[Executive Summary & Business Outlook](index=1&type=section&id=Executive%20Summary%20%26%20Business%20Outlook) This section summarizes Protara Therapeutics' Q2 2025 financial results, business updates, and pipeline milestones [Q2 2025 Financial Results and Business Update](index=1&type=section&id=Q2%202025%20Financial%20Results%20and%20Business%20Update) Protara Therapeutics announced Q2 2025 financial results and business updates, outlining pipeline progress and key upcoming milestones - Protara Therapeutics is a clinical-stage company developing **transformative therapies** for cancer and rare diseases[2](index=2&type=chunk) - CEO Jesse Shefferman stated the company is **well-positioned to advance its pipeline** in the second half of the year[3](index=3&type=chunk) - Interim results from the ADVANCED-2 trial of TARA-002 in non-muscle invasive bladder cancer (NMIBC) are expected in **1Q 2026**[3](index=3&type=chunk) - The company is on track to dose the first patient in the THRIVE-3 registrational trial of IV Choline Chloride by **end of 3Q 2025**[3](index=3&type=chunk) - An interim update from the STARBORN-1 trial in pediatric lymphatic malformations (LMs) is expected in **4Q 2025**[3](index=3&type=chunk) [Recent Progress and Pipeline Updates](index=1&type=section&id=Recent%20Progress%20and%20Pipeline%20Updates) This section details recent advancements and updates across Protara Therapeutics' clinical pipeline, including TARA-002 and IV Choline Chloride programs [TARA-002 in Non-Muscle Invasive Bladder Cancer (NMIBC)](index=1&type=section&id=TARA-002%20in%20Non-Muscle%20Invasive%20Bladder%20Cancer%20(NMIBC)) Protara Therapeutics expects interim analysis from approximately 25 six-month evaluable BCG-Unresponsive NMIBC patients in the ADVANCED-2 trial in 1Q 2026, while also exploring subcutaneous dosing and combination treatments - Interim analysis from approximately **25 six-month evaluable BCG-Unresponsive NMIBC patients** in the ADVANCED-2 trial is expected at a medical conference in **1Q 2026**[5](index=5&type=chunk)[6](index=6&type=chunk) - An update on next steps in the BCG-Naïve program is expected in **2H 2025**, following discussions with the U.S. Food and Drug Administration (FDA)[6](index=6&type=chunk) - Protara continues to investigate **subcutaneous dosing** and explore **combination treatments** with TARA-002 in NMIBC patients with CIS[6](index=6&type=chunk) [IV Choline Chloride for Patients on Parenteral Support (PS)](index=2&type=section&id=IV%20Choline%20Chloride%20for%20Patients%20on%20Parenteral%20Support%20(PS)) The company is on track to dose the first patient in the THRIVE-3 registrational Phase 3 clinical trial in 3Q 2025, with EU enrollment commencing soon, and IV Choline Chloride holding Fast Track designation - First patient dosing in THRIVE-3, a registrational Phase 3 clinical trial, is on track for the **third quarter of 2025**[7](index=7&type=chunk) - Enrollment across the EU is expected to begin in the coming months following recent clinical trial approval by the European Union Clinical Trials Regulation[7](index=7&type=chunk) - THRIVE-3 is a seamless Phase 2b/3 trial, including a dose confirmation portion (n=24) and a double-blinded, randomized, placebo-controlled portion (n=105)[7](index=7&type=chunk) - IV Choline Chloride was previously granted **Fast Track designation** by the FDA[7](index=7&type=chunk) [TARA-002 in Lymphatic Malformations (LMs)](index=2&type=section&id=TARA-002%20in%20Lymphatic%20Malformations%20(LMs)) Dosing continues in the Phase 2 STARBORN-1 trial for pediatric LMs, with an interim update anticipated in 4Q 2025, following promising safety cohort results - Dosing remains ongoing in the Phase 2 STARBORN-1 trial of TARA-002 in pediatric patients with macrocystic and mixed cystic LMs[8](index=8&type=chunk) - An interim update from the STARBORN-1 trial is intended to be provided in the **fourth quarter of 2025**[8](index=8&type=chunk) - The study's first safety cohort showed **promising results**, and TARA-002 was generally well-tolerated[8](index=8&type=chunk) [Corporate Update & Financial Highlights](index=2&type=section&id=Corporate%20Update%20%26%20Financial%20Highlights) This section covers Protara Therapeutics' recent operational achievements and its financial position as of Q2 2025 [Operational Highlights](index=2&type=section&id=Operational%20Highlights) Protara strengthened its leadership with the appointment of William 'Bill' Conkling as Chief Commercial Officer and gained broader market recognition by joining the Russell 3000 Index - William 'Bill' Conkling was appointed as **Chief Commercial Officer** in June 2025, bringing over two decades of experience in developing and commercializing novel cancer and rare disease therapeutics[11](index=11&type=chunk) - Protara was added as a member of the broad-market **Russell 3000 Index**, effective June 30, 2025[11](index=11&type=chunk) [Financial Position & Outlook](index=2&type=section&id=Financial%20Position%20%26%20Outlook) As of June 30, 2025, Protara reported approximately $146 million in cash, cash equivalents, and investments, providing an expected funding runway into mid-2027 Cash, Cash Equivalents and Investments | Metric | Amount (as of June 30, 2025, in millions) | | :----- | :--------------------------------------- | | Unrestricted Cash, Cash Equivalents and Marketable Debt Securities | $145.6 | | Expected Funding Runway | Into mid-2027 | [Second Quarter 2025 Financial Performance](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Performance) Protara experienced increased operating expenses in Q2 2025, leading to a higher net loss of $15.0 million, though net loss per share decreased to $(0.35) due to increased shares outstanding Operating Expenses (Q2 2025 vs. Q2 2024) | Expense Category | Q2 2025 (in thousands) | Q2 2024 (in thousands) | Change (YoY, in thousands) | % Change (YoY) | Primary Reason for Increase | | :---------------- | :--------------------- | :--------------------- | :------------------------- | :------------- | :-------------------------- | | Research