This week, multiple breakthroughs in the pharmaceutical and life sciences sectors have drawn attention: Kelun Pharmaceutical enters the 700 million anticoagulant track, Zhengya Dental is sprinting toward a ChiNext IPO; NMN-enhanced REM sleep EEM was analyzed for the first time, and the domestic antithrombotic drug Vecadogrel NDA was accepted. In addition, the Sichuan University team revealed a new mechanism by which PD-1 blockades induce NK cell aging; Xu Yi once instructed Lingyu to discover a new pathway for bone marrow vascular regeneration through cell burial; Zhejiang University launched a disruptive growth factor-free cell adhesion coating technology, bringing new variables to related disease treatments and industry patterns.

1. Breaking News! Kelun Pharmaceutical is aggressively attacking the anticoagulant track, aiming for 700 million yuan in star drugs

Recently, the marketing application for naxostat mesylate for injection, submitted by Hunan Kelun Pharmaceutical and Chengdu Qingshan Likang in collaboration with Chengdu Qingshan Likang, was officially accepted by the CDE, marking the entry of a leading player in this high-prosperity anticoagulant sector, long dominated by exclusive companies. As a potent serine protease inhibitor developed by Japan’s Torii Pharmaceutical, this product was approved for market in Japan in 1986. Clinically, it is used clinically for the treatment of acute pancreatitis and extracorporeal blood perfusion anticoagulation. Compared to traditional heparin drugs, it carries significantly lower bleeding risks and is irreplaceable in ICU, ECMO, continuous hemodialysis, and other critical and critical cases. The original product has yet to submit a domestic marketing application. Previously, Jiangsu Durui Pharmaceutical spent nearly 18 years completing R&D, obtained the first domestic generic qualification in 2020, and maintained a long-term market monopoly. According to the latest in-hospital database from Yaozhi.com, by 2025, domestic terminal sales of this product have exceeded 700 million yuan, with a year-on-year growth rate of 177%. Driven by the release of demand for emergency and critical care treatment, the market size is still in a rapid growth phase. In 2025, this product will see a wave of concentrated applications. In June alone, CDE accepted 12 generic applications, and leading generic drug companies such as Chia Tai Tianqing and Kelun have all completed their deployment. According to the current pace of chemical and generic drug reviews, it is expected that around 2027, the approval documents will be concentrated and implemented. If three companies pass the evaluation at that time, it will directly trigger the national centralized volume-based drug procurement, rapidly narrowing the excess dividends of the original monopoly companies, and the price system and market share structure of the entire anticoagulant sub-sector will undergo a comprehensive reshuffling.

2. Research shows that NMN can enhance REM sleep brainwaves

Recently, the neuroaging research team at Washington University in St. Louis, Missouri, published their latest findings in the cell journal iScience. For the first time, they precisely analyzed the regulatory mechanism of β-nicotinamide mononucleotide (NMN) on sleep brain power, filling a gap in previous NMN interventions to improve cognition. Related academic updates have been included in the Yaozhi.com New Drug Research Database. Unlike previous industry generalizations attributing NMN efficacy to increased full-cycle NAD+ levels, this study conducted 24-hour multi-channel implantable EEG monitoring in 3-month-old young mice and 20-month-old aged mice (equivalent to 65-year-old human physiological age) and found that intervention with equivalent daily supplemental NMN doses significantly reduced wake time by 16.8% in young mice, and simultaneous increases in total duration of rapid eye movement sleep (REM) and non-rapid eye movement sleep (NREM); For elderly models with deep REM deficits, NMN specifically increased the amplitude of the EEG theta band by 21.3%, reversing age-related REM brain activity decline. For the first time, the study identified NMN-sensitive neurons in the supramapillary nucleus (SuM) region as the core functional mediator. Further gene knockout validation showed that model mice lacking NMN-specific transporter Slc12a8 not only experienced a 32% decrease in REMθ wave activity, but also experienced clear episodic memory impairment, directly confirming the causal chain of “NMN transported by Slc12a8 to activate SuM neurons—maintain REM sleep homeostasis—and support cognitive function.” Industry insiders also point out that this effect has not yet been validated in clinical cohorts of the elderly, and the association between phase III NREM slow-wave sleep, which is responsible for core physiological repair, and NMN intervention still needs to be explored, pointing new directions for the development of indications in subsequent aging intervention pipelines.

