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Date of Report (Date of earliest event reported): January 18, 2022



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Item 7.01

Regulation FD Disclosure.


On January 18, 2022, Impel Neuropharma, Inc. (the “Company”) issued a press release in which it announced an update to the Trudhesa™ (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) launch progress and recent business highlights. A copy of the press release is attached to this Current Report on Form 8-K (this "Report") as Exhibit 99.1 and is incorporated by reference into this Item 7.01.


On January 18, 2022, the Company updated its corporate presentation, which it intends to use as part of investor presentations. A copy of the presentation is attached to this Report as Exhibit 99.2 and is incorporated by reference into this Item 7.01.

The information in this Item 7.01 (including Exhibit 99.1 and 99.2 attached hereto) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.


Item 9.01

Financial Statements and Exhibits.


Exhibit No.





Press release dated January 18, 2022

Investor presentation, dated January 18, 2022

Cover Page Interactive Data File (embedded within the Inline XBRL document)


* Furnished herewith.









Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.














Date: January 18, 2022






/s/ John Leaman







John Leaman







Chief Financial Officer





Exhibit 99.1


Impel NeuroPharma Provides Updates on TrudhesaTM Launch

and Recent Business Highlights


Trudhesa (Dihydroergotamine Mesylate) Nasal Spray for Acute Migraine Delivered Strong Q4 2021 Launch with 4,200 (TRx) Prescriptions; Exceeding Company’s Guidance Range


Achieved Broad and Favorable Trudhesa Payer Coverage with Signed Agreements Covering 80% of U.S. Commercial Lives


Planned Initiation of INP105 Proof-of-Concept Study for Autism Spectrum Disorder in Q1 2022; Results anticipated Q4 2022


SEATTLE, January 18, 2022 — Impel NeuroPharma (NASDAQ: IMPL), a commercial-stage pharmaceutical company developing transformative therapies for people suffering from diseases with high unmet medical needs, with an initial focus on the central nervous system, today provided updates on Trudhesa™ (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) launch progress and recent business highlights.


Trudhesa Launch Progress Update

Since the October 2021 commercial launch, the performance of Trudhesa has exceeded our expectations with over 4,200 prescriptions generated, surpassing the Company’s Q4 guidance of 3,000-4,000 prescriptions. To-date Trudhesa accounts for approximately three percent of new branded acute migraine prescriptions (NBRx) among Impel’s 2,000 Super Target prescribers. Notably, Super Targets initiate approximately 60,000 branded acute NBRx, representing 34 percent of the total branded acute NBRx market (rolling 13-week basis).


In addition, during this first quarter of launch, the Company has secured contracts with several leading pharmacy benefit managers (PBMs) in the U.S. which cover approximately 80 percent of U.S. commercial lives.


“Last year was an exceptional year for Impel as we successfully achieved a first cycle FDA approval of Trudhesa, and raised greater than $180 million dollars through equity and debt offerings to support the successful commercialization of Trudhesa, in addition to executing a successful launch of Trudhesa in early October,” said Adrian Adams, chairman and chief executive officer of Impel NeuroPharma. “We are naturally delighted with the strong launch performance and the significant success in the managed care area, both of which exceeded our expectations. As we enter 2022, we are singularly focused on maintaining the excellent launch momentum with Trudhesa and continuing to transform Impel into a fully integrated R&D and Commercial company.”




Impel is the first company to harness the benefits of delivery to the upper nasal space to improve the therapeutic potential of CNS therapies. Using Impel’s proprietary POD® technology, Trudhesa delivers dihydroergotamine mesylate (DHE)—a proven, well-established therapeutic for acute migraine for adults—quickly to the bloodstream through the vascular-rich upper nasal space. Trudhesa bypasses the gut and reduces potential absorption issues, offering rapid, sustained, and consistent symptom relief without injection or infusion, even when administered hours after the onset of a migraine attack.


