Insmed Incorporated · NASDAQ:INSM
Insmed — Investor Presentation (January 2022)
46 slides from Insmed's investor presentation, Jan 10, 2022
Slide 1: Unmet Patient Needs
Unmet Patient Needs % ee
Slide 2: Forward-looking statements
This presentation contains forward-looking statements that involve substantial risks and uncertainties. “Forward-looking statements,” as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a number of risks and uncert
Slide 3: Mission and vision
To transform the lives of patients with serious and rare diseases To be a globally recognized leading biotech company that empowers great people to deliver, with a profound sense of urgency and compassion, life-altering therapies to small patient populations experiencing big health problems
Slide 4: Areas of focus and technology capabilities
Refractory MAC lung disease Front Line MAC lung disease Bronchiectasis Cystic FibrosisOther neutrophil-mediated diseases Pulmonary arterial hypertensionPulmonary hypertension associated with interstitial lung diseaseOther rare pulmonary disorders Cell therapy technology & capabilitiesProtein De-immu
Slide 5: Pipeline by indication and phase
Refractory NTM: M. avium complex (MAC)Front Line Label Expansion * In the U.S., as a condition of accelerated approval, Insmed is conducting an additional clinical study to support full approval.Full approval has been granted by the European Commission and Japan’s Ministry of Health, Labour and Welf
Slide 6: ARIKAYCE
ARIKAYCE
Slide 7: MAC lung disease and ARIKAYCE
MAC lung disease is a rare, progressive, and chronic condition that can cause severe, permanent damage to the lungs Symptoms often worsen over time, including chronic cough, dyspnea, fatigue, fever, weight loss, and chest pain Caused by bacteria in the environment and is more likely to affect thosew
Slide 8: ARIKAYCE launch and approvals
ARIKAYCE was one of the U.S. Top 10 most successful non-oncology rare disease launches Consistent pricing across three major territories: U.S., EU, and Japan Approval in Japan in March 2021 Approval in Europe in late 2020 International guideline inclusion with a strong recommendation for use (1) Not
Slide 9: Diagnosed NTM and refractory MAC patients
14K Diagnosed NTMPatients (2018E)*1,400 refractory MAC patients (2018E)* 125-145K Diagnosed NTM Patients (2018E)*15K-18K refractory MAC patients (2018E)* 95-115K Diagnosed NTM Patients (2019E)*12K-17K refractory MAC patients (2019E)* *Source: Internal analysis of published NTM epidemiology, primary
Slide 10: Front line MAC study design (ARISE and ENCORE)
*Azithromycin (AZI), Ethambutol (ETH)**Patients will be enrolled into separate open label extension study Primary Endpoint Change from Baseline to Month 13 (one month off treatment) in respiratory symptom scoreKey Secondary Endpoint Proportion of subjects achieving durable culture conversion at Mont
Slide 11: Brensocatib
Brensocatib is an investigational drug product that has not been approved for any indication in any jurisdiction.
Slide 12: Bronchiectasis disease process
An environmentalinsult or disease process leads to bronchial wall destruction and dilation Structural damage impairsprotective mucociliary clearance Increased susceptibility to chronic bacterial infection and colonization Persistent inflammatory response, causing lung damage All references to bronch
Slide 13: DPP1 inhibition and brensocatib
Positive Phase 2 Data in bronchiectasis underscore potential of brensocatib DPP1 is an enzyme that catalyzes the activation of NSPs in neutrophils when they are formed in the bone marrow Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and i
Slide 14: WILLOW Phase 2 results
Exacerbation-related hospitalizationrates was higher & duration of hospitalization was longer in the placebo arm Both 10 mg & 25 mg group met primary endpoint with statistical significance Risk of exacerbation over six months reduced by 42% for 10 mg group, 38% for 25 mg group
Slide 15: ASPEN Phase 3 compared with WILLOW
256 Pts(~85 pts/arm) 1,620 Pts(540 pts/arm) 80% for a 40% reduction 90% for a 30% reduction 1.37 (actual)1.2 (planned) 1.2 Consistent Consistent 6 months 12 months Time to first exacerbation Rate of pulmonary exacerbation Rate of pulmonary exacerbation Time to first exacerbation
Slide 16: ASPEN study design
Clinic visits week 4, 16, 28, 40, 52(EOT) and 56 (EOS)Phone visits week 10, 22, 34 and 46 Stratified by:Geographic regionPseudomonas aeruginosa on sputum cultureNumber of prior PEs (2, or ≥3) in previous 12 months Off treatment 4 weeks 25 mg 10 mg Treatment period 52 weeks Baselineday 1randomization
Slide 17: Bronchiectasis prevalence
◊ Between 450K – 675K asthma patients in the US (2%-3%3)may also havebronchiectasis Between 650K –9M COPDpatients in theUS (4%1-54%2)may also have bronchiectasis *Weycker, et al. Prevalence and incidence of NCFBE among US adults in 2013. Chronic Respiratory Disease. 2017;**Estimates suggest broadly
Slide 18: Bronchiectasis as launch pad for neutrophil-mediated portfolio
Bronchiectasis to Potentially Serve as ‘Launch Pad’ for Neutrophil-mediated Portfolio Additional indications identified, to be announced in 1Q 2022 On track to release data in 2022
Slide 19: TPIP
TPIP is an investigational drug product that has not been approved for any indication in any jurisdiction.
