Following their blowout win in melanoma last month, Merck and Moderna are leading the way among a new crop of personalized cancer vaccines. Here are five companies with similar therapies hoping to break through where others have previously failed.
Merck and Moderna’s late-stage melanoma win last month marked a triumphant turnaround for the cancer vaccine space after years of middling outcomes.
The partners—whose Phase 3 data showed that their mRNA-based cancer vaccine, combined with Merck’s Keytruda, extended progression-free survival in patients with cutaneous melanoma, as compared with Keytruda alone—“finally made cancer vaccines work and it was not easy!” Christiana Bardon, co-managing partner at the investment firm MPM BioImpact, told BioSpace in an email.
Early data in the space were, by contrast, underwhelming, she said. She highlighted Dendreon’s Provenge as one example.
Approved by the FDA in 2010 for late stage prostate cancer, Provenge, an autologous cell therapy, is widely considered to be the first-ever cancer vaccine to hit the market. Despite blazing a trail, however, Provenge struggled to gain traction, with a survival benefit that hardly justified its $93,000 price tag. As a result, Dendreon declared bankruptcy around four years after Provenge’s approval.
Another cancer vaccine casualty is IO Biotech, which closed shop in April after the FDA said last year that the company did not have enough evidence to support its product candidate Cylembio.
“It turns out that a vaccine with one antigen was not enough,” Bardon said. “Vaccines need multiple antigens, and those antigens are unique to each patient.”
Indeed, Merck and Moderna’s approach directly confronts this individualized constellation of targets. The companies’ individualized neoantigen therapy, dubbed intismeran autogene, makes use of a patient’s own tumor, from which a “unique mutational signature” is identified—similar to a cancer “fingerprint”—that can then be used to produce a personalized mRNA-based vaccine, according to a news release from the partners. When administered, the resulting vaccine prepares the patient’s immune system to recognize this antigen fingerprint and attack cells containing it.
This immune-priming action is what defines the cancer vaccine class, according to a spokesperson from BioNTech, another prominent player in this space. “The term ‘cancer vaccine’ is commonly used to describe this class because vaccines stimulate the body’s immune system,” the spokesperson explained.
In the case of Merck and Moderna’s intismeran, the vaccine mechanism is therapeutic—it instructs the immune system to destroy an existing tumor, resulting in the partners’ reported survival benefits.
But, according to Bardon, there is also the possibility that these therapies could prove protective in the long run. Cancer vaccines, she told BioSpace, “may generate long-term immune responses which can prevent recurrence and increase the cure rate of patients with early-stage melanoma.”
With their Phase 3 win for intismeran, Merck and Moderna are leading the cancer vaccine race, but they’re hardly the only drugmakers in this space. Here are five more companies looking to break through.
Roche, BioNTech succeed in pancreatic cancer, miss in colorectal
At the annual American Association for Cancer Research meeting in April, Roche and BioNTech’s therapeutic vaccine candidate autogene cevumeran showed promising survival rates in patients with pancreatic cancer.
Autogene cevumeran, an mRNA-based personalized cancer immunotherapy, was originally developed by BioNTech. In September 2016, Roche, through its subsidiary Genentech, paid $310 million upfront and in near-term milestones to develop and advance cancer vaccines developed through the German company’s platform. Autogene cevumeran would eventually become one of those assets.
The partners are testing the vaccine in a Phase 1 study of 16 patients with pancreatic cancer who were given autogene cevumeran after surgical removal of the tumor. Trial participants were also treated with chemotherapy and a checkpoint inhibitor.
Results presented earlier this year showed that eight patients responded to the personalized cancer vaccine. Autogene cevumeran was able to trigger the production of immune cells that recognized and attacked cancer cells, according to a news release from Memorial Sloan Kettering Cancer Center, which sponsored the study.
Among the eight responders, seven were still alive four to six years after surgery, a survival rate of 87.5%. In contrast, the five-year survival rate for pancreatic cancer across different stages is 13%, according to the American Cancer Society.
Roche and BioNTech are testing autogene cevumeran in a Phase 2 study in combination with the pharma’s checkpoint inhibitor Tecentriq and chemotherapy. The IMcode003 study is currently recruiting patients with resected pancreatic ductal adenocarcinoma. Topline data are expected in 2031.
It hasn’t been completely smooth-sailing for autogene cevumeran, however. The candidate stumbled last month in colorectal cancer, as an independent data board recommended ending a Phase 2 study for futility—a setback that analysts at BMO Capital Markets at the time said could “reduce confidence in autogene cevumeran.”
Two more shots for BioNTech
Aside from autogene cevumeran, BioNTech has a handful of other cancer vaccines—though none are being positioned as personalized therapies.
Instead, the company’s other assets, which it calls mRNA cancer immunotherapies, work by encoding certain tumor antigens that prime patients’ immune systems to fight off malignancies of a certain type.
One of these assets is BNT113, which targets two proteins commonly found in HPV16-positive tumors. The candidate is currently being tested in combination with Merck’s mega-blockbuster PD-1 inhibitor Keytruda in the open-label Phase 2/3 AHEAD-MERIT study in newly diagnosed patients with unresectable recurrent or metastatic head and neck cancers.
