With the emergence of immunotherapy for oncology, cancer vaccines are cropping up. Therapeutic cancer vaccines work by enhancing the immune system’s response to malignant cells. In particular, personalized or individualized cancer vaccines contain different neoantigens on a patient-by-patient basis, which target specific genetic mutations expressed by each individual.
The advancement of mRNA technology is paving the way for personalized treatments in cancer vaccines, enabling their development within a short time frame of 1 to 2 months after the tissue sample collection. Meanwhile, the award of Nobel Prize 2023 to COVID-19 mRNA vaccines highlights the mRNA technology’s potential in treating infectious disease and cancer. In addition, mRNA vaccines outperform other types of vaccines, such as cell-based, viral-based, peptide-based, and DNA-based vaccines, as the first ones to show superior potency, specificity, versatility, rapid large-scale development, cost-effective manufacturing, and safety.
Autogene cevumeran by BioNTech and mRNA-4157 by Moderna-Merck (Merck is known as MSD outside of the United States and Canada) are the sole mRNA personalized cancer vaccines that have successfully advanced to the late stages of clinical trial development.
Autogene cevumeran by BioNTech. Expected Launch 2030.
BioNTech’s work towards autogene cevumeran started over a decade ago and now the vaccine has entered the late development clinical trials stage. Below, we discuss BioNTech’s milestones and efforts that resulted in autogene cevumeran, the vaccine’s MoA, the global clinical trials, and the latest PDAC update.
BioNTech’s journey to autogene cevumeran (BNT-122).
In 2012, BioNTech developed BNT-121, which showed sufficient efficacy against metastatic melanoma (phase 1). Then, in 2016, it teamed up with Genentech to research further how BNT-121 works in combination with Genentech’s atezolizumab. In the meantime, BioNTech developed BNT-122 (autogene cevumeran), expecting that it would have the potential to control metastatic relapses in solid cancer patients in late-stage, heavily pre-treated patients. As autogene cevumeran showed better efficacy than BNT-121, while both had similar safety profiles, the two partners agreed to proceed research with autogene cevumeran.
Promise of autogene cevumeran
Autogene cevumeran, a product from BioNTech’s iNeST – individualized mRNA cancer vaccines platform, is a personalized mRNA vaccine that can load up to 20 neoantigens to trigger a strong and precise immune response against each patient’s unique tumor.
Today, autogene cevumeran is one of the only two personalized therapeutic mRNA cancer vaccines in late-stage development (the other one is under development by Moderna and MSD). Autogene cevumeran, meeting the two crucial criteria required for any vaccine or treatment to reach the market, shows great potential in cancer immunotherapies.
Its manageable safety as monotherapy and in combination with atezolizumab and the significant levels of neoantigen-specific immune responses it induces in late-stage, heavily pre-treated patients hold promise for unmet cancer patient needs. (control of metastatic relapses in solid tumors).
Autogene cevumeran clinical trials
As mentioned above, autogene cevumeran is currently being evaluated clinically as a monotherapy and in combination for the treatment of various solid cancers in early stage and also in residual disease settings, globally.
Table 1: Ongoing clinical trials of Autogene cevumeran
| Therapy | Phase | Indication | NCT | PCD |
| Autogene cevumeran + Atezolizumab | Ph 1a/b | LA or met tumors | NCT03289962 | Nov 2024 |
| Autogene cevumeran + Atezolizumab + mFOLFIRINOX | Ph 1 | Adj PDAC | NCT04161755 | Nov 2024 |
| Autogene cevumeran + Pembrolizumab | Ph 2 | 1L adv melanoma | NCT03815058 | Oct 2025 |
| Autogene cevumeran | Ph 2 | ct-DNA positive adj CRC | NCT04486378 | Feb 2026 |
| Autogene cevumeran + Atezolizumab + mFOLFIRINOX | Ph 2 | Adj PDAC | NCT05968326 | May 2029 |
Table 1: Data taken from BioNTech pipeline
BioNTech has announced three-year follow-up data from a phase 1 trial evaluating autogene cevumeran in combination with atezolizumab and mFOLFIRINOX (standard of care chemotherapy). The results demonstrated, “polyspecific T cell responses up to three years and delayed tumor recurrence in patients with adjuvant PDAC.”
As of now, the company is enrolling PDAC patients in a phase 2 trial which was initiated in Oct 2023. The IMCODE003 study is evaluating autogene cevumeran in combination with atezolizumab and mFOLFIRINOX. The accrual has begun in the US and will continue in Europe and the Asia Pacific region.
Regarding the UK trials, the Memorandum of Understanding signed between the UK government and BioNTech is set to expedite autogene cevumeran trials, as Cancer Immunotherapy is one of the partnership’s three strategic pillars. BioNTech aims to design and roll out randomized cancer immunotherapy clinical trials to offer treatment to up to 10,000 patients by 2030, having started in September 2023.
mRNA-4157 by Moderna. Expected Launch 2028.
In the last decade, Moderna has developed its mRNA research and manufacturing capabilities and built partnerships to develop (among others) immunο-oncology cancer treatments, such as the mRNA-4157, a promising oncology candidate therapeutic vaccine targeting patients with adjuvant melanoma.
Journey to mRNA-4157
In 2016, MSD and Moderna formed a strategic collaboration to develop an mRNA personalized cancer vaccine in combination with pembrolizumab. As per the latest update of the terms of collaboration, both parties will jointly develop and commercialize mRNA-4157/V940.
