The world's top 10 most popular biotech inventory in 2019

Release date: 2020-01-07 Views: 0

Source: Firestone Creation


The cutting-edge technology has developed rapidly and made breakthrough progress. Adeno-associated virus (AAV) -based gene therapy and siRNA drugs have both been approved for marketing, marking the mature application of the technology. Technologies such as CRISPR and iPSC have made significant breakthroughs in 2019, taking an important step towards clinical application.

Emerging technologies are emerging, focusing on treating new diseases. The release of cystic fibrosis drugs symbolizes that humans have overcome another terminal illness. New treatments for Huntington's disease and the recovery of the dead brain have brought new light to the treatment of diseases that are currently at a loss in medicine.

CRISPR gene editing

CRISPR is a very promising hot-spot technology. It can be used as a therapeutic method, as well as for cell therapy and drug screening. In 2019, several breakthroughs have occurred in the CRISPR field.

The single-base editor (ABE) based on CRISPR technology developed by Professor David Liu in 2016 is a revolutionary technology in this field, which can realize the targeted modification of a single base without relying on DNA double-strand breaks. To reduce potential risks. However, in March 2019, multiple papers reported that single base editing would induce a large number of gene mutations due to off-target.

In October 2019, David Liu's team announced a Prime Editing technology that minimizes the off-target effect of the technology through a series of ABE protein mutants. This technological breakthrough has taken CRISPR a step closer to clinical applications, greatly expanding the scope and capabilities of genome editing, and in principle can correct about 89% of known pathogenic human genetic variations.

In November 2019, the first clinical trial of CRISPR therapy in the United States released positive data. CRISPRTherapeutics and Vertex Pharmaceuticals' CRISPR / Cas9 gene editing therapy CTX001 have achieved positive interim data in phase 1/2 clinical trials. One patient with transfusion-dependent beta thalassemia (TDT) and one patient with severe sickle cell anemia (SCD) achieved the effect of stopping dependence on blood transfusion after receiving treatment. CTX001 uses CRISPR technology to increase the ability of hematopoietic stem cells obtained from patients to express fetal hemoglobin (HbF), and then injected the modified hematopoietic stem cells back into the patient to make up for the functional defects of the adult hemoglobin, thereby alleviating the symptoms of the patient.

Professor Deng Hongkui of Peking University is committed to using CRISPR technology to eliminate HIV. The research team selected an HLA-matched stem cell transplant donor for a patient with acute lymphoblastic leukemia infected with HIV, and then used CRISPR / Cas9 technology to perform genome editing on the donor stem cells. CCR5 was knocked out and then introduced into HIV-infected recipients. The results were published in the New England Journal of Medicine in June 2019.

Gene therapy using AAV virus as vector

In May 2019, Zolgensma, a gene therapy for spinal muscular atrophy (SMA), was launched. The therapy uses AAV as the carrier and is the second viral vector gene therapy approved by the FDA. The first viral vector gene therapy, Luxturna, was approved in 2017, demonstrating that the therapy has practical value, and the approval of the second similar therapy means that the therapy is maturing. Zolgensma is also the first systemic delivery of adeno-associated virus (AAV) vector gene therapy, marking a new breakthrough in the safety, tolerance and specificity of AAV vector-based gene therapy technology. Biomarin's AAV-based gene therapy for hemophilia has been submitted to the European Medicines Agency (EMA) and is expected to be marketed next year to benefit the majority of patients with hemophilia. By then, the therapy will achieve a breakthrough from niche diseases to large indications.

siRNA (small interfering RNA)

In November 2019, following the launch of the first siRNA drug ONPATTRO (patisiran) last year, Alnylam's siRNA drug Givlaari (givosiran) was approved for marketing for the treatment of adult acute liver porphyria (AHP). Previously, Givlaari was approved by the EMA and FDA as an orphan drug, qualified for the EMA rapid approval process, and FDA breakthrough therapy, and is the world's first approved drug for the treatment of AHP.

