UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

 

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

 

Date of Report (Date of earliest event reported): September 29, 2020

 

INMUNE BIO INC.
(Exact name of registrant as specified in charter)

 

Nevada   001-38793   47-5205835
(State or other jurisdiction   (Commission   (IRS Employer
of incorporation)   File Number)   Identification No.)

 

1200 Prospect Street, Suite 525, La Jolla, CA 92037

(Address of Principal Executive Offices) (Zip Code)

 

(858) 964 3720

(Registrant’s Telephone Number, Including Area Code)

 

Not Applicable

(Former Name or Former Address, If Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class   Trading Symbol(s)   Name of each exchange on which
registered
Common Stock, par value $0.001 per share   INMB   The NASDAQ Stock Market LLC

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

 

Emerging growth company ☒

 

If an emerging growth company, indicate by check mart if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

 

 

 

 

 

 

Item 8.01 Other Events

 

INmune Bio Inc. (the “Company”) is filing as Exhibit 99.1 to this Current Report on Form 8-K a presentation (“Presentation”) for a Key Opinion Leader (KOL) webinar on the topic of treatment resistant depression (TRD) that it will present on Tuesday, September 29, 2020.

 

Item 9.01 Financial statements and Exhibits

 

(d) Exhibits.

 

Exhibit
Number
  Description
     
99.1   Presentation for Webinar

 

1

 

 

SIGNATURE

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Date: September 29, 2020 INMUNE BIO INC.
   
  By: /s/ David Moss
    David Moss
    Chief Financial Officer

 

2

 

 

Exhibit 99.1

 

HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM IN MB KOL Webinar on Treatment Resistant Depression Sept 29, 2020

 

 

Forward Looking Statements

 

 

Major Depression Cancer Alzheimer’s COVID19 PMID: 31806905

 

 

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

 

 

Treatment Resistant 7 million

 

 

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 economic and organizational aspects of the health care industry CHARLES L. RAISON MD JOHN E. SCHNEIDER, PHD

 

 

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

 

 

The Economics of Treatment - Resistant Depression Epidemiological & Cost Considerations Presentation at INmuneBio Webinar John Schneider, PhD Avalon Health Economics September 29, 2020

 

 

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 wages, etc.) • MDD is associated with significant morbidity and mortality, costs, work loss days (absenteeism), and productivity (presenteeism) TRD • A substantial proportion of “pharmaceutically treated” depression (PTD) patients does not respond to treatment with 2+ antidepressant medications despite adequate dose, duration, and adherence to treatment.* These cases are considered “treatment resistant” depression (TRD) • Proportion of MDD/PTD cases that progress to TRD is estimated to be 10% - 35% , depending on study & definition of TRD* • Some estimates as high as 50% ** • Meta - analysis = 13% - 15%*** Notes : *Based on Fine et al . Treatment Resistant Depression Incidence Estimates From Studies of Health Insurance Databases Depend Strongly on the Details of the Operating Definition, Heliyon 4 ( 2018 ) ; **CMS, 2015 ; ***AHE research, 2020

 

 

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 comparatively higher mental health *and* non - mental health care costs

 

 

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 ) Within TRD, more severe cases have substantially higher behavioral *and* non - behavioral - related costs

 

 

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 Depression. Journal of Clinical Psychiatry 79 (2018) +15 years • Mental health costs and non - mental health costs increase linearly with changes in treatment regimen

 

 

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 (Fife et al.) – How to define TRD – How to determine which patients are most likely to progress to TRD or progress within TRD (i.e., 10 - 50% is a very wide range). – This is likely a treatment heterogeneity problem, which can be addressed by biomarkers Treatment Heterogeneity A - Randomized Clinical Trial (RCT) of Drug X on all individuals with disease Y B - RCT of X on Y > age 50 C - RCT of X on Y with specific biomarker of Z Note : Assume areas under each curve would be different: A > B > C Treatment Effect

 

 

Inflammation and the Precision Treatment of Depression Charles L. Raison, MD University of Wisconsin - Madison Madison, WI

 

 

