In the sixth episode of this podcast series, UCLB’s Director of BioPharm, Dr Richard Fagan, is in conversation with Dr Chris Williams. Dr Williams is formerly a Senior Business Manager at UCLB; he is now the SVP, Corporate Development at Autolus. Chris was part of the team that founded Autolus in 2014. Autolus, as a company, is focused on the development of engineered CAR T cell therapies, which has been transformational for patients, particularly in blood cancers.
Transcript edited for clarity and context
Dr Richard Fagan 0:02
So please Hello and welcome to our sixth episode of the podcast series from UCL Business Big Talks on Big Impacts. UCL business or UCLB, as it’s known, is the commercialisation company for UCL, and this year-long podcast series celebrates the company’s 30 years of collaboration and impact.
I’m Richard Fagan. I’m director of BioPharm at UCL Business; my team of business managers is responsible for the Life and Biomedical Sciences’ area of the university. And today, it’s a pleasure to welcome Dr. Chris Williams. He’s Senior Vice President of Corporate Development at Autolus and prior to that, Chris was a member of my team at UCLB. Welcome, Chris.
Dr Chris Williams 0:56
Thanks, Rick. It’s a pleasure to be back at UCL. Great.
Dr Richard Fagan 1:04
Chris, could you tell us a bit about Autolus?
Dr Chris Williams 1:07
Yeah, so Autolus was a UCL spin out company. We founded Autolus in 2014 and Autolus, as a company is focused on the development of engineered CAR T cell therapies. So basically, take patient’s T cells and re-engineer their specificity towards the patient’s tumour. And these therapies have been transformational for patients, particularly in blood cancers. And now there were five approved products based on CAR T cell therapies.
Dr Richard Fagan 1:43
Have they looked at efficacy in solid tumours?
Dr Chris Williams 1:49
Solid tumours are much more of a challenge for any cancer therapy, and also for CAR T. So, efficacy in solid tumours hasn’t been as forthcoming with CAR T cell therapies, mainly due to complex tumour microenvironment of a solid tumour versus a blood cancer.
Dr Richard Fagan 2:12
Right. So how did you end up Autolus? Could you tell us a bit about your career?
Dr Chris Williams 2:17
We founded Autolus in 2014; and I worked on as UCL’s nominee on the Board of Directors for about 18 months, and the team at Autolus then asked if I would come and join and set up their business development function, so being there, so almost eight years now. So, work my way up through the ranks, and now lead that function at Autolus.
Dr Richard Fagan
And how big is your team?
Dr Richard Fagan
It seems fairly modest. There are four of us in the BD team, and I also oversee the IP team at Autolus; so, another four people.
Dr Richard Fagan 3:04
For those of us who are in the know, obviously, activities and business development is obvious, but could you explain to our listeners, some of those might not know what exactly does a business development team do at Autolus?
Dr Chris Williams 3:21
Yes, so we’re focused on sort of developing the assets the company through partnerships. Sometimes working with a larger company or a company with a different expertise can accelerate the development of a drug or therapeutic technology. For instance, you might want to work with a large pharma company who has access to greater development resources, and that would accelerate the development of your therapy towards a regulatory filing or an approval.
Dr Richard Fagan 4:00
Right. And can you just tell us, when did you first start at UCL Business?
Dr Chris Williams 4:08
So, I had to look this up, Rick. You asked me this question before. I started in 2009, covering one of our colleague’s maternity leave parental leave, and then, was made permanent a year later.
Dr Richard Fagan 4:29
And do you think your time at UCLB helped you with your career at Autolus or indeed, in any sort of business development function?
Dr Chris Williams 4:40
Yeah, absolutely. I think UCLB is quite unique in this space, particularly in the UK and Europe. The sort of volume and variety of different projects that you get involved in itself a real boot camp, if you like, of business development. You really can learn very rapidly. I think there are only one or two places like it in the UK; so you’re a really good grounding and environment. And the management team, the senior team, at UCLB are also hugely experienced. They’ve been doing this at UCL for a long time and bring a lot of pragmatism to the table, which is incredibly important what we do in business development.
Dr Richard Fagan 5:34
Yeah, I agree. Thanks. I assume you’re talking about me?
Dr Chris Williams 5:40
Dr Richard Fagan 5:43
Would you recommend a career in tech transfer to someone if their long-term goal was to get into corporate business development?
