Introduction: On October 12th local time, Moderna and MSD jointly announced that Merck has exercised the right to jointly develop and commercialize personalized cancer vaccine (PCV) mRNA-4157/V940 in accordance with the terms of the existing cooperation and licensing agreement. Currently, mRNA-4157/V940 is being evaluated in conjunction with Merck's anti-PD-1 therapy KEYTRUDA as an adjuvant treatment for patients with high-risk melanoma in Moderna's ongoing Phase 2 clinical trial. Under the agreement, Merck will pay Moderna $250 million.
melanoma is the most aggressive skin cancer , which grows rapidly and has the highest risk of death, accounting for only about 1% of all skin cancers, but it causes most deaths related to skin cancer. Because melanoma grows rapidly, delayed treatment time may mean the difference between life and death. In recent years, the incidence of melanoma has increased year by year, and effective treatment plans are urgently needed. At present, the treatment methods of melanoma mainly include melanoma surgery, lymph node resection, metastasis resection, targeted cancer treatment, radiation therapy, and immunotherapy. This time, Moderna and Merck jointly developed mRNA cancer vaccine to explore the treatment of high-risk melanoma patients, once again enriching the treatment methods for melanoma patients.
Pharmaceuticals have joined forces, and the dawn of cancer vaccine development has begun to emerge.
Modner is a famous mRNA vaccine manufacturer in the United States. Its therapeutic concept is to use mRNA to make the cells in patients' bodies a "in vivo factory" of drug therapy. The key medical areas that are focused on include infectious diseases, immuno-oncology, personalized cancer vaccines, rare diseases cardiovascular diseases, and autoimmune diseases . where a personalized cancer vaccine is designed to activate the immune system so that patients can produce a tailored anti-tumor response to their tumor mutation characteristics to treat cancer. Once injected into the patient, the vaccine has the potential to guide the patient's cells to express selected neoepitopes, which may help the patient's immune system more accurately identify and destroy cancer cells.
Moderna's cancer vaccine under development mRNA-4157/V940 is designed to stimulate the immune response by generating a T-cell response based on the mutation characteristics of the patient's tumor. Merck's KEYTRUDA is an anti-PD-1 therapy that works by improving the body's immune system's ability to help detect and fight tumor cells. KEYTRUDA is an humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T lymphocytes that may affect tumor cells and healthy cells.
Figure 1 Design of personalized cancer vaccine mRNA-4157 (Photo source: [5])
is currently undergoing phase II clinical trials for combination therapy, and a total of 157 high-risk melanoma patients were recruited. After completion of surgical resection, patients were randomly assigned to mRNA-4157/V940 (9 doses every three weeks) and KEYTRUDA (200 mg every three weeks) with KEYTRUDA alone for about one year until the disease recurs or unacceptable toxicity appears. KEYTRUDA was selected as the comparison drug in the trial because it is the standard of care for patients with high-risk melanoma. The primary endpoint of the trial is recurrence-free survival, with secondary endpoints including distant metastasis-free survival and overall survival, and the two companies are expected to release clinical data in the fourth quarter of this year.
Under the agreement formulated in 2016 and revised in 2018, Merck will pay Moderna $250 million to exercise the right to choose a personalized cancer vaccine, including mRNA-4157/V940, and will collaborate on the development and commercialization of cancer vaccines. The amount will be paid by Merck in the third quarter of 2022 and included in its non-GAAP results. Under this cooperation, Merck and Moderna will share costs and profits equally. Affected by this news, both Moderna and Merck's stock prices rose.
For the collaboration, Stephen Hoge, MD, Moderna, said: “Since 2016, we have been collaborating with Merck on PCV and jointly promoting mRNA-4157 as a research-specific personalized cancer treatment for use with KEYTRUDA, making significant progress. With the expectation of PCV data for the quarter, we are excited about the impact of mRNA technology as a new paradigm for cancer management.Continuing to establish a strategic alliance with Merck is an important milestone as we continue to develop our mRNA platform in promising clinical projects in multiple therapeutic areas. "Msod’s expertise in immuno-oncology combined with Moderna’s pioneering mRNA technology has led to a new customized vaccine approach," said Dr. Eliav Barr, Senior Vice President and Global Head of Clinical Development at Merck Research Laboratory. We look forward to working with Moderna in joint KEYTRUDA to promote mRNA-4157/V940. "The two giants in the biopharmaceutical industry have joined forces. I believe that this personalized cancer vaccine can achieve good therapeutic results in the future and benefit the majority of patients. The
cancer vaccine has made great progress. The dream in the field of anti-cancer is expected to realize the
cancer vaccine can be mainly divided into preventive cancer vaccines, therapeutic cancer vaccines, and personalized neogenic antigen vaccines. cervical cancer and some types of hepatocellular carcinoma are induced by viruses. Vaccines against these viruses, such as human papillomavirus and hepatitis B vaccine, can prevent and treat these cancers. , These vaccines are preventive cancer vaccines. Therapeutic cancer vaccines are divided into antigen cancer vaccines, whole-cell cancer vaccines, dendritic cell cancer vaccines, DNA cancer vaccines, etc. They mainly enhance the patient's immune system to strengthen its attack on cancer cells, thereby playing a role in destroying cancer cells. At present, cancer vaccines are developing towards breast cancer , lung cancer, colon cancer , skin cancer, kidney cancer, etc.
