Pulmatrix, Inc. · NASDAQ:PULM
Pulmatrix — Corporate Update (February 2023)
42 slides from Pulmatrix's corporate update, Feb 3, 2023
Slide 1: Dr. Stewart J. Tepper and Dr. Margaret Wasilewski, February 3, 2023
Dr. Stewart J. Tepper, Professor of Neurology at the Geisel School of Medicine at Dartmouth College Dr. Margaret M. Wasilewski, Chief Medical Officer, Pulmatrix, Inc. February 3, 2023 rn) PULMATRIX NASDAQ: PULM
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements. All statements other than statements of historical fact contained herein, including statements regarding our business plans or strategies, projected or anticipated benefits or other consequences of our plans or strategies,
Slide 3: Pulmatrix
‘N PULMATRIX PULMATRIiX is committed to the development and commercialization of novel and transformational medicines for patients all over the world, using our proprietary iSPERSE™ technology to optimally deliver both respiratory and non-respiratory therapies via the respiratory system.
Slide 4: Management Team
Management Team Deep expertise in respiratory diseases and drug delivery technology across all stages of development Ted Raad ~ CEO & Director © Previously Chief Business Officer of Pulmatrix © 20 years of commercial healthcare and life sciences leadership experience © Former Chief Commercial Office
Slide 5: PUR3100
PUR3100 Inhaled Dihydroergotamine (DHE) for Treatment of Acute Migraine ~$575M U.S. peak net revenue potential, a 1% total Rx R= share, is a conservative forecast! that fully considers the competitive landscape and generic pressure iSPERSE mitigates the manufacturing / device issues resulting in MAP
Slide 6: PUR3100: Acute Treatment of Migraine
PUR3100: Acute Treatment of Migraine Large underserved market Large Market >1 billion worldwide >38 million U.S. Affects 3x’s more women than men Td PULMATRiX Large Unmet Medical Need 75% of patients not actively treated with Rx’s due to poor efficacy 80% of patients on Rx’s would try new therapies
Slide 7: PUR3100: $575M Peak Net Revenue Potential at LOE in the U.S.
PUR3100: $575M Peak Net Revenue Potential at LOE in the U.S. Physician and Patient Feedback Payer Feedback % of patients on tript xperiencing a suboptimal response 0 generic treatment % of patients ranking “starts to show failures required improvement by 30 minutes” as the ok b #1 most important pro
Slide 8: Published Pain Freedom Data Earlier Than Two Hours
Published Pain Freedom Data Earlier Than Two Hours Pain Freedom above Placebo (%) Drug/Route Class Dose cau O.5hour hour 2hour 24 hour . Rizatriptan ismg 0 ia 22 13 60" Tablet/Wafert? [tomg 1 9 31 18 55¢ ‘Sumatriptan A Nasal Sprays _| TiPt2n omg - 10 2 2 62 Sumatriptan [50mg 2 3 il 10 50* Tablet? 10
Slide 9: Dr. Stewart J. Tepper
Dr. Stewart J. Tepper Professor of Neurology at the Geisel School of Medicine at Dartmouth College in Hanover, New Hampshire Dr. Tepper is Director of the Dartmouth Headache Center in the Department of Neurology of Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Dr. Tepper received his u
Slide 10: Migraine Current Treatment Landscape and Unmet Medical Needs
Migraine Current Treatment Landscape and Unmet Medical Needs Stewart J. Tepper, MD Professor of Neurology Geisel Schoo! of Medicine at Dartmouth
Slide 11: Why is Migraine Important?