Dr Chris Williams 5:55
Yes, I think it’s a really rich and broad environment. You can get involved in lots of aspects of business developments from very early stage, from filing a patent on a technology and supporting an idea into realisation of a potential therapeutic approach; through to being involved in clinical stage programmes (with) UCL and other universities in the UK, able to take these things all the way through to the clinics. I think it’s a really rich environment in which to learn BD. Thanks.
Dr Richard Fagan 6:42
Thanks. What was the genesis of Autolus?
Dr Chris Williams 6:45
Dr Richard Fagan
How did it come about?
Dr Chris Williams
It took a while to kind of get Autolus going. I remember meeting, Martin Pule who is the academic founder of Autolus in the Cancer Institute for a coffee, not understanding a single word that he said. He was talking (about) immunology; my background was molecular biology, and I had to learn fast. I think that’s something that we have to do in in BD.
Martin had lots of ideas, more ideas than he knew what to do with. And we began to create some structure around those ideas and pull them together into packages of inventions that could be filed into new patent applications.
We receive some support from and funding from UCL Business proof of concept fund, which should allow Martin to focus on generating data for patent filings. And we amassed a range of patents, I think, currently 23 patent families licenced from UCL into Autolus, and those became the sort of underpinnings of what we’re developing today into the clinic.
So, discovering and securing the technology was one part but also generating interest and investment interest in Autolus, we, at the time, there was a lot of focus on cell and gene therapy. There have been some exciting data from academic groups in the in the US. There’ve been some exciting stuff going on at UCL and other gene therapy areas; so is interest in investing in gene therapy. We spoke to a number of potential partners and investors and came across Sycona Partners, who were the investment arm of the Wellcome Trust and work with them to set up Autolus and secure £30 million worth of Series A funding to set up the company.
Dr Richard Fagan 9:09
And as I recall that 30 million Series A was the largest Series A that a European biotech had raised to date.
Dr Chris Williams 9:19
Yes, it was certainly notable at the time. I think what’s exciting since it’s been superseded a number of times, and we’ve had a real quick period of investment into UK and European University to rival biotech companies.
Dr Richard Fagan 9:39
And the thing that it really allowed Autolus to do, was to hit the ground running. You could hire a real experienced senior management team; you could hire individuals to work in the labs to really get the ball rolling, couldn’t you?
Dr Chris Williams 9:55
Yeah, so we were able to attract top talent from around the world to come and work on the programmes we were developing at Autolus. We hired Christian Itin, who was the CEO of Micromed, the company that developed bi-specific T cell engages, and sold out that platform to Amgen, and now have an approved therapeutic based on that approach. So we got some real pedigree into the company people who knew how to do this, and were able to apply those learnings to take Autolus programmes into the clinic.
Dr Richard Fagan 10:43
And was it always your and Martin’s intention to bundle the IP into a spin-out company, or was there ever thought of, we could licence some of this to BMS or to Novartis?
Dr Chris Williams 10:59
Well, we did do some light licencing prior with Martin’s technology, so we licenced one of his safety switches to Selectus Therapeutics; that approach is now being developed by Allergin in the US. But I think we were able to develop such a breadth of potential things and at the time, we didn’t know which one would work. So, it wasn’t a question of ‘we’ll pick this one and licence this one to Novartis’; it was we need to invest in all of these things in a in a much broader way. Maybe take four or five things into the clinic, and then we’ll back the one that that works. So it was about creating ‘shots on goal’ at the time. The intention was to make this board and ideally get the investment to develop this in a spin-out company.
Dr Richard Fagan 12:02
So Autolus is really a CAR T platform company, it got a raft of patents etcetera. Just out of interest, do you think, in order to get investment from VC investors into a platform, do you think you need to have a raft of programmes that have been developed using that programme? Or do you think they would be as interested in the platform if you had none or just one programme?
Dr Chris Williams 12:32
I think the best way of proving the potential of a platform is to take something into the clinic and show that it’s differentiated in the clinic. Otherwise, why is the partner going to take a risk on your platform? I think you have to back your own technology platform and take one or maybe more things into the clinic. That would be my approach.
Dr Richard Fagan 13:00
Yeah, of course, there’s always the danger (with) companies who have a platform that they tinker a little bit here, tinker a little bit there and they spread themselves too thin; and you never get full validation in one programme, because they jump from one thing to another.