and development | $10,770 | $6,387 | +$4,383 | +68.6% | Clinical trial activities for TARA-002 and IV Choline Chloride (+$3.9M) | | General and administrative | $5,816 | $4,274 | +$1,542 | +36.1% | Personnel-related expenses (+$0.6M), market development-related expenses (+$0.5M) | Net Loss and EPS (Q2 2025 vs. Q2 2024) | Metric | Q2 2025 (in millions) | Q2 2024 (in millions) | Change (YoY, in millions) | | :----- | :-------------------- | :-------------------- | :------------------------ | | Net Loss | $(14.960) | $(9.513) | $(5.447) | | Net Loss per Share (in dollars) | $(0.35) | $(0.45) | +$0.10 | | Weighted-average shares outstanding | 42,270,855 | 21,233,163 | +21,037,692 | [Product and Disease Overviews](index=2&type=section&id=Product%20and%20Disease%20Overviews) This section provides detailed information on Protara Therapeutics' investigational products, TARA-002 and IV Choline Chloride, and the diseases they target [About TARA-002](index=2&type=section&id=About%20TARA-002) TARA-002 is an investigational cell therapy for NMIBC and LMs, derived from the same master cell bank as OK-432, hypothesized to activate immune responses - TARA-002 is an investigational cell therapy in development for the treatment of **NMIBC and LMs**[10](index=10&type=chunk) - It has been granted **Rare Pediatric Disease Designation** by the U.S. Food and Drug Administration for LMs[10](index=10&type=chunk) - TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432 (Picibanil®), with manufacturing comparability shown[10](index=10&type=chunk) - It is hypothesized to activate innate and adaptive immune cells, producing a pro-inflammatory response and directly killing tumor cells to enhance the antitumor immune response[12](index=12&type=chunk) [About Non-Muscle Invasive Bladder Cancer (NMIBC)](index=3&type=section&id=About%20Non-Muscle%20Invasive%20Bladder%20Cancer%20(NMIBC)) NMIBC is the 6th most common cancer in the United States, accounting for approximately 80% of bladder cancer diagnoses, defined as cancer confined to the bladder's inner lining - Bladder cancer is the **6th most common cancer** in the United States, with NMIBC representing approximately **80% of bladder cancer diagnoses**[13](index=13&type=chunk) - Approximately **65,000 patients** are diagnosed with NMIBC in the United States each year[13](index=13&type=chunk) - NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle[13](index=13&type=chunk) [About Lymphatic Malformations (LMs)](index=3&type=section&id=About%20Lymphatic%20Malformations%20(LMs)) LMs are rare, congenital lymphatic vessel malformations, often diagnosed in early childhood and primarily located in the head and neck, causing significant morbidities - LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system[14](index=14&type=chunk) - Most LMs are present in the head and neck region, with **over 50% detected at birth** and **90% diagnosed before the age of three years**[14](index=14&type=chunk) - Common morbidities include compression of the upper aerodigestive tract, intralesional bleeding, impingement on critical structures, recurrent infection, and cosmetic/functional disabilities[14](index=14&type=chunk) [About IV Choline Chloride](index=3&type=section&id=About%20IV%20Choline%20Chloride) IV Choline Chloride is an investigational intravenous phospholipid substrate replacement therapy for choline-deficient patients on parenteral support, holding FDA Orphan Drug and Fast Track designations with patents expiring in 2041 - IV Choline Chloride is an investigational, intravenous phospholipid substrate replacement therapy for patients receiving parenteral support (PS)[15](index=15&type=chunk) - Choline is an important substrate for phospholipids critical for healthy liver function, gene expression, cell membrane signaling, brain development, neurotransmission, muscle function, and bone health[15](index=15&type=chunk) - Approximately **78% of patients dependent on PS are choline-deficient**, and of those, approximately **63% have some degree of liver dysfunction**[15](index=15&type=chunk) - It has been granted **Orphan Drug Designation** by the FDA for prevention/treatment of choline deficiency in long-term PN and **Fast Track Designation** as a source of choline[15](index=15&type=chunk) - U.S. patents claiming a choline composition and method for treating choline deficiency with a choline composition have terms expiring in **2041**[15](index=15&type=chunk) [About Protara Therapeutics, Inc.](index=3&type=section&id=About%20Protara%20Therapeutics%2C%20Inc.) Protara Therapeutics is a clinical-stage biotechnology company dedicated to advancing transformative therapies for cancer and rare diseases, with a portfolio including TARA-002 and IV Choline Chloride - Protara is a clinical-stage biotechnology company committed to advancing **transformative therapies** for people with cancer and rare diseases[16](index=16&type=chunk) - The company's portfolio includes lead candidate **TARA-002** for NMIBC and LMs, and **IV Choline Chloride** for patients on parenteral nutrition[16](index=16&type=chunk) [Forward-Looking Statements](index=4&type=section&id=Forward-Looking%20Statements) This section provides a disclaimer regarding forward-looking statements, highlighting inherent risks and uncertainties that could cause actual results to differ materially [Disclaimer and Risk Factors](index=4&type=section&id=Disclaimer%20and%20Risk%20Factors) Statements regarding future events are "forward-looking statements" subject to risks and uncertainties, and Protara disclaims any obligation to update them, except as required by law - Statements regarding matters that are not historical facts are "**forward-looking statements**" within the meaning of the Private Securities Litigation Reform Act of 1995[17](index=17&type=chunk) - Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied[17](index=17&type=chunk) - Factors contributing to uncertainty include risks related to financial guidance, development programs, market conditions, strategic plans, financing, and general