Slides
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Actor portrayals. EXXUA™LaunchAytu BioPharma Investor DayJanuary 20, 2026
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IntroductionJosh DisbrowCo-Founder & Chief Executive Officer
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3 Forward Looking StatementsThis presentation includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (“Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (“Exchange Act”). All statements other than statements of historical facts contained in this presentation, are forward-looking statements. Forward-looking statements are generally written in the future tense and/or are preceded by words such as “may,” “will,” “should,” “forecast,” “could,” “expect,” “suggest,” “believe,” “estimate,” “continue,” “anticipate,” “intend,” “plan,” or similar words, or the negatives of such terms or other variations on such terms or comparable terminology. All statements other than statements of historical facts contained in this presentation, are forward-looking statements. These statements are predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others, risks associated with: the Company’s overall financial and operational performance, potential adverse changes to the Company’s financial position or its business, the results of operations, strategy and plans, changes in capital markets and the ability of the Company to finance operations in the manner expected, risks relating to gaining market acceptance of its products, its partners performing their required activities, its anticipated future cash position, regulatory and compliance challenges and future events under current and potential future collaborations. The Company also refers you to (i) the risks described in “Risk Factors” in Part I, Item 1A of the Company’s most recent Annual Report on Form 10 K and in the other reports and documents it files with the United States Securities and Exchange Commission.
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4 Important Safety Information EXXUA is indicated for the treatment of major depressive disorder (MDD) in adults.INDICATIONS AND USAGE Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. EXXUA is not approved for use in pediatric patients. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation.
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5 Select Important Safety InformationEXXUA is contraindicated in patients:●with known hypersensitivity to gepirone or components of EXXUA.●with prolonged QTc interval > 450 msec at baseline.●with congenital long QT syndrome.●receiving concomitant strong CYP3A4 inhibitors.●with severe hepatic impairment.●taking, or within 14 days of stopping, MAOIs due to the risk of serious and possibly fatal drug interactions, including hypertensive crisis and serotonin syndrome. Starting EXXUA in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated. CONTRAINDICATIONS Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation.
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6 ●FDA-approved as a once-daily extended-release tablet for treatment of adults with MDD ●Member of the azapirone class, which includes Buspar® (commercially available as generic buspirone)(approved for anxiety, but not for MDD)●Mechanism of action (MOA) is distinct from SSRIs, SNRIs, and buspirone●Designed to selectively activate pre- and postsynaptic 5-HT1A receptors Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation.Buspar is a registered trademark of Mead Johnson & Company. EXXUA™ is the First and Only Selective 5-HT1A Agonist Approved for MDD in Adults
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7 Aytu BioPharma Executive Team Margaret CabanoSenior VP of OperationsJarrett DisbrowChief Business OfficerJosh DisbrowChief Executive Officer Suzane KennedyVice President of Regulatory Affairs and Quality AssuranceRyan SelhornChief Financial OfficerGreg PyszczymukaChief Commercial Officer Dr. Gerwin WestfieldSenior VP of Scientific Affairs
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8 ●Discuss the 5-HT1A receptor and its clinical importance in Major Depressive Disorder ●Highlight unmet treatment needs and their implications for antidepressant treatment selection in Major Depressive Disorder●Share EXXUA clinical trial data including efficacy and safety●Review Aytu BioPharma’s financials relating to the EXXUA license and the launch plan●Discuss Aytu BioPharma’s EXXUA commercial launch plan●Answer attendees’ questions Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation.Buspar is a registered trademark of Mead Johnson & Company. Today’s Meeting Objectives
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IntroductionGerwin Westfield, PhDSenior Vice President of Scientific Affairs
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10 The 5-HT1A Receptor and Its Clinical Importance in Major Depressive Disorder (MDD)Stephen M. Stahl, MD, PhD, DSc (Hon), DMedSci (Hon, Cambridge)Adjunct Professor of Psychiatry, University of California San DiegoClinical Professor of Psychiatry and Neuroscience, University of California, RiversideHonorary Visiting Senior Fellow, University of CambridgeDirector of Psychopharmacology Services, California Department of State Hospitals
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11 MDD Pathophysiology NorepinephrineDopamine Serotonin The monoamine-deficiency theory of depression proposes that depletion of the neurotransmitters serotonin, norepinephrine, and/or dopamine is a key underlying driver of MDD •Alterations in these neurotransmitters are believed to affect mood regulation and cognitive function Stahl SM. 5th ed. Cambridge University Press; 2021.
