TARIS Bio™ announced positive safety, tolerability and preliminary efficacy data from the full patient cohort (n=20) of its Phase 1b study of TAR-200 for the treatment of patients with muscle invasive bladder cancer (MIBC), neoadjuvant to radical cystectomy (RC). This complete dataset builds on the initial positive signal observed in the first part of the study, announced previously. Combined data from both TAR-200 study arms indicates a robust antitumor response on final histopathologic analysis after cystectomy, favorable tolerability profile, and no detectable systemic drug exposure or associated adverse events. These data provide early evidence of the potential benefit of TAR-200 in the treatment of MIBC for both patients who can receive RC and those who are unfit for surgical intervention.

"The TAR-200-101 study has revealed exciting results in patients with muscle invasive bladder cancer," said Siamak Daneshmand, M.D., Director of Urologic Oncology at the USC Institute of Urology, and principal investigator of the study. "Such evidence of response, while early, may enable definitive treatment in patients currently unfit for curative intent therapy, including treatment with checkpoint inhibitors. Moreover, TAR-200 may also ultimately enable organ preservation strategies in lieu of radical cystectomy in patients who are unfit or unwilling to undergo bladder removal."

Each arm in the multi-center study enrolled 10 subjects with organ-confined MIBC (defined as clinical T2-T3 N0M0 disease), who were scheduled to undergo RC and were deemed unfit for systemic platinum-based neoadjuvant chemotherapy. During the window between diagnosis and RC, the TAR-200 system, which continuously delivers gemcitabine in the bladder, was administered twice for seven days per dose separated by a two-week rest. There was no delay to RC for any patient in either arm, with surgery proceeding as planned on Day 28 in Arm 1 and Day 42 in Arm 2. Pathological assessment of pooled data from 20 subjects across the two arms demonstrates:

A 50% objective response rate (ORR), defined as no residual muscle invasive disease (greater than or equal to pT2 disease on post-surgical pathology)

A 40% complete response rate (CR), defined as only residual pT0 or pTis disease

No detectable systemic gemcitabine exposure, nor any typical gemcitabine-associated systemic adverse events

Excellent local tolerability and no evidence of dose-limiting toxicity

"These data provide strong, histopathologically confirmed evidence of TAR-200's anti-tumor activity and highlight our product candidate's potential to fundamentally change the management of the full spectrum of disease for patients with MIBC," said Tony Kingsley, President and CEO of TARIS. "The study results support our next stage of development that focuses first on the large portion of patients who do not receive potentially curative therapies. These patients typically have significant comorbidities and a poor overall performance status, rendering them unfit for current standards of care. With few options, these patients face rapid mortality from this unmanaged disease. We believe that TAR-200 is uniquely positioned to address this substantial and serious unmet need."

The standard of care for treatment of MIBC includes radical cystectomy (complete removal of the bladder and surrounding pelvic organs), with or without neoadjuvant chemotherapy. Radical cystectomy is a major, life-changing surgery, and many patients are medically unfit and/or unwilling to undergo this procedure. Without treatment, patients with MIBC who are not candidates for curative intent therapy quickly succumb to their disease.

TARIS is currently conducting a Phase 1b trial of TAR-200 in patients with MIBC who are ineligible for radical cystectomy, to evaluate the safety and tolerability of the system following four consecutive 21-day dosing cycles (TAR-200-103). The multicenter study rapidly over-enrolled 35 subjects – over three times the targeted number of subjects, demonstrating very high demand for a novel therapeutic option for this patient population. TARIS expects to report topline results from this study in late 2019.

Bladder cancer is the fifth most common neoplasm in industrialized countries, affecting roughly 2.7 million people worldwide. The National Cancer Institute estimates approximately 81,200 new cases and 17,240 deaths due to this disease in 2018; muscle invasive bladder cancer (MIBC) accounts for 20-25% of the newly diagnosed cases and the majority of disease-related mortality. Approximately 8,500 of these patients are unfit for radical bladder removal or chemotherapy, and the only treatment option is palliative care.

TARIS' lead investigational product, TAR-200, is designed to release the chemotherapeutic agent gemcitabine continuously in the bladder for multiple weeks. TARIS believes that TAR-200 has the potential to harness gemcitabine's both direct antitumor and immuno-oncologic activity without meaningful systemic drug exposure, yielding a powerful therapy and mitigating systemic side-effects. The TARIS System has been administered in clinical settings to over 450 individuals and over 900 doses across multiple urologic diseases. The U.S. Food and Drug Administration has granted Fast Track designation to TAR-200 in patients with organ-confined or locally advanced MIBC who are unfit for curative-intent therapy.

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