INP105 CALM 201 Study Update

Impel continues to advance its combination product candidate, INP105, an intranasal olanzapine product (a widely used atypical, second-generation antipsychotic) being developed as an acute treatment for agitation in persons with autism spectrum disorder (ASD) via Impel’s POD® technology. Since filing the investigational new drug (IND) application in November of last year, the Company has been working with the U.S. Food and Drug Administration (FDA) to finalize the Phase 2a proof-of-concept clinical protocol and anticipates the study will start in Q1 2022 with a data readout anticipated in Q4 2022.


The “CALM 201” Trial (Clinical Study in ASD Agitation with Olanzapine [INP105] Delivered to the Upper Nasal Mucosa) is a Phase 2a, proof-of concept, 2-way, 2-period crossover, double-blind study to evaluate the safety and efficacy of INP105 as an acute treatment versus placebo in people with ASD experiencing agitation. This study will evaluate the safety and tolerability of a single dose of INP105 to that of placebo in adolescents (12 to ˂ 18 years of age) with a diagnosis of ASD. The secondary objective is to explore the effect of treatment with a single dose of INP105 versus placebo in people with ASD experiencing agitation. It was hypothesized that INP105 could be a useful treatment for acute agitation episodes in the ASD population.


Acute agitation often manifests in patients with serious underlying mental health conditions such as bipolar I disorder or schizophrenia. Between 1.7 million and 7 million episodes of acute agitation have been reported to occur in U.S. hospitals and emergency room settings each year. An ideal medication for acute agitation, according to a 2005 expert consensus is easy-to-administer, non-traumatically administered, provides rapid tranquilization without excessive sedation, has a swift onset of action with sufficient duration to prevent untimely recurrence and has low risk for adverse events and drug interactions.


Further details of the CALM201 study can be found on ClinicalTrials.gov.


About INP105

INP105 is an upper nasal formulation of olanzapine administered using Impel’s novel POD® technology and being developed for the potential treatment of agitation and aggression associated with ASD. The POD is a novel, simple-to-use device designed to deliver consistent and predictable doses of drug. INP105 delivers olanzapine to the richly vascularized upper nasal space to offer rapid, consistent, and optimized bioavailability that can be administered by the patient or a caregiver. Olanzapine is the most used treatment for acute agitation, but its use is limited to intramuscular injection and in a hospital setting. INP105 is intended to be a preferred choice for



the safe and rapid treatment of acute agitation and, because it is designed to be non-invasive, it has the potential to expand the treatment setting beyond the emergency room, such as inpatient treatment or community care facilities and the patient’s home.


About Migraine

Approximately 31 million adults in the U.S. are living with migraine, and there is a need for more treatment options. In a survey of nearly 4,000 U.S. patients using oral acute prescription medication for migraine, 96 percent said they were dissatisfied with at least one aspect of their treatment—including lack of sustained relief, inconsistent relief, and lack of relief from a rapid-onset attack. Nearly half (48%) said they can still have pain two hours after taking medication and 38 percent say their headache returns within 24 hours of getting relief. Additionally, there is a need for non-oral routes of administration given the high prevalence of gastrointestinal issues among people with migraine.


Trudhesa™ Indication and Important Safety Information


Trudhesa™ is used to treat an active migraine headache with or without aura in adults. Do not use Trudhesa to prevent migraine when you have no symptoms. It is not known if Trudhesa is safe and effective in children.


Important Safety Information

Serious or potentially life-threatening reductions in blood flow to the brain or extremities due to interactions between dihydroergotamine (the active ingredient in Trudhesa) and strong CYP3A4 inhibitors (such as protease inhibitors and macrolide antibiotics) have been reported rarely. As a result, these medications should not be taken together.


