Gemtuzumab Ozogamicin

None\n Beyond the ADC Hype: Innovation is accelerating through bispecifics and dual payload strategiesAntibody drug conjugates (ADCs) mark a new era in targeted cancer therapy, delivering potent cytotoxic chemotherapy via monoclonal antibodies directly into the tumor cells — an era with potentially new standard-of-care therapies without systemic chemotherapy and its associated side-effects for cancer patients.Since approval of the first ADC Mylotarg® in 2000, 15 ADCs have been approved and 3 obtained Breakthrough Therapy Designation in 2025 alone. Now, the ADC market is poised for significant expansion, expected at $31B by 2030, reflecting a shift towards even more effective therapeutic options.Medical community enthusiasm and confidence in the success of next-gen ADCs is high enough that top pharmaceutical companies are expanding their ADC pipelines either via M&A or licensing deals, such as AbbVie’s acquisition of Immunogen in 2024 or Merck Sharp & Dohme’s licensing agreement with Daiichi Sankyo in 2023.The need for improvement persists—and with it, the imperative to innovateCurrently approved ADCs are associated with severe toxicities, including adverse events affecting the lungs, eyes and skin. Treatment resistance and tumor heterogeneity can also compromise the efficacy of those therapies. It has been shown that several mechanisms of resistance exist, from target downregulation, target mutation, to changes in internalization rates. Payload resistance is an additional growing issue that clinicians must face, as today approximately 45% of clinical-stage ADCs have a Topo1 payload class.Optimization opportunities are truly multifaceted with improvements possible for the target, linker, conjugation method, payload MOA and carrier. Emerging approaches such as bispecific antibodies and dual-payload ADCs are opening new avenues to address heterogeneity and resistance.Indeed, for these targeted therapies to achieve optimal efficacy, they must bind to cancer cells with optimal specificity and affinity. However, tumors are typically heterogeneous — meaning not all cells express the target receptor at the same level, and some may lack it entirely or become resistant by losing expression following specific treatment. This variability affects how well targeted molecules work in a certain population.“If you target two receptors, you diminish the selection effectof cells that can escape the ADC killing” said Leo Marx, Debiopharm’s Head of ADC Research and Technologies. “This is one aspect where bispecific antibodies could make a difference - the second binding site can compensate if one receptor is not expressed, helping eradicate more tumor cells while sparing healthy tissue.”Dual payload ADCs also address the resistance challenge. “What we’ve seen in our research is that 10 to 50% of cancer cells do not respond to a given cytotoxin, and there is no biomarker to select which patients would respond to one type of toxin or the other,” said Marx. “By combining them, we can increase the percentage of cancer cells that respond to ADCs and overcome resistance.”Dual payload ADCs must be designed with even more emphasis on sparing healthy cells, as they may also express the target antigen at some level. “The goal is to avoid an additive effect on the toxicity profile,” said Marx. Optimizing drug delivery via linker chemistry and conjugation strategies is also a way to mitigate on- and off-target toxicity. All these developments hold the promise to ultimately increase ADC efficacy and therapeutic index.Driving Innovation to Deliver More for Patients“Targeted therapy options are limited for patients battling tumor types such as colorectal, pancreatic and certain rare cancers, underscoring a critical need for new treatment strategies”, said Sophie Brachet, Head of Early Commercial and Access for Debiopharm. “There are therefore unexplored opportunities to improve patient outcomes in new indications, and in tumor types where ADCs are already established, they are moving earlier in the treatment paradigm and increasingly used in combination regimens. However, sequencing ADCs is becoming a growing challenge, as many ADCs share the same payload — Topo1 inhibitors — raising concerns about cross-resistance.”Oncologists are indeed introducing ADCs earlier lines of treatments in selected indications. Enfortumab vedotin (EV), approved in 2023 to treat advanced urothelial carcinoma, has become a new standard of care in first-line treatment in combination with pembrolizumab. Previously, advanced bladder cancer was typically treated with platinum-based chemotherapy, with serious side effects and limited long-term benefits.Advancing next-gen ADCs at DebiopharmThe most advanced program, Debio 1562M, a 1st-in-class CD37-targeted ADC, is being evaluated in a first-in-human trial (NCT06969430), to treat acute myeloid leukemia and myelodysplastic syndrome.