Delving into the Latest Updates on Aanastra Inc. with Synapse

Overview

Basic Info

Introduction

AANASTRA (formerly AADIGEN) specializes in the development of in vivo targeted RNA therapeutics in the treatment of cancers and genetic diseases. The company’s technology is based on proprietary RNA and proprietary peptides complexed together for targeted in vivo delivery of RNA. Our versatile breakthrough technology tackles the major stumbling block in RNA therapeutics which continues to be the systemic in vivo targeting and cellular-release of RNA-based agents. Our approach provides an effective strategy for a wide range of clinical applications and pathologies. The company was founded by Dr. Neil Desai (Abraxis, Celgene, Aadi Bioscience) and the technology and its use in the delivery of RNA therapeutics is based on the original research of Dr. Gilles Divita, who pioneered the cell penetrating peptide strategy for oligonucleotide delivery. Aanastra (Los Angeles, CA) works closely on its RNA therapeutics technology with its sister company Divincell SAS (Nimes, France).

Tags

Neoplasms

Skin and Musculoskeletal Diseases

Respiratory Diseases

mRNA

CRISPR/Cas

mRNA vaccine

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	9
Endocrinology and Metabolic Disease	2

Top 5 Drug Type	Count

mRNA	9
CRISPR/Cas	4
mRNA vaccine	1

Top 5 Target	Count

KRAS G12C x KRAS G12D x KRAS G12V	3
BRCA1(Breast cancer type 1 susceptibility protein)	3
PCSK9(Proprotein convertase subtilisin kexin type 9)	1
KRAS G12C x PARP x p53	1

AbstractThe p53 tumor suppressor mutations resulting in loss of function control tumor proliferation in 50% of human cancers. TP53 missense and nonsense mutations are present in about 50% and 7-12% of the p53 driven cancer, respectively. To date there is no effective treatment for rescuing p53 function in cancers harboring p53 nonsense mutations. We have developed a new potent strategy combining mRNA with a tumor selective nanocarrier, to rescue of p53 tumor suppressor functions as potential therapeutic approach in cancers. ADGN-531 contains proprietary p53-mRNA complexed with proprietary short amphipathic peptides that form stable neutral nanoparticles. ADGN-531 was evaluated on 20 different cancer cell lines harboring different types of p53 mutations. In-vivo efficacy of IV-administered ADGN-531 nanoparticles (weekly, 0.5 & 1.0mg/kg) was evaluated on colorectal SW403 (p53 nonsense/KRASG12V), osteosarcoma SaOs2 (p53 null) and lung H358 (p53 null/KRASG12C) mouse xenografts. Sensitivity to Veliparib (PARPi) following ADGN-531 treatment was evaluated on PARPi resistant SUM-149PT and OVCAR-8 and PARPi sensitive MDA-MB436 cells. ADGN-531/AMG-510 synergy was evaluated on H358 and M-PACA cells and H358 mouse xenograft. ADGN-531 markedly delay the growth of a large panel of cancer cells harboring p53-missense or nonsense mutations, by rescuing p53 transcriptional activity and subsequent expression of its target proteins. ADGN-531 induces cell cycle arrest in G1 due to p21 upregulation and apoptosis following BAX and PUMA activation. ADGN-531 mediated p53 function rescue is directly correlated to the type of p53 mutation in the cancer cells. ADGN-531 induces 80% cell proliferation inhibition in p53 null/nonsense cells and 20 to 50% in p53 missense cells. IV-administration of ADGN-531 resulted in dose responsive tumor growth inhibition. ADGN-531 (1.0mg/kg) induces 40-60% tumor regression SaOs2, SW403 and H358 xenografted mouse model. We demonstrated a synergistic combination between ADGN-531/AMG-510 a KRASG12C inhibitor in human lung carcinoma. ADGN-531 (0.5mg/kg, weekly)/AMG-510 (10mg/kg, daily) induces about 80% tumor regression, higher than with either single agents. We demonstrated that ADGN-531 mediated p53 rescue markedly improves (200 fold) and restores the sensitivity of ovarian and breast cancer cells to Veliparib. ADGN-531 treatments are well tolerated, no sign of clinical toxicity or inflammatory response was detected after single or repeated administrations. ADGN-531 is effective in rescuing P53 functions both in vitro and in vivo. Our study provides a proof-of-concept that restoration of tumor suppressor function by ADGN-531 could be used as a single agent therapy or in combination together with other therapies for potent combinatorial cancer treatment.Citation Format: Gilles Divita, Audrey Grunenberger, Elodie Czuba, Khadidja Boularache, Melanie Guidetti, Veronique Josserand, Neil Desai. p53 rescue of tumor suppressor function with ADGN-531 causes tumor regression both as single agent and in combination with PARPi and KRASG12Cinhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 550.

