Novel connection between cholesterol-lowering drugs and rhinovirus treatment through 27-hydroxycholesterol (27OHC) pathway. Statins affect cholesterol metabolism, producing 27OHC which has documented antiviral properties against rhinovirus—yet no studies have connected these for cold treatment.
Full mechanistic analysis available under commercial agreement.
Request AccessProposes targeting the cGAS-STING-glymphatic-gut axis, a self-amplifying inflammatory triad where gut-derived signals and misfolded α-synuclein trigger cyclic inflammation. Combines STING pathway inhibition with enhanced glymphatic clearance during sleep.
Full mechanistic analysis available under commercial agreement.
Request AccessFirst demonstration of connection between iron-dependent cell death (ferroptosis) and receptor-mediated amyloid clearance. ACSL4-driven lipid peroxidation damages Megalin receptors, impairing ApoE clearance and creating a vicious cycle of amyloid accumulation.
Full mechanistic analysis available under commercial agreement.
Request AccessCombines host-targeting antiviral approach (27OHC via statins) with localized immune training (intranasal bacterial lysate), stratified by nasal microbiome risk profiles. Represents convergence of novel mechanism and immediately actionable repurposing.
Full mechanistic analysis available under commercial agreement.
Request AccessNon-invasive therapeutic ultrasound demonstrates ability to actively promote remyelination in MS lesions through neuromodulation, offering potential disease-modifying treatment beyond symptom management.
Full mechanistic analysis available under commercial agreement.
Request AccessIdentifies sodium channel dysfunction as common pathway across multiple chronic pain conditions. Proposes repurposing ranolazine (FDA-approved for angina) to target neuropathic pain, COPD-related musculoskeletal pain, and post-seizure chronic pain through Nav1.7/1.8 channel blockade.
Full mechanistic analysis available under commercial agreement.
Request AccessFirst proposal to combine SGLT2 inhibitor's glucosuria effect with faster insulin's rapid post-prandial correction in pediatric Type 1 diabetes. Exploits complementary glucose-lowering mechanisms with different temporal profiles to prevent cardiovascular-kidney-metabolic syndrome in youth.
Full mechanistic analysis available under commercial agreement.
Request AccessFirst demonstration that mitochondrial stress biomarker GDF-15 correlates with HIV reservoir persistence independent of inflammation. Proposes targeting cellular metabolism through mitochondrial modulation as novel HIV cure strategy beyond traditional antivirals and immune activation.
Full mechanistic analysis available under commercial agreement.
Request AccessMetformin's AMPK activation suppresses mTORC1, reducing the cytokine storm response responsible for severe influenza mortality. Combining metformin with standard antiviral oseltamivir targets both viral replication and the host immune overreaction simultaneously — a dual-mechanism approach with zero prior investigation.
Full mechanistic analysis available under commercial agreement.
Request AccessHSV establishes lifelong latency in dorsal root ganglia through epigenetic silencing. HDAC inhibitors force latent virus into active replication, making it vulnerable to helicase-primase inhibitor pritelivir — a "kick and kill" strategy that could eliminate the HSV reservoir entirely rather than just suppressing outbreaks.
Full mechanistic analysis available under commercial agreement.
Request AccessFenbendazole, an FDA-approved antiparasitic, disrupts tubulin polymerisation in cancer cells through the same mechanism as established chemotherapy agents — but with a dramatically superior safety profile. Cross-condition analysis reveals synergy with PD-1/PD-L1 checkpoint inhibitors, potentially sensitising resistant tumours to immunotherapy.
Full mechanistic analysis available under commercial agreement.
Request AccessSLE patients show antigen-specific immune dysfunction against influenza vaccines while maintaining adequate COVID-19 responses — suggesting selective rather than global immunosuppression. A rituximab holiday of 3-4 months before vaccination could allow B-cell recovery and dramatically improve vaccine immunogenicity in this high-mortality population.
Full mechanistic analysis available under commercial agreement.
Request AccessHSV-2 Mollaret meningitis is assumed extremely rare in HIV patients — but may be severely underdiagnosed due to clinician bias. IVIG demonstrates a dual role: simultaneously suppressing autoimmune inflammation while enhancing antiviral immunity through Fc gamma receptor modulation. Combined with patient-initiated episodic valacyclovir, this represents a completely unexplored treatment strategy.
Full mechanistic analysis available under commercial agreement.
Request AccessFerroptosis — iron-dependent cell death through lipid peroxidation — is emerging as a central mechanism in Parkinson's neurodegeneration. Polydopamine nanoparticles act as synthetic neuromelanin, scavenging reactive oxygen species and blocking ferroptosis. Combined with deferiprone, an FDA-approved iron chelator, this dual-mechanism approach targets both systemic iron availability and local ROS accumulation — never previously attempted in Parkinson's.
Full mechanistic analysis available under commercial agreement.
Request AccessLamotrigine, an FDA-approved antiepileptic, activates the cAMP/PKA/CREB pathway to simultaneously reduce amyloid-β accumulation and tau hyperphosphorylation. Dexmedetomidine, an FDA-approved sedative, provides broad neuroprotection through α2-adrenergic receptor agonism. These two drugs target completely different but complementary Alzheimer's pathways — and have never been tested in combination. Both cross the blood-brain barrier with decades of established safety data, enabling a clinical trial within 12 months.
Full mechanistic analysis available under commercial agreement.
Request AccessStatins modulate cholesterol metabolism to enhance 27-hydroxycholesterol production — a compound with documented antiviral properties against rhinovirus. Combined with intranasal OM-85 bacterial lysate, which primes local nasal immunity through a route that bypasses the limitations of oral delivery, this dual approach attacks both viral replication and host immune defence simultaneously.
Full mechanistic analysis available under commercial agreement.
