Theravance Biopharma, Inc. · NASDAQ:TBPH
Theravance Biopharma — Earnings Presentation (August 2021)
54 slides from Theravance Biopharma's earnings presentation, Aug 3, 2021
Slide 1: Appendix
Appendix August 3, 2021 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 countries). All third party trademarks used herein are the property of th
Slide 2: Investment highlights
Decades - long track record of driving innovative products to market for diseases of high unmet need Investment highlights 2 Innovative, commercial - stage biopharma with strong development track record Diversified pipeline of organ - selective medicines for rare disease, respiratory, GI and ocular
Slide 3: Key programs for large patient populations
Program Indication US Patients 1 Research Phase 1 Phase 2 Phase 3 Filed Marketed Collaborator Ampreloxetine (TD - 9855) NRI S ymptomatic nOH ~350k Wholly - owned Organ - Selective Izencitinib (TD - 1473) GI JAKi UC ~900k CD ~800k Janssen Biotech, Inc . TD - 5202 Irreversible JAK3i Celiac Disease UC
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: Early stage pipeline, value creation opportunities
Early stage pipeline, value creation opportunities *Asthma that requires high - dosage ICS + LABAs to prevent the disease from being uncontrolled, or asthma that remains uncontrolle d despite treatment. 1. https://www.aafa.org/asthma - facts/ . 2. 1% prevalence in US, BeyondCeliac.org. 3. 2018 US po
Slide 6: Izencitinib (TD-1473/JNJ-8398)
Izencitinib (TD - 1473/JNJ - 8398) Oral gut - selective pan - JAK inhibitor to treat inflammatory bowel diseases
Slide 7: Izencitinib: a novel approach to JAK inhibition for IBD
IBD represents an area of high unmet need Favorable Phase 1b data led to late - stage IBD studies Izencitinib: a novel approach to JAK inhibition for IBD 7 Izencitinib Preclinical and clinical data package represents a potential breakthrough approach for the treatment of IBD Oral, gut - selective ag
Slide 8: 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 9: High margins of systemic safety in nonclinical studies
0 5 10 15 120 140 S y s t e m i c S a f e t y M a r g i n ( P l a s m a A U C ) Non-rodentRodent High margins of systemic safety in nonclinical studies Gut selectivity confers low systemic exposure and offers the potential for reduced adverse effects Low systemic plasma concentrations in UC patients
Slide 10: Izencitinib gut-selective pan-JAK approach designed to maximize efficacy in IBD
Izencitinib’s oral, gut - selective, pan - JAK approach is designed to maximize efficacy in IBD GI, gastrointestinal; IBD, inflammatory bowel disease; JAK, Janus kinase; UC, ulcerative colitis. 10 Vehicle treated control Izencitinib treatment CD3+ pan - T cells Blocks inflammation and penetrates dee
Slide 11: Favorable data from exploratory Phase 1b study
Favorable data from this innovative exploratory Phase 1b study 1 ‣ Confirmed gut selectivity – High colonic concentration with low systemic drug exposures, consistent with pre - clinical data – For the goal of maximized therapeutic index ‣ Demonstrated numerically higher rates of clinical outcomes w
Slide 12: Izencitinib: Phase 2b study in Crohn's disease
Izencitinib: Phase 2 study in Crohn’s disease Endpoints ‣ Primary: Improvement in CDAI score at week 12 in patients with moderately to severely active CD ‣ Exploratory: – Clinical response measured by CDAI at 12 weeks – CDAI clinical remission at 12 weeks – SES - CD change from baseline to Week 12 –
Slide 13: Izencitinib: Phase 2b/3 studies in ulcerative colitis
Izencitinib: Phase 3 studies in ulcerative colitis Endpoints ‣ Primary: – Induction & Maintenance: clinical remission by aMS components at Week 8 and Week 44 ‣ Secondary: – Induction & Maintenance: endoscopic healing, symptomatic remission, clinical response by aMS, mucosal healing, maintenance of c
Slide 14: Izencitinib: long-term study in ulcerative colitis
Izencitinib: Phase 3 study in ulcerative colitis Assessments ‣ Safety and tolerability of izencitinib administered for up to 3 years in patients with moderate - to - severe UC after participation in the Protocol 0157 Maintenance Study NCT03758443 UC, ulcerative colitis. 14 Key inclusion criteria: El
Slide 15: 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 16: Ampreloxetine (TD-9855)
Ampreloxetine (TD - 9855) Once - daily norepinephrine reuptake inhibitor to treat symptomatic neurogenic orthostatic hypotension
Slide 17: nOH profoundly impacts QoL