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12 Defining Major Depressive Disorder•Depressed mood*•Reduced interest or pleasure in activities*•Unintentional changes in appetite or weight•Insomnia or hypersomnia•Psychomotor agitation or retardation•Fatigue or loss of energy•Feelings of worthlessness or inappropriate guilt•Reduced ability to think, concentrate, or make decisions•Thoughts of death, suicidal ideation, or suicide attempt Symptoms:•Are present almost every day and represent a change in functioning•Cause distress or impairment and are not caused by a substance or another medical condition•Cannot be better explained by other diagnoses DSM-5-TR Criteria *The presence of at least 1 of the 2 symptoms is mandatory for diagnosis.DSM-5-TR, Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition, Text Revision).American Psychiatric Association. 5th ed, text revision. American Psychiatric Association; 2022.
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13 Presynaptic neuronPostsynaptic neuronSynapseNeurotransmitter (5-HT)Receptor Normal Signaling at a Serotonergic Synapse •Most synapses are “asymmetric,” as communication flows from the axon of the first neuron to the second neuron •This means that there are presynaptic elements that differ from postsynaptic elementsStahl SM. 5th ed. Cambridge University Press; 2021. Normal StateMDD State In the MDD disease state•Presynaptic autoreceptors are upregulated•Multiple subtypes of postsynaptic receptors are also upregulated•There is a relative deficiency of serotonin at the synapse
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14 Signaling at a Serotonergic Synapse in MDDPresynaptic neuronPostsynaptic neuronSynapse 5-HT1Aautoreceptor Stahl SM. 5th ed. Cambridge University Press; 2021. In the MDD disease state:•Presynaptic autoreceptors are upregulated•Multiple subtypes of postsynaptic receptors are also upregulated•There is a relative deficiency of serotonin at the synapse
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15 Mechanism of Action: SSRIs and SNRIs ●Activation of the 5-HT1A receptor is thought to promote an antidepressant effect●Activation of the 5-HT2A receptor is associated with sexual dysfunction, insomnia, and anxiety●13 other 5-HT receptor subtypes may be affected○Activation of multiple 5-HT receptor subtypes may affect appetite regulation○Not all subtypes are linked to depression SSRIs and SNRIs flood the synapse with serotonin, nonselectively binding multiple 5-HT receptor types 5-HT, serotonin; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.Stahl SM. 5th ed. Cambridge University Press; 2021.
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16 Reuptake Inhibitors Can Relieve Symptoms but Sometimes at a CostDrugs designed based on reuptake inhibition exhibit some symptom relief but also lead to off-target side effects Clinical Benefits•Improvement in core depressive symptoms vs placebo•Established efficacy across multiple drug classes•Broad symptom coverageoImproved moodoIncreased motivationoBetter sleep/appetite Mechanism-Linked Harms•Sexual dysfunction •Gastrointestinal upset oGut 5-HT signaling•Sleep disturbance, activation, autonomic symptoms•Risk shaped by transporter selectivity and patient factors Reuptake Inhibiting Drugs 5-HT, serotonin.Stahl SM. 5th ed. Cambridge University Press; 2021.
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17 Presynaptic Effects of EXXUA™5-HT1Aautoreceptor •EXXUA™ acts as a full agonist at presynaptic 5-HT1A autoreceptors, enhancing neurotransmission1,2 •5-HT1A agonism at autoreceptors is thought to facilitate downregulation of inhibitory 5-HT1A autoreceptors, reducing inhibition of serotonergic signaling and improving antidepressant efficacy3 EXXUA™Activated receptor 1. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc. 2. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 3. Shad MU. J Pers Med. 2023;13(5):773.
