Bone metastases

– First Level 1 study comparing an emerging technology head-to-head with RP in men with prostate cancer – – TULSA had no blood loss and no overnight stay, along with reduced post-procedure pain, and more rapid recovery to baseline activities and overall health – TORONTO, April 29, 2025 (GLOBE NEWSWIRE) -- Profound Medical Corp. (NASDAQ:PROF; TSX:PRN) (“Profound” or the “Company”), a commercial-stage medical device company that develops and markets customizable, AI-powered, incision-free therapies for the ablation of diseased tissue, is pleased to announce initial perioperative data from the Level 1 post-market CAPTAIN trial comparing the safety and efficacy of the TULSA procedure with radical prostatectomy (“RP”) in men with organ-confined, intermediate-risk, Gleason Score 7 (Grade Group 2 and 3) prostate cancer. The positive perioperative results were presented yesterday by Xiaosong Meng, M.D., Ph.D., an Assistant Professor in the Department of Urology at UT Southwestern Medical Center, at the American Urological Association (“AUA”) Annual Meeting. Starting in 2022, CAPTAIN patients were recruited at 20 sites in the United States, two in Canada and one in Europe. As of January 2025, 201 patients were randomized and, to-date, 194 have been treated or scheduled for treatment (69% TULSA, 31% RP). Baseline patient characteristics are balanced for TULSA vs RP, with median (IQR) age 63 (58-68) vs. 64 (59-68) years, proportions with PSA ≤10ng/mL 77% vs. 74%, and 23% vs 26% with PSA>10ng/mL. Proportions of TULSA vs. RP patients with GG2/3 disease were 76%/24% vs. 74%/26%. All patients were EPIC pad-free at baseline. Dr. Meng’s AUA presentation highlighted that TULSA provided statistically significant improvement in all assessed perioperative measures: Blood loss: TULSA median 0 (IQR 0-0) mL vs. RP 100 (100-200) mL, p<0.001.Length of stay: TULSA median 0.29 (IQR 0.27-0.32) days vs. RP 1.24 (1.12-1.36) days, p<0.001.NRS (Numeric Rating Scale) pain: Significantly lower post-operative pain after TULSA procedure vs. RP through to post-treatment day 6, p<0.05.Patient-reported health-related QOL: Significantly higher overall health on the EQ-5D-5L 0-100 VAS (Visual Analog Scale) after TULSA vs. RP for all 30 days measured after treatment, p<0.05.During the first month post-treatment, significantly fewer TULSA patients reported experiencing extreme problems or inability with mobility (0% for TULSA vs. 12% for RP, p=0.001), self-care (3% for TULSA vs. 17% for RP, p=0.005), and usual activities (17% for TULSA vs. 40% for RP, p=0.008). Dr. Meng commented, “I commend the Sponsor and the Study Investigators for taking on this audacious study, as CAPTAIN is the fist randomized controlled trial comparing a new technology to the standard of robotic radical prostatectomy to successfully recruit to target enrollment. In addition to including some of the most talented and high volume surgeons from academic hospitals and private practice, I believe successful randomization was in large part due to TULSA’s proven safety and efficacy for whole-gland ablation in intermediate-risk prostate cancer patients, which fostered equipoise between both arms. While TULSA already has a well-established body of clinical evidence, it now has hard data that shows quantitatively in a head-to-head fashion significantly superior post-treatment patient experience compared to robotic prostatectomy.” “Zero blood loss and nearly a full 24 hours less at the hospital or clinic. Dramatic reduction in post procedure pain and significant improvement with patient mobility, self-care and ability to perform usual activities,” said Arun Menawat, Profound’s CEO and Chairman. “When we see the data that says that robotic prostatectomy patients take over two weeks of recovery, on average, to feel like a TULSA patient does the day after their procedure, we can understand how TULSA patients are often out at the restaurant with their families the night of their procedure rather than laying in a hospital bed. This superior patient experience leads to high patient satisfaction and patient demand, which interestingly is the same axis that drove adoption of the surgical robot in its early days.” Dr. Menawat added, “We believe the CAPTAIN perioperative outcomes are not only central to patient demand, but are also important for insurance companies who consider Level 1 randomized controlled trials the gold standard in evidence-based research for establishing the effectiveness of interventions and making their coverage policies. We look forward to continue reporting CAPTAIN follow-up data, adding to the growing body of clinical evidence that demonstrates the unrivaled precision and flexibility of TULSA with consistent safe and effective outcomes across the full spectrum of prostate disease states.” About CAPTAIN CAPTAIN (A Comparison of TULSA Procedure vs. Radical Prostatectomy in Participants with Localized Prostate Cancer) is a prospective, multi-center randomized controlled trial aimed at comparing the safety and efficacy of the TULSA procedure (performed with the TULSA-PRO® system) with RP in men with organ-confined, intermediate-risk, Gleason Score 7 (Grade Group 2 and 3) prostate cancer. The goal of CAPTAIN is to demonstrate that the efficacy of the TULSA procedure is not inferior to RP, while demonstrating superior quality of life outcomes. The primary safety endpoint is the proportion of patients who preserve both erectile potency and urinary continence at one year after treatment. The primary efficacy endpoint is the proportion of patients who are free from any additional treatment for prostate cancer, free of metastases or prostate cancer related death by three years after treatment. Secondary endpoints include comparison of rates of complications, cost effectiveness, as well as histologic and biochemical failure. About Profound Medical Corp. Profound is a commercial-stage medical device company that develops and markets customizable, incision-free therapies for the ablation of diseased tissue. Profound is commercializing TULSA-PRO®, a technology that combines real-time MRI, AI-enhanced planning, robotically-driven transurethral ultrasound, and closed-loop temperature feedback control. The TULSA procedure, performed using the TULSA-PRO® system, has the potential of becoming a mainstream treatment modality across the entire prostate disease spectrum; ranging from low-, intermediate-, or high-risk prostate cancer; to hybrid patients suffering from both prostate cancer and benign prostatic hyperplasia (“BPH”); to men with BPH only; and also, to patients requiring salvage therapy for radio-recurrent localized prostate cancer. TULSA employs real-time MR guidance for precision to preserve patients’ urinary continence