Core Insights - Protara Therapeutics is a clinical-stage biotech company focused on developing treatments for cancer and rare diseases, with its lead program TARA-002 targeting non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs) [2][8] - TARA-002 utilizes a novel approach derived from a genetically distinct cell bank, functioning through dual mechanisms of directly killing tumor cells and stimulating an immune response [1][8] - The company is also advancing IV Choline Chloride for patients requiring parenteral nutrition, addressing a significant unmet need [10] TARA-002 Development - TARA-002 is currently being evaluated in a mid-stage study called ADVANCED-2 for NMIBC, showing promising early results with a 67% complete remission rate in BCG-unresponsive patients at six months [8][12] - In the Phase 2 STARBORN-1 trial for lymphatic malformations, two out of three pediatric patients achieved complete response after one injection, indicating a favorable safety profile [9][12] - Protara plans to deliver interim results for both trials in 1Q26 and 4Q25, respectively [8][9] Market Potential and Analyst Sentiment - Analysts project TARA-002 represents a potential market opportunity exceeding $500 million, with a strong buy consensus rating and a price target suggesting an 840% upside [12][13] - The average price target from analysts for TARA shares is $24.20, indicating a potential upside of approximately 659% [13] Financial Performance of Alpha Teknova - Alpha Teknova reported $10.3 million in revenue for 2Q25, a 7.3% year-over-year increase, with a reaffirmed full-year revenue guidance of $39-42 million [17] - The company is positioned to benefit from growth in the bioprocessing market, with expectations of over 20% revenue growth and 30%+ adjusted EBITDA margins in the long term [19][20] Analyst Ratings for Alpha Teknova - Alpha Teknova holds a strong buy consensus rating, with a price target of $12 indicating a potential one-year upside of approximately 159% [20]

Summary of Protara Therapeutics FY Conference Call Company Overview - **Company**: Protara Therapeutics (NasdaqGM:TARA) - **Date of Conference**: September 09, 2025 Key Industry and Company Insights Lymphatic Malformations - The largest data set on lymphatic malformations was generated by the University of Iowa, involving over 550 patients across 27 centers [1] - Protara is preparing a registration package for FDA submission, leveraging this data set and experience from Japan to seek accelerated approval [1] - TARA-002 is positioned as a treatment for BCG-unresponsive patients, with a focus on its unique mechanism of action compared to BCG [2][3] Mechanism of Action - TARA-002 acts as a TLR2/NOD2 activator, differing significantly from BCG, which is a TLR4 activator [2] - TARA-002 has demonstrated three-year stability at refrigerated temperatures and can be administered easily without special handling [2] - The drug upregulates key cytokines such as TNF-alpha, interferon-gamma, and IL-12, which are important for immune activation, while down-regulating IL-8, associated with recurrence [3][4] Clinical Trials and Data - Protara is currently enrolling patients in an Advanced II study for NMIBC (non-muscle invasive bladder cancer) and plans to publish interim data in February [4] - The company has reported a complete response rate of over 70% at six months and over 40% at twelve months in BCG-naive patients [6] - A significant portion of BCG-eligible patients (approximately 35%) do not receive BCG treatment, presenting an opportunity for TARA-002 [5] Safety and Efficacy - TARA-002 has shown no treatment-related grade 3 adverse events, with common side effects being mild and related to administration [7] - The administration process is straightforward, with efficacy comparable to other products in development [8] IV Choline Chloride Program - Protara is also developing IV Choline Chloride as a therapy for patients on parenteral support, addressing metabolic deficiencies [9][10] - The pivotal study aims to demonstrate elevated choline levels in serum as a primary endpoint, with interim data expected in mid-2026 [10][11] Market Potential and Future Directions - The incidence of lymphatic malformations is estimated at 1 in 2,000 to 1 in 4,000 live births, with a significant portion being macrocystic [15][16] - Protara aims to expand TARA-002's application to other maxillofacial cysts, potentially addressing a larger patient population [17] - The company holds $146 million in cash, sufficient to fund operations through 2027 and multiple catalysts in 2026 [18] Additional Important Points - Protara is actively engaging with the FDA regarding study designs for BCG alternative settings [5] - The company is focused on differentiating its product profile to drive adoption in a competitive market [7] - The ongoing studies and data collection are critical for establishing TARA-002's efficacy and safety in various patient populations [12][14]

