Until recently, New York's Mustang Bio has focused its business exclusively on cell therapies. Earlier this week, the biotech announced plans to license an ex vivo lentiviral gene therapy developed at St. Jude Children’s Research Hospital for the treatment of a rare illness known as XSCID, otherwise known as bubble boy disease.
The deal underscores what has been a year of growth for Mustang. In June, the company celebrated the opening of a 27,000-square-foot Massachusetts manufacturing plant that executives believe will be able to meet the clinical and commercial supply needs for its investigational CAR-T therapies.
BioPharma Dive spoke with the company's Chief Technology Officer Knut Niss about Mustang's new plant, its pipeline expansion and the manufacturing and business hurdles associated with two of the most challenging areas of drug development.
This interview has been condensed and edited for clarity.
BIOPHARMA DIVE: How are things going so far now that the Massachusetts facility is open? Any noticeable changes to Mustang's business?
KNUT NISS: We are now working full steam [ahead] to get ready for our first IND, which we are planning to file at the end of this year. As you can imagine, especially on the manufacturing side, there's a lot of activities.
One change is that we are onboarding quite a few people. I think we're around 30 employees right now; we were 16 I think when we opened the facility. That's one of the major changes.
The new hires: are there any specific areas they're going to?
NISS: We're staffing specially on quality assurance and quality control, and at the same time also we're adding some people for research.
And why those areas?
NISS: As you can imagine, quality control is one of the main things for us because we're making a cell therapy for a patient, which means we really want to make sure that we bring a very safe product back to the patient.
There's a few different areas we have to release of the product. We need specialists for that, who run the essays the way they need to be run, or we need a quality control for the materials we are bringing in. And overall, quality control for the facility, but that goes towards environmental monitoring, etcetera. So quality control, that's one of the most important roles to fill right now. That's actually also one of the hardest to fill because everybody else is, of course, paying attention to quality control. So we're very lucky that we're bringing in high-quality people.
What are some of the challenges or thoughts you have for assuring there's an adequate supply of your therapies for clinical testing?
NISS: In the CAR-T process — and I honestly don't know how many materials we use — but it's fair to say you use a lot of different materials. One headache I always have is to assure that we have the right materials on site when we manufacture. So the supply chain is a very important thing for us to manage that.
We are also very aware that bringing the right product to the right patient is a very critical piece in the autologous therapy, so we partnered with TrakCel, TrakCel being a company that develops a software tool to track the product from the patient to the manufacturing side and back.
And how do those types of deals come about? As a smaller CAR-T company than say a Novartis or Gilead, how does Mustang finance these partnerships?
NISS: One thing in terms of financing, we are [doing] basically what I would call stage-appropriate investments. We are going into a Phase 1 clinical trial. That is different from a pivotal trial or commercial trial in the sense of what is required.
I mentioned TrakCel. We're building that system slowly out in [phase-appropriate steps and investing] at the right time.
We obviously don't have the resources that Novartis would have, which means we need to make some compromises along the way in terms of: we would like to bring something in that is more for pivotal readiness that we are not bringing in today. We're bringing it to when we need it.
We looked at what is really critical for the success long-term, with an eye on commercial product launch already. TrakCel is a good example where we made an investment that could have been delayed, but we realized if we were to delay that particular investment, the investment we will have to do down the road would be much higher. So by bringing it in early, we can do it phase-appropriate and we don't need to play catch up later down the road.
What lessons has Mustang learned through CAR-T manufacturing that may apply or help in this new licensing deal with St. Jude?
NISS: There are many lessons. One is that process matters. The St. Jude asset is for X-SCID hematopoietic stem cells. Still a lentiviral transduction similar to what we use in CAR-T, but a much shorter process, a different cell type. Nevertheless, what we learned in the CAR-T field is that focusing early-on on designing and implementing a really commercial-ready process ... can be very efficient. Where can we make the process more efficient from a labor standpoint, from a facility utilization standpoint? That is what we learned in CAR-T that we will bring to the X-SCID program.
Looking forward, what can Mustang improve upon as it continues to manufacture its cell and gene therapy candidates?
NISS: Especially now with bringing in another program that is very different, [we're looking at] can we improve certain things there? Frankly, we are still small enough that we actually have almost daily discussions among functional lines. I think one of my learnings from coming out of big pharma is that the interaction — especially in an autologous cell therapy between functional lines — is very critical. [Quality assurance] needs to talk to manufacturing on a constant basis, but also to process development.
With the growth we're anticipating over the next few years, we will eventually hit a time where it's probably harder to manage, but at this particular point, would I improve anything? I'm not sure today, but I'm very sure that we will eventually learn that some things are not working as well as we wanted, and then fix it.