economic, industry, market, regulatory, political or public health conditions[17](index=17&type=chunk) - Protara undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law[17](index=17&type=chunk) [Financial Statements](index=5&type=section&id=Financial%20Statements) This section presents Protara Therapeutics' unaudited condensed consolidated financial statements, including balance sheets and statements of operations, for relevant periods [Unaudited Condensed Consolidated Balance Sheets](index=5&type=section&id=Unaudited%20Condensed%20Consolidated%20Balance%20Sheets) The balance sheet shows Protara's financial position as of June 30, 2025, with total assets decreasing by $24.5 million to $156.9 million, primarily due to reduced cash and cash equivalents, partially offset by increased marketable debt securities Unaudited Condensed Consolidated Balance Sheets (Selected Items, in thousands) | Item | June 30, 2025 | December 31, 2024 | Change (vs. Dec 31, 2024, in thousands) | | :-------------------------------- | :------------ | :---------------- | :--------------------------------------- | | Cash and cash equivalents | $31,496 | $162,798 | $(131,302) | | Marketable debt securities (current) | $90,720 | $7,494 | +$83,226 | | Marketable debt securities (non-current) | $23,392 | $- | +$23,392 | | Total current assets | $125,091 | $172,155 | $(47,064) | | Total assets | $156,933 | $181,454 | $(24,521) | | Total current liabilities | $9,761 | $10,961 | $(1,200) | | Total liabilities | $12,510 | $14,320 | $(1,810) | | Total stockholders' equity | $144,423 | $167,134 | $(22,711) | [Unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Unaudited%20Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For the three months ended June 30, 2025, Protara reported a net loss of $14.960 million, an increase from the prior year, driven by higher operating expenses, though net loss per share decreased to $(0.35) due to increased shares outstanding Unaudited Condensed Consolidated Statements of Operations (Selected Items, Three Months Ended, in thousands) | Item | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Change (YoY, in thousands) | % Change (YoY) | | :-------------------------------- | :------------------------------- | :------------------------------- | :------------------------- | :------------- | | Research and development | $10,770 | $6,387 | +$4,383 | +68.6% | | General and administrative | $5,816 | $4,274 | +$1,542 | +36.1% | | Total operating expenses | $16,586 | $10,661 | +$5,925 | +55.6% | | Interest and investment income (expense) | $1,626 | $1,148 | +$478 | +41.6% | | Net income (loss, in thousands) | $(14,960) | $(9,513) | $(5,447) | +57.3% (loss increased) | | Net income (loss) per share, basic and diluted (in dollars) | $(0.35) | $(0.45) | +$0.10 | -22.2% (loss per share decreased) | | Weighted-average shares outstanding, basic and diluted | 42,270,855 | 21,233,163 | +21,037,692 | +99.1% | Unaudited Condensed Consolidated Statements of Operations (Selected Items, Six Months Ended, in thousands) | Item | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Change (YoY, in thousands) | % Change (YoY) | | :-------------------------------- | :----------------------------- | :----------------------------- | :------------------------- | :------------- | | Research and development | $19,918 | $14,135 | +$5,783 | +40.9% | | General and administrative | $10,792 | $8,377 | +$2,415 | +28.8% | | Total operating expenses | $30,710 | $22,512 | +$8,198 | +36.4% | | Interest and investment income (expense) | $3,355 | $1,904 | +$1,451 | +76.2% | | Net income (loss, in thousands) | $(26,874) | $(20,608) | $(6,266) | +30.4% (loss increased) | | Net income (loss) per share, basic and diluted (in dollars) | $(0.65) | $(1.26) | +$0.61 | -48.4% (loss per share decreased) | | Weighted-average shares outstanding, basic and diluted | 41,493,714 | 16,327,056 | +25,166,658 | +154.1% | [Company Contact](index=7&type=section&id=Company%20Contact) This section provides contact information for Protara Therapeutics [Investor Relations Contact Information](index=7&type=section&id=Investor%20Relations%20Contact%20Information) This section provides the contact details for Protara Therapeutics' investor relations - Company Contact: Justine O'Malley, Protara Therapeutics, Justine.OMalley@protaratx.com, 646-817-2836[22](index=22&type=chunk)

Core Insights - Protara Therapeutics, Inc. reported financial results for Q2 2025, highlighting ongoing clinical trials and business updates [1][10] Clinical Development - The company is advancing its pipeline, particularly the ADVANCED-2 trial of TARA-002 for non-muscle invasive bladder cancer (NMIBC), with interim results expected in Q1 2026 [2][7] - Protara is on track to initiate dosing in the THRIVE-3 trial of IV Choline Chloride for patients dependent on parenteral support by the end of Q3 2025, with EU enrollment anticipated soon [4][7] - The STARBORN-1 trial of TARA-002 in pediatric patients with lymphatic malformations is ongoing, with an interim update expected in Q4 2025 [5][7] Financial Performance - As of June 30, 2025, Protara had approximately $146 million in cash and equivalents, sufficient to support operations into mid-2027 [7][16] - Research and development expenses increased to $10.8 million in Q2 2025 from $6.4 million in the same period of 2024, primarily due to clinical trial activities [16][22] - The company reported a net loss of $15.0 million, or $0.35 per share, compared to a net loss of $9.5 million, or $0.45 per share, in Q2 2024 [16][23] Corporate Updates - William "Bill" Conkling was appointed as Chief Commercial Officer in June 2025, bringing over 20 years of experience in developing and commercializing novel therapeutics [6][9] - Protara was added to the Russell 3000® Index effective June 30, 2025, enhancing its visibility in the market [9]

