Theravance Biopharma, Inc. · NASDAQ:TBPH
Theravance Biopharma — JP Morgan 2021
47 slides from Theravance Biopharma's conference presentation, Jan 11, 2021
Slide 1: JP Morgan 2021 Appendix
JP Morgan 2021 APPENDIX ~ \! a
Slide 2: Research and development portfolio of designed molecules: brain, lung, GI and eye
Research and development portfolio of designed molecules: brain, lung, GI and eye 2 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 3: YUPELRI (revefenacin) inhalation solution
YUPELRI ® (revefenacin) inhalation solution First and only once - daily, nebulized maintenance medicine for COPD
Slide 4: YUPELRI launch metrics
YUPELRI ® launch metrics Majority of YUPELRI ® volume flows through durable medical equipment channel (approximately 3 - month lag in data capture); remaining volume flows thro ugh hospitals, retail and long - term care pharmacies. Wholesale acquisition cost (WAC): $1,066 per month (or ~$35 per day)
Slide 5: Key Success Drivers for YUPELRI
LAMA, long - acting muscarinic agonist; LABA, long - acting beta agonist. 5 Launch to Date 2021 and Beyond Key Success Drivers for YUPELRI ® ‣ Established Nebulized LAMA Market Leader ‣ Continued growth of hospital accounts with YUPELRI on formulary ‣ Successful partnership with VIATRIS leading to c
Slide 6: Ampreloxetine (TD-9855)
Ampreloxetine (TD - 9855) Once - daily norepinephrine reuptake inhibitor to treat symptomatic neurogenic orthostatic hypotension
Slide 7: Ampreloxetine mechanism in symptomatic nOH
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. 7 Vasodilation Bl
Slide 8: 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. 8 Global clinical trials are being decentralized along a continuum Traditional Trial Operations Decentralized Tr
Slide 9: Ampreloxetine commercial opportunity in nOH
nOH is included in medical treatment guidelines for PD and MSA patients; once diagnosed, patients get on drug treatment quickly A concentrated group of neurologists and cardiologists treat patients with nOH; ‘at risk’ patients already identified and managed by specialty institutions TBPH ’s infrastr
Slide 10: Izencitinib (TD-1473)
Izencitinib (TD - 1473) (JNJ - 8398) Oral gut - selective pan - JAK inhibitor to treat inflammatory bowel diseases
Slide 11: Need for new medicines to treat Inflammatory Bowel Disease
Need for new medicines to treat Inflammatory Bowel Disease 11 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 12: JAK-STAT pathway signaling
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 13: Izencitinib is an oral, gut-selective pan-JAK inhibitor
Izencitinib is an oral, gut - selective pan - JAK inhibitor Journal of Crohn’s & Colitis April 20, 2020. 13 Gut selectivity Potent inhibition of Tyk2 Anti - inflammatory activity in disease model x x Lumen Vehicle treated control Izencitinib treatment x 7.5 8 8.5 9 9.5 10 Tofacitinib Izencitinib Inh
Slide 14: 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. 14 Tofacitinib 10 mg BID* Izen
Slide 15: 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 16: Leveraging respiratory expertise for potential acute treatment in a pandemic
Leveraging respiratory expertise for potential acute treatment in response to a global pandemic 1. https://coronavirus.jhu.edu/map.html, number as of 12/22. 2. IHME. 3. https://www.fda.gov/drugs/coronavirus - covid - 19 - drugs/coronavirus - treatment - acceleration - program - ctap#dashboard 1. 4.
Slide 17: Potential for TD-0903 effect in COVID-19
Potential for TD - 0903 effect Host inflammatory response to COVID - 19 drives ALI and ARDS ALI Acute Lung Injury; ARDS, Acute respiratory distress syndrome Adapted from Siddiqi HK, et al. J Heart Lung Transplant 2020 Mar 20. CRP, C - reactive protein; LDH, lactate dehydrogenase; NT - proBNP, ventri
Slide 18: TD-0903: Development plan designed to progress rapidly
TD - 0903: Development plan designed to progress rapidly SOC, standard of care. 18 Phase 2: Hospitalized COVID - 19 patients Dose 3 mg + SOC Placebo + SOC Phase 1: Healthy volunteers Single ascending dose: Single - dose safety, tolerability, PK Multiple ascending dose x 7 days: Repeat - dose safety,
Slide 19: TD-0903 Phase 1 supports initiation of Phase 2 in COVID-19
TD - 0903 Phase 1 supports initiation of Phase 2 in COVID - 19 ‣ TD - 0903 was well tolerated as single daily doses across a dose range from 1 mg to 10 mg for 7 days in healthy subjects ‣ Adverse events were assessed to be mild or moderate in severity, and none led to discontinuation of study treatm
Slide 20: Strategic opportunity: 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 21: 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 ‣ JAK inhibition was superior to cyclosporine in prevention of acute and chronic rejections ‣ Serious infections increased with systemic JAK inhibitors including CMV 1. Vincenti F, et al. Am J
Slide 22: TD-8236
TD - 8236 Potential first inhaled JAKi for asthma
Slide 23: High medical and economic burden in uncontrolled asthma