3. The NDA for the domestically produced new antithrombotic drug Vicadogrel capsules has been officially accepted

Recently, according to disclosures from the Center for Drug Evaluation (CDE) of the National Medical Products Administration, Jiangsu Weikaier Pharma’s independently developed Class 1 antithrombotic innovative drug Vicadogrel Capsules has been officially accepted by the NMPA for New Drug Marketing Application (NDA) and entered the review process. It is expected to become the first approved new generation oral P2Y12 receptor antagonist in China. Vicadogrel is a targeted improvement of the metabolic pathway defects of traditional thiapigrel drugs. Its core design bypasses the CYP2C19 gene polymorphism pathway that is highly dependent on clopidogrel metabolism, fundamentally addressing the long-standing clinical pain point of “clopidogrel resistance.” Multiple completed large-sample clinical studies show that the exposure differences of velcadogrel’s active metabolites between individuals are less than 10% of clopidogrel’s, with effective platelet suppression levels reaching as fast as 30 minutes, and the clinical dose used is only 1/20 of clopidogrel; Among atherosclerotic cardiovascular disease patients, the 12-month reduction in major adverse cardiovascular and cerebrovascular events is significantly better than clopidogrel, with overall lower bleeding risk and clear safety advantages. Currently, the domestic antithrombotic drug market has exceeded 30 billion yuan. With intensifying population aging, there is a large unmet clinical demand for clopidogrel intolerance and tiagrelor dyspnea. As the first domestically developed new generation P2Y12 inhibitor to complete superior efficacy validation, velcadogrel has clear Best-in-Class potential. Subsequent companies will simultaneously advance domestic reviews and global multicenter clinical layouts, potentially reshaping the domestic 10-billion-yuan antithrombotic drug market competitive landscape.

4. Cell Subjournal: PD-1 blockade induces NK cell aging; double blockade marks a breakthrough for pancreatic cancer

To address the core pain point of less than 10% response rate for immune checkpoint blockade (ICB) in clinical pancreatic ductal adenocarcinoma (PDAC, commonly known as the “cancer king”), the team led by Ma Xuelei and Liu Jifeng from Sichuan University officially published their findings in Cell Reports on June 19, revealing for the first time a novel drug-resistant pathway for PD-1 blockade inducing functional aging of NK cells, providing key theoretical support for breakthroughs in pancreatic cancer immunotherapy. The research team confirmed that after PD-1 blockade, IFN-γ signaling in the tumor microenvironment becomes abnormally upregulated, driving the expression of the mouse functional ligand H2-T23 (a human homologous molecule is HLA-E) on the surface of pancreatic tumor cells. This molecule specifically binds to the NK cell surface inhibitory receptor NKG2A, activating downstream p38 MAPK and STAT1/3 phosphorylation cascades, inducing NK cells to enter the SA-β-gal positive senescent phenotype, significantly downregulating perforin, Expression of effector molecules such as granular enzyme B directly weakens its tumor-killing activity. In vivo experiments confirmed that dual blockade of PD-1 and NKG2A can completely reverse the aging phenotype of NK cells, restore their innate immune killing function, promote the secretion of the chemokine CCL5 by NK cells, recruit peripheral CD8-T cells to infiltrate immune cold tumors, and synchronously activate intrinsic and adaptive immune responses. The team confirmed through pan-cancer single-cell sequencing cohort analysis that the enrichment of NK cell aging features after ICB treatment is a common mechanism across solid tumors, suggesting that this dual-target strategy has broad-spectrum ICB sensitization potential. Currently, translational research has entered the preclinical optimization stage, promising to fill the clinical gap in immunotherapy for advanced pancreatic cancer.

5. Zhengya Dental is sprinting toward a ChiNext IPO!

On June 29, local invisible orthodontics leader Zhengya Dental Hospital officially submitted its ChiNext IPO prospectus to the Shenzhen Stock Exchange, attracting widespread attention from the industry. Public information shows that founded in 2004, Zhengya Dental has built a product system covering all indications and all age groups, with steady growth in business performance for many consecutive years. Based on the number of clinical orthodontic cases delivered throughout 2025, Zhengya Dental surpassed the Invisalign brand under imported leader Aiqi Technology for the first time, rising to second place in the domestic invisible orthodontics market, directly breaking the long-standing “domestic leading manufacturer + Invisalign dual oligopoly” pattern and forming a new tripartite competitive landscape. According to industry research, Zhengya’s breakthrough core comes from an asymmetric differentiation strategy: on the B2B end, it uses cost-effective solutions to benchmark imported performance to capture the previously foreign monopoly on the public healthcare market, while overseas expansion avoids the European and American red oceans and focuses on tapping new growth in emerging markets like Southeast Asia; On the R&D side, it completely broke free from the low-price competition of small and medium brands, focusing on high-barrier tracks such as complex bony malocclusion correction and early treatment of children and adolescents throughout the entire lifecycle, building a technology-driven brand moat. Industry analysts judge that the current technical threshold in this sector has risen significantly, making it difficult to replicate the next “Zhengya” in the short term. However, if manufacturers achieve breakthroughs in core areas such as medical orthodontic materials and personalized biomechanical algorithms, there is still a chance to reshape the current market landscape.