Group 1 - Protara Therapeutics has been added to the Russell 3000 Index, effective June 30, 2025, reflecting the company's progress in executing its pipeline [1][2] - The inclusion in the Russell 3000 Index enhances Protara's visibility among the financial community, which is crucial for attracting investment and generating shareholder value [2] - The Russell US Indexes reconstitution captures the 4,000 largest U.S. stocks ranked by market capitalization, with approximately $10.6 trillion in assets benchmarked against these indices as of June 2024 [2] Group 2 - Protara is a clinical-stage biotechnology company focused on developing transformative therapies for cancer and rare diseases, with its lead candidate being TARA-002 [3] - TARA-002 is currently undergoing Phase 2 trials for non-muscle invasive bladder cancer and lymphatic malformations, targeting patients unresponsive to Bacillus Calmette-Guérin treatment [3] - The company is also developing IV Choline Chloride for patients on parenteral nutrition who cannot meet their choline needs through oral or enteral routes [3]

Core Insights - Protara Therapeutics has appointed William "Bill" Conkling as Chief Commercial Officer, bringing over 20 years of experience in developing and commercializing therapies for cancer and rare diseases [1][2][3] - The company is positioned for growth with a potentially best-in-class bladder cancer therapy and two de-risked rare disease programs, aiming to significantly impact patient outcomes [2][5] Company Overview - Protara Therapeutics is a clinical-stage biotechnology company focused on transformative therapies for cancer and rare diseases, with its lead candidate TARA-002 in development for non-muscle invasive bladder cancer and lymphatic malformations [5] - The company is conducting ongoing Phase 2 trials for TARA-002 in patients with carcinoma in situ who are unresponsive or naïve to Bacillus Calmette-Guérin treatment, as well as in pediatric patients with lymphatic malformations [5] Leadership Background - Bill Conkling previously served as President and CEO of Rafael Holdings, where he built the commercial organization and developed go-to-market strategies [2][3] - He has extensive experience in the oncology field, having led the U.S. commercial organization for the launch of Trodelvy at Immunomedics and held key roles at Novartis Pharmaceuticals, including the commercialization of Kymriah [3][4] Stock Options and Awards - As part of his employment, Mr. Conkling received an inducement grant of options to purchase 200,000 shares at an exercise price of $3.30, along with a restricted stock unit award for 50,000 shares [6] - The options will vest over four years, with 25% vesting on the first anniversary and the remainder vesting monthly over the following 36 months [6]

Protara Therapeutics (TARA) FY Conference Summary Company Overview - **Company**: Protara Therapeutics - **Focus**: Development of innovative therapies for oncology, specifically targeting non-muscle invasive bladder cancer (NMIBC) with their lead program, TAR-002 Key Points and Arguments Product Development and Mechanism of Action - **TAR-002**: An investigational, genetically distinct strain of *Streptococcus pyogenes* designed to retain immune-stimulating properties through a proprietary manufacturing process [3][4] - **Comparison with BCG**: - Both TAR-002 and BCG are bacterial immune potentiators that drive a TH1 pro-inflammatory response, critical for antitumor immunity [5] - TAR-002 acts as a TLR2 agonist, while BCG is a TLR4 agonist, leading to significantly stronger tumor cell killing and higher upregulation of pro-inflammatory cytokines like TNF-alpha and interferon-gamma [6] - TAR-002 downregulates IL-8, which is associated with bladder cancer recurrence, contrasting with BCG's upregulation of IL-8 [7] Clinical Data and Efficacy Expectations - **Durable Responses**: Nonclinical studies show around 70% of mice remain cancer-free at the 60-day mark, indicating potential for durable clinical responses [7] - **Efficacy Benchmarks**: - A competitive complete response rate (CRR) of 30% is needed to be considered viable, with 40% being competitive and 50% considered best-in-class [12][13] - Initial data suggests a CRR of 63% at six months and 43% at twelve months in BCG-naive patients, with a total CRR of 76% [41] Enrollment and Market Strategy - **Enrollment Progress**: Enrollment is progressing well, with 30 sites in the US and approvals in Japan and China, aiming for full enrollment by spring 2026 [19][20] - **Patient Population**: The study is expected to have a similar split of 75% CIS and 25% concomitant papillary patients, consistent with other studies in this patient population [23][22] Competitive Landscape and Market Opportunity - **Market Size**: The addressable market is estimated at around $5 billion, with a significant number of patients seeking to avoid cystectomy [26] - **Treatment Sequencing**: Future treatment strategies may involve sequencing immune potentiators and cytotoxic drugs, enhancing the potential for TAR-002 in the treatment landscape [26] Regulatory and Development Plans - **FDA Engagement**: Plans to engage with the FDA regarding registrational studies for TAR-002, particularly in the BCG-naive setting, acknowledging the need for alternative treatment options [43][44] - **Comparative Studies**: Proposals to use chemotherapy as a comparator in studies, reflecting real-world treatment practices [46] Upcoming Catalysts - **Key Data Releases**: Anticipated data on 25 BCG unresponsive patients by the end of the year, along with updates on other ongoing studies [50][51] Additional Important Insights - **Tolerability and Administration**: TAR-002 is noted for its favorable tolerability profile, which may facilitate its adoption in community settings where treatment disruptions are less feasible [37][38] - **Long-term Development**: The company aims to position TAR-002 as a viable alternative to BCG, especially for patients who cannot access or tolerate standard BCG therapy [42][44] This summary encapsulates the critical insights from the Protara Therapeutics conference, highlighting the company's strategic direction, product differentiation, and market potential in the oncology space.