Dr Chris Williams 13:19
Yes, focus is absolutely key in developing therapeutics and developing technologies. You’ve got to really focus on generating the data set that’s sufficient to take something to the clinical, generating that clinical proof of concept data that allows you to unlock a phase two or phase three clinical trial. Too much tinkering is not time well spent necessarily because we all have limited resources and limited capital. So, we have to spend our time wisely.
Dr Richard Fagan 14:03
So how many programmes does Autolus currently have in the clinic?
Dr Chris Williams 14:07
So currently, we got four programmes in the clinic to a late-stage preclinical programmes, one which will enter the clinic later this year, and one hopefully next year. Since we founded the company, we’ve taken seven programmes into the clinic over the last eight years. Our most advanced programme is called OB cell (not going to pronounce the long name for OB cell) but that’s a CD-19 CAR T-cell therapy for in the lead indications adult acute lymphoblastic leukaemia or ALL.
Dr Richard Fagan 14:51
So, I know there are other CD-19 CAR T’s. It’s basically a raft of them being developed out there; seems to be the favourite antigen. What differentiates Autolus’ programme?
Dr Chris Williams 15:07
Yes, so there are four CD-19 CAR T’s approved, and they’re all based on a similar antibody. So, chimeric antigen receptor takes a single chain of fee fragments of antibody and couples it to a signalling, a T-cell signalling domain to activate the T-cell and eliminate the cancer cell. The approved CAR T-cells therapies use a binder that is a very high affinity antibody, so it binds very tightly to its target (and) doesn’t let go.
When Martin designed the OB cell approach, he wanted to create something that was more physiological; so, when a T-cell naturally encounters a foreign antigen presented on the surface of a cell, its’ interaction with that target cell is very transient. So, we tried to recapitulate that with our CAR and generated a binder that has a very transient or fast-off interaction with a target cell. That allows the cell to find multiple target cells and to what we call ‘a serial killing mode’ results in a T cell that’s less exhausted and releases less cytokines.
And in the clinic, this results in CAR that has more potency and less immuno-toxicities. So, the two major toxicities we see with CAR T-cell therapies or cytokine release syndrome, which you will call was a complication of COVID infection is the overactive immune system and a new neurotoxicity. Based on the design of OB cell, we see much less cytokine release syndrome and neurotoxicity compared to the approved products, and you have much better expansion and function in in patients.
Dr Richard Fagan 17:21
I understand Autolus will be having as a poster; a couple posters at the upcoming American Society of Clinical Oncology meeting.
Dr Chris Williams 17:29
We plan to present the first full dataset from the Felix study and the Felix study is our phase two study of OB cell in adult ALL patients. And it will be an oral presentation and our colleague, Claire Roddy from UCL will be giving the presentation at the session at ASCO.
Dr Richard Fagan
Dr Chris Marshall
Yes, absolutely. It really exciting to see that programme progress from the idea that we had at UCL all the way through to what could be a pivotal clinical data set. The next steps for that programme would be to pull the clinical data together with the manufacturing package around OB cell and file that with regulatory agencies for approval.
Dr Richard Fagan 18:47
The four programmes that you have in the clinic right now, are they all underpinned by UCL intellectual property?
Dr Chris Williams 18:57
Yes. The majority of them involve patents that were filed at UCL that we’ve licenced, and actually two of those programmes in the clinic are part of a clinical collaboration with the UCL; so we work closely with the Cancer Trials Centre at UCL and conduct these early phase one studies in collaboration with UCL. The two other studies are led by Autolus and sponsored by Autolus.
Dr Richard Fagan 19:33
Right. So, is the OB cell that must be a multi-centre global?
Dr Chris Williams 19:39
Yes, it was 26 clinical sites across the US, UK and Spain. The majority of those clinical sites were in the US.
Dr Richard Fagan 19:54
Manufacturing CAR T is really quite a complex process, isn’t it? How do you manage 26 sites in delivering the CAR T to them, or them to get into the patient? Are each site doing their own manufacturing?
