Summary of Protara Therapeutics (TARA) Update / Briefing April 28, 2025 Company Overview - **Company**: Protara Therapeutics - **Focus**: Development of TARA-two, an investigational treatment for non-muscle invasive bladder cancer (NMIBC) Key Industry Insights - **Clinical Trial**: Ongoing Phase II ADVANCE-two clinical trial of TARA-two in NMIBC patients - **Treatment Landscape**: TARA-two is positioned as a competitive option in the evolving NMIBC treatment landscape, particularly for BCG unresponsive patients Core Findings and Arguments 1. **Positive Interim Results**: TARA-two demonstrated a complete response (CR) rate of 100% at any time and 100% at six months in the BCG unresponsive cohort, with rates of 80% at nine months and 67% at twelve months [12][15] 2. **Durable Responses**: The treatment shows durable responses at twelve months in both BCG unresponsive and naive cohorts, with 76% CR at any time in the naive cohort [15] 3. **Safety Profile**: TARA-two exhibited a favorable safety profile, with most adverse events being grade one and transient, and no patients discontinued due to adverse events [16] 4. **Mechanism of Action**: TARA-two activates a broader immunologic profile compared to other therapies, potentially leading to durable antitumor responses [9][14] 5. **Regulatory Engagement**: The company is in discussions with the FDA regarding the design of registrational studies for both BCG unresponsive and naive patient populations [15][81] Additional Important Insights 1. **Patient Enrollment**: The company has seen an increase in trial enrollment due to site expansion efforts, with 17 patients currently enrolled [12][28] 2. **Future Milestones**: Protara anticipates additional data updates and milestones throughout the year, including a preplanned analysis of 25 BCG unresponsive patients by the end of 2025 [19][29] 3. **Combination Therapy Potential**: The company is exploring systemic priming and combination therapies to enhance treatment efficacy and patient quality of life [45][47] 4. **Market Positioning**: TARA-two is viewed as a potential best-in-class treatment for NMIBC, with characteristics that drive adoption among healthcare providers [32][33] Conclusion - Protara Therapeutics is making significant strides in the development of TARA-two for NMIBC, with promising interim results and a strong safety profile. The company is well-positioned to capitalize on upcoming milestones and regulatory discussions, potentially transforming the treatment landscape for patients with NMIBC.

Core Insights - Protara Therapeutics, Inc. announced updated results from its Phase 2 ADVANCED-2 trial for TARA-002, a cell-based therapy for high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients, which will be presented at the American Urological Association 2025 Annual Meeting [1][2] Interim Results - The BCG-Unresponsive cohort included five patients, all evaluable at six and nine months, with three evaluable at 12 months as of April 16, 2025 [3] - The BCG-Naïve cohort included 21 patients, with 16 evaluable at six months, eight at nine months, and seven at 12 months as of April 16, 2025 [4] Safety Profile - Most adverse events were Grade 1 and transient, with no Grade 3 or greater treatment-related adverse events reported. Common adverse events included flu-like symptoms and urinary tract issues, which typically resolved shortly after administration [5] Efficacy Data - TARA-002 demonstrated a 100% complete response (CR) rate at any time in BCG-Unresponsive patients, with 67% CR rate at 12 months. In BCG-Naïve patients, the CR rate was 76% at any time and 43% at 12 months [6][7] Future Plans - The company is on track to present updated interim data from approximately 25 six-month evaluable BCG-Unresponsive patients by the end of 2025 [6][8] - A conference call and webcast to discuss the data will be held on April 28, 2025 [9] About the Trial - The ADVANCED-2 trial is assessing TARA-002 in NMIBC patients with carcinoma in situ who are BCG-Unresponsive or BCG-Naïve, with a total of approximately 100 patients in the BCG-Unresponsive cohort [10] About TARA-002 - TARA-002 is an investigational cell therapy for NMIBC and has received Rare Pediatric Disease Designation from the FDA. It is developed from a master cell bank of genetically distinct group A Streptococcus pyogenes [11] About NMIBC - NMIBC accounts for approximately 80% of bladder cancer diagnoses in the U.S., with around 65,000 new cases diagnosed annually [13] About Protara Therapeutics - Protara is a clinical-stage biotechnology company focused on developing transformative therapies for cancer and rare diseases, including TARA-002 for NMIBC and lymphatic malformations [14]