and sexual function, while killing the targeted prostate tissue via precise sound absorption technology that gently heats it to 55-57°C. TULSA is an incision- and radiation-free “one-and-done” procedure performed in a single session that takes a few hours. Virtually all prostate shapes and sizes can be safely, effectively, and efficiently treated with TULSA. There is no bleeding associated with the procedure; no hospital stay is required; and most TULSA patients report quick recovery to their normal routine. TULSA-PRO® is CE marked, Health Canada approved, and 510(k) cleared by the U.S. Food and Drug Administration (“FDA”). Profound is also commercializing Sonalleve®, an innovative therapeutic platform that is CE marked for the treatment of uterine fibroids and palliative pain treatment of bone metastases. Sonalleve® has also been approved by the China National Medical Products Administration for the non-invasive treatment of uterine fibroids and has FDA approval under a Humanitarian Device Exemption for the treatment of osteoid osteoma. Profound is in the early stages of exploring additional potential treatment markets for Sonalleve® where the technology has been shown to have clinical application, such as non-invasive ablation of abdominal cancers and hyperthermia for cancer therapy. Forward-Looking Statements This release includes forward-looking statements regarding Profound and its business which may include, but is not limited to, the expectations regarding the efficacy of Profound’s technology in the treatment of prostate cancer, BPH, uterine fibroids, palliative pain treatment and osteoid osteoma; and the success of Profound’s U.S. commercialization strategy and activities for TULSA-PRO®. Often, but not always, forward-looking statements can be identified by the use of words such as "plans", "is expected", "expects", "scheduled", "intends", "contemplates", "anticipates", "believes", "proposes" or variations (including negative variations) of such words and phrases, or state that certain actions, events or results "may", "could", "would", "might" or "will" be taken, occur or be achieved. Such statements are based on the current expectations of the management of Profound. The forward-looking events and circumstances discussed in this release, may not occur by certain specified dates or at all and could differ materially as a result of known and unknown risk factors and uncertainties affecting the Company, including risks regarding the medical device industry, regulatory approvals, reimbursement, economic factors, the equity markets generally and risks associated with growth and competition. Although Profound has attempted to identify important factors that could cause actual actions, events or results to differ materially from those described in forward-looking statements, there may be other factors that cause actions, events or results to differ from those anticipated, estimated or intended. No forward-looking statement can be guaranteed. Other factors and risks that may cause actual results to differ materially from those set out in the forward-looking statements are described in Profound's Annual Report on Form 10-K and other filings made with U.S. and Canadian securities regulators, available at www.sedarplus.ca and www.sec.gov. Except as required by applicable securities laws, forward-looking statements speak only as of the date on which they are made and Profound undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, or otherwise, other than as required by law. For further information, please contact: Stephen KilmerInvestor Relationsskilmer@profoundmedical.com T: 647.872.4849 Susan ThomasPublic Relationssthomas@profoundmedical.com T: 619.540.9195

In March 2025, the global pharmaceutical sector witnessed a surge of innovation where technology deeply integrates with clinical needs, spanning key areas such as gene therapy, antibiotic breakthroughs, targeted therapies for rare diseases, and vaccine upgrades. From Fitusiran (the world's first RNAi therapy for hemophilia) to Gepotidacin (a novel antibiotic combating drug-resistant strains), from Diazoxide Choline (the first targeted drug for Prader-Willi Syndrome) to the quadrivalent influenza vaccine (covering a broader range of viral subtypes), these new drugs not only break through the limitations of traditional treatments but also redefine disease management paradigms through precision targeting, broad-spectrum antiviral strategies, and the cost-effectiveness of biosimilars. 1. Fitusiran On March 28, 2025, Fitusiran received approval from the U.S. Food and Drug Administration (FDA) for the first time in the United States, becoming the first RNA interference (RNAi) drug to treat hemophilia A and B by inhibiting antithrombin (AT). This milestone marks a groundbreaking advancement of gene therapy technology in the field of blood disorders. The FDA's approval was based on its efficacy in significantly reducing bleeding events in clinical trials, supported by long-term safety data. In addition to the U.S., Fitusiran has also been granted priority review status by China's National Medical Products Administration (NMPA), accelerating its commercialization in key global markets. Developed by Alnylam Pharmaceuticals, Fitusiran's R&D journey exemplifies the deep collaboration of multinational pharmaceutical companies. Alnylam partnered strategically with Sanofi and its subsidiary Genzyme Corp. to jointly advance the drug's clinical trials, optimize production processes, and facilitate global registration. This collaboration leveraged Alnylam's expertise in RNAi technology and Sanofi's extensive experience in treating blood disorders. Moreover, during the R&D process, Fitusiran, due to its innovation in targeting a rare disease, successively received the FDA's "Fast Track" designation and "Orphan Drug" status, further highlighting its value in addressing unmet medical needs. Fitusiran specifically targets antithrombin mRNA via RNAi technology, blocking its translation process to reduce antithrombin levels (by approximately 80%-90%). Antithrombin, a key natural anticoagulant protein in the blood, can overly inhibit the activity of residual clotting factors (such as VIII or IX), exacerbating the bleeding tendency in hemophilia patients. By removing this inhibition, Fitusiran allows the residual clotting factors in patients to more effectively participate in hemostasis, significantly reducing spontaneous or traumatic bleeding events. Technically, the drug employs a GalNAc (N-acetylgalactosamine)-conjugated delivery system to precisely target the liver (the primary organ for antithrombin synthesis), combined with 2'-O-methylation and locked nucleic acid (LNA) chemical modifications to enhance stability, reduce off-target effects, and minimize immunogenicity, achieving a long-acting treatment with monthly subcutaneous injections. In addition to the U.S. and China, Fitusiran is also in the accelerated review stage in major markets such as the EU and Japan, with an expectation to cover major global regions by the end of 2025. Its differentiated advantages—eliminating the need for frequent clotting factor infusions, applicable to all hemophilia subtypes and inhibitor patients—make it a significant complement to existing therapies (such as factor replacement therapy and the anticoagulant Emicizumab). Furthermore, the R&D team is exploring the potential applications of Fitusiran in a broader range of indications, including von Willebrand disease, perioperative clotting management, and prevention of bleeding risks following trauma or surgery, further expanding its clinical value. 