SHERIDAN, WYOMING – July 8, 2025 – The TIGIT immunotherapy landscape has thinned dramatically amid a string of late-stage failures and corporate exits, yet several biopharma players remain committed to unlocking its clinical promise—driven by differentiated approaches and early signals of efficacy. AstraZeneca, Gilead, Agenus, and Mereo BioPharma are now at the forefront of this once-promising immuno-oncology frontier, recalibrating strategies in a space shaped by volatility and unmet potential.
AstraZeneca Bets Big on Dual Checkpoint Innovation
AstraZeneca’s rilvegostomig is one of the most advanced TIGIT assets in development today. The bispecific antibody is currently undergoing evaluation in ten Phase III trials across non-small cell lung cancer (NSCLC), gastric cancer, biliary tract cancer, and other solid tumors.
“AstraZeneca is leveraging its partnership with Daiichi Sankyo to test combinations of the TIGIT with the antibody-drug conjugate Datroway for specific subtypes of NSCLC,” said Shubh Goel, Global Franchise Head of Oncology at AstraZeneca. “The goal…is to establish rilvegostomig as a ‘best-in-class [immuno-oncology therapy] and the preferred IO backbone for combination therapies.’”
Rilvegostomig’s bispecific structure enables it to first bind to TIGIT before targeting PD-1, thereby delivering dual checkpoint inhibition while preserving effector T cells. This mechanism, Goel explained, “leads to enhanced immune activation and improving anti-tumor responses,” compared to separate PD-1 and TIGIT agents.
Initial results have been compelling. At ASCO 2025, rilvegostomig in combination with Datroway achieved a 57.5% confirmed overall response rate and 95% disease control rate in advanced NSCLC—validating the molecule’s potential to outperform traditional IO combinations.
Gilead and Arcus Pursue a “Silent” Approach to Immune Modulation
Gilead and Arcus Biosciences are co-developing domvanalimab, a TIGIT-only antibody engineered with Fc-silent properties to minimize immune-related toxicity. Administered alongside Arcus’ PD-1 inhibitor zimberelimab and chemotherapy, the combination is in late-stage development for NSCLC and upper gastrointestinal cancers.
“By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activate immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity,” said Ashish Jhingan, Program Strategy Leader of Oncology at Gilead.
This novel mechanism has delivered promising results. In the EDGE-Gastric trial, the domvanalimab combination yielded a 59% ORR overall, and 80% in high PD-L1 patients. Median treatment duration reached 49.4 weeks with a 12-month progression-free survival of 57.6%. The ongoing STAR-221 study is expected to build on these findings, with initial readouts anticipated in 2026.
Agenus Regroups Following BMS Exit
Agenus’ AGEN1777 was once a high-profile TIGIT contender under a $1.36 billion collaboration with Bristol Myers Squibb. But in January 2025, BMS exited the agreement as part of a broader pipeline refocus.
Despite the setback, Agenus retained all rights to AGEN1777 and now plans to “explore further development and/or relicensing” of the therapy. While the company has yet to define its next steps, the prior partnership did generate “significant safety data” and “indications of clinical activity.”
As part of a broader strategic realignment aimed at reducing annual spending to $100 million, Agenus’ future TIGIT plans may hinge on securing new partnerships or funding to re-ignite development.
Mereo BioPharma Looks to Out-License Etigilimab
Mereo BioPharma’s etigilimab, an IgG1 anti-TIGIT monoclonal antibody, follows a distinct path by retaining Fc functionality. This enables it to reduce regulatory T cells while preserving CD8-positive cytotoxic T cells, potentially enhancing efficacy without compromising safety.
A mid-stage study published in late 2023 showed a 25% ORR, including three complete responses and seven partial responses. Seven patients maintained clinical benefit for over a year—promising results that have yet to attract a strategic partner.
“We intend to out-license or sell etigilimab . . . to third parties for the further development, recognizing the need for greater resources to take [this asset] to market,” Mereo noted in its 2024 year-end report.
Conclusion: Can Differentiation Rescue TIGIT?
With big pharma players scaling back and many biotech programs shuttered, the TIGIT field now rests on a handful of candidates with novel designs and more precise biomarker-driven strategies. From AstraZeneca’s bispecific innovation to Gilead’s Fc-silent targeting, the next phase of TIGIT research will depend on continued clinical validation—and ultimately, investor and partner confidence.
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