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1 TI ERUMherapeutics TI ERUMherapeutics Investor Presentation
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2 TI ERUMherapeutics This presentation contains estimates and other statistical data made by independent parties and by us relating to market shares and other data about our industry. This presentationalso containsforward-looking statementswithin the meaning of The Private SecuritiesLitigationReform Act 1995. These forward-looking statementsinclude,without limitation,statementsregarding the Company’sindustry,business strategy,plans, goals and expectationsconcerningits market position,product expansion,future operations, margins, profitability,future efficiencies,and other financial and operating information. In some cases, forward-looking statementscan be identified by words such as “may,” “believes,”“intends,”“seeks,” “anticipates,”“plans,” “estimates,”“expects,” “should,” “assumes,” “continues,”“could,” “will,” “future,” “potential” or the negative of these or similar terms and phrases. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the Company’s actual results, performanceor achievementsto be materiallydifferentfrom any future results,performanceor achievementsexpressedor implied by the forward-lookingstatements. Forward- looking statements include all matters that are not historical facts. Actual future results may be materially different from what is expected due to factors largely outside the Company’scontrol,includingrisks and uncertaintiesconcerningthe outcome,impact, effects and resultsof the Company’spursuit of strategicalternatives,includingthe terms, timing, structure,value, benefits and costs of any strategic process and the Company’s ability to complete a strategictransactionat all, the Company’s ability to successfully prepare and implement commercializationplans for ORLYNVAH with a commercial partner or directly, including the Company’s ability to raise sufficientcapital, build and maintain a sales force and prepare for commerciallaunch of ORLYNVAH , if the Company is unsuccessfulat enteringinto or completinga strategictransaction,the ability of shareholdersand other stakeholdersto realize any value or recoveryas part of a wind down process if the Company is unsuccessfulat entering into or completinga strategic transaction or preparing and implementingcommercializationplans for ORLYNVAH , the market opportunityfor and the potential market acceptance of ORLYNVAH for uncomplicatedurinarytract infectionscausedby certaindesignatedmicroorganismsin adult women who have limitedor no alternativeoral antibacterialtreatmentoptions,the uncertaintiesinherentin the initiationand conductof clinicaland non-clinicaldevelopment,changesin regulatoryrequirementsor decisionsof regulatoryauthorities,changesin public policy or legislation,commercializationplans and timelines,the actions of third-party clinical research organizations,suppliers and manufacturers,the accuracy of the Company’sexpectationsregardinghow far into the futureits cash on hand will fund its ongoingoperations,the sufficiencyof the Company’scash resourcesand the Company’s abilityto continueas a going concern,the Company’sabilityto maintainits listingon the Nasdaq CapitalMarket,and other factorsdiscussedunder the caption“Risk Factors”in the Company’sQuarterlyReport on Form 10-Q for the quarterended September30, 2025 and the other documentsthe Companyfiles with the SEC from time to time. Forward- lookingstatementscontainedhereinrepresentthe Company’sbeliefsand assumptionsonly as of the date of this presentation. Exceptas requiredby law, the Companydoes not assume any obligationto update these forward-lookingstatementspublicly,or to update the reasonsactual resultscould differ materiallyfrom those anticipatedin the forward- lookingstatements,even if new informationbecomesavailablein the future. Certain informationcontainedin this presentationrelatesto, or is based on, studies,publications,surveys and other data obtainedfrom 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 been independently verified, and neither we nor the Company make any representationas to the adequacy, fairness, accuracy or completenessof, any information obtained from third-party sources. In addition,all of the market data includedin this presentationinvolvesa number of assumptionsand limitations,and there can be no guaranteeas to the accuracyor reliabilityof such assumptions. Finally,whilethe Companybelievesits own internalresearchis reliable,such researchhas not been verifiedby any independentsource. Important Notice & Disclaimers
