A Stepwise Approach to Nasal Polyp Treatment Is Emerging in the Age of Biologics

A Stepwise Approach to Nasal Polyp Treatment is Emerging in the Age of Biologics

XHA-21-10007 Presenters

Payor Insights Clinical Discussion & Relevance

Michael J. Rothrock, BS, MBA, MHA Joseph Han, MD President President Allegheny Strategic Partners LLC American Rhinologic Society

Dr. Han and Mr. Rothrock are paid consultants of Optinose.

2 Today’s Objectives

Evaluate an emerging approach for stepped-care management of nasal polyps

Discuss each step’s impact on coverage and cost

Highlight a second-line therapy in the stepped-care approach

3 Nasal Polyp Management: Challenges You Face

 Nasal polyps cost ~$5.7 billion1 annually and affect up to 4% of the population2  Traditional treatments often do not resolve symptoms3  Patients seek more costly treatments (surgery, biologics)4,5  Surgery may not be a permanent solution6  The approvals of dupilumab and omalizumab for nasal polyps are likely to drive up payor costs7,8  More biologics are on the horizon9,10

References: 1. Bhattacharyya et al. Laryngoscope. 2019;129(9):1969-1975. 2. Stevens WW, et al. J Allergy Clin Immunol Pract. 2016;4(4):565-72. 3. Palmer et al. Allergy and Asthma Proc. 2019;40(1):48-56. 4. Ference EH et al. Am J Rhinol Allergy. 2018;32(1):34-39. 5. First Data Bank; March 19, 2021. 6. DeConde et al. Laryngoscope. 2017;127(3):550-555. 7. Gu et al. Drugs Real World Outcomes. 2016;3(4):369-381. 8. Wong et al. J Manag Care Pharm. 2011;17(4):313-320. 9. National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT03085797. Accessed February 8, 2021. 10. National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT03401229. Accessed February 8, 2021.

4 Historical Approach to Treatment of Nasal Polyps

Treatment Treatment yes Recommended Continue medical management • Intranasal steroids • Saline irrigation Symptom • Oral corticosteroids (1 short course) relief? • Aspirin desensitization for AERD Treatment patients no Recommended • ESS followed by continued medical management

AERD=aspirin-exacerbated respiratory disease; ESS=endoscopic sinus surgery. Reference: Orlandi RR, et al. Int Forum Allergy Rhinol. 2016;6(suppl 1):S22-S209.

5 Emergence of a Stepped-Care Treatment Paradigm for Nasal Polyps

Additional Considerations: • Sinus surgery • Multidisciplinary evaluation • Aspirin desensitization • Steroid-eluting stents • Biologics Second-line Medications • Alternative steroid delivery methods First-line Medications (XHANCE, steroid rinses) • Saline rinse Sinus surgery and biologics • Nasal steroid sprays • Oral steroids ± antibiotics

Nasal steroid sprays

Treatment options are informed by factors such as disease severity, risk-benefit assessment, cost, response to prior treatment, and patient preference.

References: 1. Nasal polyps. SinusHealth.com. Accessed January 22, 2021. 2. Orlandi RR, et al. Int Forum Allergy Rhinol. 2021;11(3):213-739.

6 Emergence of a Stepped-Care Treatment Paradigm for Nasal Polyps

Nasal steroid sprays

Treatment options are informed by factors such as disease severity, risk-benefit assessment, cost, response to prior treatment, and patient preference.

References: 1. Nasal polyps. SinusHealth.com. Accessed January 22, 2021. 2. Orlandi RR, et al. Int Forum Allergy Rhinol. 2021;11(3):213-739.

7 Nasal steroid sprays

Low Cost But Patients May Experience Frustration

Only one conventional nasal steroid spray has an Nasal Steroid Sprays indication for nasal polyps2 >80% of patients with nasal polyps reported $0-$6,100/year (WAC)1 frustration with symptom relief when using a conventional nasal steroid3

References: 1. First Data Bank; March 19, 2021. 2. Nasonex [Prescribing Information] 2018. 3. Palmer et al. Allergy and Asthma Proc. 2019;40(1):48-56.