Financial Data and Key Metrics Changes - The company reported a 67% complete response (CR) rate in the pivotal BCG unresponsive cohort as of April, indicating strong performance in this segment [13][21]. - The target for the unresponsive dataset is a CR rate in the sixties, potentially reaching the seventies, which would be competitive with existing therapies [21]. Business Line Data and Key Metrics Changes - The lead asset, Tara 002, is positioned as a broad-spectrum immunopotentiator, with a focus on muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) [10][12]. - The company is in late-stage development across three programs, including Tara 002 and IV choline chloride phospholipid substrate replacement therapy, indicating a diversified pipeline [9]. Market Data and Key Metrics Changes - The unmet need in NMIBC is characterized by a strong motivation to reduce cystectomies, with the company aiming to address this through innovative treatment options [10][11]. - The competitive landscape includes various mechanisms of action, with the company’s product being the only broad-spectrum immunopotentiator in late-stage development [12]. Company Strategy and Development Direction - The company aims to redefine risk in its portfolio by understanding and containing risks associated with each asset, particularly in the context of evolving regulatory and manufacturing landscapes [5][9]. - The strategy includes engaging with the FDA to demonstrate that standard of care for BCG eligible patients extends beyond just BCG, incorporating other chemotherapeutics [24][26]. Management's Comments on Operating Environment and Future Outlook - Management highlighted the importance of real-world evidence in shaping trial designs and regulatory interactions, particularly in the context of BCG shortages [24][26]. - The company anticipates that as the dataset broadens, fewer patients will require reinduction, which could enhance the overall treatment profile [30]. Other Important Information - The company is conducting a single-arm open-label study for Tara 002 in pediatric nonmalignant diseases, which has garnered interest due to its potential and existing standard of care in Japan [9]. - The company emphasizes the importance of tolerability and ease of use in community settings, which could drive adoption among urologists [36][38]. Q&A Session Summary Question: What is the unmet need in NMIBC and how does Tara 002 address it? - The unmet need is categorized into three buckets, with a focus on reducing cystectomies and addressing the heterogeneous nature of the disease through various treatment modalities [10][11]. Question: What benchmarks should be set for the six-month data in the BCG unresponsive cohort? - The company targets a CR rate of around 75% in CIS only patients, with expectations that the overall CR rate will be in the sixties or seventies [21]. Question: How does the company plan to approach the FDA regarding registrational studies? - The company plans to present real-world evidence to the FDA, arguing that the standard of care includes both BCG and other chemotherapeutics due to BCG shortages [24][26]. Question: What are the key differentiating factors for Tara 002 in the NMIBC space? - Key differentiators include the drug's tolerability, safety profile, and the ability to be integrated into existing workflows without causing disruptions [36][38].

