ADG-106

DUBLIN--( BUSINESS WIRE )--The "CD137 Antibodies Clinical Trials & Market Opportunity Insight 2027" report has been added to ResearchAndMarkets.com's offering. CD137, also known as 4-1BB, has emerged as a promising target for cancer immunotherapy in recent years. The potential of CD137-targeted therapies lies in their ability to stimulate and expand cytotoxic T cells leading to improved tumor cell killing and long-lasting immune memory. As a result, the field has gained attention from researchers and pharmaceutical companies alike, with several research publications hinting at a promising future for this cancer therapeutic approach. Moreover, data emerging from early clinical trials have already begun demonstrating therapeutic benefits, providing real-time validation of CD137-targeted drug development. With no licensed medications currently on the market, CD137-targeted therapies are still in their infancy. Nonetheless, there is an abundance of candidates in the pipeline in different phases of clinical development, with phase 2 being the highest. Several major pharmaceutical companies and biotech firms, including BioNTech, Genmab, Adagene, and Shanghai Henlius Biotech, are actively pursuing drug development programs after recognizing the potential of this target. This presents a significant opportunity for both established players and newcomers in the field of immuno-oncology. The ability of CD137-targeted treatments to get past some of the drawbacks of existing immunotherapies, like immune checkpoint inhibitors, is one of their main advantages. Although checkpoint inhibitors have fundamentally altered the way that cancer is treated, only a small percentage of patients and cancer types respond well to them. The range of individuals who can benefit from immunotherapy may be increased by CD137 agonists, which may enhance or supplement the effectiveness of these currently available treatments. The most advanced CD137-targeted therapies in clinical development are agonistic antibodies. The intended effect of these compounds is to stimulate T cell survival, proliferation, and effector activities via activating CD137 signaling. Regarding anti-tumor effectiveness and safety characteristics, early clinical trials have produced encouraging results. YH004, ADG106, ADG206, and ATOR-1017 are a few CD137 agonistic antibodies that are now undergoing clinical trials. There have been challenges, nevertheless, such as dose-limiting hepatotoxicity seen in certain candidates. Due to this, other strategies are being investigated that might provide better safety and efficacy profiles, such as bispecific antibodies and tailored ligands. Combining CD137-targeted therapies with other immunomodulatory drugs is one highly intriguing area of investigation. CD137 agonists have been shown to have synergistic benefits when paired with checkpoint inhibitors, chemotherapy, targeted therapy, or even radiation therapy, according to preclinical research and early phase clinical evidence. These combination approaches may result in more potent and more persistent anti-tumor responses, which would fulfill the unmet demand for efficient treatments for malignancies that are challenging to treat. The market potential for effective CD137 antibodies is significant, considering the wide range of applications of CD137-targeted treatments in cancer. New and efficient treatment modalities are highly sought after, as the global market for cancer immunotherapy is expected to grow to many billions of dollars in the next several years. A sizeable portion of this market may be taken up by CD137-targeted treatments, especially if they show greater efficacy and can treat conditions where immunotherapies have not been very successful. Furthermore, the versatility of CD137 as a target extends beyond oncology. Recent studies point to possible uses in transplantation, autoimmune diseases, inflammatory disorders, and infectious diseases. This wide-ranging therapeutic potential could open up additional market opportunities for drug developers, willing to explore these indications. Despite the promising outlook, several challenges need to be addressed in the development of CD137-targeted therapies. These include optimizing dosing regimens to balance efficacy and safety, identifying predictive biomarkers for patient section, and developing strategies to overcome potential resistance mechanisms. Overcoming these hurdles will be crucial for the successful translation of CD137-targeted therapies from bench to bedside. In conclusion, CD137-targeted therapies represent a significant opportunity to transform treatment of cancer and various other diseases involving the immune system. The increasing comprehension of CD137 biology, in conjunction with developments in antibody engineering and combination strategies, offers a robust basis for novelty in this domain. CD137-targeted therapies have the potential to fill a significant gap in the medical community and gain a significant portion of the cancer immunotherapies market, which presents a strong case for development and innovation. CD137 Antibodies Clinical Trials & Market Opportunity Insight 2027 Report Highlights: Currently No Drug Commercially Available In Market More Than 80 Drugs In Clinical Trials Highest Clinical Trials Phase: Phase II (7 Drugs) CD137 Drugs Market Opportunity In Initial 24 Months Of Launch: > US$ 400 Million Global & Regional Trends (Clinical & Commercial) CD137 Inhibitors Clinical Trials Insight By Company, Country, Indication & Phase CD137 Therapeutic Approaches By Antibodies Classification Role Of CD137 & Clinical Progress By Indication Key Topics Covered: 1. Brief Introduction To CD137 1.1 Clinical Overview 1.2 Biological History Of CD137 1.3 CD137 Hosting An Era Of Agonists Over Antagonists 1.4 Bi-Directional Signaling In CD137 2. Global CD137 Antibody Market Outlook 2.1 Current Research & Market Scenario 2.2 Future Commercialization Opportunities 3. CD137 Antibody Clinical Developments by Regions 3.1 China 3.2 US 3.3 South Korea 3.4 Europe 3.5 Australia 4. Role Of CD137 & Clinical Progress By Indication 4.1 Cancer 4.1.1 Leukemia 4.1.2 Lymphoma 4.1.3 Lung Cancer 4.1.4 Melanoma 4.1.5 Breast Cancer 4.1.6 Colorectal Cancer 4.2 Autoimmune & Inflammatory Diseases 4.3 Microbial Infections 4.3.1 Viral Infections 4.3.2 Bacterial infections 5. Global CD137 Antibodies Clinical Trials Overview 5.1 By Company 5.2 By Country 5.3 By Indication 5.4 By Phase 5.5 By Patient Segment 6. CD137 Inhibitors Clinical Trials Insight By Company, Country, Indication & Phase 6.1 Research 6.2 Preclinical 6.3 Phase I 6.4 Phase I/II 6.5 Phase II 7. CD137 Targeting Proprietary Technology Platforms By Companies 8. CD137 Therapeutic Approaches By Antibodies Classification 8.1 Monoclonal Antibody Based Strategies 8.2 Bispecific Antibody Centered Approaches 8.3 Trispecific Antibody Established Strategies 8.4 Tetraspecific Antibody Strategies 9. Combination Therapies With CD137 Antibodies 10. Competitive Landscape ABL Bio Adagene Alligator Bioscience BeiGene Bicycle Therapeutics BioNTech Biotheus Crescendo Biologics Eutilex F-star Therapeutics Genmab I-MAB Biopharma Lyvgen Biopharma OriCell Therapeutics Pieris Pharmaceuticals Shanghai Henlius Biotech Sichuan Baili Pharmaceutical SystImmune For more information about this report visit https://www.researchandmarkets.com/r/uh1uil About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

T-cell immune responses play a vital role in the control of tumors. To induce robust and durable T-cell immune responses, the initial requirement is a signal induced by T-cell receptor (TCR) activation (Signal 1). Signal 1 is antigen-specific and it is achieved via the interaction between the T-cell receptor and the peptide-major histocompatibility complex (MHC) on the antigen-presenting cell (APC). However, Signal 1 alone is not sufficient to effectively activate T-cell immune responses, and a sufficient co-stimulatory signal (Signal 2) is required. Unlike Signal 1, Signal 2 is not antigen-specific. Signal 2 is achieved through the interaction between the co-stimulatory signal molecules expressed on APCs and T cells. Costimulatory signals are necessary for T-cell proliferation, differentiation, and survival. Without costimulatory signals, there may be an unresponsive/low response T cells, cell death, or the emergence of immune tolerance. Common co-stimulatory molecule protein families include the IgSF (Immunoglobulin Superfamily), TNRSF (Tumor Necrosis Factor Receptor Superfamily), in addition to others derived from the TIM family, CD2/SLAM family of costimulatory factors. Due to the critical role of costimulatory factors in T-cell immune activation, they have been of particular interest in the field of tumor therapy. 4-1BB4-1BB (also known as CD137 or TNFRSF9) was first discovered in 1989 and is a critical co-stimulation receptor on T cells and other immune cells. It is a member of the TNRSF protein family mentioned earlier. In 1997, Melero and colleagues found that a monoclonal antibody against 4-1BB was able to induce anti-tumour activity in T cells in mice. The main effects of 4-1BB on T cell activation include cell proliferation, cytokine release, cytotoxicity, and the formation of long-term immune memory, among others. Most of T cell activation occurs in CD8+ T cells. Two second-generation CAR-T cell therapies, Kymriah (Novartis) and CARVYKTI (Johnson&Johnson), which have been approved by the FDA, utilise 4-1BB as their co-stimulation domain. Other second-generation CAR-T therapies use CD28 as their co-stimulatory domain. Although both have shown similar tumour control rates in cancer patients, some differences were found: CD28 appears to have a higher cytokine release effect and can better promote T cell proliferation, but it also has a higher risk of neurotoxicity, while 4-1BB can foster longer-term T cell persistence. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs, indications, organizations, clinical trials, clinical results, and drug patents related to this target. 