Request AccessHIV treatment failure is driven less by drug complexity than by internalised shame — a specific psychological barrier distinct from depression. Sertraline's serotonin reuptake inhibition targets shame-based rumination cycles through the anterior cingulate cortex, directly addressing the neurobiological pathway that disrupts medication-taking behaviour.
Full mechanistic analysis available under commercial agreement.
Request AccessTegileridine is a biased μ-opioid receptor agonist that selectively activates the G-protein pain-relief pathway while avoiding the β-arrestin2 pathway responsible for respiratory depression and addiction. Combined with AI-driven real-time dosage optimisation, this approach could deliver effective chronic pain management without the overdose risk that makes traditional opioids so dangerous.
Full mechanistic analysis available under commercial agreement.
Request AccessChronic pelvic pain syndrome (CP/CPPS) has a 90%+ treatment failure rate with current therapies. Ouki identified that TNF-α directly excites pain nerves through TNFR1 receptors — a pathway completely independent of inflammation. Anti-TNF drugs like adalimumab (FDA-approved for arthritis) could work as direct analgesics in CP/CPPS not by reducing inflammation but by blocking nerve excitation at source. Zero clinical trials have ever tested this despite clear mechanistic evidence.
Full mechanistic analysis available under commercial agreement.
Request AccessIn MS, microglia and T-cells don't just cause damage independently — they actively amplify each other in a bidirectional feedback loop, creating multiplicative neurodegeneration. Ouki identified minocycline (an FDA-approved antibiotic) as a microglial inhibitor that could break this loop when combined with standard disease-modifying therapy. Additionally, current MS drug doses are identical regardless of age or sex despite documented differences in metabolism — a correctable error causing over-exposure in older patients and under-dosing in younger ones.
Full mechanistic analysis available under commercial agreement.
Request AccessCirrhosis patients are assumed to have weakened immune responses — yet decompensated cirrhosis patients show paradoxically enhanced influenza vaccine responses due to chronic TNF-α and IL-6 elevation activating dendritic cells. Ouki identified that rifaximin, an FDA-approved antibiotic that modulates gut-liver inflammation, could be used to deliberately pre-condition this inflammatory state before vaccination to optimise antibody production. This completely inverts the standard assumption that inflammation impairs vaccine efficacy.
Full mechanistic analysis available under commercial agreement.
Request AccessNirmatrelvir, FDA-approved as a COVID-19 antiviral, targets a cysteine protease structurally homologous to rhinovirus 3C protease — the enzyme essential for viral replication. Zero studies have tested nirmatrelvir against rhinovirus despite the mechanistic overlap being directly demonstrable from crystal structure data. Itraconazole independently targets the cholesterol-trafficking pathway rhinovirus exploits for replication — a completely separate mechanism offering combination potential.
Full mechanistic analysis available under commercial agreement.
Request AccessCGRP — a neuropeptide driving migraine pain — is now identified as a significant contributor to endometriosis-associated pelvic pain through peripheral sensitisation of nociceptors in ectopic lesions. Erenumab, FDA-approved for migraine, has never been tested in endometriosis despite targeting the same nociceptor pathway. Transcutaneous auricular vagus nerve stimulation offers a non-pharmacological complement addressing central sensitisation — a combination with zero prior research.
Full mechanistic analysis available under commercial agreement.
Request AccessLupus nephritis glomerular damage has a newly identified mechanism — podocyte ferroptosis driven by GPX4 depletion and lipid peroxidation — distinct from immune complex deposition. N-acetylcysteine, FDA-approved and available OTC, replenishes glutathione and directly inhibits this ferroptosis cascade. Prior NAC trials in SLE targeted oxidative stress generally — none have tested it with ferroptosis as the specific mechanistic rationale or used podocyte injury biomarkers as endpoints.
Full mechanistic analysis available under commercial agreement.
Request AccessPeanut oral immunotherapy achieves desensitisation but sustained unresponsiveness — true remission — remains elusive. Three mechanistically non-overlapping interventions identified: omalizumab neutralises free IgE reducing acute dosing reactions, Lactobacillus rhamnosus GG induces regulatory T-cells promoting durable tolerance, and peanut OIT drives antigen-specific peripheral tolerance. Each pairwise combination has been tested in isolation — the three-way combination has never been studied despite acting through completely independent pathways.
Full mechanistic analysis available under commercial agreement.
Request AccessM184V and A114S resistance mutations selected by islatravir alter HIV reverse transcriptase geometry in a way that paradoxically increases susceptibility to tenofovir — confirmed by six structural snapshots using X-ray crystallography and cryo-EM. This inverts the standard resistance-response paradigm: rather than abandoning tenofovir when resistance emerges, intensifying TAF exposure could exploit this collateral sensitivity. Zero prior clinical exploitation of this mechanism.
Full mechanistic analysis available under commercial agreement.
Request AccessAbatacept (FDA-approved for rheumatoid arthritis and GvHD prevention) blocks CD28 costimulation to suppress graft-versus-host disease. Blinatumomab (BiTE therapy for B-ALL) activates T cells via CD3 crosslinking — bypassing CD28 entirely — preserving graft-versus-leukaemia activity even under CTLA-4-Ig blockade. The two drugs can be co-administered in post-allo-HCT B-ALL relapse without sacrificing anti-tumour efficacy. Both FDA-approved. Zero prior trials combining them.
Full mechanistic analysis available under commercial agreement.
Request AccessAnti-dsDNA antibodies in lupus cross-react with NR2A and NR2B subunits of NMDA receptors in the brain via molecular mimicry, causing neuronal excitotoxicity and the cognitive dysfunction that defines neuropsychiatric SLE. Memantine, FDA-approved for Alzheimer's disease, is an uncompetitive NMDA antagonist that directly blocks these same receptor subunits. It crosses the blood-brain barrier reliably and has an established safety profile. Zero clinical trials in NPSLE despite 20 years of mechanistic evidence for this connection.