8 Nasal steroid sprays

Inhaled Nasal Steroids May Not Reach Target Sites High and Deep In the Nasal Cavity1

Site of Polyp Origination2 Conventional Spray1 ~75% of ENTs/Allergists surveyed agreed that intranasal steroids do not work well in chronic sinusitis because insufficient Nasal Polyp Treatment Target Sites Deposition medication reaches target sites of inflammation3* Opening of the frontal sinus LOW HIGH Openings of the sphenoidal sinus and posterior ethmoidal cells The clinical relevance of different Openings of the maxillary sinus deposition patterns has not been and anterior ethmoidal cells established

*Market research interviews of 402 ENTs and allergists commissioned by Optinose. Approximately 75% of ENTs/allergists indicated they at least "somewhat agreed" with the following statement: "Intra-nasal corticosteroids (e.g., Flonase) often do not work well in chronic sinusitis because not enough medication reaches the intended target site of inflammation." References: 1. Djupesland PG. Drug Deliv Transl Res. 2013:3(1):42-62. 2. Adapted from: Netter F. Atlas Of Human Anatomy, Professional Edition. Saint Louis: Elsevier Health Sciences; 2014. 3. Data on file. Optinose US, Inc.

9 Nasal steroid sprays

Conventional Sprays Show Similar Deposition Patterns, Concentrating in the Anterior/Inferior Regions of the Nasal Cavity

Example SPECT/MRI images for QNASL®, Flonase®, and Nasonex®. (Figures show 2 of the 3 external fiducial markers used to align SPECT with MRI data).*

*The clinical relevance of different deposition patterns has not been established.

All brand names are registered trademarks of their respective owners. MRI=magnetic resonance imaging; SPECT=single photon emission computed tomography.

Reference: Leach et al. J Aerosol Med. 2015;28(5):334-340. 10 Emergence of a Stepped-Care Treatment Paradigm for Nasal Polyps

Nasal steroid sprays

Treatment options are informed by factors such as disease severity, risk-benefit assessment, cost, response to prior treatment, and patient preference.

References: 1. Nasal polyps. SinusHealth.com. Accessed January 22, 2021. 2. Orlandi RR, et al. Int Forum Allergy Rhinol. 2021;11(3):213-739.

11 Confidential – Not for Further Distribution Without Prior Written Consent of Optinose Exhaled and Inhaled Fluticasone Are Not the Same When it Comes to Nasal Sprays1

XHANCE is the only FDA-approved prescription nasal spray that uses an Exhalation Delivery System to treat nasal polyps in adults and is2: Non-surgical Non-biologic Non-systemic

Please see Important Safety Information on slides 22-23.

References: 1. Djupesland PG. Drug Deliv Transl Res. 2013;3(1):42-62. 2. XHANCE [Prescribing Information]. 2017.

12 XHANCE Leverages the Optinose Exhaled Delivery System (EDS) SagittalPlane Transverse Plane Transverse

1 Exhalation elevates the soft palate, creating an airtight seal that separates the nasal cavity from the oropharynx 2 Air then enters the nostril through the sealing nosepiece, helping expand narrow nasal passages

3 Medication entrained in the breath is deposited high and deep in the nasal passages

4 Air then escapes out of the opposite nostril

Please see Important Safety Information on slides 22-23. Reference: Data on file. OptiNose US, Inc. 13 Deposition is Different With an Optinose Exhalation Delivery System (EDS) Exhalation helps deliver medication high and deep into the nose

LOW

Gamma camera images after using a nasal spray without exhalation (left) or an Optinose EDS with exhalation (right). Both images are from the same healthy subject taken 2 minutes after administration with Nasal spray without exhalation Optinose Exhalation Delivery radiolabeled solution and are representative System with exhalation of the overall findings from 211 images and 56 subjects.

The clinical relevance of different deposition patterns has not been established.

Please see Important Safety Information on slides 22-23. Reference: Djupesland PG. Drug Deliv Transl Res. 2013;3(1):42-62.

