Shooting for a heavily pre-treated niche cancer market, Bicycle reveals a ‘mixed’ data cut

Less than two months after expanding its immuno-oncology partnership with Roche’s Genentech, Bicycle Therapeutics touted some new in-house data on its lead program.

The Boston-UK biotech reported results from the dose-escalation portion of a Phase I/II trial for BT5528, observing a handful of responses among a dozen very sick patients who possess a particular tumor expression. Overall, execs viewed the data as positive, selecting a dose to use in the next portion of the study and honing in on a potential path forward in ovarian and urothelial cancers.

Investors viewed the data with tepid optimism, as Bicycle’s stock price $BCYC ticked up slightly by about 3% in early Wednesday trading. Analysts, however, didn’t view the news with such positivity, as SVB Securities’ Jonathan Chang noted the full results are “mixed.”

Dominic Smethurst

Researchers had been testing BT5528 in what CMO Dominic Smethurst described in a Wednesday morning investor call as an “all-comers trial,” with Bicycle enrolling patients who had solid tumors. Among the 45 patients dosed, 21 had ovarian cancer and eight had urothelial cancer.

A smaller group within those 29 individuals possessed the kind of tumor expression Bicycle had been seeking to evaluate — EphA2, a member of the Eph subfamily of receptor tyrosine kinases. Nine of the 21 ovarian cancer patients’ tumors expressed EphA2, in addition to three of the eight urothelial cancer patients.

Bicycle highlighted its market opportunity in Wednesday’s call by drawing attention to previous R&D failures in targeting EphA2, namely from MedImmune, Daiichi Sankyo and Merrimack. All three of those early-stage programs were discontinued due to safety: MedImmune saw blood clotting issues in its first dose cohort, Daiichi Sankyo observed significant infusion reactions and Merrimack couldn’t find the right safety/efficacy balance.

But by developing compounds similar to antibody-drug conjugates but smaller and potentially more potent, Bicycle believes it’s found a solution to this elusive target. Within the nine EphA2-positive ovarian cancer patients, Bicycle observed one complete response and one partial response, while also seeing two partial responses in the three-patient EphA2+ urothelial cancer group.

Four other ovarian cancer patients also saw their tumors shrink, but didn’t get to the partial response threshold. The median patient in Bicycle’s study received four earlier lines of therapy, with the average age of 62.

The dose with which Bicycle is electing to move forward is one where patients are treated every other week at 6.5 mg per square meter — the middle level of five dosages tested. Three of the four responding patients started at higher levels and were lowered to the 6.5 mg/m² threshold. The CR patient remained on therapy for 16 months, while the other three were between three and six months of treatment.

On safety, Bicycle didn’t see any grade 3 or higher lowered neutrophil count events at this dosing level, though it saw 10 across all dosage cohorts. Additionally, there were two grade 3 events of anemia at 6.5 mg/m² patients, out of four overall. There were no grade 3 events of skin rash, hemorrhage or eye disorders at this dosing level either, though one patient did see a minor eye disorder event arise.

In Wednesday’s call, analysts questioned execs on whether Bicycle might move forward with dosing patients at higher levels initially and then reducing them to a maintenance dosage. But CEO Kevin Lee demurred, saying they’re considering it but still looking at the data.

“Right now, we’re very comfortable with 6.5 every other week,” Lee said.

Though the focus on EphA2 is consistent with the company’s strategy, SVB’s Chang said the overall response rate in ovarian cancer was only incrementally better from the last update (2 in 9 compared to 1 in 5). And given how the overall safety profile turned out worse among EphA2 negative patients — despite noting the favorable results at the dose at which Bicycle will be moving forward — Chang expects most investors to desire “more definitive evidence” of clinical benefit.

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