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STARBORN-1 Clinical Trial Interim Update November 19, 2025
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Forward Looking Statements 2 Statements contained in this presentation regarding matters that are not historical facts are "forward looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Protara may, in some cases, use terms such as “predicts, ” “believes, ” “potential, ” “proposed, ” “continue, ” “designed, ” “estimates, ” “anticipates, ” “expects, ” “plans, ” “intends, ” “may, ” “could, ” “might, ” “will, ” “should” or other words or expressions referencing future events, conditions or circumstances that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such forward-looking statements include but are not limited to, statements regarding Protara’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Protara’s business strategy, including its development plans for its product candidates and plans regarding the timing or outcome of existing or future clinical trials; statements related to expectations regarding interactions with the U.S. Food and Drug Administration (FDA); Protara’s financial position; statements regarding the anticipated safety or efficacy of Protara’s product candidates; and Protara’s outlook for the remainder of the year and future periods. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that contribute to the uncertain nature of the forward-looking statements include: risks that Protara’s financial guidance may not be as expected, as well as risks and uncertainties associated with: Protara’s development programs, including the initiation and completion of clinical trials and the timing of required filings with the FDA and other regulatory agencies; general market conditions; changes in the competitive landscape; changes in Protara’s strategic and commercial plans; Protara’s ability to obtain sufficient financing to fund its strategic plans and commercialization efforts; having to use cash in ways or on timing other than expected; the impact of market volatility on cash reserves; failure to attract and retain management and key personnel; the impact of general U.S. and foreign, economic, industry, market, regulatory, political or public health conditions; and the risks and uncertainties associated with Protara’s business and financial condition in general, including the risks and uncertainties described more fully under the caption “Risk Factors” and elsewhere in Protara's filings and reports with the United States Securities and Exchange Commission. All forward-looking statements contained in this presentation speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Protara undertakes no obligation to update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise, except as required by law. © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. |
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Agenda Jesse Shefferman Co-founder, Director, Chief Executive Officer Jacqueline Zummo, PhD Co-founder, Senior Vice President, Chief Scientific Operations Officer Jesse G.A. Jones, MD University of Alabama – Department of Neurosurgery and Radiology, and STARBORN-1 study investigator Introduction • LMs opportunity • Executive Summary Jesse Shefferman TARA-002 in Lymphatic Malformations • TARA-002 MOA • Interim STARBORN-1 Data • OK-432 Data Review Jacqueline Zummo, PhD KOL Discussion Jesse, G.A. Jones, MD Closing Remarks Jesse Shefferman Q&A All © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 3
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*Currently in pre-clinical studies to define dosing and, once protocol is confirmed, expect to initiate P2 trial cohort. **Granted Orphan Drug Designations by the U.S. FDA for the prevention and/or treatment of choline deficiency in patients on l ong-term PN and Fast Track Designation as a source of choline when oral or enteral nutrition is not possible, insufficient, or co ntraindicated. ***TARA-002 granted Rare Pediatric Disease designation by the U.S. FDA and orphan drug designation by the European Commission f or the treatment of LMs. †Trial also includes BCG-Exposed patients. Robust De-Risked Pipeline with Multiple Upcoming Opportunities © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 4 Indication Pre-Clinical Phase 1 Phase 2 Phase 3 ONCOLOGY TARA-002 NMIBC BCG-Naïve† NMIBC BCG- Unresponsive TARA-002 Systemic Priming NMIBC BCG-Naïve TARA-002 Systemic Priming + maintenance NMIBC BCG-Naïve TARA-002 Combination NMIBC All-comers RARE DISEASES IV CHOLINE Choline for parenteral support (PS) patients** TARA-002 Lymphatic Malformations (LMs)*** ADVANCED-2 (Cohort A) Fully enrolled ADVANCED-2 (Cohort B) ADVANCED-2 (Cohort C)* STARBORN-1 THRIVE-3 ADVANCED-2 (Cohort D)*