2.Technetium Tc 99m Trofolastat Technetium Tc 99m Trofolastat is an innovative diagnostic radiopharmaceutical belonging to the category of radionuclide-conjugated drugs, primarily used for imaging diagnosis of prostate-specific membrane antigen (PSMA)-positive prostate cancer. The drug precisely labels tumor lesions by binding to PSMA, a protein highly expressed on the surface of prostate cancer cells, aiding doctors in locating primary tumors, assessing metastatic distribution, and monitoring treatment responses. Its core advantage lies in the use of the radioactive isotope technetium-99m (Tc-99m), which has a short half-life (approximately 6 hours) and high imaging sensitivity, providing clear tumor images while ensuring patient safety. On March 27, 2025, the drug was first approved in the UK, becoming the world's first radiopharmaceutical diagnostic agent based on PSMA-targeting technology, marking a significant breakthrough in prostate cancer imaging diagnostics. The mechanism of action of Trofolastat is based on the targeting of PSMA. PSMA is a membrane protein overexpressed on the surface of prostate cancer cells, particularly in metastatic or recurrent tumors. The drug specifically binds to PSMA through its chemical structure, then conjugates with Tc-99m to form a radioactive tracer. After intravenous injection into the body, PSMA-positive tumor cells take up and accumulate the drug, generating high-resolution tumor distribution maps through gamma camera imaging. Compared to traditional imaging techniques (such as CT or MRI), Trofolastat can detect PSMA-positive lesions earlier and more sensitively, especially in the assessment of bone metastases or lymph node metastases. Its short half-life reduces patient radiation exposure risks, and the widespread global availability of Tc-99m (due to its mature infrastructure) further enhances the convenience of clinical application. The drug was led in development by Progenics Pharmaceuticals, Inc., with its R&D journey exemplifying the synergistic effects of multi-party collaboration. Progenics initially discovered the targeting potential of PSMA and designed the molecular structure of Trofolastat. Subsequently, Lantheus Medical Imaging, Inc. (now part of Bracco Imaging) became a key partner, responsible for optimizing drug production, global registration, and commercial promotion, especially in the European and American markets. Additionally, the R&D team leveraged Progenics' technical accumulation in the PSMA field (such as the development experience of the therapeutic drug 177Lu-PSMA-617) to further validate the feasibility of PSMA targeting in diagnostics. Despite Progenics' acquisition by Bracco in 2023, the R&D team continued to optimize drug performance, ultimately leading to its first approval in the UK, filling the gap in PSMA-targeted diagnostic drugs. The R&D progress of Trofolastat has been rapid, entering Phase III clinical trials by 2025 and validating its diagnostic accuracy through key trials. On March 27, 2025, the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved it for the diagnosis of PSMA-positive prostate cancer, making it the first PSMA-targeted radiopharmaceutical diagnostic agent approved in Europe. The current indication focuses on the localization and staging of PSMA-positive prostate cancer, with potential future expansion to monitoring the recurrence of metastatic prostate cancer and assessing treatment effectiveness. Although similar drugs (such as Ga-68 PSMA-11) have been approved in the U.S., Trofolastat's widespread availability of Tc-99m (used in 90% of global nuclear medicine imaging) and longer imaging window (suitable for primary care hospitals) demonstrate significant market competitiveness. 3.Diazoxide Choline Diazoxide Choline (brand name: VYKAT XR) is a small-molecule chemical drug that acts as a potassium channel agonist, reducing appetite by modulating the function of potassium ion channels in cell membranes. Developed by Essentialis, Inc. and subsequently advanced to the clinical stage by Soleno Therapeutics, Inc., it was first approved in the United States on March 26, 2025, for the treatment of hyperphagia and Prader-Willi Syndrome (PWS). PWS is a genetic disorder where patients often experience extreme hunger and an increased risk of obesity due to hypothalamic dysfunction. Diazoxide Choline, by targeting the appetite regulation center, becomes the first drug to address the core pathological mechanisms of this disease. Its extended-release formulation (VYKAT XR) is designed to allow once-daily dosing, significantly improving patient adherence. The mechanism of action of Diazoxide Choline is based on the activation of potassium ions (K⁺) channels. The drug activates ATP-sensitive potassium channels (KATP), inhibiting the secretion of glucagon by pancreatic α-cells while modulating the hypothalamic appetite regulation pathway to reduce hunger and suppress binge eating behavior. In patients with Prader-Willi Syndrome, hypothalamic dysfunction leads to abnormally elevated ghrelin levels and defective leptin signaling, exacerbating uncontrolled appetite. Diazoxide Choline restores the hypothalamus's regulation of energy balance through potassium channel-mediated signaling pathways, thereby reducing the impulse to overeat. Additionally, the drug has no significant impact on insulin secretion, reducing the risk of side effects such as hypoglycemia and ensuring higher safety. The drug's development began with Essentialis, Inc., and was later taken over by Soleno Therapeutics to advance it to the clinical stage. During the R&D process, Diazoxide Choline received several special review designations from the FDA, including Fast Track status, Breakthrough Therapy designation, and Orphan Drug status (both in the U.S. and EU), highlighting its importance in treating the rare disease PWS. Additionally, the drug underwent priority review by the FDA, accelerating the approval process. Although initially explored for indications such as hypertriglyceridemia, its breakthrough efficacy in PWS became the core R&D direction. Phase III clinical trial data showed that Diazoxide Choline significantly reduced binge eating behavior, weight gain, and hospitalization rates in PWS patients. In the trial, patients receiving treatment experienced a reduction in hunger scores by over 50%, with no serious drug-related adverse events reported. After its first approval in March 2025, the indication focused on hyperphagia and Prader-Willi Syndrome, with potential future expansion to other hypothalamic dysfunction-related appetite disorders. Additionally, the R&D team is exploring its potential to improve cognitive function and behavioral symptoms in PWS patients, further enhancing the drug's comprehensive therapeutic value. 