(Press-News.org) Insilico Medicine (“Insilico”), a clinical-stage generative artificial intelligence (AI)-driven drug discovery company, today announced that five preclinical programs have been accepted as poster presentations in the American Association for Cancer Research Annual Meeting 2024 (AACR 2024) happening April 5-10 in San Diego. Abstracts are now available on the AACR website.
Insilico’s drug discovery efforts are driven by its validated and commercially viable AI drug discovery platform, Pharma.AI, which works across biology, chemistry, and clinical medicine, providing the biotechnology and the pharmaceutical industry with advanced generative AI tools to accelerate their internal research and development.
A summary of Insilico's five preclinical programs to be presented at AACR is provided below:
1. Abstract Title：Discovery and preclinical characterization of ISM9342A, a novel, potent, and orally bioavailable WRN inhibitor that suppresses MSI-H tumor growth
Session category: DNA Damage and Repair 1
Session title：Molecular/Cellular Biology and Genetics
Session date & time: April 7, 2024, 1:30 PM - 5:00 PM
Published abstract number: 412
WRN is recognized as a promising target for synthetic lethality studies in MSI-H tumors and plays a crucial role in DNA repair and maintaining genomic integrity.
In this preclinical research, Insilico introduced the design, development, and evaluation of two selective, potent WRN helicase inhibitors, ISM9432A and ISM2196. Both compounds exhibit favorable ADMET and drug-like properties. The preclinical studies showed robust anti-tumor efficacy of ISM2196 in MSI-H xenografted cancer models relative to the known WRN helicase inhibitor. The lower efficacious dose of ISM2196 relative to existing WRN helicase inhibitors makes it an ideal candidate for further investigation.
2. Abstract Title：ISM6331, a novel and potent pan-TEAD inhibitor, exhibits strong anti-tumor activity in preclinical models of Hippo pathway-dysregulated cancers
Session category: Cell Signaling Components as Therapeutic Targets
Session title：Molecular/Cellular Biology and Genetics
Session date & time: April 8, 2024, 9:00 AM - 12:30 PM
Published abstract number: 1656
TEAD proteins are recognized as key transcription factors of the Hippo pathway and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance.
Insilico delivered ISM6331, a novel and potent TEAD inhibitor against TEAD1-4 by leveraging its generative AI platform. In preclinical studies, ISM6331 showed broad anti-tumor effect in multiple cell lines and potent efficacy at low doses in animal models. ISM6331 also showed synergism with EGFR or KRAS inhibitors in inhibiting tumor cell growth and overcame drug resistance in in vitro and in vivo models. In addition, ISM6331 showed excellent pharmacokinetic properties in multiple preclinical species and was well tolerated in GLP toxicity studies. The current research indicates ISM6331 has promising potential to treat Hippo pathway-dysregulated tumors as a monotherapy as well as in combination with targeted therapies.
3. Abstract Title：ISM9182A, a novel HPK1 inhibitor, exhibits immune modulatory activity and robust monotherapy anti-tumor effects in preclinical studies
Session category: Adaptive Immunity in Tumors
Session title：Immunology
Session date & time: April 9, 2024, 9:00 AM - 12:30 PM
Published abstract number: 3967
The hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) negatively regulates immune cells including T cells, B cells and dendritic cells, and is thus considered as an attractive immuno-oncology target in many tumor types.
In this research, ISM9182A was reported as a novel, potent, and selective inhibitor of HPK1, with nanomolar enzymatic potency, good family selectivity and dose-dependent pSLP76 inhibition effects in human PBMC. Moreover, In vivo studies revealed ISM9182A exhibited favorable ADME properties and good oral bioavailability across different species, as well as potent antitumor effects in a CT-26 syngeneic mouse model.
4. Abstract Title：Discovery and preclinical characterization of ISM8001, a covalent and selective FGFR2/FGFR3 dual inhibitor with strong monotherapy anti-tumor activity against advanced solid tumors
Session category: Advances in Cancer Prognostication, Therapeutic Response, and Immune Biology
Session title：Molecular/Cellular Biology and Genetics, immunology
Session date & time: April 9, 2024, 1:30 PM - 5:00 PM
Published abstract number: 5582
Oncogenic alterations in fibroblast growth factor receptors 2 and 3 (FGFR2 and FGFR3) are key drivers in multiple solid tumors.
