Two Draper Laboratory executives discuss the non-profit’s new collaboration with Kite, and Draper’s approach to partnering with biopharmas.
Five years ago, after the federal government cut back on R&D spending, Draper stepped up its pursuit of private-sector customers in the life sciences, aerospace and energy. In the life sciences, one of the areas in which Draper began to invest was in research and technology development related to chimeric antigen receptor T-cell (CAR-T) therapies
On Tuesday, Draper expanded its footprint in the life sciences by agreeing to apply its engineering services and portfolio of cell bioprocessing technologies in a collaboration with Kite, a Gilead Company, designed to enhance Kite’s development of pipeline cell therapies. Through the collaboration, whose value has not been disclosed, Kite aims to improve its next-generation cell therapies as well as increase its cell manufacturing throughput by using Draper’s microfluidic electroporation-based platform. The end-to-end bioprocessing system consists of four modules: an acoustic separation platform, a viral transduction platform to accommodate for situations that need to continue to use viral vectors, an electroporation unit and an inline buffer exchange unit to reduce loss when changing media or washing cells.
Kite is among several companies and regulators that have partnered with Draper in biopharma. In July, the nonprofit R&D lab won a $2.19 million, three-year contract from the FDA to develop an acoustic cell separation system for use in the development of cell therapies, one of multiple advanced R&D contracts totaling $69.8 million awarded by the agency. Last year, Draper teamed up with Bristol-Myers Squibb to develop a liver tissue model for screening the toxicity of drugs. And in 2016, Draper and Pfizer partnered to create versions of Draper’s Microphysiological Systems (MPS) or “organs-on-a-chip” technology, with the goal of improving preclinical safety testing by creating more effective disease models.
Based in Cambridge, MA, with nine other locations nationwide, the Charles Stock Draper Laboratory finished the 2020 fiscal year ending June 26 with more than $672 million in operating revenue, up 7% from $626 million the previous year.
Tara Clark, Draper’s Vice President of Commercial Business, and Jenna Balestrini, Draper’s Head of Strategy and Business Development, Precision Medicine and Cell Bioprocessing, recently discussed with GEN Edge the Kite collaboration and Draper’s approach to working with biopharmas (This interview has been lightly edited for length and clarity).
GEN Edge: What are Draper’s goals in the life sciences?
CLARK: Our goals are to design and develop technologies that that we see as real pain points and improve processes that otherwise would not be able to be more efficient or more effective—including of course in CAR-T cell manufacturing. That’s one of the areas that we put some of our internal R&D money into in 2016 and we were able to come up with some really great solutions for the entire cell therapy industry.
GEN Edge: You speak of CAR-T cell pain points. What are some of those challenges? How have they been surmounted?
CLARK: There are business pain points and technical pain points. The technical challenges include the long times to manufacture therapy—anywhere from 17-21 days—based on a lot of shipping, and off-the-shelf equipment that was purposed for something else other than CAR-T cell manufacturing. Most of it is equipment of the ‘70s and ‘80s genre, so obviously there are issues with being able to link them together, to make sure that they’re robust enough for consistent manufacturing.
Companies like Kite have a real need to manage changes that happen in their process and be able to affect that with the regulators, without having to go back to tool manufacturers and try to beg and borrow for access to regulatory files, helping with regulatory questions that come up, etc. That’s what the goal is here: To try to enable some of these CAR-T cell manufacturing companies to what we call internally control their own destiny.
BALESTRINI: On the business side, there’s quite a few ramifications that come from leveraging equipment that’s not fit for purpose. So, when you hear things like a lot of cell loss, expensive biological reagents, single manufacturing provider, etc., they may not sound like catastrophic components to preventing you from hitting scale or being able to produce next generation therapies, but they really are.
We have created a series of modules that enable you to have isolation of cells and a rapid formation without using traditional magnetic beads, because those are affiliated with a lot of loss. We have in-line systems that allow you to deliver genes in very controlled ways, whether that’s virally or through electroporation and their continuous processes. We have the ability to scale, to meet the demands of high throughput requests, whether that’s an allogeneic process or an autologous process.
