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 a very good 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.

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

Targets for Metabolic disorders


Our first target is for a best-in-class program for weight-loss and diabetes control. Also, when combined with the existing GLP-1 drugs, it has the added benefit of preventing lean muscle loss


Our second target is aimed at treating MASH, an increasingly common health condition affecting large patient populations in India and other emerging markets


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