Full mechanistic analysis available under commercial agreement.
Request AccessSecukinumab's Candida susceptibility is not a side effect — it is a pharmacodynamic inevitability. IL-17A is the body's primary defence against mucosal Candida infection, and secukinumab's mechanism of action directly eliminates it. Published data identifies specific peak-risk time windows during secukinumab initiation. Time-limited fluconazole prophylaxis during these windows — rather than continuous monitoring or reactive treatment — has never been systematically studied despite the mechanism being entirely predictable from the drug's pharmacology.
Full mechanistic analysis available under commercial agreement.
Request AccessAdults are underserved by peanut oral immunotherapy programmes because their dose-related adverse event rates are substantially higher than in children — driving dropout before desensitisation is achieved. Dupilumab, FDA-approved for atopic dermatitis, asthma, and eosinophilic oesophagitis, blocks IL-4 and IL-13 signalling that drives mast cell priming during updosing. Restricting dupilumab to the updosing phase only preserves the tolerogenic IgG4 response while suppressing the dangerous Th2-driven reactions that cause abandonment. No completed RCT exists for single-food adult peanut OIT combined with dupilumab.
Full mechanistic analysis available under commercial agreement.
Request AccessSGLT2 inhibitors — already approved for diabetes, heart failure, and CKD — identified for two distinct unexplored indications. First: gout prevention via causal Mendelian randomisation evidence confirming URAT1-mediated urate excretion as the mechanism. Second: limb salvage post-endovascular therapy in diabetic peripheral arterial disease patients, where current 3-year amputation rates reach 30% with zero approved pharmacotherapy specifically targeting limb outcomes after the procedure.
Full mechanistic analysis available under commercial agreement.
Request AccessRIPK1-driven necroptotic cell death releases the nuclear DNA and RNA fragments that continuously activate TLR7 and TLR9, triggering the type I interferon burst that drives the entire SLE autoimmune cascade. Current treatments suppress this cascade downstream — belimumab, rituximab, anifrolumab. RIPK1 inhibition stops the trigger being pulled upstream. GSK2982772 already has Phase II safety data in rheumatoid arthritis. Zero registered SLE or lupus nephritis trials for any RIPK1 inhibitor despite the mechanistic logic being fully mapped.
Full mechanistic analysis available under commercial agreement.
Request AccessChildren under six represent the highest remission potential window for peanut oral immunotherapy — the immune system is most amenable to durable tolerance induction at this age. Dupilumab blocks IL-4 and IL-13 signalling upstream of IgE synthesis, reducing mucosal mast cell density and reactivity during the dangerous updosing phase. Unlike omalizumab which neutralises existing IgE downstream, dupilumab prevents new IgE generation — a mechanistically superior approach for achieving sustained unresponsiveness. No published randomised controlled trial exists for dupilumab combined with peanut OIT in children under six despite dupilumab being approved for atopic dermatitis from six months of age.
Full mechanistic analysis available under commercial agreement.
Request AccessHalofuginone, an FDA-approved antimalarial, attacks HSV-2 through two completely independent pathways simultaneously — direct virion interference AND host ProRS pathway disruption. This dual mechanism bypasses the resistance mechanisms that cause acyclovir to fail. For millions of patients with drug-resistant HSV, this could be the first genuinely new treatment option in decades.
Full mechanistic analysis available under commercial agreement.
Request AccessEndometriosis affects 10-15% of reproductive-age women and causes chronic pelvic pain through fibrotic adhesions — scar-like tissue that medicine has largely failed to treat. ACE inhibitors like lisinopril (FDA-approved for blood pressure) have well-documented anti-fibrotic effects through TGF-β pathway inhibition in heart and kidney disease. Ouki identified this same mechanism could directly target adhesion formation driving endometriosis pain. Zero studies have tested this despite a mechanistically perfect fit.
Full mechanistic analysis available under commercial agreement.
Request AccessHIV patients on antiretroviral therapy develop a premature ageing syndrome driven by mitochondrial dysfunction creating senescent "zombie cells" that accumulate and cause systemic damage. Nicotinamide riboside restores mitochondrial function through NAD+ replenishment while the dasatinib + quercetin senolytic combination eliminates accumulated senescent cells. This triple approach addresses both the cause and consequence of HIV-associated accelerated ageing — never studied in combination in HIV patients.
Full mechanistic analysis available under commercial agreement.
Request AccessCharcot neuroarthropathy is a catastrophic diabetic complication where bones in the foot spontaneously collapse due to uncontrolled inflammatory bone destruction. Denosumab (FDA-approved for osteoporosis) directly blocks the RANKL pathway driving this osteoclast overactivation. In hypogonadal diabetic men, concurrent testosterone replacement restores the hormonal balance that normally protects bone. This dual mechanism targeting both inflammation and hormonal dysregulation has never been studied despite both pathways being independently documented.
Full mechanistic analysis available under commercial agreement.
Request AccessA specific sequential pathway has been identified linking environmental toxin exposure to sustained neuroinflammation in Parkinson's — CD11b activates Src, which activates Erk, which activates NOX2, causing oxidative neuronal damage. Dasatinib, an FDA-approved cancer drug that crosses the blood-brain barrier, blocks Src kinase — a critical node in this cascade. Combined with robotic rehabilitation, Src inhibition could simultaneously reduce neuroinflammation and enhance motor learning through synaptic plasticity effects.
Full mechanistic analysis available under commercial agreement.