4-1BB is a glycosylated type-I membrane protein. It has four functional domains (known as "CRD", cysteine-rich pseudo repeats domain). The 4-1BB ligand (4-1BBL) is the binding partner of 4-1BB, which is generally expressed on the cell surface as a homotrimeric complex. Upon antigen stimulation, effective binding between 4-1BB and 4-1BBL can activate rapid receptor activation. For optimal co-stimulation (signal 2), 4-1BB needs to cluster on the cell surface. The Application of 4-1BB in Antibody Drug DevelopmentThe First Generation of 4-1BB Agonist Drugs The clinical development of 4-1BB agonist antibodies began in 2005 with the antibody drug urelumab (BMS-663513) created by Bristol-Myers Squibb (BMS). Urelumab is a humanized anti-4-1BB IgG4 subtype antibody. The early development data was promising, but there were two serious adverse events due to hepatic toxicity. Subsequent research found that while the drug was effective, its potency was very limited when administered at a safe dose (0.1 mg/kg). The second 4-1BB antibody drug developed was Pfizer's utomilumab (PF-05082566). The antibody drug is a fully human IgG2 subtype antibody and entered clinical trials in 2011. Although it did not demonstrate the safety issues seen in urelumab, its effectiveness (whether used alone or in combination with rituximab) was very limited, leading to the discontinuation of its clinical development. Urelumab and utomilumab, as the first generation of 4-1BB antibodies, displayed different agonistic activities and liver toxicities. These differences are currently thought to be due to differences in the Fc effector functions and epitope binding of these two molecules. The Fc effector function, particularly binding to FcγRIIB, is generally believed to be associated with liver toxicity (FcγRIIB cross-linking in the liver). As an IgG4 subtype, urelumab has stronger FcγRIIB binding, which is likely why it differs in liver toxicity from utomilumab (IgG2 subtype). The epitope binding is another reason for the different activities between urelumab and utomilumab. Urelumab and 4-1BB bind through an epitope on CRD1, which does not interfere with the binding of 4-1BB to its natural ligand. Utomilumab binds to 4-1BB through epitopes on CRD2 and CRD3. This binding method results in a large amount of endogenous 4-1BB ligand competing with utomilumab for binding to the 4-1BB receptor, limiting the activity of 4-1BB receptor clustering (which promotes the agonist activity of 4-1BB). This explains why urelumab (which does not affect 4-1BB receptor clustering) has higher agonist activity than utomilumab (which does affect 4-1BB receptor clustering). Second Generation 4-1BB Agonist Drugs The mediocre performance of Urelumab and Utomilumab in clinical trials did not douse the interest of many pharmaceutical companies in further exploring the 4-1BB target. Since the beginning of 2017 to the present, more than 40 4-1BB agonist drugs have entered clinical trials. Although the clinical trials of 4-1BB drugs temporarily declined in 2020 due to the COVID-19 pandemic, they showed a strong rebound afterwards. There may be more and more 4-1BB agonist drugs entering the clinic in the future, as many pharmaceutical/biotech companies are actively conducting preclinical research on 4-1BB drugs. The 4-1BB drugs that appeared after Urelumab and Utomilumab are categorized as the second-generation 4-1BB agonist drugs in this article. The second-generation 4-1BB agonist drugs mainly fall into two categories: IgG type (mono-antibody structure) and bi/multi-antibody 4-1BB agonist drugs. The mechanism of action of the IgG type second-generation 4-1BB agonist drugs has some consistency with the first-generation drugs (Urelumab and Utomilumab): they mostly rely on the cross-linking effect of Fcγ receptors, but their binding epitopes have been modified compared to the first generation. For example, the drug ADG106 developed by Suzhou Tyvance Biotech, also adopts the IgG4 subtype like Urelumab, but it does not bind to Urelumab's epitope CRD1. The concept behind this design is to have the drug be effective while reducing its toxic side effects, achieving a more precise regulation of the balance between effectiveness and safety (“sweet point” of functionality). The second type of second-generation 4-1BB agonist drugs are bi/multi-antibody agonist drugs. These drugs bind to at least one other target in addition to 4-1BB. Adding another target can increase the specificity of the drug, its cross-linking effect, and confer additional stimulatory or inhibitory activity, endowing the drug with extra anti-tumor properties. Targets commonly paired with 4-1BB include: PD-L1 (e.g., I-MAB Biopharma's TJ-L14B, Nanjing Leads Biolabs's LBL-024, Biotheus' PM1003), FAP (e.g., Roche's RG7827, Boehringer Ingelheim's BI765179) etc. In addition, the Fc end of this type of drug has been engineered to eliminate the ability to bind with Fcγ receptors but maintain the ability to bind with neonatal Fc receptors (FcRn) to ensure the half-life of the drug in the body. The aim is to suppress the liver toxicity seen in Urelumab, improving the safety of the drug. Drugs adopting this design strategy include Roche's RG7827 and RG6076, Elpiscience Biopharma's ES101, I-MAB Biopharma's TJ-L14B etc. Immunotherapy, surgery, radiation therapy, and chemotherapy together constitute the four methods of cancer treatment. In order to enhance the efficacy, surgery/chemotherapy/radiation therapy can be combined with immunotherapy as a joint treatment strategy. Currently, the combination of 4-1BB with radiation therapy and chemotherapy has been shown to have a good synergistic effect. In addition, anti-4-1BB antibodies have also been shown to improve the efficacy of other antibodies. Joint treatment plans based on 4-1BB antibodies may be a direction for future advancements in cancer treatment.