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18 Postsynaptic Effects of EXXUA™1,2 •EXXUA™ acts as a 5-HT1A–specific partial agonist, contributing to its antidepressant action*•EXXUA™ does not have actions at receptors known to be associated with sexual side effects and weight gain 5-HT2A 5-HT1A EXXUA™Activated receptor *A partial agonist is a drug that delivers a submaximal response even at full receptor occupancy.1. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc. 2. Data on file. Clinical Trial Report 134001. Organon Inc. 2001.
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19 Potential Implications for Mood, Anxiety, Cognition, and Stress Circuits Dorsal Raphe Nucleus2•5-HT1A autoreceptors control serotonergic neuron firing and determine serotonergic tone downstream mPFC1•Postsynaptic 5-HT1A modulates E/I balance •Linked to mood regulation, cognitive control, and the antidepressant response VTA1•5-HT1A–induced increases in dopamine signaling may alter motivation and anhedonia Hippocampus2•High density of postsynaptic 5-HT1A receptors•Implicated in mood, stress response regulation, and plasticity effects associated with antidepressant response Amygdala2•Postsynaptic 5-HT1A receptor activation contributes to anxiolytic effects Direction of serotonin signal pathwaysE/I, excitatory/inhibitory; mPFC, medial prefrontal cortex; VTA, ventral tegmental area.1. Díaz-Mataix L, et al. J Neurosci. 2005;25(47):10831-10843. 2. Garcia-Garcia AL, et al. Psychopharmacology (Berl). 2014;231(4):623-636.
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20 FDA-Approved Azapirones1,2 ER, extended-release; IR, immediate-release. 1. BuSpar™ (buspirone). Prescribing Information. Teva Pharmaceuticals, Inc. 2. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc. BuspironeEXXUA™ •Azapirone class: 5-HT1A agonist•Broad, low-affinity interactions, including dopamine antagonism•Dosing: multiple oral IR tablets daily•Half-life: 2 to 3 hours•Indication: management of anxiety disorders or short-term relief of symptoms of anxiety •Azapirone class: 5-HT1A agonist•Highly targeted to 5-HT1A receptor•Dosing: once-daily oral ER tablets•Half-life: 5 hours•Indication: treatment of MDD in adults
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21 Key Takeaways•MDD is thought to be in part caused by depletion of monoamine neurotransmitters across multiple brain regions1 •Nonselective mechanisms of monoamine reuptake–blocking antidepressants frequently cause treatment-emergent adverse events1 •EXXUA™ is a highly targeted 5-HT1A agonist with pre- and postsynaptic actions2,3 •5-HT1A agonism provides antidepressant effect without flooding the brain with serotonin, which can lead to off-target and undesirable side effects4 1. Stahl SM. 5th ed. Cambridge University Press; 2021. 2. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc. 3. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 4. Serretti A, et al. J Clin Psychopharmacol. 2009;29(3):259-266.
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22 Unmet Treatment Needs and Their Implications for Antidepressant Treatment Selection in Major Depressive DisorderAnita H. Clayton, MDWilford W. Spradlin Professor of Psychiatry and Neurobehavioral Sciences, University of Virginia School of MedicineProfessor of Clinical Obstetrics and Gynecology, University of Virginia School of MedicinePresident of the American Society of Clinical Psychopharmacology
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23 Prevalence of MDD: United States •An estimated 21.0 million adults in the US had at least 1 major depressive episode in 2021, representing 8.3% of all US adults•Of those, 14.5 million also experience severe impairment, representing 5.7% of all US adults 20 0 105 15Percent Past-Year Prevalence of MDD Among US Adults (2021) 8.310.36.2 18.6 9.34.57.98.96.74.8 11.2 5.1 13.9 AllFemaleMale18-2526-4950+HispanicWhiteBlack/AAAsianAI/ANNH/OPI≥2SexAge Race/Ethnicity AA, African American; AI/AN, American Indian/Alaskan Native; NH/OPI, Native Hawaiian/Other Pacific Islander.National Institute of Mental Health. Updated July 2023. Accessed December 16, 2025. https://www.nimh.nih.gov/health/statistics/major-depression
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24 Acute and Long-Term STAR*D Outcomes 1020304050607080 Step 1(n=3,671)Step 2(n=1,439)Step 3(n=390)Step 4(n=123) 40.1 16.3 36.8 55.3 19.530.6 64.6 25.613.7 71.1 34.1 13.0 % of patients RelapseIntoleranceRemissionStep 1: Patients begin with SSRI therapyStep 2: Nonremitters move to a structured switch or augmentation strategy to address inadequate responseStep 3: Patients failing Step 2 receive more intensive switch or augmentation optionsStep 4: Persistently nonremitting patients enter final-line therapies, reserved for highly treatment-resistant depressionSTAR*D, Sequenced Treatment Alternatives to Relieve Depression; SSRI, selective serotonin reuptake inhibitor.Rush AJ, et al. Am J Psychiatry. 2006;163(11):1905-1917.
