Bispecific antibodies and anti-TIGIT therapies both appear to be writing comeback stories as cancer experts head to Barcelona for the 2024 European Society for Medical Oncology Congress. Radioligand therapies and synthetic lethality assets are also attracting attention.
This week, tens of thousands of oncology professionals will descend on Barcelona for the 2024 European Society for Medical Oncology Congress, where the storied city will host deep discussions and presentations on a range of cancer therapeutics in development.
Taking place Sept. 13–17, ESMO 2024 will incorporate abstracts and presentations by the likes of AstraZeneca, Bristol Myers Squibb, GSK, BioNTech, Eisai and many more.
Among the most anticipated presentations are those on bispecific antibodies and anti-TIGIT therapies, both classes of therapies that have hit stumbling blocks in recent years. But with several candidates now in the pipeline, experts say both of these therapeutic classes could be making a comeback.
Other hot topics include radioligand therapies, where analysts are particularly looking for new targets, and synthetic lethality assets, a growing area of interest in oncology.
“It’s just a good conference,” said Daina Graybosch, senior managing director and biotechnology analyst in immuno-oncology at Leerink Partners. “They have more discussions than other conferences, so I feel like you learn more at it.”
Can TIGITs Make a Comeback?
Merck recently halted a Phase III study of its anti-TIGIT antibody vibostolimab, along with Keytruda and chemotherapy, due partly to adverse events. But Omid Veiseh, a professor of bioengineering at Rice University and director of the Rice University Biotech Launch Pad, said anti-TIGIT treatments could potentially unlock a new paradigm in checkpoint therapy. “I think TIGIT is one of the targets which could provide responses in some of the cancers that checkpoint therapies today have not been as effective in,” he told BioSpace.
Graybosch is looking forward to late-breaker presentations on iTeos Therapeutics and GSK’s anti-TIGIT therapy EOS-448 and BMS’s lymphocyte-activation gene 3 (LAG-3) candidate relatlimab, both in lung cancer.
She noted that EOS-448, being co-developed by iTeos and GSK, is the only TIGIT program that has had to go through the FDA’s Project Optimus, which aims to reform the dose optimization and dose selection paradigm in oncology drug development.
“That’s increasingly relevant because it looks like Merck had a hard time maybe with their therapeutic window,” Graybosch told BioSpace. “A lot of investors think TIGIT is a zero. I don’t think it’s a zero. It’s more about how broad is the effect.”
Veiseh also expressed excitement about LAG-3 as a target. “LAG-3 is another checkpoint that seems to be an exciting opportunity based on the clinical data that’s emerging,” he said, adding that he has seen success with this mechanism in peritoneal tumors such as ovarian cancer.
Graybosch added that BMS’s LAG-3 data is notable because BMS and Regeneron have the only active “major” LAG-3 programs in lung cancer.
Bispecific Antibodies Ready for Prime Time?
Bispecific antibodies, engineered molecules designed to simultaneously bind to two different antigens, have gained attention as a possible alternative to monoclonal antibodies. With the space expected to surpass $50 billion by 2029, they are drawing considerable interest.
Graybosch is anticipating data from bispecific competitors Summit Therapeutics and Akeso and BioNTech and Biotheus in triple-negative breast cancer and non-small cell lung cancer (NSCLC). “Those are the only two bispecifics pretty far in the class, and we can start to compare,” she said.
Mayank Mamtani, head of healthcare research at B. Riley Securities, agreed that bispecifics are a key draw at ESMO, and noted a particular interest in the Summit/Akeso data. “I think bispecifics are making a big comeback,” he told BioSpace. “These agents are being advanced to essentially supplant [Merck’s] Keytruda’s dominant position as the cancer immunotherapy backbone of choice across many solid tumors. It’s an important trend that everyone’s watching.”
Bispecifics were in vogue at the recent American Society of Clinical Oncology annual meeting, with Merus announcing data from a Phase II study showing that its bispecific antibody petosemtamab, in combination with Keytruda, produced a 67% response rate in head and neck cancer.
Veiseh described bispecifics as “fascinating.”
“They work really well when they’re binding receptors that have similar affinities,” he said. “I think the real challenge is the potential targets that one would want to go after; they’re sort of not at the same ratio.”
Veiseh went a step further, noting the concept of trispecifics. “Combinations are really what it takes to get really exciting results, I think, in terms of the difficult-to-treat cancers,” he said.
Other Presentations to Watch at ESMO
B. Riley Securities analyst Yuan Zhi, who will be attending the conference, highlighted a Phase I trial of Amgen’s synthetic lethality asset PRMT5i AMG193 in MTAP-deleted solid tumors. This trial was switched from an oral presentation to the presidential session, “likely indicating a promising clinical result from this updated readout,” according to a B. Riley investor note shared with BioSpace. Zhi noted that investors’ primary focus in this trial is on NSCLC.
The other trend on Zhi’s radar is radioligand therapies—specifically new targets beyond SSTR and PSMA, the targets of approved Novartis medicines Lutathera and Pluvicto. “Investors are asking, what’s out there outside of these two targets, outside of Lutathera, outside of Pluvicto? Because if we want [the] area to really develop into a kind of mature state, we need more targets to treat more cancers,” he said.
Another class of cancer drugs sure to be on display at ESMO, as it was at ASCO and the American Association for Cancer Research meeting this year, is antibody-drug conjugates. “I’m sure there’ll be a lot of interesting developments there,” Veiseh said.
Graybosch and Mamtani both noted the timing of the 2024 World Conference on Lung Cancer, currently taking place in San Diego, which may provide some crossover interest in this particular indication.
Stay tuned to BioSpace for coverage of key data from ESMO 2024.
