AI-powered drug discovery: update (XI)
AI-powered drug discovery: update (XI)
✴️ BPGbio, ✳️ Integrated, 🔷 Lundbeck, 🔶 Genetic Leap, ⚜️ Oxford Drug Design, 🔰 Owkin, ✅ Turbine, 👾 Algorae, 💠 Pepper and ⚛️ Atossa
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 XI” 🧵
BPGbio
Integrated Biosciences
Lundbeck
Genetic Leap
Oxford Drug Design
Owkin
Turbine AI
Algorae Pharmaceuticals
Pepper Bio
Atossa
✴️ BPGbio Inc
BPGbio is a leading biology-first AI-powered clinical stage biopharma focused on mitochondrial biology and protein homeostasis. BPGbio’s NAi platform is digitazing patient biology, using clinically annotated unbiased patient samples and causal AI to identify biological signals within the noise of billions of patient data points; revealing hidden cause and effect relationships that fuel drug discovery and de-risk drug development.
The NAi Interrogative platform consists of an industry leading and clinically annotated proprietary biobank, with purpose-built causal AI and is using the world’s fastest supercomputer, Frontier, at Oak Ridge National Laboratory (ORNL), making it a pioneer in fully-integrated high performance computing (HPC) platform in the biopharmaceutical industry for AI-driven target nomination, development and molecule design.
BPGbio Inc acquired Berg LLC (a data driven biological research and biopharma company) in January 2023 (Supercomputer-based Bayesian approach to AI pays dividends for BPGbio). Before the acquisition, BERG’s Interrogative Biology® platform discovered BPM 42522, its lead discovery molecule with anti-cancer properties. And a drug called BPM31510, an ubidecarenone-lipid conjugate nanodispersion targeting mitochondrial superoxide.
BPGbio’s Interrogative Biology® platform has already advanced a robust pipeline of late-stage drug candidates and R&D assets in oncology, neurology and rare diseases, such as:
Mitocondrial Medicine
BPM31510-IV (acts by targeting the mitochondrial machinery and tumor microenvironment, TME, to create a metabolic shift in cancer cells) for
Glioblastoma, Radiation Sensitizer, Phase 2
On September 12, 2024, BPGbio presented two posters on the ongoing Phase 2 trial (NCT04752813) of its lead candidate, BPM31510, in patients with newly diagnosed glioblastoma multiforme (GBM) at the European Society for Medical Oncology Congress 2024, taking place September 13-17 in Barcelona.
BPM31510, combined with Vitamin K and standard chemoradiation, is being tested in a single-arm Phase 2b trial across four U.S. sites, with a total target enrollment of 50 patients.
The preliminary results from the ongoing clinical trial support their biology-first, AI-driven approach, optimizing patient selection and streamlining drug development.
Pancreatic Cancer, Chemotherapy Sensitizer, Phase 2
BPM 31510, a naturally occurring coenzyme structurally similar to vitamin K, works with mitochondria to restore cellular energy processes and induce cell death in cancer cells by mimicking the potential of the BCL-2 protein family.
In the initial Phase IIa study, those who received BPM 31510 intravenously alongside chemotherapy as a second and third-line treatment, had a doubled progression free survival (PFS) when combined with gemcitabine in participants with advanced pancreatic cancer.
Primary Q10 Deficiency, Direct Replacement, Phase 2
BPM31510, is currently in active Phase 2 trials in aggressive cancers, and BPGbio is exploring Phase 3 trials for Primary CoQ10 Deficiency and Primary Mitochondrial Disease (European Bioenergetics Conference (EBEC) 2024 that took place August 26-31, 2024, in Innsbruck, Austria).
On October 1, 2024, PGbio received a Rare Pediatric Disease Designation from the US Food and Drug Administration (FDA) for BPM31510IV to treat primary coenzyme Q10 deficiency, an ultra-rare mitochondrial disorder.
BPM31510-T
Squamous Cell Carcinoma, Wound Healing, Phase 2
Epidermolysis Bullosa, Wound Healing, Phase 1
Preliminary evidence from Phase 1 clinical trial suggests BPM31510 to be well tolerated and also potentially efficacious in improving wound healing.
Preclinical data demonstrates that BPM31510 influences several components of wound healing pathways to help in the treatment of wounds.