The first siRNA drug, ONPATTRO, is effective in treating hATTR amyloidosis, and has better efficacy than the antisense nucleotide drug Tegsedi. Givlaari is the second approved siRNA drug. It uses GalNAc-modified siRNA therapy manufacturing technology for the first time, marking another mature technology in the field of nucleic acid drugs after siRNA therapy has become antisense nucleotides. Alnylam's other siRNA drug, inclisiran, has released clinical phase III positive data for the treatment of familial hypercholesterolemia (HeFH) and is expected to be approved for marketing next year.

iPSC (Induced Pluripotent Stem Cells)

Since Yamanaka invented the iPSC technology and won the Nobel Prize, iPSC has been a hot spot in the field of cell therapy. This technology has lifted the limitation of cell sources and has great potential. Japan is still leading the way in the iPSC field and has applied iPSC to the clinical treatment of macular degeneration, spinal cord injury, Parkinson's disease, corneal disease and other indications. In September 2019, a Japanese research team made iPSC into the cornea and transplanted it into women with vision loss, and another iPSC cell was approved as a treatment for spinal cord injury.

In December 2019, the National Institute of Ophthalmology (NEI) announced that it is conducting a clinical trial to test the safety of a new type of autologous iPSC-based therapy for geographic atrophy, which is a dry age-related macular One of the more severe types of degeneration (AMD). This trial is the first clinical trial in the United States to use patient-derived induced pluripotent stem cells (iPSCs) to replace tissue.

In September 2019, the FDA approved iPSC-derived CAR-NK therapy for clinical trials. The therapy is a cell therapy product from Fate Therapeutics, which targets multiple tumor-associated antigens. CAR-NK made from iPSC may become a universal therapy, and its application is a major breakthrough in the combination of iPSC and immune cell therapy.

Immune cell therapy

In 2019, the field of immune cell therapy led by CAR-T is still hot, and many breakthroughs have emerged. University College London has developed a CAT CAR-T therapy with low affinity to CD19. It is not easy to over-activate immune cells in the human body, but it can make T cells more aggressive. Clinical data show that compared with traditional CAR-T, CAT CAR-T has enhanced cell expansion, lower toxicity, and no severe CRS.

In September 2019, researchers from various institutions in China and the United States disclosed the first CAR-T cells that target the B-cell activating factor receptor (BAFF-R) expressed on cancer cells, eradicating the CD19 target in animal models. The development of resistant human leukemia cells and lymphoma cells to the therapy. The new treatment will be used in clinical trials next year to treat patients who have relapsed cancer after receiving CD19 immunotherapy, and may be used as a first-line CAR-T cell immunotherapy.

In the past two years, the proportion of research on immune cell therapy for solid tumors has gradually increased. Statistics in 2019 show that among active preclinical cell therapies, 242 are specifically designed for solid tumors, and 172 are for blood This indicates that cell therapy is gradually shifting its focus to solid tumors. For solid tumors, the researchers devised a method to enhance the efficacy of CAR-T solid tumors with a vaccine that significantly increased the number of anti-tumor T cells and allowed these cells to invade solid tumors. Studies in mice have shown that CAR-T therapy combined with "boost vaccines" can completely eliminate solid tumors in 60% of animals, while CAR-T therapy alone has almost no anti-cancer effect.

TIL therapy is also a new force against solid tumors and has made good progress this year. Iovance's TIL therapy lifileucil and LN-145 announced clinical data at the 2019 ASCO Annual Meeting, showing excellent results in clinical trials for patients with melanoma and cervical cancer, respectively.

Lifileucil achieved an objective response rate of 38% and a disease control rate of 80% in patients with metastatic melanoma who have been treated with multiple therapies. LN-145 therapy achieved a 44% remission rate and a 11% complete remission rate in the treatment of patients with cervical cancer, and obtained the breakthrough therapy designation granted by the FDA. The company plans to file lifileucil and LN-145 biologics licensing applications (BLA) in 2020.

Stem cell therapy cures HIV

In March 2019, a patient's white blood cells were replaced with HIV-resistant white blood cells by stem cell transplantation, and the patient's HIV was subsequently cleared. As early as 2009, it was reported that after a bone marrow transplant, a leukemia patient found that the body's HIV was cleared, known as the "Berlin patient." This is the second case of HIV-positive patients in the UK. Due to a diagnosis of Hodgkin's lymphoma, hematomas have resolved after a stem cell transplant, and HIV has been cleared.