4. Suraxavir Marboxil Suraxavir Marboxil is a novel small-molecule antiviral drug jointly developed by Ginkgo Pharmaceutical in collaboration with Kerui and Qingfeng Pharmaceutical. It was approved for marketing in China on March 25, 2025, becoming the first broad-spectrum anti-influenza drug targeting both influenza A and B virus infections. Its mechanism of action involves targeting key proteins of the influenza virus (presumably neuraminidase or related targets), thereby inhibiting viral replication and release. This mechanism helps to shorten the duration of illness and reduce the risk of severe complications. The approval of Suraxavir Marboxil fills a critical gap in China's broad-spectrum anti-influenza drug market and holds significant value in addressing seasonal flu outbreaks and potential pandemic threats. Its formulation (likely oral) and convenient administration make it a valuable tool for influenza treatment and prevention. Suraxavir Marboxil’s antiviral mechanism is based on the inhibition of essential viral proteins. Influenza viruses rely on neuraminidase (NA) to release newly formed viral particles from host cells. This drug is believed to bind selectively and inhibit the activity of neuraminidase, thus preventing viral spread. Compared to traditional neuraminidase inhibitors (such as oseltamivir), Suraxavir Marboxil may offer broader antiviral coverage against both influenza A and B, whereas traditional drugs typically focus on influenza A. Additionally, its molecular structure has likely been optimized to enhance efficacy against drug-resistant strains and minimize side effects. Preclinical studies have demonstrated its rapid onset, strong antiviral activity, and low toxicity in both in vitro and animal models. Clinical trial data show that Suraxavir Marboxil significantly outperforms placebo in reducing the duration of influenza symptoms and lowering the incidence of complications (such as pneumonia), with proven efficacy against both influenza A and B viruses. It has exhibited a favorable safety profile, with no reports of serious drug-related adverse events, making it suitable for children, adults, and the elderly. The current approved indication focuses on influenza A and B infections, with potential future expansion to prophylactic use in high-risk populations (e.g., immunocompromised individuals or patients with chronic illnesses). Moreover, the development team is exploring its applicability in patients with impaired liver function to expand its coverage across broader patient populations. 5. Gepotidacin Gepotidacin is a novel small-molecule antibiotic developed by GlaxoSmithKline (GSK), which received its first approval in the United States on March 25, 2025. It is indicated for the treatment of bacterial infections caused by susceptible organisms, including urinary tract infections (such as acute cystitis and gonococcal urethritis). Gepotidacin features a unique mechanism of action—dual inhibition of bacterial DNA gyrase and topoisomerase IV—which blocks bacterial DNA replication and repair, thereby rapidly eliminating pathogens. As the first approved antibiotic in the triazolopyrimidine class, Gepotidacin addresses treatment gaps caused by antibiotic resistance to traditional fluoroquinolones, especially against resistant Gram-positive and Gram-negative pathogens. Unlike conventional fluoroquinolones (e.g., levofloxacin), Gepotidacin targets both DNA gyrase (primarily in Gram-negative bacteria) and topoisomerase IV (primarily in Gram-positive bacteria), providing broad-spectrum antibacterial activity. This dual-targeted mechanism significantly reduces the risk of resistance, as bacteria must simultaneously mutate both targets to develop resistance—an event with very low probability. Preclinical studies have shown that Gepotidacin is active against multidrug-resistant organisms (such as ESBL-producing E. coli and MRSA) and lacks cross-resistance with existing antibiotics, offering a promising option for resistant infections. Its rapid bactericidal activity—reducing bacterial load within hours—also shortens the course of infection compared to traditional antibiotics. Gepotidacin's development was driven by GSK’s urgent need for novel antibiotics to address the global antibiotic resistance crisis. While no special regulatory designations (e.g., FDA Fast Track or Orphan Drug status) have been mentioned, its timely approval in 2025 was supported by positive Phase III clinical trial data and the FDA’s commitment to fostering innovation in anti-infective drug development. GSK advanced clinical trials in collaboration with global partners (e.g., Atos SE in Europe), evaluating its potential in treating complex infections, such as complicated skin and soft tissue infections. Furthermore, the drug’s oral formulation and favorable tolerability profile (with fewer gastrointestinal side effects) enhance its clinical utility. Phase III trial results indicated that Gepotidacin's efficacy in treating acute bacterial cystitis was comparable to that of levofloxacin, with better tolerability. Although its current approved indication focuses on urinary tract infections, its broad-spectrum activity suggests potential future use in complicated urinary tract infections, gonorrhea, and skin and soft tissue infections. GSK is also investigating its use in treating multidrug-resistant infections—such as carbapenem-resistant Enterobacteriaceae (CRE)—to address the growing challenge of nosocomial infections. In the future, Gepotidacin could become the preferred alternative to traditional fluoroquinolones, particularly in regions with high rates of antibiotic resistance. 