Reviva Pharmaceuticals : Corporate Presentation

REVIVA PHARMACEUTICALS HOLDINGS, INC.

Corporate Presentation

Corporate Presentation, October 2022

Forward Looking Statements

This presentation contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's RECOVER Phase 3 trial, product development and clinical trial plans, clinical and regulatory timelines, trial results, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth and financing opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions. These statements may be identified by the use of forward- looking expressions, including, but not limited to, "expect," "anticipate," "intend," "plan," "believe," "estimate," "potential," "predict," "project," "should," "would" and similar expressions and the negatives of those terms. These statements relate to future events or the Company's financial performance and involve known and unknown risks, uncertainties, and other factors, including the potential impact of the COVID19 pandemic and the potential impact of sustained social distancing efforts, on the Company's operations, clinical development and clinical trial plans and timelines, which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this presentation. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

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Key Business Highlights

Company

Overview

Clinical-stage pharmaceutical company developing new therapies for central nervous system, respiratory, and metabolic diseases

Chemical genomics driven discovery approach

IL-18;Interleukin-18.

Strong patent portfolio

Lead Asset:

Brilaroxazine

Differentiated pharmacology profile as modulator of serotonin and dopamine signaling pathways

Prioritizing ongoing pivotal Phase 3 trial in schizophrenia with topline data anticipated in mid-2023

Potential for clinical expansion in additional neuropsychiatric disorders and lung diseases

Market

Opportunity

Global addressable market size for brilaroxazine:

$10.1 B for schizophrenia by 20281 $6.2 B for bipolar disorder by 20272 $24.5 B for MDD by 20303

$29.3 B for ADHD by 20284 $11.0 B for PAH by 20305 $6.2 B for IPF by 20306

1.Schizophrenia: Verified Market Research 2021	3.	MDD: Research and Markets.Com, 2021	5.	PAH: Grand View Research, 2022
2.Bipolar Disorder: Maximize Market Research 2021	4.	ADHD: Verified Market Research, 2022	6.	IPF: Allied Market Research, 2022

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Extensive Clinical Development Pipeline

Program

Brilaroxazine - Serotonin/ dopamine modulator (NCE)

RP1208 - Triple reuptake inhibitor (NCE)

Neuropsychiatric

Pulmonary

Prioritized Target Indications*		Development Phase
Discovery	Preclinical	Phase I		Phase II	Phase III
Schizophrenia				Ongoing

Bipolar Disorder

Major Depressive Disorder

Attention Deficit Hyperactivity

Disorder

Pulmonary Arterial Hypertension

Idiopathic Pulmonary Fibrosis

Depression

Obesity

*Opportunity to expand into other indications including Parkinson's Psychosis and Alzheimer's (Psychosis/agitation)

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Addressing Significant Unmet Medical Needs

	Neuropsychiatric Programs		Pulmonary Programs
Schizophrenia	Major Depressive	Bipolar Disorder	ADHD	Pulmonary Arterial	Idiopathic Pulmonary
Disorder	Hypertension (PAH)	Fibrosis (IPF)

$10.1B		$6.2B		$6.2B
	by 20272
by 20281		$11.0B	by 20306
$24.5B
	$29.3B
	by 20303	by 20305
		by 20284

1.Schizophrenia: Verified Market Research 2021	3.	MDD: Research and Markets.Com, 2021	5.	PAH: Grand View Research, 2022
2.Bipolar Disorder: Maximize Market Research 2021	4.	ADHD: Verified Market Research, 2022	6.	IPF: Allied Market Research, 2022

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Dysfunctional Serotonin Signaling is Implicated in the Pathobiology of Psychiatric Disorders and Lung Diseases

• Brilaroxazine is a potent modulator of serotonin and dopamine signaling pathways
• Dysfunctional serotonin and dopamine signaling pathways are implicated in the pathobiology of neuropsychiatric diseases
• Dysfunctional serotonin signaling is implicated in the pathobiology of lung diseases, PAH and IPF

Bhat L. Nature 2021, 15(2): B24; Bhat L. et al, J Neurology & Neuromedicine 2018, 3(5):39-50; Bhat L. et al, European J Pharmacology 2018, 827:159-166.

