Protara Therapeutics, Inc. is a clinical-stage biopharmaceutical company committed to advancing transformative therapies for the treatment of cancer and rare diseases. With a focus on leveraging modern scientific, regulatory, and manufacturing advancements, Protara is dedicated to creating new development opportunities and bringing life-changing therapies to people with limited treatment options.
Business Overview and History
Protara Therapeutics, Inc. was founded on the principle of applying modern scientific, regulatory or manufacturing advancements to established mechanisms in order to create new development opportunities. The company was established with the goal of bringing life-changing therapies to people with limited treatment options, particularly in the areas of cancer and rare diseases.
Protara's portfolio initially included two development programs utilizing TARA-002, an investigational cell therapy based on the broad immunopotentiator, OK-432. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, which was originally granted marketing approval by the Japanese Ministry of Health and Welfare as an immunopotentiating cancer therapeutic agent. Protara secured worldwide rights to the asset excluding Japan and Taiwan and began exploring its use in oncology and rare disease indications.
The company's lead oncology program with TARA-002 was for the treatment of non-muscle invasive bladder cancer (NMIBC). Protara conducted a Phase 1 open-label clinical trial to evaluate TARA-002 in treatment-naïve and treatment experienced NMIBC patients, known as the ADVANCED-1 trial. The data from this trial suggested that intravesical TARA-002 was generally well tolerated and showed preliminary signs of anti-tumor activity. Protara subsequently completed an open-label expansion clinical trial, ADVANCED-1EXP, evaluating intravesical TARA-002 in NMIBC patients, including BCG-Naïve, BCG-Unresponsive, and BCG-Experienced patients.
In addition to the NMIBC program, Protara has also been pursuing TARA-002 in lymphatic malformations (LMs), a rare, non-malignant condition of the lymphatic vascular system. In July 2020, the FDA granted Rare Pediatric Disease designation for TARA-002 for the treatment of LMs, and in May 2022 the European Medicines Agency granted orphan drug designation to TARA-002 for the treatment of LMs. Protara initiated the STARBORN-1 Phase 2 trial in 2023 to evaluate the safety and efficacy of intracystic injection of TARA-002 for the treatment of macrocystic and mixed-cystic LMs.
The company's lead oncology program is TARA-002 in NMIBC, a type of bladder cancer found in the tissue that lines the inner surface of the bladder and has not spread into the bladder muscle. NMIBC represents approximately 80% of bladder cancer diagnoses, with around 65,000 patients diagnosed in the United States each year. Protara's TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, which is marketed as Picibanil in Japan by Chugai Pharmaceutical Co., Ltd.
In a Phase 1 open-label clinical trial, TARA-002 demonstrated a favorable safety and tolerability profile, with the majority of reported adverse events being Grades 1 and 2. Importantly, TARA-002 resulted in significantly higher upregulation of key pro-inflammatory cytokines and chemokines compared to the current standard of care, Bacillus Calmette-Guérin (BCG). Protara is currently conducting the ADVANCED-2 Phase 2 trial, which is designed to be registrational, to evaluate TARA-002 in NMIBC patients who are BCG-Naïve and BCG-Unresponsive.
In addition to the NMIBC program, Protara is also pursuing TARA-002 in the treatment of LMs, which are rare, non-malignant cysts of the lymphatic vascular system that primarily form in the head and neck region of children. In October 2023, Protara initiated the STARBORN-1 Phase 2 trial to evaluate the safety and efficacy of intracystic injection of TARA-002 for the treatment of macrocystic and mixed-cystic LMs. The company has secured the rights to a dataset from one of the largest ever conducted Phase 2 trials in LMs, in which OK-432 was administered via a compassionate use program.
Protara's portfolio also includes Intravenous (IV) Choline Chloride, an investigational phospholipid substrate replacement therapy in development for patients receiving parenteral support (PS). PS patients are unable to synthesize choline from enteral nutrition sources, and there are currently no available PS formulations containing choline. In April 2024, Protara announced alignment with the FDA on a registrational path forward for IV Choline Chloride, and the agency has granted the program Fast Track designation.
Quarterly and Annual Financial Performance
For the nine months ended September 30, 2024, Protara reported a net loss of $31.83 million, compared to a net loss of $30.20 million for the same period in 2023. Research and development expenses increased by $3.60 million, primarily due to higher clinical and non-clinical study costs related to TARA-002 and IV Choline Chloride. General and administrative expenses decreased by $1.33 million, driven by a reduction in personnel-related expenses.