ISM8001 is an orally available, highly selective dual inhibitor targeting FGFR2/3, and sparing FGFR1/4. The compound demonstrated superior potency in multiple FGFR2/3-driven efficacy models, and also in gatekeeper and molecular brake mutant-resistant models. It also showed favorable DMPK profiles, low efficacious dose, and desirable safety margin to support higher human dose.
5. Abstract Title：ISM9682A, a novel and potent KIF18A inhibitor, shows robust antitumor effects against chromosomally unstable cancers
Session category: Pharmacologic Targeting of Cell Cycle Proteins
Session title：Molecular/Cellular Biology and Genetics
Session date & time: April 9, 2024, 1:30 PM - 5:00 PM
Published abstract number: 5727
Studies have shown the potential of targeting KIF18A, a member of the kinesin-8 subfamily, against cancers exhibiting high chromosomal instability.
In this research, Insilico reports ISM9682A, a novel KIF18A inhibitor with high potency and selectivity. In preclinical studies, ISM9682A demonstrated excellent monotherapy anti-proliferative activity in multiple cancer cell lines, as well as a prolonged drug-target residence time indicated by both enzymatic and cellular assays. Notably, ISM9682A demonstrated not only robust biological potency and high selectivity, but also desirable in vitro ADMET characteristics, excellent in vivo exposure, clearance, and good oral bioavailability across multiple preclinical species.
Insilico Medicine is a pioneer in utilizing generative AI for drug discovery and development, and has delivered breakthroughs for healthcare in multiple disease areas, including fibrosis, cancer, immunology and aging-related diseases. Since 2021, Insilico has nominated 18 preclinical candidates in its comprehensive portfolio of over 30 assets and has advanced six pipelines to the clinical stage. Most recently, the company published a history of its lead AI-discovered and AI-designed drug for idiopathic pulmonary fibrosis, currently in Phase II clinical trials, in Nature Biotechnology.
About Insilico Medicine
Insilico Medicine, a global clinical-stage biotechnology company powered by generative AI, connects biology, chemistry, and clinical trial analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and generating novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. www.insilico.com
END
Insilico Medicine presents progress of 5 novel AI cancer drugs at AACR
2024-03-29
ELSE PRESS RELEASES FROM THIS DATE:
Study finds benefits in prescribing alcohol use disorder medications upon discharge from alcohol-related hospitalizations
2024-03-29
BOSTON – For adults hospitalized for alcohol-related reasons, receiving a prescription for an alcohol use disorder (AUD) medication at the time of discharge may lower their risk of return to hospital within 30 days of discharge, including emergency room visits and readmissions.
That’s according to a recent study published in JAMA Network Open led by researchers at Massachusetts General Hospital (MGH) and the University of Pittsburgh.
For the study, the investigators identified 9,834 alcohol-related hospitalizations among 6,794 Medicare Part D beneficiaries across the United States in 2016. Only 2.0% of hospitalizations involved filled ...
USC Schaeffer Center study finds few hospitals promoting potentially predatory medical payment products
2024-03-29
Fifty million Americans are on a financing plan to pay off medical or dental bills, with one-quarter of those bearing some interest. Increasingly, medical payment products (MPPs) – which include credit cards and loans administered by hospitals, physician practices, or third-party companies – have come under scrutiny by the Consumer Financial Protections Bureau, U.S. Department of Health & Human Services and the Treasury.
The agencies’ concern is that the products may be sidestepping a broad range of patient and consumer protections and inflating ...
