Looking to expand its oncology portfolio, Gilead Sciences has tapped Vir Biotechnology’s masked T-cell engager (TCE) tech in a potential $1.9 billion biobucks deal.
Under the agreement, Gilead is licensing three T-cell engagers built on Vir’s dual-masked PRO-XTEN platform, the same technology behind Vir’s potential $1.7 billion partnership formed with Astellas in February.
Vir will handle the discovery, design and optimization of three TCE candidates targeting solid tumor-associated antigens. Gilead holds exclusive rights to nominate candidates and will assume responsibility for subsequent development, manufacturing and commercialization.
The two companies have already selected the targets for the three programs, Vir CEO Marianne De Backer, Ph.D., told Fierce, although she declined to characterize the proposed indications further.
“These are three targets that we were not interested in exploring ourselves,” De Backer said. “So it really allows us the possibility to focus on our own programs in addition to bringing in non-dilutive funding through partnerships like this.”
In return, Vir will receive $90 million upfront, consisting of $65 million cash and a $25 million equity investment priced at a 30% premium. Down the line, the biopharma could also receive $45 million in near-term preclinical milestones, followed by up to $1.74 billion in additional development, regulatory and commercial milestones, as well as tiered high single-digit to low double-digit royalties on sales.
De Backer touted PRO-XTEN as a “plug and play” technology, meaning it can use the same mask on the optimized TCE rather than having to develop a new mask for each molecule.
“We are extremely efficient in coming up with powerful T-cell engagers, then using our AI engine dAIsY to optimize them,” she said.
In a statement, Flavius Martin, M.D., Gilead’s executive vice president of research, said: “We look forward to combining Gilead’s established and growing oncology capabilities, including our extensive development expertise and focus on next-generation immunotherapies, with Vir Biotechnology’s innovative discovery capabilities.”
The two California biopharmas formed the TCE alliance just as Vir is on the verge of reporting registrational data for its hepatitis delta combo, elebsiran and tobevibart, a potential competitor to Gilead’s Hepcludex.
The Vir partnership adds to a busy year of oncology dealmaking for Gilead. Earlier this year, the biopharma acquired CAR-T specialist Arcellx for $7.8 billion to gain near-market multiple myeloma candidate anito-cel, before shelling out $3.15 billion upfront to buy antibody-drug conjugate (ADC) developer Tubulis. However, Gilead’s flagship solid tumor product, TROP2-directed ADC Trodelvy, has hit multiple clinical snags, most recently in first-line non-small cell lung cancer.
This year also saw Gilead orchestrate a three-way acquisition of Ouro Medicines, which featured a BCMAxCD3 TCE candidate designed for autoimmune diseases.
In a recent interview with Fierce, Gilead’s CEO Dan O’Day said the company’s efforts to diversify into oncology and immunology have reached “critical mass,” and that future M&A activities would focus on complementing this foundation.
TCEs have emerged as powerful anti-tumor agents by directing immune cells to destroy cancer cells, though their application in solid tumors has often been limited by toxicity. To reduce these side effects, Vir’s PRO-XTEN tech engineers TCEs with masks that cover both the tumor-associated binding domain and the T-cell binding domain. The molecule therefore remains inactive until it reaches the tumor, where tumor-specific proteases cleave the masks to unleash its cancer-killing effect.
The tech already attracted Astellas, which paid $315 million upfront in February in a mix of cash and equity to license Vir’s PSMAxCD3 candidate VIR-5500. The drug has produced promising phase 1 data and recently earned an FDA “fast track” designation in prostate cancer.
Astellas and Vir have six expansion cohorts in the works for VIR-5500 across various prostate cancer settings, including in combination with Astellas and Pfizer’s Xtandi or docetaxel in first-line metastatic castration-resistant prostate cancer, as well as with Bayer’s Nubeqa in metastatic hormone-sensitive prostate cancer. The two firms plan to advance the PSMA TCE into phase 3 next year, De Backer said.
Vir’s internal pipeline also includes a HER2 TCE, dubbed VIR-5818, with phase 1 dose escalation data expected later this year. Previously, Vir showed some encouraging initial data in metastatic, microsatellite stable colorectal cancer patients from an early-stage basket trial. De Backer said the company is still exploring which indication to focus the molecule on.
The dual-masking platform could enable more deals for Vir in the future, the CEO suggested.
“There’s this great synergy between our protein-engineering capability and our masking technology, and we have really optimized that process quite a bit,” De Backer said.
“We have many more opportunities to explore and exploit that technology platform than we can ever handle, so we have selected a number of programs that we want to progress on our own,” she added. “But there’s certainly an opportunity to do more deals in the masked T-cell engager space.”
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