We have created the ability for a company to pivot according to whatever their pipeline looks like. We can accommodate from start to finish and from separation to gene delivery, to in-line washing steps. Those factors combined, leveraging the precision control that microfluidics can handle to you, really enables you to do modern day cell therapy production. But as things change in terms of your biological needs, as FDA guidance changes, you can really accommodate that with these systems.
GEN Edge: What advantages do Draper’s microfluidics approaches confer over other approaches?
BALESTRINI: Microfluidics allows you to have really interesting things that happen physics-wise on the micro scale. You can start to manipulate fluid paths and use that to your advantage. And the example of electroporation, when you start to use sheet flow dynamics, you can prevent cells from coming in contact with things like hydrolytic byproducts, or things that normally would kill the cells. You can partition them or you can co-localize them with your payload, so you can maximize your amount of transfection in gene delivery.
You can conduct away heat in a controlled way. The architecture itself provides a boundary to have a tighter degree of control than you otherwise would, so that enables you to have a more consistent product at the end of the day. What we’re after is not just making a consistent product, but one that’s going to work for the patient, one that’s going to be made much more cheaply. Cell therapy becomes what its potential is — having a wide accessibility because it’s affordable, to be able to unleash the ability to make allogeneic processing because your throughputs are so high. These are things that you can really achieve if you have precision control of things like sheer, and pressure, and heat. You really open up the possibilities of what you can do to cells before damaging them, in terms of gene insertion or handling. Those are the things that we want to capture on these platforms.
GEN Edge: What technologies will Draper look to apply in the Kite collaboration?
BALESTRINI: We have a few different systems that we’re putting into place. That includes cell separation, that includes two different gene delivery modalities using a viral transduction system that co-localizes virus in cells so that you can minimize your time and virus required to get to high levels of transduction.
Our electroporation system is truly continuous and allows the user to modify the waveforms according to whatever they need. That’s really cool, because as we know a lot about some of the modern day, say, mRNAs, cytosolic deliveries, what you can do to get high levels of transfection. DNA is a bit of an uncharted territory. We don’t really know for everyone’s specific biology what’s the best wave forms and combinations to give them.
These systems really allow the user to figure that out, and to be able to have the highest level of delivery without killing their cells along the way. Getting through two cell membranes (outer and inner) with genes without killing the cells on the way, without destroying those organelles, is quite the challenge. Being able to fine tune what you expose your cells to is pretty important.
GEN Edge: What treatments will Draper be working on with Kite? Kite’s pipeline mentions several indications in development for Axi-cel and Brexu-cel, as well as KITE-718 and KITE-439.
CLARK: There’s four modules that we have licensed development rights to Kite for the field of use of cancer. Individual modules can be developed either for any indication they have now, or any future indication. They are standalone modules at this time. It’s a complicated agreement in that it could have application for some of their developments way into the future. Right now, the field of view that we’re working is cancer, broadly.
GEN Edge: Would there be flexibility to expand into indications beyond oncology through this collaboration?
CLARK: There has been no discussion beyond oncology.
BALESTRINI: Back to the example of the magnetic beads: Those have a high level of specificity. But if you’re using, say, acoustic sound waves like we are to remove cells from a solution, you can change that to whatever form factor you need. So the same platform under different strengths can be leveraged to make sickle-cell anemia therapies, or start to work within stem cells.
CLARK: This does not include any kind of gene modification of stem cell therapies for innate disease. This is all around immune cell treatment in cancer.
GEN Edge: How did the companies come together?
CLARK: It started from a press release that we put out about our microfluidic electroporation platform. We had the relationships that when they saw the release, it resonated with them. They contacted us.
BALESTRINI: That press release with our initial data is, I think, what resonated with Kite.
GEN Edge: How did Draper come to focus on improving cell therapy?
BALESTRINI: I joined in 2016. And right around then, when Tara brought the vision of wanting to go into cell therapy, she came to Draper and said, precision control is something we desperately need in this field.
There’s two things that happen when you have inefficiencies. When we talk about loss of cells, what happens is, if you’re a patient that’s sick, and you have barely any starting material just to start with, that can wipe you out of being able to get something like this.