Protara Therapeutics (TARA) Conference Call Summary Company Overview - Protara Therapeutics is a development-stage company focused on oncology and rare diseases, with two main franchises: oncology (specifically bladder cancer) and rare diseases [2][3] Oncology Segment TARA-002 Program - TARA-002 is a genetically distinct strain of Streptococcus pyogenes, currently in registrational studies for non-muscle invasive bladder cancer (NMIBC) [2] - The program aims to leverage established biological mechanisms and evolving science to accelerate development and commercialization [2] - Previous data releases showed a 100% complete response rate in a small cohort of BCG-unresponsive carcinoma in situ (CIS) patients, with 80% at six months and over 60% at 12 months [5][6] - Upcoming data release will include 18-month data for both BCG-unresponsive and BCG-naive patients [7][8] Competitive Landscape - Competitive response rates are discussed, with a threshold of 50% complete response at six months to be part of the conversation, and 75% or higher considered a "category killer" [9][10] - Protara aims to differentiate TARA-002 by its ease of administration, similar to BCG, and a favorable safety profile [29][30] Enrollment and Regulatory Pathway - Enrollment is proceeding as expected, with a focus on the right patient population [31] - The company is actively adding international sites to enhance enrollment, particularly in the BCG-unresponsive cohort [31] - Discussions with the FDA regarding the regulatory pathway for BCG-naive patients are ongoing, with updates expected by the end of the year [44] Rare Disease Segment IV Choline Chloride Program - The Thrive 3 trial is a phase 2B3 seamless design study, currently facing enrollment challenges in the U.S. due to competition for hospital beds [46][47] - European sites are expected to enroll significantly more patients, with one site in France having 500 patients on parenteral support [49][50] - Initial data from the Thrive 3 trial is anticipated by the summer of 2026 [51] Key Priorities - The primary focus for the upcoming year is on patient enrollment across both oncology and rare disease programs [52][54] Additional Insights - The management team has extensive experience in biotech and drug development, which informs their strategic approach [3] - Protara's strategy includes a focus on manufacturing capabilities and cost of goods sold, which allows for competitive pricing and distribution flexibility [30]

PART I – FINANCIAL INFORMATION This section presents Protara Therapeutics, Inc.'s unaudited condensed consolidated financial statements and detailed notes on accounting policies, financial instruments, and equity activities [Item 1. Condensed Consolidated Financial Statements](index=6&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements) This section presents Protara Therapeutics, Inc.'s unaudited condensed consolidated financial statements and detailed notes on accounting policies, financial instruments, and equity activities [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Condensed Consolidated Balance Sheets (in thousands) | Metric (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Cash and cash equivalents | $31,496 | $162,798 | | Marketable debt securities | $90,720 | $7,494 | | Total current assets | $125,091 | $172,155 | | Total assets | $156,933 | $181,454 | | Total current liabilities | $9,761 | $10,961 | | Total liabilities | $12,510 | $14,320 | | Total stockholders' equity | $144,423 | $167,134 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands) | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $10,770 | $6,387 | $19,918 | $14,135 | | General and administrative | $5,816 | $4,274 | $10,792 | $8,377 | | Total operating expenses | $16,586 | $10,661 | $30,710 | $22,512 | | Net income (loss) | $(14,960) | $(9,513) | $(26,874) | $(20,608) | | Net