04 Apr 2023·Cancer Research

Abstract 1717: KRAS mutant gene editing prevents tumor growth in vivo and overcomes acquired resistance to KRASG12C inhibitor

Author: Divita, Gilles ; Czuba, Elodie ; Josserand, Veronique ; Guidetti, Melanie ; Desai, Neil ; Guzman-Gonzales, Veronica ; Grunenberger, Audrey

AbstractMutations on KRAS codon12 are among the most commonly observed mutations in pancreatic, colorectal and lung cancers. To date, only treatment targeting KRASG12C mutation have been successful in the clinic and approved. However, it is hampered by adaptive resistance, mainly associated with the emergence of other KRAS mutations and high amplification of KRASG12C allele. We have developed a new potent strategy combining gene editing with a tumor selective nanocarrier, to impair cancer cell proliferation by directly targeting G12D, G12V,and G12C mutations of the KRAS oncogene. ADGN-121, ADGN-122 and ADGN-123 are gene-editing complexes containing proprietary sgRNA targeting KRASG12D, KRASG12V or KRASG12C with mRNACas9 complexed with proprietary short amphipathic peptides that form stable neutral nanoparticles. The complexes were evaluated on pancreas, colorectal and lung cancer cells harboring KRASG12D, V, or C mutations. KRAS mutant indel frequency was evaluated by T7E1 method. In-vivo efficacy of IV-administered ADGN/mRNACas9gRNA (0.25-1.0mg/kg, 2 injections at day 1 & 7) was evaluated in Panc1 (KRASG12D) and SW403 (KRASG12V) mouse xenografts. ADGN-123 in combination with AMG-510 (KRASG12C inhibitor) was evaluated on H358, PACA2 and SW837 cells, exhibiting an acquired resistance to AMG-510. ADGN-121,-122 and -123 efficiently and selectively silenced KRASG12D, KRASG12V KRASG12C , respectively, in colorectal, pancreatic and lung cancer cells resulting in reduction of cell proliferation by 80% and inhibition of ERK and/or AKT phosphorylation. Only two IV-administrations of ADGN-121 containing gRNAG12D abolished Panc1 tumor growth in a dose dependent manner, resulting in tumor regression of 60-70% at 1.0mg/kg. ADGN-122 containing gRNAG12V abolished SW403 tumor growth with a tumor regression of 70% at 1.0 mg/kg. In contrast, no effect on tumor growth was observed with nonspecific gRNA. The combinations of ADGNs with drugs currently used on clinic have been evaluated. We demonstrated a synergistic combination ADGN-121/Abraxane in pancreatic carcinoma and ADGN-122/Capecitabine in colon Adenocarcinoma. We showed, that ADGN-123 containing gRNAG12C can effectively reduce the proliferation and inhibit ERK and AKT phosphorylation of AMG-510 acquired resistance cells and that no resistance occurs after ADGN-123 treatment. ADGN treatments are well tolerated, no sign of clinical toxicity, inflammatory response or emergence of other KRAS mutation was detected after single or repeated administrations. ADGNs were effective in targeting selectively mutated KRAS both in vitro and in vivo. Our study provides a proof-of-concept that ADGN can be applied to target driver mutations of cancers in vivo and permanently disrupt the oncogenic alleles, leading to major tumor regression. ADGN-123 can be used as a strategy to overcome resistance associated to small molecule inhibitors of KRASG12C.Citation Format: Gilles Divita, Veronica Guzman-Gonzales, Audrey Grunenberger, Elodie Czuba, Melanie Guidetti, Veronique Josserand, Neil Desai. KRAS mutant gene editing prevents tumor growth in vivo and overcomes acquired resistance to KRASG12C inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1717.