Promise of mRNA-4157
The combination of mRNA-4157 with pembrolizumab has shown promising results in reducing the risk of disease recurrence or death in patients with adjuvant melanoma, as demonstrated in a phase 2b clinical trial (KEYNOTE-942/ mRNA-4157-P201).
mRNA-4157 clinical trials
The table below shows the ongoing trials of mRNA-4157 in combination with pembrolizumab at early-stage and late-stage development for different types of cancer.
Table 2: Ongoing clinical trials of mRNA-4157
| Therapy | Phase | Indication | NCT | PCD |
| mRNA-4157 + Pembrolizumab | Ph 1 | Solid tumors | NCT03313778 | Jun 2025 |
| mRNA-4157 + Pembrolizumab | Ph 2 | Adj high-risk melanoma | NCT03897881 | Sep 2029 |
| mRNA-4157 + Pembrolizumab | Ph 3 | Adj NSCLC | NCT06077760 | Jun 2030 |
| mRNA-4157 + Pembrolizumab | Ph 3 | Adj high-risk melanoma | NCT05933577 | Oct 2029 |
Table 2: Data taken from www.clinicaltrials.gov (search term mRNA-4157)
Phase 2b KEYNOTE-942/mRNA-4157-P201 study data shows that “mRNA-4157 in combination with pembrolizumab at three years follow up reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death was decreased by 62% as compared to pembrolizumab alone in adjuvant melanoma”. These positive results have granted to mRNA-4157 in combination with pembrolizumab the FDA Breakthrough Therapy Designation, and the EMA Priority Medicines (PRIME) scheme for the treatment of adjuvant melanoma.
Considering the above designations, the companies in discussion with the regulatory authorities have already begun a pivotal phase 3 clinical trial in melanoma and have dosed the first patient in Australia. The companies are also evaluating mRNA-4157 with pembrolizumab in a second phase 3 study in NSCLC (V940-002). mRNA-4157 will also be evaluated in other tumor types in 2024. Moderna and Merck anticipate the potential launch of the vaccine by 2028.
The personalized cancer treatment era is here. Do non-mRNA-based vaccines pose a threat to BioNTech and Moderna?
The global market for cancer vaccines is projected to reach USD 26.89 billion by 2032, while the market for personalized cancer vaccines is expected to reach USD 3.7 million by 2030, bringing profits to those who will capitalize on these market opportunities. This will also be the case for BioNTech and Moderna if their efforts are successful, as there is no direct competition while there are unmet patient needs.
Currently, there are cancer vaccines approved, such as PROVENGE for prostate cancer, BCG vaccine, and ADSTILADRIN for bladder cancer. Still, none offer personalized protection against one’s unique cancer mutation, and none was developed employing mRNA-based technology.
Focusing on the personalized cancer vaccines space and looking beyond mRNA technology, the following companies are key players: Gritstone Bio working on Granite (self-amplifying mRNA, ph 2) ; Transgene on TG-4050 (Modified Vaccinia Ankara virus-based vaccine, ph 2); Sotio on DcVac/Ov (Dendritic cell-based vaccine, ph 2) and DcVac/Pc (Dendritic cell-based vaccine, ph 2); and VBI vaccines: VB-1901 (Cytomegalovirus based vaccine, ph 2). Meanwhile, Agenus and Genocea Biosciences have terminated their early-stage clinical research for business reasons.
The non-mRNA personalized vaccines are unlikely to compete with BioNTech and Moderna since those assets are still in the early phases of development, and the companies developing them are also early-stage companies with few or no approved products. Small biopharma companies would need partnerships and funding to proceed with further development, which would delay the development altogether. Also, autogene cevumeran and mRNA-4157 have been evaluated in larger population groups than the non-mRNA personalized vaccines, where the first ones have clearly demonstrated clinical benefit.
What does the future hold in the personalized mRNA cancer vaccine space? Which patients will benefit the most?
Developing personalized mRNA cancer vaccines is not without hurdles. Firstly, issues like instability, innate immunogenicity, and inefficiency in vivo — all associated with mRNA-based vaccine delivery — and cost issues put barriers to new players entering the space. And even though manufacturing mRNA vaccines is associated with low cost, loading them based on each patient’s unique neoantigens adds complexity, further increasing the therapy’s cost. Stemirna Therapeutics, a Chinese company involved in personalized mRNA cancer vaccine development (LPP-PCV) phase 1 trial, has reported no recent developments. BioNTech and Moderna will not have any active threats from other mRNA-based personalized cancer vaccines immediately after launch.
Considering the 458,918 new PDAC cases that are diagnosed every year, PDAC’s grim prognosis, and the less than 10% average 5-year survival rate, the potential improvement in prognosis through autogene cevumeran could mark a significant milestone in cancer care, raising hope for pDAC patients all over the world.
BioNTech vs Moderna. Who will cross the finish line first?
The journey toward mRNA personalized cancer care is underway, and the coming decade holds the promise that could redefine the narrative of cancer prognosis and treatment modalities.
If approved, autogene cevumeran and mRNA-4157 would be the first personalized cancer vaccines to enter the market. Their indications do not overlap currently, but there is a possibility of competition between the two in the future.
BioNTech is about to begin the Phase 3 enrollments, while Moderna has already started the dosing of the patients. With the MoU with the UK government, BioNTech plans to launch autogene cevumeran by 2030, while Moderna projects to launch mRNA-4157 by 2028.
Moderna’s years of work on mRNA technology pay off. The company that won the COVID-19 vaccine bet, though it had never launched a drug until 2020, finds itself again neck and neck with BioNTech in a battle for the next breakthrough in cancer immunotherapy.
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Sources:
How mRNA Vaccines Might Help Treat Cancer – NCI
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