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25 Impact of Tolerability Concerns on Adherence, Persistence, and Quality of Life•50% to 60% of patients fail to achieve remission with first-line SSRIs•Even if they achieve symptom remission, many patients often do not reach full functional recovery (eg, cognitive function, workplace productivity, etc.)•Nearly half of all patients with MDD have been shown to discontinue their first-line treatment•When left untreated, 2/3 of patients with MDD contemplate suicide, and 10% to 15% die by suicide 3 months3 months6 months6 months12 months12 months100% 0%Relapse rate 100% 0%Relapse rate 33% 60% 30% 50%70% After 1 TreatmentAfter 4 Treatments In remissionNot in remissionSSRI, selective serotonin reuptake inhibitor. Stahl SM. 5th ed. Cambridge University Press; 2021.
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26 Switching and Discontinuation Patterns A study of 56,521 outpatients beginning antidepressant therapy found that 8.6% switched medications within the first 90 days1 Among young adults with depression, the switching rate can be as high as ~17.4%2 Many patients who switch may do so because of poor tolerance/adverse effects rather than inefficacy3 In an outpatient survey on SSRI use, patients reporting “moderately or extremely bothersome” side effects had ~3× higher odds of switching within 3 months3 Rates of SwitchingReasons for Switching SSRI, selective serotonin reuptake inhibitor.1. Marcus SC, et al. Psychiatr Serv. 2009;60(5):617-623. 2. Andersson L, et al. Soc Psychiatry Psychiatr Epidemiol. 2022;57(4):647-657. 3. Bull SA, et al. JAMA. 2002;288(11):1403-1409.
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27 Up to65%experience weight gain with long-term use3experience treatment-emergent sexual dysfunction (TESD)1 ●May occur during acute and maintenance phases of treatment4●Can further increase the high risk of obesity and cardiovascular disease in patients with MDD3 ●Low desire/libido, reduced arousal, trouble achieving orgasm, and lack of energy●TESD is associated with worsening depression, diminished relationship satisfaction, lower self-esteem, and even suicidality2 ~50%Sexual dysfunction and weight gain are significant causes of treatment discontinuation with antidepressants1 Common Antidepressant AEs can Exacerbate MDD Of patients taking antidepressants: AE, adverse event.1. Montejo AL, et al. J Clin Psychiatry. 2001;62(suppl 3):10-21. 2. Jacobsen PL, et al. Neurol Psychiatry Brain Res. 2020;36:57-64. 3. Mouawad M, et al. Arch Clin Biomed Res. 2025;9(3):183-195. 4. Deshmukh R, et al. Cleve Clin J Med. 2003;70(7):314-322.
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28 SEXUAL DYSFUNCTION & WEIGHT GAIN The Bidirectional Association Between MDD and Common Antidepressant AEs MAJOR DEPRESSIVE DISORDER Depression increases the risk of sexual dysfunction by 50% to 70%1 and increases the risk of obesity by 58%2 Sexual dysfunction and obesity increase the risk of depression by 130% to 200%1 and 55%, respectively2 bidirectional association 1. Atlantis E, et al. J Sex Med. 2012;9(6):1497-1507. 2. Luppino FS, et al. Arch Gen Psychiatry. 2010;67(3):220-229.
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29 Implications for EXXUA™ Positioning in Clinical Practice1-3 EXXUA™ does not carry a warning about the risk of sexual dysfunction unlike many antidepressants that act on serotonin receptors●Sexual dysfunction was not reported as an AE with an incidence ≥2% and greater than placebo in pooled MDD studies No clinically significant increase in body weight compared with placebo ●Mean increase of 1 kg with EXXUA™ vs 0 kg with placebo in Study 1 and 0.3 kg with EXXUA™ vs 0.1 kg with placebo in Study 2 ●No weight-related AEs were observed in long-term extension studies AE, adverse event.1. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005. 3. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc.