income (loss) per share, basic and diluted | $(0.35) | $(0.45) | $(0.65) | $(1.26) | [Condensed Consolidated Statements of Changes in Stockholders' Equity](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Changes%20in%20Stockholders'%20Equity) - Total stockholders' equity decreased from **$167,134 thousand** at December 31, 2024, to **$144,423 thousand** at June 30, 2025, primarily due to a net loss of **$14,960 thousand** for the three months ended June 30, 2025, and **$11,914 thousand** for the three months ended March 31, 2025[21](index=21&type=chunk) - Common stock shares outstanding increased from 35,044,772 at December 31, 2024, to 38,581,863 at June 30, 2025, driven by conversions of Series 1 Preferred Stock, exercise of pre-funded warrants, and the Underwriters' Option[21](index=21&type=chunk) - Additional paid-in capital increased from **$412,077 thousand** to **$416,161 thousand**, reflecting proceeds from equity issuances and stock-based compensation[21](index=21&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Condensed Consolidated Statements of Cash Flows (in thousands) | Cash Flow Activity (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Net cash used in operating activities | $(26,963) | $(18,066) | | Net cash used in investing activities | $(106,077) | $26,045 | | Net cash provided by financing activities | $1,738 | $42,016 | | Net increase (decrease) in cash and restricted cash | $(131,302) | $49,995 | | Cash and cash equivalents and restricted cash - end of period | $32,241 | $90,326 | [Notes to Unaudited Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) [1. Organization and Nature of the Business](index=10&type=section&id=1.%20Organization%20and%20Nature%20of%20the%20Business) - Protara Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on cancer and rare diseases, with development programs for TARA-002 (non-muscle invasive bladder cancer and lymphatic malformations) and IV Choline Chloride (patients receiving parenteral support)[25](index=25&type=chunk) - The Company has no current or near-term revenues and will require additional capital to fund its drug development efforts, though current financial resources are deemed sufficient for at least the next twelve months[26](index=26&type=chunk)[27](index=27&type=chunk) [2. Summary of Significant Accounting Policies](index=10&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) - The financial statements are unaudited and prepared in accordance with GAAP and SEC rules for interim statements, and should be read with the 2024 Annual Report on Form 10-K[36](index=36&type=chunk) - Stock-based compensation for stock options, RSUs, and ESPP is measured at fair value on grant date and recognized over the vesting period, using models like Black-Scholes for options and ESPP[29](index=29&type=chunk)[30](index=30&type=chunk)[31](index=31&type=chunk)[32](index=32&type=chunk)[33](index=33&type=chunk)[34](index=34&type=chunk) - The Company is evaluating new FASB ASUs (2023-09 on Income Tax Disclosures and 2024-03 on Expense Disaggregation Disclosures) but does not anticipate a material impact on its consolidated financial statements from ASU 2023-09[38](index=38&type=chunk)[39](index=39&type=chunk) [3. Fair Value of Financial Instruments](index=11&type=section&id=3.%20Fair%20Value%20of%20Financial%20Instruments) - Fair value measurements are categorized into a three-level hierarchy based on input observability (Level 1: quoted prices in active markets; Level 2: observable inputs other than Level 1; Level 3: unobservable inputs)[41](index=41&type=chunk)[42](index=42&type=chunk)[43](index=43&type=chunk) Fair Value of Financial Assets (in thousands) | Financial Asset (in thousands) | Level 1 (June 30, 2025) | Level 2 (June 30, 2025) | Total (June 30, 2025) | | :----------------------------- | :---------------------- | :---------------------- | :-------------------- | | Money market funds | $30,983 | - | $30,983 | | Restricted cash (money market funds) | $745 | - | $745 | | Corporate bonds | - | $81,141 | $81,141 | | U.S. Treasury securities | $32,971 | - | $32,971 | | **Total** | **$64,699** | **$81,141** | **$145,840** | Fair Value of Financial Assets (in thousands) | Financial Asset (in thousands) | Level 1 (Dec 31, 2024) | Level 2 (Dec 31, 2024) | Total (Dec 31, 2024) | | :----------------------------- | :--------------------- | :--------------------- | :------------------- | | Money market funds | $162,297 | - | $162,297 | | Restricted cash (money market funds) | $745 | - | $745 | | U.S. Treasury securities | $7,494 | - | $7,494 | | **Total** | **$170,536** | **-** | **$170,536** | [4. Marketable Debt Securities](index=13&type=section&id=4.