Do not use Trudhesa if you:

Have any disease affecting your heart, arteries, or blood circulation.
Are taking certain anti-HIV medications known as protease inhibitors (such as ritonavir or nelfinavir).
Are taking a macrolide antibiotic such as clarithromycin or erythromycin.
Are taking certain antifungals such as ketoconazole or itraconazole.
Have taken certain medications such as triptans or ergot-type medications for the treatment or prevention of migraine within the last 24 hours.
Have taken any medications that constrict your blood vessels or raise your blood pressure.
Have severe liver or kidney disease.
Are allergic to ergotamine or dihydroergotamine.


Before taking Trudhesa, tell your doctor if:

You have high blood pressure, chest pain, shortness of breath, heart disease; or risk factors for heart disease (such as high blood pressure, high cholesterol, obesity, diabetes, smoking, strong family history of heart disease or you are postmenopausal, or male over 40); or problems with blood circulation in your arms, legs, fingers, or toes.



You have or had any disease of the liver or kidney.
You are taking any prescription or over-the-counter medications, including vitamins or herbal supplements.
You are pregnant, planning to become pregnant or are nursing, or have ever stopped medication due to an allergy or bad reaction.
This headache is different from your usual migraine attacks.


The use of Trudhesa should not exceed dosing guidelines and should not be used on a daily basis. Serious cardiac (heart) events, including some that have been fatal, have occurred following the use of dihydroergotamine mesylate, particularly with dihydroergotamine for injection, but are extremely rare.


You may experience some nasal congestion or irritation, altered sense of taste, sore throat, nausea, vomiting, dizziness, and fatigue after using Trudhesa.

Contact your doctor immediately if you experience:

Numbness or tingling in your fingers and toes
Severe tightness, pain, pressure, heaviness, or discomfort in your chest
Muscle pain or cramps in your arms or legs
Cold feeling or color changes in 1 or both legs or feet
Sudden weakness
Slurred speech
Swelling or itching


The risk information provided here is not comprehensive. To learn more, talk about Trudhesa with your healthcare provider or pharmacist. The FDA-approved product labeling can be found at www.Trudhesa.com or 1-800-555-DRUG. You can also call 1-833-TRUDHESA (1-833-878-3437) for additional information.


About Impel NeuroPharma

Impel NeuroPharma, Inc. is a commercial-stage biopharmaceutical company developing transformative therapies for people suffering from diseases with high unmet medical needs, with an initial focus on diseases of the central nervous system. Impel offers and is developing treatments that pair its proprietary Precision Olfactory Delivery (POD®) technology with well-established therapeutics. In addition to Trudhesa (dihydroergotamine mesylate) nasal spray, which is approved in the United States for the acute treatment of migraine with or without aura in adults, Impel is also developing INP105 for the acute treatment of agitation and aggression in patients with autism, and INP107 for OFF episodes in Parkinson’s disease.


Cautionary Note on Forward-Looking Statements

This press release contains “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including, but not limited to, the potential clinical benefits of Trudhesa™, the market opportunities of Trudhesa within the migraine market, the speed of uptake and market growth of Trudhesa, and the timing of announcements of clinical results and clinical development activities of Impel’s product



candidates. Forward-looking statements can be identified by words such as: “believe,” “may,” “will,” “potentially,” “estimate,” “continue,” “anticipate,” “intend,” “could,” “would,” “project,” “plan,” “expect” or the negative or plural of these words or similar expressions. These statements are subject to numerous risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including but not limited to, Impel’s ability to maintain regulatory approval of Trudhesa, its ability to execute its commercialization strategy for Trudhesa, its ability to develop, manufacture and commercialize its other product candidates including plans for future development of its POD devices and plans to address additional indications for which Impel may pursue regulatory approval, whether results of preclinical studies or clinical trials will be indicative of the results of future trials, and the effects of COVID-19 on its clinical programs and business operations. Many of these risks are described in greater detail in Impel’s filings with the Securities and Exchange Commission. Any forward-looking statements in this press release speak only as of the date of this press release. Impel assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.