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30 EXXUA™ Demonstrates a Neutral Sexual Profile -1-0.500.511.522.533.5 -1-0.500.511.522.533.5MenWomen Change in DISF-SR domains score *High rates of missing DISF-SR data led to a prespecified decision (prior to unblinding) not to conduct inferential statistical testing.DISF-SR, Derogatis Inventory for Sexual Function–Self-Report.Data on file. Clinical Trial Report 134001. Organon Inc. 2001. Domain 1 PlaceboEXXUA™ Domain 1Sexual Cognition/ FantasyDomain 2 Sexual Arousal/ Excitement Domain 3Sexual Behavior/ ActivityDomain 4 Orgasm/Ability to Reach OrgasmDomain 5Sexual Satisfaction/ Relationship SatisfactionDomain 5Domain 2Domain 3Domain 4Domain 1Domain 5Domain 2Domain 3Domain 4
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31 Key Takeaways•21.0 million adults in the US live with MDD1•Many patients discontinue or switch treatments due to bothersome side effects2•The safety and tolerability of EXXUA™ have been established in over 1,900 patients3•EXXUA™ provides antidepressant efficacy without causing sexual dysfunction or clinically significant weight gain4,5 1. National Institute of Mental Health. Updated July 2023. Accessed December 16, 2025. https://www.nimh.nih.gov/health/statistics/major-depression 2. Bull SA, et al. JAMA. 2002;288(11):1403-1409. 3. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc. 4. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 5. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005.
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32 Christoph Correll, MDProfessor of Psychiatric Neuroscience, Institute of Behavioral Science, Feinstein Institutes for Medical ResearchProfessor, Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellProfessor and Chair, Department of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy, Charité University Medicine EXXUA™ Clinical Trial Data: Efficacy and Safety
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33 Primary and Secondary Endpoints Study 11 and Study 22 were 8-week, randomized, double-blind, placebo-controlled, flexible-dose, Phase 3 studies in adults with MDD Treatment schedule: Initial dosage of 18.2 mg once daily was titrated to 36.3 mg once daily on Day 4. Dosage could be increased to 54.5 mg once daily after Day 7 and 72.6 mg once daily after an additional 7 daysPrimary efficacy measure: Change from baseline in the 17-Item Hamilton Depression Rating Scale (HAM-D17) total score at Week 8 Secondary endpoints: Included change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression–Severity (CGI-S) at Week 8 1. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005.
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34 Baseline CharacteristicsStudy 1 (N=202)1Study 2 (N=238)2 Mean age39 38Female 61%68%Race Caucasian73%65%Black 9%23%Other 18%12%Course of illnessFirst episode33%23%Chronic 15%8%Recurrent after partial recovery19%10%Recurrent after full recovery33%59%1. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005.
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35 EXXUA™ Demonstrates Significant Symptom Improvement Compared With Placebo (1 of 4)1,2 ●EXXUA™ demonstrated statistically significant improvement from baseline in the HAM-D17 total score at Week 8 vs placebo (P=0.018 and P=0.032, respectively)In Study 1 and 2 Treatment groupMean baseline scoreLS mean change from baseline Placebo-subtracted difference (95% CI) Study 1EXXUA™ (n=101)(18.2 to 72.6 mg/day)22.7−9.04 −2.47(−4.41, -0.53)Placebo (n=103)22.8−6.75 Study 2EXXUA™ (n=116)(18.2 to 72.6 mg/day)23.9−10.22−2.45(−4.47, −0.43)Placebo (n=122)24.2−7.96 Change from baseline in the HAM-D17 total score at Week 8In Study 1, the final dose of EXXUA™ was 72.6, 54.5, and 36.3 mg/day in 64%, 20%, and 17% of patients, respectively.In Study 2, the final dose of EXXUA™ was 72.6, 54.5, 36.3, and 18.2 mg/day in 66%, 22%, 10%, and 2% of patients, respectively. CI, confidence interval; LS, least-squares.1. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005.
