AI-complemented Mechanism Agnostic Targeted Therapies across Indications

Pipeline

Pipeline

Satya’s Pipeline comprises First-In-Class and Best-In-Class
Targets focused on DDR pathway and Oncogenes.

Target MOA / Indication Bio Marker Rights Early Discovery Lead Optimization Pre - Clinical IND
RAD51:BRCA2 Disruptor DDR; PARPi-Resistant Ovarian and Breast Cancers RAD51 Global
SOS1 Oncogene; NSCLC, CRC EGFR Mutation & Pan RAS Mutation Global
PKMYT1 DDR / Cell Cycle CCNE1 Amplification Partnered
First-in-class biology (Platform) Oncology/ Inflammation Undisclosed Partnered
PARG (Covalent Inhibitor) DDR; Breast and Ovarian Cancers HRD Global
Metabolic pathways Obesity & complementary care Undisclosed Global

RAD51:BRCA2 DISRUPTOR

SAT-122 is a first-of-its-kind disruptor of RAD51:BRCA2 interaction, a novel mechanism in the DDR space

SAT-122 shows significantly superior activity in patient-derived primary cells compared to Olaparib and PARG inhibitors

  • The centrality and functionality of RAD51 in the DDR pathway confers upon it a broad role in various replication stress-induced cancers. Thus, there is a potentially wide patient base that can be treated with this class of drugs.
  • Our candidate compound, by specifically targeting RAD51:BRCA2 inhibition: a) transiently prevents nuclear RAD51 foci formation; b) has no effect on RAD51 expression; c) does not affect any of the other functionalities of RAD51 (ATP hydrolysis, multimerization or DNA binding); and d) is unlikely to lead to overt toxicities
  • SAT-122 is preferentially active towards RAD51 high & BRCA2 WT tumors while sparing normal cells
  • SAT-122 is initially being clinically positioned for PARPi-resistant ovarian and breast cancer patients, a high clinically unmet need. These patients have high RAD51 foci both as a biomarker and driver of resistance.
  • SAT-122 is designed to offer a potentially significantly better safety window compared to other HR pathway inhibitors including CHK 1/2 and ATR inhibitors.

Ref: Annals of Oncology 29: 1203 1210, 2018; Clinical Breast Cancer Volume 18, Issue 2, April 2018, Pages 184-188; Clin Cancer Res. 2017 November 01; 23(21):67086720 Cancer Cell International (2023) 23:231 BMB Rep. 2019; 52(2): 151-156] Plos one 17.8 (2022): e0266645. Cancers 13.12 (2021): 2930. Nature Communications 14.1 (2023): 7003.

SAT-122, the IND-candidate, has demonstrated excellent efficacy in multiple ovarian cancer xenograft models, as a single angle and in combination with chemo and PARP inhibitors while demonstrating an excellent safety profile

SOS1


  • SOS1 is a guanine nucleotide exchange factor for RAS proteins involved in activating Ras. Inhibition of SOS1 results in lowering the Ras-GTP activated state, inhibiting the RAS-MEK-ERK pathway and lowering proliferation, in both WT and the various mutant Ras isoforms.
  • SOS1 inhibition is synthetic lethal with activating SHP2 mutations (10-20% of many of solid tumors).
  • SOS1 acts as a potential driver in late stage Hepatocellular Carcinoma (HCC) & Receptor Tyrosine Kinase (RTK) resistant mutant EGFR bearing cancers.

Satyas SOS1 inhibitors demonstrate complete pERK and pAKT inhibition across various cell lines and best-in-class efficacy in a KRAS driven cancer xenograft model.

PARG


  • Despite the success of PARP inhibitors, drug resistance is a clinical hurdle. Loss of PAR glycohydrolase (PARG) is identified as a major resistance mechanism. PARG depletion restores PAR formation and partially rescues PARP1 signaling. Thus, PARG ihhibition provides an therapeutic opportunity to sensitize PARP inhibitors further.
  • Additionally, PARG inhibition disrupts DNA damage repair cycle and leads to cell death. PARG depleted/ inhibited cells show increased sensitivity to DNA damage agents.
  • Covalent inhibition offers a significantly higher and more sustained PD resulting in a best-in-class pharmacological profile.

We anticipate identification of a differentiated candidate compound by end-2024

PKMYT1


The WEE1 kinase family consists of three serine/threonine kinases sharing conserved molecular structures and encoded by the following genes:

  • WEE1 (WEE1 G2 Checkpoint Kinase)
  • PKMYT1 (membrane-associated tyrosine- and threonine-specific cdc2- inhibitory kinase)
  • WEE1B (WEE2 oocyte meiosis inhibiting kinase)

PKMYT1 kinase functions as negative regulator of CDK1. Inhibiting its function leads to unscheduled activation of CDK1 selectively in CCNE1-overexpressing cells, promoting early mitosis in cells undergoing DNA synthesis

Ghelli Luserna di Ror, Andrea, et al., 2020


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