Paul Kerr discusses Antibody Humanization with Pharma TV

Fusion Antibodies managing director Paul Kerr recently met with PharmaTV News’ Adrian Dawkes to dissuss our Antibody Humanziation platform.

Fusion Antibodies managing director Paul Kerr recently met with PharmaTV News‘ Adrian Dawkes to dissuss our Antibody Humanziation platform. Check out the video interview above or the video transcript below.

Video Transcript

Adrian Dawkes: Hello and welcome to Pharma Television News review, here at the Anglonordic life science conference 2016 in London. On the show today I have Paul Kerr, the managing director of Fusion Antibodies. Paul, welcome.

Paul Kerr: Ok, thanks for having me Adrian

Adrian: Pleasure. Fusion Antibodies – It’s a name that’s been around a little while but I think your company has been through a couple of changes. Perhaps you could start at the beginning and give us the story.

Paul: Well I’ll give you the short version of the story or it would be a very long interview. Basically we were founded as a spin off from Queen’s University in 2000. And when we started we were primarily a therapeutic drug discovery company, in antibody drug development, in oncology. So for the next ten years we perused developing a number of targets in the oncology space. But when I took over as managing director, we really pivoted over to being a full service CRO company in the antibody humanization and cell line development space and putting some of our R and D targets secondary and running them on the more virtual model.

Adrian: And what was the driver for that? Because normally people kind of flip the other way. They start off doing a service business and thinking actually I could develop some drugs, why don’t I do that because the riches are beyond imagination. But you went the other way. Was it financial? What was the driver for this?

Paul: Financial. By the time one of our lead targets, Cathepsin S was ready to go towards the clinic, we got hit by the tsunami of the credit crunch of 2008 and 2009. And, really we had to re evaluate exactly how we were going to move forward and keep the whole company moving forward so we had to basically flip everything right over. So we reached a really critical point where we needed a substantial injection of cash to go to the clinic and cGMP production, and it was just at the wrong time.

Adrian: You did the smart thing. Survival mode, gathered some business and it’s grown from there?

Paul: Absolutely. Well, prior to being first and foremost being a drug discovery company and drug development company, we also did a little bit of CRO work, just through the contacts we had. It wasn’t really the main thing. The main thing was the drug discovery, but, as you said, as you go forward with the drug discovery, it is a huge investment. And so, really, to survive we needed cash, we needed to go back to what we’re really good at, engineering antibodies, sequencing antibodies and humanization of antibodies. So moving forward we developed a next generation CDRx grafting platform, an in silico computer based algorithm, that combined looking at the CDR definitions of Kabat, Chothia, IMGT. To make a more rapid robust method of humanization and really we developed that and went round in 2012, 2013 to sort of promote that to clients around the world. So that has been a fantastic success and led us to a path of profitability.

Adrian: Well that’s great to hear that the model you’ve adopted has made a successful business out of that. And the business is founded in antibody engineering, as you’ve just said CDR grafting, it’s an area I’m familiar with from another life when I worked for a company that did the same thing back in the 80’s. So that’s a technology that’s been around for a while. But you mentioned some words there, in silico, where we’ve done a special algorithm. What are you guys doing different to differentiate? Becuase there are a lot of companies out there doing antibody engineering of some sorts.

Paul: True. Well what we went back to focus on, we know that a lot of people doing antibody engineering are trying to humanize or make humanized variants. To get around the main CDR grafting patents they looked at other methods of achieving that and getting a little bit of IP around that but we felt that maintaining the conformational integrity of the antibody was the highest priority for manufacturability. So we wanted to not only make the best humanized candidates we could in terms of conformational integrity but also look at the manufacturability from the get go in terms of expression and cell line development. So when we made the humanized variants we would make a matrix and screen those in small amounts to ensure, of course, that we’ve maintained the integrity of the antibody in terms of its binding, characteristics to the parental and then also we wanted to select ones that had the capability of going all the way to commercialisation. So really planning for success at the very outset.

Adrian: So you’ve got some special methodology where you do what you do, but you can pin point and say, actually that’s the antibody that’s going to make it all the way through to scale up and manufacturing into the clinic and become potentially if it’s efficacious and safe, a therapeutic product.