Company Overview - Protara Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing transformative therapies for cancer and rare diseases [2] - The company's lead candidate, TARA-002, is an investigational cell-based therapy aimed at treating non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs) [2] - Protara is conducting an ongoing Phase 2 trial for TARA-002 in NMIBC patients with carcinoma in situ (CIS) who are unresponsive or naïve to Bacillus Calmette-Guérin (BCG) treatment, as well as a Phase 2 trial in pediatric patients with LMs [2] Upcoming Events - Protara management will participate in the H.C. Wainwright & Co. 3 Annual BioConnect Investor Conference with a fireside chat scheduled for May 20, 2025, at 12:30 pm ET in New York [3] - The company will also take part in the TD Cowen 6 Annual Oncology Innovation Summit, which will be held virtually on May 27, 2025, at 1:30 pm ET [3] Additional Information - Protara is also developing IV Choline Chloride, an investigational phospholipid substrate replacement for patients on parenteral nutrition who cannot meet their choline needs through oral or enteral routes [2] - Live webcasts of the investor conferences will be available on the company's website and archived for a limited time [1]

PART I – FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements](index=6&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements) Q1 2025 unaudited condensed consolidated financial statements report a $11.9 million net loss, increased cash usage, and decreased total assets [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2025, total assets decreased to $168.6 million, primarily due to a significant reduction in cash and cash equivalents, while liabilities and equity also declined Condensed Consolidated Balance Sheets (in thousands) | | As of March 31, 2025 | As of December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $91,461 | $162,798 | | Total current assets | $126,532 | $172,155 | | **Total assets** | **$168,559** | **$181,454** | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $7,018 | $10,961 | | **Total liabilities** | **$10,075** | **$14,320** | | **Total stockholders' equity** | **$158,484** | **$167,134** | | **Total liabilities and stockholders' equity** | **$168,559** | **$181,454** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For Q1 2025, the net loss increased to $11.9 million due to higher operating expenses, primarily from increased research and development activities, resulting in a net loss per share of $(0.29) Condensed Consolidated Statements of Operations (in thousands) | | For the Three Months Ended March 31, | | :--- | :--- | :--- | | | **2025** | **2024** | | Research and development | $9,148 | $7,748 | | General and administrative | $4,976 | $4,103 | | **Total operating expenses** | **$14,124** | **$11,851** | | **Income (Loss) from operations** | **$(14,124)** | **$(11,851)** | | Other income (expense), net | $2,210 | $756 | | **Net income (loss)** | **$(11,914)** | **$(11,095)** | | **Net income (loss) per share, basic and diluted** | **$(0.29)** | **$(0.97)** | | Weighted-average shares outstanding, basic and diluted | 40,707,937 | 11,420,948 | [Condensed Consolidated Statements of Cash Flows](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to $14.7 million in Q1 2025, with a significant shift to cash used in investing activities, resulting in a net decrease of $71.3 million in cash and equivalents Condensed Consolidated Statements of Cash Flows (in thousands) | | For the Three Months Ended March 31, | | :--- | :--- | :--- | | | **2025** | **2024** | | Net cash provided by (used in) operating activities | $(14,713) | $(10,379) | | Net cash provided by (used in) investing activities | $(58,354) | $23,100 | | Net cash provided by (used in) financing activities | $1,730 | $(76) | | **Net increase (decrease) in cash and cash equivalents and restricted cash** | **$(71,337)** | **$12,645** | | Cash and cash equivalents and restricted cash - beginning of period | $163,543 | $40,331 | | **Cash and cash equivalents and restricted cash - end of period** | **$92,206** | **$52,976** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) The notes describe the company as a clinical-stage biopharmaceutical firm with no revenue, detailing recent capital raises and R&D expense drivers, while affirming sufficient financial resources for the next twelve months - The company is a clinical-stage biopharmaceutical company focused on therapies for cancer and rare diseases, including TARA-002 for NMIBC and LMs, and IV Choline Chloride for patients on parenteral support[26](index=26&type=chunk) - The company believes its current financial resources are **sufficient to fund operations for at least twelve months** from the financial statement issuance date[28](index=28&type=chunk) - In April 2024, the company completed a private placement, resulting in net proceeds of **approximately $42.0 million**[68](index=68&type=chunk) - In December 2024, the company closed a public offering with net proceeds of **approximately $93.4 million**. In January 2025, the underwriters partially exercised their option, providing additional net proceeds of **approximately $2.5 million**[79](index=79&type=chunk)[83](index=83&type=chunk) R&D Expenses by Program (in thousands) | Program | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | TARA-002 in NMIBC | $3,557 | $2,789 | | TARA-002 in LMs | $549 | $933 | | IV Choline Chloride | $2,515 | $258 | | Other research and development | $2,335 | $3,394 | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=29&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses clinical program advancements, increased R&D expenses, a $11.9 million net loss, and $157.5 million in cash, deemed sufficient for the next year [Overview and Clinical Program Updates](index=29&type=section&id=Overview%20and%20Clinical%20Program%20Updates) Protara, a clinical-stage biopharmaceutical company, is advancing TARA-002 for NMIBC and LMs, and IV Choline Chloride, with positive interim Phase 2 data and plans for a registrational Phase 3 trial in Q3 2025 - The lead oncology program is TARA-002 for NMIBC. The ADVANCED-2 Phase 2 trial is ongoing, with Cohort B expected to be registrational[117](index=117&type=chunk)[119](index=119&type=chunk) - Interim