Similar to the "Berlin patient" case, the transplanted donor cells also carry a CCR5 mutation. The case shows that the “Berlin patient” is not an isolated case, it brings hope to millions of HIV patients. A cure for HIV may come soon, and it may only be necessary to transplant a graft with cells carrying CCR5 mutations.

Cystic fibrosis drugs

In October 2019, the innovative therapy Trikafta (elexacaftor / tezacaftor and ivacaftor) was approved by the FDA for marketing and can treat 90% of patients with cystic fibrosis. This combination therapy was shortlisted for Science Magazine's 2019 Breaking Science News "Annual Breakthrough".

Cystic fibrosis (cystic fibrosis) is a rare, shortened life-span inherited disease that causes patients to accumulate abnormally thick mucus in organs such as the lungs, causing chronic lung infections and progressive lung damage, and ultimately leads to death. Cystic fibrosis has not been effective for a long time and was once considered terminally ill. In 2012, Kalydeco (ivacaftor), the first drug to treat cystic fibrosis, was launched, but only about 4% of patients benefited. The approval of Trikafta triple therapy has achieved a cure rate of 90% for cystic fibrosis, symbolizing another terminal illness being overcome by humans.

Siglectin-15 antibody

Siglectin-15 is another blockbuster immune checkpoint molecule after PD-1 / PD-L1. It was identified and developed by Professor Zhanping, one of the PD-1 antibody discoverers, and established Nextcure to carry out related industrial transformation.

In November 2019, the results of the Phase I clinical trial of Siglec-15 monoclonal antibody NC318 were updated: NC318 had an ORR of 20% (2/10) in 10 patients with evaluable PD-1 resistant non-small cell lung cancer, including 1 CR, 1 case of PR, and good safety. Due to the positive results, Nextcure's stock rose 248%.

Since the expression of Siglec-15 and PD-L1 are mutually exclusive, it indicates that Siglec-15 antibodies may be effective in patients who do not respond to PD-1 / PD-L1 antibody therapy, and can compensate for PD-1 / PD-L1 therapy. Insufficient results, so the pharmaceutical industry has high hopes for NC318 to become the next PD-1. The NC318 monotherapy data is extremely impressive and the patient is well tolerated. The results are basically close to the data from the early trials of the immune checkpoint inhibitor PD-1 monoclonal antibody.

"Small molecule glue" for Huntington's disease

In October 2019, a team of multidisciplinary teams, such as Lu Bozheng and Ding Yan's Group of the School of Life Sciences, Fudan University, and Fei Yiyan's Group of the Department of Light Science and Engineering, School of Information Science and Engineering, Fudan University, pioneered an initiative based on autophagy. Atmospheric Binding Compounds (ATTEC) original concept of drug development, and cleverly screened based on compound chip and cutting-edge optical methods to find small molecule compounds that specifically reduce the pathogenic proteins of Huntington's disease. The research team called the compound "small molecule glue", which can look directly at the bull's eye, firmly stick the autophagy-related protein LC3 and Huntington's (HTT) protein together, and then encapsulate the HTT protein into the autophagosome for degradation. . At the same time, the "small molecule glue" only targets mutated HTT proteins and does not adhere to wild-type HTT proteins, making it safe and sound.

The molecular mechanism of Huntington's disease is not very clear, and there are no specific therapeutic drugs. This technological innovation brings a new dawn to the clinical treatment of Huntington's disease.

Human brain recovered hours after death of artificial system

In April 2019, Yale University scientists reported that the isolated pig brain was connected to the BrainEx system a few hours after death. This system can simulate pulsating blood flow at normal body temperature (37 ° C) and inject oxygen-containing artificial substances brain. Perfusion successfully restored circulation in the brain tissue, which also led to the preservation of neuronal structures, including the preservation of hippocampal cells.

Surprisingly, the connection to BrainEx also helped restore the electrical activity and inflammatory response of neurons. In addition, neurons are able to utilize oxygen and metabolize glucose. However, perfusion does not restore more complex neuron functions such as consciousness or perception, nor does it find whole brain activity and function. However, this study did raise human awareness of brain science, challenged our understanding of the meaning of death and its relationship with complex brain functions, and put forward new ethical requirements for related research. In addition, this study proposes an important technical tool that provides technical possibilities for the restoration of brain function.

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