AI-powered drug discovery: update (XIII)
Companies with assets in preclinical and clinical trials: 💠 Cernais, 👾 Bullfrog, ✴️ Adnexus, 🔷 Nested and 🔶 Rakovina
“Don't be pushed around by the fears in your mind. Be led by the dreams in your heart.”
By Roy T. Bennett, The Light in the Heart
For the previous newsletters of this series of updates specifically on AI drug discovery companies with assets in preclinical and clinical trials 👉
Index for “AI-powered drug discovery: update part XIII” 🧵
💠 Cernais Srl
Cernais, an AI-powered drug discovery and RNA Therapeutics start-up from the Department of Biology at the University of Pisa in Italy, is utilizing its proprietary AI-powered approach to modulate the expression of X-linked genes aiming to restore cellular function and alleviate symptoms associated with Rett Syndrome, CDKL5 Deficiency Disorder and other diseases. They also offer fully personalized custom (end-to-end strategic AI screening) and repurposing screening services (refinement and repurposing of screened drugs).
Cernais designs drug therapies that can interfere with both mRNA and non-coding RNA. These therapies require several stages, including the design of the inhibitory molecule, its synthesis in the laboratory and encapsulation in nanoparticles or other carriers for administration in cells or preclinical models.
So far, through a third-generation screening they have identified drug candidates that have been validated at the preclinical stage for the treatment of Rett syndrome and CDKL5 deficiency disorder and they are currently testing these molecules in iPSC-derived neurons (and organoids) and animal models. This approach can be used to develop therapeutics for any X-linked or autosomal disease genes.
In particular, the Rett syndrome (RTT) is a rare and devastating neurological disorder caused by a mutation on the X chromosome, primarily affecting girls, that are born with impaired cognitive abilities and autistic behaviors, often from their first year of life due to a mutation in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. While MeCP2 mutations are lethal in most males, females survive birth but show severe neurological defects, since the X-chromosome inactivation (XCI) is a random process and approximately 50% of the cells silence the wild-type (WT) copy of the MeCP2 gene. Thus, reactivating the silent WT copy of MeCP2 could provide therapeutic intervention for RTT.
Currently, they are working with the identified inhibitors of the JAK/STAT pathway as XCI-reactivating agents, both by in vitro and ex vivo assays. In particular, they demonstrated that AG-490, a Janus Kinase 2 (JAK2) kinase inhibitor, and Jaki, a pan JAK/STAT inhibitor, are capable of reactivating MeCP2 from the inactive X chromosome, in different cellular contexts (A small-molecule screen reveals novel modulators of MeCP2 and X-chromosome inactivation maintenance).
Cernais just won the "Best Tuscany Start-Up 2024" competition.
👾 Bullfrog AI Holdings Inc
Bullfrog AI Holdings Inc, through its subsidiaries, operates as a digital biopharmaceutical company that focuses on AI/ML driven analysis of data sets in medicine and healthcare in the United States. bfLEAP™, developed at the prestigious Johns Hopkins University Applied Physics Laboratory and exclusively licensed to BullFrog AI for use in the drug development industry, is a unique graph analytic AI platform that rapidly detects anomalies and uncovers hidden associations within disparate, multimodal and incomplete data sets. This potent analytical tool leverages supervised and unsupervised ML to drive unbiased, transparent and explainable results, helping researchers ethically unlock invaluable insights.
At its core, the bfLEAP™ platform is designed with a keen focus on biological and clinical data sets, creating comprehensive data networks ready for in-depth analysis, and can be used for drug discovery, patient segmentation, drug repurposing, target discovery and enhanced clinical trial analysis.
On May 16, 2024, BullFrog announced significant advancements in its collaboration with the Lieber Institute for Brain Development (LIBD), including the identification of potential drug targets for multiple neuropsychiatric conditions. The collaboration between BullFrog AI and LIBD, announced in September 2023, leverages the bfLEAP™ platform to mine LIBD’s comprehensive brain data, that includes transcriptomic, genomic, DNA methylation, cell-line, clinical and imaging data from over 2,800 brain samples. Early results announced in January 2024 highlighted the ability to stratify brain expression data, revealing biological subtypes within psychiatric disorders.
BullFrog AI and LIBD have made remarkable progress in identifying novel subgroups between and within neuropsychiatric disorders, including major depression, schizophrenia and bipolar disorder and the team has successfully clustered patients by expression levels of gene isoforms across multiple brain regions. For each identified cluster, key genes have been pinpointed that explain cluster membership. To prioritize these genes for wet lab validation, BullFrog AI is now applying state-of-the-art causal AI/ML, a crucial step for confirming the therapeutic potential of the identified targets.
On October 09, 2024, BullFrog AI Announced Publication of Data Supporting Potential of Liver Disease Treatment Candidate BF-114. In particular, the study led by Dr. Lopa Mishra and published in Cell Reports, provided new mechanistic evidence for the role of BF-114 target β2-spectrin in obesity, MASLD (non-alcoholic fatty liver disease), MASH (metabolic dysfunction-associated steatohepatitis) and HCC (liver cancer). The findings suggested that targeting β2-spectrin with BF-114 can prevent the progression of liver diseases. BF-114 is currently in the discovery phase.
Apart BF-114, Bullfrog is working also with:
BF-222 (SMALL MOLECULE): GLIOBLASTOMA, PHASE 1
Their most advanced drug asset, a novel formulation of mebendazole, is a repurposed small molecule therapeutic that has been formulated to improve bioavailability and increase the likelihood of demonstrating efficacy.
BF-223 (SMALL MOLECULE): GLIOBLASTOMA, PHASE 1
BF-223 is a novel mebendazole prodrug that has shown in animal studies that it possesses significantly improved solubility and oral bioavailability compared to mebendazole, thereby enhancing its potential utility as a therapeutic agent.
On September 26, 2023, BULLFROG AI ANNOUNCED POSITIVE DATA FROM PRECLINICAL STUDY EVALUATING NOVEL PRODRUG OF MEBENDAZOLE FOR TREATMENT OF GLIOBLASTOMA.
MODIFIED HSV-1: COLORECTAL CANCER, DISCOVERY
Finally, the VP of AI, Dr. Enrique García-Rivera presented at Google's inaugural Cancer AI Symposium on October 30, 2024, in Boston showcasing BullFrog’s proprietary bfLEAP™ platform. Apart highlighting the company's collaboration with the Lieber Institute for Brain Development, Dr. García-Rivera introduced BullFrog AI's novel 'AlgoLLM' system for gene prioritization, which uses large language models to streamline the discovery of actionable insights in neuropsychiatric disorders and other diseases.