Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Technical Presentation (September 2020)
33 slides from Inmune Bio's technical presentation, Sep 29, 2020
Slide 1: Harnessing the Power of the Innate Immune System: KOL Webinar on Treatment Resistant Depression
HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM IN MB KOL Webinar on Treatment Resistant Depression Sept 29, 2020
Slide 2: Forward Looking Statements
INmuneBir 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 o
Slide 3: Major Depression, Cancer, Alzheimer's, COVID19
Major Depression Cancer Alzheimer’s COVID19 PMID: 31806905
Slide 4: Major Depression: Common, Fatal, Disabling
Common Fatal Disabling Major Depression 25 million adults in US Leading cause of disability worldwide (years lived with disability) 40,000 US adults 10 th leading cause of death Slide courtesy of Andy Miller
Slide 5: Treatment Resistant
Treatment Resistant 7 million
Slide 6: TRD Webinar Panelists
TRD Webinar panelists Named “one of the world’s most influential researchers” by Web of Science Mary Sue and Mike Shannon Distinguished Chair for Healthy Minds, Children & Families, Professor University of Wisconsin - Madison CEO and Founder of Avalon Health Economics 25 years of experience studying
Slide 7: Agenda
Agenda John Schneider, PhD The Economics of Treatment - Resistant Depression 1 Clinical trial 3 Q & A 4 2 Charles L. Raison, MD Inflammation and the Precision Treatment of Depression
Slide 8: The Economics of Treatment-Resistant Depression
The Economics of Treatment - Resistant Depression Epidemiological & Cost Considerations Presentation at INmuneBio Webinar John Schneider, PhD Avalon Health Economics September 29, 2020
Slide 9: Epidemiology of Treatment Resistant Depression (TRD)
9 1. Epidemiology of Treatment Resistant Depression (TRD) MDD • Major depressive disorder (MDD) has a prevalence in the U.S. of about 8%* • Prevalence of MDD has been growing, and is expected to worsen as a result of the pandemic and the resulting recession (e.g., due to stress, job loss, lower wage
Slide 10: Economics of TRD: Direct & Indirect Costs
10 2a. Economics of Treatment Resistant Depression: Direct & Indirect Costs Source: Amos et al., Direct and Indirect Cost Burden and Change in Employment Status in Treatment Resistant Depression. Journal of Clinical Psychiatry 79 (2018) TRD also has substantially higher disability costs TRD has comp
Slide 11: Economics of TRD, by Severity
11 2b. Economics of Treatment Resistant Depression, by Severity Source : Pilon et al . Is Clinician Impression of Depression Symptom Severity Associated with Incremental Economic Burden in Privately Insured US Patients with Treatment Resistant Depression . Journal of Affective Disorders 255 ( 2019 )
Slide 12: Economics of TRD, Regimen Changes
12 2c. Economics of Treatment Resistant Depression, Regimen Changes Source: Russell et al., The Cost Consequences of Treatment - Resistant Depression. Journal of Clinical Psychiatry 65 (2004) Source: Amos et al., Direct and Indirect Cost Burden and Change in Employment Status in Treatment Resistant
Slide 13: Discussion: Main Points / Challenges
13 3. Discussion Main Points / Challenges 1. TRD 2x more costly than MDD (Amos et al.) 2. More severe TRD is more costly than mild to moderate TRD (Pilon et al.) 3. TRD patients who switch treatment regimens more frequently have higher costs (Russell et al.; Amos et al.) 4. Additional challenges (Fi
Slide 14: Inflammation and the Precision Treatment of Depression
Inflammation and the Precision Treatment of Depression Charles L. Raison, MD University of Wisconsin - Madison Madison, WI
Slide 15: Did Depression Evolve Out of Sickness?
Did Depression Evolve Out of Sickness? Raison CL, et al. Semin Clin Neuropsychiatry . 2001;6(4):277 - 294. ● Loss of pleasure* ● Loss of appetite* ● Weight loss* ● Cognitive disturbance* ● Decreased sexual energy* ● Fatigue* ● Physical slowness * ● Sleep disturbance * ● Social isolation* ● Increased
Slide 16: Lessons from Interferon-alpha
Lessons from Interferon - alpha
Slide 17: Inflammation Causes Depression Responsive to Antidepressants
Inflammation Causes Depression Responsive to Antidepressants Musselman D et. al. N Engl J Med . 2001;344:961. Weeks on IFN - alpha Survival Free of Major Depression (%) 0 2 4 6 8 10 12 0 20 40 60 80 100 Placebo Paroxetine
Slide 18: p38 Activates TNF and Predicts Development of IFN-alpha Depression
p38 Activates TNF and Predicts the Development of IFN - alpha Depression 0 10 20 30 0 10 20 30 20 40 80 100 MFI score at 4 weeks Delta p - p38 r =0.72, p =0.013 % p - p38 - positive lymphocytes 5 15 25 35 MADRS score at 4 weeks Delta p - p38 r =0.85, p =0.001 MADRS <15 MADRS ≥15 Delta p - p38 0 5 10
Slide 19: TNF Signaling Associated with Immune-Based Depression
TNF Signaling Associated with Immune - Based Depression Raison et al. Mol Psychiatry 2010;15(5):535 - 47
Slide 20: Plasma TNF Elevated in Patients with MDD
Plasma TNF Elevated in Populations of Patients with Major Depressive Disorder (MDD) Liu et al. J Affect Disord 2012; 139: 230 - 239
Slide 21: Inflammatory Markers in Depression
CRP = C - reactive protein; IL = interleukin; LPS = lipopolysaccharide; PHA = phytohaemagglutinin ; TNF - α = tumor necrosis factor alpha. Stieglitz J, et al. Brain Behav Immun . 2015;49:130 - 139.
