Corbus Pharmaceuticals Holdings, Inc. · NASDAQ:CRBP
Corbus Pharmaceuticals — Conference Presentation (January 2021)
26 slides from Corbus Pharmaceuticals's conference presentation, Jan 27, 2021
Slide 1: Targeting CB1 and CB2 for Human Therapeutics
Targeting CB1 and CB2 for Human Therapeutics e NYAS Targeting the Endocannabinoid System for Treatment of Human Diseases PHARMACEUTICALS Barbara White, MD Chief Medical Officer and Head of Research 27 JAN 2021 NASDAQ: CRBP @corbuspharma wy com
Slide 2: Barbara White Disclosures
Barbara White Disclosures » Corbus Pharmaceuticals, Inc. - employee, stock owner - Will discuss investigational agents that are not approved for human therapeutic use in any disease by any regulatory agency
Slide 3: CB1 Agonists
CB1 Agonists
Slide 4: Some approved therapeutic uses of CB1 agonists and cannabidiol
Some approved therapeutic uses of CB1 agonists and cannabidiol Dronabinol (synthetic THC) Nambiximols (plant-based THC/CBD) Supportive Nervous Genetic Care System Diseases Anorexia, Diseases Tuberous weight loss Niuscie sclerosis (HIV/AIDS) oe complex spasticity from Nausea and multiple vomiting fro
Slide 5: CB1 Antagonists/ Inverse Agonists
CB1 Antagonists/ Inverse Agonists
Slide 6: Some reported potential therapeutic uses of CB1 antagonists/inverse agonists
Some reported potential therapeutic uses of CB1 antagonists/inverse agonists Rimonabant (CB1 inverse Metabolic Fibrotic Other diseases agonist, sical Se 2008) ; diseases diseases Ascitase = Weight-loss (previous Lung fibrosis® Cognitive defects'° approval) 7 Cardiac fibrosis® Prader-Willi Diabetes!
Slide 7: Novel Corbus CB1 inverse agonists with limited blood-brain barrier penetration
Novel Corbus CB1 inverse agonists with limited blood-brain barrier penetration 5 Plasma and brain levels of rimonabant 30 minutes post 20 mg/kg IP injection. Han, FASEB J 2018; 33:4314 » Inhibit CB1 which regulates metabolism, inflammation, and fibrosis » Must limit brain exposure because of on-targ
Slide 8: Corbus CB1 inverse agonists are active in diet-induced obesity model
Corbus CB1 inverse agonists are active in diet-induced obesity model Vehicle 2 I Vehicle 1 A Pioglitazone 30 mg/kg QD 110-4 Mf cmpdc 5 mg/kg BID V Rimonabant 10 mg/kg QD A Cmpd C 10 mg/kg BID @ Cmpd D5 mg/kg BID Cmpd D 10 mg/kg BID 110 100 100 o Oo o Oo Body Weight change (%) Body Weight change (%)
Slide 9: Corbus CB1 inverse agonists improve glucose tolerance
orbus CB1 inverse agonists improve glucose tolerance IB Vehicle 1 © Vehicle 2 300 [Ml Cmpd C 5 mg/kg BID A Pioglitazone 30 mg/kg QD A Cmpd C 10 mg/kg BID 300 W Rimonabant 10 mg/kg QD a @ Cmpd D5 mg/kg BID a r)) Cmpd D 10 mg/kg BID D = 200 £ 200 fe} ° § 100 S$ 100 oO 1o) a es a a | Basal 30 60 90 120
Slide 10: CB2 Agonists
CB2 Agonists
Slide 11: Some reported potential therapeutic uses of CB2 agonists
Some reported potential therapeutic uses of CB2 agonists Autoimmune Fibrotic Cancer CNS Other Diseases Diseases Diseases © Gystislibrosis * Systemic sclerosis! * Skin fibrosis Fscit ae Seeny > ALS Atopicidermatitis aa ; f » Anti-metastasis ‘ . » Interstitial cystitis * Dermatomyositis’ * Lung fibros
Slide 12: CB2 are expressed on activated immune cells and fibroblasts
CB2 are expressed on activated immune cells and fibroblasts CB2 agonists reduce production of pro- inflammatory mediators and activate resolution of inflammation CB2 agonists reduce production of pro-fibrotic growth factors, myofibroblast transformation, and collagen production Lenabasum is a synthe
Slide 13: Inflammation, immune and fibroblast activation, fibrosis
INFLAMMATION IMMUNE & FIBROBLAST ACTIVATION LANG TRIGGERING Ys Chronic & systemic ye —e< NZ Se FIBROSIS Patient images provided by the Scleroderma Foundation
Slide 14: CB2 knock-out mice develop systemic sclerosis-like disease
CB2 knock-out mice develop systemic sclerosis-like disease CB2-/- mice exposed to hypochlorite, which generates oxygen radicals, fail to resolve innate immune response with persistent inflammation, autoimmunity (anti-DNA topoisomerase | antibodies), increased fibroblast proliferation, and excessive
Slide 15: Lenabasum, a CB2 agonist, reduced fibrosis in an animal model of systemic sclerosis lung disease
Lenabasum, a CB2 agonist, reduced fibrosis in an animal model of systemic sclerosis lung disease Vy ne Controt es LEXY cicomycin Lung fibrosis induced with bleomycin fs ies ; « Lung fibrosis is induced with bleomycin « Lenabasum, whether started prophylactically before bleomycin or therapeutically 1
