Pipeline
Satya’s Pipeline comprises First-In-Class and Best-In-Class
Targets focused on DDR pathway and Oncogenes.
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
87%
SOS1
Oncogene; NSCLC, CRC
EGFR mutation & Pan RAS mutation
Global
76%
PKMYT1
DDR/ Cell cycle
CCNE1 amplification
Partnered
The program (ALVX-A) is partnered with Alivexis, Inc., a US/ Japanese biotech
KIF18A
DDR; Solid tumors
CIN+ve cells
Global
49%
PARG
(covalent inhibitor)
DDR; Breast and Ovarian cancers
HRD
Global
35%
Undisclosed, First-in-class mechanism
DDR; Solid tumors
Undisclosed
Global
9%
Pipeline
Satya’s Pipeline comprises First-In-Class and Best-In-Class
Targets focused on DDR pathway and Oncogenes.
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
91%
SOS1
Oncogene; NSCLC, CRC
EGFR mutation & Pan RAS mutation
Global
77%
PKMYT1
DDR/ Cell cycle
CCNE1 amplification
Partnered
The program (ALVX-A) is partnered with Alivexis, Inc., a US/ Japanese biotech
KIF18A
DDR; Solid tumors
CIN+ve cells
Global
49%
PARG
(covalent inhibitor)
DDR; Breast and Ovarian cancers
HRD
Global
35%
Undisclosed, First-in-class mechanism
DDR; Solid tumors
Undisclosed
Global
11%
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):6708–6720 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
Satya’s SOS1 inhibitors demonstrate complete pERK and pAKT inhibition across various cell lines and best-in-class efficacy in a KRAS driven cancer xenograft model.
Ref: Adapted from Cancers 15.20 (2023): 5015
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
Eva Gogola et al, Cancer Cell June 2019
KIF18A
- Chromosomal instability (CIN), characterized by frequent mis-segregation of chromosomes during mitosis, is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that comprise the mitotic spindle. Thus, CIN +ve tumor cells may respond differently than normal diploid cells to treatments that target mitotic spindle regulation. KIF18A is required for proliferation of CIN +ve cells derived from triple negative breast cancer or colorectal cancer tumors but not in near-diploid cells. CIN +ve tumor cells exhibit mitotic delays, and increased cell death following inhibition of KIF18A. Sensitivity to KIF18A knockdown is strongly correlated with centrosome fragmentation. (Carolyn Marquis et al., Nature Communications, 2021).
Satya's KIF18A inhibitor is a highly differentiated best-in-class compound characterized by superior pharmacokinetic properties (clearance in 12 hrs compared to 48 hrs in competitor compounds) potentially leading to superior safety and druggability
Louise Jannsen et al., Current Biology September 2018
PKMYT1
- The program (ALVX-A) is partnered with Alivexis, Inc., a US/ Japanese biotech
- 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
- 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 (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