is among the top ten indications for mRNA drugs, tumor immunotherapy ranked second only after the new coronavirus. In April, John, Ph.D., of the Netherlands Cancer Institute Haanen demonstrates data from the first human trial of the ongoing mRNA-based cancer vaccine of BioNTech, which evaluates the efficacy of BNT211 in patients with advanced solid tumors.
BNT211 includes two drug products, an autologous CAR-T cell therapy against the carcinoembryonic antigen CLDN6 and a CAR-T cell amplified RNA vaccine encoding CLDN, which is based on BioNTech's mRNA-lipoplex technology to improve the durability of adoptively transferred cells Sex and functional. Indications include testicular cancer , ovarian cancer, endometrial cancer, fallopian tube cancer, sarcoma and gastric cancer . The results of the
trial show that 6 of the 214 evaluable patients showed partial remission, 5 patients had stable condition and reduced target lesions . In addition to showing overall targeting efficacy, the feasibility of mRNA technology in the field of infectious diseases was also verified.
at the 2022 American Clinical Society Annual Meeting, Vinod of MSK Cancer Center Dr. Balachandran shared the safety and tolerability research results of BioNTech's mRNA-based personalized new antigen-specific cancer vaccine BNT122 combined with PD-L1 antibody Atezolizumab and mFOLFIRINOX chemotherapy in phase I clinical trials of surgical resection for patients with pancreatic cancer.
Figure 2 The study phase of BNT122 in various cancers (Photo source: BioNTech official website) The results of the
trial show that data read from 16 patients treated with BNT122 showed that BNT122 was well tolerated in combination with atezolizumab, and that the treatment induced a new neoantigen-specific T-cell response in 50% of patients. Based on these data, BioNTech and Genentech are planning a randomized study to further evaluate the efficacy and safety of BNT122 combined with atezolizumab and chemotherapy in patients with resection of pancreatic ductal adenocarcinoma.
BioNTech and Regeneron Pharmaceuticals are collaborating to develop an mRNA vaccine for advanced melanoma BNT111, the vaccine is in phase II. At the end of last year, the FDA awarded the vaccine fast track title based on "the existing preclinical and clinical data that shows that BNT111 may overcome the limitations of drug-resistant advanced melanoma that cannot be treated with inoperable."
Figure 3 BNT111 is in phase II clinical (Photo source: BioNTech official website)
In addition, for Moderna, in addition to mRNA-4157/V940, it also has KRAS vaccine (mRNA-5671), checkpoint vaccine (mRNA-4359), and other vaccines in the field of cancer treatment.
Figure 4 Moderna is in the R&D stage mRNA cancer vaccine (Photo source: Moderna official website)
believes that with the further deepening of R&D, the cancer vaccine will definitely benefit the majority of cancer patients!
Written by | Muzijiu
Typeset | Wen Zhengze
End
Reference materials:
[1]https://investors.modernatx.com/news/news-details/2022/Merck-and-Moderna-Announce-Exercise-of-Option-by-Merck-for-Join t-Development-and-Commercialization-of-Investigational-Personalized-Cancer-Vaccine/default.aspx
[2]https://www.163.com/dy/article/HJHTKQ3705349C3E.html
[3]https://investors. biontech.de/news-releases/news-release-details/biontech-presents-positive-preliminary-phase-12-data-first-class/
[4]https://investors.biontech.de/news-releases/news-release-details/p ositive-phase-1-data-mrna-based-individualized-neoantigen
[5]https://s29.q4cdn.com/435878511/files/doc_presentations/2022/09/Moderna-Final-R-D-Day-Slides_PDF-(09.08.22).pdf
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