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© 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 5 LMs Represent a Significant Pediatric Rare Disease Opportunity with No Currently Approved Therapies Lymphatic Malformations (LMs) are rare, non-malignant, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system1 LMs are diagnosed in early childhood and can cause significant morbidity affecting breathing, swallowing, feeding, and speaking2 Macrocystic LMs Microcystic LMs Mixed Cystic Large cysts >1-2 cm diameter, well-defined fluid-filled spaces Small, infiltrative lesions with tiny cystic spaces Combination of both macro and microcystic components TARA-002 has the potential to treat macrocystic and mixed cystic LMs, which most often are present in the head and neck region 1Brouillard P, et al. J Clin Invest. 2014;124:898-904.; 2Ha J, et al. Curr Ped Rev. 2014;10:238-248 TARA- 002 TARA- 002
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Lymphatic Malformations Incidence: 1,400-1,800 LM cases per year1 © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 6 Bringing the First FDA-approved Therapy to Market for Macrocystic and Mixed Cystic LMs Provides a Significant Rare Disease Opportunity Prevalence Seeking Treatment ~20,000 patients Macrocystic2 ~47% Microcystic2 ~21% Mixed2 ~32% 1Internal company estimates; 2 Hyvonen H, et al. Journal of Ped Surgery 2022 Unmet Medical Need Not a target for TARA-002 No FDA approved therapies for macro- and mixed cystic LMs Current treatment options include: • Surgical excision with a high complication rate including infection, scarring or nerve injury, as well as a high recurrence rate • Unapproved, off-label use of sclerosants, which have various side effects and carry the risk of serious side effects for pediatric patients
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TARA-002 HAS ROBUST SUPPORTING CLINICAL DATA IN LMS FROM PREDECESSOR COMPOUND, OK-432 • OK-432 has shown strong safety and efficacy results in 500+ U.S. pediatric LMs patients in University of Iowa-led study • Approved in Japan as standard of care for LMs for 30 years STARBORN-1 DATA INDICATE TARA-002 HAS COMPARABLE SAFETY & EFFICACY TO OK-432 • 100% of evaluable patients achieved clinical success • TARA-002 demonstrated favorable safety and tolerability profile with no serious adverse events reported HIGH UNMET NEED WITH POTENTIAL TO TREAT OTHER MAXILLOFACIAL CYSTS • Granted Rare Pediatric Disease Disorder (RPDD) in 2021 • Historical literature and patient experience show TARA-002 may also be effective in treating other maxillofacial cysts © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 7 Executive Summary: TARA-002 Provides a De-Risked Opportunity for a Significant Unmet Need
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LMs Overview & TARA-002 MOA © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 8
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© 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 9 TARA-002 is an Investigational, Genetically Distinct Strain of Streptococcus Pyogenes that is Inactivated While Retaining its Immune-Stimulating Properties First Immune Response Further Recruitment of Immune Cells Breakdown of the Lymphatic Lining Lymphatic Fluid Aspiration TARA-002 Injection
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© 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 10 Following the Immune Cascade Triggering Vessel Collapse, the Formation of Mature Fibrous Tissue Prevents Cyst Recurrence Improved Fluid Drainage Fibrotic Adhesion Healing and Tissue Remodeling Vessel Collapse and Long-Term Stabilization Lymphatic Fluid Drainage
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TARA-002 IN LMS Interim STARBORN-1 Data Update and OK-432 Data Review
