Selected Pipeline Programs

Pioneering the discovery and development of transformative medicines

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.

Program

Disease Area

Discovery

Preclinical

Clinical

ER

Breast Cancer

Discovery

IKZF2

Oncology

Discovery

CBP/p300

Oncology

Discovery

SMARCA2/4

Oncology

Discovery

AR

Prostate Cancer

Discovery

STAT3

Oncology/Immunology

Discovery

Additional Programs

Oncology/Immunology

Discovery

Target 1

Oncology

Discovery

Target 2

Oncology

Discovery

Selected Data Spotlight

PCT-4206

PVT-4206: Potential Best-in-class Heterobifunctional Estrogen Receptor α Degrader

PVT-4206 is a 5-fold More Potent ER Antagonist than ARV-471 In Vitro

  • Biochemical antagonism assay was established to measure ER inhibition

  • Inhibition of ER signaling and anti-tumor efficacy in breast cancer cells can result from ER degradation and/or antagonism

PVT-4206 is a Potent ER Degrader In Vitro

  • ER HiBiT assay was established
    in MCF-7 cells

  • Absence of estradiol (physiological agonist of ER) in media mimics treatment with an aromatase inhibitor

PVT-4206 Treatment in MCF7 Xenografts Leads to Tumor Growth Inhibition (TGI) and Tumor Shrinkage Over a Range of Doses

  • Once daily administration of PVT-4206 leads to dose responsive tumor growth inhibition of MCF-7 tumor xenografts

  • Tumor regressions are evident at 10 and 30 mpk doses of PVT-4206

  • A 3-fold lower dose of 10 mpk PVT-4206 provides equivalent efficacy to a higher 30 mpk dose of ARV-471

AR

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.

STAT3

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.

Undisclosed

We have multiple undisclosed degrader programs spanning degrader modalities in various stages of development.