Through integrating a foundational degrader portfolio, extensive internal drug hunting expertise, and VantAI’s proprietary ‘Protein Contact First’ deep learning platform, we are advancing a robust degrader pipeline that spans a range of therapeutic areas and novel molecular targets.
ER
Breast Cancer
IKZF2
Oncology
CBP/p300
Oncology
SMARCA2/4
Oncology
AR
Prostate Cancer
STAT3
Oncology/Immunology
Additional Programs
Oncology/Immunology
Target 1
Oncology
Target 2
Oncology
We have multiple orally-administered androgen receptor (AR) protein degraders in development. Our AR degraders are designed to shut down the AR pathway by targeting and degrading the AR protein: the primary driver of prostate cancer.
In preclinical testing, our degraders have demonstrated high potency and selectivity, and they have produced encouraging tolerability data in toxicology studies completed to date. We have demonstrated in vitro activity in wild type AR as well as in multiple clinically relevant AR cell lines with known mutations.
The table below shows the DC50, or the concentration at which half-maximal degradation is achieved at 24 hours, of ARD-1671 in four different cell lines: vertebral cancer of the prostate (“VCaP”), which exhibits wild-type AR; and three cell lines exhibiting mutant AR: lymph node cancer of the prostate (“LNCaP”), 22RV1 and MDA-PCa-2b. Each of these cell lines are well-defined populations of cells that have been immortalized from human prostate cancer patients. Our lead AR candidate is in IND-enabling development.
We are developing signal transducer and activator of transcription 3 (STAT3) degraders for the treatment of STAT3-driven hematologic malignancies and immuno-oncology indications.
STAT3 is a transcription factor that regulates many biological processes and has been implicated as a direct driver of multiple tumor types. STAT3 controls – among other processes – differentiation, survival, proliferation and angiogenesis, typically in response to growth factors and cytokines. Due to potency and selectivity challenges, STAT3 has traditionally been considered to lack an easily druggable pocket. We believe the preclinical data we have generated to date suggest the potential of STAT3 degraders to overcome these challenges.
Our STAT3 degrader discovery program has identified a lead compound, SD-436, that potently and rapidly degrades the target with high specificity with respect to degradation of other STAT proteins. SD-436 exhibits promising potency against wild type STAT3 in human peripheral blood mononuclear cells (PBMCs) as well as a mutated STAT3 protein (K658R) in the Pfeiffer cell line, with degradation achieved at low nM concentrations. In a leukemia xenograft tumor model with an activated STAT3 pathway, IV administration of SD-436 resulted in deep reductions in tumor volume. The lowest dose tested, 5 mg/kg weekly, achieved rapid and complete tumor regression.
We have multiple undisclosed degrader programs spanning degrader modalities in various stages of development.