Did irregular shifts in clinical trial progression at Flagship’s Repertoire foreshadow the termination of its immuno-oncology program?

‍Background: Repertoire Immune Medicine was born of Flagship Pioneering’s 2019 merger of its two portfolio companies, Cogen Immune Medicines and Torque Therapeutics -- marrying the foundational immune decoding and immuno-oncology platforms of each, respectively.

In April 2021, the newly-formed biotech raised $189M (in total, raising over $350M) to support its next stage of development and launched its first clinical phase candidate, RPTR-147. In February of 2021, a second candidate, RPTR-168, began clinical trials targeting HPV-16+ solid tumors. 

Red flags: Irregularities began to surface in the RPTR-147’s program on May 15, 2020, when STAT Trials Pulse detected that the trial had closed recruitment with only 25% of its anticipated patients, enrolling 20 rather than the anticipated 80 patients. 

Eight months later, on December 15, 2020, a new pre-news signal surfaced that the study had re-entered recruitment, simultaneously delaying its primary completion date by 17 months. At the same time, the study set a new enrollment target of 240 participants, an 11x increase from its actual enrollment of 20 patients. On May 10, 2022, the trial further delayed its projected primary completion date by more than three years, to July 2026. 

On August 31, 2022, the RPTR-147 trial closed recruitment for a second time, only having enrolled 23 of its anticipated 240 patients. On the same day, STAT Trials Pulse detected an irregularity in Reportoire’s other candidate study, the RPTR-168 trial targeting HPV-16+ tumors, as it closed recruitment with only 7 of its anticipated 24 patients. 

The big picture: Substantial decreases in enrollment like those highlighted above are crucial early signals to note: falling substantially below enrollment targets may change the validity of initial trial design and efficacy assumptions. This can impact a trial's ability to achieve target power and statistically reliable results. 

‍The impact: On November 7, 2022, Repertoire Immune Medicines officially announced that it would be discontinuing its two clinical programs, RPTR-147 and RPTR-168, specifying that the initial data showed little effect. On December 6, 2022, both trials were officially terminated on clinicaltrials.gov, citing the end of the development of the programs.

‍The fallout: The aftermath of these pipeline cuts was considerable, as Repertoire simultaneously announced the replacement of their CEO and layoffs for nearly half their staff. With no clinical pipeline currently in place, the remainder of Repertoire’s post-overhaul staff has shifted focus on its DECODE platform, intending to identify novel therapeutic targets. Thus far, no new clinical activity has been initiated and the ‘Programs’ & ‘Pipeline’ sections of their site have been removed completely.

‍The bottom line: Irregularities in Repertoire’s active pipelines signaled red flags over two years before their program termination was publicly announced, leading to a complete overhaul of the company’s staff and focus. 

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