Maplirpacept

Created with Canva Dreamlab † Leading companies spent $1.4 billion upfront on licensing deals and embarked on vast R&D programs. Clinical setbacks mean many companies are unlikely to ever recoup their investments. TIGIT was once the hottest target in immuno-oncology. Just a few years later, the pipeline has thinned significantly as a who’s who of drugmakers have retreated from the mechanism in response to lackluster clinical data. Some R&D programs are ongoing, but the rapid retreat means the industry has already burnt billions of dollars on deals and development for failed candidates. Bristol Myers Squibb , Gilead, GSK and Novartis paid $1.4 billion upfront between them to join Merck and Roche in the TIGIT race. The figure excludes the $175 million Gilead paid to enter into a multi-asset deal that gave it the right to license candidates including Arcus Biosciences’ domvanalimab, but includes the $275 million the big biotech handed over when it took up its option on the anti-TIGIT antibody. The deals collectively included more than $5 billion in milestones. However, the overwhelming majority of them were unpaid when BMS, GSK and Novartis dropped their TIGIT programs. Gilead is still developing its asset and could owe Arcus up to $500 million in milestones tied to approvals in the U.S. Even without the regulatory milestones, Gilead has bet more on TIGIT than some of its peers. The outlay includes $740 million in equity investments in Arcus. Gilead paid an average of $27.58 per share across the three purchases. Arcus currently trades below $10. The fate of domvanalimab will go a long way in determining what return, if any, Gilead gets on its investment in Arcus. TIGIT Development Costs TIGIT development costs are embedded in the vast R&D budgets of the biopharma companies advancing the candidates. Roche’s broad tiragolumab development program accounted for some of the almost $15 billion the Swiss drugmaker spent on R&D last year, but publicly available figures lack details of the company’s spending on TIGIT. Similarly opaque accounts obscure TIGIT spending at other companies. Programs partnered with smaller biotechs shed some light on TIGIT development costs. GSK and iTeos Therapeutics agreed to spend $900 million on the global development plan for their TIGIT drug. The asset’s failure in Phase II means GSK and iTeos likely only spent a fraction of that amount, but the figure provides a ballpark estimate of what companies with large late-phase programs may have invested. Roche has tested tiragolumab in 10 Phase III studies with a collective enrollment target of almost 4,600 patients. Merck’s Phase III vibostolimab program spanned five studies with a collective enrollment target of more than 4,600 patients. Gilead, Arcus and AstraZeneca, which is partnered on a domvanalimab trial, have sponsored three Phase III studies that are enrolling almost 3,000 patients among them. If GSK and iTeos’ spending plan is indicative of R&D costs at other companies, Gilead, Merck and Roche may have spent billions of dollars between them taking their TIGIT assets through mid- and late-phase trials. Gilead’s relationship with Arcus provides another datapoint. Arcus received between $161 million and $165 million from its collaboration partners as reimbursement for R&D costs in 2022, 2023 and 2024. Mechanisms other than TIGIT will account for some of the spending. Equally, the figures do not capture spending on Gilead-led activities, which Arcus said increased in 2024. ITeos’ accounts provide another glimpse at the cost of TIGIT development. As of the end of March, the biotech had raised more than $1.1 billion across public and private financing rounds and its deal with GSK. ITeos, which is closing down over its TIGIT flop, had $624 million in cash and investments. The difference between the amount iTeos had raised and the amount it was holding was more than $500 million. A History of Failed Oncology Bets Spending on TIGIT adds to the mountain of money that drug developers have plowed into an alphabet soup of targets that at one time were seen as the next big thing in cancer immunotherapy. IL-2 attracted interest in 2018 and 2019, when BMS paid Nektar Therapeutics $1.85 billion to co-develop a molecule and Sanofi acquired Synthorx for $2.5 billion. Both programs ended in failure. Other companies placed bets on CD47. Gilead acquired Forty Seven for $4.9 billion in 2020 and Pfizer snapped up Trillium Therapeutics for $2.3 billion the following year. Pfizer continues to list maplirpacept, a CD47 candidate acquired in the Trillium takeover, in its pipeline, but Gilead’s travails have dampened expectations. Gilead gave up on Forty Seven’s magrolimab last year after a series of setbacks. TIM-3, 4-1BB, ICOS, OX40 and CD73 are among the other targets that have attracted heavy investment, including triple-digit upfront licensing fees, over the years. Active clinical development is continuing in some areas but the targets are yet to live up to the early excitement, such as the report that 4-1BB drug candidates were driving “pretty phenomenal responses” in cancer patients. Work on LAG-3 delivered an approved drug, BMS’ Opdualag, but sales have been fairly modest by the standards of leading immuno-oncology products. Opdualag, a fixed-dose combination of PD-1 and LAG-3 blockers, generated sales of $928 million last year. BMS is on course to reach the blockbuster threshold this year, with sales in the first quarter coming in at $252 million. As excitement about TIGIT and the other targets has faded, PD-1/L1xVEGF-A bispecifics have emerged as the industry’s next big hope. With China’s Akeso validating the mechanism, albeit without allaying concerns about overall survival and efficacy in global trials , leading biopharma companies have moved swiftly to secure riders in immuno-oncology’s new hottest race. In the nine months since Akeso’s ivonescimab beat Keytruda, BioNTech, BMS, Merck and Pfizer have paid more than $4 billion upfront among them for rights to PD-1/L1xVEGF-A bispecifics. The outlay will rise by at least $2 billion as BMS makes noncontingent payments and could top $20 billion if the deals hit their milestones. The fallout from failure would make the TIGIT turmoil look like a tempest in a teapot.