Post: Biologics 2.0 – From monoclonal antibodies to multispecific therapeutics
Biologics have come a long way, from first-generation monoclonal antibodies to highly engineered molecules designed with precision in mind. Today’s biologics are smarter, more specialized, and increasingly patient-specific. So what is next? In this post, we explore the key scientific and clinical shifts shaping the future of biologics and why targeted therapies are redefining modern medicine.
A 30-Year Evolution of Biologics
Biologics are therapeutic products derived from living organisms, encompassing various substances such as proteins, nucleic acids, and cells. These complex molecules target specific biological processes, particularly in treating autoimmune disorders and cancers. Biologics are distinct from traditional chemically synthesized drugs because they are produced in living systems, such as microorganisms or animal cells, making their manufacturing more complex and costly than conventional drugs.
The FDA began authorizing biologics in 1982 when human insulin, as the first biological product, received approval. Over the past three decades, biological therapeutics have evolved from niche therapies into a cornerstone of treatment across oncology, autoimmune diseases, and rare disorders. Biologics have significantly improved outcomes for patients who did not respond to traditional treatments, especially in chronic and complex diseases (Garud et al., 2024; Doherty et al., 2022).
In ulcerative colitis, for example, increased biologic use has led to a marked reduction in surgical interventions like colectomy (Doherty et al., 2022).
Advances in biotechnology, such as DNA recombination and protein engineering, have enabled the development of safer, more effective therapeutics with enhanced selectivity and stability.
Following the progress in biologics research, manufacturing has become more demanding, requiring specialized facilities and careful attention to stability and delivery (McGonigle, 2024; Saylor, 2014). Formulation science and drug design are now integral to early development stages.
Enter the Age of Multi-Functional Molecules
The novel biologics expand far beyond monoclonal antibodies. Biologics such as bispecific antibodies, antibody-drug conjugates (ADCs), and fusion proteins represent the forefront of next-generation therapies, especially in cancer treatment. They are characterized by improved specificity, efficacy, and safety by combining targeting and therapeutic functions in novel ways.
Bispecific antibodies (BsAbs) bind two different targets simultaneously, often bridging immune cells with tumor cells to amplify immune-mediated killing, increasing specificity and reducing resistance (Lancman et al., 2020; Szijj & Chudasama, 2021; Maruani, 2018; Hong et al., 2023).
We know over 100 BsAbs formats, with several FDA-approved, many more in clinical trials, and multispecific molecules, such as trispecific antibodies (targeting three molecules), emerge on the horizon (Lancman et al., 2020; Szijj & Chudasama, 2021; Maruani, 2018; Hong et al., 2023).
Antibody-drug conjugates (ADCs) are antibodies armed with cytotoxic payloads that deliver the drug directly into diseased cells (e.g., tumor), reducing systemic toxicity (Lancman et al., 2020; Rathi & Meibohm, 2015; Tsuchikama et al., 2024; Hong et al., 2023).
Hundreds of ADCs are in development, with several approved for cancer therapy. BsADCs, which combine bispecific targeting with cytotoxic payloads, are in early clinical stages and show improved efficacy and specificity (Gu et al., 2024; Hong et al., 2023; Wang et al., 2024; Zhong et al., 2023; Shang et al., 2022). Novel ADC formats include:
- bispecific ADCs (BsADCs),
- conditionally active ADCs,
- immune-stimulating ADCs,
- and dual-drug ADCs.
Each type is designed to overcome resistance, tumor heterogeneity, and side effects (Tsuchikama et al., 2024; Gu et al., 2024; Hong et al., 2023).
Finally, researchers also developed a class of molecules named fusion proteins. These therapeutics combine antibody fragments (predominantly Fc region) with other functional protein domains to enhance targeting or immune activation (Rathi & Meibohm, 2015). Ongoing research concentrates on nanobodies and other novel scaffolds for optimizing pharmacokinetics and therapeutic effects (Rathi & Meibohm, 2015).
All these innovative approaches expand the therapeutic landscape, addressing previous limitations and broadening patient benefits.
From "One-Size-Fits-All" to Targeted Therapies
Thanks to genomics and advanced molecular profiling, biologics can now be personalized to the individual. This is the foundation of modern targeted therapies: treatments tailored to genetic mutations, immune signatures, and even subcellular targets, enabling improved outcomes and safety profiles.