Core Viewpoint - Protara Therapeutics is set to present updated safety and efficacy data from the Phase 2 ADVANCED-2 trial of TARA-002 for non-muscle invasive bladder cancer (NMIBC) on April 28, 2025, with data showcased at the American Urological Association 2025 Annual Meeting on April 26, 2025 [1][2] Group 1: Company Overview - Protara Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing transformative therapies for cancer and rare diseases [7] - The company's lead candidate, TARA-002, is an investigational cell-based therapy aimed at treating NMIBC and lymphatic malformations (LMs) [7] - Protara is also developing IV Choline Chloride for patients on parenteral nutrition [7] Group 2: Clinical Trial Details - The ADVANCED-2 trial (NCT05951179) is a Phase 2 open-label study assessing TARA-002 in NMIBC patients who are BCG-unresponsive or BCG-naïve [3] - The trial includes approximately 100 BCG-unresponsive patients and 31 BCG-naïve patients, with the BCG-unresponsive cohort designed to be registrational [3] Group 3: Product Information - TARA-002 is derived from a master cell bank of genetically distinct group A Streptococcus pyogenes, similar to OK-432, which is marketed in Japan [4] - The therapy is hypothesized to activate immune cells and induce a pro-inflammatory response, enhancing the antitumor immune response [5] Group 4: Disease Context - NMIBC accounts for about 80% of bladder cancer diagnoses, with approximately 65,000 new cases diagnosed annually in the United States [6]

NEW YORK, April 15, 2025 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced the appointment of Leonardo Viana Nicacio, M.D., as Chief Medical Officer. Dr. Nicacio brings to Protara nearly 20 years of broad oncology, drug development, regulatory and commercial experience across leading biopharmaceutical and health technology companies. “We are delighted to welcome Dr. Nicaci ...

NEW YORK, April 10, 2025 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced that two presentations and a panel discussion highlighting the ongoing Phase 2 open-label ADVANCED-2 trial of TARA-002 in patients with non-muscle invasive bladder cancer (NMIBC) will be featured at the upcoming American Urological Association (AUA) 2025 Annual Meeting taking place from April 26, 20 ...

Protara Therapeutics (TARA) appears an attractive pick, as it has been recently upgraded to a Zacks Rank #2 (Buy). This upgrade primarily reflects an upward trend in earnings estimates, which is one of the most powerful forces impacting stock prices.The Zacks rating relies solely on a company's changing earnings picture. It tracks EPS estimates for the current and following years from the sell-side analysts covering the stock through a consensus measure -- the Zacks Consensus Estimate.The power of a changin ...

Data to be featured during oral presentation at the American Society for Parenteral and Enteral Nutrition 2025 Nutrition Science & Practice ConferenceDosing of first patient in THRIVE-3 registrational trial of IV Choline Chloride in patients dependent on parenteral support expected in 1H 2025 NEW YORK, March 19, 2025 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (NASDAQ:TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced that da ...