Request AccessB-cell depletion drugs like rituximab excel at preventing new MS lesions but cannot repair existing damage causing persistent motor and cognitive deficits. Transcranial direct current stimulation (tDCS) promotes remyelination through neuroplasticity mechanisms that address exactly this repair gap. Combining rituximab — which reduces inflammation — with tDCS — which promotes active repair — targets both disease processes simultaneously. This complementary combination has zero prior research despite the logic being immediately apparent.
Full mechanistic analysis available under commercial agreement.
Request AccessLeronlimab, FDA-approved for CCR5-tropic HIV as an entry inhibitor, identified for a mechanistically distinct application — active HIV reservoir reduction. CCR5+ CD4+ T-cells are disproportionately enriched in the latent HIV reservoir. Blocking CCR5 may selectively deplete these reservoir-maintaining cells, actively shrinking the reservoir rather than merely preventing new infections. This inverts the standard understanding of leronlimab from antiviral to reservoir depleter. Zero trials have tested this specific hypothesis despite the mechanistic rationale being directly supported by reservoir immunology data.
Full mechanistic analysis available under commercial agreement.
Request AccessSix consecutive weeks of convergent signals across independent research groups have now culminated in the identification of small molecule candidates that mimic partial OSK (OCT4+SOX2+KLF4) reprogramming in cardiac tissue without viral vector delivery. Adult cardiomyocytes cannot divide — heart attack damage is permanent because the regenerative capacity is lost. Partial reprogramming without c-Myc transiently restores this capacity without oncogenic risk. The small molecule angle resolves the primary clinical translation barrier. Multiple independent groups are converging on the same mechanism without coordination.
Full mechanistic analysis available under commercial agreement.
Request AccessSemaglutide, the most commercially significant drug on the planet, identified for Alzheimer's disease via direct GLP-1 receptor signalling in microglia — suppressing neuroinflammation and promoting microglial polarisation toward a neuroprotective state. Mechanistically distinct from liraglutide's tested approach due to superior CNS penetration and longer half-life producing sustained receptor occupancy. The neuroinflammatory pathway — not weight loss or metabolic effects — is the proposed mechanism. No completed semaglutide-specific Alzheimer's trial exists despite the EVOKE liraglutide trial establishing GLP-1 receptor agonism as a credible neuroinflammatory target.
Full mechanistic analysis available under commercial agreement.
Request AccessRipretinib, FDA-approved for KIT-mutant gastrointestinal stromal tumour (GIST), identified for KIT-mutant colorectal cancer — a subtype affecting 2-5% of CRC patients with no approved KIT-targeted therapy despite the same activating KIT mutations being the defining target in GIST. The mechanistic bridge is direct: same drug, same mutation class, different tumour histology. The gap is clinically inexplicable given the complete overlap in target biology. Zero clinical trials exist for ripretinib in colorectal cancer despite the mechanistic rationale requiring no additional preclinical validation.
Full mechanistic analysis available under commercial agreement.
Request AccessNalmefene, FDA-approved for alcohol use disorder, identified for chronic overlapping pain conditions via its unique mixed opioid receptor profile. Unlike naltrexone which fully blocks all opioid receptors, nalmefene partially activates kappa receptors while blocking mu — kappa activation produces analgesic and anti-neuroinflammatory effects directly relevant to central sensitisation, the shared pathological substrate of fibromyalgia, chronic pelvic pain, and related conditions. Zero pain trials exist for nalmefene despite this receptor profile being mechanistically distinct from and potentially superior to existing opioid modulator approaches in central sensitisation syndromes.
Full mechanistic analysis available under commercial agreement.
Request AccessDapagliflozin, FDA-approved for diabetes, heart failure, and CKD, identified for diabetic cardiomyopathy in patients without established heart failure — the pre-symptomatic window where structural cardiac damage is accumulating but no HF diagnosis exists. Current approved indications require established HF. Dapagliflozin's cardioprotective mechanisms — reducing cardiac inflammation, oxidative stress, and mitochondrial dysfunction — operate independently of glycaemic control and are directly relevant at this earlier disease stage. Intervening before HF develops could alter the trajectory of the most common cause of death in diabetic patients.
Full mechanistic analysis available under commercial agreement.
Request AccessAmbroxol, a mucolytic available OTC in Europe for 50+ years, identified as a GBA1 pharmacological chaperone for GBA1-associated Parkinson's disease — the most common genetic risk factor for Parkinson's, affecting 5-15% of patients. Ambroxol stabilises misfolded GBA1 protein, restoring lysosomal glucocerebrosidase activity and reducing alpha-synuclein accumulation via the lysosomal-autophagic pathway. The AiM-PD trial has established proof-of-concept. Ambroxol remains unlicensed for Parkinson's despite 50+ years of established safety data, OTC European availability, and a directly validated mechanistic target — representing a classic repurposing gap where commercial incentives have failed to drive regulatory development.
Full mechanistic analysis available under commercial agreement.
Request AccessSimvastatin, a generic statin costing pennies per pill with a 30+ year safety record, identified for secondary progressive MS via direct neuroprotection — mechanistically distinct from all approved DMTs which target inflammation. The MS-STAT2 trial demonstrated significant reduction in brain atrophy rate. No regulatory submission has been made despite positive clinical data — the defining example of the repurposing gap where generic drug economics prevent development of a proven treatment. The commercial incentive to develop a generic drug through regulatory approval does not exist; the clinical need does.
Full mechanistic analysis available under commercial agreement.
Request AccessDichloroacetate (DCA), an investigational compound with established safety data from rare metabolic disorder trials, identified for endometriosis via the Warburg effect. Endometriotic lesions exhibit aerobic glycolysis — the same cancer-like metabolic reprogramming that allows cells to survive and proliferate in hostile ectopic environments. DCA inhibits pyruvate dehydrogenase kinase, forcing cells back to oxidative phosphorylation and selectively impairing lesion survival without affecting normal tissue. Zero endometriosis trials exist for DCA despite the metabolic parallel between endometriosis lesions and cancer cells being directly demonstrable from published metabolomics data.