“Debio 1562M is our front running clinical-stage program, among a broad and well-balanced ADC pipeline. We aim to drive innovation with first-in-class ADCs and differentiated best-in-class ADCs—leveraging novel bispecific designs and dual cytotoxic payload strategies.” commented Brachet.The pipeline encompasses HER3-based bispecific ADCs, including the promising HER3-HER2 pair, with alternative payloads to the Topo1 class or dual payloads. The Swiss-based team is also uncovering novel targets, identifying new antigens on cancer cells, especially those on hard-to-treat solid tumors.The Swiss, oncology focused biotech has developed a proprietary technology, on which all their ADC programs are built. The MultiLINKTM Technology Suite encompasses a range of linkers and conjugation technologies which uniquely allow building of dual payload ADCs at elevated DAR without impacting aggregation and exposure. In preclinical models, the MLINK Duo ADCs demonstrated excellent activity and enabled the resistance observed in models treated only with single-payload ADCs to be overcome. Research is also on-going on synergistic and non-cytotoxic novel payload classes.“MultiLINKTM linker technology is engineered with hydrophilic components to offset the toxicity caused by lipophilic payloads,” added Marx. “We’ve shown that even with dual payload constructs — for example, eight molecules of one drug combined with eight molecules of another on a single antibody — we maintain excellent PK and low clearance in preclinical models.”“Our ultimate ambition is for these next-gen ADCs to further enhance patient outcomes, particularly overall survival. We strive to fulfill the promise of precision chemotherapy and achieve the goal of replacing traditional chemotherapy as the standard treatment for select  cancers.” said Brachet.Debiopharm focuses on R&D and then partners with major pharmaceutical companies to bring medicines to the market and make them accessible to as many patients as possible throughout the world. Contact us to discuss your next project.

According to a report by Grand View Research, the Antibody-Drug Conjugates (ADCs) market has entered a new phase of rapid growth since 2019, maintaining an annual growth rate exceeding 30%. In 2023, the market size surpassed the $10 billion milestone for the first time, reaching an estimated $11.32 billion. It is projected to grow at a compound annual growth rate (CAGR) of 9.2% from 2024 to 2030, ultimately reaching $27.37 billion by 2033. Notably, Enhertu is expected to achieve an annual sales figure of $3.5 billion in 2024. The transaction status of ADCs in Patsnap SynapseComposition and Mechanism of Action of ADCsAs a cutting-edge therapeutic approach, ADCs achieve precise targeting of tumor cells by covalently linking highly cytotoxic drugs (typically small-molecule drugs) with monoclonal antibodies (mAbs). This allows ADCs to utilize the high specificity of monoclonal antibodies to recognize and bind to specific antigens on the surface of tumor cells. The cytotoxic drugs are then selectively delivered to these cells, enabling targeted destruction while minimizing damage to healthy cells. This selectivity has made ADCs a vital component of modern oncology treatments. With ongoing advancements, ADCs are increasingly significant in precision medicine. Structure of ADCs [1]The basic structure of ADCs comprises three key components: the monoclonal antibody, the linker, and the cytotoxic payload. The monoclonal antibody identifies and binds to antigens on tumor cell surfaces. The linker ensures stable attachment of the antibody and cytotoxic drug, preventing premature release before reaching the target cells. Once delivered, the cytotoxic payload is released inside the target cell, often through endocytosis. The payload then disrupts cellular structure or function, leading to apoptosis. For example, the released payload can affect the cell cycle by inhibiting DNA synthesis, interfering with spindle formation, or inducing DNA double-strand breaks, ultimately triggering programmed cell death. This mechanism not only effectively eradicates tumor cells but also reduces off-target toxicity due to intracellular drug release. Additionally, by fine-tuning the chemical properties of the linker, researchers can design ADCs that remain stable in the bloodstream and release their payload only upon reaching the target cells. Key Characteristics of Approved ADCs [1]Through such precise targeting, ADCs provide new therapeutic options for difficult-to-treat cancers while minimizing damage to healthy tissues. Furthermore, ongoing innovations in linking technologies and drug carriers are enhancing therapeutic efficacy and significantly reducing side effects during treatment. Factors Driving the Growth of the ADC Drug MarketThe primary factors driving the growth of the antibody-drug conjugate (ADC) market include the following: First, the ongoing research and development activities in the fields of cancer biology and immunology have deepened our understanding of the tumor microenvironment, enabling scientists