%20Marketable%20Debt%20Securities) - All marketable debt securities are classified as available-for-sale, with unrealized gains and losses reported in accumulated other comprehensive income (loss)[52](index=52&type=chunk) Marketable Debt Securities (in thousands) | Marketable Debt Securities (in thousands) | Amortized Cost (June 30, 2025) | Unrealized Gains (June 30, 2025) | Unrealized Losses (June 30, 2025) | Estimated Fair Value (June 30, 2025) | | :---------------------------------------- | :----------------------------- | :------------------------------- | :-------------------------------- | :----------------------------------- | | U.S. Treasury securities (current) | $27,920 | $31 | $(1) | $27,950 | | U.S. Treasury securities (non-current) | $5,001 | $20 | - | $5,021 | | Corporate bonds (current) | $62,790 | $17 | $(37) | $62,770 | | Corporate bonds (non-current) | $18,324 | $52 | $(5) | $18,371 | | **Total** | **$114,035** | **$120** | **$(43)** | **$114,112** | Interest and Investment Income (in thousands) | Interest and Investment Income (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Interest income | $1,223 | $1,130 | $2,778 | $1,809 | | Accretion of discount (Amortization of premium), net | $389 | $7 | $555 | $75 | | Dividend income | $14 | $11 | $22 | $20 | | **Total** | **$1,626** | **$1,148** | **$3,355** | **$1,904** | [5. Prepaid Expenses and Other Current Assets](index=17&type=section&id=5.%20Prepaid%20Expenses%20and%20Other%20Current%20Assets) Prepaid Expenses and Other Current Assets (in thousands) | Prepaid Expenses and Other Current Assets (in thousands) | June 30, 2025 | December 31, 2024 | | :--------------------------------------- | :------------ | :---------------- | | Prepaid research and development | $1,279 | $853 | | Prepaid insurance | $318 | $622 | | Accrued interest on marketable debt securities | $890 | - | | Other prepaid expenses and current assets | $388 | $298 | | **Total** | **$2,875** | **$1,863** | [6. Other Assets](index=17&type=section&id=6.%20Other%20Assets) Other Assets (in thousands) | Other Assets (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------------- | :------------ | :---------------- | | Prepaid research and development, non-current | $3,039 | $3,245 | | Other non-current assets | $29 | $27 | | **Total** | **$3,068** | **$3,272** | [7. Accrued Expenses and Other Current Liabilities](index=17&type=section&id=7.%20Accrued%20Expenses%20and%20Other%20Current%20Liabilities) Accrued Expenses and Other Current Liabilities (in thousands) | Accrued Expenses and Other Current Liabilities (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------------------------------- | :------------ | :---------------- | | Research and development costs | $1,445 | $2,740 | | Employee costs | $1,484 | $2,533 | | Other expenses | $334 | $135 | | **Total** | **$3,263** | **$5,408** | [8. Leases](index=17&type=section&id=8.%20Leases) - Operating lease expense was **$338 thousand** for both three-month periods ended June 30, 2025 and 2024, and **$676 thousand** for both six-month periods[63](index=63&type=chunk)[64](index=64&type=chunk) - As of June 30, 2025, the weighted-average remaining lease term for operating leases was 37 months, with a weighted-average discount rate of 7.0%[65](index=65&type=chunk) Operating Lease Payments (in thousands) | Operating Lease Payments (in thousands) | Amount | | :------------------------------------ | :----- | | 2025 (excluding six months ended June 30, 2025) | $715 | | 2026 | $1,429 | | 2027 | $1,429 | | 2028 | $718 | | 2029 | $87 | | **Total future operating lease payments** | **$4,378** | | Less: imputed interest | $430 | | **Present value of future minimum lease payments** | **$3,948** | [9. Commitments and Contingencies](index=19&type=section&id=9.%20Commitments%20and%20Contingencies) - The Company has commitments under license and collaboration agreements, lease agreements, and employment agreements, including annual payments, milestone payments, and royalties[66](index=66&type=chunk) - Management believes that the ultimate outcome of any legal proceedings and claims arising in the ordinary course of business would not have a material adverse impact on the Company's financial position or results of operations[67](index=67&type=chunk) [10. Stockholders' Equity](index=19&type=section&id=10.