Mandatory standards for the indoor environment would result in immense benefits to the health and productivity of people around the world
2024-03-29
This publication is a call to action for governments and agencies to develop, legislate and enforce IAQ standards. Boerstra: “Traditionally, governments have regulated outdoor air. But inhabitants of industrialized countries now spend more than 90% of their time indoors.” As a result, indoor pollutants have major consequences for our long-term health. Bluyssen: “For example, we now know that tiny airborne particles can pass directly from lungs to bloodstream, where they cause all kinds of diseases.” And indoor air is also a prime transmitter of pathogens, as demonstrated by the COVID-19 ...
Chickadees have unique neural “barcodes” for memories of stashing away food
2024-03-29
Your ability to remember and recall moments in time is important for recording life-defining moments and everyday information like where you parked the car. Now researchers reporting in the journal Cell on March 29 have new insight into how those episodic memories are encoded in the brain based on studies of how chickadees store food.
Their study finds that chickadees activate unique neural patterns, which they liken to barcodes, each time they cache food in a certain spot. When they go back to retrieve that stored food, their brains light back ...
Chickadees are memory geniuses. Their barcode-like neural activity may be to thank
2024-03-29
NEW YORK, NY — Black-capped chickadees have extraordinary memories that can recall the locations of thousands of morsels of food to help them survive the winter. Now scientists at Columbia's Zuckerman Institute have discovered how the chickadees can remember so many details: they memorize each food location using brain cell activity akin to a barcode. These new findings may shed light on how the brain creates memories for the events that make up our lives.
"We see the world through our memories of objects, places and people," said Dmitriy Aronov, PhD, a principal investigator at Columbia’s Zuckerman Institute and an ...
Tiny orchid flowers pollinated by tiny flies
2024-03-29
Researchers Yuta Sunakawa, Ko Mochizuki, and Atsushi Kawakita of the University of Tokyo discovered the first orchid species pollinated by gall midges, a tiny fly species. This is the first documented case of an orchid species found to be pollinated by gall midges, and it makes the orchids the eleventh such plant family. The findings were published in the journal Ecology.
The family of orchids is rich both in numbers and variety. Their range of shapes and sizes is due to having evolved to attract different animal pollinators. However, scientists have only mapped ...
Researchers develop AI-based tool paving the way for personalized cancer treatments
2024-03-29
In the ongoing fight against cancer, scientists around the globe are exploring innovative approaches to unlock the mysteries of the human immune system — the complex network of organs, cells and proteins that defends the body against disease.
A team led by Arizona State University scientists have developed an AI-based learning tool called HLA Inception that’s uncovered new information about how an individual person’s immune system responds to foreign cells.
Focusing on a group of proteins called Major Histocompatibility Complex-1(MHC-1), the AI-based tool, in seconds, can classify the specific group of proteins unique for ...
Reports of COVID-19 vaccine adverse events in predominantly republican vs democratic states
2024-03-29
About The Study: This study found that the more states were inclined to vote Republican, the more likely their vaccine recipients or their clinicians reported COVID-19 vaccine adverse events. These results suggest that either the perception of vaccine adverse events or the motivation to report them was associated with political inclination.
Authors: David A. Asch, M.D., M.B.A., of the University of Pennsylvania in Philadelphia, is the corresponding author.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2024.4177)
Editor’s ...
Patient out-of-pocket costs for biologic drugs after biosimilar competition
2024-03-29
About The Study: The findings of this study suggest that biosimilar competition was not consistently associated with lower out-of-pocket costs for commercially insured outpatients, highlighting the need for targeted policy interventions to ensure that the savings generated from biosimilar competition translate into increased affordability for patients who need biologics.
Authors: Benjamin N. Rome, M.D., M.P.H., of Brigham and Women’s Hospital in Boston, is the corresponding author.
To access the embargoed study: ...
New Brigham research highlights combining prostate MRI with a blood test to avoid unnecessary prostate biopsies
2024-03-29
MRI of the prostate, combined with a blood test, can help determine if a prostate lesion is clinically significant cancer, new research suggests
A new meta-analysis by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, suggests that doctors and patients can avoid unnecessary prostate biopsies by combining MRI of the prostate findings with prostate-specific antigen (PSA) density. This new approach to diagnosing clinically significant prostate cancer can decrease patient ...