BPGbio’s Epidermolysis Bullosa drug candidate (BPM31510) received FDA Orphan-Drug Designation in May 2018.
BPM31510-Oral
Sarcopenia, Mitochondrial Respiration, Phase 2
The Phase 2 BPGbio’s BPM31510 sarcopenia trial will recruit 40 patients between the ages of 65-90 for this study. Patients will be treated for 28 days and subsequently analyzed for physical and metabolic fitness.
Protein Homeostasis
BRG399
Solid Liquid Tumors, Secondary CVD Prevention, Preclinical
Tubulin Polymerization, Neutrophil Inflammation, Preclinical
HDD
Huntington’s Disease, muHtt Homeostasis
Researchers demonstrated that treatment with the UBE2K discharge inhibitor, BPG-0812, a small molecule drug candidate, slowed the discharge of ubiquitin from UBE2K. The results of this study suggested that modulating UBE2K activity can effectively disrupt the aggregation of mutant Htt, presenting a promising new pathway for therapeutic intervention for Huntington’s Disease.
Targeted Protein Degradation, Preclinical (IND enabled)
Oncology, E2-based TPD (Discovery)
On October 7, 2024, BPGbio and the University of Oxford’s Centre for Medicines Discovery announced a five-year research collaboration focused on advancing novel protein degradation technologies, particularly in oncology and central nervous system (CNS) diseases (for example Parkinson’s), with the goal of unlocking new therapeutic pathways.
Apart the drug candidates the company’s diagnostic pipeline includes:
A prostate diagnostic test pstateDx:
pstateDx™, is an AI-discovered prostate cancer protein biomarker diagnostic, a non-PSA based unique molecular diagnostic blood test that measures Filamin A, a key biological driver of prostate cancer. pstateDx™ has demonstrated enhanced capability of providing a risk score to differentiate between Benign Prostatic Hyperplasia (BPH) and aggressive prostate cancer at the time of initial screening.
And tests being developed and validated for the detection of:
Parkinson’s disease, ParkinsonDx,
BPGbio has discovered a panel of novel biomarkers for identification and stratification of Parkinson’s Disease which have been validated in a CLIA laboratory setting. BPGbio has trademarked its parkinsonDx™ panel and is exploring partnerships to commercialize this innovative product. The test is currently not commercially available in the United States.
Pancreatic cancer, PancDx,
Breast cancer and
Liver disease.
On September 25, 2024 BPGbio and Joslin Diabetes Center, the world's leading diabetes care and research center, announced the publication of a study titled "Light-responsive adipose-hypothalamus axis controls metabolic regulation" in the peer reviewed journal Nature Communications (BPGbio and Joslin Diabetes Center Announce Publication Showing Game-Changing Effects of Blue Light in the Reduction of Fat Cells). The study highlights a light-sensitive protein that can reduce adipose tissue and the findings offer a game-changing novel approach to managing obesity and its associated metabolic disorders.
Finally, on October 15, 2024 BPGbio announced its participation in the US Pharma Partnering Summit, scheduled for October 16, in Boston. BPGbio executive Vivek K. Vishnudas, Ph.D., Chief Technology Officer and R&D Site Head, will present a session titled, "A Novel and Differentiated Approach to Targeted Protein Degradation - Leveraging the Ubiquitin Conjugating Enzyme (E2) Family."
✳️ Integrated Biosciences Inc
Integrated Biosciences, a California startup with MIT and Harvard roots founded in 2022, combines synthetic biology and AI to target cellular stress responses linked to conditions such as neurodegeneration, cancer, diabetes and osteoarthritis. Having pioneered the first AI-driven discovery of a structural class of antibiotics last year (Discovery of a structural class of antibiotics with explainable deep learning), the company is now developing a portfolio of preclinical-stage assets to treat multiple age-related diseases for:
Modulating Aging Cells (IND-enabling),
Integrated Biosciences with the power of AI has just discovered novel senolytic compounds (that are highly selective for Bcl-2) that have the ability to suppress age-related processes such as fibrosis, inflammation and cancer, (Artificial intelligence identifies anti-aging drug candidates targeting ‘zombie’ cells).
Discovering small-molecule senolytics with deep neural networks
In particular, molecular docking simulations of compound binding to several senolytic protein targets (combined with time-resolved fluorescence energy transfer experiments) indicated that these compounds act in part by inhibiting Bcl-2, a regulator of cellular apoptosis. By testing one compound, BRD-K56819078, in aged mice they found that it significantly decreased senescent cell burden and mRNA expression of senescence-associated genes in the kidneys.
