HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM Modulating an Innate Immune Response Against Diseases INMB CORPORATE PRESENTATION May 2020
FORWARD LOOKING STATEMENTS This presentation contains “forward -looking statements” Forward-looking statements reflect our current view about future events. When used in this presentation, the words “anticipate,” “believe,” “estimate,” “expect,” “future,” “intend,” “plan,” or the negative of these terms and similar expressions, as they relate to us or our management, identify forward-looking statements. Such statements, include, but are not limited to, statements contained in this presentation relating to our business strategy, our future operating results and liquidity and capital resources outlook. Forward-looking statements are based on our current expectations and assumptions regarding our business, the economy and other future conditions. Because forward – looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Our actual results may differ materially from those contemplated by the forward-looking statements. They are neither statements of historical fact nor guarantees of assurance of future performance. We caution you therefore against relying on any of these forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, without limitation, our ability to raise capital to fund continuing operations; our ability to protect our intellectual property rights; the impact of any infringement actions or other litigation brought against us; competition from other providers and products; our ability to develop and commercialize products and services; changes in government regulation; our ability to complete capital raising transactions; and other factors relating to our industry, our operations and results of operations. There is no guarantee that any specific outcome will be achieved. Investment results are speculative and there is a risk of loss, potentially all loss of investments. Actual results may differ significantly from those anticipated, believed, estimated, expected, intended or planned. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We cannot guarantee future results, levels of activity, performance or achievements. Except as required by applicable law, including the securities laws of the United States, we do not intend to update any of the forward-looking statements to conform these statements to actual results. 2
INVESTMENT SUMMARY Immunology company, advancing through Phase I and Phase II clinical trials ▪ Catalyst rich programs with multiple readouts in 2020 and 2021 ▪ Two platforms with novel approaches targeting the innate immune system ▪ DOMINANT NEGATIVE TUMOR NECROSIS FACTOR (DN-TNF) PLATFORM First dominant-negative protein to enter clinic selectively targeting inflammation without immunosuppression NK CELL PRIMING PLATFORM INKmune primes patient’s NK cells to eliminate residual disease Over 65 publications from multiple universities worldwide on both platforms with extensive in vivo data ▪ Notable shareholder and director, Xencor ▪ Insiders own ~50% ▪ 3
PIPELINE Focused on Developing Therapies that Target the INNATE IMMUNE System DN-TNF PLATFORM DISEASE FIELD PRE-CLINICAL PHASE I PHASE II (POC) PIVOTAL NEXT MILESTONE 1H-21 Trastuzumab Resistance initiate p2 ONCOLOGY 1H-21 NASH Initiate p2 GI 2H-20 Alzheimer’s Disease Complete p1 CNS 3Q-20 COVID-19 Initiate p2 NK PRIMING DISEASE FIELD PRE-CLINICAL PHASE I PHASE II (POC) PIVOTAL NEXT MILESTONE PLATFORM 1H21 Ovarian initiate p1 CANCER 2H20 Myelodysplastic Syndrome Initiate p1 ONCOLOGY 4
DN-TNF PLATFORM T E C N O L O G Y NEXT GENERATION TNF INHIBITOR -SAFER AND SELECTIVE TO TARGET MARKETS EXISTING TNF INHIBITORS MUST AVOID 5
TUMOR NECROSIS FACTOR (TNF) The “Master” Cytokine LCN2 PRO-INFLAMATORY ANTI-INFLAMATORY IL 6 sTNF promotes translation ▪ of IL6, Lipocalin 2 and other downstream cytokines sTNF Plasma Concentration Block sTNF and ▪ downstream pro- inflammatory cytokines do not occur Time Adapted from Andreasen et al 2008 6