Phase 2 findings released in September 2024 showed that when used with Keytruda, BNT113 resulted in an unconfirmed overall response rate of 40% at 12 months. Interim data from the randomized, controlled part of the Phase 2/3 study, which is testing the combo regimen as a first-line treatment option, are expected this year, according to BioNTech’s second quarter presentation.
Aside from BNT113, BioNTech is also advancing BNT116, which encodes six antigens associated with non-small cell lung cancer (NSCLC). A mid-stage study of the candidate in combination with Regeneron’s PD-1 inhibitor Libtayo in first-line NSCLC is ongoing, with data likewise set to be released this year. Early data published in November 2024 demonstrated a 10% partial response rate, with 70% of the 20 treated patients reaching stable disease.
OSE Immunotherapeutics pushes off-the-shelf vaccine
Stepping up to compete against BioNTech is OSE Immunotherapeutics, which is advancing its own investigational cancer vaccine Tedopi.
Tedopi is a T cell epitope–based therapy designed as an off-the-shelf vaccine that primes an immune response against five antigens commonly associated with tumors—a broad targeting profile not unlike BNT116. Like BioNTech, OSE is testing Tedopi in NSCLC, in combination with Bristol Myers Squibb’s PD-1 blocker Opdivo and the chemotherapy docetaxel. This regimen is being tested in the Phase 2 Combi-TED trial, with topline data slated for later this year.
The French biotech is also running the Phase 3 Artemia study, focusing on patients with metastatic disease who have undergone at least one prior line of treatment. This trial is currently recruiting with initial data expected late next year.
Aside from NSCLC, OSE is also studying Tedopi in pancreatic and ovarian cancers, for which separate mid-stage trials are ongoing.
In May, OSE toplined mid-stage ovarian cancer data for a regimen of Tedopi and Keytruda. Patients treated with the combo saw a significant 47% drop in the risk of death or disease progression as compared with supportive care. Comparing the doublet against the vaccine alone showed that Keytruda boosted Tedopi’s progression-free survival benefit by 28%, which fell short of statistical significance.
Elicio rides Merck/Moderna’s tailwinds
For Elicio Therapeutics, the success of Merck and Moderna’s vaccine in melanoma last month strengthened the case for the Boston biotech’s own cancer vaccine ELI-002.
“Class validation is now empirical, not theoretical,” analysts at Rodman & Renshaw wrote in an Aug. 19 note. “The bull case for ELI-002 has partly rested on antigen-directed adjuvant vaccination being a viable mechanism class.”
Elicio could use this additional confidence in ELI-002, after the asset in June failed to significantly improve disease-free survival in a mid-stage study of patient with KRAS-driven pancreatic cancer. At the time, however, the biotech blamed the miss on a higher proportion of patients with residual tumor cells at or within 1 mm of the surgical margin.
Posthoc analyses showed better survival outcomes in the subset of patients whose tumors had been completely removed by surgery. Elicio will focus on this patient population in late-stage development.
This approach of targeting specific patient groups likely to benefit from treatment “looks like an emerging field standard,” not just an Elicio-specific maneuver to improve late-stage chances, according to Rodman & Renshaw.
The firm in particular pointed to Merck and Moderna’s success “in a similarly biomarker-informed, fully-resected population,” which suggests that “precision selection over broad . . . dosing is becoming the standard registrational path for adjuvant vaccines.”
Designed to target lymph nodes, ELI-002 makes use of a KRAS peptide antigen that can elicit an immune response against a broad spectrum of KRAS mutations, according to Elicio’s website. The therapy also includes a proprietary adjuvant to further boost the immune response.
Despite fail, Agenus advances dual-antibody therapy
Capping off this list is Agenus and its immunotherapy combo BOT+BAL, which consists of the anti-CTLA-4 antibody botensilimab and PD-1 inhibitor balstilimab.
While Agenus doesn’t label BOT+BAL as such, the asset works a lot like how a cancer vaccine might. A combination of the two antibodies, BOT+BAL is designed to activate the immune system and enhance activity against cancer cells. In particular, Agenus hopes to leverage this approach to awaken “cold” tumors, transforming cancers that have historically been inert to immunotherapies into an immune-responsive diseases.
But the BOT+BAL bet hasn’t always played out well for Agenus. In April, the investigational combo, when used alongside a cell therapy from MiNK Therapeutics, the VEGFR2 antagonist Cyramza and chemotherapy, failed to trigger a response in any of 15 patients with gastroesophageal adenocarcinoma.
Agenus nevertheless has a broad development program for BOT+BAL, particularly in colorectal cancer, for which there are several studies of different stages testing various regimens of the investigational therapy. The most mature of these, the Phase 3 ROBBIN trial, is designed to test a neoadjuvant course of BOT+BAL in high-risk patients with stage II and III microsatellite-stable (MSS) colon cancer.
In July, Agenus secured $85 million upfront—as well as $255 million in potential future payments—in a private placement push to help bankroll ROBBIN and push BOT+BAL’s development through key value inflection points, including an early pathologic response readout, expected in the back half of 2027.
Aside from colorectal cancer, BOT+BAL is also being tested in a mid-stage study for solid tumors.