%20Stockholders'%20Equity) - As of June 30, 2025, **38,581,863 shares** of common stock were issued and outstanding, up from 35,044,772 at December 31, 2024[69](index=69&type=chunk) - During the six months ended June 30, 2025, approximately **2,376 shares of Series 1 Convertible Preferred Stock** were converted into **2,376,244 shares of common stock**, reducing outstanding preferred shares to 5,615[71](index=71&type=chunk)[72](index=72&type=chunk) - The April 2024 Private Placement generated net proceeds of approximately **$41,964 thousand** from the sale of common stock and pre-funded warrants, with associated common warrants exercisable at $5.25 per share[75](index=75&type=chunk) - The December 2024 Public Offering resulted in net proceeds of approximately **$93.4 million**, and the partial exercise of the Underwriters' Option in January 2025 generated an additional **$2.5 million** net proceeds[86](index=86&type=chunk)[90](index=90&type=chunk) [11. Stock-Based Compensation](index=23&type=section&id=11.%20Stock-Based%20Compensation) - The Company operates several equity incentive plans (2014, 2017, 2020 Inducement, 2024 EIP) and an Employee Stock Purchase Plan (2024 ESPP) to grant stock options, RSUs, and other awards[91](index=91&type=chunk)[97](index=97&type=chunk)[100](index=100&type=chunk)[102](index=102&type=chunk)[104](index=104&type=chunk) - The 2024 EIP was amended to increase shares available for grant by **2,800,000** to **4,300,000 shares**[102](index=102&type=chunk) RSU Activity | RSU Activity | Non-vested as of Dec 31, 2024 | Granted | Forfeited | Vested | Non-vested as of June 30, 2025 | | :------------- | :---------------------------- | :------ | :-------- | :----- | :----------------------------- | | Restricted Stock Units | 295,914 | 355,131 | (9,689) | (130,411) | 510,945 | | Weighted Average Grant Date Fair Value | $2.69 | $4.27 | $3.41 | $3.32 | $3.61 | Stock Option Activity | Stock Option Activity | Outstanding as of Dec 31, 2024 | Granted | Exercised | Forfeited | Outstanding as of June 30, 2025 | | :-------------------- | :----------------------------- | :------ | :-------- | :-------- | :------------------------------ | | Options | 3,855,478 | 1,735,363 | (2,842) | (24,972) | 5,563,027 | | Weighted Average Exercise Price | $7.30 | $4.17 | $2.91 | $3.46 | $6.34 | Stock-Based Compensation Expense (in thousands) | Stock-Based Compensation Expense (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Stock options | $736 | $953 | $1,448 | $2,028 | | Restricted stock units | $167 | $111 | $288 | $262 | | **Total** | **$903** | **$1,064** | **$1,736** | **$2,290** | [12. Net Income (Loss) per Common Share](index=29&type=section&id=12.%20Net%20Income%20(Loss)%20per%20Common%20Share) Net Income (Loss) per Common Share (in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Net income (loss) attributable to common stockholders (in thousands) | $(14,960) | $(9,513) | $(26,874) | $(20,608) | | Weighted-average shares outstanding, basic and diluted | 42,270,855 | 21,233,163 | 41,493,714 | 16,327,056 | | Net income (loss) per share, basic and diluted | $(0.35) | $(0.45) | $(0.65) | $(1.26) | - Due to net loss positions, basic and diluted EPS are the same, as potential common equivalent shares (April 2024 Common Warrants, Series 1 Convertible Preferred Stock, Stock options, Restricted stock units) were anti-dilutive[115](index=115&type=chunk) [13. Segment Information](index=29&type=section&id=13.%20Segment%20Information) - The Company operates as a single reportable segment, with the CEO acting as the chief operating decision maker (CODM) who reviews consolidated net income (loss) and total consolidated assets[116](index=116&type=chunk) Research and Development Expenses (in thousands) | Research and Development Expenses (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | TARA-002 in NMIBC | $4,898 | $2,164 | $8,455 | $4,954 | | TARA-002 in LMs | $477 | $598 | $1,027 | $1,531 | | IV Choline Chloride | $1,852 | $539 | $4,367 | $797 | | Other research and development | $3,317 | $2,849 | $5,651 | $6,242 | | **Total R&D