On March 5, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported a business update and announced financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Protara Therapeutics, MAR 5, 2025, View Source [SID1234650904]).
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"Following a year of significant progress and execution across our pipeline, we remain well positioned to deliver on our mission to bring transformative therapies to patients with cancer and rare diseases," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "Notably, supported by positive six-month data from our Phase 2 ADVANCED-2 trial in non-muscle invasive bladder cancer (NMIBC), we continue to believe TARA-002 could represent a differentiated, meaningful addition to the treatment paradigm, both as a monotherapy and in potential combination with other agents. We continue to expect to report initial data from 12-month evaluable patients in our ADVANCED-2 trial by mid-year."
Mr. Shefferman added, "Beyond our NMIBC program, we remain on track to commence our pivotal THRIVE-3 trial of intravenous (IV) Choline Chloride in the first half of the year. We also look forward to providing an interim update from our ongoing Phase 2 STARBORN-1 trial of TARA-002 in lymphatic malformations (LMs) by the end of the first half of 2025. With our cash runway extending into 2027, we look forward to achieving many critical milestones across all of our development programs as we work to deliver new treatment options to patients in need."
Recent Progress and Highlights
The Company is on track to report 12-month data by mid-year from its ongoing Phase 2 open-label ADVANCED-2 trial in evaluable NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive and BCG-Naïve. In December 2024, the Company reported positive interim results in which the complete response (CR) rate across BCG exposures was 72% (13/18) at six months and 70% (14/20) at any time, with 100% (9/9) of patients maintaining a CR from three months to six months. In addition, two of three patients maintained a CR at nine months. TARA-002 showed a favorable safety profile, with no Grade 2 or greater treatment-related adverse events and no treatment discontinuations due to adverse events.
Interim results from approximately 25 six-month evaluable BCG-Unresponsive patients are expected to be announced by the end of 2025. As previously communicated, the BCG-Unresponsive cohort is designed to be registrational in alignment with the 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment Draft Guidance for Industry issued by the U.S. Food and Drug Administration (FDA).
Following regulatory alignment with the FDA, the Company expects to provide an update on the design of its planned BCG-Naïve registrational trial by the end of the first half of 2025.
Protara continues to investigate systemic subcutaneous dosing through priming and maintenance combined with intravesical dosing, as well as exploring combination treatment with TARA-002 in NMIBC patients with CIS. Given what has been observed to date with TARA-002’s mechanism of action and strong safety profile, the Company believes it holds significant potential for use in both systemic dosing and combination therapy and is finalizing various opportunities.
IV Choline Chloride for Patients on Parenteral Support (PS)
The Company plans to initiate THRIVE-3, a registrational Phase 3 clinical trial, in the first half of 2025. THRIVE-3 is a seamless Phase 2b/3 trial with a dose confirmation portion (n=24) followed by a double-blinded, randomized, placebo-controlled portion to assess the efficacy and safety of IV Choline Chloride over 24 weeks in adolescents and adults on long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated (n=100). IV Choline Chloride was previously granted Fast Track designation by the FDA.
TARA-002 in LMs
Protara remains on track to provide an interim update on the Phase 2 STARBORN-1 trial of TARA-002 in pediatric patients with macrocystic and mixed cystic LMs by the end of the first half of 2025. The Company previously announced the completion of the study’s first safety cohort, in which TARA-002 showed promising results and was generally well-tolerated.
Fourth Quarter and Full Year 2024 Financial Results
As of December 31, 2024, cash and cash equivalents, and marketable debt securities totaled $170.3 million. The Company expects its cash and cash equivalents, and marketable debt securities will be sufficient to fund its planned operations and data milestones into 2027.
Research and development expenses for the fourth quarter of 2024 increased to $9.5 million from $6.4 million for the prior year period, and for the full year increased to $31.7 million compared to $25.0 million for 2023. The fourth quarter and full year increases were primarily due to an increase in expenses related to clinical trial and non-clinical activities for TARA-002 and IV Choline Chloride.
General and administrative expenses for the fourth quarter of 2024 increased to $4.8 million from $4.7 million for the prior year period, and for the full year decreased to $17.5 million compared to $18.6 million for 2023. The full year decrease was primarily due to a decrease in personnel-related expenses.
For the fourth quarter of 2024, Protara incurred a net loss of $12.8 million, or $0.48 per share, compared with a net loss of $10.2 million, or $0.90 per share, for the same period in 2023. Net loss for the year ended December 31, 2024 was $44.6 million, or $2.17 per share, compared with a net loss of $40.4 million, or $3.57 per share, for the year ended December 31, 2023. Net loss for the fourth quarter of 2024 included approximately $0.9 million of stock-based compensation expenses. Net loss for the year ended December 31, 2024 included approximately $4.1 million of stock-based compensation expenses.
About TARA-002
TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.
When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma IL-6, IL-10, IL-12. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.
About Non-Muscle Invasive Bladder Cancer (NMIBC)
Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.
About Lymphatic Malformations (LMs)
LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of three years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.
About IV Choline Chloride
IV Choline Chloride is an investigational, intravenous phospholipid substrate replacement therapy in development for patients receiving parenteral support (PS). Choline is a known important substrate for phospholipids that are critical for healthy liver function that also play an important role in modulating gene expression, cell membrane signaling, brain development and neurotransmission, muscle function, and bone health. PS patients are unable to synthesize choline from enteral nutrition sources, and there are currently no available PS formulations containing choline. Approximately 80% of patients dependent on PS are choline-deficient and of those approximately 63% have some degree of liver dysfunction, which can lead to hepatic failure. Every year in the U.S. there are approximately 90,000 people who require PS at home and of those approximately 30,000 are on long-term PS. IV Choline Chloride has the potential to become the first U.S. Food and Drug Administration (FDA) approved IV choline formulation for PS patients. It has been granted Orphan Drug Designation by the FDA for the prevention and/or treatment of choline deficiency in patients on long-term PN and been granted Fast Track Designation as a source of choline when oral or enteral nutrition is not possible, insufficient, or contraindicated. The U.S. Patent and Trademark Office has issued us a U.S. patent claiming a choline composition and a U.S. patent claiming a method for treating choline deficiency with a choline composition, each with a term expiring in 2041.