Boundless Bio is in a bind. A phase 1/2 trial has revealed the shortcomings of Boundless’ lead candidate, prompting the company to lay off one-third of its staff and pivot to a combination of two molecules that struggled as monotherapies.
San Diego-based Boundless pulled off a $100 million IPO last year to fund phase 1/2 trials of BBI-355 and BBI-825 in solid tumors. The biotech opted against advancing its RNR inhibitor BBI-825 in December after seeing a lack of dose-proportional exposure. Boundless emerged from the setback focused on reporting preliminary clinical proof-of-concept safety and antitumor activity data on its CHK1 inhibitor BBI-355.
The preliminary data killed off hopes of developing BBI-355 as a single agent with continuous dosing. The phase 1/2 study in patients with oncogene-amplified solid tumors saw hematological toxicity at or near doses associated with clinical activity. The narrow therapeutic window torpedoed monotherapy plans.
Boundless also tested the candidate in combination with the EGFR inhibitor erlotinib and FGFR inhibitor futibatinib, which Taiho Oncology sells as Lytgobi. However, the combinations were not well tolerated at the doses the biotech believes are needed for robust, sustained anti-tumor activity. The findings drove the biotech to stop further development in the current arms of the phase 1/2 trial.
With neither BBI-355 nor BBI-825 making the grade as a monotherapy, Boundless has decided to test the two candidates in combination. The biotech said there is a strong mechanistic rationale for the cocktail, which it believes is free from overlapping toxicity and can eliminate the need for continuous dosing.
The combination has shown synergistic cytotoxicity in cancer cell lines and tumor regression in mouse xenograft models using weekly dosing at exposures not associated with hematological toxicity, according to Boundless. The biotech plans to start clinical development of the combination this year.
Boundless also revealed it has selected BBI-940 as the development candidate from its kinesin degrader program. The company remains on track to file to study the candidate in humans in the first half of next year. Boundless is making cuts to extend its cash runway beyond proof-of-concept clinical readouts for its combination and BBI-940.
Earlier this month, Boundless said its cash runway extended into 2027. Now, the company has extended the runway into the first half of 2028 by laying off about one-third of its staff. Boundless had 64 employees as of March 21. The biotech had 72 employees one year earlier but laid off staff in August 2024 in response to slow enrollment in the BBI-355 trial.