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Neuropsychiatric Programs

Schizophrenia | Bipolar Disorder | Major Depressive Disorder | ADHD

Schizophrenia Prevalence and Unmet Needs

No Therapies Adequately Address Symptoms of Schizophrenia

Schizophrenia affects ~1.1% of the world's	Need for therapies that adequately address the
population and ~3.5 million people in the	complex mix of positive & negative symptoms,
US1 and ~24 million globally2	mood, and associated cognitive impairment3

	Suboptimal		Poor Tolerability/
	Efficacy4,5,6		Side Effects5
Not all symptoms addressed	Poor Tolerability/Side Effects
•	Negative symptoms	•	Neurological (EPS, akathisia)
•	Cognitive deficits	•	Endocrine (hormones
•	Mood symptoms		imbalance, sexual dysfunction)
		•	Metabolic (obesity, diabetes,
			cholesterol)

High Discontinuation/

Non-Compliance6,7

Estimated discontinuation rates

• 30-50%in short-term treatment of acute patients
• 42-74%in long-term treatment of stable patients

1. Mentalhealth.net American Addiction Centers Resource,https://www.mentalhelp.net(March 18, 2022)
2. https://www.who.int/news-room/fact-sheets/detail/schizophrenia(March 18, 2022)
3. Mentalhealth.net American Addiction Centers Resource,https://www.mentalhelp.net/schizophrenia/statistics/(April 24, 2021)
4. Torres-GonzalezF et al, Neuropsychiatric Disease and Treatment 2014, 10:97-110.

1. Stroup T S and Gray N, World Psychiatry 2018, 17:341-356.
2. Bhat L et al, J Neurology and Neuromedicine 2018, 3(5): 39-50.

7. Levin, S.Z. et al., Schizophrenia Research 2015, 164:122-126

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Psychiatric Disorders are Primarily Driven by Dysfunctional Serotonin and Dopamine Signaling

Targeting serotonin and dopamine receptors can treat schizophrenia and comorbid symptoms

D2, D3, D4	5-HT1A,5-HT2A,
5-HT2B,5-HT7

Cognitive

Positive deficits symptoms

5-HT1A,5-HT2A,

5-HT2B,5-HT7

Mood

Negative

symptoms Agitation

5-HT1A,5-HT2A,

5-HT2B, D4

D1, D2, D4,

5-HT2A,5-HT2B,5-HT7

DA and 5-HT drive pathobiology and symptom domains in schizophrenia, bipolar disorder, major depressive disorder, and attention/deficit hyperactivity disorder

GlutamateGABA

Serotonin

Dopamine

Muscarinic	Nicotinic
Receptors	Receptors

Glutamate, GABA, muscarinic and nicotinic receptors are downstream targets which are affected by dysfunctional dopamine and serotonin signaling system

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Serotonin and Dopamine Receptors are Primary Targets for Approved Antipsychotics

1st-Generation	2nd-Generation	3rd-Generation	Next-Generation
Dopamine D2 Receptor	Dopamine & Serotonin	Dopamine & Serotonin	Dopamine & Serotonin
Antagonists	Partial	Partial
Receptor Antagonists
	Agonist/Antagonist	Agonist/Antagonist
Positive Symptoms	Positive >>> Negative Symptoms	Positive > Negative Symptoms	Negative >> Positive > Cognition, Depression
Haldol	Risperdal, Zyprexa, Seroquel	Abilify	Brilaroxazine - Phase 3 underway
D	D2 / 5-HT2A	D /	5-HT	D2/4 / 5-HT2A/2B/7
2		2	2A

Developmental antipsychotics against downstream targets have failed to demonstrate clinically acceptable efficacy and/or safety

Bitopertin (Roche)

Phase 3

Discontinued

Glutamate

Receptor

	MK-0777 (Merck)
	Phase 2/3
	Discontinued
GABA	Nicotinic
Receptor	Receptor

Encenicline (Forum)

Phase 3

Discontinued

Bradanicline (Targacept)

Phase 2

Discontinued

Xanomeline (Eli Lilly)

Phase 2

Discontinued

Muscarini

1. Receptor

Bitopertin: https://en.wikipedia.org/w/index.php?title=Bitopertin&oldid=992765453" (March 18, 2022); MK-0777:https://adisinsight.springer.com/drugs/800024505(March

18, 2022); Encenicline: https://adisinsight.springer.com/drugs/800027229(March 18, 2022); Bradanicline: https://en.wikipedia.org/wiki/Bradanicline(March 18, 2022);

Xanomeline: https://adisinsight.springer.com/drugs/800001727(March 18, 2022)

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