Protara Therapeutics, Inc. (TARA) Earnings

Management highlights

- Unmet Medical Need & Disease Background * Lymphatic malformations are rare, congenital, progressive abnormal growths of lymphatic channels driven by PIK3CA-AKT1 mTOR pathway mutations; they grow proportionally with patients, triggered by hormonal changes (puberty, pregnancy) and trauma (including surgery), can cause life-threatening complications, cosmetic disfigurement, and high healthcare burden. * There are currently no FDA-approved therapies for LM; existing off-label treatments (surgery, ethanol sclerotherapy, bleomycin, other ablative agents) have major limitations: surgery carries high recurrence risk and can stimulate lesion growth, ablative agents are non-targeted irritants with severe toxicity, inconsistent efficacy, and require invasive monitoring/general anesthesia. * The total addressable market for TARA-002 in macrocystic/macrodominant mixed LM is estimated at over $1 billion, with ~1,500 new diagnoses annually and ~25,000 total treatable patients currently living with LM in the US. - TARA-002 Drug Profile & Regulatory Status * TARA-002 is an inactivated, genetically distinct strain of Streptococcus pyogenes that leverages modern manufacturing to improve on the profile of OK-432 (the predecessor compound that has been a standard of care for LM in Japan for 30 years). Its mechanism of action is targeted immune activation: after direct cyst injection, it activates the body's immune system to eliminate mutated epithelial cells lining the cysts, promote tissue remodeling, and resolve lesions long-term with minimal off-target damage. * TARA-002 has received multiple FDA regulatory designations: Rare Pediatric Disease Designation, Orphan Drug Designation, Breakthrough Therapy Designation, and Fast Track Designation, and is eligible for a priority review voucher upon approval. * The FDA recently moved TARA-002 LM review from the Office of Vaccines Research and Review to the Office of Therapeutic Products (OTP), the same division that reviews TARA-002 for NMIBC with significant experience in pediatric rare diseases; the FDA confirmed no changes to STARBORN-1 trial design, no additional pivotal trial is required, and the non-clinical package is complete. - STARBORN-1 Pivotal Trial Interim Results * STARBORN-1 is a single-arm, baseline-controlled pivotal Phase 2 trial enrolling 29 patients aged 6 months to <18 years with macrocystic/macrodominant mixed LM. Interim data as of April 10, 2026 (16 patients) shows: 83% of all patients who completed treatment achieved clinical success (defined as ≥60% volume reduction), 100% of evaluable patients at the 8-week post-treatment timepoint achieved clinical success, 80% of responders achieved success with 1-2 doses only. All 7 patients evaluated at 32 weeks post-treatment remain disease-free, with no serious adverse events reported and most adverse events being mild/moderate and transient. Two patients originally diagnosed as LM that were reclassified as ranula (another maxillofacial cyst) both achieved clinical success, supporting potential expansion to other indications.

Guidance

- The STARBORN-1 pivotal trial is on track to complete full enrollment by the end of 2026. - Protara plans to submit a Biologics License Application (BLA) for TARA-002 for the treatment of macrocystic/macrodominant mixed lymphatic malformations to the FDA in the second half of 2027. - If approved, management expects TARA-002 will be labeled for the full age range of patients enrolled in STARBORN-1 (6 months to <18 years), with no age-based approval restriction anticipated. - Management plans to explore expansion of TARA-002 to additional indications including ranula and thyroglossal duct cysts, which represent a significant additional market opportunity, after advancing the core LM program toward registration. - Commercial preparation is underway for a focused launch targeting the ~100 high-volume vascular anomaly centers that account for 80% of LM sclerotherapy procedures, enabling commercial success with a modest-sized commercial organization.

Segment performance

Protara Therapeutics is a clinical-stage biotechnology company with three core development programs, no commercial product segments currently generating revenue: 1) TARA-002 for lymphatic malformations (LM, the focus of this call, in pivotal Phase 2 STARBORN-1 trial), 2) TARA-002 for non-muscle invasive bladder cancer (NMIBC, with recently announced positive data), and 3) IV choline chloride for parenteral nutrition-dependent patients, in an ongoing registrational Phase 3 trial. No revenue or segment contribution percentage data was provided in this transcript.

Risks & headwinds

- There is an initial learning curve for OTP reviewers to get up to speed on the TARA-002 LM program, though management has not observed this to cause significant delay to date. - Final FDA approval is not guaranteed, and actual trial results and regulatory outcomes may differ from current expectations, consistent with all clinical-stage drug development. - Existing off-label treatments have inconsistent outcomes due to lack of standardized study and dosing, but there may be provider resistance to adopting a new on-label therapy despite its improved profile. - Enrollment in rare disease pediatric trials can be slower than initially anticipated, though management reports enrollment is accelerating and remains on track for the 2026 completion target.

Analyst Q&A

• Q: What is the practical impact of moving TARA-002 review from the FDA vaccine division to OTP?

  A: OTP has extensive experience reviewing small, targeted clinical programs for pediatric rare genetic diseases and already reviews Protara's NMIBC program for TARA-002, which streamlines regulatory communication. Dialogue with the review team has become more collaborative and responsive under OTP, with faster feedback than typical for other FDA divisions. There is a short learning curve for new OTP reviewers, but this has not caused significant delays, and the move is overall net positive for the program.

• Q: Do you see recently announced competing PIK3/mTOR pathway programs as a competitive threat for your LM program?

  A: Competing systemic/topical PIK3/mTOR pathway agents are not a competitive threat to TARA-002, as these agents have only shown limited efficacy for microcystic LM, not macrocystic/macrodominant LM which is TARA-002's target indication. Existing systemic/topical agents do not effectively treat the macrocystic disease architecture that TARA-002 targets, and TARA-002 is the only program currently pursuing approval for macrocystic LM. Protara welcomes development of new treatments for all LM subtypes, but does not see competing programs as a material concern.

• Q: How is enrollment progressing in the STARBORN-1 trial, and what is the current outlook for meeting the end-of-2026 enrollment target?

  A: Enrollment was slow in the initial age-escalation cohorts (starting with older patients who had lower urgency for new treatment) but has accelerated significantly now that positive interim data is available. More investigative sites are requesting to join the trial due to growing physician enthusiasm, and the majority of new enrollees are in the 2-10 year old age range, which is the trial's sweet spot. Enrollment remains on track to complete by the end of 2026 as guided.

• Q: Why has TARA-002 worked for patients who failed all existing off-label LM therapies?

  A: All existing sclerotherapy agents work through non-targeted irritation or destruction of the lesion via dehydration or protein denaturation, which damages healthy surrounding tissue and often fails to fully eliminate mutated cyst lining. TARA-002 has a unique, targeted mechanism of action that triggers a specific immune response against the mutated epithelial cells that cause the malformation, while sparing healthy tissue, which explains its efficacy in treatment-refractory patients. This targeted mechanism also produces a far more favorable safety profile than existing agents, leading most investigators to already consider it a first-line treatment option if approved.