data from the ADVANCED-2 trial (BCG-Unresponsive cohort) showed a **100% complete response (CR) rate** at six months (5/5 patients) and **67% at 12 months** (2/3 patients)[120](index=120&type=chunk) - The company plans to initiate THRIVE-3, a registrational Phase 3 trial for IV Choline Chloride, in the third quarter of 2025[130](index=130&type=chunk) - The STARBORN-1 Phase 2 trial for TARA-002 in LMs is ongoing, with interim data showing **two of three patients achieved a complete response** after one injection[132](index=132&type=chunk)[133](index=133&type=chunk) [Results of Operations](index=34&type=section&id=Results%20of%20Operations) Total operating expenses increased to $14.1 million in Q1 2025, driven by higher R&D costs for the IV Choline Chloride program and increased G&A expenses, while other income also rose Comparison of Operations (in thousands) | | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Research and development | $9,148 | $7,748 | $1,400 | | General and administrative | $4,976 | $4,103 | $873 | | **Total operating expenses** | **$14,124** | **$11,851** | **$2,273** | | **Net income (loss)** | **$(11,914)** | **$(11,095)** | **$(819)** | - The increase in R&D expenses was primarily due to a **$2.6 million** increase in direct expenses for product candidates, mainly a **$2.3 million** increase for the IV Choline Chloride program[146](index=146&type=chunk) - The increase in G&A expenses was primarily due to a **$0.4 million** increase in personnel-related expenses and a combined **$0.4 million** increase in market development and investor relations activities[147](index=147&type=chunk) [Liquidity and Capital Resources](index=35&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2025, the company held $157.5 million in unrestricted cash and marketable securities, with $14.7 million used in operations, and believes current resources are sufficient for the next twelve months - As of March 31, 2025, the company had **$157.5 million** in unrestricted cash and cash equivalents and marketable debt securities[149](index=149&type=chunk) - The company believes its current financial resources are **sufficient to satisfy estimated liquidity needs for at least twelve months**[151](index=151&type=chunk) Cash Flow Summary (in thousands) | | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(14,713) | $(10,379) | | Net cash (used in) provided by investing activities | $(58,354) | $23,100 | | Net cash provided by (used in) financing activities | $1,730 | $(76) | - The **$81.5 million** change in investing cash flow was primarily due to a **$65.8 million** increase in purchases of marketable debt securities and a **$15.6 million** decrease in proceeds from maturities[155](index=155&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=39&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section is not applicable to the company for this reporting period - **Not applicable**[164](index=164&type=chunk) [Item 4. Controls and Procedures](index=39&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal control over financial reporting during the quarter - Management concluded that as of March 31, 2025, the company's disclosure controls and procedures were **effective at the reasonable assurance level**[166](index=166&type=chunk) - There were **no changes in internal control over financial reporting** during the quarter ended March 31, 2025, that have materially affected, or are reasonably likely to materially affect, internal controls[168](index=168&type=chunk) PART II – OTHER INFORMATION [Item 1. Legal Proceedings](index=40&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any legal proceedings that are expected to have a material adverse effect on its business - The company is **not currently a party to any legal proceedings that management believes would likely have a material adverse effect** on the business[170](index=170&type=chunk) [Item 1A. Risk Factors](index=40&type=section&id=Item%201A.%20Risk%20Factors) There have been no material changes to the risk factors previously disclosed in the company's Annual Report on Form 10-K for the year ended December 31, 2024 - There were **no material changes to the risk factors** previously disclosed in the Annual Report on Form 10-K for the year ended December 31, 2024[171](index=171&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=40&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) During Q1 2025, 1,191 shares of Series 1 Convertible Preferred Stock were converted into 1,190,996 shares of common stock, stemming from a January 2020 private placement - During the three months ended March 31, 2025, **1,191 shares** of Series 1 Convertible Preferred Stock were converted into **1,190,996 shares** of common stock[172](index=172&type=chunk) [Item 5. Other Information](index=40&type=section&id=Item%205.%20Other%20Information) During the first quarter of 2025, no director or officer of the company adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement - **No director or officer adopted or terminated** a Rule 10b5-1 trading arrangement or non-Rule 10b5-1 trading arrangement during the quarter[176](index=176&type=chunk) [Item 6. Exhibits](index=41&type=section&id=Item%206.%20Exhibits) This section provides an index of all exhibits filed as part of the Quarterly Report on Form 10-Q, including corporate governance documents, agreements related to securities, and officer certifications

