TIGIT Failures Cast Shadow Over Immuno-Oncology Investments

Major pharmaceutical companies have invested billions in TIGIT-targeted immunotherapy programs, only to face significant setbacks and financial losses. This trend highlights the ongoing challenges in developing effective cancer treatments and raises questions about the industry's approach to high-risk, high-reward drug development.

Costly Bets on TIGIT Technology

Leading pharmaceutical firms, including Bristol Myers Squibb, Gilead, GSK, and Novartis, collectively spent $1.4 billion on upfront licensing deals to enter the TIGIT race. These agreements also included potential milestone payments exceeding $5 billion. However, clinical setbacks have led to the discontinuation of several programs, with companies unlikely to recoup their initial investments.

Gilead's partnership with Arcus Biosciences stands out as a particularly expensive venture. The company invested $740 million in Arcus equity at an average of $27.58 per share, significantly higher than Arcus's current trading price of below $10. The fate of their TIGIT candidate, domvanalimab, will largely determine the return on this substantial investment.

Extensive Clinical Programs and R&D Costs

The scale of TIGIT-related clinical trials has been immense. Roche tested tiragolumab in 10 Phase III studies with nearly 4,600 patients, while Merck's vibostolimab program included five Phase III studies targeting over 4,600 patients. Gilead, Arcus, and AstraZeneca have sponsored three Phase III studies enrolling almost 3,000 patients.

While exact figures are not publicly disclosed, estimates based on similar programs suggest that companies like Gilead, Merck, and Roche may have spent billions on mid- and late-phase TIGIT trials. For instance, GSK and iTeos Therapeutics had agreed to spend $900 million on their global development plan before its failure in Phase II.

TIGIT Setbacks in Context of Oncology R&D Challenges

The TIGIT disappointments add to a series of costly failures in cancer immunotherapy development. Previous high-profile setbacks include:

1. IL-2 therapies: BMS paid Nektar Therapeutics $1.85 billion for co-development rights, while Sanofi acquired Synthorx for $2.5 billion. Both programs ultimately failed.

2. CD47 therapies: Gilead acquired Forty Seven for $4.9 billion, and Pfizer bought Trillium Therapeutics for $2.3 billion. Gilead has since abandoned its CD47 candidate, magrolimab.

3. Other targets: Significant investments in TIM-3, 4-1BB, ICOS, OX40, and CD73 have yet to yield substantial clinical success.

These failures underscore the risks associated with pursuing novel immunotherapy targets and the need for a more cautious approach to large-scale investments in early-stage oncology programs.