Second is that every step of loss you have, you have to make up for that on the back end with expansion. So you put these in plastic dishes that don’t have any of the signals that they have in the body, and they start to lose the properties that make them good at hunting cancers or pathogens in the first place. Shortening that process isn’t just to drive down the cost of goods, but it’s also to make that therapy work well. That’s one of the things that we’ve been thinking about from the beginning.
When we started in 2016, again brought on by Tara’s vision, we went into the field and talked to something like 60 different cell therapy companies to figure out their pain points. What’s going to really drive them to be able to make radical changes in medicine, by making these cell therapies accessible beyond third line refractory applications for patients? What is it going to take to get to earlier access? A lot of was driving down the cost. A lot of it was closing and automating it. A lot of it was accounting for the loss of starting material and being able to make systems that can work on very big difficult genes to deliver to cells under challenging conditions.
A lot of the equipment that folks started with was a great start. But it was not going to really get us there as a field.
In our discussions in 2016 with all these companies, we started to realize things like viral vectors. When we say we’re reducing viral vector, that was almost 75% of the cost at that time to make cell therapies. If we could cut that virus amount two or threefold, and decrease the time for the full process, it’s a multiple win. We created a microfluidic system that takes the cells in the virus and closely co-localizes them in a controlled way, so that you get more equal distribution of virus to cell, so you don’t have to worry about cells having inconsistencies or pathological side effects from having too many lentiviral vectors inserted. But also, we can just make them a better system at the end of the day.
GEN Edge: What is the significance of the Kite collaboration? It’s not your first collaboration in cell therapy. Is it the largest?
CLARK: It depends on how you define collaboration, but this is the first public one that we’re able to share.
BALESTRINI: One of the big advantages of not being a product developer is we’re not trying to push a product. We’re an innovation house, so folks have been pretty open with us about what their pain points are, luckily so. That way, we can start to really address whatever it is that they need and not try to retrofit a solution. So those 60 companies are really trying to figure out what those solutions need to look like. I’d say we’ve had ongoing work with more than a dozen of them.
GEN Edge: Does the Kite collaboration auger more activity for Draper in cell therapy or cancer immunotherapy going forward?
CLARK: We have many collaborations ongoing already in this space. People are trying to at this point to hone in on what their visions are. We don’t want to drive what their visions are. They know that we’re state-of-the-art engineering, and marrying engineering and biology. That’s what our niche is, and that’s what we can offer to them. We aren’t a typical engineering design company. We really take on the tough challenges that people have.
We think that there’s more opportunities in the space of cell therapy. But right now, the ones that we’re committed to making successful are these four independent modules for Kite in the field of cancer.
GEN Edge: Can you quantify by revenue or activity how much biopharma accounts for within Draper? How much is that expected to grow in the next year or two?
CLARK: Our mission is to get our technologies out there for the good of the American taxpayer. A lot of what is being developed Draper is for the good of our nation. This [Kite collaboration] is just an extension of things that we’re developing for the good of our nation.
We have biologic solutions that we’ve developed for the government that we can’t really talk about on this call. But given that we’re nonprofit, we look at our overall bio groups together and we don’t really report on any revenue numbers specific to that, because it’s all part of the government mission and the American taxpayer.
GEN Edge: With the Kite collaboration, will more people be brought into Draper as a result?
CLARK: We’re always looking to add quality biologists and engineers here. The good thing about Draper is we have a really deep bench. There’s roughly 1,400 technical staff here, which is comprised of biologists, physicists, and engineers of every flavor you can imagine. That’s not just biopharma. We’re somewhat of a matrix engineering technical organization, so any program that comes into Draper can tap any of us.
BALESTRINI: A lot of the engineers will work on both pharma programs and government programs, which is good for cross pollination of need. A lot of the next generation of tools that I think we’ll be able to offer spill over from different applications in the government, looking at off-target gene editing machine learning, AI that’s developed across the building for other precision medicine applications. We have a huge space program. And a lot of that technology and precision engineering can be translated, believe it or not, into biomedical spaces.