14 XHANCE and Flonase® Are Not Bioequivalent

30 C AUC Treatment max 0-∞  A single pharmacokinetic study XHANCE 372 mcg (pg/mL) (pg · h/mL) was conducted in healthy subjects to establish a bridge XHANCE 186 mcg 17.2 (n=86) 111.7 (n=56) between XHANCE and Flonase® XHANCE 186 mcg XHANCE 372 mcg 25.3 (n=86) 171.7 (n=55)  3-way, 3-treatment, crossover 20 Flonase 400 mcg 13.4 (n=85) 126.0 (n=42) study Flonase 400 mcg Systemic exposure to FP with XHANCE • XHANCE 186 mcg is higher than with Flonase, even at • XHANCE 372 mcg lower doses

• Flonase 400 mcg Plasma FP 10  Primary objective was to

assess and compare the Concentration(pg/mL) systemic exposure of a single dose of 186 and 372 mcg of XHANCE with 400 mcg of Flonase (fluticasone propionate) in healthy subjects 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Hours From Dosing Please see Important Safety Information on slides 22-23. All brand names are registered trademarks of their respective owners.

AUC=area under the curve; Cmax,= maximum serum concentration; FP=fluticasone propionate. Reference: Messina JC, et al. Clin Ther. 2019;41(11):2343-2356. 15 NAVIGATE I & II: Phase III studies demonstrated XHANCE efficacy and safety1

Similar randomized, placebo-controlled, multicenter studies to assess XHANCE in the treatment of nasal polyps (N=646)1

1 2-4 Treatment-experienced Double-blind Studies (16 weeks) Open-label Extension Study (8 weeks) study population1 Majority (91%) reported EDS-placebo BID (n-162) prior nasal steroid use XHANCE 372 mcg BID (n=82) More than half (54%) reported prior sinus XHANCE 186 mcg BID (n=160) surgery or polypectomy Secondary endpoints (not controlled for multiplicity): XHANCE 372 mcg BID (n=162) Complete response (polyps eliminated) Reduction in surgical eligibility assessed using standardized criteria Sino-Nasal Outcomes Test – 22 items Coprimary endpoints: Defining symptoms Reduction in total polyp grade at Week 16 Work productivity Reduction of nasal congestion/obstruction Quality of sleep symptoms at Week 4 Patient global impression of change

Please see Important Safety Information on slides 22-23. BID=twice a day; EDS=exhalation delivery system. References: 1. XHANCE [Prescribing Information]. 2017. 2. Leopold DA. J Allergy Clin Immunol. 2019; 143:126-34. 3. Sindwani et al. Am J Rhinol Allergy. 2019;33(1):69-82. 4. Data on file, Optinose U.S., Inc.

16 Improvement in All 4 Defining Symptoms Week 0 4 8 12 16 Coprimary Endpoint 0 -0.2 EDS-placebo BID (n=80) Statistically significant onset -0.4 § XHANCE 186 mcg BID (n=80) of action was generally -0.6 observed within 2 weeks for § § -0.8 XHANCE 372 mcg BID (n=82) vs Baseline vs § § congestion score § LS Mean Change -1 § § Week 4; Coprimary Endpoint § P ≤ .001. Secondary Endpoints* -1.2 Congestion/Obstruction Week 0 4 8 12 16 Week 0 4 8 12 16 Week 0 4 8 12 16 0 0 0

-0.2 -0.2 -0.2 -0.4 -0.4

-0.6 -0.6 -0.4

-0.8 -0.8 vs Baseline vs vs Baseline vs vs Baseline vs -0.6 LS Mean Change LS Mean Change LS Mean Change -1 -1

-1.2 -1.2 -0.8 Pain and Pressure Rhinorrhea Sense of Smell Please see Important Safety Information on slides 22-23. BID=twice a day; LS=least square; mcg=micrograms. *Although secondary endpoints were pre-specified, they were not adjusted for Reference: Leopold DA et al. J Allergy Clin Immunol. 2019;143(1):126-134. multiplicity; therefore, results require cautious interpretation. 17 Reduction in Nasal Polyp Grade (NAVIGATE II) LS mean change in bilateral polyp grade—coprimary endpoint, week 16 (N=242)

Week 0 4 8 12 16 20 24 0 XHANCE 186-mcg BID treatment group (Secondary Endpoint)* -0.2 Double-blind period Open-label extension: All patients received -0.4 XHANCE 372 mcg BID of patients experienced a -0.6 ≥1-point reduction in polyp ‡ % -0.8 63 grade vs 43.5% with -1 § § EDS-placebo at week 16. § -1.2 §

Nasal Polyp Polyp Nasal Grade -1.4 § * Multiplicity adjustments were not applied

LS Mean Mean LS Change Bilateral in -1.6 for secondary endpoints; therefore, -1.8 results require cautious interpretation.