6. Encofosbuvir Encofosbuvir is a novel small-molecule direct-acting antiviral (DAA) developed jointly by Sunshine Lake Pharma and YiChang HEC ChangJiang Pharmaceutical. On March 25, 2025, it was approved in China as the first domestically produced pan-genotypic treatment for hepatitis C, indicated for the treatment of chronic hepatitis C virus (HCV) infection. The drug targets a key step in the HCV lifecycle, exerting potent antiviral effects by inhibiting viral RNA replication. Encofosbuvir specifically targets the HCV NS5B RNA-dependent RNA polymerase, a core enzyme involved in viral replication. By competitively binding to the active site of NS5B polymerase, it inhibits the elongation of viral RNA chains, thereby blocking viral RNA synthesis and assembly. As a nucleotide analog prodrug, Encofosbuvir is metabolized in vivo into its active form, which is incorporated into the viral RNA chain, resulting in premature chain termination and complete suppression of viral replication. Its pan-genotypic activity stems from its broad inhibitory effect across all major HCV genotypes (1–6), and it retains efficacy against common resistance-associated substitutions (e.g., Y93H). Compared to traditional interferon-based regimens, Encofosbuvir offers a significantly higher sustained virologic response (SVR) rate and lower resistance barrier, greatly improving treatment success while reducing adverse effects. Encofosbuvir was developed from Sunshine Lake Pharma’s antiviral drug platform, with clinical development and manufacturing supported by Humanwell Healthcare. During its development, the team optimized the drug design to align with the epidemiological characteristics of hepatitis C in China (primarily genotype 1b), and efficacy and safety were validated through multicenter Phase III clinical trials. Although no special review designations were noted, the drug’s swift approval in 2025 reflects regulatory support for domestic innovation in China. Clinical trials demonstrated that Encofosbuvir, either as monotherapy or in combination with ribavirin (RBV), achieved SVR12 rates exceeding 95% in patients with chronic hepatitis C, including those with cirrhosis. It showed a favorable safety profile, with common adverse events limited to mild fatigue or headache and no reports of serious hepatotoxicity or hematological toxicity. Currently approved for pan-genotypic chronic hepatitis C, future indications may include acute HCV infection and post-liver transplantation recurrence. Additionally, fixed-dose combinations with novel antivirals, such as NS3/4A protease inhibitors, are under exploration to further simplify treatment regimens and enhance adherence. The launch of Encofosbuvir not only provides Chinese hepatitis C patients with a cost-effective therapeutic option but also represents a major milestone in the localization of global antiviral drug development. Its pan-genotypic coverage and short-course regimen can significantly improve treatment accessibility, particularly in regions with limited healthcare resources. With its broader application, China is well-positioned to accelerate progress toward the World Health Organization (WHO)’s goal of eliminating viral hepatitis as a public health threat by 2030. Moreover, the successful development of Encofosbuvir offers technical insights for antiviral drug development targeting other RNA viruses such as hepatitis B and HIV, highlighting China's growing innovation capacity in the antiviral therapeutics sector. 7. Influenza Vaccine (Split Virion, Quadrivalent) The Influenza Vaccine (split virion, quadrivalent), developed by Anhui Longcom Biologic Pharmacy, is a multivalent prophylactic vaccine approved in China on March 18, 2025, for the prevention of influenza virus infection. Utilizing a virus-splitting technique, the vaccine separates influenza viruses into key antigenic components (such as hemagglutinin and neuraminidase), removes viral nucleic acids, and retains immunogenic elements to stimulate an immune response. It induces antibody production against influenza A subtypes H1N1 and H3N2, as well as B lineages Victoria and Yamagata. As a quadrivalent formulation, it offers broader coverage than trivalent vaccines, effectively addressing the high mutation rates of circulating influenza strains, particularly the predominant seasonal strains. Its approval fills a market gap for high-end domestically produced influenza vaccines in China, providing an affordable and effective option for seasonal influenza prevention. The vaccine's mechanism of action involves antigen presentation and activation of humoral immunity. The split virion fragments, especially hemagglutinin proteins, are recognized by the immune system and presented by dendritic cells to T lymphocytes, which in turn activate B cells to produce specific IgG antibodies. These antibodies bind to hemagglutinin on the virus surface, blocking receptor binding to host cells and marking viral particles for macrophage clearance. The vaccine also induces immune memory, offering long-term protection and reducing the risk of reinfection. The quadrivalent design, covering two A and two B influenza strains, significantly enhances cross-protection against variant strains, particularly in high-risk populations such as children, the elderly, and individuals with chronic illnesses. The splitting process ensures vaccine safety by eliminating the risk of infection associated with whole-virus vaccines, while preserving antigenic epitopes for robust immune responses. Due to the segmented genome structure of influenza viruses, frequent mutations occur annually, leading to hundreds of millions of global infections and hundreds of thousands of deaths. As a populous nation, China faces considerable challenges in influenza control. The mismatch between the traditional vaccine development cycle (approximately 6–8 months) and the rapid mutation rate of the virus highlights the urgent need for broad-spectrum, efficient vaccines. Anhui Longcom Biologic Pharmacy's quadrivalent influenza vaccine was developed in alignment with China's influenza epidemiology. By dynamically monitoring strain variations and selecting WHO-recommended dominant strains for seasonal formulation, the vaccine ensures optimal protection. Clinical trial data show that the vaccine achieves a seroprotection rate (antibody titer ≥40) exceeding 90% in both adults and children, providing significant protection against covered influenza strains. Reported adverse reactions are mostly mild, including injection site pain and low-grade fever, with no reports of severe allergic events. The current approved indication is prevention of influenza virus infection for individuals aged six months and older, with strong recommendations for high-risk groups such as healthcare workers, the elderly, and people with chronic conditions. Future directions may include emergency use during outbreaks of specific variant strains, or co-administration with COVID-19 vaccines to address co-infection risks. Additionally, the development team is investigating the vaccine's immunogenicity in immunocompromised patients to optimize vaccination strategies. 