Core Points - Protara Therapeutics, Inc. has closed an underwritten public offering of 13,690,000 shares of common stock at a price of $6.25 per share, along with pre-funded warrants for 2,325,372 shares at $6.249 each, raising approximately $100 million in gross proceeds [1][2][3] Group 1: Offering Details - The offering includes a 30-day option for underwriters to purchase an additional 2,402,305 shares at the public offering price [1] - The net proceeds will be used to fund the clinical development of TARA-002 and other clinical programs, as well as for working capital and general corporate purposes [1] Group 2: Underwriters - TD Cowen, Cantor, LifeSci Capital, Oppenheimer & Co., and Scotiabank served as joint book-running managers for the offering [2] Group 3: Regulatory Information - The shares and warrants were issued under an effective shelf registration statement declared effective on November 14, 2023, by the U.S. Securities and Exchange Commission [3]

Core Insights - Protara Therapeutics, Inc. is advancing TARA002, a cell therapy for non-muscle invasive bladder cancer (NMIBC), with interim data from the Phase 2 ADVANCED-2 trial to be presented at the Society of Urologic Oncology's annual meeting in December 2024 [1][3] - The ADVANCED-2 trial includes BCG-unresponsive and BCG-naïve patients, with a focus on safety and efficacy data from approximately 20 enrolled patients [2][3] - TARA-002 is derived from a master cell bank of genetically distinct group A Streptococcus pyogenes and has shown manufacturing comparability with OK432, an approved immunopotentiator [3][4] Company Overview - Protara Therapeutics is a clinical-stage biotechnology company focused on developing therapies for cancer and rare diseases, with TARA-002 as its lead candidate for NMIBC and lymphatic malformations [6] - The company is also developing IV Choline Chloride for patients on parenteral nutrition [6] Industry Context - NMIBC accounts for approximately 80% of bladder cancer diagnoses in the U.S., with around 65,000 new cases each year, making it a significant area of focus for treatment advancements [5]

NEW YORK, Nov. 06, 2024 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced that management will participate in a fireside chat at the Guggenheim Inaugural Healthcare Innovation Conference on Wednesday, November 13, 2024, at 2:00 pm ET in Boston. A live webcast of the fireside chat can be accessed by visiting the Events and Presentations section of the Company’s website: htt ...

Core Insights - Protara Therapeutics announced the results of the THRIVE-1 study, highlighting a significant prevalence of choline deficiency and liver dysfunction in patients dependent on parenteral support [1][2][4] - The company is developing IV Choline Chloride as a potential treatment to address this unmet medical need, with plans to initiate a pivotal trial in Q1 2025 [1][3][6] Study Findings - The THRIVE-1 study involved 78 patients, revealing that 78% were choline deficient, and 63% of those with deficiency exhibited liver dysfunction, including steatosis and cholestasis [2][4] - The study underscores the critical need for intravenous choline supplementation in this patient population [2][3] Product Development - IV Choline Chloride is an investigational therapy aimed at providing choline when oral or enteral nutrition is insufficient or contraindicated [2][7] - The product has received Orphan Drug Designation from the FDA for preventing choline deficiency in patients on parenteral support [8] Market Opportunity - Approximately 40,000 patients in the U.S. on long-term parenteral support could benefit from an IV formulation of choline [8] - Currently, there are no approved IV choline products for patients dependent on parenteral support, despite recommendations from professional medical societies [5][3] Company Commitment - Protara is dedicated to bringing the first approved IV formulation of choline to the parenteral support community and is preparing for a registrational trial [3][6]