Full mechanistic analysis available under commercial agreement.
Request AccessLow-dose naltrexone (LDN), FDA-approved for opioid dependence at 50mg but used off-label at 1.5-4.5mg, identified for Long COVID neuroinflammation via TLR4 antagonism — a mechanism completely distinct from its standard-dose opioid receptor blockade. At low doses LDN acts as a TLR4 antagonist and microglial modulator, suppressing the post-viral neuroinflammatory cascade that characterises Long COVID's neurological manifestations. Long COVID's neuroinflammatory substrate is now well characterised by PET and CSF studies. No properly powered RCT exists despite widespread off-label use, extensive mechanistic rationale, and easily accessible dosing.
Full mechanistic analysis available under commercial agreement.
Request AccessItaconate derivatives — cell-permeable forms of the endogenous immunometabolite produced by activated macrophages — identified for rheumatoid arthritis via macrophage immunometabolic reprogramming. This mechanism is entirely distinct from all approved RA biologics which target cytokine signalling downstream of macrophage activation. 4-Octyl itaconate and dimethyl itaconate redirect macrophage metabolism toward an anti-inflammatory state by inhibiting succinate dehydrogenase and activating NRF2-mediated antioxidant responses. Zero clinical trials exist in RA despite compelling preclinical data from multiple independent groups demonstrating efficacy in collagen-induced arthritis models.
Full mechanistic analysis available under commercial agreement.
Request AccessDeucravacitinib, FDA-approved for psoriasis, identified for lupus nephritis via selective allosteric TYK2 inhibition. TYK2 sits at the convergence of type I interferon, IL-12, and IL-23 signalling — three pathways simultaneously driving lupus nephritis pathology. Deucravacitinib's allosteric mechanism binds the regulatory rather than catalytic domain, producing superior selectivity versus JAK inhibitors and avoiding the safety concerns that have complicated JAK inhibitor use in autoimmune disease. Phase II data supports efficacy in broader SLE. Lupus nephritis specifically — the leading cause of morbidity in SLE — remains untested despite TYK2 being mechanistically central to renal inflammation in this disease.
Full mechanistic analysis available under commercial agreement.
Request AccessDupilumab, FDA-approved for asthma, atopic dermatitis, and EoE, identified for the Type 2 eosinophilic COPD endotype — a biomarker-definable subgroup with blood eosinophils ≥300 cells/μL representing 25-30% of COPD patients. BOREAS trial data supports efficacy. The precise patient selection criterion — eosinophil threshold — is the novel finding that defines who responds and enables a targeted development programme in a disease where undifferentiated trial designs have consistently failed. COPD's heterogeneity is the reason previous broad trials failed; the biomarker-stratified approach resolves this.
Full mechanistic analysis available under commercial agreement.
Request AccessFenfluramine, FDA-approved for Dravet syndrome and Lennox-Gastaut syndrome, identified for KCNQ2/KCNQ3 potassium channelopathy epilepsy via serotonergic sigma-1 receptor activation — which directly modulates KCNQ channel function, the precise molecular defect in this channelopathy. This is a mechanistically grounded extension of fenfluramine's existing rare epilepsy approvals into a related channelopathy with a directly demonstrable mechanistic overlap. Zero trials exist despite fenfluramine's established rare epilepsy safety profile and the direct molecular connection between its mechanism and the KCNQ channelopathy target.
Full mechanistic analysis available under commercial agreement.
Request AccessTofacitinib, FDA-approved for ulcerative colitis, rheumatoid arthritis, and psoriatic arthritis, identified specifically for small bowel Crohn's disease — a subtype mechanistically distinct from colonic Crohn's and currently excluded from tofacitinib's Crohn's development programme. JAK1-dominant signalling in small bowel epithelium differs from the JAK3-dominant colonic environment. Tofacitinib's mixed JAK1/3 profile is mechanistically better suited to small bowel disease than the JAK1-selective agents being developed for Crohn's broadly. Zero small bowel-specific tofacitinib trials exist despite this mechanistic rationale being directly derivable from published JAK signalling pathway data in intestinal epithelium.
Full mechanistic analysis available under commercial agreement.
Request AccessLow-dose naltrexone identified for ME/CFS via glial cell modulation — suppressing the chronic neuroinflammatory state underlying post-exertional malaise, the defining and most debilitating feature of ME/CFS. At 1.5-4.5mg LDN acts as a glial modulator via TLR4 antagonism, mechanistically distinct from its standard-dose opioid receptor blockade. Neuroinflammation in ME/CFS is now measurable by TSPO-PET imaging, providing a validated biomarker endpoint for clinical trials. No properly powered RCT exists in ME/CFS despite compelling mechanistic rationale, extensive patient-reported benefit, and an easily accessible, inexpensive intervention.
Full mechanistic analysis available under commercial agreement.
Request AccessTralokinumab, FDA-approved for atopic dermatitis, identified as a peanut OIT adjunct via selective IL-13 blockade — mechanistically distinct from dupilumab which blocks both IL-4 and IL-13. IL-13 drives mucosal mast cell priming and eosinophilic oesophagitis risk during OIT updosing; IL-4 drives the IgG4 class switching that underlies durable tolerance. Selective IL-13 blockade could reduce adverse events and dropout while preserving the IL-4-dependent tolerogenic response — a mechanistic advantage over dupilumab for the specific application of OIT augmentation. Zero OIT trials exist for tralokinumab despite this mechanistic distinction being directly derivable from published cytokine biology.
Full mechanistic analysis available under commercial agreement.