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 pain* ● Fever * ● Sad mood † ● Suicidal ideation † ● Worthlessness/guilt † ● Loss of pleasure* ● Loss of appetite* ● Weight loss* ● Cognitive disturbance* ● Decreased sexual energy* ● Fatigue* ● Physical slowness * ● Sleep disturbance * ● Social isolation* ● Increased pain complaints* ● Increased body temperature * ● Sad mood † ● Suicidal ideation † ● Worthlessness/guilt † DEPRESSION SICKNESS

 

 

Lessons from Interferon - alpha

 

 

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

 

 

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 15 20 ** MADRS ≥15 MADRS <15 9 AM 11 AM 1 PM 3 PM 5 PM 7 PM 9 PM 0 5 10 15 20 IFN - alpha *** 60 *** Felger JC et al. Brain Behav Immun 2011;25(6):1094 - 8.

 

 

TNF Signaling Associated with Immune - Based Depression Raison et al. Mol Psychiatry 2010;15(5):535 - 47

 

 

Plasma TNF Elevated in Populations of Patients with Major Depressive Disorder (MDD) Liu et al. J Affect Disord 2012; 139: 230 - 239

 

 

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.

 

 

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):1044 - 1053.

 

 

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 either 3 infusions of the TNF antagonist infliximab vs a salt water placebo at baseline, Week 2, and Week 6. Depressive symptoms were assessed pre - treatment and at weeks 1, 2, 3, 4, 6, 8, 10, and 12. Weeks 4 12 3 10 1 6 2 Baseline 8 Infusion Infusion Infusion n=30 n=30 INFLIX (5 mg/kg) PLACEBO Randomization Clinician - Administered Psychiatric Assessments (HAM - D, CGI) Adverse Events Evaluation Blood Draw for Inflammatory Markers and Safety Labs TRD Pts (n=60) Stratification Male vs Female CRP > 2 vs CRP ≤ 2 30 25 20 15 10 0 5 4 12 Adjusted Mean HAM - D - 17 Weeks 3 10 1 6 2 Baseline 8 Infliximab Placebo

 

 

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.

 

 

TNF Antagonism for Bipolar Depression MADRS = Montgomery – Åsberg Depression Rating Scale. McIntyre RS, et al. JAMA Psychiatry . 2019;76(8):783 - 7 90.

 

 

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 - (5 - methyl - 3 - oxo - 1,2 - oxazol - 4 - yl) p ropanoic acid receptor; D1 = dopamine 1 receptor 1; D2 = dopamine 2 receptor; DDC = dopamine decarboxylase; KMO = kynurenine 3 - monooxygenase; NMDAR = N - met hyl - D - aspartic acid receptor; NO = nitric oxide; NOS = nitric oxide synthase; PAH = phenylalanine hydroxylase; ROS = reactive oxygen species; TH = t yrosine hydroxylase. Felger JC, et al. Neuropsychopharmacology . 2017;42(1):216 - 241.

 

 

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 infliximab has no overall benefit in patients with unipolar or bipolar depression, but shows a signal in the sub - group of patients with elevated inflammation or ELA, which is associated with increased inflammation • Medically - healthy patients with MDD and increased inflammation show unique changes in brain function and connectivity and tend to demonstrate increased anhedonia (loss of pleasure) • Improved, more specific TNF antagonists may represent novel “precision medicine” based treatments for this sub - group of depressed patients.

 

 

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 Criteria • Failed 2 anti - depressants • CRP >3 mg/L • Anhedonia Endpoints (Baseline, 2, 6 weeks): • Imaging (MRI/fMRI) • Blood inflammation • Clinical scales Primary Goal Improve functional connectivity and reduce biomarkers of inflammation and Secondary Goal Improve clinical measures of motivation

 

 

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 ▪ Behavioral Biomarker – Motivation and anhedonia

 

 

30 30 Questions & Answers

 

 

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

 

 

32 32 Backup slides

 

 

( 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 those with CRP <1 mg/L (*p<0.05,**p<0.01) ( C ), and significant VS - vmPFC FC (yellow - red intensity) was not observed in the patients with CRP >3 mg/L Primary outcome: Functional Connectivity between the striatum and Prefrontal cortex