1

News (Medical) associated with Aanastra Inc.

03 Apr 2024

·www.globenewswire.com

Aanastra Inc to Present Multiple Posters on RNA Therapeutics at the American Association for Cancer Research (AACR) Annual Meeting 2024

LOS ANGELES and NIMES, France, April 03, 2024 (GLOBE NEWSWIRE) -- Aanastra, Inc., a biopharmaceutical company focused on developing novel RNA therapeutics targeting Tumor Suppressors and Oncogenes, today announced poster presentations at the 2024 American Association for Cancer Research (AACR), taking place April 5-10, 2024, in San Diego, CA. AACR poster presentation details are below: Title: " In vivo rescue of p53 tumor suppressor function with ADGN-531 across Pan-p53 alterations "Session Title: Mechanisms of Drug Action Location: Poster Section 26, Board Number 17Abstract Number: 640Date/Time: Sunday Apr 7, 2024 1:30 PM - 5:00 PMPresenting Author: DIVITA Gilles, PhD Title: " Selective deletion of the KRAS mutant gene with ADGN-121 and ADGN-122 peptide-RNA nanoparticles: A new strategy to overcome acquired resistance to KRASG12C and KRASG12D small molecule inhibitors "Session Title: Vector Systems, Oncolytic Virotherapy, and Gene TherapyLocation: Poster Section 27, Board Number 3Abstract Number: 7236Date/Time: Wednesday Apr 10, 2024 9:00 AM - 12:30 PM Presenting Author: DIVITA Gilles, PhD Title: " Peptide-mRNA complex mediated restoration of BRCA-1 tumor suppressor function in BRCA-1 mutated cancers as a new therapeutic strategy "Session Title: Vector Systems, Oncolytic Virotherapy, and Gene TherapyLocation: Poster Section 27, Board Number 4Abstract Number: 7237Date/Time: Wednesday Apr 10, 2024 9:00 AM - 12:30 PM Presenting Author: DIVITA Gilles, PhD More information can be found on the AACR meeting website. About Aanastra, Inc. Aanastra Inc (formerly Aadigen Inc) is a start-up biopharmaceutical company focused on treating cancer using its novel RNA therapeutics strategy to target aberrant Tumor Suppressor Genes and Oncogenes. The technology driving Aadigen’s approach is based on proprietary RNA combined with proprietary peptides that are able to target various tissues and tumors in vivo unlike commonly used strategies for RNA delivery including viral and lipid-based methods. Aanastra’s strategy for aberrant Tumor Suppressor Rescue using proprietary mRNA and gene editing of mutated Oncogenes have shown remarkable antitumor effects in animal models of various cancers that have mutated P53, KRAS or BRCA1. The utility of Aanastra’s technology has also been demonstrated outside of cancer in animal models of hemophilia A to normalize Factor VIII levels and in cholesterol lowering applications by targeting PCSK9. Aanastra (Los Angeles, CA) works closely with its sister company Divincell SAS (Nimes, France) in the development of its RNA therapeutics. More information on the Company's strategy is available on the Aanastra website at www.aanastra.com and connect with us on LinkedIn.

AACRsiRNA

100 Deals associated with Aanastra Inc.

Login to view more data

100 Translational Medicine associated with Aanastra Inc.

Login to view more data

Corporation Tree

Boost your research with our corporation tree data.

login

or

view full example data

Boost your research with our corporation tree data.

Pipeline

Pipeline Snapshot as of 23 Dec 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

14

Login to view more data

Current Projects

Drug(Targets)	Indications	Global Highest Phase

ADGN-531 ( KRAS G12C x PARP x p53 )	Neoplasms More	Preclinical
ADGN-CRP-104	Pulmonary Fibrosis More	Preclinical
ADGN-902 ( BRCA1 )	Breast Cancer More	Preclinical
PCSK9 GENE EDITING ( PCSK9 )	Hypercholesterolemia More	Preclinical
ADGN-CRP-102	Liver Diseases More	Preclinical