As of September 30, 2024, Protara had $81.50 million in cash, cash equivalents, and marketable debt securities, compared to $65.60 million as of December 31, 2023. This increase in liquidity was primarily due to the completion of a private placement in April 2024, which resulted in net proceeds of approximately $42.00 million.
For the full year 2023, Protara reported a net loss of $40.42 million, with research and development expenses of $24.99 million and general and administrative expenses of $18.62 million. The company's annual operating cash flow was negative $37.56 million, and its annual free cash flow was negative $37.60 million.
In the most recent quarter, Protara reported no revenue, as the company is still in the clinical stage and has not yet commercialized any products. The net loss for the quarter was $11.22 million, which represents an increase compared to the same period in the prior year. This increase was primarily due to higher research and development expenses related to the ongoing clinical trials for TARA-002 in NMIBC and LMs, as well as for the IV Choline Chloride program.
The company's operating cash flow for the most recent quarter was negative $8.43 million, and its free cash flow was negative $8.44 million. As Protara is still in the development stage, it does not have year-over-year revenue growth to report.
Protara currently operates only in the United States, as it is a small-cap company focused on developing its pipeline of investigational therapies.
Liquidity
Protara's liquidity position has improved significantly over the past year. The company's cash, cash equivalents, and marketable debt securities increased from $65.60 million at the end of 2023 to $81.50 million as of September 30, 2024. This enhancement in liquidity was primarily driven by the successful completion of a private placement in April 2024, which generated net proceeds of approximately $42.00 million. This strong cash position provides Protara with the financial resources to continue advancing its clinical programs and support its ongoing operations.
As of the most recent financial reporting, Protara had $51.76 million in cash and cash equivalents. The company's debt-to-equity ratio is 0.058, indicating a low level of debt relative to equity. Protara's current ratio and quick ratio are both 9.845, suggesting a strong ability to meet short-term obligations. The available credit line for the company has not been disclosed.
Risks and Challenges
As a clinical-stage biopharmaceutical company, Protara faces the inherent risks associated with drug development, including the potential for delays or failures in clinical trials, regulatory hurdles, and the challenge of securing sufficient funding to advance its pipeline. The company's reliance on the successful development and commercialization of its lead product candidates, TARA-002 and IV Choline Chloride, exposes it to concentration risk.
Additionally, Protara operates in a highly competitive industry, where it must compete with other biopharmaceutical companies for talent, funding, and market share. The company's future success is dependent on its ability to navigate the regulatory landscape, forge strategic partnerships, and effectively manage its clinical and commercial activities.
Outlook and Guidance
Protara remains focused on the advancement of its pipeline, with several key milestones expected in the coming years. The company anticipates reporting interim data from the ADVANCED-2 trial of TARA-002 in NMIBC patients in the fourth quarter of 2024, followed by interim 12-month results in mid-2025.
In the LMs program, Protara expects to share initial results from the next cohort of the STARBORN-1 trial of TARA-002 in the first half of 2025. The company also plans to initiate the registrational THRIVE-3 trial of IV Choline Chloride in the first quarter of 2025, following the receipt of Fast Track designation from the FDA.
Protara's continued focus on its pipeline, coupled with its strong cash position, positions the company to navigate the challenges of the biopharmaceutical industry and advance its mission of transforming the treatment landscape for cancer and rare diseases.
Conclusion
Protara Therapeutics is a clinical-stage biopharmaceutical company with a diverse pipeline of innovative therapies targeting cancer and rare diseases. The company's lead programs, TARA-002 in NMIBC and LMs, and IV Choline Chloride for patients receiving parenteral support, demonstrate Protara's commitment to addressing significant unmet medical needs. With a focus on leveraging modern advancements and a strong cash position, Protara is well-positioned to continue its pursuit of transformative therapies and create value for its stakeholders.
The company has reported positive data from its TARA-002 clinical trials, including a 38% complete response rate at 3 months in a pooled analysis of NMIBC patients across its clinical studies. In the LMs program, interim data from the first safety cohort of the STARBORN-1 trial showed that two out of three patients achieved a complete response after a single injection of TARA-002.
Protara's financial position remains stable, with $81.5 million in cash, cash equivalents, and marketable debt securities as of September 30, 2024. While the company continues to incur losses due to ongoing research and development activities, its strong liquidity position provides runway to advance its clinical programs and support ongoing operations.
As Protara progresses its pipeline and approaches key clinical milestones, investors and stakeholders will be closely watching for updates on the ADVANCED-2 trial in NMIBC, the STARBORN-1 trial in LMs, and the initiation of the THRIVE-3 trial for IV Choline Chloride. The company's success in these programs could potentially transform the treatment landscape for patients with limited options in these challenging disease areas.