-2 Furthermore, open label results may be Week 16 confounded by evaluator bias. ‡ P ≤ 0.01. Coprimary Endpoint § P ≤ 0.001. EDS-placebo BID (n=79) XHANCE 186 mcg BID (n=80) XHANCE 372 mcg BID (n=82) Baseline grade: placebo, 3.8; XHANCE 186 mcg BID, 3.9; XHANCE 372 mcg BID, 3.8. Results shown are from NAVIGATE II and are consistent with results observed in NAVIGATE I. Please see Important Safety Information on slides 22-23. BID=twice daily; EDS=exhalation delivery system; LS=least square; mcg=micrograms. Reference: Leopold et al. J Allergy Clin Immunol. 2019; 143(1):126-134. 18 Improvement in Congestion Response in Patients Previously on a Conventional Nasal Steroid Spray vs Overall Study Population Patients Who Were on a Conventional Nasal Steroid Spray1 Overall Study Population2 (N = 218) (N = 482) Week Week 0 4 8 12 16 0 4 8 12 16 0 0

-0.2 -0.2

-0.4 -0.4 -0.53 Change* -0.6 -0.58 Change* -0.6

Mean -0.8 Mean -0.8 -0.85 LS LS -1 -1.01 -1 -0.98 -1.03 -1.2 -1.2 EDS-placebo XHANCE 186 mcg BID XHANCE 372 mcg BID EDS-placebo XHANCE 186 mcg BID XHANCE 372 mcg BID (n = 77) (n= 69) (n = 72) (n = 161) (n = 160) (n = 161)

*Least squares mean change from baseline in patient-reported AM instantaneous diary scores for nasal symptoms on a scale from 0-3 (0=none, 1=mild, 2=moderate, 3=severe).

These results are descriptive and should be interpreted with caution. The characteristics of the subgroup at baseline were also consistent with the overall study population Please see Important Safety Information on slides 22-23. References:: 1. Senior BA et al. Int Forum Allergy Rhinol. 2020;10.1002/alr.22693. 2. Data on file. OptiNose US, Inc.

19 Reduction in Bilateral Polyp Grade Response in Patients Previously on a Conventional Nasal Steroid Spray vs Overall Study Population Patients Who Were on a Conventional Nasal Steroid Spray1 Overall Study Population2 (N = 218) (N = 482) Week Week 0 4 8 12 16 0 4 8 12 16 -0.1 -0.1

-0.3 -0.3

-0.5 -0.46 -0.5 -0.59

Change* -0.7 Change* -0.7

-0.9 -0.9 Mean Mean -1.1 -1.1 LS -1.13 LS -1.18 -1.3 -1.3 -1.28 -1.5 -1.47 -1.5 EDS-placebo XHANCE 186 mcg BID XHANCE 372 mcg BID EDS-placebo XHANCE 186 mcg BID XHANCE 372 mcg BID (n = 77) (n = 69) (n = 72) (n = 161) (n = 160) (n = 161)

*Least squares mean change from baseline in bilateral polyp grade.

These results are descriptive and should be interpreted with caution. The characteristics of the subgroup at baseline were also consistent with the Please see Important Safety Information on slides 22-23. overall study population References: 1. Nasal polyps. SinusHealth.com. Accessed January 22, 2021. 2. Orlandi RR, et al. Int Forum Allergy Rhinol. 2021;11(3):213-739.

