Robust portfolio
A novel pipeline
Program
Proposed Indications
Discovery
Preclinical
Phase 1
Milestones
Antibody-Drug Conjugates (ADCs)
(PYX-201)
NSCLC, Breast
IND: 2H22
Immuno-Oncology (IO)
(PYX-106)
Neck, NSCLC
IND: 2H22
Multiple Modalities
& Joint Ventures
Tumors
(PYX-203)
AML, MDS
(PYX-102)
Solid Tumors
Antibody-Drug Conjugates (ADCs)
In developing our ADCs, we identified promising tumor targets and acquired highly specific antibodies to these tumor targets. Our technology platform, Flexible Antibody Conjugation Technology (FACT), is designed to enable us to develop highly controlled ADCs. Our ADCs are designed to employ site-specific conjugation of potent cytotoxic payloads to highly selective antibodies for a precise drug-antibody ratio, or DAR, with an enhanced therapeutic index.
PYX-201
A holistic antitumor strategy
PYX-201 is a non-internalizing ADC that binds to extradomain-B (EDB) fibronectin, an integral component of the extracellular matrix in the tumor that is overexpressed in many malignancies and is minimally expressed in most normal adult tissues. After binding, its highly cell-permeable auristatin payload is enzymatically released, which directly attacks cancer cells and other components that form the supportive tumor infrastructure. Auristatin elicits an antitumor immune response by inducing immunogenic cell death and dendritic cell maturation. While its effects are primarily due to its non-internalizing activity, a fraction of PYX-201 may also be internalized, further enhancing its antitumor activity.
Immuno-oncology (IO)
We are building a diverse portfolio of immunotherapies that target broad immune regulatory mechanisms as well as novel immune checkpoints with the potential to transform the cancer treatment landscape. Our approach draws from externally developed programs and our internal discovery engine based on the work of Pyxis Oncology’s founding scientist.
PYX-106
A complimentary approach to PD-1/PD-L1 targeted therapies
PYX-106 is a fully human monoclonal antibody designed to target Siglec-15, an immune suppressor that is broadly expressed across different tumor types as well as macrophages. Since Siglec-15 and PD-L1 have limited overlap, PYX-106 could address PD-1/PD-L1 non-responders across a variety of tumor types and may be integral in combination with other immunotherapies.
PYX-106 demonstrated a significantly longer half-life of seven days in an exploratory non-human primate study and a six-fold greater binding affinity to Siglec-15 compared to current benchmarks, which could allow for less frequent dosing while maintaining optimal activity.
Paused Programs
PYX-203
A superior ADC for the treatment of hematologic cancers
PYX-203 targets and binds to the interleukin-3 receptor, also known as CD123, a rapidly internalizing target that is overexpressed in hematologic cancers by leukemic blasts and stem cells. After internalization, its highly potent cyclopropylpyrroloindoline (CPI) payload is enzymatically released and trafficked to the nucleus, where it crosslinks DNA interstrands. CPI is engineered for enhanced tolerability and may allow PYX-203 to reach a broader patient population. CPI is resistant to drug efflux pumps and could confer superior cancer-killing activity. The antibody is also engineered to have a modified Fc region to mitigate off-tumor toxicity.
PYX-102
An IO strategy to relieve immune inhibition and activate an antitumor response
PYX-102 targets killer cell lectin-like receptor subfamily G member 1 (KLRG1), an inhibitory receptor expressed on T cells and natural killer (NK) cells. Its ligands, E- and N-cadherin are expressed in numerous solid cancers. By blocking KLRG1 signaling, PYX-102 may relieve immune inhibition in these tumors while rescuing KLRG1-mediated suppression of human CD8+ T cells. PYX-102 has significant potential as a monotherapy and in combination treatment strategies.
Overview
We are building a proprietary catalog of new targets as the foundation for the next generation of Pyxis Oncology ADCs and immuno-therapies. Building on the work by Pyxis Oncology’s founding scientist Dr. Tom Gajewski and applying innovative bioinformatics and translational tools, we are identifying tumor specific targets, including cell surface and stromal antigens. Further, our approach has the potential to uncover additional mechanisms relevant for immune modulation in the tumor microenvironment.
