Over the past two years, we have probably written about Protara Therapeutics (Nasdaq: TARA) more than any other company in our universe. The equity has performed well since our initial December 2023 note ($1.88), despite the company arguably lacking a major data catalyst. However, that is scheduled to change as the company will report key interim data from its registrational ADVANCED-2 study in BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients treated with TARA-002 next week at ASCO-GU. During recent corporate presentations, the company’s CEO, Jesse Shefferman, has indicated that TARA-002’s efficacy in BCG-unresponsive NMIBC may be comparable to that reported in the BCG-naive NMIBC setting in December of last year. If that plays out with next week’s data, we believe Protara’s equity will re-rate significantly higher.
Data History
Protara’s ADVANCED-2 study is testing TARA-002 in two cohorts of NMIBC patients: BCG-unresponsive and BCG-naive. The company last reported interim data from the BCG-unresponsive cohort in April 2025, showing a 100% any-time complete response (CR) rate, a 100% six-month CR rate, and a 67% 12-month CR rate with TARA-002. These impressive data were derived from a very small sample, with only five patients evaluable at 6 months and three at 12 months. Compared with its NMIBC peers, these data are the best seen to date. However, given the small sample size, it is unfair to compare five patients from the TARA-002 data with approved and development-stage NMIBC treatments, which have data from >80 patients. Hence, the importance of next week’s results for Protara, which should include data from approximately 25 six-month evaluable BCG-unresponsive patients. These data will enable a more appropriate cross-study comparison of TARA-002’s efficacy with other NMIBC treatments.
Late last year, Protara released data from the BCG-naive cohort of the ADVANCED-2 study. Those results showed that TARA-002 achieved an impressive 72% any-time CR rate (21/29), a 69% six-month CR rate (18/26), and a 50% 12-month CR rate (7/14). The company plans to initiate the pivotal ADVANCED-3 study with TARA-002 in BCG-naive patients imminently. However, we are more interested in whether TARA-002’s BCG-naive efficacy foreshadows what investors can expect from next week’s BCG-unresponsive data.
Different But The Same…
Leading up to next week’s data at ASCO-GU, CEO Shefferman has emphasized in recent presentations that TARA-002 should perform similarly regardless of an NMIBC patient’s BCG exposure. During his January JP Morgan presentation, he said, “We do not believe that a BCG-unresponsive patient is biologically different from a naive patient in the context of (TARA) 002.” In that presentation, he went on to say that it wouldn’t be surprising if TARA-002 replicated the naive results in the unresponsive setting. He stated, “…if in February (ASCO-GU), we have a 72% complete response rate at 6 months and a 50% complete response rate at 12 months in our unresponsive patients, we would be unsurprised; and very happy with that because those numbers in the unresponsive setting are clearly through a threshold of relevance from an efficacy perspective…” (Please note that Shefferman misspoke when he referred to TARA-002’s six-month CR rates as 72%, when in fact it was 69%. The 72% he refers to is the anytime CR rate, the study’s primary endpoint.)
*Assuming BCG-Naive Like Results
If TARA-002’s BCG-unresponsive interim efficacy were to be similar to the BCG-naive data, as Shefferman implies, then Protara would have a product that appears to have equivalent efficacy with the anticipated market leaders, CG Oncology’s (Nasdaq: CGON) cretostimogene (creto) and J&J’s Inlexzo (affectionately known as the pretzel). Furthermore, TARA-002 offers notable safety and ease of administration advantages over other BCG-unresponsive NMIBC therapies, which could resonate with uro-oncologists, especially those in community settings, where the majority of patients are treated. Which begs the question: could TARA-002, with efficacy equivalent to (or close to) creto and the pretzel, but with superior safety and ease of use, become a first-line treatment for BCG-unresponsive NMIBC?
Does First-Line Even Matter?
It’s fun as a Protara shareholder to speculate that TARA-002 could become first-line in BCG-unresponsive NMIBC, but realistically, it doesn’t need to be first-line to be a billion-dollar drug. Recall that the last resort for recurrent NMIBC is cystectomy, a procedure with significant morbidity that dramatically impacts a patient’s quality of life. We have previously quoted a well-respected sell-side analyst who, in a CG Oncology note a few years ago, wrote, “The critical point to re-emphasize is that these patients generally are not rapidly progressive to metastatic disease, which means they will likely cycle through multiple lines of therapy – creating significant TAMs in 2L (post-BCG) and 3L and even 4L NMIBC….we expect blockbuster product opportunities well into the 4L setting – so plenty of room for all these emerging NMIBC players.”
Expectations
Next week, investors should expect anytime and six-month CR rates from approximately 25 BCG-unresponsive patients, and 12-month CR rates from 10-12 BCG-unresponsive patients. As we have suggested, CEO Shefferman has hinted that CR rates in line with the company’s December BCG-naive data are a distinct possibility. However, investors shouldn’t despair if next week’s interim data falls slightly short of the bar set by the naive data. In our view, an anytime CR rate in the mid-60% range, a six-month CR rate of ≥60%, and a 12-month CR rate of ≥40% remain competitive, especially given TARA-002’s other differentiating attributes. Then again, if next week’s BCG-unresponsive data are similar to the CR rates reported in the naive data, Protara is sitting on a blockbuster opportunity, and its market cap should re-rate accordingly.
Two Final Comments
The ASCO-GU abstracts are scheduled for release on Monday, February 23rd. This should include all six-month evaluable patients through October 21, 2025, the abstract submission deadline. However, we expect Protara’s poster presentation on Friday, February 27th, to include a more recent data cutoff and, therefore, more patients than appear in Monday’s abstract.
Lastly, it will have been almost three months since Protara’s $75 million financing, syndicated by a group of banks led by J.P. Morgan. Every bank in the syndicate had covered Protara prior to the financing or has initiated coverage since then, except for J.P. Morgan. It appears J.P. Morgan has decided to wait for the BCG-unresponsive data before initiating. Positive BCG-unresponsive data followed by a J.P. Morgan initiation could be a winning formula for Protara shareholders. We will have to see.