Request AccessAmenamevir, approved in Japan for herpes zoster, identified for HSV-1 encephalitis — the most devastating HSV complication carrying 70% untreated mortality and significant neurological sequelae even with acyclovir treatment. Amenamevir targets the HSV helicase-primase complex rather than DNA polymerase, retaining full antiviral activity against acyclovir-resistant strains — a growing clinical problem with no approved alternative. Resistance to acyclovir does not confer cross-resistance to helicase-primase inhibitors. Amenamevir is not approved in the UK or US. Zero HSV-1 encephalitis-specific trials exist for any helicase-primase inhibitor.
Full mechanistic analysis available under commercial agreement.
Request AccessNiclosamide, FDA-approved as an antihelminthic for tapeworm with an established safety profile, identified for rhinovirus via autophagy disruption — delivered intranasally to target the nasal epithelium directly where rhinovirus replicates. Rhinovirus hijacks autophagosomes for viral replication; niclosamide disrupts autophagosome-lysosome fusion, blocking this process without affecting normal cellular function. Intranasal delivery bypasses niclosamide's poor oral bioavailability that has limited systemic antiviral applications. Zero rhinovirus-specific intranasal niclosamide trials exist despite the autophagy hijacking mechanism being well characterised and the intranasal route resolving the bioavailability barrier.
Full mechanistic analysis available under commercial agreement.
Request AccessCashew allergy is driven by Ana o 3, an allergen that binds mast cells with exceptional affinity — producing anaphylaxis rates and OIT dropout rates significantly higher than peanut allergy. Dupilumab's IL-4/IL-13 blockade reduces mucosal mast cell priming and IgE synthesis upstream, directly addressing the mechanism that makes tree nut OIT so difficult to complete. The IL-4/IL-13 pathway is identical to that implicated in peanut allergy — the mechanistic transfer is direct. Zero tree nut-specific dupilumab OIT trials exist despite the mechanism being immediately transferable from peanut research.
Full mechanistic analysis available under commercial agreement.
Request AccessLow-dose naltrexone identified for chronic pain neuroinflammation with TSPO-PET imaging as a validated companion biomarker — enabling both patient selection and treatment response monitoring. Microglial activation is now measurable in individual patients via TSPO-PET, transforming LDN from a speculative off-label intervention into a hypothesis with a defined neuroinflammatory patient selection criterion and an objective endpoint. LDN has never been trialled in primary chronic pain with neuroinflammatory imaging as the primary endpoint despite clear mechanistic rationale.
Full mechanistic analysis available under commercial agreement.
Request AccessA defined sequential protocol targeting the two compartments of progressive MS inflammation simultaneously — ofatumumab depletes peripheral B-cells first, then tolebrutinib penetrates the CNS to address compartmentalised microglial inflammation that anti-CD20 therapy cannot reach. The sequencing — peripheral depletion then CNS targeting — avoids immunosuppression overlap and makes the trial design immediately practical. Both drugs are approved. Zero studies have tested this specific sequential induction-to-maintenance protocol despite the mechanistic rationale being directly derived from each drug's established pharmacology.
Full mechanistic analysis available under commercial agreement.
Request AccessType I interferon signature is elevated specifically in anti-CCP positive rheumatoid arthritis patients — a definable biomarker subgroup representing the majority of RA cases. TYK2 sits directly upstream of type I interferon signalling, making deucravacitinib's allosteric TYK2 inhibition mechanistically precise for this subgroup. The biomarker-stratified design — anti-CCP positivity as the selection criterion — enables an immediately actionable trial. Deucravacitinib is approved for psoriasis. Zero rheumatoid arthritis trials exist for any TYK2 inhibitor despite the interferon-TYK2 pathway being directly implicated in seropositive disease.
Full mechanistic analysis available under commercial agreement.
Request AccessUpadacitinib induces rapid remission via JAK1 inhibition with broad systemic anti-inflammatory activity. Vedolizumab then maintains remission via gut-selective lymphocyte trafficking blockade without systemic immunosuppression — preserving the systemic immune response that upadacitinib suppressed during induction. The sequential design exploits each drug's strength at the right phase: rapid induction followed by targeted gut-selective maintenance. Both are approved for inflammatory bowel disease. Zero clinical studies have tested this specific sequential induction-to-maintenance protocol despite the complementary mechanisms being directly derivable from each drug's established pharmacology.
Full mechanistic analysis available under commercial agreement.
Request AccessTezepelumab, FDA-approved for severe asthma, blocks TSLP — the epithelial alarm signal released by gut and skin in response to allergen exposure that initiates the entire allergic cascade before IL-4, IL-13, or IgE are produced. As an OIT adjunct, tezepelumab targets the cascade at its most upstream point — preventing dose escalation reactions at their source rather than managing them downstream as omalizumab and dupilumab do. This represents a mechanistically distinct and potentially superior intervention point for OIT augmentation. Zero peanut OIT trials exist for tezepelumab despite TSLP's role in food allergy sensitisation being well established.
Full mechanistic analysis available under commercial agreement.
Request AccessSeven consecutive weeks of convergent signals across independent research groups have culminated in the confirmation of small molecule candidates capable of mimicking partial OSK (OCT4+SOX2+KLF4) reprogramming in cardiac tissue without viral vector delivery. Adult cardiomyocytes cannot divide — heart attack damage is permanent because regenerative capacity is lost. Partial reprogramming without c-Myc transiently restores this capacity without oncogenic risk. Two specific compound classes are now emerging across multiple independent groups without coordination — the convergence pattern that precedes genuine pre-clinical breakthrough. This finding sits at the intersection of drug repurposing and cellular reprogramming and represents the most frontier signal in the Ouki archive.
Full mechanistic analysis available under commercial agreement.