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36 EXXUA™ Demonstrates Significant Symptom Improvement Compared With Placebo (2 of 4)1,2 Mean Change From Baseline in HAM-D17 Total Score by Treatment Week1 *Percentage of patients at each final dose strength: 72.6 mg (66%), 54.5 mg (22%), 36.3 mg (10%), and 18.2 mg (2%).1†P=0.032 vs placebo.2LS, least-squares; SE, standard error.1. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005. Statistically significant separation from placebo as early as 3 weeks
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37 EXXUA™ Demonstrates Significant Symptom Improvement Compared With Placebo (3 of 4)Mean MADRS Total Score by Treatment Week353025 15 5 20 10 Baseline2468 ******** Mean ± SE MADRS Score **P<0.01; ***P<0.005.SE, standard error.Bielski RJ, et al. J Clin Psychiatry. 2008;69(4):571-577.
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38 EXXUA™ Demonstrates Significant Symptom Improvement Compared With Placebo (4 of 4)VariableEXXUA™ (N=116),mean±SEPlacebo (N=122),mean±SEP valuea HAM-D17 Baseline23.9±0.324.2±0.3Mean change−10.2±0.8−8.0±0.70.032MADRSBaseline30.3±0.330.8±0.3Mean change−13.7±1.0−9.9±1.0b0.008HAM-D28 Baseline33.9±0.534.3±0.5Mean change−15.0±1.1−11.8±1.00.032 HAM-D6 Baseline12.6±0.113.0±0.1Mean change−5.6±0.4−4.2±0.40.016 CGI-S Baseline4.3±0.14.3±0.1Mean change−1.3±0.1−0.9±0.1b0.015 aChange from baseline to Week 8 (reduced model without center attraction); EXXUA™ vs placebo, least mean squares approach. bN=121. HAM-D6, 6-Item Hamilton Depression Rating Scale; HAM-D28, 28-Item Hamilton Depression Rating Scale; SE, standard error.Bielski RJ, et al. J Clin Psychiatry. 2008;69(4):571-577.
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39 40 Reduction in HAM-D17 Measures With EXXUA™Proportion of Patients With MDD Treated With EXXUA™ (N=116) or Placebo (N=122), as Assessed by the HAM-D17 ***** **** 01020304050Percentage of patients Percentage of patients RespondersRemitters 23468Time (weeks)23468Time (weeks) PlaceboEXXUA™ PlaceboEXXUA™ Responders are patients who experienced at least a 50% reduction from their baseline scoreRemitters are patients with a HAM-D17 total score ≤7 *P<0.05; **P<0.01.Bielski RJ, et al. J Clin Psychiatry. 2008;69(4):571-577. 0102030 50
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40 No Treatment-Emergent Sexual Dysfunction *High rates of missing DISF-SR data led to a prespecified decision (prior to unblinding) not to conduct inferential statistical testing.DISF-SR, Derogatis Inventory for Sexual Function–Self-Report.Data on file. Clinical Trial Report 134001. Organon Inc. 2001. DISF-SR scores showed no signal of TESD among EXXUA™-treated subjects who completed assessments -2024681012 MaleFemale PlaceboEXXUA™ Change in DISF-SR score* •Higher DISF-SR scores indicate improved sexual functioning •Similar patterns favoring EXXUA™ were observed across the 5 DISF-SR domains oDesire, arousal, sexual behavior, orgasm, and drive•EXXUA™ was not associated with TESDn=20n=32n=47n=47
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41 No Clinically Significant Increase in Body Weight Compared With Placebo 1. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005. Treatment groupMean weight change≥7% weight gainOverall signal Study 11 EXXUA™ (n=101)(18.2 to 72.6 mg/day)+1.0 kgRare, no difference between groups Small, clinically insignificant mean increase Placebo (n=103)0.0 kgNo meaningful weight gain Study 22 EXXUA™ (n=116)(18.2 to 72.6 mg/day)+0.3 kgRare, no difference from placeboNo meaningful weight gain in either groupPlacebo (n=122)+0.1 kg