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3 TI ERUMherapeutics ● ORLYNVAHTM, a penem antibiotic, for the treatment of uncomplicated urinary tract infections (uUTIs), was approved by the FDA in October2024 – ORLYNVAHTM is a proprietary, patent-protected bilayer tablet combining the prodrug, sulopenem etzadroxil, with probenecid – First and only FDA-approved oral penem; indicated for treatment of uUTIs in the community – ORLYNVAHTM has a targeted spectrum of activity against relevant pathogens most likely to cause urinary tract infections – ORLYNVAHTM has demonstrated a favorable safety profile across four Phase 3 clinical trials ● ORLYNVAHTM is the first new treatment commercially launched in the United States (August 2025) for uUTIs in the last 25 years – Multi-drug resistant bacteria are a significant and growing global health threat – Significant U.S. market for uUTI therapies, estimated at approximately 40 million prescriptions annually1 ● Approximately 2/3 or 26 million of those prescriptions2 are written for at-risk patients3, which would be the target patients for sulopenem ● The four leading oral treatments for uUTI account for ~75% of the prescription market4 but have resistance rates near or above 20%5 and all have additional safety concerns ● Lack of innovation in an underserved area of women’s health ● ORLYNVAHTM is well positioned relative to other potential new market entrants ● ORLYNVAHTM has a long runway to capture value – Combination of patents and data protection in the U.S. expected to provide protection into 2039 ● Patent information for four U.S. patents for ORLYNVAHTM are listed in FDA’s Orange Book – Foreign patent protection expiring no earlier than 2039 (JP, AU, KR, MX, CN) – Iterum also has an IV formulation of sulopenem for complicated infections in a hospital setting but does not plan to pursue U.S. approval, at this time Executive Summary 1 Extrapolated from EVERSANA METYS Pharmacy Claims, EVERSANA ACTICS Data and Medical Claims and previous market research 2 Extrapolated from Eversana longitudinal medical and pharmacy claims 3 At-risk patients are elderly, diabetic, have a history of recurrent infections or other co-morbidities that negatively impact their immune system 4 Extrapolated from EVERSANA METYS Pharmacy Claims, EVERSANA ACTICS Data and Medical Claims, and previous market research 5 Dunne MW et al. A multicenter analysis of trends in resistance in urinary Enterobacterales isolates from ambulatory patients in the United States: 2011–2020. BMC Infect Dis. 2022;22:194
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4 TI ERUMherapeutics ● Despite growing rates of antimicrobial resistance, there have been no new antimicrobial therapies launched over the last three decades in the uUTI space. ● At-risk uncomplicated urinary tract infections (uUTI) patients – due to age, co-morbidities history of recurrent infections, or suspected resistance - are most in need of new alternatives. ● Orlynvah now provides at-risk adult women with uUTI with a potential novel solution that they have needed. ● As the first oral penem therapy, Orlynvah brings the demonstrated efficacy and safety of IV penem therapies used in the hospital, to at-risk patients in the community that are in need of new alternatives. ● Orlynvah is a proprietary, patent-protected bilayer tablet combining the prodrug, sulopenem etzadroxil, with probenecid – One tablet twice per day for 5 days – Orlynvah demonstrated higher response rates compared to amoxicillin clavulanate and increased response rates compared to ciprofloxacin in quinolone resistant infections – Orlynvah demonstrated safety in two pivotal uUTI clinical trials ● Orlynvah is a unique and highly differentiated new treatment as the first and only oral penem product approved by the FDA The Launch of ORLYNVAHTM Is a Significant Advance