High medical and economic burden in uncontrolled asthma *Asthma that requires high - dosage ICS + LABAs to prevent the disease from being uncontrolled) or asthma that remains uncontrolle d despite treatment. World Health Organization; 2. https://www.aafa.org/asthma - facts/; 3. Sadatsafavi, M., et a
Slide 24: TD-8236: Phase 1 clinical trial design
TD - 8236: Phase 1 clinical trial design FeNO, fractional exhaled nitric oxide; ICS, inhaled corticosteroids; MAD, multiple - ascending dose; MoA , Mechanism of Action; PK, pharmacokinetic; PD, pharmacodynamic; pSTAT , phosphorylated signal transducer and activator of transcription; SAD, single - as
Slide 25: TD-8236: Positive Phase 1 trial in healthy subjects and asthma patients
TD - 8236: Positive Phase 1 trial in healthy subjects and patients with mild and moderate - to - severe asthma ‣ Biomarkers of JAK target engagement (pSTAT1 and pSTAT6) significantly reduced in lungs of T2 high and T2 low moderate/severe asthmatics on top of inhaled corticosteroids ‣ Ongoing analysi
Slide 26: No impact of TD-8236 on the Late Asthmatic Response
-50 -40 -30 -20 -10 0 10 20 30 40 -0.4 -0.2 0.0 0.2 0.4 Favors Placebo Favors TD - 8236 Favors TD - 8236 Favors Placebo No impact of TD - 8236 on the Late Asthmatic Response (LAR) ‣ TD - 8236 was generally well tolerated as a single - daily dose administered for 14 consecutive days 26 Primary Endpoi
Slide 27: TD-8236 FeNO reductions consistent across Phase 1 and 2
-50 -40 -30 -20 -10 0 10 20 30 40 TD - 8236 FeNO reductions consistent across Phase 1 and 2 ‣ FeNO reductions observed in moderate - to - severe asthmatics taking inhaled corticosteroids ICS, inhaled corticosteroids; LAC, lung allergen challenge; LS, least - squares; CI, confidence interval. 27 Phas
Slide 28: TD-5202
TD - 5202 Organ - gut selective irreversible JAK3 inhibitor to treat inflammatory intestinal diseases
Slide 29: Celiac disease has no current treatments and serious health consequences
Celiac disease has no current treatments and serious health consequences 29 1. http://www.drschaer - institute.com/us/celiac - disease/epidemiology - 1033.html 2. 1% prevalence in US, BeyondCeliac.org. 3. 2018 US population 327M Census.gov. 4. Reunala T, et al. Dermatitis Herpetiformis: A Common Ext
Slide 30: JAK3-dependent cytokines 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 has the potential to avoid systemic immunosuppressi
Slide 31: 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. 31 TD - 5202: generally well - to
Slide 32: Inhaled ALK5i
Inhaled ALK5i Potential best - in - disease therapy for the treatment of idiopathic pulmonary fibrosis (IPF)
Slide 33: Limited treatment options for IPF
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 34: 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. 34 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 35: Targeting the TGFβ pathway
TGFβ, transforming growth factor β. 35 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 36: 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 37: ALK5 inhibition directly interrupts FMT in IPF
ALK5 inhibition directly interrupts FMT 1 in IPF FTM, fibroblast to myofibroblast transition 37 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 38: Current treatment options have no effect on FMT
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 39: Lung selectivity avoids unwanted systemic side effects
Wound repair Bone healing Cardiovascular homeostasis Tumor suppression Endocrine function Lung selectivity avoids unwanted systemic side effects Modified from: Akhurst RJ, Hata A. Nat Rev Drug Discov 2012;11:790 - 811. TGFβ, transforming growth factor β. 39 Maintaining key systemic regulatory roles
Slide 40: Ocular JAKi
Ocular JAKi Potential best - in - disease, pan - JAK inhibitor with long - acting ocular anti - inflammatory activity
Slide 41: Diabetic macular edema causes blindness in diabetics
Diabetic macular edema causes blindness in diabetics 41 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 Opi
Slide 42: Inflammation, not just VEGF, is a key driver of DME
Inflammation, not just VEGF, is a key driver of DME Intraocular anti - VEGF agents 42 1. Gonzalez VH, et al. Am J Ophthalmol 2016;172:72 - 79. 2. VEGF, vascular endothelial growth factor. Current Pharmacological Treatments Intraocular steroids Hyperglycemia Disruption of blood - retinal barrier Vasc
Slide 43: Unmet need for an anti-inflammatory drug: 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. 43 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 44: Ocular pan-JAK inhibition may address key disease pathways in DME
Ocular pan - JAK inhibition has the potential to address key disease pathways in DME 44 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 45: 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 pan - JAK inhibitor designed for eye selectivity with projected dosing interval of at least three months 45 Single intravitreal injection of TD - Eye JAKi in R
Slide 46: 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 47: YUPELRI indication and 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