Dr Chris Williams 20:11
Yes, you are right. Manufacturing of CAR T-cell therapies can be very challenging and it’s an area that we focused a lot on since we founded that company. We have a team based in Stevenage in the UK that manufacture for all of our clinical studies and they also support the global logistics that are necessary to get a leukapheresis from a patient, transport that to our manufacturing sector of the UK, engineer the cells and then transport that back to the patient for infusion.
So, the cycle which we call so vein to vein is very important; it’s very important to get that as short as possible and you we have built a commercial scale operation, in order to allow us to do that, and we are able to turn products around very efficiently wherever the patient is located. And very pleased that that team has been able to tackle that key challenge of our field.
Dr Richard Fagan 21:48
Are any of the approved CD-19 CAR Ts or indeed any CAR T approved by NICE for sale in the UK?
Dr Chris Williams 21:59
Yes, Yescarta and Tecartus from Kite Gilead are approved for treatment of mantle cell lymphoma and diffuse large B-cell lymphoma. Kymriah is also approved for treatment of paediatric ALL and diffuse large B-cell lymphoma. These are all gone through the nice reimbursement process, which looks at the long-term outcomes of these patients and assesses reimbursement on that basis. And if you think about a therapy that can provide, potentially, curative outcomes for these patients, these products are priced accordingly.
Dr Richard Fagan 22:51
So, knock wood, one day we’ll be seeing the Autolus OB-cell on the market here in the UK?
Dr Chris Williams 22:59
Absolutely, I hope so. It’d be really exciting to see something that was developed in the UK, all the way through, you know, phase one and phase two clinical trials and end up available to for the treatment of UK patients and patients globally.
Dr Richard Fagan 23:19
Absolutely. So, what would you say (and I don’t know if you can add to this) the long-term vision for Autolus is?
Dr Chris Williams 23:32
The vision, what we’re intensely focused on at the moment is, is developing the package for regulatory submission for a B-cell for the first indication, which should be adult ALL. We also have early phase clinical studies in different types of B-cell cancers, and it would be nice to realise the potential of OB cell in those different indications through other phase two phase three clinical studies.
Dr Richard Fagan 24:09
So, is that what you do? First of all, get it approved for ALL but then, expand the indication maybe into paediatric or something along those lines?
Dr Chris Williams 24:24
Yes, certainly into paediatric ALL but also, you know, other lymphomas rather than leukemias that could be addressed with OB cell.
Dr Richard Fagan 24:35
Right. So, in the long term, (and I’m sure you have all this success) do you see Autolus like the next UK or UK-based Genentech or Biogen or something along those lines?
Dr Chris Williams 24:53
Wouldn’t that be great to be a Genentech or a Biogen! I think it would be great if we could create a UK biotech that had that sort of longevity, like a Genentech or a Biogen. I guess we’ve had some companies like that in the past, like Cell tech and Medi as well, which of those technologies still survive within larger companies. We would love cell and gene therapy to be in the UK for the long term, based on what we’re doing at Autolus.
Dr Richard Fagan 25:41
Now, absolutely, and as you know, that’s one of the sweet spots for UCL and as a result of that, the majority of our clinical pipeline, of which we have 22 different assets in clinical trials right now (a number of which are Autolus’) are very heavily weighted towards cell and gene therapy.
Dr Chris Williams 26:09
I think it’s a fantastic melting pot for new approaches that you have at UCL, and it’d be great to see some of these products I know you’ve had. Some of Amit Nathwani’s products go all the way through to approval recently. Hopefully, we’ll get a few more in the next few years; true testament to, sort of, the ingenuity and drive of some of the academics we have at UCL.
Dr Richard Fagan 26:40
No, I agree. Although, certainly with OB cell and with myself with Amit, the recently approved Roctavian, I wasn’t involved in the actual development of it, but I feel like I’ve been involved in getting drugs, something went all the way to market and quite proud of that. I’m sure you’ll feel the same way with OB cell once it gets approved. There are not many people who could say that, Chris.
Dr Chris Williams 27:09
Yeah, it’d be exciting, but we’ll keep our feet firmly on the ground. There’s a lot of work to be done before we can talk about approvals.
Dr Richard Fagan 27:20
Yeah. Great. Well, that’s it for me. Thank you very much, Chris. Really appreciate you coming in and if you want your old job back, you know where we are.
Dr Chris Williams 27:29
Thanks very much, Rick. Pleasure to catch up and talk about UCL and old times. So, thank you.
Dr Richard Fagan