Modulating Cellular Stress (Discovery),
Protecting Against Cellular Damage (Discovery),
Inflammation and Inflammaging (Discovery),
Biomechanical function and aesthetics (Discovery).
On October 3, 2024, Integrated Bio landed $17M to accelerate longevity drug development. The funding round was led by Sutter Hill Ventures, with participation from Lifespan Vision Ventures, Root Ventures, Civilization Ventures, Illumina Ventures Labs and several others.
Sinopia
Sinopia Biosciences, Inc., a biotechnology company advancing novel therapeutics identified using its proprietary computational drug discovery platform, announced that it has been awarded a Phase II SBIR grant totaling $2.2M from the National Institute of Dental and Craniofacial Research (NIDCR) to advance its oral mucositis program to lead discovery and optimization.
For more about Sinopia’s pipeline
🔷 H. Lundbeck A/S
H. Lundbeck A/S (CPH: HLUN-A) is a Danish international pharmaceutical company engaged in the research, development, manufacturing, marketing and sale of pharmaceuticals across the world. On October 2, 2024, Lundbeck tapped Charles River for AI-enabled neuro drug discovery, partnering with the service provider to use Logica in its research projects. Charles River established Logica in partnership with Valo Health, the Flagship Pioneering-backed startup that has brought together ML, tissue biology and patient data to try to change how drugs are discovered and developed. Lundbeck will apply the platform to its work on disorders of the central nervous system.
Apart from the recent collaboration with Charles River to use Logica, Lundbeck partnered also with Accenture, a global leader in AI and data science, to use AI to qualify new drug targets for headache disorders. As a result of the collaboration, Lundbeck was able to find potential drug targets associated with headache disorders, such as migraine, 80% faster than traditional methods.
Currently you can find in their pipeline:
Hormonal / neuropeptide signaling candidates:
Eptinezumab (anti-CGRP mAb) for migraine prevention
Eptinezumab is a monoclonal immunoglobulin G1 (IgG1) antibody that binds to human calcitonin gene-related peptide (CGRP) with high specificity and high affinity for the CGRP α- and β-form. CGRP is a signaling molecule in the pathophysiology of migraine and cluster headache.
On June 13, 2024, Lundbeck US, the US subsidiaries of H. Lundbeck A/S, announced 11 data presentations at the 66th Annual Scientific Meeting of the American Headache Society (AHS) including new analyses of clinical data and real-world studies of VYEPTI® (eptinezumab-jjmr) (Lundbeck to Present a Breadth of Migraine and Cluster Headache Data at the 66th Annual Scientific Meeting of the American Headache Society):
New data from a post-hoc analysis of the Phase 3 PREVAIL study showing chronic migraine patients treated with VYEPTI® (eptinezumab-jjmr) achieved sustained reductions in headache frequency and severity, and the majority experienced monthly headache day (MHD) reductions to less than four MHDs over two years, a potential indicator of preventive treatment optimization.
Post-hoc analysis of Phase 3 PROMISE-2 study showing that longer interictal periods between headache days were associated with positive changes in headache-related life impact in patients with chronic migraine.
Analyses from real-world REVIEW observational study evaluated meaningful endpoints, yielding insights in chronic migraine patients and their experience with VYEPTI. Study results showed patients on VYEPTI self-reported a doubling of “good” days per month, and 86% of patients on VYEPTI reported improvements in brain fog after treatment.
Moreover, they created a model to understand how eptinezumab works in children by using data from adults and 28 children (Population pharmacokinetics of eptinezumab in paediatric patients with migraine and dose selection for phase 3 paediatric migraine studies).
Eptinezumab (anti-CGRP mAb) for cluster headache
Phase 3
Lu AG09222 (anti-PACAP mAb) for migraine prevention
Lu AG09222 is an investigational monoclonal antibody designed to bind and inhibit signaling mediated by pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide that is implicated in migraine pathophysiology.
On March 18, 2024, Lundbeck initiated the PROCEED Phase IIb study to evaluate the efficacy and safety of Lu AG09222, a potential first-in-class therapy for migraine prevention.