Clinical Trials and Drug Development - TARA-002 is currently in a Phase 1 open-label clinical trial for non-muscle invasive bladder cancer (NMIBC), with positive preliminary data showing favorable tolerability and anti-tumor activity at the 40KE dose[83]. - In the ADVANCED-1 trial, a complete response (CR) rate of 50% was observed in BCG-Unresponsive/Experienced patients with CIS-only, while the overall CR rate across 16 evaluable patients was 38%[87]. - The ongoing ADVANCED-2 trial is assessing TARA-002 in NMIBC patients, with preliminary results from a risk-benefit analysis expected in Q4 2024, involving approximately 10 patients[89]. - TARA-002 has received Rare Pediatric Disease designation for the treatment of lymphatic malformations (LMs) and is currently being evaluated in the STARBORN-1 Phase 2 trial[95][97]. - The STARBORN-1 trial aims to enroll approximately 30 patients, with the primary endpoint being the proportion of participants demonstrating clinical success in treating macrocystic and mixed-cystic LMs[97]. - The company is exploring higher dosing at an 80KE dose and combination therapies to enhance the treatment paradigm for NMIBC[90]. - TARA-002 is being developed for multiple oncologic indications and rare diseases, with worldwide rights secured excluding Japan and Taiwan[81]. Financial Performance and Capital Needs - The company has not generated any revenue from product sales and does not expect to do so in the near term, indicating a need for additional capital to finance ongoing and future clinical trials[99]. - As of June 30, 2024, the company had an accumulated deficit of approximately $221.0 million and expects to continue incurring significant operating losses for the next few years[100]. - The company reported cash, cash equivalents, and marketable debt securities of approximately $89.6 million as of June 30, 2024, an increase from $65.6 million as of December 31, 2023[116]. - Research and development expenses for the three months ended June 30, 2024, were approximately $6.4 million, a decrease of $0.9 million compared to the same period in 2023[111]. - General and administrative expenses for the three months ended June 30, 2024, were approximately $4.3 million, a decrease of $0.6 million compared to the same period in 2023[111]. - The net loss for the three months ended June 30, 2024, was approximately $9.5 million, a decrease of $1.8 million compared to a net loss of $11.3 million for the same period in 2023[109]. - For the six months ended June 30, 2024, the company incurred a net loss of approximately $20.6 million, compared to a net loss of $20.3 million for the same period in 2023[116]. - The company completed a private placement on April 10, 2024, raising approximately $42.0 million in net proceeds by selling 9,143,380 shares of common stock[101]. - Net cash used in operating activities was $18.1 million for the six months ended June 30, 2024, a decrease of $4.2 million compared to $22.3 million for the same period in 2023[121]. - The company reported net cash provided by investing activities of $26.0 million for the six months ended June 30, 2024, compared to $32.2 million for the same period in 2023[122]. - The company believes its current financial resources are sufficient to meet estimated liquidity needs for at least twelve months from the date of the report[117]. Legal and Compliance - The company has operating lease obligations primarily for its corporate headquarters and manufacturing facilities in North America[123]. - There are no recorded liabilities for certain contracts that require indemnification against third-party claims, as amounts cannot be reasonably estimated until a specific claim is asserted[124]. - The company has contingent milestone payments related to development, regulatory approval, and commercialization agreements, which are not included in the balance sheet due to their uncertain timing[125]. - As of June 30, 2024, the company's management evaluated the effectiveness of its disclosure controls and procedures, concluding they were effective at a reasonable assurance level[128]. - There were no changes in internal control over financial reporting during the quarter ended June 30, 2024, that materially affected the company's internal control[130]. - The company is not currently involved in any legal proceedings that are likely to have a material adverse effect on its business[130].

NEW YORK, June 24, 2024 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced the grant of inducement non-qualified stock options to purchase an aggregate of 118,400 shares of common stock to Lisa Schlesinger, Protara's newly appointed Vice President, Head of New Product Development and Market Access. About Protara Therapeutics, Inc. Justine O'Malley Protara Therapeutics Justi ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | Title of each class | Trading Symbol(s) | Name of each exchange on which registered | | --- | --- | --- | | Common Stock, $0.001 par value per | TARA | The Nasdaq Capital Market | | share | ...