Clinical Trials and Development - TARA-002 is currently in the ADVANCED-2 Phase 2 trial for non-muscle invasive bladder cancer (NMIBC), with Cohort A expected to enroll 27 patients and Cohort B expected to enroll 75-100 patients[22][23] - The company plans to share 12-month interim data from Cohort A by mid-2025 and complete an interim analysis for Cohort B by the end of 2025[23] - The THRIVE-3 Phase 2b/3 trial for IV Choline Chloride is set to initiate in the first half of 2025, targeting 100 patients[28][39] - In September 2024, interim data from the STARBORN-1 trial showed that 2 out of 3 patients achieved a complete response after one injection of TARA-002 for lymphatic malformations[32] - The ongoing Phase 2 ADVANCED-2 trial reported a CR rate of 72% (13/18) at six months for BCG-exposed patients, with 100% (4/4) CR in BCG-Unresponsive patients[55] - The company plans to share interim 12-month data from the ADVANCED-2 trial by mid-2025 and is in discussions with the FDA regarding a registrational trial for TARA-002 in BCG-Naïve patients[57] - TARA-002 is currently undergoing a Phase 2 clinical trial (STARBORN-1) with approximately 30 pediatric patients aged 6 months to less than 18 years[88] - In the first cohort of the trial, 66.7% of patients treated with TARA-002 achieved a complete response after one dose[88] Product Designations and Regulatory Status - TARA-002 has received Orphan Drug Designation for lymphatic malformations and Rare Pediatric Disease Designation from the FDA[30][36] - IV Choline Chloride has been granted Orphan Drug Designation by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN[74] - The FDA has granted Fast Track Designation to IV Choline Chloride as a source of choline when oral or enteral nutrition is not possible[74] - The FDA granted Rare Pediatric Disease Designation for TARA-002 in July 2020, which may provide eligibility for a priority review voucher[93] - The European Commission granted Orphan Drug Designation to TARA-002 in May 2022[94] Financial and Operational Status - The company has not generated any revenue from product sales and does not expect to do so in the near term, indicating a need for additional capital to finance ongoing clinical trials[34] - The company has a limited operating history and has never generated any revenues, focusing on organizing, staffing, and developing pipeline assets like TARA-002 and IV Choline Chloride[218] - The company has not yet demonstrated the ability to successfully complete registrational clinical trials or commercialize any product candidates[218] - As of December 31, 2024, the company had 33 employees, with 20 engaged in research and development activities[210] - The company has undergone a merger, completing the reorganization with ArTara Subsidiary, Inc. on January 9, 2020, structured as a reverse merger[211] - The company has no products approved for commercial sale and has not generated any revenue from product sales or otherwise[218] Manufacturing and Capacity - TARA-002 manufacturing facility has an annual capacity of 20 million vials, with potential to expand capacity by 500%[63] - 47 successful consecutive batches of TARA-002 were manufactured by the end of 2024[63] - The manufacturing process for TARA-002 is modernized but equivalent to that of OK-432, with no Form 483s issued during the latest FDA inspection[95] Intellectual Property and Agreements - The company holds U.S. Patent 8,865,641 B2 for IV Choline Chloride, which provides protection until 2035, and additional patents expiring in 2041[121][135] - The agreement with Chugai Pharmaceutical provides exclusive access to materials and technical support for the development of TARA-002, valid through June 17, 2030[44] - Under the Chugai Agreement, the company is responsible for the development and commercialization of TARA-002 outside of Japan and Taiwan[96] - The company will pay Chugai Pharmaceutical a low single-digit million fee for each additional indication approval under the Chugai Agreement[97] - The company has a sponsored research agreement with The University of Iowa, providing $30,000 annually for project funding[103] - The company entered into a license agreement with The Feinstein Institute for Medical Research, granting an exclusive worldwide license for the treatment of fatty liver disease, with tiered royalties of 1.0% to 1.5% on net sales[114] Safety and Efficacy - TARA-002 demonstrated a favorable safety profile, with the majority of adverse events being Grades 1 and 2, and no Grade 3 or higher treatment-emergent adverse events reported[53] - Non-clinical studies indicate that TARA-002 may have superior tumor cell killing compared to BCG, with significant upregulation of pro-inflammatory cytokines[58] - In the ADVANCED-1 trial, TARA-002 showed a complete response (CR) rate of 38% across 16 evaluable patients, with a CR rate of 63% in CIS-only patients[53] Market and Competitive Landscape - The company is building its commercial infrastructure to launch and commercialize oncology and rare disease programs in key geographies, focusing on areas with high patient concentration[41] - The company faces competition from various pharmaceutical and biotechnology companies in the commercialization of its products[131] - The marketability of approved products may suffer if adequate coverage and reimbursement are not provided by government and third-party payors[199] Regulatory Compliance and Challenges - The FDA regulates the company's drug development processes, and failure to comply with regulations may result in sanctions[136][137] - The FDA requires completion of preclinical laboratory tests and animal studies in accordance with cGLP regulations before marketing biopharmaceutical products in the U.S.[138] - An IND must be submitted to the FDA and becomes effective 30 days after receipt unless safety concerns are raised, allowing clinical trials to commence[141] - Human clinical trials are conducted in three phases, with Phase 3 typically requiring two adequate and well-controlled trials to demonstrate efficacy[144] - The FDA aims to review standard applications for new molecular entities within ten months and priority reviews within six months after filing[149] - The NDA or BLA submission requires a substantial application user fee, which is typically increased annually[148] - Compliance with various federal and state healthcare regulations is essential, including adherence to the Anti-Kickback Statute and the False Claims Act, which impose significant penalties for violations[181][183] Pricing and Reimbursement - The company faces uncertainty regarding coverage and reimbursement for product candidates, which is critical for new product acceptance in the market[193][194] - Third-party payors increasingly challenge pricing and medical necessity, making reimbursement for branded drugs particularly difficult[197] - Legislative changes in the U.S. healthcare system may impact the marketing approval and profitability of product candidates[200] - The company must navigate complex pricing and reimbursement schemes in foreign markets, which may include mandatory clinical trials for cost-effectiveness[198]