Slide 20: Prostanoid therapy challenges and TPIP potential
Prostanoidshave long beena cornerstone therapy for PAH, but clinical use has faced challenges related to rapid metabolism anddose-limiting tolerability issues TPIP could address the shortcomings of existing prostanoid therapies by potentially:Providing prolonged, localized pulmonary vasodilationOffe
Slide 21: TPIP formulation and inhaler device
TPIP* is a dry powder formulation of treprostinil palmitil, a prodrug of the prostacyclin vasodilator treprostinilOnce delivered to the lung, treprostinil palmitil is hydrolyzed by endogenous esterases to active treprostinilThe inhalation device is a simple capsule-based dry powder inhaler (DPI) dev
Slide 22: Preclinical efficacy measures in PAH models
Fulton Index = weight rationRight Ventricle / (Left Ventricle + Septum)Pulmonary Pressuremean Pulmonary Arterial PressureObliteration% of non-obliterated vesselsWall thicknessSmall vessel wall thicknessMuscularization% of muscularized vesselsCardiac Outputamount of blood pumped by the heartper minut
Slide 23: TPIP Phase 1 findings
Supports the potential for improved tolerability,efficacy and convenience Safety profile was generally well tolerated, AEs were mild and consistent with inhaled prostanoidTolerability was improved with an up-titration approachFindings suggest TPIP may be safely dosed at nominal doses far in excess o
Slide 24: TPIP Phase 2 plans in PAH and PH-ILD
Phase 2aData expected in 1H 2022 Phase 2bSite initiation complete (late 2021) PAH PH-ILD Phase 2Study initiation expected early 2022
Slide 25: TPIP versus existing PAH therapies
IV or Subcutaneous Inhaled (nebulized) Oral Oral Inhaled(dry powder) Continuous 4x per day 2x or 3x per day 2x per day Once daily Yes Yes Yes Yes To be evaluated in Phase 2 (encouraging preclinical & P1 data) Yes Yes Yes Yes No No Yes(but only as add-onto monotherapy) Yes To be evaluated in Phase 3
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Slide 27: Research platform pillars
Therapeutic proteinsViral capsids Transgenes Enzymes Targeting 1 new IND / YearPlans to accelerate following anticipated successful data from Pillars 1-3 ProteinDe-immunization GeneTherapyReduce viral load Improve safetyTarget rare monogenic diseases GeneEditingIn-vivo gene editingCorrective transge
Slide 28: Cash and capital position
Based on current expectations, this capital supports major data readouts as of 9/30/21 as of 9/30/21 *Excludes stock options, unvested RSUs, shares underlying outstanding convertible notes, and any shares to be issued pursuant to future milestones achieved related to recent business acquisitions
Slide 29: Anticipated milestones
Completed enrollment in WILLOW launch NEJM publication of WILLOW data Positive preclinical data & initiated clinical studies Development in additional indications Advance into P2b for PAH Japan launch(underway) IND readycandidate PAH P2a data and PH-ILD P2 trial initiation PK/PD data in P2 for CF Ad
Slide 30: Investor relations contact
investor.relations@insmed.com 646-351-0954 We are committed to bringing forth technologies and medicines in therapeutic areas with thegreatest potential to make adifference in patients’ lives. 30
Slide 31: Appendix
Slide 32: Patents and regulatory exclusivity
Approval has been granted in the U.S., EU, and Japan for ARIKAYCE US 4 patents issued to 2034Japan, EU, Australia, China counterpart patents issued to 2034 US, Europe, Japan, Chinain-licensed compound patent exclusivity until 2035 U.S. multiple issued patents to2035 12-year regulatory exclusivityEU
Slide 33: Manufacturing capacity
300kg capacity 2mm capacity 50g capacity 10,000 capsules capacity 200L capacity To come online450L capacity
Slide 34: WILLOW study design
Stratified by Pseudomonas aeruginosa on sputum culture and use of macrolides EOS, end of study; EOT, end of treatment; NE, neutrophil elastase; ppFEV1, percent predicted forced expiratory volume in 1 second; QD, once daily. Phase 2 WILLOW Study: NCT03218917 Clinic visits day 1, week 2, week 4,8, 12,