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5 TI ERUMherapeutics ● Launched on August 20, 2025 – Q3 2025 product sales of $0.4M (includes some stocking of specialty pharmacy locations serving our geographies) ● Over 100 unique physician prescribers in the first few months post-launch – Approximately half of those physicians have prescribed Orlynvah to more than one patient ● Current fill rate of prescriptions is approximately 40% - expect that ratio to increase with payer decisions around coverage and access ● Health care providers see the utility in Orlynvah for their patients – Physicians are pleased to have a new, oral option to treat their uUTI patients – Clinical experience has been solid, as expected ● Early Orlynvah usage has included women with recurrent infections (more than 1 uUTI within 3 months) as well as usage to avoid hospital admissions to receive IV therapy ● High interest from key thought leaders and group practices which have generated follow-up discussions Orlynvah Performance Highlights
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6 TI ERUMherapeutics ● Positive feedback from both Pharmacy Benefit Managers (PBMs) and health plans across both commercial and Medicare Part D formularies ● Iterum’s National Account Managers continue to engage strategically with key stakeholders across the U.S. payer landscape, highlighting Orlynvah’s differentiated value proposition ● Received a signed rebate agreement with one of the top 3 Medicare Part D PBMs; enables Orlynvah to be added to their Medicare Prescription Drug plan and Medicare prescription drug plan formularies for coverage beginning in 2026 or 2027, depending on individual plan structures ● Submitted bids to commercial and Medicare Part D PBMs; aiming to secure long term formulary positioning later this year and into Q1 2026 ● Coverage now approximately 16% of insured lives, with increasing adoption by employer groups and payer formularies integrating Orlynvah into their standard benefit design Orlynvah Market Access Highlights
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7 TI ERUMherapeutics ● Specialty Pharmacy Distribution – We currently have 10 targeted geographies with field representatives; these representatives continue to call on their existing target physicians – Supplemental resources to be added during Q4 2025; additional field representatives as well as virtual sales representatives to increase reach and efficiency – With the combination of the existing and supplemental resources, we expect to provide equivalent coverage of at least 20 target geographies ● Traditional Specialty Distribution – In order to satisfy inquiries from physicians outside of our called-on network, specialty distribution has been established with McKesson and Cencora Orlynvah Sales Territory Coverage
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8 TI ERUMherapeutics BacterialResistanceDrivingNeedforNewOralTherapies High resistancerates affectingthe most populousregions of the U.S. Nonduplicate (first isolate of a species within 30 days), noncontaminant Enterobacterales urinary isolates from ambulatory ad ult patients (≥18 years) from 338 ambulatory care facilities across the United States. A ESBL-producing (913,343 isolates) BFluoroquinolone Nonsusceptible (970,219 isolates); Source:Aronin, et al International Journal of Infectious Diseases 2022;119:142-145; Data and analyticsprovidedby BD Insights Research Database. >20% of outpatient urinary gram-negative isolates are resistant to quinolones in the most populous areas of the U.S. • Penems are the recommended treatment for ESBL-producing Enterobacterales infections. • ~10% of community urinary tract infections are due to an ESBL-positive organism • OrlynvahTM is the only approved ORAL penem antibiotic in the U.S. Geographic Distribution of Enterobacterales Resistance in Ambulatory Settings by Zip Code in the U.S., 2018-2020
