Theravance Biopharma, Inc. · NASDAQ:TBPH
Theravance Biopharma — Q3 2020 Earnings Presentation
40 slides from Theravance Biopharma's earnings presentation, Nov 5, 2020
Slide 1: Appendix Slides — Third Quarter 2020 Financial Results and Business Update
APPENDIX SLIDES — Third Quarter 2020 Financial Results and Business Update November 5, 2020 THERAVANCE BIOPHARMA ® , THERAVANCE ® , the Cross/Star logo and MEDICINES THAT MAKE A DIFFERENCE ® are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other count
Slide 2: Our science: Organ-selective molecules designed to optimize therapeutic index
Our science Organ - selective molecules designed to optimize therapeutic index
Slide 3: Targeting the right disease with the right molecular design
Theravance Biopharma difference: Targeting the right disease with the right molecular design TI, therapeutic index. 3 α STAT P STAT P STAT JAK β γ JAK N UCLEUS P STAT P STAT TI TI
Slide 4: Research and development portfolio of designed molecules: brain, lung, GI and eye
Research and development portfolio of designed molecules: brain, lung, GI and eye 4 Molecular Design Biology Medicinal Chemistry DMPK Development and Commercial Symptomatic nOH (Neurogenic orthostatic hypotension) Asthma Lung Transplant Rejection IPF (idiopathic pulmonary fibrosis) COPD (chronic obs
Slide 5: Key programs supported by proven development and commercial expertise
Program Indication Research Phase 1 Phase 2 Phase 3 Filed Marketed Collaborator Ampreloxetine (TD - 9855) NRI S ymptomatic nOH Wholly - owned Organ - Selective TD - 1473 GI JAKi UC CD TD - 5202 Irreversible JAK3i Inflammatory intestinal diseases YUPELRI ® (revefenacin) LAMA COPD TD - 0903 Inhaled JA
Slide 6: TD-0903 Program
TD - 0903 Program Nebulized lung - selective pan - JAK inhibitor to treat: ► Acute hyperinflammation of the lung in COVID - 19 ► Chronic inflammation for the prevention of lung transplant rejection
Slide 7: Leveraging respiratory expertise for potential acute treatment in response to a global pandemic
Leveraging respiratory expertise for potential acute treatment in response to a global pandemic 1. https://coronavirus.jhu.edu/map.html, number as of 9/10. 2. IHME. 7 US patients 1 >6M patients become hospitalized 2 ~2.4% No vaccine available Current treatment: Supportive therapy As of July 1, 2020:
Slide 8: First-in-disease opportunity for the prevention of lung transplant rejection
S TRATEGIC O PPORTUNITY First - in - disease opportunity for the prevention of lung transplant rejection ‣ Calcineurin inhibitors (tacrolimus) ‣ Anti - proliferative agents (MMF) 1. http://www.transplant - observatory.org/data - charts - and - tables/ . 2. United Network for Organ Sharing (UNOS), ht
Slide 9: Pan-JAK inhibitors can prevent transplant rejections
Month 6 0 5 10 15 20 F i r s t B P A R R a t e ( % ) Pan - JAK inhibitors can prevent transplant rejections Noninferiority trial of tofacitinib vs cyclosporine (CsA) in kidney transplant recipients 1 ‣ JAK inhibition was superior to cyclosporine in prevention of acute and chronic rejections ‣ Seriou
Slide 10: Ampreloxetine (TD-9855)
Ampreloxetine (TD - 9855) Once - daily norepinephrine reuptake inhibitor to treat symptomatic neurogenic orthostatic hypotension
Slide 11: Reduced quality of life and limited therapeutic options for symptomatic nOH patients
Reduced quality of life, significant care - giver burden and limited therapeutic options for symptomatic nOH patients 11 1. Mathias C, et al. J Neurol 1999;246:893 - 8. 2. Ha AD, et al. Parkinsonism Relat Disord 2011;17:625 - 8. 3. Not all patients are treated with prescription medication. P ATIENT
Slide 12: Designed to reduce symptoms of nOH by prolonging the effect of endogenous norepinephrine
Untreated nOH NE Release at Neurovascular Junction Systolic Blood Pressure Designed to reduce symptoms of nOH by prolonging the effect of endogenous norepinephrine 1. Palma JA, Kaufmann H. Mov Disord Clin Pract 2017;4:298 - 308. NE, norepinephrine; NET, norepinephrine transporters. 12 Vasodilation B
Slide 13: Ampreloxetine: Potential for meaningful and durable symptom improvement
Ampreloxetine: Potential to provide meaningful and durable symptom improvement to underserved patients Baseline OHSA #1 (Orthostatic Hypotension Symptom Assessment Question 1) >4 points. Negative change indicates improvement in symptoms; improvement of 1 point is defined as the MCID (minimal clinica
Slide 14: Decentralized trials move activities from the clinic to home
