Lyra Therapeutics : Corporate Presentation - January 2021

CORPORATE PRESENTATION

JANUARY 2021

DISCLAIM ER

This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding the

company's lead product candidate LYR-210, the presentation of top-line results relating to the Company's Phase 2 LANTERN clinical trial for LYR-210 and the Company's plans to initiate a pivotal Phase 3 study for LYR-210 in CRS for both non-polyp and polyp patients. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause the company's actual results, performance or

achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following:

the fact that the company has incurred significant losses since inception and expects to incur losses for the foreseeable future; the company's need for

additional funding, which may not be available; the company's limited operating history; the fact that the company has no approved products; the fact that the company's product candidates are in various stages of development; the fact that the company may not be successful in its efforts to identify and successfully commercialize its product candidates; the fact that clinical trials required for the company's product candidates are expensive and time-consuming, and their outcome is uncertain; the fact that the FDA may not conclude that certain of the company's product candidates satisfy the requirements for the

Section 505(b)(2) regulatory approval pathway; the company's inability to obtain required regulatory approvals; effects of recently enacted and future

legislation; the possibility of system failures or security breaches; effects of significant competition; the fact that the successful commercialization of the company's product candidates will depend in part on the extent to which governmental authorities and health insurers establish coverage, adequate reimbursement levels and pricing policies; failure to achieve market acceptance; product liability lawsuits; the fact that the company relies on third parties for the manufacture of materials for its research programs, pre-clinical studies and clinical trials; the company's reliance on third parties to conduct its preclinical

studies and clinical trials; the company's inability to succeed in establishing and maintaining collaborative relationships; the company's reliance on certain suppliers critical to its production; failure to obtain and maintain or adequately protect the company's intellectual property rights; failure to retain key personnel or to recruit qualified personnel; difficulties in managing the company's growth; effects of natural disasters; the fact that the global pandemic caused

by COVID-19 could adversely impact the company's business and operations, including the company's clinical trials; the fact that the price of the company's common stock may be volatile and fluctuate substantially; significant costs and required management time as a result of operating as a public company and any securities class action litigation. These and other important factors discussed under the caption "Risk Factors" in the company's Quarterly Report on

Form 10-Q filed with the SEC on November 10, 2020 and its other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. While the company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change.

2

INVESTM ENT SUM M ARY

Disrupting the treatment paradigm for intranasal drug delivery, starting with CRS

Developing Long-Acting Intranasal Implants for CRS

• Only therapy to achieve a benefit as much as six months after a single treatment

• 14M Chronic Rhinosinusitis (CRS) patients in U.S.; $6B addressable market

• No FDA approved medicines for non-polyp(70-90% of CRS patients)

Positive LANTERN Phase 2 Results for LYR-210 Announced 4Q 2020

• Rapid, durable, and clinically meaningful symptom improvement

• 100% had clinically meaningful symptom improvement at Week 24 (7500 mcg)

• First implant to demonstrate benefit in both polyps & non-polyps
• Supports pathway to regulatory submission for pivotal trial in 2021

Potential Multiple Expansion Opportunities through XTreoTM Platform

• LANTERN supports XTreo as a tunable, long-acting, local, drug delivery platform
• LYR-220,for CRS patients with prior sinus surgery, expected to enter clinic in 2021

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LYR A'S PROPRIETA RY

XTREO T M PLATFORM

BIOCOMPATIBLE		ENGINEERED		VERSATILE
MESH		ELASTOMERIC		POLYMER-DRUG
SCAFFOLD		MATRIX		COMPLEX

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ENGINEERED ELASTOM ERIC MATRIX

A D A P T S T O N A S A L A N AT O M Y

Shape-memory

• Adaptive elastic tension
• Resists deformation
• Designed to maintain persistent positioning

Designed to be

Self-retaining

• Exerts outward retention force at the target location
• Designed to remain in place as tissue remodels

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FOCUSED INITIAL DEVELOPM EN T PIPELIN E

LYR-210 and LYR-220: Designed to address the full spectrum of CRS patients

Candidate	Pre-clinical	Phase 1	Phase 2	Phase 3	Next
Milestone
	Chronic Rhinosinusitis
					LYR-210		LYR-220
LYR-210	Surgically Naïve Patients
		End of Phase 2
Long-acting
				FDA Meeting
Mometasone
				Mid 2021
Furoate