[Q1 2024 Business and Financial Overview](index=1&type=section&id=Protara%20Therapeutics%20Announces%20First%20Quarter%202024%20Financial%20Results%20and%20Provides%20Business%20Update) Protara Therapeutics reported strong Q1 2024 progress, securing $45 million in financing and advancing key clinical programs for TARA-002 and IV Choline Chloride [Recent Progress and Highlights](index=1&type=section&id=Recent%20Progress%20and%20Highlights) Protara Therapeutics achieved key milestones in Q1 2024, including a $45 million private placement and positive clinical data for TARA-002 and IV Choline Chloride - In April 2024, Protara successfully closed a **$45.0 million** private placement led by RA Capital Management and Acorn Bioventures[4](index=4&type=chunk) - Current cash resources, combined with private placement proceeds, are expected to fund operations and data milestones into **2026**[3](index=3&type=chunk)[5](index=5&type=chunk)[13](index=13&type=chunk) - Positive three-month data was reported from the TARA-002 clinical program in non-muscle invasive bladder cancer (NMIBC), with interim ADVANCED-2 trial data expected in **2H 2024**[3](index=3&type=chunk)[5](index=5&type=chunk) - An agreement was reached with the U.S. FDA on a clear registrational path for IV Choline Chloride in patients dependent on parenteral nutrition (PN)[3](index=3&type=chunk)[5](index=5&type=chunk) [Clinical Program Updates](index=2&type=section&id=Clinical%20Program%20Updates) Protara Therapeutics provides updates on its TARA-002 program for NMIBC and LMs, and IV Choline Chloride for PN patients, detailing clinical progress and regulatory alignment [TARA-002 in NMIBC](index=2&type=section&id=TARA-002%20in%20NMIBC) TARA-002 demonstrated a 38% complete response rate in NMIBC CIS patients with a favorable safety profile, and the ADVANCED-2 trial is progressing - TARA-002 achieved an overall three-month complete response (CR) rate of **38%** in 16 evaluable carcinoma in situ (CIS) patients in its high-risk NMIBC program[9](index=9&type=chunk) - The CR rate was **63%** in CIS-only patients, **13%** in CIS +Ta/T1 patients, and **43%** in BCG-Unresponsive/Experienced patients[9](index=9&type=chunk) - TARA-002 was well-tolerated, with no Grade 3 or greater treatment-related adverse events reported[9](index=9&type=chunk) - The Phase 2 ADVANCED-2 trial for TARA-002 in BCG-Unresponsive and BCG-Naïve NMIBC patients expects preliminary results in **2H 2024**[9](index=9&type=chunk) [IV Choline Chloride for Patients on PN](index=2&type=section&id=IV%20Choline%20Chloride%20for%20Patients%20on%20PN) Protara aligned with the FDA on a registrational pathway for IV Choline Chloride, broadening its indication for patients on long-term parenteral nutrition - In April 2024, the company aligned with the FDA on a registrational path for IV Choline Chloride for patients dependent on parenteral nutrition (PN)[7](index=7&type=chunk) - The indication was broadened from IFALD to a choline source for patients on long-term PN unable to synthesize it orally or enterally[7](index=7&type=chunk) [TARA-002 in LMs](index=2&type=section&id=TARA-002%20in%20LMs) The Phase 2 STARBORN-1 trial for TARA-002 in pediatric lymphatic malformations is actively enrolling, targeting 30 patients with a primary endpoint of significant LM volume reduction - Dosing and enrollment are progressing in the STARBORN-1 Phase 2 trial for TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs[8](index=8&type=chunk)[3](index=3&type=chunk) - The trial plans to enroll approximately **30 patients**, with clinical success defined as a **60% to 100%** reduction in total LM volume from baseline as the primary endpoint[8](index=8&type=chunk) [First Quarter 2024 Financial Results](index=3&type=section&id=First%20Quarter%202024%20Financial%20Results) Protara Therapeutics reported its Q1 2024 financial results, detailing changes in net loss, operating expenses, and its cash position, along with future funding projections [Financial Performance](index=3&type=section&id=Financial%20Performance) Protara reported an increased net loss of $11.1 million in Q1 2024, primarily due to higher research and development expenses for the TARA-002 program Financial Performance Summary | Financial Metric | Q1 2024 | Q1 2023 | | :--- | :--- | :--- | | Research and development expenses | $7.7 million | $5.1 million | | General and administrative expenses | $4.1 million | $4.6 million | | Total operating expenses | $11.9 million | $9.7 million | | Net loss | $11.1 million | $9.0 million | | Net loss per share | $0.97 | $0.80 | - The increase in R&D expenses was mainly due to a **$1.8 million** rise in TARA-002 clinical and non-clinical costs and a **$1.1 million** increase in personnel-related expenses[13](index=13&type=chunk) - The decrease in G&A expenses was primarily driven by a **$0.5 million** reduction in personnel-related costs, including stock-based compensation[13](index=13&type=chunk) [Financial Position](index=3&type=section&id=Financial%20Position) As