Request AccessAmbroxol identified for GBA1-associated Parkinson's with a fully actionable precision medicine trial design — GBA1 mutation status as patient selection criterion, lysosomal GCase activity as primary pharmacodynamic endpoint, and alpha-synuclein as secondary endpoint. GBA1 mutations are the most common genetic risk factor for Parkinson's, affecting 5-15% of patients. Proof-of-concept exists from the AiM-PD trial. No regulatory submission has been made despite a complete biomarker-stratified trial design being immediately available — the commercial incentive to develop a 50-year-old generic mucolytic through regulatory approval does not exist. The clinical need does.
Full mechanistic analysis available under commercial agreement.
Request AccessSub-anaesthetic ketamine microdosing identified for central sensitisation reset via NMDA receptor modulation — transiently disrupting the maladaptive synaptic strengthening that maintains chronic pain hypersensitivity and allowing the pain system to recalibrate. A specific 5-day repeated low-dose infusion protocol produces durable sensitisation reset without dissociative effects — mechanistically distinct from ketamine's anaesthetic and emerging antidepressant applications. No randomised controlled trial has tested this specific protocol with central sensitisation as the primary target and TSPO-PET neuroinflammatory imaging as a companion biomarker endpoint.
Full mechanistic analysis available under commercial agreement.
Request AccessResmetirom, FDA-approved for metabolic liver disease via thyroid hormone receptor beta agonism, identified for endometriosis — endometriotic lesions express THRβ and exhibit lipid metabolic dysregulation identical to the hepatic mechanism resmetirom addresses. THRβ activation impairs the metabolic adaptations that allow endometriotic lesions to survive and proliferate in ectopic locations. A metabolic approach to endometriosis entirely distinct from current hormonal treatments, which suppress the hormonal environment rather than targeting lesion metabolism directly. Zero endometriosis trials exist for resmetirom or any THRβ agonist.
Full mechanistic analysis available under commercial agreement.
Request AccessBimekizumab identified for psoriatic arthritis patients who have failed IL-17A-selective inhibitors — secukinumab or ixekizumab. IL-17F continues driving joint inflammation in these patients through a pathway that IL-17A-selective agents cannot block. Bimekizumab's dual IL-17A and IL-17F blockade addresses the residual inflammatory pathway responsible for ongoing joint destruction after IL-17A inhibitor failure. The patient selection criterion — prior IL-17A inhibitor failure — defines an immediately actionable trial population. Zero studies have tested this specific sequencing strategy despite the mechanistic rationale being directly derivable from each drug's established pharmacology.
Full mechanistic analysis available under commercial agreement.
Request AccessRintatolimod identified for the RNase L-dysfunctional ME/CFS subgroup — impaired RNase L antiviral pathway activity is measurable and defines a specific ME/CFS subtype driven by innate immune dysregulation. Earlier rintatolimod trials in ME/CFS showed modest signals in unselected populations — the key finding is that biomarker-stratified trial design using RNase L dysfunction as the selection criterion has never been conducted. Mechanistically distinct from the neuroinflammatory LDN approach — targeting upstream innate immune dysregulation rather than downstream microglial activation, addressing a different ME/CFS subtype through a non-overlapping mechanism.
Full mechanistic analysis available under commercial agreement.
Request AccessOmalizumab identified for simultaneous peanut and cashew oral immunotherapy in co-sensitised patients — peanut and tree nut allergies frequently co-occur, making sequential treatment burdensome and prolonged. Omalizumab's pan-IgE neutralisation reduces reactivity across multiple allergens simultaneously, enabling concurrent multi-food desensitisation protocols that would carry unacceptable anaphylaxis risk without biologic cover. The OUTMATCH trial established multi-food OIT proof of concept. The specific peanut plus cashew simultaneous protocol in co-sensitised patients — the most clinically relevant combination given co-occurrence rates — has not been evaluated as a defined trial endpoint.
Full mechanistic analysis available under commercial agreement.
Request AccessTezepelumab identified for tree nut oral immunotherapy via TSLP blockade — cashew Ana o 3 allergen exposure triggers TSLP release from gut epithelium during OIT dose escalation, initiating the allergic cascade that drives the exceptionally high dropout rates in tree nut immunotherapy. Blocking TSLP upstream before dose escalation begins prevents the cascade at its source rather than managing consequences downstream. The Ana o 3 severity argument makes the case for upstream TSLP blockade stronger in tree nut OIT than in peanut OIT — where the equivalent finding was identified the previous week. Zero tree nut-specific tezepelumab trials exist.
Full mechanistic analysis available under commercial agreement.
Request AccessTelmisartan, approved for hypertension, is uniquely positioned among angiotensin receptor blockers as the only ARB with documented blood-brain barrier penetration at therapeutically relevant concentrations. Inside the brain, it suppresses microglial activation in the substantia nigra via dual RAS/PPARγ mechanism — the renin-angiotensin system pathway drives neuroinflammation independently of its cardiovascular role, and PPARγ activation provides additional anti-inflammatory effects. Zero Parkinson's trials exist for telmisartan despite its BBB penetration being the key pharmacological differentiator from every other ARB in clinical use.
Full mechanistic analysis available under commercial agreement.
Request AccessAuranofin, an FDA-approved gold compound used for rheumatoid arthritis, identified for HIV reservoir reduction via selective oxidative stress induction. HIV-infected cells are more vulnerable to thioredoxin reductase inhibition than uninfected cells due to the additional metabolic burden of active viral replication machinery — auranofin exploits this differential vulnerability to selectively deplete reservoir-harbouring cells without broad immune damage. A second mechanistically distinct reservoir reduction approach alongside CCR5 blockade, addressing the fundamental barrier to HIV cure from a completely different angle. Zero HIV reservoir-specific auranofin trials exist.
Full mechanistic analysis available under commercial agreement.