8. Ivarmacitinib Sulfate Ivarmacitinib sulfate is a selective Janus kinase (JAK) inhibitor jointly developed by Jiangsu Hengrui Pharmaceuticals and Reistone Biopharma. It was approved for marketing in China on March 18, 2025, for the treatment of ankylosing spondylitis. The drug functions by targeting and inhibiting JAK kinases and their downstream signaling pathways, thereby blocking the transmission of pro-inflammatory cytokines such as IL-6 and IL-23. This suppression mitigates the inflammatory responses triggered by excessive immune system activation. As the first domestically developed JAK inhibitor in China, Ivarmacitinib received accelerated approval through “breakthrough therapy” designation, addressing a significant unmet need in targeted therapy for ankylosing spondylitis. It offers a novel treatment option, especially for patients who are unresponsive or intolerant to traditional therapies like TNF-α inhibitors. The drug is also being investigated for other autoimmune conditions such as atopic dermatitis, alopecia areata, and ulcerative colitis, demonstrating broad clinical potential. The mechanism of action of Ivarmacitinib centers on inhibition of the JAK-STAT signaling pathway. JAK kinases are key mediators in cytokine signaling (e.g., IL-6, IL-17, IL-23), which are overexpressed in inflammatory autoimmune diseases such as ankylosing spondylitis and psoriatic arthritis. By selectively inhibiting JAK1/3 isoforms, Ivarmacitinib blocks signal transduction following cytokine-receptor binding, reduces the release of pro-inflammatory cytokines, and alleviates joint inflammation, skin damage, and systemic immune responses. During development, the research team optimized the molecular structure to enhance isoform selectivity, reduce off-target effects, and improve oral bioavailability, making it suitable for long-term treatment. As a domestically developed innovative drug, Ivarmacitinib responds to the urgent demand for effective and safe targeted therapies for autoimmune diseases. Supported by Hengrui’s robust R&D capabilities, the drug was rapidly translated from laboratory research to clinical application. Phase III clinical trial results showed that Ivarmacitinib significantly improved joint pain, morning stiffness, and functional impairment in patients with ankylosing spondylitis, with a favorable safety profile (the main adverse effects being mild elevation of liver enzymes and headache). Its currently approved indication is ankylosing spondylitis, with potential future indications including moderate-to-severe atopic dermatitis (now in Phase III), alopecia areata (Phase II data showing >50% hair regrowth rate), and ulcerative colitis. The research team is also exploring its efficacy in psoriatic arthritis and non-segmental vitiligo, aiming for integrated management of multisystem diseases through immune modulation. Notably, after early collaboration with Arcutis Biotherapeutics ended, Hengrui continued clinical development independently, underscoring its leadership in domestic innovation. Compared with existing JAK inhibitors, Ivarmacitinib offers several differentiating advantages: ·Higher JAK isoform selectivity, minimizing inhibition of JAK2 (which is involved in hematopoiesis) and thereby reducing risks of thrombosis and anemia; ·Longer half-life (~24 hours), allowing for once-daily dosing and improved patient adherence; ·Localized anti-inflammatory effect, targeting affected tissues (e.g., skin, joints) while minimizing systemic immunosuppressive side effects.These features make Ivarmacitinib particularly competitive in balancing efficacy and safety, especially in the long-term management of chronic inflammatory diseases. 9. Teprotumumab N01 Teprotumumab N01 is a monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), independently developed by Innovent Biologics. It was approved in China on March 11, 2025, for the treatment of moderate-to-severe Graves' ophthalmopathy (GO). By inhibiting the IGF-1R signaling pathway, the drug reduces orbital inflammation, fibrosis, and muscle edema, thereby improving symptoms such as proptosis, diplopia, and visual impairment. Graves' ophthalmopathy is an autoimmune thyroid-associated eye disease characterized by the activation of the IGF-1/IGF-1R pathway, which triggers downstream signaling cascades (e.g., PI3K/Akt/mTOR), leading to orbital fibroblast proliferation, collagen deposition, and cytokine release. Teprotumumab N01 binds with high affinity to the α-subunit of IGF-1R, blocking the activation of the IGF-1 pathway, suppressing fibroblast activation and inflammation, and reducing orbital tissue swelling and fibrosis. The research team enhanced the drug’s specificity and safety by optimizing the antibody structure, including modifications to the Fc region to reduce immunogenicity. Approval was based on strong Phase III trial results: compared to placebo, patients receiving Teprotumumab experienced an average reduction of 3.3 mm in proptosis (P<0.001), and 80% showed symptom improvement (e.g., reduced diplopia, stabilized vision). Adverse events were primarily mild injection site reactions. Teprotumumab N01 is indicated for patients with moderate-to-severe active Graves' ophthalmopathy (e.g., Clinical Activity Score ≥3) who are either intolerant or unresponsive to corticosteroids. Its differentiated advantages are threefold: 1.Precision targeting of the IGF-1R pathway: Specifically blocks IGF-1R activation, directly inhibiting abnormal proliferation of orbital fibroblasts and associated inflammation, thus reducing fibrosis and edema. This avoids systemic side effects of corticosteroids, such as osteoporosis, blood glucose fluctuations, and immunosuppression. 2.Robust and sustained efficacy: Phase III data showed a 3.3 mm average reduction in proptosis after six months, with marked improvement in diplopia and orbital pressure. These benefits were maintained over a 12-month follow-up period and significantly outperformed placebo. 