Therapeutic antibody potential in 2024

DDW’s Megan Thomas speaks to industry experts and thought leaders about the potential for therapeutic antibodies in 2024. Many of the best-selling drugs in 2023 were monoclonal antibody (mAB) therapies, including Keytruda (pembrolizumab), Humira (adalimumab), and Dupixent (dupilumab)1. This won't come as a surprise when you look at industry milestones achieved in 2023 and looking ahead, this shows no signs of slowing down. Artificial intelligence (AI) AI is on everyone’s minds as we head into 2024; of course, this is across not just the drug discovery spectrum but is particularly relevant to therapeutic antibodies. This is reflected in collaboration and investment patterns; in 2023, Antiverse, a biotechnology company developing a computational antibody drug discovery platform, raised seed funding totalling £1.4 million, comprising new investment and match funding from the UKI2S Innovate Accelerator. The company also partnered with a top 20 pharma company and has been successful in identifying antibody candidates for a target of interest, with greater diversity (2.3x) and accuracy compared to alternative bioinformatics pipeline selection methods. Ben Holland, Co-Founder and CTO of Antiverse, notes that AI and machine learning now touch 10% of drug discovery projects. He says: “Developability prediction is often used in antibody development to reduce wet lab experiments and accelerate the drug discovery process. We anticipate developability prediction becoming widespread and somewhat commoditised, but with a continually rising bar, it will remain an important technology.” AI’s significance is also evident in the science, where immuno-oncology company Aulos Bioscience recently revealed interim results from an ongoing Phase I/II trial of an AI-designed monoclonal antibody (mAb), AU-007, in solid tumours. According to Aron Knickerbocker, Aulos Bioscience’s Chief Executive Officer, the new data supports the company’s belief that AU- 007 offers a novel mechanism of action among interleukin-2 (IL-2) therapeutics in development, as demonstrated by AU-007’s pharmacodynamic and safety profile to date. Advancing mAbs There has been a steep growth and expansion curve when it comes to mAbs, especially when considering the FDA approvals that occurred in 2023, including examples such as FDA clearance to Transcenta to proceed with its TranStar 301 global Phase III pivotal trial of Osemitamab (TST001) for gastric cancer, as well as the FDA Fast Track designation for Alentis Therapeutics’ investigational mAb, ALE.C04, which is indicated to treat patients with recurrent or metastatic CLDN1-positive head and neck squamous cell carcinoma (HNSCC). Not to mention, Pfizer’s Elrexfio (elranatamab- bcmm) was granted accelerated approval for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM), and FDA approval of AstraZeneca’s Beyfortus (nirsevimab-alip) for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season. Looking forward, Lia Sylvestri, Director Customer Experience & Engagement, TrakCel, notes that significant advancements in mAbs research are anticipated with leading companies, such as Roche, Regeneron, and Eli Lilly, who are expected to drive breakthroughs in precision medicine, tailoring mAbs for diverse diseases. She says: “Innovations include next-generation antibodies with improved efficacy and reduced side effects. Research will likely focus on expanding applications in infectious diseases and autoimmune disorders.” Meanwhile, Richard Hammond, CTO of Sphere Fluidics, comments that the development of mAb-based therapies has rapidly taken off within the last few decades, which he owes to advances in molecular biology and high-throughput screening technologies. These enable researchers to better manipulate biological molecules or identify the best candidates to progress to the next stage of development. Hammond says: “Many of the most popular drugs in 2023 are mAb-based therapies, which we predict will continue in 2024. We also predict that the number of new candidate drugs being identified or entering clinical trials that are mAbs will also increase. This is due in part to advances in antibody discovery platforms, such as ours that use droplet-based microfluidics technology to streamline and accelerate the initial screening process. “Expanding synthetic biology capabilities are also enabling the development of novel mAb-based drug candidates, such as bispecific mAbs and conjugated mAbs. Increasing recognition of the potential and applicability of mAb-based therapies is being reflected through the increased funding and number of research projects, which we predict will continue to rise well beyond 2024 in line with global demands. For example, the rising incidence of cancer – a disease where treatment using mAb-based therapies is increasingly appropriate – will continue to drive market growth, as well as the need to develop novel therapies for diseases where therapeutic options are limited or are difficult to target.” Adoptive T cell therapy Carole Nicco, CSO of BioSenic, adds that mAb immunotherapy is the most widely used approach and has achieved tremendous success. She says: “Adoptive T-cell therapy (ACT), particularly T-cell-based transplantation, is attracting increasing attention and is advancing rapidly since the FDA approval of CAR-T therapy for the treatment of relapsed/refractory acute lymphoblastic leukaemia and B-cell malignancies. “Other ACTs such as TIL, TCR, NK cell, Treg, and MDSC therapies are now emerging. High response rates have been reported for both mAb and CAR T-cell cancer therapy; however, treatment refractoriness and disease relapse still occur and represent an ongoing clinical challenge. Although several issues regarding ACTs, such as safety, efficacy and persistence, need to be addressed, ACTs are being continuously produced and an increasing number of commercial products are being approved, mainly due to their advantages such as simple composition and controllable scalability. In the future, the combination of CAR T-cell therapy with local small molecules, such as BioSenic's arsenic trioxide, may be a combinatorial strategy to overcome the limitations of each monotherapy.” DDW Volume 25 – Issue 1, Winter 2023/2024 – Therapeutic Antibodies Guide Reference: https://www.ipharmacenter.com/ post/best-selling-drugs-of-2023-top- 10-drugs-by-revenues-best-selling- pharmaceuticals-ipharmacenter About the author Megan Thomas is Multimedia Editor of DDW. She has worked across a range of B2C and B2B publications, and was a digital editor at the British Medical Association. She has an undergraduate degree in Print Journalism, Film & Media and a master’s degree in Creative Writing.