Next-generation sequencing and biomarker analysis now allow identification of unique genetic, proteomic, and immune features in each patient’s disease, supporting the selection of therapies that specifically target these abnormalities (Adashek et al., 2020; Tsimberidou et al., 2020; Subbiah & Kurzrock, 2018; Manzari et al., 2021; Hua et al., 2021; Zhu et al., 2024; Chen, 2017).
Notable examples of personalization in medicine:
- Molecular subtyping in breast cancer, where precision therapies (e.g., endocrine therapy, CDK4/6 inhibitors, immunotherapy, tyrosine kinase inhibitors) have nearly doubled progression-free survival for HR+/HER2- patients (Zhu et al., 2024).
- Gene-directed (tissue-agnostic) therapies use adaptive designs to match therapies to patient profiles based on molecular markers, regardless of cancer type (Tsimberidou et al., 2020; Subbiah & Kurzrock, 2018).
- Organelle-targeted and advanced delivery systems direct drugs to specific cellular compartments, reducing toxicity and improving efficacy (Manzari et al., 2021; Yang et al., 2022).
- Precision dosing based on biomarkers enables individualized drug dosing to optimize efficacy and reduce toxicity (Polasek & Peck, 2024).
Teplizumab and the Future of Disease Prevention
Teplizumab (Tzield) is a powerful example of the biologics’ evolution from broad immunosuppression to precision, targeted therapy for disease prevention. This first FDA-approved therapy delays the onset of stage 3 type 1 diabetes (T1D) in individuals who have stage 2 type 1 diabetes. Unlike conventional treatments that manage symptoms, it acts at the immune level before the disease manifests.
Teplizumab is a monoclonal antibody that targets CD3 on T cells, modulating the immune response to prevent the autoimmune destruction of insulin-producing pancreatic beta cells. This possibly prevents T1D progression (Novograd & Frishman, 2023; Misra & Shukla, 2023; Keam, 2023; Thakkar et al., 2023).
In phase 2, a randomized, placebo-controlled, double-blind trial involving 76 participants, a single 14-day infusion course delayed the onset of clinical T1D by an average of three years in high-risk individuals, with effects that persist over time (Misra & Shukla, 2023; Białek et al., 2023; Keam, 2023; Seewoodhary & Silveira, 2023).
Teplizumab represents the move toward precision medicine: using targeted biologics to intercept disease at the preclinical stage. Its success paves the way for similar targeted biologics in other autoimmune diseases and highlights the importance of early detection and intervention.
What is Next for Biologics?
The field continues to advance with:
- N-of-one therapies – treatments developed and tailored specifically for a single individual, often based on that person’s unique genetic or molecular profile. These therapies are especially relevant for rare diseases caused by unique genetic variants, with no standard treatment.
- Biosimilars – biological medicines highly similar to an already approved reference biologic product, with no clinically meaningful differences in safety, purity, and efficacy.
- Hybrid constructs – engineered molecules that combine features from different proteins or domains to create a new therapeutic entity.
- Novel delivery formats – from subcutaneous injections to oral and inhaled biologics for greater patient convenience.
At Ardigen, we support this transformation with AI-driven solutions, from early research to candidate selection. Here is how:
1. Better Target Understanding
Efficacy starts with precision. We utilize AI to map and thoroughly analyze drug targets for their therapeutic relevance and safety. Researchers can mitigate off-target risks early by modeling the target’s biological function and potential cross-reactivity.
- More Promising Leads
Biologics discovery demands expanded screening space. Our models generate a wide variety of potential candidates. Exploring a much larger space than traditional methods increases the chance of finding the most active and specific molecules.
- Smarter Candidate Selection
Finding the right molecule goes beyond affinity. Ardigen’s AI models evaluate candidates based on:
- safety (immunogenicity risk),
- how easy they are to develop (protein stability, solubility, aggregation propensity),
- functionality (target binding, biological activity).
This ensures that selected hits are relevant for downstream development and manufacturing.
- Precise Interaction Insights for Safety
Understanding how a molecule interacts with its target is critical. Our Binder-Target Interface Analysis provides insights into biologics-target molecular interactions, helping to reduce off-target effects.
Curious how it works? Let’s turn data into novel biologics!
Request a demo to see how Ardigen’s AI platform can streamline your discovery pipeline—from target to clinic.