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9 TI ERUMherapeutics 0 5 10 15 20 25 30% resistance Nitrofurantoin Cipro TMP-SMX Cefazolin Prescribing Considerations Prescribing Challenges for Key Oral Therapies in uUTI At 20% resistance or above, Infectious Diseases Society of America (IDSA) no longer recommends empiric usage and physician research highlights need to change products prescribed; additionally, each of the below oral therapies have key safety challenges to consider ● Nitrofurantoin (Macrobid) – Should not be used for pyelonephritis, does not reach therapeutic concentration in kidneys, contraindicated in patients with creatinine clearance <60mL/min (~ 30% of patients) ● Ciprofloxacin (Cipro) – FDA/EMA does not recommend usage in uncomplicated infections: should be reserved for patients who have no other treatment options (product shown to have potential risk of tendonitis, tendon rupture, peripheral neuropathy, CNS effects and exacerbation of myasthenia gravis) and risk is further increased in older patients ● Trimethoprim-Sulfamethoxazole (Bactrim) – Monitor patients for adverse events (rash, hyperkalemia) or use alternative antibiotic ● Cephalexin (Keflex) – Has drug interaction with metformin that can lead to hypoglycemia; potential to trigger seizures, especially if dose not reduced in renal failure patients *Resistance rates for Enterobacterales from Iterum’s 301 and 310 studies combined using urinary breakpoints; per the FDA, CLSI-published urinary cefazolin breakpoints should be used to predict the susceptibility of oral cephalosporins including cephalexin (Keflex)
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10 TI ERUMherapeutics ● Gepotidacin (GlaxoSmithKline) - uUTI – NDA approved by FDA on March 25, 2025; potential commercial launch in Q4 2025 ● Pivmecillinam (Alembic Pharmaceuticals, Inc.) – NDA approved by FDA on April 24, 2024; potential commercial launch in Q4 2025 ORLYNVAHTM is well positioned on both product profile and potential launch timing uUTI Oral Development Pipeline
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11 TI ERUMherapeutics Phase 3 Study Designs - uUTI 9 The number of patients with Augmentin® resistant pathogens was inadequate to test for superiority in this population Sulopenem 500 mg / Probenecid 500 mg po bid Amoxicillin 875 mg/ Clavulanate 125 mg po bid uUTI 2,222 patients D1 D12 Test of Cure D5 End Dosing D28 Follow-up FDA/EMA Primary Endpoint Cure at Day 12 (clinical and microbiologic success) (Non-Inferiority margin:-10.0%)9 Conducted under Special Protocol Assessment (SPA) Agreements with FDA Sulopenem 500 mg / Probenecid 500 mg po bid Ciprofloxacin 250 mg po bid uUTI 1,671 patients D1 D12 Test of Cure D3 D5 End Dosing D28 Follow-up FDA/EMA Primary Endpoint Cure at Day 12 (clinical and microbiologic success) (Non-Inferiority margin: -10%) REASSURE SURE-1
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12 TI ERUMherapeutics REASSURE uUTI Study: Micro-MITT population Micro-MITT population Sulopenem n/N (%) Augmentin® n/N (%) Difference (95% CI) P value Augmentin®-susceptible Population Overall Response (TOC) 296/480 (61.7) 243/442 (55.0) 6.7 (0.3, 13.0) 0.019 Clinical Response (TOC) 371/480 (77.3) 339/442 (76.7) 0.6 (-4.8, 6.1) Microbiological Response (TOC) 361/480 (75.2) 295/442 (66.7) 8.5 (2.6, 14.3) Combined (Augmentin®-susceptible and Augmentin® Non-susceptible Populations) Overall Response (TOC) 318/522 (60.9) 260/468 (55.6) 5.4 (-0.8, 11.5) 0.044 Clinical Response (TOC) 397/522 (76.1) 358/468 (76.5) -0.4 (-5.7, 4.9) Microbiological Response (TOC) 390/522 (74.7) 315/468 (67.3) 7.4 (1.8, 13.1) Non-inferior to Augmentin® in the Augmentin®-susceptible population, as well as statistically superior Micro-MITT = microbiological modified intention to treat TOC = Test of Cure CI = Confidence Interval