nOH profoundly impacts QoL Study 0169 primary endpoint: Change from baseline in OHSA Question 1 OHSA measures core nOH symptom: Dizziness / lightheadedness due to brain hypoperfusion Clinically significant endpoint: 1 - point OHSA improvement 1. https://www.parkinson.org/Understanding - Parkinsons/S
Slide 18: Ampreloxetine: once-daily, potent and selective norepinephrine reuptake inhibitor
Ampreloxetine: a once - daily, potent and selective norepinephrine reuptake inhibitor with a differentiated MOA for treating nOH Current nOH treatment options: ‣ No durable effect ‣ Multiple daily dosing ‣ Black box warning for SH 1. Kaufmann H, et al. Mov Disord. 2019;34(suppl 2). Poster presented
Slide 19: Ampreloxetine: meaningful and durable symptom improvement
Ampreloxetine: potential to provide meaningful and durable symptom improvement to underserved patients All subjects who complete Study 169 may enroll into 170; all subjects who complete 170 may enroll into extension study/171. Baseline OHSA #1 (Orthostatic Hypotension Symptom Assessment Question 1)
Slide 20: Ampreloxetine: Phase 3 registrational program
Ampreloxetine: Phase 3 registrational program Placebo - controlled, randomized withdrawal study *Negative change indicates improvement in symptoms; improvement of 1 point is defined as the MCID (minimal clinically importa nt difference). Discontinuation rates for the Phase 3 trials as of Jan. 2020:
Slide 21: Ampreloxetine: Phase 3 safety study and extension
Ampreloxetine: Phase 3 program 6 - month safety study + 3 - year optional extension Assessments ‣ Through Week 26: – Physical and neurological exams – Vital signs – ECGs – Clinical laboratory tests – Concomitant medications *Through week 26; for FDA filing NCT04095793 AE, adverse event; C - SSRS, Co
Slide 22: 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. 22 Global clinical trials are being decentralized along a continuum Traditional Trial Operations Decentralized T
Slide 23: Ampreloxetine potential to transform Theravance Biopharma
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 infrastru
Slide 24: Nezulcitinib (TD-0903) Program
Nezulcitinib (TD - 0903) Program Nebulized lung - selective pan - JAK inhibitor to treat: ► Acute hyperinflammation of the lung in COVID - 19 ► Chronic inflammation for the treatment and prevention of lung transplant rejection
Slide 25: Nezulcitinib: breaking new ground with inhaled JAKi
Nezulcitinib (TD - 0903): breaking new ground with inhaled JAKi 1. https://www.kff.org/coronavirus - covid - 19/fact - sheet/coronavirus - tracker/ as of 4.29.21 2. https://coronavirus.jhu.edu/map.html as of 4.25.21 3. https://covid.cdc.gov/covid - data - tracker/#vaccinations as of 5.3.21 4. https:
Slide 26: Nezulcitinib: Phase 2 study in hospitalized COVID-19 patients
Nezulcitinib: Randomized, double - blind, placebo - controlled Ph 2 study in hospitalized patients with COVID - 19 requiring oxygen support Objectives ‣ Primary: Number of respiratory - free days from randomization through Day 28 ‣ Secondary: Tolerability, PK ‣ Exploratory : Clinical status, duratio
Slide 27: Nezulcitinib across COVID-19 disease progression
Asymptomatic or pre - symptomatic Mild illness Moderate illness Severe illness Critical illness COVID recovery Features Positive SARS - CoV - 2 test; no symptoms Mild symptoms (e.g., fever, cough, or change in taste or smell); no dyspnea Clinical or radiographic evidence of LRT disease; oxygen satur
Slide 28: Nezulcitinib trend of improvement in 28-day all-cause mortality
Nezulcitinib showed a trend of improvement in 28 - day all - cause mortality rate and time to mortality (ITT) 1. Hazard ratio (nezulcitinib vs placebo) and 95% CI calculated from Cox proportional hazards model adjusting for baseline ag e s trata (≤60 vs >60 years). 2. Unstratified log - rank p - val
Slide 29: Executive summary of safety results
Executive summary of safety results Safety data based on 205 treated patients. 29 Nezulcitinib n=103 Placebo n=102 Adverse events 34.0% 41.2% Serious adverse events 9.7% 15.7% Liver abnormalities or disease 9.7% 7.8% Serious infections 1.0% 2.0% Venous thromboembolism 0 4.9% ‣ Nezulcitinib was well
Slide 30: Nezulcitinib Phase 2 COVID-19 trial summary
Nezulcitinib Phase 2 COVID - 19 trial summary ‣ Efficacy outcomes, n=210 (ITT) – Primary: No statistically significant difference between nezulcitinib and placebo for RFDs from randomization through Day 28 – Secondary: No difference in change from baseline at Day 7 in SaO 2 /FiO 2 ratio, proportion
Slide 31: TD-8236
TD - 8236 Potential first inhaled JAKi for asthma
Slide 32: 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. 1. World Health Organization; 2. https://www.aafa.org/asthma - facts/; 3. Sadatsafavi, M., e
