Time flies, and 2022 will be over in less than a month! Looking back on 2022, a number of innovative treatments with new mechanisms have been launched; important breakthroughs have been made in the development of new drugs for Alzheimer’s disease, ALS, chronic hepatitis B and other stubborn diseases; modification of the human genome and xenogeneic organ transplantation seem to exist in science fiction movies. Technology has taken an important step towards human trials; and the application of artificial intelligence, which often appears in science fiction movies, in the field of biomedicine can be described as changing with each passing day.

In this article, WuXi AppTec’s content team has collected a number of milestone developments that have attracted widespread attention in the biomedical field this year. We invite readers to select the top ten breakthroughs in the biomedical field in 2022. Based on readers’ voting results and internal discussions among WuXi AppTec’s content team, we will announce the top ten breakthroughs in biomedicine in 2022 at the end of the year.

01. The first TCR therapy is launched

In January this year, the US FDA approved the launch of Kimmtrak, the first T cell receptor (TCR) therapy. It is a bispecific protein targeting gp100 developed by Immunocore. It consists of a high-affinity soluble TCR and a CD3 receptor on the surface of T cells. The combined effector domains are fused. It is not only the first TCR therapy approved by the FDA, but also the first bispecific T cell adapter protein approved by the FDA for the treatment of solid tumors.

02. The first LAG-3 antibody was approved

In March this year, Bristol-Myers Squibb announced that the U.S. FDA approved its “first-in-class” anti-LAG-3 antibody drug relatlimab for use in combination with the anti-PD-1 antibody Opdivo to treat patients with unresectable or metastatic melanoma. This is the first immunotherapy targeting a new immune checkpoint protein approved by the US FDA in the past 10 years.

03. The first new type of diabetes drug approved in the past 10 years

In May this year, Eli Lilly announced that the U.S. FDA approved its glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor dual agonist Mounjaro (tirzepatide) for use with A combination of diet and exercise can improve blood sugar control in adults with type 2 diabetes. This represents the first new type of diabetes drug in nearly 10 years.

04. The first oral treatment for alopecia areata was approved

In June this year, the oral JAK inhibitor baricitinib (English trade name Olumiant) jointly developed by Eli Lilly and Incyte was approved by the US FDA for the treatment of adult patients with severe alopecia areata. This is the first FDA-approved systemic treatment for alopecia areata. Bringing hope of restoring hair growth to approximately 147 million patients worldwide.

05. The first fecal microbiome therapy is approved by the FDA

On November 30 this year, the US FDA approved the listing of Rebyota, a microbiome therapy developed by Ferring Pharmaceuticals, for use in adult patients over 18 years old with Clostridium difficile infection (CDI) to prevent the recurrence of infection after antibiotic treatment. This is the first fecal microbiome therapy approved by the FDA, representing a breakthrough in the development of microbiome therapies from scratch. In addition to Rebyota, the biologics license application for SER-109, an oral microbiome therapy developed by Seres Therapeutics, has also been granted priority review status.

06. Innovative treatment for ALS approved by FDA

In September this year, the U.S. FDA approved Relyvrio (an oral fixed-dose formulation of sodium phenylbutyrate and taurine diol) developed by Amylyx for the treatment of amyotrophic lateral sclerosis (ALS). This is the third FDA-approved therapy for this century-old disease with a 100% fatality rate.

07. The pace of gene therapy marketing is accelerating, and 5 innovative therapies have been approved for marketing.

Gene therapy brings patients the hope of lifelong benefit from a single treatment. As gene therapy technology matures, the frequency of therapy approval has accelerated significantly in recent years. This year, five gene therapies have been approved by US or EU regulatory agencies. They are Upstaza, Zynteglo, Roctavian, Skysona and Hemgenix, which are used to treat aromatic L-amino acid decarboxylase deficiency (AADCD) and beta thalassemia respectively. Hemophilia A, and cerebral early active adrenoleukodystrophy (CALD), and hemophilia B.

08. The pace of marketing of bispecific antibody therapies has accelerated, and 5 therapies have been approved for marketing.

Similar to gene therapy, bispecific antibodies also represent an innovative treatment model that significantly improves the flexibility of antibody drugs by combining with two different antigens. This year, five bispecific antibody/protein drugs have been approved for marketing globally. In addition to the aforementioned Kimmtrak, they also include Roche’s Vabysmo and Lunsumio, Janssen’s Tecvayli and Kangfang Biologics’ cardunilimab. Among them, Vabysmo is the first dual-antibody drug to treat ophthalmic diseases, and cardunilimab is the first bispecific antibody to target both PD-1 and CTLA-4.