to design ADC drugs that are both more efficient and have fewer side effects. Second, the growing global incidence of cancer has increased the demand for innovative treatment modalities. ADCs have garnered attention for their efficacy in addressing cases that are challenging for traditional chemotherapy. Lastly, advancements in drug delivery technologies, particularly the optimization of linker systems, have significantly enhanced the safety and efficacy of ADCs. Additionally, regulatory support for the accelerated approval of ADC drugs and active strategic collaborations among biotechnology companies have greatly facilitated the development and marketization of ADC therapies. Delivery of ADCsThe delivery of ADCs is a complex and precise process aimed at ensuring that the drug accurately reaches tumor cells and releases its cytotoxic payload. Traditional naked antibodies can be administered directly via intravenous injection and rely on their high affinity for antigens on the surface of tumor cells for targeting. However, their rapid clearance from the body may reduce therapeutic efficacy. To address this limitation, chemical modifications, such as PEGylation (polyethylene glycol conjugation), have been introduced to enhance the stability of ADCs and extend their plasma half-life. This allows ADCs to remain in the bloodstream for a longer duration, increasing the likelihood of reaching tumor sites. Types of Linkers in ADCs [2]Linker technology is a critical component of ADC design and can be classified into two main categories: cleavable linkers and non-cleavable linkers. Cleavable linkers are designed to release the cytotoxic payload under specific conditions, such as enzymatic activity in the lysosome or changes in pH. Non-cleavable linkers, on the other hand, remain stable within the cell until the drug portion is released, ensuring that the cytotoxic molecules are delivered at the correct time and location. Types of Components in ADCs [3]Moreover, nanoparticle technologies like liposomal encapsulation have been employed to protect ADCs from degradation and enhance cellular uptake. Liposomes, as an effective drug carrier system, can transport ADCs across biological barriers and precisely release the drug at target sites, thereby improving drug delivery efficiency. Polymer matrix systems offer another approach to enhancing the stability and delivery efficacy of ADCs. By integrating ADCs into polymer matrices, the physicochemical properties of the drugs, such as solubility and stability, can be improved, optimizing therapeutic outcomes. The combined application of these delivery strategies can effectively overcome biological barriers, ensuring that ADCs reach tumor cells efficiently and safely while minimizing adverse effects on healthy tissues. With continued innovation and development, the delivery efficiency and safety of ADC drugs are expected to improve further, providing cancer patients with more precise and effective treatment options. Indications for ADC DrugsTop 10 ASOs targets in Patsnap SynapseBreast Cancer: For patients with HER2-positive breast cancer, multiple ADC drugs are available. For example, Genentech's Kadcyla (Trastuzumab Emtansine), the first approved ADC drug for breast cancer, has demonstrated efficacy in treating HER2-positive metastatic breast cancer. Additionally, Daiichi Sankyo/AstraZeneca's Enhertu (Trastuzumab Deruxtecan) has shown exceptional therapeutic efficacy not only in HER2-positive breast cancer but also achieved groundbreaking progress in patients with HER2-low expressing breast cancer. Hematologic Malignancies: ADC drugs also have broad applications in hematologic malignancies. For instance, Pfizer’s Besponsa (Inotuzumab Ozogamicin) is approved for the treatment of CD22-positive acute lymphoblastic leukemia (ALL). Similarly, Seattle Genetics/Takeda’s Adcetris (Brentuximab Vedotin) is used for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma. Solid Tumors: In the field of solid tumor treatment, ADC drugs also demonstrate significant potential. Astellas Pharma’s Padcev (Enfortumab Vedotin-ejfc) is approved for the treatment of locally advanced or metastatic urothelial carcinoma. Immunomedics' Trodelvy (Sacituzumab Govitecan-hziy) is indicated for metastatic triple-negative breast cancer and other solid tumors. Top 10 ASOs Indications in Patsnap SynapseThese ADC drugs employ a unique mechanism by combining highly specific monoclonal antibodies with potent cytotoxic agents to achieve targeted destruction of tumor cells, while minimizing damage to healthy tissues. As ADC technology continues to advance and clinical research progresses, it is anticipated that more ADC drugs targeting different indications will emerge in the future, providing patients with a broader range of personalized treatment options. Regional Analysis of ADC DevelopmentGlobally, ADCs are experiencing robust growth, with North America and Europe leading the field due to their advanced technologies and mature regulatory