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6 years to < 18 years 2 years to < 6 years 6 months to < 2 years Phase 2a: Safety Lead-In Phase 2b: Expansion Age De-escalation Age De-escalation DMC Review DMC Review DMC Review Phase 2 STARBORN-1 Trial © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 12 Enroll N = 20 Expansion Expansion Expansion Enroll N = 3 Enroll N = 3 Enroll N = 3 STARBORN-1 is a Single Arm, Open-Label Safety and Efficacy Study of TARA-002 in Pediatric Patients with Macrocystic & Mixed-cystic LMs (N=29) • Patients receive up to four injections of TARA-002 spaced approximately six weeks apart • DMC review with FDA for each safety lead-in cohort before expansion and age de-escalation • Clinical Success is defined as the proportion of patients who have either a complete response (90 - 100% reduction from baseline in total LM volume) or substantial response (60% - 90% reduction) CT.gov identifier: NCT05871970
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© 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 13 Response was assessed via central imaging (MRI or CT) or via Investigator assessment (physical exam, visual inspection and ul trasound). Clinical success is defined as complete (90-100% reduction) or substantial (60-90% reduction) response of the cyst from baseline in total LM volume. Note: Response assessment includes all patients who have completed treatment; Excludes 2 subjects who are still in treatment *Patients who received at least one intracystic injection of the study intervention. ^ Patients who completed the 8-week post-treatment assessment. 20% 70% 10% N = 10 Withdrew Complete Response Substantial Response 80% 80% CLINICAL SUCCESS RATE AT 8-WEEKS POST-TREATMENT* Data cut-off: 12-Nov-2025 88% 12% N = 8 Complete Response Substantial Response 100% 100% CLINICAL SUCCESS RATE AT 8-WEEKS POST-TREATMENT IN EVALUABLE PATIENTS^ STARBORN-1 Interim Results: TARA-002 Demonstrated Clinical Success in 80% of Patients that Completed Treatment and 100% of Evaluable Patients 2 Patients withdrew before 8-week post-treatment assessment • 1 participant was mis-diagnosed and had a rare form of cancer and did not respond to treatment • 1 participant dropped out after achieving a marked resolution of the LM: received 2 doses (160 ml aspiration at first dose reduced to 10 ml aspiration at second dose)
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© 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 14 STARBORN-1 Interim Results: Evaluable Patients Across Cyst Types • 2 patients have reached the 32-weeks post-treatment assessment and remain disease free • One patient deemed a complete response was subsequently diagnosed with a ranula (a different type of maxillofacial cyst from LMs) 83% 17% Macrocystic LMs (N = 6) Mixed-cystic LMs (N = 1) Ranula (N = 1) Complete Response Substantial Response STRONG RESPONSE ACROSS CYST TYPES IN EVALUABLE POPULATION: MACROCYSTIC LMs, MIXED CYSTIC LMs, RANULAS 100% 100% 100%
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STARBORN-1 Interim Results: Clinical Response Overview Cohort / Patients* LM Type Age Number of Doses of TARA-002 Assessment of Response 8 Weeks after Last Injection Ph2a: 6 - 18 years 1 Ranula (Dx’d macro)** 14 1 Complete Response 2 Mixed cystic 12 1 Complete Response 3 Mis-diagnosed cancer 15 3 Withdrew Ph2a: 2 - 6 years 1 Macrocystic 4 1 Complete Response 2 Macrocystic 4 1 Complete Response 3 Macrocystic 3 2 Complete Response 4 Macrocystic 2 2 Complete Response Ph2b Expansion: 6 - 18 years 1 Macrocystic 6 2 Substantial Response 2 Macrocystic 8 4 Complete Response 3 Macrocystic 15 2 Withdrew – Demonstrated a Notable Resolution of the LM Response was assessed via central imaging (MRI or CT) or via Investigator assessment (physical exam, visual inspection and ul trasound). Clinical success is defined as complete (90-100% reduction) or substantial (60-90% reduction) response of the cyst from baseline in total LM volume. *Excludes 2 patients who are still in treatment; **Later diagnosed as a Ranula patient © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 15Data cut-off: 12-Nov-2025
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© 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 16 TARA-002 Has a Favorable and Well-Tolerated Safety Profile Number of Patients, N = 12 Any Grade Grade 1 Grade 2 Grade 3 Grade 4/5 TEAEs, n (%) 8 (66.7) 8 (66.7) 6 (50.0) 1 (8.3) 0 (0.0) Related TEAEs, n (%) 7 (58.3) 7 (58.3) 4 (33.3) 1 (8.3) 0 (0.0) Related TEAEs >10%, n (%) Swelling 3 (25.0) 0 (0.0) 2 (16.7) 1 (8.3) 0 (0.0) Fatigue 3 (25.0) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) Headache 2 (16.7) 2 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) Injection site pain 2 (16.7) 2 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) Injection site rash 2 (16.7) 2 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) Pyrexia 2 (16.7) 2 (16.7) 0 (0.0) 0 (0.0) 0 (0.0) AESIs, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Serious TEAEs, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Related TEAEs leading to study drug withdrawal, n (%) 1 (8.3) 0 (0.0) 1 (8.3) 0 (0.0) 0 (0.0) • Most AEs were mild to moderate. • No SAEs or AESIs have occurred to date. • Related AEs and systemic reactions are in line with typical systemic responses to bacterial immunopotentiation and the established safety profile of OK-432. AESI = adverse event of special interest; TEAE = treatment emergent adverse event Data cut-off: 12-Nov-2025
