Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — HC Wainwright NASH Day 2019
25 slides from Inmune Bio's conference presentation, Oct 21, 2019
Slide 1: Targeting Soluble TNF to Treat NASH
Targeting Soluble TNF to Treat NASH RJ Tesi MD President and CEO INmune Bio Inc V1
Slide 2: Forward looking statements
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 the
Slide 3: Inflammation plays a leading role in NAFLD/NASH
“A key finding is that inflammatory pathways,… are linked to both histological activity as well as fibrosis; a fact which can be potentially leveraged for therapeutics” Sanyal et al Nature 2019 HC Wainwright NASH Day 21 October 2019 Inflammation plays a leading roll in NAFLD/NASH 3
Slide 4: Guiding Principles of INMB NASH program
Guiding Principles of INMB NASH program Fibrosis is not the target! Eliminating the causes of inflammation will effectively treat NASH. HC Wainwright NASH Day 21 October 2019 4
Slide 5: 3 cycles of Chronic Inflammation in NASH
Obesity Insulin Resistance Peripheral Inflammation Intestinal Inflammation Mesenteric fat Regional Inflammation lipotoxicity Innate immune activation Local Inflammation N A S H 3 cycles of Chronic Inflammation in NASH HC Wainwright NASH Day 21 October 2019 5
Slide 6: TNF is the "master" cytokine
TNF is the “master” cytokine HC Wainwright NASH Day 21 October 2019 6
Slide 7: NeuLiv inhibits soluble TNF
NeuLiv inhibits soluble TNF • 17 kDal mutated protein +10 kDal linear PEG • Identical to human TNF except for 6 amino acid substitutions • Once a week dosing by subQ injection 7 Receptor binding, "DE loop" domain (subunit A) Receptor binding , "small" domain (subunit A) Mutation A145R Receptor bindi
Slide 8: TNF biology is complicated
TNF biology is complicated … HC Wainwright NASH Day 21 October 2019 8 TNFR1 TNFR2 tmTNF (good) sTNF (bad) Normal TNF Biology TNFR1 TNFR2 tmTNF (good) sTNF (bad) Approved TNF inhibitors X X TNFR1 TNFR2 tmTNF (good) sTNF (bad) NeuLiv X
Slide 9: NeuLiv neutralizes sTNF by Dominant-Negative technology
NeuLiv neutralizes sTNF by Dominant - Negative technology Active TNF + Inflammation Normal sTNF activity TNFR NeuLiv Active TNF + Inactive heterotrimers or sTNF bind TNFR No Inflammation Heterotrimers cannot bind TNFR NeuLiv neutralizes sTNF 9 HC Wainwright NASH Day 21 October 2019
Slide 10: Differences: selective vs non-selective TNF inhibition
Non - selective TNF inhibitor NeuLiv Decreases inflammation YES YES Increased risk of infection YES NO Increased risk of cancer YES NO Causes demyelination YES NO Neuroprotective NO YES Enhances neuroplasticity NO YES Differences: selective vs non - selective TNF inhibition NeuLiv: Next Generation T
Slide 11: Baseline: High Fat/High Fructose Diet
Baseline: High Fat/High Fructose Diet HC Wainwright NASH Day 21 October 2019 13% kcal from fat n ormal water 42% kcal from fat 30% fructose water Normal HF/HF Glucose (mg/dl) 99 96 Insulin ( μ U/ml) 11 50 HOMA - IR 2.4 7.9 Triglycerides (mg/dl) 37 51 Cholesterol (mg/dl) 40 169 0% 10% 20% 30% 40% 50%
Slide 12: Targeting Peripheral Inflammation
Obesity Insulin Resistance N A S H Targeting Peripheral Inflammation HC Wainwright NASH Day 21 October 2019 12
Slide 13: NAFLD: high fat/high fructose diet
NAFLD: high fat/high fructose diet – 13 weeks HC Wainwright NASH Day 21 October 2019 B o d y W e i g h t ( g ) 25 27 29 31 33 35 37 39 41 43 B a s e l i n e W e e k 1 W e e k 2 W e e k 3 W e e k 4 W e e k 5 W e e k 6 W e e k 7 W e e k 8 W e e k 9 W e e k 1 0 w e e k 1 1 w e e k 1 2 w e e k 1 3 B o d