frameworks. These regions benefit from abundant research and development resources, coupled with extensive expertise. Additionally, their stringent drug approval standards provide a solid foundation for the high-quality advancement of ADCs. The North American market serves as the central hub for ADC research and development, boasting numerous leading biopharma companies at the forefront of technological innovation and clinical application of ADCs. Regulatory agencies in this region, such as the U.S. Food and Drug Administration (FDA), have accumulated substantial experience in evaluating and approving ADCs, paving the way for their expedited entry into the market. Similarly, the European market should not be overlooked. The European Medicines Agency (EMA) has set rigorous standards and guidelines to promote high-quality ADC development. Moreover, Europe’s strong foundation in biopharmaceuticals further strengthens its contribution to ADC advancements. In Asia, particularly China, the ADC market is rapidly emerging as a key driving force in global ADC development. China’s vast patient population and rapidly growing demand for healthcare services create a significant market opportunity for ADCs. Additionally, the Chinese government has introduced a series of policies encouraging the development of innovative drugs. Coupled with the rise of domestic pharmaceutical companies and advancements in technology, China has made remarkable progress in ADC development. With the ongoing transformation of the global ADC industry, more novel ADCs have been approved, increasing treatment choices and intensifying the competitive dynamics within the market. Intensified investment and R&D efforts from leading pharmaceutical companies indicate that ADC drugs will witness additional growth opportunities in the coming years. Key Players in the ADC Development MarketCompetitive Landscape of ASOs in Patsnap SynapseSeattle Genetics, now known as Seagen, is one of the pioneers in the ADC sector. As a leader in ADC development, Seagen possesses extensive research experience and has launched several marketed ADC products. Among its notable achievements, Adcetris (brentuximab vedotin) became the first approved treatment specifically for anaplastic large-cell lymphoma and the first new therapy in nearly 40 years to receive FDA approval as a frontline option for relapsed Hodgkin lymphoma. Seagen has also developed Padcev (enfortumab vedotin-ejfc) for the treatment of locally advanced or metastatic urothelial cancer. Beyond its clinical success, Seagen has expanded its influence through collaborations with various companies, cementing its position as a leader in the ADC field. Genentech, a member of the Roche Group, holds a significant position in ADC development. The company has actively contributed to ADC innovation, focusing on treatments for various cancer indications. One of its flagship ADC products, Kadcyla (ado-trastuzumab emtansine), has been approved for patients with HER2-positive early breast cancer. Genentech’s sustained investment and innovation in the ADC field make it a formidable force driving advancements in ADC technology. Pfizer possesses a diverse portfolio in the ADC space, dedicating itself to developing ADC therapies for hematologic malignancies. The company has launched several ADC products through partnerships and continues to expand its pipeline. For example, Pfizer’s Mylotarg (gemtuzumab ozogamicin) and Besponsa (inotuzumab ozogamicin) are used to treat acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), respectively. Notably, Pfizer further strengthened its leadership in the ADC sector by acquiring Seagen for $43 billion in 2023. These companies play a significant role in the development of ADC drugs, not only driving advancements in ADC technology but also providing new treatment options for patients. With the continuous progress of ADC technology and the growing market demand, these companies will continue to play an essential role on a global scale. ConclusionADCs demonstrate tremendous potential in precision medicine as an emerging therapeutic modality. By targeting specific antigens on cancer cells, ADCs can effectively deliver cytotoxic drugs, achieving selective tumor cell killing and offering novel treatment options for hard-to-treat cancers. In recent years, the successful market entry of various ADC drugs has not only highlighted the efficacy and safety of ADC therapies in clinical applications but also signaled the arrival of more innovative drugs, which will benefit a broader patient population. 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! Refrence  1.Dumontet, C., et al., Antibody-drug conjugates come of age in oncology. Nat Rev Drug Discov, 2023. 22(8): p. 641-661.2.Bargh, J.D., et al., Cleavable linkers in antibody-drug conjugates. Chem Soc Rev, 2019. 48(16): p. 4361-4374.3.Drago, J.Z., S. Modi, and S. Chandarlapaty, Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol, 2021. 18(6): p. 327-344.