Financial Performance - Protara reported a net loss of $12.8 million, or $0.48 per share, for Q4 2024, compared to a net loss of $10.2 million, or $0.90 per share, in Q4 2023[14]. - For the full year 2024, the net loss was $44.6 million, or $2.17 per share, compared to a net loss of $40.4 million, or $3.57 per share, in 2023[14]. - The company reported a net income (loss) per share of $(0.48) for the three months ended December 31, 2024, compared to $(0.90) for the same period in 2023[21]. - Comprehensive loss for the year ended December 31, 2024, was $44,563,000, compared to $39,763,000 in 2023, reflecting an increase of 12%[21]. - Net loss for the year ended December 31, 2024, was $44,596,000, compared to a net loss of $40,420,000 in 2023, indicating a deterioration of 10%[21]. Cash and Investments - Cash, cash equivalents, and investments totaled $170 million as of December 31, 2024, expected to support operations into 2027[5]. - Cash and cash equivalents rose significantly to $162,798,000 in 2024, up from $39,586,000 in 2023, marking an increase of 311%[19]. - Interest and investment income for the year ended December 31, 2024, was $4,171,000, up from $3,193,000 in 2023, an increase of 30%[21]. Research and Development - Research and development expenses for Q4 2024 increased to $9.5 million from $6.4 million in the prior year, and for the full year increased to $31.7 million from $25.0 million in 2023[14]. - Research and development expenses increased to $31,704,000 in 2024 from $24,989,000 in 2023, a rise of 27%[21]. - Protara continues to explore combination treatment opportunities with TARA-002 in NMIBC patients, indicating significant potential for systemic dosing and combination therapy[8]. - The complete response (CR) rate in the ADVANCED-2 trial for TARA-002 was 72% (13/18) at six months and 70% (14/20) at any time[4]. - Initial data from 12-month evaluable patients in the ADVANCED-2 trial is expected to be reported by mid-2025[3]. - Protara plans to initiate the THRIVE-3 trial of intravenous Choline Chloride in the first half of 2025, with a total of 100 patients expected to be enrolled[6]. - The company expects to provide an interim update from the STARBORN-1 trial of TARA-002 in pediatric lymphatic malformations by the end of the first half of 2025[5]. Operating Expenses - Total operating expenses for the year ended December 31, 2024, were $49,154,000, compared to $43,613,000 in 2023, reflecting an increase of 13%[21]. - General and administrative expenses for Q4 2024 increased slightly to $4.8 million from $4.7 million in the prior year, while full-year expenses decreased to $17.5 million from $18.6 million in 2023[14]. Assets and Equity - Total assets increased to $181,454,000 in 2024 from $78,954,000 in 2023, representing a growth of 130%[19]. - Total stockholders' equity rose to $167,134,000 in 2024, up from $68,321,000 in 2023, an increase of 144%[19]. - The number of common shares outstanding increased to 35,044,772 in 2024 from 11,364,903 in 2023, representing a growth of 208%[19].

Core Insights - Protara Therapeutics, Inc. is focused on developing transformative therapies for cancer and rare diseases, with significant progress reported in their clinical pipeline [2][16] - The company announced positive six-month data from the Phase 2 ADVANCED-2 trial for TARA-002 in non-muscle invasive bladder cancer (NMIBC) and plans to report initial 12-month data by mid-2025 [2][5] - Protara is set to initiate the pivotal THRIVE-3 trial for intravenous Choline Chloride in the first half of 2025, targeting patients on parenteral support [4][5] Recent Progress and Highlights - Positive interim results from the ADVANCED-2 trial showed a complete response (CR) rate of 72% at six months for NMIBC patients [6] - The company has a cash position of $170 million as of December 31, 2024, which is expected to fund operations into 2027 [5][14] - The THRIVE-3 trial will assess the efficacy and safety of IV Choline Chloride over 24 weeks in patients unable to receive oral or enteral nutrition [4][15] Financial Results - For Q4 2024, Protara reported a net loss of $12.8 million, or $0.48 per share, compared to a net loss of $10.2 million, or $0.90 per share, in Q4 2023 [14][20] - Research and development expenses increased to $9.5 million in Q4 2024 from $6.4 million in the prior year, primarily due to clinical trial activities [14][20] - Total operating expenses for the full year 2024 were $49.2 million, up from $43.6 million in 2023 [20]