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42 Safety Considerations With 5-HT1A–Selective Agents: Overview Most common adverse reactions were dizziness, nausea, insomnia, abdominal pain, and dyspepsia1 •≥5% and twice the incidence of placebo Dizziness was mild to moderate and transient2 •Incidence dropped from 33.9% at Week 1 to 19% by Week 2 and 2.9% by Week 6 in Study 2 Safety and tolerability of EXXUA™ were evaluated in 1,976 adult patients with MDD in Phase 2 and 3 clinical studies1 AE, adverse event.1. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005. Discontinuation due to AEs was 3% for placebo and 7% for EXXUA™2 •No treatment-related serious AEs led to discontinuation, and no deaths occurred in the studyAEs reported with EXXUA™ were predominantly early in onset and time limited, with rapid attenuation over the first several weeks of treatment
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43 Full Profile of AEs From Clinical Trial DataAdverse reactionPlacebo (n=230) (%)EXXUA™ 18.2 to 76.2 mg (n=226) (%)Dizziness*10 49Nausea13 35Headache*20 31Feeling sleepy or tired*14 15Insomnia*5 14Diarrhea9 10Upper respiratory tract infection7 8Dry mouth5 8Vomiting4 7Abdominal pain*3 7Dyspepsia2 6*The following terms were combined: dizziness=lightheadedness, dizziness, dizziness postural; headache=headache, sinus headache, tension headache; feeling sleepy or tired=fatigue, sedation, somnolence; insomnia=initial insomnia, insomnia, middle insomnia, terminal insomnia; abdominal pain=abdominal discomfort, abdominal pain, abdominal pain upper.AE, adverse event.Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005.
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44 Full Profile of AEs From Clinical Trial DataAdverse reactionPlacebo (n=230) (%)EXXUA™ 18.2 to 76.2 mg (n=226) (%)Increased appetite3 5Constipation3 4Nasopharyngitis3 4Nasal congestion2 4Paresthesia1 4Hyperhidrosis0 4Palpitations0 4Weight increased1 3Agitation0 3Feeling jittery0 3Heart rate increased0 2Lethargy0 2 AE, adverse event.Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005.
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45 QTc Warning and Mitigation Strategies ●ECG prior to initiating EXXUA™ is recommended during dosage titration and periodically during treatment●Correct for electrolyte abnormalities prior to initiating EXXUA™ ECG monitoring EXXUA™ prolongs the QTc interval●The largest mean increase in QTc interval was 18.4 msec at 2-fold the exposure of the maximum recommended dose (100 mg) with an immediate-release formulation, which was discontinued●No reported cases of QT prolongation as an AE in either of the Phase 3 trials Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation. AE, adverse event; ECG, electrocardiogram.EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc.
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46 Key Takeaways1-3 •Study 1 and Study 2 were 8-week, randomized, double-blind, placebo-controlled, flexible-dose, Phase 3 studies in adults with MDD•In these studies, EXXUA™ demonstrated significant improvement from baseline in MADRS total score by Week 4•Statistically significant remission in symptoms was achieved over placebo as early as Week 3 as assessed by HAM-D17 score changes•No signal was detected for TESD or clinically significant weight gain•EXXUA™ prolongs the QTc interval, and ECG monitoring is recommended•Discontinuation due to AEs was 7% for EXXUA™, and all common AEs were described as mild-to-moderate, which tended to resolve early in treatmentAE, adverse event; ECG, electrocardiogram.1. Data on file. Clinical Trial Report 134001. Organon Inc. 2001. 2. Data on file. Clinical Study Report FKGBE007. Fabre-Kramer Pharmaceuticals, Inc. 2005. 3. EXXUA™ (gepirone). Prescribing Information. Fabre-Kramer Pharmaceuticals, Inc.
