What are the mRNA drugs for the treatment of tumors and rare diseases?

Starting in 2020 with an RNA virus and ends with an mRNA vaccine, the mRNA vaccine has made its debut in the prevention of the new coronavirus, at least from clinical trial results, so this year has been defined as the first year of mRNA technology. The main technical threshold in the development of
mRNA drugs lies in stability and delivery, and if the difficulties can be solved, coupled with the potential of mRNA to synthesize any protein, in addition to being used to prevent infectious diseases, it can also be used as protein supplementation or alternative therapy to treat other diseases;
, mRNA drugs have great potential for the prevention of infectious diseases, cancer and the treatment of a wide range of diseases, including rare diseases.
the treatment of mRNA tumor vaccine can be divided into two categories, including dextry cell (DC)-based mRNA vaccine and directly injected mRNA vaccine.
DC vaccine obtains mRNA through in-body transcription and transfed to DC, mRNA translates into the cytotones to form antigens that activate the DC, injecting the activated DC into the body to stimulate the immune system response and kill tumor cells.
direct injection of the mRNA vaccine is the granulocyte-macrophage collection stimulation factor (GM-CSF) as an adage, the coded antigen mRNA injected into the patient, thereby stimulating the body to produce antibodies, inhibit tumor cell growth.
companies that are currently making rapid progress in the development of mRNA oncology vaccines are Mainna, BioNTech and CureVac.
the late stage pipeline BNT-112BNT-112 for the treatment of tumor mRNA is an mRNA-based tumor vaccine consisting of 5 expression tumor-related antigens (RBL038, RBL039, RBL-040, RBL-041, and RBL-045).
use the liposome technology of the FixVAC platform to treat metastatic desopathic prostate cancer with intravenous drugation.
Phase I/II clinical trial of BNT-112 in association with cemiplimab and/or acetic acid Goscherelin was launched in July 2019.
BNT-113BNT-113 was developed by BioNTech and Astellas subsidiary Ganymed.
BNT-113 is an mRNA vaccine wrapped in liposomes that encodes HPV-16-derived E6 and E7 modified sequences for HPV16 plus cancers, including head and neck squamous cell carcinoma, cervical cancer, penile tumors, anal tumors, metastatic head and neck squamous cell carcinoma (HNSCC), oral tumors, pharyngology tumors, and throat tumors.
phase I/II clinical study was launched in April 2018, and a Phase II clinical trial for HPV-head and neck cancer is planned for the second half of 2020, as well as a Phase II clinical trial for the non-removable recurrence or metastatic HPV16 plus head and neck squamous cell carcinoma in BNT-113 combined keytruda.
RG-6180RG-6180 was jointly developed by Genentech and BioNTech and uses BioNTech's IVACMUTANOME platform.
RG-6180 is a personalized mRNA-based cancer vaccine that encodes specific tumor-specific antigens in patients' tumors for intravenous drugging to treat solid tumors, including melanoma, non-small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancer.
October 2017, the 8/Ib clinic for RG-6180 monodratives or in pairs with arterial mono-drugs for topical advanced or metastatic solid tumors (including melanoma, non-small cell lung cancer, bladder cancer, colorectal cancer, tri-negative breast cancer, kidney cancer, and head and neck cancer) was conducted to assess the safety and pharmacological dynamics of RG-6180.
data released this year show that most adverse events (AEs) are grade 1-2, with infusion-related reactions, cytokine release syndrome, fatigue, nausea and diarrhea occurring in ≥15 percent of patients.
8%, 1 patient achieved complete remission, and 49% of patients achieved disease stabilization.
January 2019, the phase II clinical trial of RG-6180 in the combined Pabliju monoantigen for first-line treatment of advanced melanoma was launched.
phase 2-3 NSCLC and Phase II clinical trials for colorectal cancer patients in 2020.
mRNA-2416mRNA-2416 is a lipid nanoparticle-encoded human OX40 ligation mRNA that uses Moderna's proprietary lipid-based delivery system for the treatment of cancers, including recurring/regressive malignant solid tumors, lymphomas and ovarian cancers.
2017, Phase I/II clinical trials were initiated for patients with relapsed/recurring malignant solid tumors or lymphomas.
according to data released in November 2018, drug-related adverse events were at least magnitude 3 and there were two cases of severe adverse events, and preliminary analysis showed an increase in OX40L protein expression in tumors and immune cells after treatment.
applied to the FDA to modify the clinical trial program, adding mRNA-2416 single-drug Phase II cohorts for the treatment of advanced ovarian cancer and phase II extended queues for mRNA-2416 combined durvalumab in Phase I clinical studies.
4/5 adverse events associated with mRNA-2416 were not reported in further data released this year.
14 patients with disease stabilization (SD), of which 6 ≥ 14 weeks, 15 patients progressed.
mRNA-4157mRNA-4157 was developed in collaboration with Moderna and Mercadon, using Moderna's mRNA vaccine technology.
mRNA-4157 is a personalized mRNA-based vaccine for the treatment of cancer, including skin melanoma.
Phase 1 clinical trial evaluated the safety, toerability, and immunogenicity of mRNA-4157 monodratives in patients with removed solid tumors or combined Keytruda in patients with non-removable solid tumors.
results released last year showed that 11 patients in the single-drug treatment group remained disease-free for 75 weeks, while among the 20 patients in the combined treatment group, the number of complete remissions, partial remissions, disease stabilization and disease progression was 1, 5, 6 and 8, respectively.
after the trial, adding 17 patients who were resistant to PD-1 inhibitors.