Slide 33: TD-8236: Phase 1 clinical trial design
TD - 8236: Phase 1 clinical trial design CXCL, chemokine (C - X - C motif) ligand; FeNO, fractional exhaled nitric oxide; ICS, inhaled corticosteroids; IFN, interferon; IgE, immunoglobulin E; IL, interleukin; ILC2, type 2 innate lymphoid cells; MAD, multiple - ascending dose; MoA, Mechanism of Actio
Slide 34: 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 ICS ‣ Ongoing analysis of effect of TD -
Slide 35: 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 35 Primary Endpoi
Slide 36: 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 CI, confidence interval; FeNO, fractional exhaled nitric oxide; ICS, inhaled corticosteroids; LAC, lung allergen
Slide 37: TD-5202
TD - 5202 Organ - gut selective irreversible JAK3 inhibitor to treat inflammatory intestinal diseases
Slide 38: Celiac disease has no current treatments and serious health consequences
Celiac disease has no current treatments and serious health consequences 38 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. Nutrients 2018;10;pii: E602; 5. Guan
Slide 39: JAK3-dependent cytokines play central role in 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 40: 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; BID, twice daily; C max,ss , maximal steady - state concentration; ECG, electrocardiogram; IC 50 , inh
Slide 41: Inhaled ALK5i
Inhaled ALK5i Potential best - in - disease therapy for the treatment of idiopathic pulmonary fibrosis (IPF)
Slide 42: 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 43: 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. IPF, idiopathic pulmonary fibrosis. 43 1.0 0.8 0.6 0.4 0.2 0.0 0 5 10 15 Years Probability of Surviva
Slide 44: Targeting the TGFβ pathway
TGFβ, transforming growth factor β. 44 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 45: Selectively targeting the TGFβ pathway through ALK5 inhibition
Selectively targeting the TGFβ pathway through ALK5 inhibition Adapted from: Neuzillet C, et al. Oncotarget 2013;5:78 – 94. α SMA, α - smooth muscle actin; ERK, extracellular signal - regulated kinase; IPF, idiopathic pulmonary fibrosis; JNK, c - Jun N - terminal kina se; PI3K, phosphatidylinositol
Slide 46: ALK5 inhibition directly interrupts FMT in IPF
ALK5 inhibition directly interrupts FMT in IPF ALK5i, transforming growth factor β receptor I kinase inhibitor; α SMA, α - smooth muscle actin; FMT, fibroblast to myofibroblast transition. 46 Reference Standard ALK5i Log [M] % inhibition of α SMA - 9 - 8 - 7 - 6 - 5 0 50 100 150 FMT a SMA expressed
Slide 47: Current treatment options have no effect on FMT
Current treatment options have no effect on FMT at clinically relevant concentrations 1. https://www.tga.gov.au/sites/default/files/auspar - nintedanib - esilate - 160208.pdf . 2. Ogura T, et al. Eur Respir J. 2015;45:1382 - 92. C max , maximal concentration; FMT, fibroblast to myofibroblast transit
Slide 48: 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. ALK5i, TGFβ receptor I kinase inhibitor; TGFβ, transforming growth factor β. 48 M
Slide 49: Ocular JAKi
Ocular JAKi Potential best - in - disease, pan - JAK inhibitor with long - acting ocular anti - inflammatory activity
Slide 50: Diabetic macular edema causes blindness in diabetics
Diabetic macular edema causes blindness in diabetics 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 Opin 2
Slide 51: Inflammation, not just VEGF, is a key driver of DME
Inflammation, not just VEGF, is a key driver of DME 51 1. Gonzalez VH, et al. Am J Ophthalmol 2016;172:72 - 79. DME, diabetic macular edema; VEGF, vascular endothelial growth factor. Current Pharmacological Treatments Intraocular steroids Hyperglycemia Disruption of blood - retinal barrier Vascular
Slide 52: Unmet need for an anti-inflammatory drug in DME
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. IL - 6, interleukin - 6; IP - 10, interferon γ - induced protein 10; JAK, Janus kinase; MC
Slide 53: Ocular pan-JAK inhibition addresses key disease pathways in DME
Ocular pan - JAK inhibition has the potential to address key disease pathways in DME 53 DME, diabetic macular edema; IL - 6, interleukin - 6; IP - 10, interferon γ - induced protein 10; JAK, Janus kinase; MCP - 1, monocyte chemoattractant protein - 1; pSTAT, phosphorylated signal transducer and a ct
Slide 54: Pan-JAK inhibitor designed for eye selectivity with long dosing interval
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 54 JAK, Janus kinase. Single intravitreal injection of
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