Next generation biologics offer a number of advantages over traditional monoclonal antibodies and companies are increasingly choosing to invest more money and facilities in these more complex molecules. However, with numerous challenges around getting these products to clinical trials, there is still the need for companies to balance their portfolios.
We spoke to four industry experts about the benefits, investment and challenges around these biologics.
What advantages do these next generation biologics have over traditional mAbs?
“The increasing understanding of the complexity of biology suggests the development of multi-functional biologics. Modifying mAbs towards multi-functionality is only possible to some extent in an efficient manner. Alternative platforms have proven to be more productive.” - Dr H. Kaspar Binz, CEO & Founder at Binz Biotech Consulting GmbH
“The next generation biologics and bioconjugates provide the advantage of multiple functionality and specificity. Additionally, some of the multi domain biologics that are built on a smaller size framework like a nanobody or peptide conjugates have the ability to access solid tumors much more efficiently.” - Vibha Jawa, Director at Merck
“Hopefully they will have advantages! They should offer transformational efficacy, improved safety profiles and be cheaper. We should always develop the most appropriate treatment and not advance complex therapeutics out of scientific ego; our only goal should be to help our waiting patients.” - Adrian Hobson, Research Fellow at Abbvie
“WuXiBody® is a novel proprietary bispecific antibody platform, binding to two different targets (A and B) or epitopes (A1 and A2) simultaneously. Comparing with traditional mAbs, WuXiBody® has different mechanism of action, and may open up opportunities for realizing novel therapeutic concepts, otherwise impossible by using conventional mAbs. For example, a WuXiBody® molecule can direct immune cells to tumor cells. Additionally, WuXiBody® is quite flexible in binding valence. It can provide 1+1, 1+2 or 2+2 binding sites to target A and B, so the scientists can fine tune the binding valency, binding strength and binding geometry of the molecules. This allows scientists to obtain a molecule with optimal binding to the 2 different targets based on their biology needs.” - George Wang, PHD MBA, Vice President of Biologics Discovery at WuXi Biologics
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Why are companies choosing to invest more money and facilities in these more complex molecules?
“Traditional mAbs have delivered excellent drugs to most known druggable pathways. Now that the first simple antagonistic mAbs are becoming generic and most pathways have been addressed industry realizes that it will be increasingly difficult to create simple mAb products. There will be further excellent mAb drugs, but at the same time it is clear that the increasing understanding of the complexity of biology will favor the use of multi-functional biologics. And there is plenty of room for innovation in this space.” – Dr Binz, Binz Biotech Consulting
“With better understanding and innovation of the protein engineering platforms, large number of biopharma and biotech would like to invest in and safe drugs where there is minimal toxicity and a better efficacy by targeting to cell specific markers. The complex molecules also provide an ability to take the functionally of multiple ways to prime the immune system and deal with the disease in a multifaceted approach.” - Vibha Jawa, Merck
“The goal transformational efficacy. Companies see these more complex molecules as offering a path forward to enabling this.” - Adrian Hobson, Abbvie
“Because bispecific antibody opens up complete new areas and may help to realize some novel therapeutic concepts otherwise impossible by using conventional mAbs. Such molecules may improve current treatment for some of the most devastating human diseases with huge unmet medical needs, such as cancers, infectious and autoimmune diseases.” - Dr Wang, WuXi Biologics
How are companies best balancing their portfolios?
“Companies are well advised to balance their pipeline with programs of different biology risk profiles, i.e. moonshot vs. low-hanging fruit programs. The more traditional mAb companies realize that the mAb-concept life-cycle is advanced and are looking into new approaches. Of course they try to continue with mAbs, but at the same time they are also considering joining approaches which are early in their life-cycle. This includes novel multi-functional biologics platforms and also completely different approaches like gene-therapy, CAR-T, or CRISPR approaches.” – Dr Binz, Binz Biotech Consulting
“The identified target is developed in multiple modalities like bispecifics, trisepcifics, nanobodies, small molecule / peptides as well as combination regimens.” - Vibha Jawa, Merck
“Companies always struggle to balance their portfolios. Many have both small molecule and biologics portfolios. Then within the biologics portion they need targets with a high probability of success and others that are more exploratory. Depending on the companies comfort with risk determines how they then balance this.” - Adrian Hobson, Abbvie
“It’s a balance of risk and benefit. The risk includes new biology, increased development cost, increased complexity of clinical development. The benefits are improved clinical outcome: improved efficacy or reduce adverse effects. Since some of the new platforms, such as WuXiBody®, have significant advantages over other platforms - not only in flexibility to address biology questions but also on CMC and manufacturing sides, it will significantly reduce R&D cost to comparable to conventional antibodies. I believe that more companies would invest in this area.” - Dr Wang, WuXi Biologics
What are the biggest challenges with getting these products to clinical trials? What preparation can industry do?
“The experience for alternatives to antibodies so far has been very positive regarding the interaction with regulatory authorities. The complexity of biology is a more relevant, yet also addressable challenge. As the knowledge increases steadily I am confident that we are only at the beginning of seeing alternatives to antibodies reveal their full strengths.” – Dr Binz, Binz Biotech Consulting
“The safety and immunogenicity risk as well as expression, manufacturing and purification would need to be reassessed due to the complexity of the structure of such modalities.” - Vibha Jawa, Merck
“Access to clinical trials is a major bottleneck especially when there is already a good product on the market and you are advancing what is hoped to be a transformational approach.” - Adrian Hobson, Abbvie
“For bispecific molecules such as WuXiBody®, the biggest challenge is biology-related, such as identifying appropriate target pairs, selecting right animal models to demonstrate superiority, and eventually translating preclinical findings into desired clinical efficacy and safety.” - Dr Wang, WuXi Biologics
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