Request AccessLow-dose naltrexone and memantine identified as a combination targeting central sensitisation through two non-overlapping mechanisms simultaneously — LDN suppresses microglial neuroinflammation via TLR4 antagonism upstream, while memantine blocks the NMDA receptor-mediated synaptic strengthening that maintains the sensitised pain state downstream. Neither drug alone fully addresses the dual-driver model of central sensitisation. Both are approved. The specific combination targeting both the inflammatory driver and the synaptic mechanism simultaneously has never been tested in a randomised controlled trial.
Full mechanistic analysis available under commercial agreement.
Request AccessIberdomide, a cereblon E3 ligase modulator developed for multiple myeloma, identified for refractory SLE via targeted degradation of Ikaros and Aiolos — transcription factors that are master regulators of plasmablast differentiation, the process producing the autoantibody-secreting cells driving lupus pathology. Targeted protein degradation rather than receptor blockade — mechanistically distinct from every approved SLE biologic. Phase II SLE data is emerging. Refractory lupus nephritis specifically, where conventional biologics have failed, remains untested despite the mechanistic rationale being directly transferable from the myeloma indication.
Full mechanistic analysis available under commercial agreement.
Request AccessMavrilimumab identified for biologic-refractory rheumatoid arthritis — patients who have failed TNF inhibitors, IL-6 inhibitors, JAK inhibitors, and CD20 depletion. GM-CSF receptor blockade targets synovial macrophage activation through a pathway entirely distinct from every current biologic class, retaining mechanistic activity in patients who have exhausted all approved options. Phase II data exists demonstrating efficacy and tolerability. Mavrilimumab is not yet approved — the regulatory gap between existing Phase II evidence and an approved indication for refractory RA represents the specific commercial opportunity.
Full mechanistic analysis available under commercial agreement.
Request AccessBaricitinib, approved for rheumatoid arthritis, atopic dermatitis, and acute COVID-19, identified for Long COVID via dual mechanism — suppressing the persistent type I interferon neuroinflammatory signature while simultaneously addressing autoantibody-mediated autonomic dysfunction in a significant subset of patients. The existing COVID-19 approval establishes safety precedent in the same viral context, making the Long COVID extension mechanistically and regulatorily logical. No completed Long COVID RCT exists for baricitinib despite its interferon-suppressing mechanism directly targeting the most well-characterised neuroinflammatory pathway in Long COVID pathology.
Full mechanistic analysis available under commercial agreement.
Request AccessA sequential biologic protocol identified for peanut OIT patients who have failed standard approaches — omalizumab neutralises existing free IgE during the dangerous dose escalation phase, then dupilumab prevents new IgE synthesis to consolidate durable tolerance during maintenance. The two drugs address different points in the IgE lifecycle: omalizumab neutralises what exists, dupilumab prevents what is being produced. Sequential use is mechanistically superior to either drug alone in the most difficult-to-treat patients. No trial has tested this specific sequential protocol in OIT-refractory patients despite the mechanistic logic being directly derivable from each drug's established pharmacology.
Full mechanistic analysis available under commercial agreement.
Request AccessThe Omalizumab → Dupilumab sequential biologic protocol identified this week for peanut OIT surfaces simultaneously for tree nut OIT — with an even stronger mechanistic argument. Ana o 3's exceptional affinity for mast cell-bound IgE makes the initial IgE neutralisation phase with omalizumab even more critical during cashew OIT dose escalation than during peanut OIT. The transition to dupilumab for sustained IgE synthesis suppression and tolerance consolidation follows identical mechanistic logic. Two conditions, same protocol, stronger case in tree nut given Ana o 3 severity profile. No tree nut-specific sequential biologic OIT trial exists.
Full mechanistic analysis available under commercial agreement.
Request AccessTegileridine identified for fibromyalgia and chronic neuropathic pain via biased μ-opioid receptor agonism — activating the analgesic G-protein pathway while avoiding the β-arrestin pathway responsible for tolerance, dependence, and respiratory depression. No studies exist combining biased μ-opioid agonism with fibromyalgia as the primary indication despite central sensitisation being a direct target of μ-opioid signalling.
Full mechanistic analysis available under commercial agreement.
Request AccessAtogepant, FDA-approved for migraine prevention, blocks the CGRP receptor on trigeminal afferents. Radiation therapy to the head and neck damages trigeminal ganglia, upregulating CGRP and producing a chronic neuropathic pain syndrome in survivors — a population with high disease burden and no mechanism-targeted treatment. No gepant-class drug has ever been evaluated in radiation-induced oropharyngeal pain despite the pathway being directly implicated by the same mechanism atogepant already blocks in migraine.
Full mechanistic analysis available under commercial agreement.
Request AccessTertiary Lymphoid Structures begin forming during the relapsing-remitting phase of MS — not only in progressive disease as previously assumed. Anti-CD20 therapy depletes peripheral B-cells but cannot penetrate the CNS parenchyma. BTK inhibitors cross the blood-brain barrier and suppress compartmentalised microglial inflammation that current DMTs cannot reach. The two mechanisms are non-overlapping: combining them early, before TLS consolidate into CNS-compartmentalised structures, could alter the long-term trajectory toward progressive MS — the transition that current treatments consistently fail to prevent.
Full mechanistic analysis available under commercial agreement.
Request AccessPatients with high peanut-specific IgE and low sIgG4/sIgE ratio represent a tolerance-resistant subgroup who fail oral immunotherapy at disproportionate rates and currently have no effective treatment pathway. Dupilumab blocks IL-4 and IL-13 signalling upstream of IgE production — mechanistically distinct from omalizumab which neutralises existing IgE downstream — while simultaneously reducing mucosal mast cell priming that drives the dose reactions causing OIT dropout. No RCT has tested this stratified approach.
Full mechanistic analysis available under commercial agreement.
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