Impel, POD and the Impel logo are trademarks of Impel NeuroPharma, Inc. To learn more about Impel NeuroPharma, please visit our website at https://impelnp.com/.


# # #




Media Relations:

Melyssa Weible
Elixir Health Public Relations
Phone: (1) 201-723-5805



Investor Relations

Christina Tartaglia

Stern Investor Relations

Phone: 212-362-1200

Email: christina.tartaglia@sternir.com




Slide 1

Impel NeuroPharma, Inc. Corporate Presentation January 2022 Exhibit 99.2

Slide 2

Safe Harbor Statement This presentation and the accompanying oral commentary by Impel NeuroPharma, Inc. (“we,” “us,” “our,” “Impel” or the “Company”) contains forward-looking statements that are based on our management’s beliefs and assumptions and on information currently available to our management. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our future financial performance, business plans and objectives, timing and success of our planned development activities, our ability to obtain regulatory approval, the potential therapeutic benefits and economic value of our product candidates, potential growth opportunities, competitive position, industry environment and potential market opportunities and the impact of the COVID-19 pandemic on our business and operations. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. These factors, together with those that may be described in greater detail in the filings that we have filed with the Securities and Exchange Commission (“SEC”), may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. By attending or receiving this presentation you acknowledge that you will be solely responsible for your own assessment of the market and our market position and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of our business. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. This presentation includes information concerning certain product candidates that are under clinical investigation, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. The product candidates are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Slide 3

Impel – Our Foundational Premise Biopharma Company focused on developing and commercializing transformative therapies for patients with unmet needs DEVELOPING TRANSFORMATIVE THERAPIES TARGETED FORMULATIONS of well-established therapeutics designed for upper nasal space delivery via our POD technology Giving patients freedom and control with on-demand, standard of care therapeutics that work rapidly Injection-like Clinical Outcomes, Achieved Non-invasively POD technology designed to provide rapid absorption and consistent drug biodistribution VASCULAR-RICH UPPER NASAL SPACE is potentially an optimal entry point

Slide 4

The Impel Opportunity Trudhesa™ - Significant Commercial Opportunity Large, growing and dynamic market with significant unmet need Highly Targeted Commercialization Strategy Initial 60-person salesforce; targeting 8K physicians (35% of Market Rxs) Plans to invest into the opportunity – increase salesforce to 120 in early 2023 INP105: Poised to Fill a Major Unmet Need Targeted for acute treatment of agitation and aggression in autism POD® Technology: Clinically Validated and Broad Utility Unique approach targeting upper nasal space; broad disease area applicability Proven and Experienced Leadership

Slide 5

The Post-Triptan Acute Migraine Treatment Landscape Compelling Entry Point TRUDHESA Recognized Standard of Care Treatment

Slide 6

Our Goal – Bring “Standard of Care” DHE Efficacy to Market Rapidly Promotable data for launch Track EFFICACY 3 De facto placebo control Acute Efficacy at 1st Exposure PRE-POST DESIGN: TRUDHESA vs. last dose of existing standard treatment Unique, large L/T database >5,650 migraines treated Long-Term Efficacy at 6 and 12 Months CONSISTENCY OF RESPONSE: TRUDHESA open label study Additional MARKET-ENABLING Analyses No placebo control required 1 PK data: TRUDHESA vs. IV DHE or Migranal Proven Drug: DHE 2  150 patients TRUDHESA 2x/month for 6 months (and  50 patients for 12 months) New Administration: Upper Nasal Cavity Show SAFETY Show BIOCOMPARABILITY at lowest effective dose APPROVAL Requirements Completed End 2017 Completed 1Q 2020 Phase 3 STOP 301

Slide 7

Trudhesa – Comparable to IV DHE; Surpassed Migranal PK Levels AUC in the First Two Hours – Thought to Be Critical to DHE Efficacy and Tolerability Trudhesa Delivers Comparable Blood Levels vs. IV DHE vs. MIGRANAL 4x increase in Cmax 3x increase in AUC Much improved consistency of dosing, similar to IV infusion Similar blood levels (20 mins - 48 hours) without early Cmax spike associated with nausea & vomiting Treatments

