Biologics 2024: conference highlights

The Biologics 2024 conference was held from 13–15 March 2024 in London, UK. The Bioanalysis Zone team were in attendance and had an exciting few days attending talks, viewing posters and networking with new and familiar faces. In this report our Editors discuss some of their highlights from the conference.

Integrating artificial intelligence (AI) and machine learning (ML) into biologics discovery workflows

AI was a key theme throughout the conference as undeniably AI and ML have huge potential to enhance drug development. Rebecca Croasdale-Wood (AstraZeneca; Cambridge, UK) discussed how her team are using AI and ML to predict structures, developability and affinity to help improve lead optimization. She highlighted how AI can help with data analysis and decision making by looking at data points and selecting lead molecules, ultimately leading to the better design of antibody libraries. She detailed how the complexity of antibodies is ever increasing (ADCs, bispecifics, trispecifics etc.) so it is important to embrace AI and ML to validate predictions as these technologies are impacting pipeline products through data generation, lead optimization and in silico developability screening.

Panel discussion: antibody discovery in 2024 – what does the future hold?

It usually takes 6–8 years for a therapeutic antibody to be approved. Bryce Nelson (Orion Pharma; Turku, Finland) discussed the increasing interest in bispecifics. Bispecifics are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. He also commented on the theme of AI and ML and how these technologies can help with decision making to help speed up data review, bringing key learnings to the next project.

Antibodies to watch: progress in 2024 and key clinical development metrics

Silvia Crescioli (The Antibody Society; London, UK) explained how the number of antibody therapeutics that are entering clinical studies and being granted market approvals world-wide are increasing. Therapeutic antibodies that entered first clinical studies in the 2000–2019 period have an approval success rate in the range of 14–32% with higher rates associated with antibodies for non-cancer indications and recent development. She concluded with a short summary for 2024 – so far one antibody has received therapeutic approval – termed Crovalimab – and 32 antibodies are in regulatory review in at least one country or region.

CMC considerations for large volume oligos

Producing oligonucleotides at high volume is exceptionally costly, usually adding considerably to the development stage. In this talk, Louis Diorazio (AstraZeneca; Cambridge, UK) described some of the challenges associated with the delivery of large-volume oligo therapeutics, including their significant environmental impact, with a huge amount of waste being generated during manufacturing. In particular, oligo ‘building blocks’ have a disproportionate environmental impact that is often overlooked. Louis also noted the importance of ethics and transparency, as well as access to healthcare when considering the societal impacts of oligo therapeutics. However, Louis demonstrated that oligos can have a much lower carbon footprint than small molecules and can be dosed less frequently.

Perspectives on immunogenicity risk and challenges for antigenicity

Although being able to accurately predict immunogenicity is highly desirable, there are currently no tools that exist to accurately predict human ADA incidence. This means that mitigating these risks is a must. Speaker Samuel Pine (Sanofi; Paris, France) covers antigenicity —the innate ability of a given molecule to induce an adaptive immune response— compared to immunogenicity —the ability of a given substance to provoke an immune response. He then went on to explain Sanofi’s risk-based approach to antigenicity profiling, using low vs moderate/high-risk models. Not only does this mitigate a clinical risk, i.e., the impact on patients, but also a development risk, including the cost and resources needed to bring the drug to the market.

Stage-appropriate bioassays for the successful development of ADCs

In this joint session, Rob Holgate (Abenza; CA, USA) began by sharing Abenza’s experience with ADCs and how ADC specificity and cytotoxicity have made them an important class of targeted therapeutics for cancer. He discussed the ideal properties of drug candidates —high yield, adequate quality, efficacious, low immunogenicity— but reminded us that these ideals are not usually reflected in reality. Erika Kovacs (also Abzena) then took over to cover bioassays during drug development to assess these ideals and highlighted that choosing the most stage-appropriate assay is key now that the ADC and bioconjugate space is expanding.

Panel discussion: current industry trends in oligonucleotide discovery and development

Including David Evans (Sirnaomics; MD, USA), Christopher Heart (Creyon Bio; CA, USA), Lukasz Kielpinski (Roche; Basel, Switzerland) and Filippo Sladojevich (Roche; Basel, Switzerland).

We have experienced a 40-year run of oligo development and we’re now at a stage where there are monthly developments in the oligo space. The panel discussed the latest challenges with oligo discovery and development, including tissue targeting, and highlighted the beneficial capabilities of AI for predicting reagent efficacy, data handling, etc. The key concern that was raised was the issue of dealing with published patent applications, with algorithms and key oligo sequences essentially off-limits to many. The team also shared their thoughts on the current delivery models and how we can leverage the oligo features that make them stand out from small molecules.