20 Well-characterized Safety Profile (NAVIGATE I and II) AEs occurring in ≥3% of patients and more common than placebo1*

EDS-placebo BID XHANCE 186 mcg BID XHANCE 372 mcg BID Adverse Event (AE) (N=161) (N=160) (N=161) n (%) n (%) n (%) Epistaxis 4 (2.5) 19 (11.9) 16 (9.9) Nasopharyngitis 8 (5.0) 3 (1.9) 12 (7.5) Nasal septal erosion/ulceration 3 (1.9) 11 (6.9) 12 (7.5) Nasal congestion 6 (3.7) 7 (4.4) 9 (5.6) Acute sinusitis 6 (3.7) 7 (4.4) 8 (5.0) Headache 5 (3.1) 8 (5.0) 6 (3.7) Pharyngitis 2 (1.2) 2 (1.3) 5 (3.1) Nasal mucosal ulceration 2 (1.3) 6 (3.8) 4 (2.5) Nasal mucosal erythema 6 (3.7) 9 (5.6) 8 (5.0) Nasal septal erythema 3 (1.9) 6 (3.8) 7 (4.3) Data characterizing safety for up to 1 year were also obtained in 2 open-label studies in 928 patients with chronic sinusitis with or without nasal polyps2,3 Please see Important Safety Information on slides 22-23. *AEs reported in patients with nasal polyps in placebo-controlled studies. BID=twice daily; EDS=exhalation delivery system. References: 1. XHANCE [Prescribing Information]. 2017. 2. Sher et al. J Allergy Clin Immunol 2017;139(2):AB66. 3. Palmer et al. Int Forum Allergy Rhinol. 2018;00:1-8.

21 Important Safety Information Contraindications Hypersensitivity to any ingredient in XHANCE.

Warnings and Precautions Local Nasal Effects: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma. Close monitoring for glaucoma and cataracts is warranted. Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. Discontinue XHANCE if such reactions occur. Immunosuppression: potential increased susceptibility to or worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue XHANCE slowly. Patients with major risk factors for decreased bone mineral content should be monitored and treated with established standards of care.

Please see Important Safety Information continued on slide 23.

22 Important Safety Information (cont’d)

Adverse Reactions The most common adverse reactions (incidence ≥ 3%) are epistaxis, nasal septal ulceration, nasopharyngitis, nasal mucosal erythema, nasal mucosal ulcerations, nasal congestion, acute sinusitis, nasal septal erythema, headache, and pharyngitis.

Drug Interactions Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid effects.

Use in Specific Populations Hepatic impairment. Monitor patients for signs of increased drug exposure.

Please see accompanying full Prescribing Information.

Please see additional Important Safety Information on slide 22.

23 Emergence of a Stepped-Care Treatment Paradigm for Nasal Polyps

Nasal steroid sprays

Treatment options are informed by factors such as disease severity, risk-benefit assessment, cost, response to prior treatment, and patient preference.

References: 1. Nasal polyps. SinusHealth.com. Accessed January 22, 2021. 2. Orlandi RR, et al. Int Forum Allergy Rhinol. 2021;11(3):213-739.

24 Confidential – Not for Further Distribution Without Prior Written Consent of Optinose Sinus surgery and biologics

Patients Often Progress to Costly Options In Search of Symptom Relief1-3 Sinus surgery remains frequent despite broad use of conventional inhaled nasal steroids

• Among patients with nasal polyps, 52% reported having undergone surgery for sinus symptoms1

Endoscopic sinus surgery (ESS) charges exclusive of ESS performed every year 3 ~500K professional fees (estimate includes all ESS procedures, regardless of $17,300* presence of nasal polyps)4

*Average charge for all ESS procedures in patients with or without nasal polyps from 2009-2011, adjusted for inflation (2021) based on a 2.69% average annual medical inflation rate. Data from reference 3. References: 1. Palmer et al. Allergy and Asthma Proc. 2019;40(1):48-56. 2. DeConde et al. Laryngoscope. 2017;127(3):550-555. 3. Ference EH et al. Am J Rhinol Allergy. 2018;32(1):34-39. 4. Henriquez et al. Laryngoscope. 2013 Nov;123(11):2615-9.

