The Two Faces of Nobel Prize Transformation: BioNTech vs. Moderna

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The Two Faces of Nobel Prize Transformation: BioNTech vs. Moderna

On October 2nd, the pioneers of mRNA technology, Drew Weissman and Katalin Karikó, were awarded the Nobel Prize in Physiology or Medicine.

Coincidentally, on October 4th, a research team from Moderna made a significant announcement in tandem with this news, publishing their latest research direction on mRNA-LNP (Lipid Nanoparticle) vaccines for monkeypox in the scientific journal “Science Translational Medicine.”

The Two Faces of Nobel Prize Transformation: BioNTech vs. Moderna

Reportedly, compared to the existing monkeypox vaccine from Danish company Bavarian Nordic, mRNA-LNP demonstrated a certain advantage in mouse models, encoding four highly conserved MPXV antigens in its design. This led to better neutralization activity against monkeypox and other lethal poxvirus diseases, as well as more effective inhibition of intercellular transmission.

Interestingly, this disclosure of preclinical research closely followed their competitor BioNTech. Furthermore, Professor Jia Weiguo, the founder of Zhongsheng Fu Nuo Health, and the team of Yang Xiaoming from China National Pharmaceutical Group (Sinopharm) had already published their research on mRNA monkeypox in Nature Communications at the end of September.

Indeed, this race to the forefront is quite common between these two companies.

As inheritors of Nobel Prize technology, Moderna is clearly benchmarking itself against its rival, BioNTech.

Last month, BioNTech, along with its partner, the Coalition for Epidemic Preparedness Innovations (CEPI), announced a $90 million project for the development of a monkeypox vaccine, rapidly advancing the clinical development of their BNT166 monkeypox vaccine.

Currently, mRNA-LNP technology’s most widespread transformative achievements are primarily related to the coronavirus. Beyond COVID-19 vaccines, research outcomes related to respiratory syncytial virus and influenza vaccines, among other respiratory infections, are likely to see transformation and successful market entry in the coming years.

Regarding oncology applications, although some research directions differ, both Moderna and BioNTech are actively exploring them.

For instance, BioNTech has seen initial success in combining PD-1/L1 antibodies with personalized cancer vaccines in melanoma. Moderna quickly followed with a combination of Merck’s K drug and their personalized cancer vaccine, reducing the risk of death in melanoma by 44%.

BioNTech has developed a combination of CLDN6 mRNA with CAR-T therapy, and Moderna has its CLDN18.2 CAR-T combination in development with Kyowa Kirin.

What’s intriguing is that both companies seem to have a sense of “mRNA-izing everything,” with BioNTech leaning more toward oncology applications, while Moderna appears to be more dependent on mRNA technology with a broader range of applications.

Clearly, the ability to “mRNA-ize everything” does not guarantee success, as pioneers often encounter setbacks. For instance, collaborations between Moderna and AstraZeneca ended in failure, and BioNTech recently discontinued two pipeline projects.

First, Moderna’s mRNA-ized VEGF-A for heart bypass surgery, AZD8601, was returned by AstraZeneca in July. Another project, MEDI1191, an IL-12 mRNA therapy for cancer treatment, faced the same fate when AstraZeneca “returned” it in November, and it was subsequently removed from Moderna’s pipeline.

BioNTech also removed mRNA BNT141, encoding CLDN18.2 dual antibodies, and mRNA BNT115, encoding three ovarian-specific tumor-associated antigens, from its pipeline.

In the realm of challenging drug targets, Moderna is developing personalized cancer vaccines specifically for KRAS mutations. They have also mRNA-ized OX40L antibodies with mRNA-2752, encoding OX40L/IL-23/IL-36γ.

Regarding indications, BioNTech focuses less on self-immunity and rare diseases, with hardly any pipeline projects in these areas. Instead, they concentrate on various platforms for oncology, such as ADC platforms and cell therapy platforms, possibly including previous deals with Emcure Pharmaceuticals. This suggests that BioNTech does not rely solely on mRNA technology.

Moderna has a stronger presence in rare disease research, with at least seven rare disease pipeline projects. Their design approach mostly centers on encoding proteins that healthy individuals have but rare disease patients lack.

The Two Faces of Nobel Prize Transformation: BioNTech vs. Moderna

In the field of self-immunity, Moderna has had a clearer history of failures.

For example, in Moderna’s Q2 2022 earnings report, they disclosed the discontinuation of the development of IL-2 mRNA-6231 due to early clinical data and competitive factors. Currently, only mRNA-6981, which encodes PD-L1 to suppress immune cells, remains, and its preclinical research appears to have stagnated for quite some time without specific disclosures since 2021, raising concerns about its reliability.

Especially for self-immunity patients, there may be questions about whether encoding PD-L1 carries a risk of cancerogenesis, as no PD-1/PD-L1 agonist has been able to prove this point.

In comparison, BioNTech’s approach seems more conservative, focusing mainly on oncology with a few mRNA vaccines for infectious diseases.

This might be attributed to Ugur Sahin, the company’s CEO and founder, who is an expert in tumor immunology.

Moderna, on the other hand, appears to have a stronger desire for stable cash flow and has adopted a more diverse pipeline strategy, including a significant focus on rare diseases.

These differing pipeline strategies may provide valuable insights for the future development of mRNA vaccine companies.