Expenses** | **$10,770** | **$6,387** | **$19,918** | **$14,135** | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=31&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses Protara Therapeutics' financial condition, operational results, clinical trial progress, and liquidity for the reported periods [Overview](index=31&type=section&id=Overview) - Protara Therapeutics is a clinical-stage biopharmaceutical company developing transformative therapies for cancer and rare diseases, with a portfolio including TARA-002 for non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs), and IV Choline Chloride for patients on parenteral support (PS)[121](index=121&type=chunk)[122](index=122&type=chunk) - TARA-002 in NMIBC: Interim data from ADVANCED-2 trial showed a **100% complete response (CR) rate** at any time in BCG-Unresponsive patients (5/5), with CR rates of **100% at six months**, **80% at nine months**, and **67% at 12 months**. For BCG-Naïve patients, the CR rate at any time was **76% (16/21)**[126](index=126&type=chunk)[127](index=127&type=chunk) - IV Choline Chloride: FDA alignment on a registrational path for a broader indication as a source of choline for PS patients. THRIVE-1 study found **78% of PS patients were choline deficient**. A registrational Phase 3 clinical trial (THRIVE-3) is planned for Q3 2025, with EU-CTR approval already secured[133](index=133&type=chunk)[134](index=134&type=chunk)[135](index=135&type=chunk) - TARA-002 in LMs: STARBORN-1 Phase 2 trial interim data showed **two out of three patients achieved a complete response** after one injection. An interim update is expected in Q4 2025[137](index=137&type=chunk)[138](index=138&type=chunk) - The Company has an accumulated deficit of approximately **$271.9 million** as of June 30, 2025, and expects to incur significant operating losses as it advances product candidates[141](index=141&type=chunk) [Results of Operations](index=35&type=section&id=Results%20of%20Operations) Results of Operations (in thousands) | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Change | | :-------------------- | :------------------------------- | :------------------------------- | :----- | | Research and development | $10,770 | $6,387 | $4,383 | | General and administrative | $5,816 | $4,274 | $1,542 | | Total operating expenses | $16,586 | $10,661 | $5,925 | | Net income (loss) | $(14,960) | $(9,513) | $(5,447) | | Interest and investment income | $1,626 | $1,148 | $478 | - Research and development expenses increased by **$4.4 million** for the three months ended June 30, 2025, primarily due to increased direct expenses for ADVANCED-2 NMIBC clinical trial and startup costs for THRIVE-3 IV Choline Chloride clinical trial[151](index=151&type=chunk) Results of Operations (in thousands) | Metric (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Change | | :-------------------- | :----------------------------- | :----------------------------- | :----- | | Research and development | $19,918 | $14,135 | $5,783 | | General and administrative | $10,792 | $8,377 | $2,415 | | Total operating expenses | $30,710 | $22,512 | $8,198 | | Net income (loss) | $(26,874) | $(20,608) | $(6,266) | | Interest and investment income | $3,355 | $1,904 | $1,451 | | Other income | $481 | - | $481 | - General and administrative expenses increased by **$2.4 million** for the six months ended June 30, 2025, mainly due to higher personnel-related expenses and market development costs[156](index=156&type=chunk) [Liquidity and Capital Resources](index=37&type=section&id=Liquidity%20and%20Capital%20Resources) - As of June 30, 2025, unrestricted cash, cash equivalents, and marketable debt securities totaled **$145.6 million**, down from **$170.3 million** at December 31, 2024[158](index=158&type=chunk) - Net cash used in operating activities increased to **$(27.0) million** for the six months ended June 30, 2025, compared to **$(18.1) million** in the prior year, driven by increased net loss and working capital adjustments[164](index=164&type=chunk) - Net cash used in investing activities was **$(106.1) million** for the six months ended June 30, 2025, a significant change from **$26.0 million** provided in the prior year, primarily due to increased purchases of marketable debt securities[165](index=165&type=chunk) - Net cash provided by financing activities decreased to **$1.7 million** for the six months ended June 30, 2025, from **$42.0 million** in the prior year, reflecting proceeds