Slide 22: A Closer Look at the Association of Inflammation with Depression
A Closer Look at the Association of Inflammation with Depression 100 Controls MDD IL - 6 pg/ mL P =.000 650 600 550 500 450 400 350 300 250 200 150 Inflammatory Sub - Group Non - inflammatory Sub - Group IL - 6 = interleukin 6. Kim YK, et al. Prog Neuropsychopharmacol Biol Psychiatry . 2007;31(5):10
Slide 23: TNF Antagonism for Treatment Resistant Depression
TNF Antagonism for Treatment Resistant Depression TRD = treatment - resistant depression; HAM - D = Hamilton Rating Scale for Depression; CGI = Clinical Global Impression. Raison CL, et al. JAMA Psychiatry . 2013;70(1):31 - 41. 60 patients with TRD were randomized on a 1 - to - 1 basis to receive ei
Slide 24: TNF Antagonism Works in Depressed Patients with Elevated Inflammation
TNF Antagonism Works in Depressed Patients with Elevated Inflammation Infliximab Placebo 60 50 40 30 20 0 10 Med + Low High Responders d uring Study (%) Hs - CRP ( tertiles ) Hs - CRP = high - sensitivity CRP. Raison CL, et al. JAMA Psychiatry . 2013;70(1):31 - 41.
Slide 25: TNF Antagonism for Bipolar Depression
TNF Antagonism for Bipolar Depression MADRS = Montgomery – Åsberg Depression Rating Scale. McIntyre RS, et al. JAMA Psychiatry . 2019;76(8):783 - 7 90.
Slide 26: Inflamed Depressed = Different Brain
Inflamed Depressed = Different Brain DS = dorsal striatum; IFN = interferon; SMA = supplementary motor area; SN = substantia nigra; vmPFC = ventromedial prefronta l c ortex; VS = ventral striatum; VTA = ventral tengmental area; 3 - HAO = 3 - hydroxyanthranilic acid oxygenase; AMPAR = 2 - amino - 3 -
Slide 27: Conclusions
Conclusions • Inflammatory stimuli (i.e. IFN - alpha) promote depression, in part through increased TNF signaling • Groups of depressed individuals show increased TNF and other inflammatory biomarkers, resulting from a sub - group with elevated inflammation • Non - specific TNF antagonism with infli
Slide 28: Phase 2 Double-Blind Placebo-Controlled Study of XPro1595 in TRD
Phase 2 double blind placebo - controlled study of XPro1595 in Patients with treatment resistant depression and biomarkers of inflammation and anhedonia Emory & University Alabama Birmingham Andrew Miller MD, Jennifer Felger PhD, Richard Shelton MD 6 weeks • XPro1595 (1mg/kg) N=45 • Placebo N=45 Cri
Slide 29: Selecting Patients and Determining Response Using Biomarkers
Selecting patients using ▪ Biological Biomarker - blood CRP ▪ Behavioral Biomarkers - Anhedonia Novel use of biomarkers in Psychiatry Determining Response ▪ Non - invasive biological biomarkers of CNS response ▪ Functional connectivity (fMRI) ▪ Neuroinflammation (MRI) ▪ Blood inflammatory biomarkers
Slide 30: Questions & Answers
30 30 Questions & Answers
Slide 31: Contact Us
CONTACT US 31 HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM INMB INmune Bio Inc. 1200 Prospect Str. Suite 525 La Jolla, CA 92037 (858) 964 - 3720 www.inmunebio.com THANK YOU FOR YOUR PARTICIPATION
Slide 32: Backup Slides
32 32 Backup slides
Slide 33: Functional Connectivity Between Ventral Striatum and vmPFC
( A ). Functional connectivity (FC) between the ventral striatum (VS) and a cluster in ventromedial prefrontal cortex ( vmPFC ) was negatively associated with inflammation (plasma C - reactive protein [CRP]) in patients with depression (B) Patients with higher levels of CRP had lower FC compared to