25 Sinus surgery and biologics

Costly Surgery May Not Be a Permanent Solution Patients with nasal polyps may require multiple ESS procedures due to recurrent or incompletely resolved symptoms1

60% 35% 20%

An estimated 60% of Despite surgery, 35% Approximately 20% of patients patients had symptoms recurrence of polyps at will require revision surgery reappear within 1 year2 6 months1 within 5 years3

References: 1. DeConde et al. Laryngoscope. 2017;127(3):550-555. 2. Wynn R et al. Laryngoscope. 2004 May;114(5):811-3. 3. Velez F et al. Poster presented at: AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018: Boston, MA.

26 Sinus surgery and biologics

XHANCE Showed a Reduction in the Number of Patients Eligible for Surgery from Baseline* (NAVIGATE I & II) Secondary endpoint** Week 16 NAVIGATE I1 NAVIGATE II2 0% * Surgical eligibility was study defined and (n=82) (n=80) (n=80) (n=80) (n=82) (n=80) assessed using standardized criteria, (10%) occurring concurrently: moderate-to-severe congestion ≥3 months, use of conventional (20%) topical steroids ≥6 weeks, current or previous (30%) use of saline lavage for ≥6 weeks, and bilateral nasal polyposis with an NP grading (40%) score of ≥2 in at least 1 nostril. The patients (39%) (42%) deemed "eligible" may or may not have been (50%) (45%) offered surgery.

(60%) (58%) ** Multiplicity adjustments were not applied (62%) (70%) (66%) for secondary endpoints; therefore, results require cautious interpretation. (80%) Reduction in % of Patients Eligible for Surgery in % Eligible of Patients Reduction

EDS-placebo (n-161) XHANCE mcg BID (n=160) XHANCE 372 mcg BID (n=161)

Please. see Important Safety Information on slides 22-23. BID=twice a day; EDS= exhalation delivery system. References: 1. Adapted from Sindwani et al. Am J Rhinol Allergy. 2019;33(1):69-82. 2. Adapted from Leopold DA. J Allergy Clin Immunol. 2019; 143:126-34. 27 Sinus surgery and biologics

Use Of Biologics for Nasal Polyp Treatment Is Likely to Drive An Increase In Payor Costs1,2

Cost drivers for biologics1,2: Nasal polyp indications are approved/expected for multiple biologics4-7 Acquisition cost Biologic Status Multiple indications drive utilization dupilumab Approved Office visits/clinical follow-ups omalizumab Approved mepolizumab Phase III Completed $30,200*-$41,600†/year benralizumab Phase III Completed (WAC)3

*Based on a Xolair® dose of 300mg every 4 weeks. † Based on a Dupixent ® dose of 300mg every 2 weeks. All brand names are registered trademarks of their respective owners.

References: 1. Gu et al. Drugs Real World Outcomes. 2016;3(4):369-381. 2. Wong et al. J Manag Care Pharm. 2011;17(4):313-320. 3. First Data Bank; March 19, 2021. 4. US Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-rhinosinusitis-nasal-polyps. Accessed March 16, 2021. 5. Roche.com https://www.roche.com/media/releases/med-cor-2020-12-01.htm. Accessed February 8, 2021. 6. National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT03085797. Accessed February 8, 2021. 7. National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT03401229. Accessed February 8, 2021.

28 Emergence of a Stepped-Care Treatment Paradigm for Nasal Polyps

Nasal steroid sprays

Treatment options are informed by factors such as disease severity, risk-benefit assessment, cost, response to prior treatment, and patient preference.

References: 1. Nasal polyps. SinusHealth.com. Accessed January 22, 2021. 2. Orlandi RR, et al. Int Forum Allergy Rhinol. 2021;11(3):213-739.