Slide 16: Lenabasum, a CB2 agonist, reduced fibrosis in an animal model of SSc lung disease
Lenabasum, a CB2 agonist, reduced fibrosis in an animal model of SSc lung disease Vy ne Controt es LEXY cicomycin Lung fibrosis induced with bleomycin bap we a Lung fibrosis is induced with bleomycin (bleomycin versus control) Lenabasum, whether started prophylactically before bleomycin or therapeut
Slide 17: Lenabasum improved inflammation and fibrosis in skin biopsies from SSc patients in a Phase 2 study
N oO ”n 4) x oO oO Y) op) Lenabasum, a CB2 agonist, improved inflammation and fibrosis in skin biopsies from SSc patients in a Phase 2 study More improvement or stability of histological findings of inflammation and fibrosis in paired skin biopsies after 12 weeks treatment with lenabasum versus plac
Slide 18: Systemic sclerosis subjects treated with lenabasum added to immunosuppressants had stable lung function
Systemic sclerosis subjects treated with lenabasum 20 mg BID added to immunosuppressants > 2 years duration had stable lung function FVC, mL over 1 year 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Weeks IST = immunosuppressant therapies. Post-hoc analyses, per protocol population of subjects who complete
Slide 19: Acceptable lenabasum safety profile in Phase 3 RESOLVE-1 study
Acceptable lenabasum safety profile in Phase 3 RESOLVE-1 study Treatment-emergent Adverse Events Riesehe Eonahasum Eanebasum ab) (TEAE) 5mg 20mg N=123,n(%) | N=120,n(%) N= 120,n(%) Yn Bltenabacumic cater Any TEAE 106 ( 86.2) 110 ( 90.2) 110 (91.7) 14) profile was favorable, Any Serious TEAE 18 (14.6
Slide 20: Lenabasum reduced PEx rates in post-hoc analyses in cystic fibrosis subjects
Lenabasum reduced PEx rates in post-hoc analyses in subjects with similar baseline lung functio (FEV1 40-<90% predicted) and CFTR-modulator use PEx rate per Subject per 28 Weeks (relative reduction vs PBO) Primary PEX Primary PEX Secondary Secondary ~ Phase 2b study in subjects with CFTR definition
Slide 21: Some potential activities of CB2 agonists in cancer
Some potential activities of CB2 agonists in cancer Anti-proliferative effects’, block cell cycle progression? ° Pro-apoptotic effects on tumor cells® » Reduce EGF/EGFR and GF-I/IGF-IR pathways* « Attenuate downstream functions of CXCR4° or Her2® , which form heterodimers with CB2 ° Attenuate bone-c
Slide 22: Novel Corbus CB2/CB1 agonists inhibit breast cancer cell growth
Novel Corbus CB2/CB1 agonists inhibit breast cancer cell growth IC.) HM concentrations that cause 50% inhibition of breast cancer cell growth Triple negative Her2+ ER+ mpd ina henge . ae empe BT-474 ete SKBR3 iis T-47D | MCF-7 AA 34 5.4 4.5 AA 5A 3.5 5.2 AA 5.4 >10 BB 3.6 8.1 10.7 BB 5.4 5.2 6.1 BB
Slide 23: CB2 agonists provide dose-dependent and time-dependent inhibition of growth of triple negative breast cancer cell line
CB2 agonists provide dose-dependent and time-dependent inhibition of growth of triple negative breast cancer cell line MDA-MB-468 z 5 6x105 me 8 a -O- 1.25uM < 8 4x105 Oo 2.5uM 8 i—7 8 8 2 3 2105 € & 5 g a Luminescence (RLU) Luminescence (RLU) Time (h) Time (h) Human triple negative breast cancer ce
Slide 24: A CB2 agonist inhibits Her2 phosphorylation and Her2+ tumor cell growth in a xenograft model
A CB2 agonist inhibits Her2 phosphorylation and Her2+ tumor cell growth in a xenograft model > 44004 = venice Compound DD inhibited HER2 phosphorylation & -@- Cmpd DD 5 mg/kg BID in HCC1954 breast cancer cells & 1200 4 Cmpd DD 10 mg/kg BID 0.25: aa -® BKM-120 35 mg/kg QD oO iss 2 1000 = 0.15 2 800 o
Slide 25: IC50 concentrations that cause 50% inhibition of cancer cell growth
IC, UM concentrations that cause 50% inhibition of cancer cell growth Non-small cell lung cancer cells Glioblastoma cells Cmpd | SW1573 A549 HCC827 Cmpd U251 SF216 AA 45 TA 6.4 AA 3.8 9.0 BB 8.6 9.0 7.8 BB 5.9 14.0 cc 3.3 8.4 13.3 cc 3.6 10.5 DD 46 12.6 13.0 DD 3.5 18.5 EE 6.2 8.4 13.2 EE 4.3 18.3 F
Slide 26: Summary and conclusions
Summary and conclusions CB1 agonists have already been approved for treatment of anorexia, weight loss, nausea, vomiting, muscle spasticity, rare seizures, and tuberous sclerosis Novel CB1 inverse agonists with low brain: plasma ratios have been identified, and some have activity in animal models of
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