective ADCs.
Current immuno-oncology (I/O) therapeutics’ shortcomings
Over the past decade, I/O therapeutics has brought a unique approach to cancer treatment that harnesses the body’s immune system to kill cancer cells, but limitations persist. Cancer cells commonly express specific molecules that suppress the anticancer immune response. Immunotherapies, such as checkpoint inhibitors, target the pathways that cancer cells exploit to evade the immune system. Despite the progress we have seen, many patients do not respond to currently approved immunotherapies.
The advent of I/O therapeutics, particularly immune checkpoint inhibitors, has shifted the treatment paradigm for oncology. The immune system has the capability to recognize and eliminate cancer, but tumor cells take advantage of immune checkpoint pathways, which normally prevent autoimmunity, to suppress and evade immune effector cell activity.
While these drugs provide significant therapeutic benefit for durable responders, response rates remain low for most patients, particularly for tumors with low levels of tumor-infiltrating lymphocytes (TILs). These non-inflamed (i.e., “cold”) tumors can suppress the adaptive immune response through a variety of mechanisms within the tumor microenvironment.
Deeper investigation around dysfunctional TILs in inflamed tumors and signaling pathways preventing immune cells from entering cold tumors is essential to paving the way to develop new therapies to overcome immune suppression in the tumor microenvironment and facilitate the infiltration of TIL into the tumor tissue to bring the benefits of I/O to more patients in need.
Our approach to I/O
Pyxis is advancing a diverse portfolio of immunotherapies that target broad immune regulatory mechanisms as well as novel immune checkpoints.