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TARA-002 Demonstrated Meaningful Results in LMs Patients Treated in the STARBORN-1 Study BEFORE AFTER BEFORE AFTER 17 Medical photography from 2 patients pre- and post-treatment with TARA-002 in STARBORN-1 trial
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69% CLINICAL SUCCESSǂ IN IMMEDIATE TREATMENT GROUP 6 MONTHS AFTER ENROLLMENT 84%* CLINICAL SUCCESSǂ IN PATIENTS WITH MACROCYSTIC LESION TYPES 69% 7.5% Immediate Treatment Group (N=110) Delayed Treatment Group Pre-Treatment** (N=40) ITT: Observations 6 Months After Enrollment 62% 28% 0% 22% 32% Macrocystic LMs (n=77) Mixed (n=47) Microcystic LMs (n=14) Complete or Substantial Response by Radiographically Confirmed Lesion Type** • Patients with radiographically confirmed macrocystic lesions had the greatest chance for clinical success • In those patients with mixed lesions, clinical success was still achieved • During this same period, 7.5% of patients in the delayed treatment group experienced spontaneous regression of LM • Treatment: 1-4 injections at 8-week intervals max of 0.2mg/session (2KE) P < 0.0001 84% 60% ǂ Clinical Success was defined as complete or substantial response. *Reflects data prior to dosing with OK-432. After dosing, the clinical success rate was 66%, which was not statistically different from the Immediate Treatment Group. **Results were analyzed by lesion type across all treatment groups. 1Results based on retrospective analysis of source verified data that included the full dataset of subjects enrolled in random ized study between January 1998 and August 2005, including data in the published study (Smith et al. 2009) which included subjects enrolled between January 1998 and November 2004. Robust Clinical Results from OK-4321, Predecessor to TARA-002 © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. 18 Substantial Response Complete Response 1TARA-002 is developed from the same master cell bank as OK-432 University of Iowa study results
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Robust Clinical Results from OK-4321, Predecessor to TARA-002 © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 19 Completed clinical study of OK-432 in U.S. suggests effectiveness with strong support for safety profile BEFORE AFTER BEFORE AFTER BEFORE AFTER BEFORE AFTER 1TARA-002 is developed from the same master cell bank as OK-432 University of Iowa study results
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KOL Discussion Jesse G.A. Jones, M.D., University of Alabama – Department of Neurosurgery and Radiology, and STARBORN-1 study investigator © 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. |
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Closing Remarks
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Q&A 22 Jesse Shefferman Co-founder, Director, Chief Executive Officer Jacqueline Zummo, PhD Co-founder, Senior Vice President, Chief Scientific Operations Officer Jesse G.A. Jones, MD University of Alabama – Department of Neurosurgery and Radiology, and STARBORN-1 study investigator
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Thank you!
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APPENDIX
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© 2025 Protara Therapeutics. All Rights Reserved – Do Not Copy or Distribute. | 25 STARBORN-1 Interim Results: Demographics and Baseline Characteristics Two patients who were initially diagnosed with macrocystic LMs at baseline had a change in diagnosis of their target cyst (post-treatment): One had a change in diagnosis to a ranula. Another had a change in diagnosis to low grade mucoepidermoid carcinoma. Data cut-off: 12-Nov-2025 N = 12 Age, mean (years) 8.3 (4.77) Sex, female, n/N (%) 6 (50.0) Race, white, n/N (%) 9 (75.0) Ethnicity, not Hispanic, n/N (%) 8 (66.7) Lymphatic Malformation Type, n/N (%) Macrocystic 11 (91.7) Mixed cystic 1 (8.3) de Serres Stage, n/N (%) I 3 (25.0) II 2 (16.7) III 6 (50.0) M 1 (8.3)