Lu AG13909 (anti-ACTH mAb) for neurohormonal dysfunctions
Lu AG13909 is a humanized anti-adrenocorticotropic hormone (anti-ACTH) monoclonal antibody that blocks the binding of ACTH to the melanocortin 2 receptor in the adrenal glands, thereby decreasing the neurohormonal signaling of ACTH.
On June 3, 2024, Lundbeck presented innovative first in human trial design of Lu AG13909 for potential treatment of congenital adrenal hyperplasia.
Circuitry / neuronal biology candidates:
Brexpiprazole
Brexpiprazole is a small molecule and a potent serotonin–dopamine activity modulator. It acts as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors, and as an antagonist at serotonin 5-HT2A and noradrenaline α1B/α2C receptors. The serotonergic, dopaminergic and especially the noradrenergic systems are believed to be involved in PTSD (post-traumatic stress disorder) symptomatology.
On July 31, 2024, Otsuka Pharmaceutical Development & Commercialization, Inc and Lundbeck presented new post hoc pooled analyses of Phase 3 trials evaluating the safety and efficacy of REXULTI® (brexpiprazole) in patients with agitation associated with dementia due to Alzheimer’s disease (Otsuka and Lundbeck Present New REXULTI® (brexpiprazole) Post Hoc Efficacy Data Analyses for Agitation Associated with Dementia Due to Alzheimer’s Disease at Alzheimer’s Association International Conference (AAIC) 2024).
Long-term data analysis suggested that REXULTI was associated with a sustained, clinically meaningful response over 24 weeks with a consistent rate of improvement.
Lu AF28996 (D1-D2 agonist) for Parkinson's disease
Lu AF28996 is a small molecule with agonistic properties towards D1 and D2 receptors. Concerted D1 and D2 dopamine receptor stimulation may play an important role in motor control of Parkinson’s disease patients.
Phase 1
MAGLi programs for Neurology
The MAGL inhibitor programs consists of several small molecules and highly selective inhibitors of monoacylglycerol lipase (MAGL), the primary enzyme responsible for the degradation of the endocannabinoid ligand 2-arachidonoylglycerol (2-AG). Enhancing the actions of 2-AG on CB1 and CB2 receptors may restore altered neuronal transmission and decrease neuroinflammation and thereby it may produce beneficial effects across a range of symptoms and related indications within Neurology.
Phase 1
Protein aggregation, folding and clearance candidates:
Lu AF82422 (anti-alpha-synuclein mAb) for Synucleinopathies (MSA)
Lu AF82422 is a monoclonal antibody (mAb) targeting alpha-synuclein. Misfolding, aggregation and extracellular spreading of alpha-synuclein is believed to play a major role in disease pathology and progression in Multiple System Atrophy (MSA), Parkinson’s disease and other neurodegenerative disorders.
On March 5, 2024, Lundbeck confirmed that it is now preparing to initiate a Phase III study with the drug candidate Lu AF82422, which has shown potential to slow the progression of MSA (Lundbeck prepares for Phase III study of MSA drug after encouraging data).
Neuroinflammation / Neuroimmunology candidates:
Lu AG22515 (CD40L blocker)
Lu AG22515 is a CD40L blocker, which interferes with the activation of the adaptive immune response by inhibiting the CD40L/CD40 co-stimulatory interaction on immune cells; an interaction which plays a role in the pathophysiology of several immune-mediated diseases.
Lu AG22515 is a therapeutic candidate being developed under a licensing and collaboration agreement between Lundbeck and AprilBio Co., LTD (SAFA™ technology platform).
On October 03, 2024, Lundbeck initiated clinical trial in immunology for Lu AG22515 in Thyroid Eye Disease.
Moreover, Iambic Therapeutics (formerly known as Entos) and Lundbeck have just entered into a strategic research collaboration focused on the discovery of a small-molecule therapeutic for the treatment of migraine. In the research partnership announced on September 26, 2024 📢 with Lundbeck, Iambic will use its AI drug discovery platform to accelerate research into neurological disease (migraine).
For more about Iambic’s pipeline:
Finally, on October 14, 2024 Lundbeck and Longboard Pharmaceuticals, Inc (NASDAQ: LBPH) announced an agreement for Lundbeck to acquire Longboard, in a Strategic Deal, Significantly Enhancing Its Neuroscience Pipeline.