Astellas is aiding Vir Biotechnology’s oncology pivot with a $1.7 billion global collaboration focused on a potential best-in-class T-cell engager (TCE) for prostate cancer.
Under the leadership of CEO Marianne De Backer, Ph.D., Vir is trading a stake in its PSMA-targeted bispecific VIR-5500 for a $335 million upfront and near-term capital infusion from Astellas.
The PSMAxCD3 bispecific leverages Vir’s PRO-XTEN dual-masking technology, which is designed to keep the therapy inactive until it’s unmasked within the tumor. The drug is reporting updated phase 1 data at the 2026 ASCO Genitourinary Cancers Symposium (ASCO GU) that the partners believe are promising.
The alliance validates Vir’s shift from an infectious disease focus toward immuno-oncology in a strategic move that De Backer launched by licensing the PRO-XTEN platform and three clinical-stage TCEs—including VIR-5500—from Sanofi in 2024. For Astellas, the deal could reinforce the Japanese pharma’s position in the prostate cancer market as its Pfizer-partnered Xtandi (enzalutamide) starts to lose patent protection and market exclusivity in different territories this year.
The perfect match
Astellas emerged as “the perfect partner” after a “competitive” process, De Backer told Fierce Biotech in an interview. As the world’s No.1 company in prostate cancer with “very deep expertise internally on clinical development,” Astellas is “the partner of choice in this field,” she said.
De Backer joined Vir in 2023 after leading business development at the pharmaceutical branch of Bayer, which is also experienced in prostate cancer based on its next-generation androgen receptor inhibitor Nubeqa (darolutamide).
“The field is moving very, very fast. And we believe that we could accelerate the program by working together with someone who has a really strong track record in the space,” De Backer said, adding that the partnership could also broaden the patient populations that could be explored for VIR-5500.
Along with the ASCO GU data revelation, Vir said it expects to move VIR-5500 into phase 3 testing in 2027. While the company has so far been testing the drug in metastatic castration-resistant prostate cancer (mCRPC), it now also aims to initiate phase 1 dose-expansion cohorts in metastatic hormone-sensitive prostate cancer in the second quarter of 2026.
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“It’s the promise of what T-cell engagers can deliver,” Anthony Jarkowski, primary focus lead of immuno-oncology at Astellas, said in the joint interview with Fierce, when asked about the company’s rationale for the deal. “What we see from VR-5500 is really a good efficacy profile, and importantly, the safety profile looks really manageable.”
Besides its deep experience in prostate cancer, Astellas is also not entirely new to TCE work; the company has a Claudin18.2xCD3 agent currently in clinical development for stomach cancer.
The $335 million includes $240 million in cash, $75 million in an equity investment at a 50% premium to Vir’s 30-day average share price, and a near-term $20 million milestone. The San Francisco biotech is also eligible to receive up to $1.37 billion in additional development, regulatory and sales milestones, plus tiered, double-digit royalties on future ex-U.S. sales.
Astellas and Vir will share development costs 60-40. In the U.S., Vir will have the option to co-promote VIR-5500, with profits or losses shared equally. Astellas will be solely responsible for commercialization outside the U.S.
Vir’s original licensing deal with Sanofi means some proceeds from the Astellas pact will be shared with the French pharma.
Updated phase 1 data
Astellas and Vir are venturing into a highly competitive field. In PSMA alone, Novartis is already making commercial progress with its blockbuster radioligand therapy Pluvicto. And Janux Therapeutics’ masked TCE, JANX007, is currently ahead of VIR-5500 in the development race.
Further, Amgen’s STEAP1-targeting xaluritamig and Johnson & Johnson’s KLK2-targeting pasritamig are both TCE candidates designed to treat prostate cancer.
Despite existing treatment options, an unmet medical need still exists in prostate cancer, as only about 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) can live to five years after diagnosis, according to Vir.
Rather than introducing a radioactive foreign agent, a TCE activates a patient’s own T cells to fight the tumors, potentially avoiding some side effects. But TCEs come with their own toxicity problems due to that immune activation mechanism, most notably cytokine release syndrome (CRS). That’s where Vir’s PRO-XTEN comes in.
Compared with Janux’s single-masking technology, Vir’s dual masks cover both the tumor-associated antigen side and the CD3 component. This allows for additional protection before reaching the target tumor, enabling a great therapeutic index, De Backer explained.
Updated efficacy data to be presented at ASCO GU showed that 14 (82%) heavily pretreated mCRPC patients who got the highest evaluated doses (3,000 μg/kg or above) of VIR-5500 achieved a 50% or greater reduction in PSA levels from baseline, while nine (53%) saw at least a 90% reduction. These endpoints are called PSA50 and PSA90, respectively.
The PSA responses were notably improved from the initial data that Vir reported a year ago from several lower-dose cohorts, and they now look very similar to the 86% PSA50 and 54% PSA90 that Janux reported in December among late-line patients who received its selected phase 1b dosing regimen.
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Out of 11 patients evaluable for tumor responses under the RECIST criteria who received the highest doses, VIR-5500 led to an objective response rate of 45%, including four confirmed responses and one unconfirmed response. By comparison, Janux recently reported a 30% ORR among 27 patients without breaking up confirmed and unconfirmed cases, a decline from the previous 50% ORR generated in eight evaluable patients.
As for safety, a potential key differentiator for VIR-5500, Vir again stated that prophylactic steroids were not required to prevent serious CRS events, and no IL-6 inhibitors were used to manage CRS.
CRS was observed in 29 (50%) of all 58 patients, and Vir described the events as “generally restricted to grade 1.” No grade 3 or above CRS was seen in the go-forward dose that Vir has selected, De Backer told Fierce. However, the chief executive didn’t say whether any grade 3 events were recorded in other subgroups. More detailed data will be presented at ASCO GU on Feb. 26.
Among all patients who got various doses of VIR-5500 monotherapy, grade 3 or above treatment-related adverse events occurred in seven (12%) patients.
“It is remarkable to see these early signs of profound anti-tumor activity in heavily pretreated mCRPC patients, and the favorable tolerability with minimal CRS to date means VIR-5500 could play a role in treating earlier disease,” Johann de Bono, the phase 1 trial’s principal investigator and a prostate cancer expert from The Institute of Cancer Research in the U.K., said in a Feb. 23 statement.
“What really stood out to us is how they’re balanced—efficacy and toxicity,” Jarkowski said.
Vir’s dual-masking technology could also give VIR-5500 a preferable dosing frequency compared to its rival. Janux’s recent data came from a dosing schedule of once every week—and the company also has some early data for a once-every-other-week regimen—whereas Vir’s drug was administered once every three weeks (Q3W). However, both are still more frequent than Pluvicto’s once-every-six-weeks schedule, although Pluvicto administration is currently limited to designated treatment centers thanks to its radioactive nature.
De Backer argued that Q3W dosing is “already very attractive, even if you want to move to earlier lines or outpatient setting.” Both De Backer and Jarkowski added that Vir and Astellas will work together to decide what to explore in the future.
Vir said it has concluded dose-escalation in late-line mCRPC and “has defined a preliminary go-forward dose” for expansion, with monotherapy dose-expansion in this setting planned for the second quarter. Dose-escalation of VIR-5500 in combination with Xtandi is ongoing in early-line mCRPC, with dose expansion also expected to start in Q2.