Why is Migraine Important? elt is very common elt is very disabling elt is very treatable
Slide 12: Prevalence and Incidence of Migraine
Prevalence and Incidence of Migraine
Slide 13: Migraine Prevalence: Population-Based Studies
Migraine Prevalence: 3 Population-Based Studies: The Most Common Neurological Illness AMS | AMS II: py AMPP: I Joes 1999 2007 17.6% 18.2% 17.6% 12.1% 12.6% 11.7% | | 18 Total Males Females Stewart et al. JAMA. 1992;267:64-69, Lipton et al. Headache. 2001;41:646-657. Lipton et al. Neurology. 2007;68:
Slide 14: Prevalence of Migraine
Prevalence of Migraine Ss SCNAODOSNRGDAS % of US Population Overall Females Males Age-Associated Prevalence Migraine Prevalence (%) a of Migraine —Females ~Males 20 30 40 50 60 70 80 100 Age (Years) Lipton RB et al. Headache. 2001;41:646-657. (AMS II)
Slide 15: Global Prevalence: World Health Organization (WHO), 2016
Global Prevalence: World Health Organization (WHO), 2016 *In 2016, had migraine #6 of the 10 greatest causes of years lived with disability * Migraine was one of the two leading causes of YLDs in developed countries, and in the top five worldwide + “Migraine (including medication-overuse headache, w
Slide 16: Migraine Years Lived with Disability (YLDs): WHO (2016)
Migraine Years Lived with Disability (YLDs): WHO (2016) sat H et i = oy Fol pe Same sae Coy ee : Bee senor braye — Seve Ha erarere Sue Brin z Hodgkin’ * Niteicon nee 00) 200 de CSS os i rasogn dO oom H sophie iin, fom] ee Bf inc peti nie vw ~003- —— a -0-04- Orch seit Asesinas) Lancet 2017;390:1211-
Slide 17: Acute Migraine Treatment
Acute Migraine Treatment
Slide 18: Clinical Goals for Acute Treatment of Migraine
Clinical Goals for Acute Treatment of Migraine * Pain-Free within 2 hours * Works deep in a migraine, when a patient is disabled, including waking up with a full-blown + Freedom from Most Bothersome Symptom within 2 migraine or later in the day when the attack hours, picked by patients from sensitiv
Slide 19: Triptans, Ergots, NSAIDs
Triptans, Ergots, NSAIDs * Triptans and ergots are serotonin (5-HT),—/p agonists * Ergots also have non-serotonin activity + Both classes inhibit release of CGRP * NSAIDs inhibit migraine inflammation DC
Slide 20: Triptan Groups
Triptan Groups Group 1 Group 2 Faster onset, high potency Slower onset, lower potency + Sumatriptan (IMITREX): oral, liquid + Naratriptan (AMERGE)-oral nasal, nasal powder, SC * Sumatriptan/ naproxen (TREXIMET)- oral * Zolmitriptan (ZOMIG)- oral, liquid nasal + Rizatriptan (MAXALT)- oral + Almotript
Slide 21: Gepants and Lasmiditan
Gepants and Lasmiditan * Gepants (ubrogepant/UBRELVY™ and rimegepant/NURTEC®) are only dosed orally and have a slower onset of action (20% pain free at 2h) * Gepants block the CGRP receptor, so they only work in those with a CGRP biology * Lasmiditan (REYVOW®) is FDA scheduled, associated with signi
Slide 22: Currently Available Ergots
Currently Available Ergots ¢ Ergotamine tartrate (CAFERGOT®) « Dihydroergotamine (DHE): * Injectable: SC, IV * Liquid nasal (MIGRANAL®, TRUDHESA®)
Slide 23: Unmet Acute Treatment Needs
Unmet Acute Treatment Needs * Access ¢ Triptans don’t work deep into a migraine (central sensitization) * Triptans are associated with migraine recurrence requiring re-treatment, often up to 40% * Triptans are associated with genesis of acute medication overuse headache and chronic migraine * Lack o
Slide 24: Unique Properties of DHE
Unique Properties of DHE DHE Non-Oral Delivery + Works in the brain and outside the brain + Useful with nausea and vomiting * Targets multiple receptors to provide optimal response + Bypasses the gut + Fast onset: + Can be quicker in onset * MAP pulmonary DHE showed pain freedom in <30 + Useful in m
Slide 25: Liquid Nasal DHE as MIGRANAL
Liquid Nasal DHE as MIGRANAL® Liquid nasal DHE as MIGRANAL?® is available only in a patient-unfriendly device, delivers inconsistent results, and is ridiculously expensive (Valeant/Bausch) During a migraine, the patient must: Remove the tin collar and not get cut Remove the rubber stopper = Remove t
Slide 26: Liquid Nasal DHE as TRUDHESA
Liquid Nasal DHE as TRUDHESA® Open Liquid DHE vial: Remove the collar and rubber stopper Remove plastic cover from the TRUDHESA device at the bottom Screw on liquid DHE vial from the bottom Prime the device Spray once in both nostrils Throw it away (4 to a box) OF OT ONS Spray Nozzle S Finger Grips
Slide 27: Summary of Acute Landscape and Unmet Needs
Summary of Acute Landscape and Unmet Needs * Triptans do not work deep into attacks, can be poorly tolerated, are associated with recurrence and transformation to chronic migraine, and have poor non-oral formulations + Gepants have a CGRP biology with 20% 2-hour Pain-Free « Lasmiditan, which works o
Slide 28: Exposure and Efficacy: Thoughts on the Pharmacokinetics of DHE
Exposure and Efficacy: Thoughts on the Pharmacokinetics of DHE
Slide 29: DHE Pharmacokinetics 1: IV/ IM/ MAP Inhalable/ MIGRANAL Nasal
DHE Pharmacokinetics 1: IV/ IM/ MAP Inhalable/ MIGRANAL Nasal —IM1mg | Too high, nausea & vomiting —lVimg —Semprana 1 mg orstpumenary- Nor AppRovED —Migranal 2 mg Liquid nasa spray-4 spraystotal a a rget zone for :, efficacy 8 ng/ml is potential threshold concentration for efficacy ° LF By ‘0 20 150
Slide 30: DHE pK 2: IV/ MIGRANAL Nasal/ TRUDHESA Nasal
DHE pK 2: IV/ MIGRANAL Nasal/ TRUDHESA ® Nasal 100,000 4 —mWOHEL me 10,000 4 See § i Migranal 2.mg ea oe Be AG . “@- TrudhesaiNp-1041.45 me BS Oe) 8, = 1000 4 = a og = BE 100 28 Be 38 30 10-4 T T Shrewsbury SB, et al, Headache. 2019;59:264-408; Kellerman Du, et al. J Aerosol Med Pulm Drug Deliv. 201
Slide 31: DHE pK: IV/ MAP inhalable/ Satsuma Nasal/ TRUDHESA
DHE pK: IV/ MAP inhalable/ Satsuma Nasal/ TRUDHESA® Nominat | Com | Tax | AUCs, | Therapeutic Dose | (pg/ml) | (min) | (pg-h/ml) | Gain over 100000 > MORE LO M9: cr) Placebo at 2h Come kitegit~-- MAP00004 0.88 mg Failed 2h endpoint: STS101 5.2 mg IV DHE*? 44,000 ie 7,700? = a = 10000 INP103 1.45 mg
Slide 32: Conclusions on pK
Conclusions on pK + We want lower C,,,, to avoid AEs (<50,000 pg/ml) + Do we want a Ta, to avoid AEs (>10 minutes) ? max + We want optimal C,,,,, for efficacy (2000-2500 pg/ml) * Prefer inhalable to parenteral or nasal
Slide 33: Thank You!