from the Underwriters' Option exercise versus the 2024 April Private Placement[166](index=166&type=chunk) - The Company believes its current financial resources are sufficient for at least twelve months from the filing date, but acknowledges capital market volatility and economic conditions may impact future capital availability[160](index=160&type=chunk)[162](index=162&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=41&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section confirms no applicable quantitative and qualitative disclosures about market risk for the reporting period - Not applicable for this reporting period[174](index=174&type=chunk) [Item 4. Controls and Procedures](index=41&type=section&id=Item%204.%20Controls%20and%20Procedures) Management evaluated disclosure controls and procedures, concluding their effectiveness with no material changes in internal control over financial reporting - Management, including the principal executive and financial officers, evaluated the effectiveness of disclosure controls and procedures as of June 30, 2025, and concluded they were effective at a reasonable assurance level[175](index=175&type=chunk)[176](index=176&type=chunk) - There were no changes in internal control over financial reporting during the quarter ended June 30, 2025, that materially affected, or are reasonably likely to materially affect, internal control over financial reporting[178](index=178&type=chunk) PART II – OTHER INFORMATION [Item 1. Legal Proceedings](index=42&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in legal proceedings expected to have a material adverse effect on its business - The Company is not currently involved in any legal proceedings deemed to have a material adverse effect on its business[180](index=180&type=chunk) [Item 1A. Risk Factors](index=42&type=section&id=Item%201A.%20Risk%20Factors) No material changes to risk factors were reported from the prior Annual Report on Form 10-K - No material changes to the risk factors previously disclosed in the Annual Report on Form 10-K for the year ended December 31, 2024[181](index=181&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=42&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales of equity securities or use of proceeds were reported for the period - None to report[182](index=182&type=chunk) [Item 3. Defaults Upon Senior Securities](index=42&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) No defaults upon senior securities were reported during the period - None to report[183](index=183&type=chunk) [Item 4. Mine Safety Disclosures](index=42&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Mine safety disclosures are not applicable to the company - Not applicable[184](index=184&type=chunk) [Item 5. Other Information](index=42&type=section&id=Item%205.%20Other%20Information) CEO Jesse Shefferman terminated a Rule 10b5-1 trading arrangement on June 11, 2025 - CEO Jesse Shefferman terminated a Rule 10b5-1 trading arrangement on June 11, 2025, which had provided for the sale of up to 76,501 shares of common stock[185](index=185&type=chunk) - No other director or officer adopted or terminated a Rule 10b5-1 or non-Rule 10b5-1 trading arrangement during the three months ended June 30, 2025[186](index=186&type=chunk) [Item 6. Exhibits](index=43&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Quarterly Report, including employment agreements and certifications Exhibits | Exhibit No. | Description | | :------------ | :---------- | | 10.1† | Executive Employment Agreement with Leonardo Nicacio, M.D. | | 10.2*† | Executive Employment Agreement with William Conkling. | | 10.3*† | 2024 Equity Incentive Plan, as Amended. | | 31.1* | Certification of Principal Executive Officer. | | 31.2* | Certification of Principal Financial Officer. | | 32.1** | Certification of Principal Executive Officer and Principal Financial Officer Pursuant to 18 U.S.C. Section 1350. | | 101.INS* | Interactive Data Files (Inline XBRL). | | 104 | Cover Page Interactive Data File. | [SIGNATURES](index=44&type=section&id=SIGNATURES) The report includes duly authorized signatures from the CEO and CFO, affirming the filing on August 11, 2025 - The report was signed by Jesse Shefferman, Chief Executive Officer, and Patrick Fabbio, Chief Financial Officer, on August 11, 2025[196](index=196&type=chunk)

[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].