Slide 8

Trudhesa – Impressive Efficacy from STOP301 Study Migraines Treated 4th 12 weeks 3rd 12 weeks 2nd 12 weeks 1st 12 weeks 2,559 1,736 502 476 38% 35% 38% 34% 38% Percentage of subjects with 2 Hr Pain Freedom First Dose TRUDHESA 52% Percentage of subjects with 2 Hr MBS Freedom Consistent 2 Hr Pain Freedom over 5,273 Migraines Treated 74% of Enrolled Patients Continued Through 24 Weeks and 90% Enrolled Through 52 Week Extension

Slide 9

Trudhesa – Impressive Migraine Relapse-Free Data 86% of patients with migraines achieved pain freedom at 2 hours and are migraine and rescue med free at 48hrs % of TRUDHESA Patients Not Requiring Rescue Med or Recurrence of Migraine at 24 and 48 Hours (Of Those Pain Free at 2 Hours) *by week 21-24.

Slide 10

Trudhesa – Impressive Reduction in Hospital, ER and Urgent Care Visits * EAER is a standardized metric used by payors to judge the effectiveness of a medication in lowering medical costs # Hospitalizations # ER Visits # Urgent Care Visits INCIDENCE (n) Exposure Adjusted Event Rate (EAER)* ~73% Reduction in ER Visits Achieving a 100% Reduction in Hospitalizations / Urgent Care Provides Tangible Economic Value to Payors Baseline TRUDHESA

Slide 11

Trudhesa – Addressing Unmet Needs in Acute Migraine Treatment TRUDHESA AN ‘IDEAL’ MIGRAINE MEDICINE: 38% First Migraine treated pain free at 2 hours (354 pts.) 86% Migraine free at 48 hours (for those pain free at 2 hours, weeks 21-24) NO Treatment window limitations 74% Completed 24 week treatment period; 90% continued to 52 weeks 84% Agreed TRUDHESA “easy to use” FAST ACTING LONG LASTING RELIEF CAN BE TAKEN AT ANY TIME during migraine SUSTAINED RESPONSE and FEW OR NO SIDE EFFECTS EASY to incorporate into everyday life

Slide 12

Trudhesa Market Opportunity and Commercialization Strategy

Slide 13

Trudhesa – Product Positioning and Rationale Core Product Positioning: We believe Trudhesa demonstrates strong clinical utility for multiple patient types in the post triptan failure landscape Rationale: Oral and injectable treatments possess major limitations for many patients during a migraine attack DHE offers fast-onset efficacy, with continued protection from a single dose at any point during an attack Upper nasal space delivery is not limited by migraine-associated GI issues that impede oral treatments

Slide 14

Migraine – Large Growing Market with Ongoing Unmet Need Source: Symphony Health 27M 21M 24M 95% 5% 88% 12% 81% 19% +14% +13% Non Triptan Mkt +44% ‘21 vs ‘20 Triptan Mkt +1% ‘21 vs ‘20 75% 25% 30M +11%

Slide 15

Migraine: Despite New Product Launches, Unmet Need Continues Of the Patient Switching Away ~35% Moved to Another CGRP and ~20% Moved to Triptan Nurtec ODT and Ubrelvy Patient Claims Show ~50% Therapy Abandonment 90 Day Post Start Source: Symphony Health Patient Claims 56% 46%

