By Jesse Shefferman
Over the years, we have all grown familiar with the traditional biotech scientific playbook. New companies are founded with the goal of realizing the therapeutic potential of newly discovered, potentially exciting scientific advances. The average time from discovery to commercialization is over ten years, so patients, physicians, and other key stakeholders wait, hopeful that this potential therapeutic candidate will be one of the approximately 7% of programs to make it through clinical development to regulatory approval.[1]
While novel discoveries are necessary to advance the standards of care in many diseases, many of today’s backbone therapies in areas such as oncology, immunology and rare diseases, exist as a result of creative re-imagination of therapeutics that were originally intended for different uses.
Today, there remain potentially dozens of overlooked medicines, scattered across the globe, undervalued for various reasons, and ready for the right team to unlock their potential and deliver them to patients in need of new treatment options.
We founded Protara Therapeutics on this very principle. We apply modern scientific, regulatory, and manufacturing advancements to established mechanisms in order to create new, accelerated development opportunities. Using this philosophy, we have built a pipeline of de-risked assets addressing rare disease and oncology.
Modernizing the Science
When our team was first evaluating in-licensing opportunities, we came across a bacterial therapeutic developed in Japan in the 1970s to reinvigorate the immune system following highly immunodepletive chemotherapeutic regimens. This therapy was eventually approved in Japan in solid tumors, including lung, gastric, head, neck and thyroid cancers, as well as lymphatic malformations, and has been successfully and safely administered to thousands of patients.
When we heard about this interesting immune-based treatment with a large patient safety database and significant evidence of efficacy, we knew we owed it to patients to dig deeper and explore new potential applications. We asked ourselves, “could this medicine be reimagined in our current scientific and therapeutic landscape?”
We acquired the global development rights, outside of Japan and Taiwan, for this therapeutic, TARA-002, known as Picibanil or OK-432 in Japan, from Chugai Pharmaceuticals. TARA-002 is a genetically distinct strain of Streptococcus pyogenes that is inactivated while retaining its immune-stimulating properties. It was probably one of the first oncology immunotherapies, only at the time it’s likely no one understood that potential.
We were able to assess TARA-002 using a modern lens to further identify its potential in oncology. For decades, the literature suggested this therapy was an agonist for TLR4, a well-understood pathway for the human body’s recognition of pathogens. However, when we ran our modern HEK assay to interrogate TARA-002’s mechanism, we determined that it was actually a Nod2-TLR2 agonist. This represents just one of the ways our approach helps breathe new life and understanding into established therapeutics.
TARA-002 is now our lead investigational cell therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs). By rigorously examining the underlying biology for this established therapeutic, we were able to open up a contemporary understanding of its mechanism of action, enabling Protara to more precisely address the unmet needs of new and underserved patient populations.
How Manufacturing Impacts Access
Many modern biotechnology companies address manufacturing scalability in the later stages of developing therapies, once proof of concept has been established. In the case of TARA-002, our team understood that demonstrating manufacturing expertise in the earliest stages of development would play a critical role in delivering TARA-002 to new patient populations beyond those historically treated in Japan with OK-432.
We began the TARA-002 development program knowing we would need to modernize OK-432’s manufacturing process to ensure TARA-002 complied with U.S. Pharmacopeia while still demonstrating comparability to OK-432, thereby incorporating the historic data and non-clinical findings from OK-432 into the TARA-002 program.
The standard of care for NMIBC, where we have re-imagined OK-432’s oncology history through TARA-002, is currently Bacillus Calmette-Guérin (BCG), another bacterial immunopotentiator, which has faced significant shortages for many years due to manufacturing issues. These shortages have led to an urgent need for new therapies to treat NMIBC. Our manufacturing facility has a 20 million vial capacity with the ability to expand capacity by five times. We have completed U.S. Food and Drug Administration (FDA) inspections and expect to begin commercial manufacturing of TARA-002 (Picibanil) for the Japanese market in the near future.
By combining our deepened mechanistic understanding of TARA-002 with our manufacturing knowledge, we were able to implement efficiencies that make it possible to manufacture TARA-002 compliantly and at scale, unlocking the exciting potential of this potential new therapy.
Setting the Stage for Positive Regulatory Interactions
The third pillar of our approach is ensuring therapies have defined regulatory pathways with the option to obtain multiple potential approvals.
De-risked candidates are de-risked for a reason, typically because they have demonstrated some level of safety and efficacy in patients. Leveraging these data, it is often possible to design clinical studies that address the most pressing regulatory questions while prioritizing efficiency.
For our second pipeline candidate, intravenous (IV) choline chloride, a phospholipid substrate replacement therapy for patients receiving parenteral support, the majority of whom are at significant risk of liver disease, we were able to align with the FDA on the design of a streamlined Phase 3 clinical trial requiring a single pharmacokinetic endpoint demonstrating an increase in choline levels.
This simple and effective registrational study design is an essential part of our plan to bring this much needed medication to patients quickly, and underscores the importance of evaluating therapies in the context of evolving regulatory dynamics, in this case, the recent creation of the FDA division for hepatology and metabolics where the Investigational New Drug (IND) application for Choline is domiciled.
Overall, we believe there are many candidates across our industry that have rich clinical databases and significant therapeutic potential but suffer from a lack of proper understanding and creative approach. If developed with the right combination of scientific, manufacturing and regulatory expertise, we are confident these medicines can be developed efficiently to address the unmet needs of patients who desperately require new treatment options.
Learn more about Protara’s unique approach here.
[1] IQVIA Institute for Human Data Science, “Global Trends in R&D 2025,” March 2025