There is undoubtedly a great deal of research going on within the antibody space, a significant number of therapeutics in the clinic and a lot of upcoming developments to watch out for. So in preparation for the European Antibody Congress 2014, we took some time out to conduct interviews with key members of the speaker faculty who are leaders in the antibody space – which we’ll release weekly, so please keep an eye out for the series of interviews to follow!
Read on for an interview with SpectraMab‘s first CSO, Georg Fey’s (GF), to learn of his responses to the latest industry developments and challenges, and to gain a unique perspective on this sector.
What’s the most exciting project you/your company is working on at the moment in the antibody space?
GF: Bringing the triplebody SPM-2 (with scFv binding sites for CD33, CD16 and CD123 arranged in a tandem linear array) through late preclinical development into a first-in-human clinical trial for the treatment of AML (Acute Myeloid Leukaemia). To test the hypothesis that this agent will not only be able to help eliminating bulk leukaemia cells, but also leukaemia stem cells and the dreaded Minimal Residual Disease (MRD) cells considered responsible for the fatal relapses.
What do you think is going to be the biggest ‘game changer’ in this sector in the next 18 months – whether it be new product approvals, ground-breaking research or the uptake of new technologies?
GF: CARs and CAR-T cells will be developed for a number of targets and will be brought into first in man clinical trials.
Are there any new technology platforms that you’re watching closely, the implementation of which you think could have a big impact on your work, or the wider antibody space?
GF: Watching out for all new molecular formats of antibody-derived agents, which permit “dual targeting”, i.e. to address simultaneously two different target antigens on the same target cell and thus to refine the attack on double-positive cancer cells and achieve their preferential elimination. Formats such as Roche’s “Crossmabs” , Genmab’s “Duomabs”, Biotecnol’s “Tribodies”, SpectraMab’s “Triplebodies”, “Molecular Partners” dual-targeting agents based on novel binding domains, derived for example from ankyrin repeats, Genentechs “Two-in-one” antibodies and Abbvie’s and Merrimack’s dual-targeting agents.
What is the biggest challenge to overcome with regards to the engineering of bispecifics?
GF: To produce them in a stable manner, so that they do not form aggregates and have sufficient long term storage stability, and to produce them in sufficient production yields; to get them to react both with their human target antigens and the respective targets on primate cells, in order to permit toxicity studies in primates.
We’re now seeing a shift from bispecific development to trispecifc, tetraspecific molecules and beyond. What are your thoughts on these more complex molecules – and what’s the potential?
GF: These new formats offer fantastic new possibilities, both in terms of targeting cancer cells with increased selectivity over normal healthy targets, targeting cancer stem cells and the Minimum Residual Disease (MRD) cells responsible for early relapses, and in recruiting and activating effector cells via more than one signal. Remember that T-cells classically require two signals to become activated. Similarly, such agents will permit 2-signal activation of NK-cells and other effectors, and possibly even to convert tissue-associated macrophages (TAMs) found in many solid tumour tissues from “pro-tumorigenic” cells into “anti-tumour” cells. The potential is also large in applications in chronic inflammatory and autoimmune disorders and in eye diseases such as AMD, Acute Macular Degeneration, with a greater number of patients in need than the cancer patients.
We’ve recently seen the first approval of a mAb biosimilar in the EU, and there are many more antibody biosimilars in development. What do you think the effect of biosimilar mAb approval in highly regulated markets is going to have on the antibody space?
GF: As long as Biosimilars are effective and help us to combat disease, they are welcome. It remains to be seen by long-term studies whether their side effects are similar to those of the original agent or different. However, if they are equally potent and help to bring the price for antibody therapeutics down by stoking competition, then this is good news for the field. The price of antibody therapeutics is currently far too high, so that only a small segment of patients in need can afford them. Remember that the British public health care system cannot afford to make Herceptin/TrastuzumabTM available to women with early stage breast cancer, although they would benefit from the treatment, because this would bankrupt the health care system. This is inacceptable. Similarly, in developing countries with a weak solidary health care system, antibody therapeutics are not affordable for a large segment of patients in need. If these people can afford access to biosimilars, and if biosimilars bring the price of regular antibody-therapeutics down through competition, then this will be welcome news to millions of patients in need. Profits of the industry will not suffer from it – on the contrary: the market volume will increase, and therefore, competition by biosimilars is good not only for the patients, but also for the producers and marketers of antibody-derived therapeutics.
If you could have dinner with any academic, industry or regulatory person working within the antibody space today, to discuss their work and thoughts on this sector – who would it be, and why?
GF: Patrick Bäuerle and Stanley Frankel from Micromet/AMGEN and Carl June from Philadelphia. The first developed the BiTEs, and this was a revolutionary development in the field, because these agents are exclusively built from scFv-domains and lack the Fc-domains of conventional IgGs, and still are highly effective. We can take a page from their playbook, because in order to build new agents with multiple binding sites, it will be too tedious to have the Fc-domains present. For many years, most experts in the field doubted, that one could do without Fc-domains, and the colleagues from Micromet/AMGEN are the pioneers who showed, that this was possible anyway, and blasted a new trail for the entire field. Carl June and others developed the CARs and CAR-transfected T-cells, and this is likely to be the next biggest development in cancer therapy.
If you’d like to hear more from key leaders of the antibody space, join us at the European Antibody Congress 2014 in Geneva on 10-12 November 2014. We look forward to welcoming you and hope you enjoyed the read!