Decentralized trials move activities from the clinic to home ‣ Site - centric operating model ‣ Burden on site resources ‣ Patient burden Source: Theravance Biopharma Clinical Operations. 14 Global clinical trials are being decentralized along a continuum Traditional Trial Operations Decentralized T
Slide 15: TD-1473 (JNJ-8398)
TD - 1473 (JNJ - 8398) Oral gut - selective pan - JAK inhibitor to treat inflammatory bowel diseases
Slide 16: Need for new medicines to treat Inflammatory Bowel Disease
Need for new medicines to treat Inflammatory Bowel Disease 16 HRQoL, health - related quality of life; IBD, inflammatory bowel disease. 1. GBD 2017 Inflammatory Bowel Disease Collaborators. Lancet 2020;5:17 - 30. 2. https://www.crohnscolitisfoundation.org/sites/default/files/2019 - 02/Updated%20IBD%
Slide 17: JAK-STAT pathway: orchestrating signaling of multiple pro-inflammatory cytokines
STAT - induced Inflammation α N UCLEUS STAT P STAT P STAT P STAT P STAT JAK β γ JAK JAK inhibitor JAK - STAT pathway: orchestrating signaling of multiple pro - inflammatory cytokines Clark JD, et al. J Med Chem 2014; 57:5023 - 5038. EPO, erythropoietin; GM - CSF, granulocyte - macrophage colony - st
Slide 18: TD-1473 is an oral, gut-selective pan-JAK inhibitor
TD - 1473 is an oral, gut - selective pan - JAK inhibitor Preclinical data package for TD - 1473 represents a potential breakthrough approach to the treatment of IBD Journal of Crohn’s & Colitis April 20, 2020. 18 Gut selectivity Potent inhibition of Tyk2 Anti - inflammatory activity in disease mode
Slide 19: Systemic exposures low; tissue concentrations at or above JAK inhibition levels
Systemic exposures low; tissue concentrations at or above JAK inhibition levels *Tofacitinib concentrations extracted from J Pharmacol Exp Ther 348:165 – 173, January 2014. BID, twice daily; IC 50 , concentration to produce 50% maximal inhibition; PK, pharmacokinetics. 19 Tofacitinib 10 mg BID* TD -
Slide 20: TD-1473: Late-stage studies in Crohn's disease and ulcerative colitis
TD - 1473: Gut - selective pan - JAK inhibitor Late - stage studies in Crohn’s disease and ulcerative colitis Phase 2 Crohn’s and Phase 2b/3 ulcerative colitis studies ongoing Phase 2 Crohn’s and Phase 2b ulcerative colitis data expected Q3 2021 Global collaboration with Janssen leverages joint deve
Slide 21: TD-5202
TD - 5202 Organ - gut selective irreversible JAK3 inhibitor to treat inflammatory intestinal diseases
Slide 22: Celiac disease has no current treatments and serious health consequences
Celiac disease has no current treatments and serious health consequences 22 1. 1% prevalence, BeyondCeliac.org. 2. 2018 US population 327M Census.gov. 3. Theravance Market Research. S TRATEGIC O PPORTUNITY P ATIENT P OPULATION US patients 1,2 3.3M No approved treatment Only available intervention is
Slide 23: JAK3-dependent cytokines play central role in pathogenesis of celiac disease
JAK3 - dependent cytokines play central role in pathogenesis of celiac disease ‣ Proof - of - relevance from recent positive Phase 2 data with systemic JAK3 inhibitor in alopecia areata, another T - cell mediated disease ‣ Localized JAK3 inhibition important to avoid systemic immunosuppression (gene
Slide 24: TD-5202 First-in-Human Overall Results Summary
TD - 5202 First - in - Human Overall Results Summary ‣ No serious or severe AEs were reported ‣ All treatment - emergent AEs in TD - 5202 - treated subjects were mild in severity AE, adverse event; C max,ss , maximal steady - state concentration; NK, natural killer. 24 TD - 5202: generally well - to
Slide 25: Inhaled ALK5i
Inhaled ALK5i Potential best - in - disease therapy for the treatment of idiopathic pulmonary fibrosis (IPF)
Slide 26: Limited treatment options with modest efficacy and poor tolerability
Limited treatment options 2 currently approved therapies, with modest efficacy and poor tolerability S TRATEGIC O PPORTUNITY P ATIENT P OPULATION Inhaled ALK5i Potential first - in - class inhaled ALK5 inhibitor anti - fibrotic agent for IPF Despite treatment with the current SOC, IPF patients conti
Slide 27: Significant opportunity remains for effective IPF treatments
Significant opportunity remains for effective IPF treatments ‣ Mortality with IPF remains high – <50% alive 3 years after diagnosis 1 1. King TE, et al. Am J Respir Crit Care Med 2001;164:1171 - 81. 27 1.0 0.8 0.6 0.4 0.2 0.0 0 5 10 15 Years Probability of Survival Male Female To arrest disease prog