Paul: Absolutely, and what we’re concentrating on is our expertise in the antibody humanization. Designing that, and the cell line development, so providing the tools to allow our clients from large pharma right down to mid tech biotech’s to spin out companies. To provide them the necessary materials and materials at the right point and the right time in the right format so they can do the actual scientific testing. The reason why the antibody was selected in the first instance. And moving forward we’ve a network of high quality service providers from drug discovery through Mab Discovery in Munich to Protogen for analytics, Biaffin for biacore analysis and we also have a partner for cGMP production and we use their cell lines, Celonic in Basil in Switzerland. And in the oncology side for cell line development and in vitro, in vivo trials we have a partner in Paris called Early Stage Drug Discovery.

Adrian: Ok but there’s no focus in the service business other than it’s antibodies, you’ll do it across therapeutic areas, whatever people come to you and say make me an antibody you can do it.

Paul: Absolutely, and whatever that antibody is we will engineer it to the best possible humanized variant.

Adrian: Do they have to give you a murine antibody as a starting point? Where’s the start?

Paul: Starting point is a sequence, either murine, we’ve done murine, we’ve optimised our CDRx algorithm murine, mouse, rat, rabbit also, we’ve definitely been specialising a lot in rabbit because we also see that they do produce higher affinity antibodies and we’ve also been involved in a few llama projects and even humanizing a chicken. So in the last 4 or 5 years we’ve done about 55 humanization projects from Japan, Europe, and US.

Adrian: And presumably you’ve been doing that a while. Are some of these in the clinic already?

Paul: Well we know that there’s 4 of the first, let’s say 20 or so antibody projects we’ve been involved in 3 or 4 years ago, they are now starting to enter the clinical trials this year and early next year

Adrian: And are they behaving as you predicted?

Paul: Well because we we’re fee-for-service, some of them are large pharma based companies and we don’t actually know. And it’s only through meeting people and they are telling us, “oh, that’s progressing”. We don’t even know what the target is for them or anything in some of the cases. In some of the smaller companies we would have more feedback so from this it’s been excellent.

Adrian: No news is good news in that respect.

Paul: Well, I think as long as it’s going forward into the clinic, we’re delighted.

Adrian: How do you line up against the HuCAL mouse or other technologies that give you totally human antibodies rather than the CDR grafted of which there are, drawing on my ancient history, you still get some anti-human responses around the CDRs maybe towards the variable regions where you have to make slight adjustments. Do you still see that or is the technology moved on?

Paul: We think the technology has moved on. We can do further enhanced polishing steps. When we do the humanization we do identify, we do an in silico epitope screen and we identify T cell epitiopes potentially inside the CDRs. But primarily in our first matrix of humanized variants we tend to highlight them but leave them alone because, first and foremost those T cell epitopes may be critical for the formation of why that antibody is unique and why it was selected in the first place. So we first do the humanization and in consultation with the clients we say “we can make additional substitutes here to remove any possible immunogenicity”. So it’s a second stage polishing step that we would offer.

Adrian: So what’s the business model? Do you risk share? Do you have reach-throughs to the drugs? Or is it just pay and play and go away?
Paul: When we started it was just basically pay and play and on they go but now as we have matured and got a lot more confidence in the technologies that we have and in what we are putting into the drug discovery process and development for the clients we have now moved towards a success fee based payments. Every deal is negotiable so some people want to pay the money and it’s theirs but more lately we have been doing more risk share reward, success payments. It’s still royalty free but it’s basically a reduced upfront payment and then a success payment when it hits the clinic or different milestones.

Adrian: Ok. And are you generating IP for your partners or do they rely upon IP that you hold? They have to licence.

Paul: No when we do the service the partner has the full rights to use the technology. There’s no additional contract negotiations required. So it really is fee for service with just straight forward one off success payments. Very simple.  So what we’re trying to do is encourage more and more people who are using the mouse or other, rabbit, antibodies to allow them to come earlier to get them humanized and get the drug candidate and work on that as soon as possible.

Adrian: And you’ve still got a few things from the old days in the drug discovery days going on?

Paul: Absolutely yea, one of our main antibody target was fsn0503 an anti cathepsin S protease inhibitor and we’ve partnered up with a company in Australia called Clarity Pharmaceuticals who do a fantastic job in adding their technology in terms of imaging to find out exactly where it goes and also use their radio nucleotides in terms of imaging and as a therapeutic agent to add extra bang and killing power to the molecule that we’ve created.

Adrian: Well Paul it’s great to hear that you’ve made a success out of an antibody engineering company and generating good business and excellent products that hopefully make their way to the clinic. Thanks for joining us today.

Paul: Ok, Thank you Adrian.