In the third quarter 2021 financial results, BioNTech not only introduced the latest progress in mRNA infectious disease vaccines, but also introduced the various applications of mRNA technology in the treatment of cancer, showing the broad prospects of mRNA technology.
Keppel Ltd. 1Q 2024 Business Update Presentation Slides
Application of m rna technology in cancer therapy
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Application of mRNA Technology In Cancer
Therapy
On October 1, 2021, BioNTech announced that a personalized mRNA cancer vaccine
BNT122 (RO7198457), developed in cooperation with Roche's Genentech, has
completed its first patient administration in a Phase 2 clinical trial for the treatment of
colorectal cancer. On November 19, 2021, BioNTech announced that the US FDA has
granted fast-track qualification to its mRNA cancer vaccine BNT111, which for the
treatment of advanced melanoma.
As a biotechnology company that has been working on mRNA technology for many
years, BioNTech is committed to expanding the application of mRNA technology in other
fields. In the third quarter 2021 financial results, the company not only introduced the
latest progress in mRNA infectious disease vaccines, but also introduced the various
applications of mRNA technology in the treatment of cancer, showing the broad prospects
of mRNA technology.
▲ The broad prospects of mRNA technology ( source: BioNTech)
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Infectious Disease Vaccines
In terms of infectious disease vaccines, the mRNA COVID-19 vaccines have been used
in hundreds of countries and regions around the world. Over the past three months,
significant progress has been made in expanding the use of COVID-19 vaccines to
populations and scaling up vaccination. The results of clinical trials have shown that the
mRNA COVID-19 vaccines can stimulate a strong immune response in children aged 5 to
11 years and is 90.7% effective in preventing symptomatic COVID-19.
▲mRNA vaccine shows good protective efficacy in children aged 5 to 11 years (source: BioNTech)
The advantage of mRNA technology is that vaccines encoding pathogen antigens
can be rapidly generated and multiple pathogen-related antigens can be encoded in
a single mRNA. This makes it a powerful option for developing vaccines for
infectious diseases. In addition to the COVID-19 vaccines, the mRNA quadrivalent
influenza vaccine jointly developed by BioNTech and Pfizer has recently entered the
phase 1 clinical development stage. In addition, there are 9 infectious disease vaccines in
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the R&D pipeline that are in the preclinical development stage for the prevention of
malaria, HIV, tuberculosis and other diseases.
mRNA cancer vaccines
Before the development of the COVID-19 vaccines, BioNTech already had a pipeline of
mRNA-based cancer vaccines. Similar to the principle of infectious disease vaccines, the
mechanism of cancer vaccines is to introduce tumor-related antigens, stimulate the body's
immune response, and use the immune system to destroy cancer cells.
BioNTech's cancer vaccine platforms fall into two broad categories, iNeST and
FixVac. Among them, iNeST technology platform generates mRNA cancer vaccines
targeting neoantigens. Tumor cells produce neoantigens due to genetic mutations that
are not present in healthy cells. The body's immune system recognizes these antigens
and produces an immune response to them. However, the expression levels of these
neoantigens in many tumors are too low to trigger a strong anti-cancer immune
response.
INeST vaccines use mRNA to encode neoantigens expressed in a patient's tumor.
When injected into the body, they express high levels of neoantigen proteins that
trigger a powerful immune response. The iNeST vaccine can express up to 20 different
neoantigens, triggering a more comprehensive immune response against tumor cells and
preventing them from escaping the immune system.
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▲Introduction of iNeST technology platform (source: BioNTech)
BNT122 is an individualized neoantigen specific immunotherapy (iNeST). It is a cancer
vaccine generated using the iNeST technology platform. INeST immunotherapy is an
individualized cancer therapy tailored to a specific patient's tumor. They contain
unmodified, pharmacologically optimized mrnas that encode up to 20 patient-specific
neoantigens. Neoantigens are proteins produced by cancer cells due to genetic
mutations that are different from healthy cells and can be recognized by immune cells.