Slide 16

Disciplined Go-To-Market Approach Concentrated prescriber base allows for high market coverage at launch Source: Symphony Health Our Focus: Targeting Highest Productive Writers # Reps Mkt Coverage Physicians Targeted Neuro Avg Yearly TRx / HCP PCP Avg Yearly TRx / HCP Wave 1 60 ~35% ~8k (5.6k Neuro + 2.4k PCP) ~90% of Neuro Mkt ~5% of PCP Mkt 1,474 678 Wave 2 +60 ~45% ~16k (6.3k Neuro + 9.7k PCP) ~100% of Neuro Mkt ~25% of PCP Mkt 1,085 489 Wave 2 Increases the Number of Reps to 120 and Expands Coverage to 16k HCPs Covering 45% of Market 60 Reps ~8k High Productive HCP’s ~35% Mkt Coverage 120 Reps ~16k High Productive HCP’s ~45% Mkt Coverage

Slide 17

~5.6k Impel Target HCPs are highly productive and early adopters of new branded treatments Impel Target Audience of only 8k HCPs Generate ~65% of All Branded Acute Therapy TRx’s Source: Symphony Health (data thru Jun’21) Branded Acute Mkt = Gepants, Cambia, Treximet, Tosymra, Reyvow, Zomig Impel Target Audience Driving Branded Acute (Gepants) Utilization Rapid adoption of Gepants driving Acute Market share uptake among Targets ~65% Share ~35% Share

Slide 18

Case in Point – Ubrelvy and Nurtec ODT Both Showing Highly Concentrated Prescriber Bases in Migraine Source: Symphony Health (Prescriber counts since launch thru Dec’21) 2.4k Writers Generate 50% of TRx (91% Neuros & 93% Impel Targets) 6.5k Writers Generate Next 25% of TRx (45% Neuros & 46% Targets) 57.7k Writers 25% of TRx 1.8k Writers Generate 50% of TRx (92% Neuros & 91% Impel Targets) 4.7k Writers Generate Next 25% of TRx (56% Neuros & 57% Targets) 49.2k Writers 25% of TRx Source: Symphony Health (Prescriber counts since launch thru Dec’21) Ubrelvy: ~8.9k Writers Generate ~75% of TRx Since Launch Nurtec ODT: ~6.5k Writers Generate ~75% of TRx Since Launch

Slide 19

Target HCPs Segmented to Prioritize Highest Value Prescribers ~500 Pre-Launch Targets & Top Centers ~8% of Migraine Market TRx Pre-Launch Educate & Prepare Market Immediate Launch Focus Drive Rapid Rx Uptake ~2k Super Target HCPs Very High Mkt Value & DHE Believers ~20% of Migraine Market TRx ~55% of DHE TRx ~8k Target HCPs High Value Prescribers ~35% of Migraine Market TRx ~60% of DHE TRx Continued Launch Focus With Current Sales Team Q4’21 2022

Slide 20

Trudhesa – Achieved Strong Market Access Position Utilization management confirms post-triptan position - broadly comparable to Gepant competitors No change to previous gross-to-net projections Negotiations with Optum ongoing Project ~85% of U.S. commercial lives covered by end of Q2 ~44M Lives ~44M Lives Optum 6 Month Moratorium ~17M Lives ~10M Lives ~24M Lives ~4M Lives Signed Contracts Covering 80% of U.S Commercial Lives

Slide 21

Trudhesa Pricing Reflective of Value and Innovation * WAC Price represents cost for 1 retail prescription package

Slide 22

Focus on Execution to Continue Strong Launch Trajectory Prioritizing Influential Top Accounts High salesforce touchpoints with top 2k Target HCPs Expanding penetration into remaining 6k targets Targeted Digital Promotion Focus content on target HCPs Deliver meaningful brand information to key patient audiences Leverage KOL advocacy Expanded speaker program to execute virtual and live programs Seamless Access to Trudhesa “Hassle Free” prescribing with Trudhesa Direct pharmacy partnership and “bridge” copay support program

Slide 23

Trudhesa – Strong Early Prescription Performance Early Launch Execution Commercial launch October 4th, 2021 ~650 Prescribers as of January 7th and growing at a rate of ~50 a week Avg ~7 Rx’s per Prescriber ~95% of Prescribers are Target HCPs or Affiliated to a Target HCP 63% of new patients refilling second prescription Launch to Date Trudhesa Cumulative nTRx Source: Symphony Health Normalized TRx (4 PODs per Rx)