6. Xuyi Dr. Zeng Lingyu’s team reveals the mechanism by which cell burial promotes bone marrow vascular regeneration

On June 24, Zeng Lingyu’s research group at Xuzhou Medical University published original findings online in the top pathological biology journal Cell Death & Differentiation, clarifying for the first time the core mechanism by which macrophage cytoburial reprogramming promotes angiogenesis phenotypes after transplantation, providing a new intervention direction to address the pain points of microvascular injury and delayed hematopoietic reconstruction after clinical medulla clearance. Allogeneic hematopoietic stem cell transplantation is one of the curative options for malignant blood diseases, but the pretreatment process for marrow debridement almost completely destroys the original microvascular network in the bone marrow, resulting in hindered colonization of hematopoietic stem cells after transplantation. About 20% of patients experience primary transplant dysfunction. Previously, there was a lack of effective interventions targeting rapid regeneration of bone marrow blood vessels. The research team found that after marrow cleansing, the large number of dead cells in the bone marrow are not simply removed as metabolic waste; the dual signals released by these cells can synergistically activate macrophage-promoting angiogenic functions: S1P secreted by dead cells can preactivate macrophage HIF-1α gene transcription, and degradation of apoptotic cell-derived vesicles (ApoBDs) increases intracellular cholesterol levels in macrophages, thereby activating the nuclear receptor LXRα; Nucleated LXRα can directly bind to HIF-1α and inhibit its ubiquitination degradation, ultimately significantly upregulating downstream VEGFA expression. In vivo functional experiments confirmed that after macrophage-specific blocking of the LXRα/HIF-1α axis, vascular regeneration efficiency dropped by 62% after bone marrow transplantation in mice, and the hematopoietic reconstruction cycle was significantly prolonged. This achievement breaks the previous academic understanding that nephragm only exerts immune-clearing functions, expands the research boundaries of nepotial functions, and provides a brand-new candidate for developing hematopoietic transplant-adjuvant drugs targeting the macrophage pathway.

7. Sci Adv: Human-machine collaboration accelerates TYR inhibitor R&D

Abnormal activation and overexpression of tyrosinase (TYR) are the core pathological mechanisms of pigment-disturbing diseases such as melasma and melanosis, and are key targets driving melanoma invasion and metastasis. For a long time, traditional drug development models have been empirically dependent and constrained by high trial-and-error costs, making it difficult to simultaneously meet the development needs of candidate molecules with high inhibitory activity, high subtype selectivity, and low off-target toxicity. Recently, the Bai Renren team at Hangzhou Normal University published original findings in the top international comprehensive academic journal Science Advances, proposing the industry’s first unified R&D framework that integrates AI from scratch generation with dual-track pilot optimization, providing a reusable new paradigm for AI-assisted drug implementation. This framework specifically addresses the common pain points of poor molecular druggability and unfeasible synthetic pathways in previous deep reinforcement learning (RL) drug generation models. By adopting fragment-level constrained growth strategies, it anchors the thresholds of drug-like properties and synthetic accessibility at the generation stage, quickly obtaining the initial lead AI10 that meets initial screening activity targets. Researching an innovative dual-track optimization path for both humans and machines: the derivative AI10-m15, obtained through empirical targeted modification by pharmaceutical and chemical experts, inhibits IC50 at the thanamolar level of TYR in vitro, offering excellent in vivo safety; The fully AI-driven pathway breaks away from the empirical path-dependent approach of traditional pharmaceutical chemistry, producing a novel chemical type AI10-a2 based on a non-classical framework, which offers 27 times better subtype selectivity for TYR than existing inhibitors. System comparison and validation show that the dual-pathway complements each other, reducing the lead compound optimization cycle by more than 60% compared to a single R&D model, clearing the initial core barriers for TYR-targeted first-in-class drug development.

