German biotech Tubulis has shared updated data from a phase 1 study of the antibody-drug conjugate (ADC) TUB-040, the star behind Gilead’s decision to buy the company for $3.15 billion upfront in April.
TUB-040 was confirmed to shrink tumors in 61% of 46 patients treated with 1.67-3.3 milligrams per kilogram of the therapy, with no patients given less than 1.67 mg/kg showing a response. Average progression-free survival was 11 months, according to the company's presentation at the American Society of Clinical Oncology annual meeting in Chicago on Saturday.
The results come from the Napistar 1-01 trial, a first-in-human study of TUB-040 in patients with platinum-resistant ovarian cancer. The ADC targets a sodium-dependent phosphate transporter, NaPi2b, which is expressed in the vast majority of ovarian cancer cells.
TUB-040’s response rate is “higher than what you see with other developments in the platinum-resistant area,” Gilead’s Chief Medical Officer Dietmar Berger, M.D., Ph.D., told Fierce Biotech on the sidelines of ASCO. The 11-month survival mark tops the five months achieved by standard of care, he pointed out.
In addition to relapsing after platinum-based chemotherapy, many of the patients had also previously been treated with Genentech’s Avastin or a PARP inhibitor. On average, patients in the study had been given four different therapies before trying TUB-040.
On the safety front, all patients had a treatment-related adverse event, with the most common side effects being nausea and fatigue. Of the 67 patients evaluated across dose levels, 42% had grade 3 or worse neutropenia, with 27% and 18% experiencing anemia and thrombocytopenia of similar severity, respectively.
The ADC’s toxicity rates are lower than others in its class, according to Berger, which will make it easier to pair with platinum-based chemotherapy in earlier lines of therapy—which Gilead is now testing.
“You get no lung tox[icity], you get no ocular tox[icity],” Berger told Fierce. “You get a really good therapeutic index.”
But the prime focus for TUB-040 is platinum-resistant ovarian cancer. Gilead is now in advanced discussions with the FDA on possible designs for a phase 3 trial, Mika Derynck, M.D., the company’s head of oncology clinical development, told Fierce at ASCO.
Tubulis fits into Derynck’s broader oncology vision of diversified risk, she explained. That means going after tried-and-true mechanisms like ADCs, while still pursuing immuno-oncology targets and eyeing more challenging science lurking in the tumor microenvironment.
“Gilead really wants to only put forward transformational drugs,” she said. “We don't want to do me-too—certainly not biosimilar or anything like that—which means that we have to do a lot of innovation.”
Gilead grabbed Tubulis amid a flurry of deal-making this year that also saw the Bay Area biopharma acquire its longtime CAR-T partner Arcellx and the T-cell-engager-focused Ouro Medicines. While TUB-040 was a key reason for the Tubulis buyout, Berger said, the platform Tubulis had built was the pièce de résistance. With the acquisition closing just last week, the German outfit is now poised to operate as a research hub for Gilead.
“We'll have an ADC innovation center in Munich, and that is based on the work that Tubulis is doing,” Berger said. The biotech’s unique approach allows for flexibility in the toxic payload used in its ADCs, he explained, which could even enable expansion outside of cancer into Gilead’s other focus areas of inflammation and virology.
“The underlying platform we continue to be excited about,” he said. “We still believe it's a good deal.”