Slide 14: Decreased Peripheral Inflammation
Decreased Peripheral Inflammation HC Wainwright NASH Day 21 October 2019 0 10 20 30 40 50 60 70 80 90 Normal NeuLiv HF/HF HF/HF NeuLiv Leptin (ng/ml) 0 1 2 3 4 5 6 7 8 9 Normal NeuLiv HF/HF HF/HF NeuLiv IL6 ( pg /ml) 0 10 20 30 40 50 60 70 80 90 Normal NeuLiv HF/HF HF/HF NeuLiv LCN2 ( μ g/ml) from R
Slide 15: Targeting Regional Inflammation
Intestinal Inflammation Mesenteric fat N A S H Targeting Regional Inflammation HC Wainwright NASH Day 21 October 2019 15
Slide 16: NeuLiv improves intestinal leak and inflammation
NeuLiv improves intestinal leak and inflammation • Decreases colonic inflammation • Upregulates tight junction proteins in small intestine and colon to decrease leaky gut HC Wainwright NASH Day 21 October 2019 16 HF/HF Normal NeuLiv adapted from Rodriguez/Tansey 2019 HF/HF Normal
Slide 17: Mesenteric fat: aka Pot Belly
Mesenteric fat: aka – Pot Belly • Mesenteric fat is highly inflamed • Mesenteric inflammation correlates with steatosis • Mesenteric inflammation correlates with insulin resistance HC Wainwright NASH Day 21 October 2019 from Conrad 2016 17
Slide 18: Targeting Local Inflammation
lipotoxicity Innate immune activation N A S H Targeting Local Inflammation HC Wainwright NASH Day 21 October 2019 18
Slide 19: NAFLD: high fat/high fructose diet
NAFLD: high fat/high fructose diet – 13 weeks • NeuLiv decreases steatosis and liver weight HC Wainwright NASH Day 21 October 2019 Control NeuLiv Structurally similar to controls 20x adapted from Rodriguez/Tansey 2016/2019 19
Slide 20: NeuLiv decreases hepatic inflammation
NeuLiv decreases hepatic inflammation • Decrease LCN2 • No effect of mRNA IL1 or IL6 • Decrease Tlr2 mRNA – Tlr2 expressed by hepatocytes when there are bacterial products in blood supply • Blood LCN2 is a biomarker of hepatic inflammation HC Wainwright NASH Day 21 October 2019 20 adapted from Rodri
Slide 21: Untargeted hepatic metabolomics
Untargeted hepatic metabolomics • Unique metabolic phenotypes • HF/HF diet associated with insulin impairment, fatty acid, phospholipid, branched chain amino acid and purine metabolism • NeuLiv can reverse some of the disruptions associated with HF/HF diet HC Wainwright NASH Day 21 October 2019 21 a
Slide 22: STAM model
S T A M m o d e l HC Wainwright NASH Day 21 October 2019 22
Slide 23: STAM model: NAFLD Activity Score and Fibrosis Score
STAM model: N AFLD A ctivity S core and Fibrosis Score HC Wainwright NASH Day 21 October 2019 0 1 2 3 0 1 2 3 0 1 2 Control 2 4 1 - - - 1 6 3 3 1 NeuLiv 4 4 - - - - 5 3 8 - - hepatocyte ballooning lobular inflammation steatosis Control 4.4 ц 0.8 NeuLiv 2.9 ц 0.8 NAS (mean ц SD) Parameter (mean ц SD)
Slide 24: Neutralizing sTNF reverses pathology of NAFLD/NASH
Neutralizing sTNF reverses pathology of NAFLD/NASH • Decreases inflammation from peripheral and mesenteric fat • Decreases insulin resistance • Decreases intestinal leak • Prevents hepatocyte death • Prevents hepatic fibrosis Next Steps • Design and implement a Phase II clinical trial in NASH • Vali
Slide 25: NeuLiv Phase II clinical trial in NASH
NeuLiv Phase II clinical trial in NASH • Non - biopsy trial - patient selection using Perspectum imaging technology • Enroll F2/F3 patients • 12 - week trial with imaging at week 6 and 12 • NeuLiv 1mg/kg subQ once a week • Final design pending – Two or three arm study: 30 - 40 patients per arm HC Wa