8. Wang Lu/Wu Wei’s team reveals a new mechanism of somatic cell development transposon silencing

On June 18, Wang Lu and Wu Wei’s team from the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, published original findings in somatic transposon regulation online in the top international academic journal Molecular Cell. For the first time, they analyzed a new regulatory axis of conserved transposon silencing across species, filling a long-term gap in maintaining genomic stability during development. Transposons (TE) account for 30%~80% of eukaryotic genome sequences. Their abnormal transposons directly trigger genome insertion mutations and chromatin structural disturbances, which are highly related to various pathological processes such as developmental malformations, hematopoietic dysfunction, tumorigenization, and neurodegenerative changes. Previous studies have confirmed that heterochromatin and various histone modifications participate in transposon inhibition, but the synergistic mechanisms of different regulatory modules and the upstream activation pathway of ligatin H1 have long remained unclear. The research team broke through traditional detection technology bottlenecks and established a whole-genome transposon event capture system at single-cell resolution. In two completely different somatic dynamic development scenarios—Drosophila hindgut regeneration and mouse embryonic erythrogenesis—the team jointly identified the core functional factor Cramp1: Cramp1 can specifically bind to the promoter region of histone gene clusters, directly driving transcriptional upregulation of ligerin H1; H1 further interacts functionally with methyltransferase Nsd, efficiently catalyzing H3K36me2-modified deposition and forming highly compressed inhibitory heterochromatin, completely blocking transcription activation and subsequent skipping events at the chromatin level. This achievement is the first to establish a complete regulatory pathway for Cramp1-H1-Nsd-H3K36me2, providing a new direction for developing transposon activation-related disease targets.

9. After antibiotics failed, a team in Shandong reshaped their antibacterial strategy with “stapler peptides.”

The latest monitoring data from the World Health Organization shows that approximately 1.27 million people worldwide die each year from infections related to antibiotic resistance. The rapid spread of multidrug-resistant “superbugs” has reduced the effectiveness rate of many commonly used traditional antibiotics to less than 30%, and the gap in new antimicrobial pipelines has become a core unmet need urgently needed to be filled in global public health. Recently, the research team led by Li Yulei and Chen Danyu at Shandong First Medical University announced a breakthrough in their staple peptide antibacterial technology pipeline. To address common industry pain points in the drug development process of natural antimicrobial peptides, such as high hemolytic toxicity and poor in vivo hydrolysis stability, the team started from the membrane cleavage mechanism of natural antimicrobial peptides. Using the lead template peptide SLP-0 as the modified substrate, they precisely regulated peptide amphiphilic balance through all-hydrocarbon side-chain cyclized staple peptide modification technology, preserving the antibacterial activity of bacterial cell membrane breakup. It significantly reduces toxic side effects on human red blood cells. The representative molecule SLP-7 has a hemolytic rate less than 40% of the original template, and it exhibits nanomolar inhibitory activity against more than ten clinically high-risk resistant bacteria, including methicillin-resistant Staphylococcus aureus and carbapenemicone-resistant Enterobacteria. It is reported that the team recently completed commercialization of three core patents, each centered on SLP-4, SLP-6, and SLP-7 as core molecules, covering three differentiated clinical directions: systemic anti-infection, local wound treatment, and medical implant infection prevention, forming a complementary patent portfolio. Currently, global antimicrobial peptide drug development has entered a critical stage of translation. This technology can also increase the serum enzymatic hydrolysis half-life of peptides by more than eight times. The project is currently in the final stages of laboratory validation, and will rapidly advance process scale-up, GLP safety evaluation, and other preclinical work.

10. Cell adhesion can be controlled without growth factors! This coating patent from Zhejiang University breaks away from traditional thinking

Recently, the original invention patent “Application of a Material Adjustable for Cell Adhesion in Screening Endothelial and Smooth Muscle Cells” by the Ji Jian team from the Department of Polymer Science and Engineering at Zhejiang University was officially listed for transfer, with a starting price of 1.8 million yuan. This technology breaks free from the traditional framework of bioactive modification, offering a disruptive factor-free solution for the surface functional modification track of implantable medical devices. Currently, mainstream global cell adhesion regulation technologies rely on exogenous bioactive components such as growth factors and fibronectin for specific adhesion guidance. Common industry pain points include short in vitro activity half-lives of proteins, large variation in modification effects between batches, in vivo tendency to induce nonspecific inflammation and immune rejection, and high quality control costs for large-scale mass production. These have long limited the rapid improvement of endothelialization efficiency in core implantable interventional products such as cardiovascular stents and artificial blood vessels. The team innovatively uses a fully polyelectrolyte layer-by-layer self-assembly process, precisely changing the surface Young’s modulus (softness and hardness) by precisely adjusting the coating’s microscopic thickness, enabling precise selective adhesion and distinction between endothelial cells and smooth muscle cells. The technology does not involve any exogenous active biological components, thoroughly avoiding traditional technical shortcomings such as inactivation, batch differences, and immunogenicity. The process is compatible with almost all medical metals, polymers, and ceramic substrates, with extremely low preparation thresholds and strong mass production replicability. Currently, this technology can simultaneously cover two high-value tracks: cell sorting research reagents and functional modification of implantable interventional devices, filling the domestic industrialization gap in factor-free mechanical regulation of cell adhesion. In the medium to long term, it offers cost and clinical safety advantages far exceeding traditional modification routes, with broad potential for domestic substitution.

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