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47 Q & A
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48 Financial OverviewRyan SelhornChief Financial Officer
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49 EXXUA Key Deal Terms•Fixed Payments:•$3M paid at execution•Additional $3M paid within forty-five (45) days of 1st anniversary of Commercial Launch•Second upfront payment increases to $5M if Net Sales for the first 12 months > $35M•Royalties (% of Net Sales):•28% ‘base’ royalty•3% cap on cost of goods sold•Increased royalty rate if annual Net Sales are greater than $300M•Upon royalty trigger or LOE, royalty rates are reduced•Milestone payments beginning at $100 million in annual Net Sales•$5 million milestone payment paid at $100 million
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50 Financial Highlights•$32.6 million in cash as of 9/30/25•No additional cash requirement expected through profitability •TTM Adjusted EBITDA of $6.7M•TTM operating cash burn of $1.4M•Original EXXUA launch investment budget of $10M reduced to $6-8M due to efficiencies & cost management•EXXUA expected gross margin of 66-68%•Compares to TTM companywide GM of 67.6% •Term loan outstanding of $12.5M as of 9/30/25•Reduced high interest liabilities by $7.4M in TTM
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Commercial Launch PlanJosh DisbrowCo-Founder & Chief Executive Officer
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52 EXXUA: A Clear Position in the MDD Market EXXUA has a unique profile due to its MOA, which helps explain the lack of impact on sexual function or weight – key issues for many MDD patients BrandNovel Mechanism of ActionNo Impact of Sexual FunctionWeight Neutral Once Daily DosingEXXUA™ SSRIs SNRIs Wellbutrin®/Bupropion Trintellix® Auvelity® Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation.
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Commercial Launch PlanGreg PyszczymukaChief Commercial Officer
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54 EXXUA Promotional Mix & Commercial Priorities •Efficient, multi-faceted launch with emphasis on sales force promotion and metrics-based performance management •Targeted virtual promotion and pull-through to support broad customer adoption•Focused non-personal, web-based promotion to increase brand awareness and adoption•Broad Aytu RxConnect footprint for enhanced patient access, adoption, & adherence•Full retail distribution to achieve broad-based availability•New Chemical Entity (NCE) education led by cost-effective Medical Affairs-led publication and KOL support EXXUA Launch FocusSales force promotion Broad Aytu RxConnect Full retail distribution New Chemical Entity (NCE) education Strategic payor assessments Focused non-personal, web-based promotion Targeted virtual HCP promotion Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation.
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55 Focused on Psychiatric Practices Aligned to psychiatry with existing Aytu relationships to maximize initial launch: Brand centricAligned to Aytu RxConnect pharmacies High antidepressant Rx volume Sources: 1. Symphony PrescriberSource® PayerFocus – 12 months ending Nov 25; patients aged 18+, approved HCP specialties only; 2. dbo.rpt_copay_detail_bc; 12 months ending Nov 25; 3. Symphony Metys® - USC 64300 – 12 months ending Nov 25; patients aged 21+ and unknown •Annual MDD Market Opportunity:•Aligned Territories: 140.0 million TRx1 •Target HCPs: 18.5 million TRx1 •~5,500 Target HCPs at initial launch1 •100% of Target HCPs are aligned RxConnect pharmacies2 •>50% of branded product TRx volume written by psychiatrists3 High EXXUA Potential
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56 Commercial Infrastructure ●Lean, direct sales force covers core branded MDD prescribers in our current sales footprint●Sales force augmented by rolling CSO model to support rapid expansion opportunities●Further support enabled through in-house analytics platform, virtual/tele-sales and select, efficient direct-to-patient initiatives Efficient, experienced, and leverageable commercial infrastructure for Rx Portfolio through initial 40 territories allows for rapid scalable promotional expansion opportunities Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation.
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57 Aytu RxConnect Patient Access Program ●Developed in-house to drive patient adherence and increased script pull-through of Aytu’s Rx brands●Over 1,000 pharmacies nationwide with 100% sales territory coverage; fully supported by in-house pharmacy support team●Offers prescribers and patients predictable, hassle-free, and affordable access to Aytu brands for all commercially insured patients●Reduces pharmacy call backs relating to access barriers (availability, coverage, prior authorizations, step edits, etc.)●Increases Rx ‘stickiness’ through greater patient adherence (i.e., higher refill rate) Aytu RxConnect is a proprietary, best-in-class patient access program, supported by an efficient commercial infrastructure, to support patient access to Aytu Rx products. Please see Important Safety Information throughout and Full Prescribing Information for EXXUA at this presentation. Rx Connect Platform Best-in-class Analytics Specialty Distributors & Partners Non-personal Promotion Focused SpecialtySales Force
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58 Q & A
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