09. Phase 3 clinical trial of Alzheimer’s disease antibody therapy significantly delays cognitive decline

In September this year, Eisai and Biogen jointly announced that the investigational therapy lecanemab has achieved major results in a Phase 3 clinical trial for the treatment of patients with mild Alzheimer’s disease and mild cognitive impairment (MCI) caused by Alzheimer’s disease. The endpoint, compared with placebo, was a 27% reduction in the rate of decline in measures of patients’ cognition and daily functioning. This result represents an important breakthrough in Phase 3 clinical trials of amyloid-targeting Alzheimer’s disease therapies.

10. Clinical trial results of multiple weight loss treatments are positive

After Novo Nordisk’s semaglutide was approved by the FDA to treat common obese patients, innovative weight loss treatments have successively obtained positive results in clinical trials. In April this year, Eli Lilly announced that it is developing a glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor dual agonist tirzepatide, which is the first to treat obesity or overweight people. Achieved the co-primary endpoint in a registrational global Phase 3 clinical trial. The subgroup treated with the highest dose of tirzepatide experienced an average weight loss of 22.5% (approximately 24 kg), and 63% of subjects lost at least 20% weight!

Pfizer’s two oral GLP-1 receptor agonists, danuglipron and PF-07081532, also obtained positive results in early clinical trials.

CagriSema developed by Novo Nordisk also obtained positive results in a phase 2 clinical trial for the treatment of type 2 diabetes. CagriSema contains the GLP-1 receptor agonist semaglutide and long-acting amylin. ) analogues of cagrilintide. Patients treated with CagriSema lost 15.6% of their body weight after 32 weeks.

11. Functional cure of hepatitis B goes one step further

The reason why chronic hepatitis B virus infection is difficult to cure is that the covalently closed circular DNA in the patient’s body and the hepatitis B virus DNA integrated into the cell genome can continuously produce hepatitis B surface antigen (HBsAg) and provide a template for viral replication. Traditional treatments cannot remove these genomic components. However, using various methods such as RNAi, antisense oligonucleotides and base editing, scientists have found ways to target components of the hepatitis B genome. This year, GSK’s ASO therapy and Vir Biotechnology’s RNAi therapy both achieved long-term clearance of HBsAg and anti-hepatitis B protein antibody seroconversion in clinical trials, bringing new hope for the functional cure of chronic hepatitis B.

12. Single base editing technology enters clinical development stage

Single base editing technology can rewrite one letter in the DNA sequence without cutting the double strands of DNA. Compared with gene editing technology based on CRISPR-Cas9, it may theoretically bring higher safety. This year is a landmark year for the development of single base editing therapies. Verve Therapeutics’ single base editing therapy completed the first patient administration in July this year, becoming the first in vivo base editing therapy to enter the clinical development stage. Today, Beam Therapeutics’ CAR-T therapy using single base editing was also approved by the FDA for clinical trials. This breakthrough comes only 6 years after the first scientific paper on single base editing technology was published, showing the rapid transformation of cutting-edge technology.

13. Pig organ transplant enters human trial stage for the first time

In January this year, academics at the University of Maryland transplanted a heart from a pig into a patient with severe heart disease for the first time. The pig heart worked normally in the patient’s body for nearly two months and showed no obvious signs of immune rejection. Although the patient’s condition worsened and passed away two months later, the study of this case provided valuable experience for future xenotransplantation. This year, a number of case studies on pig kidney transplantation and pig heart transplantation were published in the top medical journal “The New England Journal of Medicine.” After years of research in animal models, pig organ transplantation is expected to enter clinical trials in the near future.

14. Artificial intelligence has repeatedly achieved breakthroughs in designing new molecules.

In 2021, artificial intelligence (AI) algorithms represented by AlphaFold achieved a major breakthrough in accurately predicting protein structure. This achievement was also listed as the 2021 Scientific Breakthrough by the Science website. In 2022, AlphaFold not only predicted the structure of almost all known proteins on earth. AI algorithms have also made repeated breakthroughs in designing new protein drugs. Professor David Baker’s team at the University of Washington has published multiple papers in top scientific magazines such as Nature, Cell and Science, introducing the ability to use computer software to design new molecules that bind to target proteins. In just one year, the team’s computer software has been able to design protein molecules or macrocyclic peptides that tightly bind to almost any target protein of interest, and has shortened the time required to design a protein from “months” to “seconds”. These breakthroughs are expected to bring new revolutions in areas such as vaccines and new drug development.