29 Confidential – Not for Further Distribution Without Prior Written Consent of Optinose $30,200*-$41,600†/year Costly, systemic, Biologics 1,2 (WAC)1 and injectable

Endoscopic $17,300‡ Sinus Surgery ESS charges exclusive Costly, invasive, 3,4 (ESS) of professional fees3 and frequent

Approved for the treatment of nasal polyps5 1 $6,606/year Non-surgical5 (WAC) Non-biologic5 Non-systemic5

Inhaled Nasal $0-$6,100/year Low cost, but frequent 6 Steroids (INS) (WAC)1 progression to surgery

Please see Important Safety Information on slides 22-23. *Based on a Xolair® dose of 300 mg every 4 weeks. † Based on a Dupixent ® dose of 300mg every 2 weeks. All brand names are registered trademarks of their respective owners. ‡Average charge for all ESS procedures in patients with or without nasal polyps from 2009-2011, adjusted for inflation (2021) based on a 2.69% average annual medical inflation rate. Data from reference 3. References: 1. First Data Bank; March 19, 2021. 2. US Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-rhinosinusitis-nasal-polyps. Accessed March 28, 2021. 3. Ference EH et al. Am J Rhinol Allergy. 2018;32(1):34-39. 4. DeConde et al. Laryngoscope. 2017;127:550-555. 5. XHANCE [Prescribing Information]. 2017. 6. Palmer et al. Allergy and Asthma Proc. 2019;40(1):48-56.

30 Consider Positioning XHANCE After Conventional Nasal Steroid Sprays and Before Biologics for the Management of Nasal Polyps

 Progression directly from conventional INS to surgery and biologics represents the costly lengths that patients will go in search of symptom relief.1-3 Given the high cost of  XHANCE offers a different way to deliver a nasal steroid, using the Optinose EDS to biologics, XHANCE may be a 4,5 deposit fluticasone high and deep in the nasal passages where polyps originate. great option following INS for  The annual cost of XHANCE is substantially less than biologics or sinus surgery.6,7 the treatment of nasal polyps due to its safety, limited  The approvals of dupilumab and omalizumab and the anticipated approval of other systemic drug exposure, and biologics for nasal polyps are likely to drive costs through acquisition, utilization deposition of medication high 8,9 driven by multiple indications and clinical follow-ups. and deep in the nasal cavity.10

CONTRAINDICATIONS: Hypersensitivity to any ingredient in XHANCE. WARNINGS AND PRECAUTIONS: • Local Nasal Effects: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma.

Please see Important Safety Information on slides 22-23. EDS=exhalation delivery system, INS=intranasal steroids. References: 1. Adapted from Velez F et al. Poster presented at: AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA. 2. DeConde AS et al. Laryngoscope. 2017;127(3):550-555. 3. Palmer JN et al. Allergy Asthma Proc. 2019;40(1):48-56. 4. Djupesland PG. Drug Deliv Transl Res. 2013:3(1):42-62. 5. XHANCE [Prescribing Information]; 2017. 6. First Data Bank; March 19, 2021. 7. Velez F et al. Poster presented at: ACAAI 2019 Annual Scientific Meeting; November 7-11, 2019; Boston, MA. 8. Gu T et al. Drugs Real World Outcomes. 2016;3(4):369-381. 9. Wong BJ et al. J Manag Care Pharm. 2011;17(4):313-320. 10. Senior BA et al. Int Forum Allergy Rhinol. 2020;10.1002/alr.22693.

31 Considerations for Implementing Policy Changes to Limit the Rising Costs of Biologics

Example UM criteria for implementing step edits to restrict the use of biologics: TARGET AGENT Dupixent® (dupilumab) Calculate the number of patients PRIOR AUTHORIZATION CRITERIA FOR APPROVAL 1 1. The patient has a diagnosis of chronic rhinosinusitis with nasal polyposis treated by a specialist for nasal polyps AND the following: who are likely candidates for biologics A. The patient has had an inadequate response to sinonasal surgery OR B. The patient is NOT a candidate for sinonasal surgery OR Model the impact of shifting share C. The patient has had an inadequate response to oral systemic 2 corticosteroids in the past 90 days from biologics to XHANCE OR D. The patient has a documented intolerance to oral systemic corticosteroids AND 2. The patient will continue standard maintenance therapy (e.g., nasal saline irrigation, 3 Consider changing policy language intranasal corticosteroids) in combination with the requested agent to position XHANCE before biologics AND 3. The patient has had an inadequate response to XHANCE for minimum of 3 months OR 4. The patient has a documented intolerance to XHANCE

Please see Important Safety Information on slides 22-23. UM=utilization management.

32 Q&A THANK YOU