[Recent Progress and Highlights](index=2&type=section&id=Recent%20Progress%20and%20Highlights) Protara reported significant Q1 2025 clinical progress, including positive interim ADVANCED-2 trial results for TARA-002 in NMIBC and plans to initiate the THRIVE-3 trial for IV Choline Chloride in Q3 2025 [TARA-002 in NMIBC](index=2&type=section&id=TARA-002%20in%20NMIBC) - At the AUA 2025 Annual Meeting, updated interim results from the ADVANCED-2 trial were presented, showing promising complete response (CR) rates for TARA-002[8](index=8&type=chunk) ADVANCED-2 Trial Interim Results (as of April 16, 2025) | Patient Cohort | CR Rate (Any Time) | 12-Month CR Rate | | :--- | :--- | :--- | | BCG-Unresponsive | 100% (5/5) | 67% (2/3) | | BCG-Naïve | 76% (16/21) | 43% (3/7) | - TARA-002 was generally well-tolerated, with the majority of adverse events being Grade 1 and transient, and no Grade 3 or greater treatment-related adverse events reported[8](index=8&type=chunk) - Future milestones include announcing interim results from approximately 25 six-month evaluable BCG-Unresponsive patients by the end of 2025 and providing an update on the planned BCG-Naïve registrational trial design in H2 2025[8](index=8&type=chunk) [IV Choline Chloride for Patients on Parenteral Support (PS)](index=2&type=section&id=IV%20Choline%20Chloride%20for%20Patients%20on%20Parenteral%20Support%20%28PS%29) - The company plans to initiate THRIVE-3, a registrational Phase 3 clinical trial, in the **third quarter of 2025**[6](index=6&type=chunk) - THRIVE-3 is a seamless Phase 2b/3 trial to assess the efficacy and safety of IV Choline Chloride in adolescents and adults on long-term parenteral support[6](index=6&type=chunk) - IV Choline Chloride has previously been granted Fast Track designation by the FDA[6](index=6&type=chunk) [TARA-002 in Lymphatic Malformations (LMs)](index=2&type=section&id=TARA-002%20in%20Lymphatic%20Malformations%20%28LMs%29) - Dosing is progressing in the Phase 2 STARBORN-1 trial for pediatric patients with macrocystic and mixed cystic LMs[7](index=7&type=chunk) - An interim update from the STARBORN-1 trial is planned for the **second half of 2025**[7](index=7&type=chunk) [Corporate Update](index=3&type=section&id=Corporate%20Update) In April 2025, Protara significantly strengthened its leadership team with the strategic appointments of a new Chief Medical Officer and a new Chief People Officer, bringing extensive experience in oncology, drug development, and life sciences organizational growth - Appointed Leonardo Viana Nicacio, M.D., as Chief Medical Officer. Dr. Nicacio has nearly **20 years of experience** in oncology, drug development, and regulatory affairs, previously serving at Stemline Therapeutics[9](index=9&type=chunk) - Appointed Shane Williams, Ph.D., as VP, Head of Human Resources, Chief People Officer. Dr. Williams has a strong background in driving growth and building high-performing teams, most recently at Century Therapeutics[9](index=9&type=chunk) [First Quarter 2025 Financial Results](index=3&type=section&id=First%20Quarter%202025%20Financial%20Results) Protara reported a net loss of **$11.9 million** for Q1 2025, up from **$11.1 million** in Q1 2024 due to increased clinical trial and personnel costs, while maintaining a strong financial position with **$157.5 million** in cash, cash equivalents, and investments, projected to fund operations into 2027 Q1 2025 vs. Q1 2024 Financial Performance (in millions, except per share data) | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Research & Development Expenses | $9.1 | $7.7 | | General & Administrative Expenses | $5.0 | $4.1 | | Net Loss | $11.9 | $11.1 | | Net Loss Per Share | $0.29 | $0.97 | - The increase in R&D expenses was mainly due to a **$2.6 million** rise in clinical trial activities for TARA-002 and IV Choline[13](index=13&type=chunk) - The increase in G&A expenses was primarily driven by higher personnel-related costs and professional fees[13](index=13&type=chunk) [Financial Statements](index=6&type=section&id=Financial%20Statements) This section includes the unaudited condensed consolidated balance sheets as of March 31, 2025, compared to December 31, 2024, and the unaudited condensed consolidated statements of operations for the three-month periods ending March 31, 2025, and 2024 [Unaudited Condensed Consolidated Balance Sheets](index=6&type=section&id=Unaudited%20Condensed%20Consolidated%20Balance%20Sheets) Balance Sheet Summary (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $91,461 | $162,798 | | Total current assets | $126,532 | $172,155 | | Total assets | $168,559 | $181,454 | | Total current liabilities | $7,018 | $10,961 | | Total liabilities | $10,075 | $14,320 | | Total stockholders' equity | $158,484 | $167,134 | [Unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Unaudited%20Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Statement of Operations Summary (in thousands, except per share data) | Account | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Total operating expenses | $14,124 | $11,851 | | Income (Loss) from operations | $(14,124) | $(11,851) | | Net income (loss) | $(11,914) | $(11,095) | | Net income (loss) per share | $(0.29) | $(0.97) | | Weighted-average shares outstanding | 40,707,937 | 11,420,948 |

Core Insights - Protara Therapeutics reported significant progress in 2025, particularly with positive interim results from the ADVANCED-2 trial of TARA-002 for non-muscle invasive bladder cancer (NMIBC) [2][5] - The company plans to initiate the THRIVE-3 Phase 3 clinical trial for IV Choline Chloride in Q3 2025, targeting patients on parenteral support [4][5] - Protara's financial results for Q1 2025 show a net loss of $11.9 million, with cash reserves expected to support operations into 2027 [14][24] Recent Progress and Highlights - TARA-002 demonstrated a complete response (CR) rate of 100% in BCG-Unresponsive patients and 76% in BCG-Naïve patients during the ADVANCED-2 trial [6] - The company expects to announce interim results from approximately 25 six-month evaluable BCG-Unresponsive patients by the end of 2025 [5][6] - Leadership team strengthened with key appointments, including Dr. Leonardo Viana Nicacio as Chief Medical Officer [9] Financial Overview - As of March 31, 2025, Protara had cash, cash equivalents, and investments totaling $158 million, sufficient to fund operations into 2027 [5][14] - Research and development expenses increased to $9.1 million in Q1 2025 from $7.7 million in the prior year, primarily due to clinical trial activities [14][24] - General and administrative expenses rose to $5.0 million in Q1 2025 from $4.1 million in the prior year [14][24] Product Development - TARA-002 is being evaluated for NMIBC and lymphatic malformations (LMs), with ongoing trials expected to yield interim updates in the second half of 2025 [8][11] - IV Choline Chloride is positioned as a potential first FDA-approved IV choline formulation for patients on parenteral nutrition [16] - The company continues to explore combination treatments and dosing strategies for TARA-002 in NMIBC patients [6][12]