Slide 24

Strengthening Prescriber Base and Depth of Prescribing Launch Focus: Generate Immediate Uptake in Prescribing Launch Focus: Creating Depth & Breadth Current Prescribers Avg 2.7 nTRx’s Avg 2.8 nTRx’s Avg 7.2 nTRx’s 34% 41% 13% 13% 250 482 632 250 482 632 63% 16% 22%

Slide 25

Trudhesa Refill Rates Aligned with Efficacy Data New Patient Refill Rates ~63% of Trudhesa Patients eligible for a refill have received second Rx Suggests many patients are not reserving Trudhesa only for rescue Trudhesa New Patient Refill Rate 1 Internal Pharmacy data

Slide 26

Trudhesa - Use in Broad Pool of Patients Source: Symphony Source of Business data Prescribers Showing Broad Mix of Patient Types When Using Trudhesa ~35-40% of Trudhesa Patients Being Either Switched From or Added to Gepants

Slide 27

Among Early Prescribers Trudhesa Filling a Need in the Post-Triptan Market Source: Symphony NBRx data (n=481) thru 12/31 Acute Branded Market = Trudhesa, Nurtec ODT, Ubrelvy Share of Acute Branded Market NBRx Among Current Trudhesa Prescribers

Slide 28

Current and Projected Self-Reported Patient Share Mean % of patients treated with an acute therapy Trudhesa – Encouraging Feedback from Prescribers 94% 99% 58% 24% 97% 99% 63% 68% Current: Next 6 months: Physician Satisfaction Trudhesa Reyvow Ubrelvy Nurtec ODT (acute) Aided and Unaided Awareness Trudhesa experience leads to high satisfaction levels Prescribers anticipate that next month patient initiations will be almost double that of the prior month. (2.9 to 5.5 patients) Source: Spherix Independent Research: quantitative data collected from 79 US neurologists; Dec 2021 Physicians anticipate that their Trudhesa share will rise rapidly. Prescriber base is expected to roughly triple in the next six months

Slide 29

First quarter of launch has exceeded our expectations: Symphony Health reported 4213 TRx of Trudhesa in Q4 - exceeding guidance of 3000-4000 TRx Signed contracts with 3 key PBMs providing coverage to 80% of commercial lives while maintaining GTN projections – exceeding guidance of 40% As of December 31st , there were over 600 unique HCPs have prescribed Trudhesa to date of which over 395 are Super Targets Super Targets have generated ~86% launch to date TRx’s Super Target New to Brand Share in the acute branded market is ~ 3% Refill rates are encouraging at 63% Trudhesa Early Performance - Summary

Slide 30

Pipeline Growth Opportunities

Slide 31

INP105 – Potential to Provide Rapid and Non-Traumatic Acute Treatment of Agitation and Aggression in Autism 220k ER Visits/Year 830K ~40% of ASD Patients Exhibit Agitation 2M Patients Receive Drug Treatment 3.5M Children and Adults in the U.S. Living with ASD At-home INP105 has the potential to reduce ER visits Market Opportunity Rapidly growing incidences of ASD and growing unmet needs in treatment are likely to increase the demand for effective treatments Individuals with ASD have a high incidence of secondary problems with mood lability, tantrums, self-injurious behavior and aggressiveness toward others Current Treatment Options Antipsychotics including olanzapine offer safe and effective option1 Risperidone and aripiprazole are FDA approved drugs for irritability associated with ASD but not considered long term solutions by many KOLs2 Unmet Need Despite two approved therapies, 68% of children and adolescents with ASD have a history of demonstrating aggression to a caregiver and 49% to a non-caregiver3 Current options require daily dosing, tend to produce weight gain and increase diabetes risk; require close monitoring Roberts J, Gracia Canales A, Blanthorn-Hazell S, Craciun Boldeanu A, Judge D. Characterizing the experience of agitation in patients with bipolar disorder and schizophrenia. BMC Psychiatry. 2018;18(1):104-018-1673-3. doi:10.1186/s12888-018-1673-3. Primary market research completed by ZS Pharma on behalf of Impel NeuroPharma, n = 65 autism specialists Kanne SM, Mazurek MO. Aggression in children and adolescents with ASD: prevalence and risk factors. J Autism Dev Disord. 2011 Jul;41(7):926-37al.