Slide 28: Targeting the TGFβ pathway
TGFβ, transforming growth factor β. 28 S CARRING TISSUES Collagen deposition Stimuli Genetic susceptibility Repetitive injury AEC damage TGF β A LVEOLAR E PITHELIAL C ELLS (AEC) T YPE 2 T YPE 1 Normal M YOFIBROBLASTS Fibrogenesis, proliferation Targeting the TGFβ pathway A core signaling pathway tha
Slide 29: Selectively targeting the TGFβ pathway through ALK5 inhibition
a SMA , a - smooth muscle actin; ERK, extracellular signal - regulated kinase; JNK, c - Jun N - terminal kinase; PI3K, phosphatidylinositol - 4,5 - b isphosphate 3 - kinase; Smad2/3, mothers against decapentaplegic homolog 2/3; TGFR (ALK5), TGFβ receptor. Adapted from: Neuzillet C, et al. Oncotarget
Slide 30: ALK5 inhibition directly interrupts FMT in IPF
ALK5 inhibition directly interrupts FMT 1 in IPF FTM, fibroblast to myofibroblast transition 30 Reference Standard ALK5i Log [M] % inhibition of α SMA - 9 - 8 - 7 - 6 - 5 0 50 100 150 FMT a SMA expressed a SMA reduced Negative control ALK5i treated
Slide 31: Current treatment options have no effect on FMT at clinically relevant concentrations
Current treatment options have no effect on FMT at clinically relevant concentrations FTM, fibroblast to myofibroblast transition; C max , maximal concentration; IC 50 , half maximal inhibitory concentration. 1. https://www.tga.gov.au/sites/default/files/auspar - nintedanib - esilate - 160208.pdf .
Slide 32: Lung selectivity avoids unwanted systemic side effects
Wound repair Bone healing Cardiovascular homeostasis Tumor suppression Endocrine function Lung selectivity avoids unwanted systemic side effects Minimizing systemic inhibition of a cytokine essential for homeostasis Modified from: Akhurst RJ, Hata A. Nat Rev Drug Discov 2012;11:790 - 811. 32 Maintai
Slide 33: Ocular JAKi
Ocular JAKi Potential best - in - disease, pan - JAK inhibitor with long - acting ocular anti - inflammatory activity
Slide 34: Diabetic macular edema causes blindness in diabetics
Diabetic macular edema causes blindness in diabetics 34 1. © 2016 DR/Decision Resources, LLC. All rights reserved. Reproduction, distribution, transmission or publication is prohibit ed. Reprinted with permission. 2. Romero - Aroca , World J Diabetes 2011;2(6): 98 - 104. 3. Lee et al Curr Med Res Op
Slide 35: Inflammation, not just VEGF, is a key driver of DME
Inflammation, not just VEGF, is a key driver of DME Intraocular anti - VEGF agents 35 1. Gonzalez VH, et al. Am J Ophthalmol 2016;172:72 - 79. Current Pharmacological Treatments Intraocular steroids Hyperglycemia Disruption of blood - retinal barrier Vascular leakage DME VEGF Retinal capillary damag
Slide 36: Unmet need for an anti-inflammatory drug: opportunity for eye-selective JAK inhibition
0.00 0.25 0.50 0.75 1.00 1.25 VEGF IL-6 IP-10 MCP-1 Unmet need for an anti - inflammatory drug: opportunity for eye - selective JAK inhibition Adapted from Sohn HJ, et. al. Am J Ophthalmol 2011; 152:686 - 694. 36 Effect of anti - VEGF Effect of Steroids 0.00 0.25 0.50 0.75 1.00 1.25 VEGF IL-6 IP-10
Slide 37: Ocular pan-JAK inhibition could address key disease pathways in DME
Ocular pan - JAK inhibition has the potential to address key disease pathways in DME 37 TD - EyeJAKi inhibits key DME inflammatory pathways: JAK2 JAK1 IL - 6 Tyk2 JAK1 Interferons MCP - 1 IP - 10 TD - EyeJAKi ‣ IL - 6 and interferon signaling pathways in human primary cells ‣ IL - 6 induced pSTAT3 a
Slide 38: A potent pan-JAK inhibitor designed for eye selectivity
0 1 2 3 0.000001 0.00001 0.0001 0.001 0.01 0.1 1 10 100 1000 Time (months) C o m p o u n d c o n c e n t r a t i o n ( g / m L o r g / g ) A potent pan - JAK inhibitor designed for eye selectivity with projected dosing interval of at least three months 38 Single intravitreal injection of TD - EyeJAK
Slide 39: About YUPELRI (revefenacin) inhalation solution
About YUPELRI ® (revefenacin) inhalation solution YUPELRI ® (revefenacin) inhalation solution is a once - daily nebulized LAMA approved for the maintenance treatment of COPD in the US . Market research by Theravance Biopharma indicates approximately 9 % of the treated COPD patients in the US use neb
Slide 40: YUPELRI (revefenacin) Important Safety Information
YUPELRI ® (revefenacin) inhalation solution YUPELRI ® inhalation solution is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD) . Important Safety Information (US) YUPELRI is contraindicated in patients with hypersensitivity to revefenacin or any co