3.Good safety and convenient administration: No severe immune-related adverse events (e.g., neutropenia or liver enzyme abnormalities) were observed; only mild injection site reactions occurred. The drug is administered via intravenous infusion, suitable for outpatient treatment and enhancing patient adherence. Looking forward, Teprotumumab N01 may be used preventatively in early or mild GO to delay disease progression and could be explored in combination with radiotherapy or surgery to optimize outcomes in severe cases. This would further expand its clinical value. The approval of Teprotumumab N01 marks a breakthrough in targeted therapy for rare diseases in China. Its development process—from antibody screening to clinical validation—demonstrates Innovent’s comprehensive capabilities in biologic innovation. Currently, the only similar product worldwide is Lilly’s Teprotumumab, approved by the U.S. FDA in 2019. However, Teprotumumab N01, through differentiated design (e.g., longer half-life enabling dosing every three weeks) and localized clinical data, significantly reduces treatment costs and benefits more Chinese patients. Furthermore, its development model provides a reference for targeted therapies in other autoimmune-related ophthalmic diseases (e.g., dry eye disease associated with Sjögren’s syndrome), enhancing China’s global competitiveness in ophthalmologic biologics. 4o 10. Denosumab-bnhtDenosumab-bnht is a biosimilar of denosumab developed by Germany-based Fresenius Kabi, approved in the United States on March 25, 2025, for the treatment of various skeletal-related disorders. As a monoclonal antibody biosimilar, it functions by targeting and inhibiting the receptor activator of nuclear factor kappa-Β ligand (RANKL), mirroring the mechanism of the reference product. By optimizing the manufacturing process, it offers a more cost-effective treatment option for patients. Structurally, functionally, and in terms of safety and efficacy, Denosumab-bnht is highly consistent with the originator drug, and is indicated for conditions such as osteoporosis, giant cell tumor of bone (GCTB), glucocorticoid-induced osteoporosis, hypercalcemia of malignancy, and multiple myeloma, particularly in cases of bone density loss or skeletal damage caused by abnormal bone metabolism. The drug works by blocking the interaction between RANKL and its receptor RANK on the surface of osteoclast precursors and mature osteoclasts. This inhibition suppresses the differentiation, activity, and survival of osteoclasts, thereby reducing bone resorption and maintaining bone density. This mechanism significantly lowers fracture risk in osteoporosis patients, particularly postmenopausal women and cancer patients at risk of bone metastases. Moreover, by modulating bone metabolism, it helps manage the progression of GCTB and alleviate tumor-related bone destruction and pain. As a biosimilar, Denosumab-bnht demonstrates equivalence to the originator in pharmacokinetics, immunogenicity, and clinical efficacy, while simplified manufacturing enhances accessibility. In clinical practice, Denosumab-bnht has broad indications: for osteoporosis, a subcutaneous injection every six months significantly improves patient compliance and reduces the risk of vertebral, non-vertebral, and hip fractures; in GCTB, it can reduce tumor size and relieve bone pain; for emergency treatment of malignancy-associated hypercalcemia, a single injection rapidly lowers serum calcium levels and improves prognosis. Additionally, the drug can prevent skeletal-related fractures in patients with multiple myeloma or solid tumors and reduce the need for radiation therapy. Phase III clinical trials have shown no statistically significant difference in efficacy compared to the originator, with a favorable safety profile. Common adverse reactions include injection site reactions and hypocalcemia, while severe allergic reactions are rare. From a development and market positioning perspective, Denosumab-bnht followed a rigorous biosimilar development pathway, including structural characterization, animal studies, and clinical comparison trials to ensure interchangeability with the reference product. Fresenius Kabi, leveraging its experience in the biosimilar field, optimized antibody production to reduce costs and provide a cost-effective option for both patients and healthcare systems. Its approval marks further expansion of biosimilars in the treatment of skeletal disorders, and in the U.S. market, its pricing advantage is expected to accelerate substitution of the originator drug, offering critical therapeutic opportunities for underserved populations, including those in developing countries. 11. Liraglutide BiosimilarThe liraglutide biosimilar developed by Zhuhai United Pharmaceutical is the first GLP-1 receptor agonist biosimilar approved in China. It was granted market approval on March 18, 2025, for the treatment of type 2 diabetes. Jointly developed by Zhuhai United Pharmaceutical and its subsidiaries, this product contains liraglutide, a recombinant glucagon-like peptide-1 (GLP-1) analog highly homologous to human GLP-1, which lowers blood glucose by mimicking endogenous GLP-1's physiological effects. As a biosimilar, it exhibits high structural, functional, safety, and efficacy similarity to the reference drug (Novo Nordisk’s Victoza), while optimized production processes and cost control provide a more affordable treatment option—particularly beneficial for China's large type 2 diabetes population. The mechanism of action centers on GLP-1 receptor activation: it stimulates glucose-dependent insulin secretion from pancreatic β-cells, suppresses glucagon secretion from α-cells to reduce hepatic glucose output, delays gastric emptying, and increases satiety, thereby lowering both blood glucose levels and body weight. With a half-life of 12–14 hours, it supports once-daily subcutaneous administration. Its fatty acid side chain modification reduces immunogenicity and lowers the risk of allergic reactions. These characteristics result in comprehensive benefits for glycemic control, cardiovascular protection, and weight management, making it suitable for patients inadequately managed by oral antidiabetic drugs or those with insulin resistance. Clinically, the liraglutide biosimilar offers multiple advantages in managing type 2 diabetes. Phase III clinical trials showed no statistically significant difference in HbA1c reduction compared to the originator drug, with average reductions ranging from 1.5% to 2.0%, and significantly lower risk of hypoglycemia due to its glucose-dependent mechanism. In addition, it promotes weight loss (average reduction of 3%–5%) and offers cardiovascular benefits by improving lipid profiles and slowing the progression of atherosclerosis. Regarding safety, the most common adverse events are mild gastrointestinal reactions (e.g., nausea, diarrhea), which tend to decrease over time; no serious immunogenic events were observed. Looking ahead, the clinical use of this biosimilar may expand to other metabolic syndrome-related conditions, such as obesity and non-alcoholic fatty liver disease (NAFLD). Long-term cardiovascular benefits observed in the originator drug’s post-marketing studies could also support its positioning as a preferred option for diabetic patients