of March 31, 2024, Protara held $55.2 million in cash and equivalents, projecting sufficient funding into 2026 with recent financing - Cash, cash equivalents, and investments in marketable debt securities totaled **$55.2 million** as of March 31, 2024[13](index=13&type=chunk) - The company expects its cash position, including approximately **$42.0 million** in net proceeds from the April 2024 private placement, will fund operations into **2026**[13](index=13&type=chunk) Balance Sheet Overview | Balance Sheet Item | March 31, 2024 | December 31, 2023 | | :--- | :--- | :--- | | Total current assets | $57.9 million | $68.7 million | | Total assets | $68.1 million | $79.0 million | | Total liabilities | $9.7 million | $10.6 million | | Total stockholders' equity | $58.4 million | $68.3 million | [About Protara's Pipeline and Disease Areas](index=3&type=section&id=About%20Protara%27s%20Pipeline%20and%20Disease%20Areas) This section provides an overview of Protara's key pipeline assets, TARA-002 and IV Choline Chloride, and the disease areas they target, NMIBC and LMs [About TARA-002](index=3&type=section&id=About%20TARA-002) TARA-002 is an investigational cell therapy for NMIBC and LMs, derived from OK-432, hypothesized to activate immune responses and induce immunogenic cell death - TARA-002 is an investigational cell therapy developed from the same master cell bank as OK-432, a marketed immunopotentiator in Japan and Taiwan[11](index=11&type=chunk) - The therapy is believed to activate innate and adaptive immune cells, leading to pro-inflammatory cytokine release, and directly kills tumor cells to enhance antitumor immune response[12](index=12&type=chunk) [About Non-Muscle Invasive Bladder Cancer (NMIBC)](index=4&type=section&id=About%20Non-Muscle%20Invasive%20Bladder%20Cancer%20%28NMIBC%29) NMIBC is the sixth most common cancer in the U.S., accounting for approximately 80% of bladder cancer diagnoses, with 65,000 new cases annually - NMIBC constitutes about **80%** of bladder cancer diagnoses in the United States, with approximately **65,000** new patients each year[14](index=14&type=chunk) [About Lymphatic Malformations (LMs)](index=4&type=section&id=About%20Lymphatic%20Malformations%20%28LMs%29) Lymphatic Malformations (LMs) are rare congenital lymphatic vessel defects, often diagnosed in early childhood, leading to complications like airway obstruction - LMs are rare congenital malformations of lymphatic vessels, with over **50%** detected at birth and **90%** diagnosed before the age of three[15](index=15&type=chunk) - Common morbidities include airway obstruction, intralesional bleeding, and impingement on critical structures[15](index=15&type=chunk) [About IV Choline Chloride](index=4&type=section&id=About%20IV%20Choline%20Chloride) IV Choline Chloride is an investigational intravenous therapy for PN patients unable to synthesize choline, with potential to be the first FDA-approved treatment for this critical deficiency - IV Choline Chloride is being developed for patients on parenteral nutrition (PN) who are unable to synthesize choline and are at risk of liver damage[16](index=16&type=chunk) - It has the potential to be the first FDA-approved IV choline formulation for PN patients and has been granted Orphan Drug Designation by the FDA[16](index=16&type=chunk) [Detailed Financial Statements](index=6&type=section&id=Detailed%20Financial%20Statements) This section presents the unaudited condensed consolidated balance sheets and statements of operations for Protara Therapeutics, providing a detailed view of its financial position and performance [Unaudited Condensed Consolidated Balance Sheets](index=6&type=section&id=PROTARA%20THERAPEUTICS%2C%20INC.%20AND%20SUBSIDIARIES%20Unaudited%20Condensed%20Consolidated%20Balance%20Sheets) The balance sheet as of March 31, 2024, shows total assets of **$68,134 thousand**, down from **$78,954 thousand** at year-end 2023, with total liabilities at **$9,728 thousand** Unaudited Condensed Consolidated Balance Sheets | | **As of March 31, 2024 (in thousands)** | **As of December 31, 2023 (in thousands)** | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $52,231 | $39,586 | | Marketable debt securities | $2,992 | $25,994 | | Total current assets | $57,913 | $68,705 | | **Total assets** | **$68,134** | **$78,954** | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $5,501 | $6,149 | | **Total liabilities** | **$9,728** | **$10,633** | | **Total stockholders' equity** | **$58,406** | **$68,321** | | **Total liabilities and stockholders' equity** | **$68,134** | **$78,954** | [Unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=PROTARA%20THERAPEUTICS%2C%20INC.%20AND%20SUBSIDIARIES%20Unaudited%20Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For the three months ended March 31, 2024, Protara reported total operating expenses of **$11,851 thousand**, resulting in a net loss of **$11,095 thousand** or **$0.97 per share**. The comprehensive loss was **$11,065 thousand** Unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss | | **For the Three Months Ended March 31,** | | | :--- | :--- | :--- | | | **2024 (in thousands)** | **2023 (in thousands)** | | **Operating expenses:** | | | | Research and development | $7,748 | $5,143 | | General and administrative | $4,103 | $4,589 | | **Total operating expenses** | **$11,851** | **$9,732** | | **Loss from operations** | **($11,851)** | **($9,732)** | | Interest and investment income | $756 | $687 | | **Net loss** | **($11,095)** | **($9,045)** | | **Net loss per share, basic and diluted** | **($0.97)** | **($0.80)** | | **Comprehensive loss** | **($11,065)** | **($8,826)** |