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INP105 – Acute Treatment of Agitation and Aggression in Autism *Nominal times used for mean plot INP105 - SIMILAR PK TO OLANZAPINE INJECTION, BUT FASTER TO PEAK BLOOD LEVELS Rapid Tmax, Cmax and AUC of INP105 matches 5mg olanzapine RAPID ONSET Faster to peak blood level than IM WELL-TOLERATED Minimal syncope POD DELIVERY Non-invasive delivery administered by self or caregiver TARGETS UNMET NEED Currently no approved therapies for acute agitation in autism Target Product Profile Phase IIa Proof of Concept Trial – The CALM 201 Study – Anticipated to be initiated in late Q1 2022 Clinical Development to Date – Phase 1B INP105 ACES (agitation scale) change matches IM 5 mg (N=20) 5 mg (N=10) (N=10)

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INP105 – Proposed CALM-201 Study CALM-201: Phase 2a Study of Safety and Efficacy in Adolescents with Autism Spectrum Disorder Single Dosing, 5mg, at Onset of Agitation Primary Endpoint is Safety Primary In-Person Efficacy Rating w/ ACES scale Study Sites will be In-Patient Autism Centers Video Rating w/ BARS, ABC-I, CGI-I, Others Efficacy measured over 60 minutes Est. N=24 Subjects Completing Q3 2021 Q4 2021 Q1 2022 Q2 2022 Q3 2022 Q4 2022 Study Preparation, IND Study Execution Topline Results Anticipated CALM-201 Study Schematic Anticipated Timeline Clinical study in ASD Agitation with oLanzapine (INP105) delivered to upper nasal Mucosa

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Impel Portfolio – Broad IP Protection Propellant Drug Formulation * Patent counts as of June 30, 2021 STRONG PENDING PRODUCT IP Specific device designs Novel formulations PK & Method-of-Use Claims INP104, INP105, INP103 and INP107 exclusivity to 2039 WORLDWIDE COVERAGE* U.S. issued patents = 6 International issued patents = 29 Pending patent applications = 80 Wholly owned global rights BROAD ISSUED PLATFORM IP Covers device with propellant, diffuser, nozzle and separated drug Covers propellant driven drug with nose-to-brain transport > 50% POD exclusivity to 2031

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Impel – Our Recent and Upcoming Achievements INP104 NDA Acceptance for Review January 2021 Successful $80M IPO April 2021 Successful $50M Debt Financing July 2021 FDA Approval of Trudhesa September 2, 2021 Successful $48M Follow-on Offering September 9, 2021 Trudhesa Commercial Launch October 2021 Anticipated Initiation of INP105 PoC Study Qtr1 2022 Journey Towards Transformation

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Experienced Management Team JOHN LEAMAN, MD Chief Financial Officer JOHN HOEKMAN, PhD Chief Technology and Development Officer LYNN GOLD Senior Vice President, Regulatory Affairs JENNIFER BERMAN Vice President, Marketing LEN PAOLILLO Chief Commercial Officer STEPHEN SHREWSBURY, MD Chief Medical Officer SHEENA AURORA, MD VP Medical Affairs, Migraine JERRY PENN Vice President, Market Access & Trade ADRIAN ADAMS Board Chairman & Chief Executive Officer NEUROSCIENCE INSTITUTE HEADACHE CENTER