with elevated cardiovascular risk. Conclusion The global drug approvals in March 2025 highlight three trends in biomedicine: the clinical translation of gene and RNA therapies, breakthroughs in antibiotics and antivirals, and the broader accessibility of biosimilars and vaccines. In gene therapy, Fitusiran became the world’s first RNAi treatment to offer once-monthly management for hemophilia by suppressing antithrombin. Novel treatments such as Teprotumumab N01 (an IGF-1R monoclonal antibody) and Encofosbuvir (a pan-genotypic DAA for hepatitis C) target precise signaling pathways or viral replication mechanisms, offering breakthroughs for rare diseases and chronic infections. In the antibiotic field, Suraxavir Marboxil emerged as a novel weapon against resistant bacteria by dual inhibition of DNA enzymes, while Mashurashave, China’s first broad-spectrum influenza drug, addressed resistance and treatment complexity with its single-dose regimen. On the public health front, Denosumab-bnht and the liraglutide biosimilar enhance treatment accessibility for osteoporosis and diabetes through cost reductions. Meanwhile, quadrivalent influenza vaccines employing split-virus technology improve coverage against multiple viral subtypes, strengthening public health preparedness. The approvals of Diazoxide Choline (for Prader-Willi syndrome) and Ivarmacitinib (a JAK inhibitor for ankylosing spondylitis) further extend the application of targeted therapies in metabolic and autoimmune disorders. Finally, the innovation and global partnerships of Chinese pharmaceutical companies—such as Hengrui and Innovent Biologics—are accelerating the integration of global R&D resources. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

LAKE ZURICH, IL, USA I March 27, 2025 I Fresenius announced that the Biologics License Application (BLA) for the denosumab biosimilars Conexxence ® (denosumab-bnht) and Bomyntra ® (denosumab-bnht) of its operating company Fresenius Kabi, has been approved by the U.S. Food and Drug Administration (FDA). These denosumab biosimilars are approved for all indications of the reference products: Prolia ® (denosumab) and Xgeva ® (denosumab), respectively. In addition, the Fresenius operating company has reached a global settlement with Amgen concerning its denosumab biosimilars. “We are pleased to have reached a global settlement with Amgen for our denosumab biosimilar candidates and to continue to provide patients around the globe with access to high-quality biological medicines. This marks our sixth FDA biosimilar approval, expanding our portfolio to provide more affordable therapies to patients in the U.S.,” said Dr. Sang Jin Pak, President Fresenius Kabi Biopharma. The FDA approval is based on comprehensive analytical development and similarity assessment supported by two comparative clinical studies: a pharmacokinetic, pharmacodynamic, and immunogenicity study in healthy volunteers, and an efficacy, pharmacodynamic, safety, and immunogenicity study in women with postmenopausal osteoporosis. About Conexxence ® (denosumab-bnht) and Bomyntra ® (denosumab-bnht) Conexxence ® (denosumab-bnht) is approved for use in various adult patient populations at high risk for fractures, including those with osteoporosis, individuals undergoing certain cancer treatments that affect bone density, and patients receiving long-term glucocorticoid therapy. In the US Conexxence ® (denosumab-bnht) is a black box warning product and includes a Risk Evaluation and Mitigation Strategy (REMS) program , which aims to educate prescribers and patients about the risk of severe hypocalcemia in patients with advanced chronic kidney disease, including those on dialysis. Conexxence ® (denosumab-bnht) is contraindicated during pregnancy and in case of known hypersensitivity to denosumab products. For more information aboutConexxence ® please see theimportant safety information and full prescribing information for the U.S. here . Bomyntra ® (denosumab-bnht) is approved for use to prevent skeletal-related events in adult patients with multiple myeloma and bone metastases from solid tumors. It is also used to treat hypercalcemia of malignancy that is refractory to bisphosphonate therapy and giant cell tumor of bone in adults and skeletally mature adolescents. Bomyntra ® (denosumab-bnht) is contraindicated in case of hypocalcemia and known hypersensitivity to denosumab products. For more information aboutBomyntra ® please see theimportant safety information and full prescribing information for the U.S. here . About Fresenius Kabi As a global healthcare company, Fresenius Kabi is Committed to Life. The company’s products, technologies, and services are used for the therapy and care of patients with critical and chronic conditions. With more than 43,000 employees and present in more than 100 countries, Fresenius Kabi’s expansive product portfolio focuses on providing access to high-quality and lifesaving medicines and technologies. In Biopharma, Fresenius Kabi offers cutting-edge biosimilars for autoimmune diseases and oncology. With leading market positions in Clinical Nutrition, a broad portfolio of enteral and parenteral products makes a distinct difference in patients’ nutritional status – notably as the only corporation offering both product groups. In MedTech, the company provides vital infusion pumps, cell and gene therapy devices, disposables, and more. Fresenius Kabi is a global leader in supplying blood collection bags and devices, supporting blood banks and health care facilities worldwide. The company’s I.V. Generics and Fluids for infusion therapy help save millions of lives every year, in emergency medicine, surgery, oncology, and intensive care. Fresenius Kabi takes a holistic approach to health care and uniquely combines experience, expertise, innovation, and dedication – making a difference in the lives of 450 million patients annually. With Vision 2026, as part of the #FutureFresenius strategy, the company is developing, producing, and selling new products and technologies and aspires to expand its position as a leading global provider of therapies, improve patient care, generate sustainable value for stakeholders – shaping the future of health care. Fresenius Kabi is an operating company of the Fresenius Group, founded in 1912, along with Helios and Quirónsalud. As ONE team, the companies in the Fresenius Group are committed to providing lifesaving and life-changing health care solutions on a global scale. For more information, please visit www.fresenius-kabi.com and www.fresenius-kabi.com/us in the United States. To learn about U.S. career opportunities at Fresenius Kabi, visit us at www.fresenius-kabi.com/us/join-us and follow us on LinkedIn and Facebook . SOURCE: Fresenius Kabi