Clinical Development - TARA-002 is currently in clinical development for non-muscle invasive bladder cancer (NMIBC), which accounts for approximately 80% of bladder cancer diagnoses in the U.S., with around 65,000 new cases annually[19][40][41]. - The ongoing ADVANCED-1 trial has shown positive preliminary data, indicating favorable tolerability and anti-tumor activity of TARA-002 at the 40KE dose, with no dose limiting toxicities observed[20][22]. - The company initiated the ADVANCED-2 Phase 2 trial in September 2023, aiming to enroll at least 102 patients with high-grade carcinoma in situ (CIS) to further assess TARA-002's safety and efficacy[24]. - The Phase 1 trial of TARA-002 included nine patients, with three achieving a complete response at the 20KE dose, and five out of six patients with high-grade tumors showing high-grade recurrence-free survival at week 12[22][24]. - The company is conducting pre-clinical studies to better understand TARA-002's mechanism of action and its potential in combination therapies for NMIBC[25]. - The company is conducting ADVANCED-1EXP and ADVANCED-2 clinical trials for TARA-002, with preliminary data expected in the first half of 2024[43]. - ADVANCED-2 trial aims to enroll at least 102 patients with high-grade CIS, with preliminary results from a risk-benefit analysis expected in the second half of 2024[44]. - The company has initiated the STARBORN-1 trial in October 2023 to evaluate TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs[60]. - TARA-002 has received Rare Pediatric Disease designation from the FDA for the treatment of lymphatic malformations (LMs), with a new Phase 2 trial (STARBORN-1) initiated in October 2023 to evaluate its safety and efficacy in pediatric patients[26][27]. Financial Condition - The company has not generated any revenue from product sales and does not expect to do so in the near term, indicating a need for additional capital to finance ongoing and future clinical trials[30]. - Significant operating losses and negative cash flows are expected to continue for the foreseeable future as the company executes its research and development plan[175]. - The company will require substantial additional funds for preclinical studies and clinical trials, with future capital needs depending on various factors including product pipeline and regulatory approvals[177]. - Raising additional capital may dilute stockholders' ownership interests and could be difficult to obtain under current economic conditions, including rising inflation and interest rates[179]. - The company has never generated any revenue and has a limited operating history, making it difficult to evaluate future viability[173]. Regulatory and Compliance - The company must navigate extensive regulatory requirements for drug approval, including preclinical and clinical trials, and submission of an IND to the FDA[116]. - The FDA aims to review standard applications within ten months and priority reviews within six months after acceptance[124]. - The FDA may require post-marketing studies to monitor safety and efficacy after product commercialization[126]. - The FDA can withdraw product approval if compliance with regulatory requirements is not maintained[132]. - The company is subject to various federal, state, and local regulations, including compliance with the Anti-Kickback Statute and the False Claims Act, which impose significant penalties for violations[139][141]. - The company must comply with the federal Physician Payments Sunshine Act, requiring annual reporting of certain payments to healthcare professionals, with penalties for inaccurate reporting[147]. - The company faces uncertainty regarding coverage and reimbursement for its product candidates, which is critical for new product acceptance in the market[151][156]. - The company may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and cost-effectiveness of its products to obtain reimbursement[154]. - The company must participate in government healthcare programs, such as the Medicaid Drug Rebate Program, to receive Medicare Part B reimbursement for eligible drugs[145]. - The company is required to report certain price metrics to the government, with penalties for inaccurate submissions, affecting pricing strategies[146]. - The company must navigate complex data privacy and security regulations, including HIPAA and state laws, which may complicate compliance efforts[144]. Product Development and Market Potential - The company is exploring opportunities to expand the use of TARA-002 in combination with other therapies and in indications beyond NMIBC and LMs[35]. - The company anticipates competition from existing treatment methods for NMIBC, including intravesical BCG TICE manufactured by Merck & Co., Inc.