Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please can you give a brief introduction to anti-cancer drug conjugates?
Antibodies and in the case of Ablynx, Nanobodies, can be raised and selected to bind with high affinity selectively to cancer cells in a tumour. Cancer cells are exquisitely sensitive to certain toxins such as the PBDs produced by Spirogen.
By linking the PBDs to tumour targeting nanobodies a drug is produced that has the selectivity of a nanobody and the potency of a PBD.
The advantage of this approach is that more of the drug is delivered to the disease and less to healthy organs. This antibody drug conjugate (ADC) approach has proved highly effective in the clinic.
Ablynx and Spirogen have recently announced a research collaboration to evaluate the potential of a novel anti-cancer drug conjugate. Please can you outline what each company will be contributing to this collaboration?
Ablynx has developed a robust and broadly applicable platform for the identification of highly specific VHH antibodies (Nanobodies). With this platform Ablynx has identified Nanobodies against a target which is expressed by a broad spectrum of tumors.
The Nanobodies are highly specific and small enough to allow for deep tumor penetration and target-specific accumulation and internalization. There features are an important prerequisite for a targeted delivery approach of a toxic compound.
Spirogen has developed highly potent cytotoxic drugs that maintain efficacy in drug resistant cells. These drugs have been developed with chemistry that allows them to be linked to antibodies and nanobodies.
Spirogen also has the expertise to carry out the linking chemistry and to analyse and purify the resulting ADCs.
What are the aims of the collaboration?
Initially the aim is to demonstrate in vitro and in vivo efficacy of the Nanobody PBD-conjugates.
After that, such Nanobody-DCs will be developed either as part of the collaboration or in partnership with pharmaceutical and biotechnology companies.
How did the collaboration originate?
Ablynx has carefully selected Spirogen since their linker-toxin platform seems to be the best match for our Nanobodies. We belief that high specificity, the small size of Nanobodies in combination with half-life extention technology and the opportunity for site-directed coupling of a highly potent linker-toxin are important prerequisites for an ADC-approach.
Spirogen, having the potent drug technology, sees that a very tumour-specific technology like the nanobody, that doesn’t have the same size as a full antibody, has certain advantages – particularly in solid tumours.
Spirogen has been looking at a number of potential partners in this area and we had known Ablynx for many years and feel that the combination of these two technologies together should work well in this particular area.
How long is the collaboration expected to last?
The initial phase will last up to one year, anticipating success in this, a longer term collaboration is envisaged.
Why do you think research collaborations are important?
ADCs are a good example of why collaborations are important. World class biotechnology involved in developing the Nanobodies is married to the world class chemistry of the PBDs and linkers to produce the ADCs.
There are few if any companies globally that have the capacity and core technology and intellectual property to bring together cancer target, antibody, toxin and linker to develop a clinically effective ADC. This is typical of many fields of drug development today.
Professor Gilles Vassal from the Institut Gustave Roussy, Paris-Sud University, France has recently been quoted as saying “Fostering open collaborations with many groups from industry, regulatory bodies, academia, governments, and patient advocacy will be crucial to speeding up drug development”. Do you agree with this statement and are there any plans for collaborating with more institutions in the future?
Yes, both Ablynx and Spirogen collaborate extensively with institutions, universities and companies to develop drugs using their technologies.
How do you think the future of oncology research will develop?
Increasingly cancer therapies are targeted to patients that can be shown to have tumours with a specific biology as exhibited by certain markers.
It is tempting to think in terms of target identification, target acquisition, payloads and delivery systems as an analogy for the genetics, diagnostics, targeting molecules and therapeutic effectors that will make up the future of cancer therapies such as ADCs.
Do you think collaborations will play a big part in the future of drug development?
Certainly, in fact I think they already do. With antibody drug conjugates you’re bringing together protein engineering, biologics development together with very specialised and exquisitely potent small molecules and the linkers that allow you to conjugate those things together.
It is very unlikely, even in very large Pharma companies, that you will have all the expertise you need to be able to pull those things together and manufacture them and take them to the clinic.
And so, almost necessarily in the development of this kind of technology, you have to have collaboration.
What are Ablynx’s and Spirogen’s plans for the future?
Both Spirogen and Ablynx will further capitalize on their world-class technology platforms.
Our specific plans will depend on the outcome of the feasibility study we are planning to perform. If we anticipate a positive outcome, we have the opportunity to further extend the collaboration. Both companies have the capacity to develop ADC drugs through into the clinic. Hopefully if we produce good data from both technologies together, then Spirogen’s plans will be to drive development forward in collaboration with Ablynx and potentially in time with another party.
Where can readers find more information?
About Dr Andreas Menrad and Dr Chris Martin
Andreas Menrad joined Ablynx from Genzyme where he served as General Manager and Vice President Antibody Therapeutics.
Prior to his position at Genzyme, Andreas held science and management positions in preclinical research dermatology and oncology at Schering AG, Berlin, Germany. During his career in pharmaceutical industry, Andreas progressed both NCE and NBE from bench to bedside.
Andreas Menrad received his PhD from the University of Stuttgart and held a research position as a post doctoral fellow at the Wistar Institute in Philadelphia, USA.
Dr. Chris Martin is the Chief Executive Officer of Spirogen Ltd and is also a Director and Collaboration Manager for ADC Therapeutics Sarl. He was a co-founder of Spirogen Ltd in 2000, and is a member of the board of directors of both Spirogen and ADCT.
For Spirogen, Chris led the origination and completion of numerous collaboration transactions, including agreements with two of the leading industry players in the ADC area Genentech and Seattle Genetics. Chris received his DPhil from Oxford University.