Protara Therapeutics FY Conference Summary Company Overview - **Company**: Protara Therapeutics (NasdaqGM:TARA) - **Lead Program**: TARA-002, a bacterial therapeutic for Non-Muscle Invasive Bladder Cancer (NMIBC) and lymphatic malformations Key Points on TARA-002 and NMIBC - **Mechanism of Action**: TARA-002 is a whole cell bacterial therapeutic engineered to retain antigens while eliminating toxicities associated with traditional treatments. It aims to stimulate a broad immune response without the adverse effects of streptolysin or Streptococcus pyogenes exotoxin [8][10] - **Historical Context**: Originally developed by Chugai Pharmaceutical in the 1970s, TARA-002 (formerly OK-432) has been used in over 65,000 patients in Japan for various cancers, demonstrating significant survival benefits [9][10] - **Current Efficacy Data**: - **BCG-unresponsive Patients**: - 68% complete response (CR) at 6 months, the highest reported in the field [23] - 65% CR at any time [24] - 33% CR at 12 months from a recent update [34] - **BCG-naive Patients**: - 72% CR at any time, 68% CR at 6 months, and 58% CR at 12 months [48] - **Regulatory Pathway**: The FDA has approved a single-arm open-label study for BCG-unresponsive patients, with a focus on CR at 6 months as the primary endpoint [41][57] Competitive Landscape - **Market Positioning**: TARA-002 is positioned as a compelling alternative to existing treatments, with a focus on safety, tolerability, and ease of administration. It is expected to have a significant market share due to its unique mechanism and favorable safety profile [89][92] - **Revenue Potential**: The addressable patient population for TARA-002 is estimated to exceed 20,000 in the frontline plus BCG-exposed settings, which presents a substantial revenue opportunity [41] Lymphatic Malformations Program - **Regulatory Update**: A Type C meeting with the FDA is scheduled, expected to clarify the regulatory path for TARA-002 in treating lymphatic malformations [100] - **Market Opportunity**: The company targets macrocystic and mixed cystic lesions, with an estimated 800 addressable patients annually in the U.S. [110] Choline Program - **Overview**: IV Choline Chloride is aimed at patients on parenteral support, with a significant portion being choline deficient. The FDA has agreed on a pivotal study with a primary endpoint of serum choline elevation [116] Conclusion - Protara Therapeutics is positioned for significant growth with multiple registrational studies underway, focusing on TARA-002 for NMIBC and lymphatic malformations, alongside the choline program. The company emphasizes a strong safety profile, efficacy, and a clear regulatory pathway as key drivers for future success [117][120]

TARA-002 in Lymphatic Malformations (LMs) - LMs represent a significant pediatric rare disease opportunity with no currently approved therapies[8] - TARA-002 has the potential to treat macrocystic and mixed cystic LMs, which most often are present in the head and neck region[11] - The incidence of LMs is approximately 1,400-1,800 cases per year, with a prevalence of approximately 20,000 patients seeking treatment[14] - Macrocystic LMs account for approximately 47%, microcystic LMs for approximately 21%, and mixed LMs for approximately 32% of cases[14] STARBORN-1 Interim Data - In the STARBORN-1 trial, TARA-002 demonstrated clinical success in 80% of patients that completed treatment[30] - Among evaluable patients in STARBORN-1, TARA-002 showed a 100% clinical success rate at 8-weeks post-treatment[30] - In evaluable patients, 83% with macrocystic LMs, 100% with mixed-cystic LMs and 100% with Ranula achieved complete or substantial response[35] - In the STARBORN-1 trial, 66.7% of patients experienced any grade TEAEs, with 8.3% experiencing Grade 3 TEAEs and no Grade 4/5 TEAEs[39] OK-432 Data Review - OK-432, the predecessor compound to TARA-002, has shown strong safety and efficacy results in over 500 U S pediatric LMs patients in a University of Iowa-led study[18] - OK-432 demonstrated a 69% clinical success rate in the immediate treatment group 6 months after enrollment[46] - OK-432 showed an 84% clinical success rate in patients with macrocystic lesion types[46]