THE BIOLOGY OF CURRENT TNF INHIBITORS X Current Inhibitors Are Not Selective and Block Both Forms of TNF Negative effects of TNF are a result of sTNF WHEREAS tmTNF X X Transmembrane-bound Soluble TNF (‘sTNF’) PROVIDES (‘tmTNF’) GOOD BAD IMMUNOSUPPORTIVE AND NEUROPROTECTIVE FUNCTION IMPORTANT TO HOST SURVIVAL TNFR2 TNFR1 Internalization Adapted from MacEwan et al 2002 7
TNF BIOLOGY. HOW DN-TNF WORKS DIFFERENCES: DN-TNF Neutralizes ONLY Soluble TNF and Leaves Transmembrane TNF Selective vs. and the Receptors Functional Non-Selective TNF Inhibition DN Non- Selective TNF Decreases Y Y “BAD” sTNF with DN-TNF Only “GOOD” tmTNF continues to inflammation does not bind to receptors bind to TNFR1 and TNFR2 Increased risk Y N of infection Increased risk Y N of cancer Causes Y N demyelination TNFR1 TNFR2 TNFR1 Neuroprotective N Y Internalization Enhances N Y neuroplasticity Adapted from MacEwan et al 2002 8
SELECTIVE TARGETING FUNCTIONAL tmTNF PREVENTS PREVENTS DEMYLINATION IMMUNOSUPPRESSION Non-selective TNF Inhibition Causes Demyelination, Non-selective TNF Inhibition Causes Immunosuppression DN-TNF Promotes Remyelination CUPRIZONE Model of Multiple Sclerosis % Survival DN-TNF ETANERCEPT Anti-inflammatory NOT Anti-inflammatory AND immunosuppressive immunosuppressive Days Post-Infection REMYELINATION 9
Clinical Trial to Test Neuroinflammation as the Common Denominator of ALZHEIMER’S DISEASE 10
sTNF A VALIDATED TARGET IN ALZHEIMERS DISEASE RISK OF ALZHEIMER’S DISEASE IN MAN Risk of general population Adapted from Chou et al. 2016 8.5M claims AD risk is not reduced by other anti-inflammatory treatments Despite positive AD activity, non-selective TNF inhibitors increase the risk of cancer, infection, and MS 11
PHASE 1 AD TRIAL IMMUNOLOGIC BIOMARKERS Phase IB trial in Alzheimer’s patients with biomarkers of inflammation BEHAVIORAL BIOMARKERS OF INFLAMMATION SLEEP DISORDERS DEPRESSION PSYCHOSIS APATHY AGGRESSION DESIGN BIOLOGICAL BIOMARKERS OF INFLAMMATION 18 patients in 3 cohorts ▪ Weekly XPro1595™ SubQ injections for 3 months ▪ Biomarkers of inflammation at 0, 6, 12 weeks ▪ MRI INCLUSION Must have 1 inflammatory biomarker (local lab): FreeWater content of white matter ▪ hsCRP>1.5 ▪ ESR>10 CSF ▪ HbA1C >6% BLOOD ▪ APOE4 positive Inflammation & Inflammation & Neurodegeneration Neurodegeneration ( Roche NeuroTool kit ) ( Roche NeuroTool kit ) ENDPOINTS ▪ Safety BREATH ▪ Change in inflammation (blood, CSF , Brain, breath, behavior) Volatile Organic Compounds ▪ Change in neuropsychiatric symptoms, cognition, QOL 12
WHITE MATTER FREE WATER: A Biomarker For Neuroinflammation White Matter Free Water WMFW - sex and age matched NC and AD subjects Normal aging AD From Dumont 2019 13
Clinical Trial to Determine if Targeting Soluble TNF (sTNF) may Prevent Catastrophic Complications of COVID-19 14
BLUNTING CYTOKINE STORM AND HYPERINFLAMMATION TNF levels elevated in COVID-19 Patients ▪ Cytokine storm caused by increase expression of sTNF , 250 IL1, and IL6 ▪ sTNF significantly elevated in blood of patients 200 ▪ Neutralizing sTNF should decrease expression of IL1 and IL6 150 ▪ Ideal therapy has 5 characteristics: ▪ Safe and well tolerated 100 ▪ Not immunosuppressive 50 ▪ Easy to use Normal TNF level ▪ Rapid onset <10pg/ml 0 *p<0.05 Non-ICU ICU ▪ Targets inflammation Diao2020 15
WHY sTNF AND IS NOT IMMUNOSUPPRESSIVE WHY ? Approved cytokine inhibitors (anti-TNF/IL6/IL1) are immunosuppressive ▪ Stops inflammation ▪ QUELLOR does not compromise immune response to viral infection ▪ QUELLOR improves immune response to bacterial infection including M. ▪ Not immunosuppressive tuberculosis or parasitic infection (not shown) ▪ Rapid onset ▪ Corticosteroids very immunosuppressive - contraindicated in COVID-19 ▪ No contra-indications No Change in Survival after EEE or Coxsackie B3 infection ▪ Easy to use EEE injected ▪ Safe and well tolerated ▪ Crosses BBB (Blood Brain Barrier) Quellor labeled as XPro1595 Viral data from NIAID contract 2020 16
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