	Chronic Rhinosinusitis
LYR-220	Operated Patients
Long-acting	Enter Clinic
Mometasone	End 2021
Furoate

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WITH POTENTIAL FOR EXPAN SION INDIC ATION S

Lyra's XTreoTM platform has potential applications to other indications where long- term delivery would improve local bioavailability and enhance efficacy or safety

Potential Expansion Indications:

							3
1	Chronic Rhinosinusitis	3	Nasal Delivery for	1
Allergic Rhinitis	CNS Disorders	2	4

2

Ear Conditions

4

Rare Disorders

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WHAT IS CHRONIC RHINOSINU SITIS (CRS)?

Chronic Rhinosinusitis: The "Unrecognized Epidemic"1

				United States
				~14M CRS Prevalent Patients2
CRS Cardinal Symptoms1		~8M	CRS Patients Treated by Physicians Annually3
Nasal obstruction		Nasal discharge		~4M	CRS Patients Failing Medical
and congestion			Management Annually4
Facial pain and		Olfactory loss
pressure

1) Tan BK et al. Am J Respir Crit Care Med, 2013;188(11):1275-7; 2) Battacharrya. Ann Otol Rhinol Laryngol, 2011; Jul;120(7):423-7; 3) Jang et al. Otolaryngol Head Neck Surg, 2018; 4) Baguley et al. Int Forum Allergy Rhinol, 2014;4(7):525-32

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CHRONIC RHINOSIN U SITIS

Current treatments do not control CRS symptoms in the majority of patients

FIRST-LINE THERAPY		SECOND-LINE THERAPY
	Surgical Treatments +
Medical Management
	Medical Management

				65%		20%		100%
	~50%	of patients fail		have		elect		require
	medical management1		recurrent		revision		ongoing
					CRS2		surgery3		medical
										management4

1) Young et al. Allergy Rhinol, 2012; 3:e8-e12; 2) Schaitkin et al. Laryngoscope, 1993; 103; 3) Stein et al. Laryngoscope,2018; 128(1): 31-36; 4) Rosenfeld et al. Otolaryngology-Head and Neck Surgery, 2015; 152(2S)

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CHRONIC RHINOSIN U SITIS

An unmet need for better treatment options exists for most patients

4M400K

fail medical	get surgery1
management

Up to 90%

of patients are left with suboptimal treatment options

1) Young, L. Cet al. Allergy & Rhinology, 2012; 3(1), 8-12

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LY R - 210 & LYR - 220

Designed for the full range of CRS patients treated by an ENT regardless of polyp status

For Surgically Naïve CRS Patients

For Operated CRS Patients

LYR-210		~4M			LYR-220
			60%	40%
Mometasone Furoate	Patients		XL
							Mometasone Furoate

Polyp

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LY R - 2 1 0

Only product candidate designed to provide 6 months of CRS therapy with a single treatment

FDA-approved API/steroid:

Mometasone furoate

Designed to provide continuous treatment as an alternative to surgery

Administered nasally via a single-use applicator

Office-based procedure with topical anesthesia

Middle

Turbinate

Middle

Meatus

Not detectable by patients

Designed to be replaced every 6 months

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LAN TER N PH ASE 2 STUDY

Despite COVID-19, we believe LANTERN significantly de-risked the Phase 3 pivotal study

EfficacyPrimaryEndpoint	EndpointsOther
	LYR-210 (2500 μg)

						Safety & Symptom
	LYR-210 (7500 μg)			Follow-up Post
						Removal
	Control*
Week 4	Week 24 (EOT)	Week 48 (EOS)
		Removal			Safety
		Procedure			Follow up

LANTERN results support selection of dose and timing of the primary symptomatic endpoint for Phase 3

EOT = End of Treatment, EOS = End of Study

*Control = Sham procedure followed by daily saline irrigation

Randomized, Blinded, Controlled, Dose-ranging

Enrollment curtailed at 67 due to COVID-19

• 110 - 150 planned
• 1:1:1 randomization

Evaluated efficacy in adult subjects with CRS who have failed medical management as an alternative to surgery

16 sites in Europe, Australia, New Zealand

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LY R - 2 1 0

LANTERN

PHASE 2 STUDY

Well-tolerated throughout the

24-week treatment period at both doses

WELL-TOLERATED SAFETY PROFILE AT BOTH DOSES

No treatment-related SAEs

Treatment-related AE's in more than 1 subject:

• Epistaxis: 3 subjects at 2500 mcg
• Rhinitis: 3 subjects at 7500 mcg
• Rhinorrhea: 2 subjects at 2500 mcg
• Headache: 2 subjects in control

All treatment-related AEs mild or moderate apart from one event:

• Increased viscosity of upper respiratory secretion at 2500 mcg

Treatment-related AE's in control and 7500 mcg groups

occurred at comparable rates

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LAN TER N PH ASE 2 STUDY

Significant benefit observed along regulatory and clinical measures of efficacy

SinoNasal Outcome Test (SNOT-22)

Global instrument widely used by ENTs in practice

Gold standard validated CRS-specific instrument

22 patient reported questions (0-5 scale, total = 110)

Minimal clinically important difference (MCID) of -8.91

Cardinal Symptom Assessment

Preferred by FDA for regulatory approval in CRS

Sponsor plans to select 2-4 cardinal symptoms:

• Obstruction congestion
• Nasal discharge
• Facial pain/pressure
• Loss of sense of smell

No minimal clinical importance difference (MCID) established

1) Hopkins C et al. Clin. Otolaryngol. 2009, 34, 447-454

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LY R - 2 1 0
LANTERN	DOSE DEPENDENT SYMPTOM
PHASE 2 STUDY
IMPROVEMENT BY 4CS 1 , 2
				LYR-210 (7500µg)		LYR-210 (2500µg)	Control
Rapid symptom improvement		0.0
that becomes more pronounced		-1.0
over 24 weeks	4CSin	-2.0
Found 6-month benefit from a single	CFBL	-3.0					p=0.067
administration		-4.0
				p=0.086		p=0.012	p=0.016
				p=0.021
		-5.0
		0	4	8	12	16	20	24
Showed benefit in both polyp and						Weeks
non-polyp patients

1. 4 cardinal symptom score includes nasal obstruction/congestion, rhinorrhea, facial pain/pressure and anosmia (score of 0-12 based on 7-day average symptom score); 2) Data represents the least square mean. Missing data and data post use of rescue medication was imputed by LOCF method

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LY R - 2 1 0
LANTERN	S Y M P TO M I M P R O V E M E N T B Y S N O T - 2 2 1 , 2
PHASE 2 STUDY	TH E C L I N I C AL G O L D S TAN D AR D
				LYR-210 (7500µg)	LYR-210 (2500µg)	Control
		0
Rapid, durable and clinically
meaningful results based on		-10
gold standard measurement						19 point improvement over control
	22	-20					>2x the MCID of 8.9 points3
	SNOTin -
>2X the MCID of 8.9 points relative	-30						p=0.072
to control	CFBL	-40		p=0.039	p=0.076		p=0.028
						p=0.008		p=0.001
							p=0.001
70% of patients in the 7500 mcg		-50
	0	4	8	12	16	20	24
group improved ≥ MCID at week					Weeks
4; 100% by week 24

1. SinoNasal Outcome Test is a patient reported score from 0 - 110 based on symptoms; 2) Data represents the least square mean. Missing data and data post use of rescue medication was imputed by LOCF method; 3) Minimal clinically important difference

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S N O T- 22 SCORE COMPARISON*

LYR-210 performance is highly competitive

Absolute change of ~40 points and clinically meaningful (>8.9 points) difference relative to control for 7500 mcg dose

CFBL IN SNOT-22 at 16 Weeks

		LYR-210	XHANCE	XHANCE
		LANTERN	NAVIGATE I	NAVIGATE II
	0
SNOT-22	-10
-20
in
CFBL	-30
	-40
		Difference	Difference	Difference
	-50	-15.0		-8.6	-9.7
	1.6x MCID
		TREATMENT	CONTROL

CFBL IN SNOT-22 at 24 Weeks

		LYR-210	DUPIXENT	XOLAIR	XOLAIR
		LANTERN	SINU24	POLYP 1	POLYP 2
	0
22	-10
SNOT-	-20
in
CFBL	-30
	-40
		Difference	Difference	Difference	Difference
	-50	-19.0	-21.1	-16.1	-15.0
	2.1x MCID

TREATMENT CONTROL

*Data from separate trials with different inclusion/ exclusion criteria and patient populations

Sources:

XHANCE: Sindwani, et al., Am J Rhinol Allergy 2019, Vol. 33(1) 69-82; Lepard et al., J Allergy Clin Immunol, 2019;143:126-34

DUPIXENT: Bachert, et al., Lancet 2019; 394: 1638-50

XOLAIR: Gevaert et al, J Allergy Clin Immunol, 2020, 146(3), 595-605

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PATH FORWAR D

Positive Phase 2 results should position Lyra to move forward to pivotal Phase 3 program

Expectations for Phase 3LYR-210 Expected Milestones

Single Phase 3 study with 7500 mcg dose	2021

300 - 350 patients, US-centric

Timing of primary symptomatic endpoint consistent with recent approved products

1 Q	2 Q	3 Q	4 Q
	• End of Ph2 FDA		• LYR-220 Phase 2
	Meeting		start

Timing of Symptomatic Endpoints of Products Approved for CRS with Polyps

Merck	Optinose	Intersect ENT	Regeneron/Sanofi	Novartis/Genentech
Nasonex®	XHANCE®	SINUVA®	DUPIXENT®	XOLAIR®
2004	2017	2017	2019	2020

4-Week	24-Week

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COM M ERCIAL: LYR - 210 /2 2 0

Competitive comparison indicates potential advantages

OptiNose	Regeneron/Sanofi	Intersect ENT		LYR-210/220
Xhance®	Dupixent®		Sinuva®

Steroid nasal spray	Monoclonal antibody	Short-term steroid stent	6-mo continuous
for uncontrolled disease	for surgical relapse	intranasal
(fluticasone, BID)
(anti-IL4, SQ injection)	(mometasone furoate)	steroid therapy

Local effect

Requires no patient compliance

For non-polypand polyp CRS

6-month continuous treatment with one application

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COM M ERCIAL: CURRENT THER APY PRICING

Broad range of price points provides pricing flexibility for LYR-210

	Merck	OptiNose	Intersect ENT	Regeneron/Sanofi		Sinus Surgery
	Nasonex®	Xhance®		Sinuva®	Dupixent®
	Steroid nasal spray	Steroid nasal spray	Short-term steroid stent	Monoclonal antibody	Functional Endoscopic
	for surgical relapse	for uncontrolled disease
	(mometasone furoate, BID)	(fluticasone, BID)		Sinus Surgery
	(mometasone furoate)	(anti-IL4, SQ injection)
ANNUAL	~$3,000	~$6,000 to $11,000	~$10,000		~$36,000		Average
PRICE		~$14,000

Source: Product package inserts and IBM Micromedex RED BOOK

21

COM M ERCIAL: LYR - 210 /2 2 0

Potential to fit well into ENT reimbursement models

Professional Fee	Product Fee
Office procedure	Reimburse via a J-Code
LYR-210/220 placed with nasal endoscopy	Purchase through buy-and-bill or specialty pharmacy
Leverage existing CPT codes	5%-10%mark-up per unit
for placement and removal

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Commercialization

Strategy

Promote product awareness among ENTs and patients

Secure broad payer coverage

Ensure reimbursement confidence and facilitate processing of claims

Limit product acquisition "hassle-factor"

Field Force

(75-100)

Field Based	Market
Reimbursement
Access Team
Experts (15 - 20)
LYRA
	COMMERCIALIZATION
	MODEL

Reimbursement	Product
Support Hub	Distribution

23

INVESTM ENT SUM M ARY

Disrupting the treatment paradigm for intranasal drug delivery, starting with CRS

Developing Long-Acting Intranasal Implants for CRS

• Only therapy to achieve a benefit as much as six months after a single treatment

• 14M Chronic Rhinosinusitis (CRS) patients in U.S.; $6B addressable market

• No FDA approved medicines for non-polyp(70-90% of CRS patients)

Positive LANTERN Phase 2 Results for LYR-210 Announced 4Q 2020

• Rapid, durable, and clinically meaningful symptom improvement

• 100% had clinically meaningful symptom improvement at Week 24 (7500 mcg)

• First implant to demonstrate benefit in both polyps & non-polyps
• Supports pathway to regulatory submission for pivotal trial in 2021

Potential Multiple Expansion Opportunities through XTreoTM Platform

• LANTERN supports XTreo as a tunable, long-acting, local, drug delivery platform
• LYR-220,for CRS patients with prior sinus surgery, expected to enter clinic in 2021

24