Based on interim data released last month, tumor volume reduction occurred only in HPV-HNSCC patients and not in MSSS-CRC patients in 10 hpV-head and neck squamous cell carcinoma (HPV-HNSCC) and 17 microsatellite stable colorectal cancer (MSS-CRC) patients.
in the HPV-HNSCC group, the total remission rate (ORR) was 50% (5/10), 2 patients achieved complete remission (CR), 3 patients were partially relieved (PR), the medium progression-free lifetime (mPFS) was 9.8 months, and the disease control rate (DCR) was 90% (9/10).
The number of patients with complete remission, partial remission, disease stabilization, and disease progression in HPV-HNSCC and MSS-CRC patients who were not treated with immuno-checkpoint inhibitors was 2 and 0, 3 and 0, 4 and 1 and 16, respectively.
NCI-4650NCI-4650 was developed by Moderna in collaboration with the U.S. National Cancer Institute and uses Moderna's mRNA vaccine technology.
NCI-4650 is a personalized mRNA-based vaccine for new antigens expressed in tumor cells in individual patients for the treatment of metastasis cancers, including melanoma, gastrointestinal and genitourinary tract cancers.
In Phase I/II clinical trials in patients with metastases, gastrointestinal and genitourinary cancers, according to published data, 17.5% of the mutation sequences in the vaccine main chain were able to induce T-cell responses for mutant peptides after vaccination;
CV-8102CV-8102 is an RNA-based single-stranded, non-coding TLR-7/8 and RIG-1 astigation developed using CureVac RNAdjuvant technology to treat cancer and infectious diseases.
September 2017, a Phase I clinical study was conducted to evaluate patients with CV-8102 monodal drugs or PD-1 therapies for advanced melanoma, skin squamous cell carcinoma, head and neck squamous cell carcinoma, or adenoblastic cystic cancer.
has published data showing some efficacy, safety, in 50 patients with advanced solid tumors, the use of CV-8102 alone or in association with PD-1 drugs is safe and well-to-bear, occurring in ≥10% of patients with adverse events such as fever, fatigue, chills, headache and injection site pain.
authorized to develop BI-1361849 in collaboration with CureVac and Unilfarma.
This is an intradermal vaccine based on the RNActive technology platform that contains modified mRNAs encoding 6 tumor-related antigens (NY-ESO-1, MAGE-C2, MAGE-C1, Survivin, 5T4, and MCC1) for the treatment of non-small cell lung cancer (NSCLC).
phase I clinical study evaluated the effectiveness and safety of BI-1361849 combined topical radiotherapy in patients with phase IV NSCLC .
most commonly reported adverse events (AEs) are mild and moderate injection site reactions and flu-like symptoms, with no serious adverse events.
0, 1, 12 and 12 patients with complete remission, partial remission, disease stabilization and disease progression were 0, 1, 12 and 12, respectively.
the medium non-progressed lifetime and the medium total survival period were 2.9 and 14 months, respectively.
, combined with low-dose radiotherapy and standard maintenance therapy for phase IV NSCLC, BI-1361849 has good tolerance and immunogenicity.
December 2017, phase I/II clinical trials of BI-1361849 in the United States in association with durvalumab and tremelimumab for the treatment of NSCLC were initiated.
mRNAbased immunotherapies was developed by eTheRNA using its proprietary TriMix technology, a Belgian biotech company founded in 2013 to develop immunotherapy to treat cancer and infectious diseases using the proprietary mRNA TriMix platform.
this mRNA-based immunotherapy contains three types of mRNA encoded with caTLR4, CD40L, and CD70 proteins, which work together to optimally activate degenerate cells for breast cancer treatment.
phase I/II trials were conducted in patients with triple-negative breast cancer.
rare disease treatment in the field of rare disease treatment, the rapid progress of mRNA drugs including Moderna treatment of methyl propylene blood disease (MMA) mRNA-3704 and Translate Bio treatment of cystic fibrosis (CF) MRT-5005, has entered phase 2 clinical phase.
mRNA-3704mRNA-3704, a late-stage pipeline mRNA-3704 drug for rare diseases, is an mRNA therapy that encodes human methyl propylene coenzyme A mutant enzyme (MUT) in lipid nanoparticles (LNP), developed by Moderna using its N2GL proprietary preparation technology to enable liver cells to produce hMUT enzymes by administering methyl diacetic acidemia (MMA).
May 2019, phase I/II clinical trials were launched in MMA patients and the programme design was adjusted to accelerate the clinical development of the drug.
2011, MRT-5005Translate Bio is dedicated to converting mRNA into therapeutic drugs.
the company acquired Shire's MRTTM platform in 2016 and used it to develop mRNA therapy candidates.
MRT-5005 aims to deliver mRNA from the cystic fibrosis transfilm conductivity regulator (CFTR) protein, which encodes normal function, to the lungs through atomization for the treatment of cystic fibrosis (CF).
May 2018, a Phase I/II clinical study was conducted to assess the safety and toerability of MRT-5005 in adult CF patients as a single-dose and multi-dose climbing experiment.
July 2019, interim data on single-dose climbing trials in 12 patients were published.
data showed that a significant increase in ppFEV1 (the percentage of predicted forced exhalation within one second) was observed after a single dose (mainly medium dose), while no significant improvement was observed in patients in the placebo group and the 8 mg dose group.
8 days after the dose was given, the ppFEV1 levels of 3 patients in the 16 mg dose group and 1 patient in the 24 mg dose group increased by 15.7% and 21.4% respectively over the baseline average.
the drug at low and medium dose levels.
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