[114]. - The commercial success of TARA-002 and IV Choline Chloride will depend on physician and patient adoption, which is influenced by factors such as safety, effectiveness, and reimbursement availability[198]. - If TARA-002 or IV Choline Chloride fails to achieve broad adoption, the company's operating results and financial condition will be adversely affected[199]. - The company currently has limited marketing capabilities and no sales organization, which poses risks to the successful commercialization of its product candidates[210]. Intellectual Property and Licensing - The company has acquired an exclusive, worldwide license to U.S. Patent 8,865,641 B2, which provides protection until 2035 for a method of treating fatty liver disease[102]. - The company has entered into a license agreement for exclusive rights to the IND and regulatory assets related to IV Choline Chloride[69]. - The License Agreement with The Feinstein Institute grants exclusive rights to develop products for treating fatty liver disease, retaining rights for non-commercial research by the Institute[93]. - The company agreed to pay tiered royalties of between 1.0% and 1.5% of all net sales to the Institute, along with maintenance payments of $15,000 starting on the second anniversary of the License Agreement[94]. - A total of $375,000 in one-time milestone payments is due upon achieving certain regulatory approval milestones, with $100,000 already paid[95]. - The Chugai Agreement, effective June 17, 2019, grants exclusive rights for the development and commercialization of a new therapeutic product, TARA-002, in territories outside Japan and Taiwan[77]. - Under the Chugai Amendment, the exclusivity period for Chugai's support has been extended to June 30, 2021, with potential further extensions[78]. - The company is obligated to pay Chugai a low single-digit million fee for each additional indication approval during the agreement[78]. Risks and Challenges - The clinical success of TARA-002 and IV Choline Chloride is contingent on timely completion of ongoing Phase 1 and 2 clinical trials, which may face delays or increased costs[181]. - Undesirable side effects from product candidates could delay or prevent regulatory approval and affect market acceptance[191]. - The company may face limitations in using net operating loss carryforwards due to ownership changes, which could increase future tax obligations[180]. - Preliminary and interim data from clinical trials may change as more patient data become available, potentially impacting business prospects[187]. - Product liability exposure exists, with substantial liability risks if claims are successful and insurance coverage is inadequate[215]. - The company faces risks of reputational harm and substantial liabilities from product liability claims[216]. - The agreement with Chugai Pharmaceutical allows for third-party access to materials and support for TARA-002 after exclusivity ends[212]. - Potential for adverse effects on revenue generation if competing therapies are developed by third parties[212]. Manufacturing and Supply Chain - The company utilizes a modernized proprietary manufacturing process for TARA-002, contracted with a cGMP-compliant CDMO[66]. - The company has contracted a cGMP-compliant CDMO for the end-to-end manufacturing of IV Choline Chloride in the United States[76]. - Manufacturing facilities are subject to continual review and inspections by the FDA for compliance with regulations[213]. - The company relies on CDMOs to produce drug candidates in accordance with cGMP regulations for clinical trials and commercial products[106]. Orphan Drug Designation - The FDA has granted Orphan Drug Designation for IV Choline Chloride, which is being developed for patients receiving parenteral nutrition, addressing a significant unmet medical need[29]. - Orphan drug designation is granted for drugs intended to treat rare diseases affecting fewer than 200,000 individuals in the U.S.[127]. - A product with orphan designation receives seven years of exclusivity upon first FDA approval for the designated disease[128]. - The FDA granted Rare Pediatric Disease designation for TARA-002 for the treatment of lymphatic malformations (LMs)[64]. - TARA-002 has received Rare Pediatric Disease Designation for the treatment of LMs, but may not qualify for a priority review voucher if approved[195]. - The Rare Pediatric Disease Priority Review Voucher program is authorized until September 30, 2024, with eligibility for drugs designated before this date if approved by September 30, 2026[196].