Thank You!
Slide 34: Margaret Wasilewski, MD
Margaret Wasilewski, MD Pulmatrix Chief Medical Officer
Slide 35: PUR3100 Phase 1 Clinical Study to Evaluate Safety, Tolerability and Pharmacokinetics
PUR3100 Phase 1 Clinical Study to Evaluate Safety, Tolerability and Pharmacokinetics Objective to demonstrate safety and comparative bioavailability of PUR3100 (pulmonary inhaled) relative to |'V DHE Randomized Dou Healthy Volunteers 24 subjects Randomized to dose group PULMATRiX le- Inhaled Placebo
Slide 36: PUR3100 Achieved All Phase 1 Study Objectives and TPP
PUR3100 Achieved All Phase 1 Study Objectives and TPP To determine the safety and tolerabi of single doses of inhaled PUR3100 in healthy adult subjects To characterize the systemic pharmacokinetics (PK) of single doses of inhaled PUR3100 in healthy adult subject Cinax therapeutic window between ~1,0
Slide 37: PUR3100 Four Hour Exposure Profile is Similar to IV
PUR3100 Four Hour Exposure Profile is Similar to IV Equivalent T,,, With C,.a, below the range typically associated with nausea eoeed - mg = PUR31000.5 mg © Tmax iS at the first time point (5 min) for “+ PURS100 10mg all subjects at all PUR3100 doses Tinax “+ PURS100 18mg 5. Hy © Cyax at every dose
Slide 38: PUR3100 Kinetics Compared to MAP0004
PUR3100 Kinetics Compared to MAP0004 e+ MAPOOOS 1 mg ~*+ MAPO004 2 mg PUR3100 is quicker to T,,,, and has higher C,,,,, per delivered dose — PUR31000.5 mg — PUR3100 1.0 mg . Trax Trex — PUR3100 1.5 mg © Tmax at 5 min for all PUR3100 doses F > 50% Nausea versus 12 minutes in MAP Phase 1 15000 jnesest
Slide 39: PUR3100 Has Improved Kinetics to Marketed DHE Therapies
PUR3100 Has Improved Kinetics to Marketed DHE Therapies PUR3100 is quicker to T,,,,, and has higher C,,,, relative to intranasal o> Manag os INPO4 1.45 mg — PURSI0005 m9 = pursioo 0g Tmax Tmax Tmax pursito sng © Trax at 5 min for all PUR3100 doses versus 30 minutes for in INP1041 and 50 minutes for
Slide 40: PUR3100: No Vomiting and Less Nausea Than IV DHE
PUR3100: No Vomiting and Less Nausea Than IV DHE 420 IV D.H.E. 45 1 mg SNR 4 & Nausea chest tightness i i so 2 Tess Senet Nausea Incidence in 405 VDE. 451mg 00000. 3 30 Nausea Vom ; ce VT z i Relation to Crax 123 IVDHE 45 tmg 48100 4 7 Nausea 114 VDE. 451mg 25500. 5 12 Nausea Vom 7 220 I DHE. 451mg
Slide 41: Inhaled DHE Therapy Potential Advantages
Inhaled DHE Therapy Potential Advantages What Migraine — | Fast onset of action Migraine upon 24+ hour headache Inhaled preferred Absence of: through early T,,2, awakening, quick to relief through over intranasal, ; nausea, lethargy, and sustained peek intensity, rescue sustained target convenient d
Slide 42: Thank You! Questions?
Thank You! Questions?