BNT122 has been administered to the first patient in a phase 2 clinical trial for
adjuvant treatment of colorectal cancer patients after surgery to prevent cancer
recurrence. It is used in combination with the PD-1 inhibitor pembrolizumab, and a phase
2 clinical trial for the first-line treatment of patients with advanced melanoma is also being
recruited.
The cancer vaccine generated by the iNeST technology platform is a "tailored"
individualized cancer vaccine, which expresses unique neoantigens expressed on tumors
of different patients. However, some antigens expressed on tumors are highly expressed
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in most cancer patients. BioNTech’ s FixVac technology platform aims to use mRNA to
express these shared tumor-associated antigens, which can target antigen-presenting
cells and activate antigen-specific T cell responses. One of its advantages is that it can be
generated and saved in advance, and can be used by patients immediately.
▲Introduction of FixVac technology platform (source: BioNTech)
BNT111, an investigational cancer immunotherapy for the treatment of advanced
melanoma, is one of four product candidates for BioNTech's FixVac platform, which uses
a combination of tumor-associated antigens encoded by mRNA to trigger powerful and
precise immune response against cancer for cancer therapy. On November 19, BioNTech
announced that the U.S. FDA has granted the fast-track qualification for the tumor
immune mRNA vaccine BNT111 for the treatment of advanced melanoma.
BNT111 is an intravenous liposomal RNA vaccine that encodes four non-mutated,
tumor-associated antigens-NY-ESO-1, MAGE-A3, tyrosinase, and TPTE, covering >90%
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of patients with skin melanoma. These antigens have limited expression in normal tissues,
but they are widespread in melanoma and have high immunogenicity.
BNT112 is an mRNA vaccine for the treatment of prostate cancer. It encodes 5 kinds
of tumor-associated antigens that appear in prostate cancer patients. Currently, it is used
as a single agent or in combination with PD-1 inhibitors to treat patients with prostate
cancer in phase 1/2 clinical trials. Preliminary clinical trial results showed that
vaccine-induced immune responses were observed in seven vaccine-treated patients with
metastatic castration-resistant prostate cancer, and T-cell immune response against all
tumor-associated antigens carried by the vaccine was observed in two patients. Moreover,
a decrease in prostate-specific antigen (PSA) levels was observed in two patients
receiving BNT112 monotherapy, which is a manifestation of anti-tumor activity.
Since cancer vaccines can stimulate immune responses, enhancing the efficacy of
immunotherapy is an important direction of development in combination with other
immunotherapies. BioNTech's therapeutic vaccine can also be used in combination
with CAR-T therapy in addition to immune checkpoint inhibitors.
Using mRNA vaccines to improve the efficacy of
CAR-T therapy
CARVac is a unique CAR-T cell amplified mRNA vaccine developed by BioNTech. It is
designed to encode antigens targeted by CAR T cells using mRNA. CARVac can
selectively induce antigen presenting cells in lymph nodes to express antigens targeted by
CAR T cells, thereby stimulating CAR T cell expansion in patients.
CARVac that expresses CLDN6 (a protein that is not expressed in healthy tissues but is
expressed in ovarian cancer, lung cancer and other cancer types) is combined with
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CAR-T cell therapy targeting CLDN6, which has been shown in solid tumor models It can
improve the expansion and effectiveness of CAR-T cells.
Dr. Uğur Şahin, CEO of BioNTech, pointed out that the success of COVID-19
vaccine provides a good opportunity to expand the application of mRNA in cancer
vaccines and other therapeutic modalities. In addition to the above applications, the use of
mRNA to express therapeutic antibodies or cytokines are being explored, which may
further expand the range of diseases that mRNA therapy can treat, including inflammatory
diseases, autoimmune diseases and allergies. With the continuous advancement of RNA
technology, the entire biomedical field will benefit from it.
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References:
[1] BioNTech Announces Third Quarter 2021 Financial Results and Corporate Update. Retrieved
November 9, 2021
[2] Next Generation Immunotherapy. Retrieved November 9, 2021
[3] Third Quarter 2021, Corporate update and financial results. Retrieved November 9, 2021
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[1] mRNA Technology: Current Trends and Prospects
[2] mRNA Technology: Development And Three Major Applications In Future