[Business Update and Highlights](index=1&type=section&id=Business%20Update%20and%20Highlights) Protara anticipates a milestone-rich 2024, advancing its pipeline with TARA-002 data for NMIBC and LMs, and FDA engagement for IV Choline Chloride [TARA-002 in NMIBC](index=1&type=section&id=TARA-002%20in%20NMIBC) Protara advances TARA-002 for NMIBC with preliminary Phase 1b results expected in 1H 2024 and Phase 2 data in 2H 2024 - Preliminary results from the Phase 1b ADVANCED-1EXP trial are expected in **1H 2024**, evaluating TARA-002 in up to **12** CIS patients. The primary endpoint is the complete response (CR) rate at three months[4](index=4&type=chunk)[5](index=5&type=chunk) - Preliminary data from the Phase 2 ADVANCED-2 trial, based on a risk-benefit analysis of approximately **10** patients at the six-month mark, is expected in **2H 2024**[5](index=5&type=chunk)[6](index=6&type=chunk) - The ADVANCED-2 trial will enroll at least **102** NMIBC patients with CIS, including both BCG-naïve (n=27) and BCG-unresponsive (n=75-100) cohorts[6](index=6&type=chunk) [TARA-002 in LMs](index=2&type=section&id=TARA-002%20in%20LMs) The Phase 2 STARBORN-1 trial for TARA-002 in pediatric LMs is dosing patients, targeting substantial LM volume reduction - Dosing is progressing in the STARBORN-1 Phase 2 trial, which will enroll approximately **30** pediatric patients with LMs[7](index=7&type=chunk) - The primary endpoint is clinical success, defined as a complete response (**90-100%** volume reduction) or substantial response (**60-90%** volume reduction) in the LM[7](index=7&type=chunk) - The company expects to share Phase 1b proof of concept (POC) and preliminary Phase 2 data for TARA-002 in NMIBC later in **2024**[3](index=3&type=chunk) - Dosing is underway in the Phase 2 STARBORN-1 trial of TARA-002 for pediatric patients with lymphatic malformations (LMs)[3](index=3&type=chunk)[7](index=7&type=chunk) - The company continues engagement with the U.S. FDA to determine the next steps for the IV Choline Chloride development program[8](index=8&type=chunk) [Fourth Quarter and Full Year 2023 Financial Results](index=2&type=section&id=Fourth%20Quarter%20and%20Full%20Year%202023%20Financial%20Results) Protara held **$65.6 million** cash as of Dec 31, 2023, funding operations into Q2 2025, with a reduced **$40.4 million** net loss for 2023 - Cash, cash equivalents, and investments totaled **$65.6 million** as of December 31, 2023, expected to fund operations into **Q2 2025**[5](index=5&type=chunk)[10](index=10&type=chunk) Full Year Operating Expenses (2023 vs 2022) | Expense Category | Full Year 2023 | Full Year 2022 | Change Driver | | :--- | :--- | :--- | :--- | | Research & Development | $25.0 million | $16.8 million | Increase in clinical trial and non-clinical activities for TARA-002. | | General & Administrative | $18.6 million | $20.7 million | Reduction in personnel costs and D&O insurance premiums. | Net Loss and EPS (Q4 & Full Year 2023 vs 2022) | Period | Metric | 2023 | 2022 | Note | | :--- | :--- | :--- | :--- | :--- | | **Q4** | Net Loss | $(10.2)M | $(39.0)M | 2022 included a $29.5M non-cash goodwill impairment charge. | | | EPS | $(0.90) | $(3.46) | | | **Full Year** | Net Loss | $(40.4)M | $(66.0)M | | | | EPS | $(3.57) | $(5.86) | | [Product Pipeline and Disease Overview](index=3&type=section&id=Product%20Pipeline%20and%20Disease%20Overview) Protara's pipeline features TARA-002 for NMIBC and LMs, and IV Choline Chloride for parenteral nutrition patients [About TARA-002](index=3&type=section&id=About%20TARA-002) TARA-002, an investigational cell