Slide 35: WILLOW efficacy and safety results
10 mg 25 mg p-value ^ 0.027 0.044 Hazard Ratiop-value ^ 0.580.029 0.620.046 Brensocatib was generally well- tolerated in the WILLOW studyMost common adverse events (AEs) in patients treated with Brensocatib were cough, headache, sputum increase, dyspnea, fatigue, and upper respiratory tract infectio
Slide 36: Exacerbation-related hospitalizations
a Exacerbations cited by investigator as primary reason for hospitalization. 8.0% 6.1% 4.6% 0% 2% 4% 6% 8% 10% Patients (%) 10.1 7.0 6.5 0 2 4 6 8 10 12 Days (N) Exacerbation- related hospitalization rates was higher & duration of hospitalization was longer in the placebo arm
Slide 37: WILLOW subgroup data
Chalmers et al, ERS International Congress 2020, 7-9 September. RCT4135 BSI, bronchiectasis severity index; FEV1, forced expiratory volume in 1 secondaBulgaria/Poland
Slide 38: WILLOW supporting data
Chalmers et al, ERS International Congress 2020, 7-9 September. RCT4135
Slide 39: WILLOW adverse events
3 (3.5) 3 (3.7) 4 (5.5) 9 (10.6) 6 (7.4) 6 (6.7) 19 (22.4) 11 (13.6) 10 (11.2) 9 (10.6) 5 (6.2) 4 (4.5) 3 (3.5) 0 4 (4.5) 67 (78.8) 75 (92.6) 74 (83.1) 10 (11.8) 15 (18.5) 12 (13.5) 3 (3.5) 8 (9.9) 12 (13.5) 6 (7.1) 9 (11.1) 9 (10.1) 2 (2.4) 3 (3.7) 9 (10.1) 9 (10.6) 5 (6.2) 4 (4.5) 9 (10.6) 5 (6.2)
Slide 40: Pulmonary hypertension classification
1.1. Idiopathic PAH (IPAH) 1.2. Heritable 1.2.1. BMPR2 1.2.2. ALK1, ENG, SMAD9, CAV1, KCNK3 1.2.3. Unknown 1.3. Drug- and toxin-induced 1.4. Associated with 1.4.1. Connective tissue diseases HIV infectionPortal hypertensionCongenital heart diseasesSchistosomiasis1’ Pulmonary veno-occlusive disease a
Slide 41: Treprostinil palmitil preclinical pharmacokinetics
M. R. Corboz, et al. (2017) J. Pharmacol. Exp. Ther. 363:348–357. 10XCmax 0.01 0.1 101 100 1000 10000 0 5 10 15 20 25 Lung TRE eq (ng/g) Time (h) Treprostinil Palmitil 42 μg/kg Treprostinil Palmitil 108 μg/kg Treprostinil 215 μg/kg Treprostinil Palmitil Treprostinil Inhaled TP Inhaled TP Inhaled TPI
Slide 42: Plasma treprostinil concentration versus Tyvaso
Cmax (ng/mL) 0.089 0.958 AUC0-24(ng*h/mL) 0.614 0.872 Tmax (h) 1.02 0.258 T1/2 (h) 5.69 0.485 Han et al. (2016) Single-Dose Pharmacokinetics of C16TR for Inhalation (INS1009) vs Treprostinil Inhalation Solution. ERS International Congress, September 3-7, London, United Kingdom, abs 3505 (poster PA23
Slide 43: TPIP Phase 1 study design
225 µg QD×7 days 6 subjects QD×7 days 2 subjects 112.5 µg 6 subjects 225 µg 6 subjects 450 µg 6 subjects 675 µg 6 subjects 2 subjects 112.5 µg QD ×4 days } 6 subjects 225 µg QD ×3 days QD×7 days 2 subjects Informed by prior TPIS Phase 1 study All doses were administered using 112.5 µg capsulesTPIS:
Slide 44: TPIP treatment-emergent adverse events
* Moderate TEAEs: 225 µg – 1 subject with nausea and vomiting; 675 µg – 2 subjects with hypotension, 1 subject with chest discomfort, low oxygen saturation and dyspneaIncludes all AEs that occurred in more than two subjects, as well as others of interest TEAEs were Consistent with Inhaled Prostanoid
Slide 45: TPIP titration adverse events
* Moderate TEAEs: 225 µg – 1 subject with chest discomfort (subject discontinued day 2), 1 subject with throat irritation (day 2-7), 1 subject with syncope (day 1)Includes all AEs that occurred in more than two subjects, as well as others of interest 5 (83.3) 6 (100) 4 (100) 15 (93.8) 6 (100.0) 4 (6
Slide 46: Current PAH landscape and new PH opportunities
Current PAH LandscapePrevalence of PH[1] WHO Group 1[2][in U.S. as of 2019] New PH OpportunitiesPrevalence of PH ILD[4]& PH COPD[5] in WHO Group 3[2][in U.S. as of 2019] Opportunities Beyond PHPrevalence of Chronic Fibrosing ILD[2] [in U.S. as of 2019] Chronic Fibrosing ILD Patients >100,000 Patient