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13 TI ERUMherapeutics SURE-1 uUTI Study: Micro-MITT population Micro-MITT population Sulopenem n/N (%) Ciprofloxacin n/N (%) Difference (95% CI) P value Quinolone Non-susceptible Population Overall Response-Test of Cure (TOC) 92/147 (62.6) 50/139 (36.0) 26.6 (15.1, 37.4) < 0.001 Reason for Failure: Asymptomatic bacteriuria 27 (18.4) 38 (27.3) Clinical Response (TOC) 122/147 (83.0) 87/139 (62.6) 20.4 (10.2, 30.4) < 0.001 Overall Response-End of Treatment (EOT) 95/147 (64.6) 42/139 (30.2) 34.4 (23.1, 44.8) < 0.001 Quinolone-susceptible Population Overall Response (TOC) 247/370 (66.8) 326/415 (78.6) -11.8 (-18.0, -5.6) Reason for Failure: Asymptomatic bacteriuria 47 (12.7) 16 (3.9) Clinical Response (TOC) 300/370 (81.1) 349/415 (84.1) -3.0 (-8.4, 2.3) Overall Response (EOT) 240/370 (64.9) 271/415 (65.3) -0.4 (-7.1, 6.2) Combined (Quinolone-susceptible and Quinolone Non-susceptible Populations) Overall Response (TOC) 339/517 (65.6) 376/554 (67.9) -2.3 (-7.9, 3.3) Reason for Failure: Asymptomatic bacteriuria 74 (14.3) 54 (9.7) Clinical Response (TOC) 422/517 (81.6) 436/554 (78.7) 2.9 (-1.9, 7.7) Overall Response (EOT) 335/517 (64.8) 313/554 (56.5) 8.3 (2.4, 14.1) 0.006 Microbiologic eradication was defined as <103 CFU/mL of baseline pathogen isolated at a follow -up visit, as determined by using whole genome sequencing; Green circle represents outcome within the specified non-inferiority margin
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14 TI ERUMherapeutics ORLYNVAHTM Has Demonstrated A Favorable Safety Profile(10) Sulopenem N= 1940 n/N (%) Augmentin N= 1107 n/N (%) Ciprofloxacin N=827 n/N (%) Treatment Emergent Adverse Events (‘TEAEs’) 416 (21.4) 136 (12.3) 115 (13.9) Drug-related TEAE 297 (15.3) 85 (7.7) 51 (6.2) TEAE leading to discontinuation of study drug 21 (1.1) 4 (0.4) 8 (1.0) TEAE leading to discontinuation from study 4 (0.2) 1 (0.1) 1 (0.1) Serious Adverse Events (‘SAE’) 6 (0.3) 5 (0.5) 2 (0.2) Drug-related SAE 1 (0.1)(11) 0 0 SAE leading to premature discontinuation of study drug 1 (0.1) 2 (0.2) 0 SAE leading to death 1 (0.1)(12) 0 0 Treatment-Emergent Adverse Events Occurring in at Least 2% of Patients Diarrhea 193 (9.9) 45 (4.1) 21 (2.5) Nausea 79 (4.1) 32 (2.9) 30 (3.6) Headache 42 (2.2) 17 (1.5) 18 (2.2) 10 Data from both SURE-1 and REASSURE uUTI studies; sulopenem column is a combined total for the sulopenem arm from SURE-1 and REASSURE studies 11 Angioedema, resolved next day. 12 Patient diagnosed with lung cancer on Day 5, died >5 months after completion of study from their cancer.
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15 TI ERUMherapeutics ORLYNVAHTM patents and regulatory exclusivity provide extensive protection Long Runway to Capture Value Iterum’s patent portfolio also contains additional patents granted in the US, Australia, Canada, Mexico, China and South Korea and pending patent applications in a number of other jurisdictions including Europe and Brazil. Note, the Company submitted patent information for four U.S. patents for ORLYNVAHTM have been listed in FDA’s Orange Book. Oral sulopenem – composition of matter U.S. EP JP 3,418,762 2015 2020 2025 2030 2035 Patent Term Extension Potential Pediatric Extension 2040* JP Data Exclusivity JP Oral sulopenem – composition of matter US Marketing Exclusivity Granted – GAIN Act Oral sulopenem & probenecid – composition of bilayer tablet Oral sulopenem & probenecid – composition of bilayer tablet 20102005 Oral sulopenem & probenecid – method of use Potential Patent Term Extension
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16 TI ERUMherapeutics Key Metric September 30, 2025 Cash and cash equivalents (millions) $11.0 Pfizer Promissory Note* $21.2 Ordinary shares outstanding (millions)** ~52.8 Financial Overview * Pursuant to our exclusive license with Pfizer for sulopenem we were obligated to make a regulatory milestone payment of $20m to Pfizer upon approval of oral sulopenem. In accordance with the license we elected to defer payment for two year and delivered promissory note to Pfizer in the amount of $20.0 million in October 2024. In May 2025, the promissory note was amended and extends the repayment of the note to October 2029. This note accrues interest at an annual rate of eight percent for the first two years and then ten percent for the next three years on a daily compounded basis until paid in full. ** Based on shares outstanding as of November 13, 2025 Iterum has sufficient cash to fund its operating expenses into the second quarter of 2026
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17 TI ERUMherapeutics TI ERUMherapeutics