therapy, treats NMIBC and LMs by activating immune cells and inducing tumor cell death - TARA-002 is an investigational cell therapy developed from the same master cell bank as OK-432 (Picibanil®)[11](index=11&type=chunk) - It works by activating immune cells to produce pro-inflammatory cytokines and by directly killing tumor cells, triggering an antitumor immune response[12](index=12&type=chunk) - TARA-002 has been granted Rare Pediatric Disease Designation by the FDA for the treatment of LMs[11](index=11&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 U.S. cancer, accounting for **80%** of bladder cancer diagnoses with **65,000** new cases annually - NMIBC represents approximately **80%** of bladder cancer diagnoses in the U.S[13](index=13&type=chunk) - There are approximately **65,000** new NMIBC diagnoses in the United States each year[13](index=13&type=chunk) [About Lymphatic Malformations (LMs)](index=3&type=section&id=About%20Lymphatic%20Malformations%20(LMs)) LMs are rare congenital lymphatic malformations, often diagnosed in early childhood, causing serious health issues - LMs are rare, congenital malformations of lymphatic vessels, with **90%** diagnosed before the age of **3**[14](index=14&type=chunk) [About Intravenous (IV) Choline Chloride](index=3&type=section&id=About%20Intravenous%20(IV)%20Choline%20Chloride) IV Choline Chloride is an investigational orphan drug for choline deficiency in PN patients, vital for liver function - IV Choline Chloride is a replacement therapy for PN-dependent patients, as current PN formulations lack choline[15](index=15&type=chunk) - It has been granted Orphan Drug Designation by the FDA for preventing choline deficiency in PN patients[15](index=15&type=chunk) [Consolidated Financial Statements](index=5&type=section&id=Consolidated%20Financial%20Statements) Protara's total assets were **$79.0 million** as of Dec 31, 2023, with total liabilities at **$10.6 million** and equity at **$68.3 million** [Consolidated Balance Sheets](index=5&type=section&id=Consolidated%20Balance%20Sheets) Protara's total assets were **$79.0 million** as of Dec 31, 2023, with total liabilities at **$10.6 million** and equity at **$68.3 million** Consolidated Balance Sheets (in thousands) | | Dec 31, 2023 | Dec 31, 2022 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $39,586 | $24,127 | | Marketable debt securities (current & non-current) | $25,994 | $78,129 | | Total current assets | $68,705 | $86,146 | | **Total assets** | **$78,954** | **$113,290** | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $6,149 | $5,740 | | Total liabilities | $10,633 | $11,207 | | Total stockholders' equity | $68,321 | $102,083 | | Total liabilities and stockholders' equity | $78,954 | $113,290 | [Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Protara reported a **$40.4 million** net loss for 2023, a reduction from **$66.0 million** in 2022 due to no goodwill impairment Consolidated Statements of Operations (in thousands, except per share data) | | For the Year Ended Dec 31, 2023 | For the Year Ended Dec 31, 2022 | | :--- | :--- | :--- | | Research and development | $24,989 | $16,808 | | General and administrative | $18,624 | $20,737 | | Loss on impairment of goodwill | - | $29,517 | | **Total operating expenses** | **$43,613** | **$67,062** | | **Loss from operations** | **$(43,613)** | **$(67,062)** | | Interest and investment income | $3,193 | $1,110 | | **Net loss** | **$(40,420)** | **$(65,952)** | | **Net loss per share, basic and diluted** | **$(3.57)** | **$(5.86)** | | **Comprehensive Loss** | **$(39,763)** | **$(66,429)** |