October 22, 2021 PAO-10-21-CL-14
Mike Nicholson (MN): The idea for Inceptor Bio emerged when our founder Shailesh Maingi was building the consulting firm Kineticos, helping his clients scale, grow, and overcome issues, while simultaneously investing in earlier-stage companies and new technologies. Shailesh combined this expertise, knowledge, and network with a personal mission to join the fight against cancer, conceiving Inceptor Bio as an ideal tool to drive innovation in cell and gene therapy.
MN: Instead of creating another fully integrated company around one asset or platform, Inceptor licenses technology around individual platform companies to maximize the chances of success. By supporting multiple companies, we’re increasing our odds; if one potential product fails in preclinical or phase I, we can move on and continue to advance other products, potentially all the way to commercial. Likewise, we can comfortably grow companies as we see fit and, if we have a winner, we have options on how to maintain the relationship, whether we take advantage of an M&A opportunity, let them remain independent, or keep them internal. Our objective is to allow those programs or companies to progress as is appropriate, allowing the technology to move forward as research verifies the hypotheses.
MN: Indeed, there are even other companies within biotech that have a similar model. However, there are key differences in how the sub-companies are established and organized and how ownership works. Inceptor is very interested in holding onto control longer, so we maintain all of the upside in our companies. We are also building our own manufacturing capabilities to support our companies and while we may use those capabilities to support outside partnerships, we have no intention of doing fee-for-service work. Particularly in cell therapy and gene therapy, it’s beneficial to have manufacturing in-house, where possible.
MN: It starts with Shailesh; Shailesh has a long career based on building organizations. Kyle Kimble, our Vice President of Intellectual Property and Legal Affairs, is a Ph.D. chemist who has practiced law with a focus on intellectual property, which is key to our model. We’re not in the business of discovery, we’re focused on development. As such, we obtain our technologies via licensing from academic partners and a key component of that is making sure that the intellectual property is right from the beginning and sets us up for success.
Abe Maingi is our Vice President of Business Operations, and he played a crucial role in getting the business up and running. The core team for a number of months was Shailesh, Abe, Kyle and, me, though we have recently started to grow pretty significantly. We’re now up to around 10 people, which doesn’t seem that large, but it’s more than double what we recently were, and we expect to grow significantly in the next year. To manage this growth and help strengthen our company culture, we’ve brought on Christine Wilson to lead human resources.
It’s clear that our model requires a tremendous amount of capital. To date, we’ve raised about $26 million. We need strong leadership within our financial operations, budgeting, and forecasting, We were able to add incredible depth and experience in finance by adding Jason Lawrence who was most recently involved with Ask Bio.
Matt Haines, most recently from AveXis and Novartis, is leading our manufacturing operations, and he has really elevated our game. Likewise, we are quickly growing our R&D team with a number of talented scientists.
We also have an advisory team that includes regulatory, business, and scientific experts with some of the top names in the industry, including Mark Bamforth and Richard Snyder.
MN: As you look at companies and technologies spinning out of academic groups, it tends to be from the same universities, specifically institutions like Stanford, MIT, Harvard, and Johns Hopkins. While there are a lot of other universities out there, they don’t have the same access to capital or industry connections. To address this, we’ve taken a broad approach to interface with schools and have focused on the R1 universities. Rather than saying, “We’re looking for this specific technology,” we note that we’re interested in gene and cell therapy and ask, “What do you have?”
Through this year alone, we have looked at over 600 technologies. We’re searching for disruptive innovations that we believe can be developed into a drug. The first technology that we licensed happens to be located around the corner from us at the University of North Carolina at Chapel Hill; it is a novel co-stimulatory domain for use in CAR-T cells. The scientist who discovered this application for this domain is a virologist who was developing the technology initially in the context of targeting HIV.
If we had limited our search to cancer biologists and the most cutting-edge CAR-T programs against oncology targets, we would have missed this, but we were looking for great technology. With this domain, when it’s plugged into the chimeric antigen receptor molecule that is the base for CAR-T, it appears to endow CAR-T cells with properties that we believe will be superior for targeting solid tumors.
The second technology we’re excited about is a CAR macrophage program. It’s conceptually the same idea as a CAR-T approach, where you still use a chimeric antigen receptor, except we engineer macrophages rather than T cells. There are only a handful of companies in the CAR-M space, and the technology we’ve licensed is outside of the CAR — it’s a modification to the macrophages that increases their ability to engulf and consume other cells. If those macrophages engage with the tumor type that we’re targeting via the CAR molecule, they will be endowed with a superior ability to engulf and break down those tumor cells, which we believe will increase the odds of a downstream immune response by educating the innate immune system through the presentation of antigens from that tumor.
Our third program, which we’ve not disclosed in much detail, is in CAR-NK, where we’re primarily focused on manufacturing challenges.
MN: The reason our first three platforms are all CAR-based is because, as much as we want to try everything, we also want to make sure that we’re capturing synergies and learnings as we go — if we were to pick three completely nonrelated approaches that would be minimized, and we plan to build on these technologies and offerings as we advance them.
MN: The challenge with the CDMO market, particularly in gene and cell therapy, is capacity. It is estimated that CDMOs only have enough capacity for 5% of what is being developed. Timelines are another challenge. When contracting and lead time are factored in, it’s months before process development can even be started — and that’s not compatible with our model.
The idea of AMP+ begins with the desire to internalize this process so we can move at our desired pace. With AMP+, we are looking at both existing platforms and technologies that we think will be applicable for building multiple manufacturing approaches and also assessing new technology, whether it’s being licensed from schools or other companies.
MN: I’ve told you about CAR-T, CAR-M, CAR-NK. The other thing that we are very interested in — and one of the other reasons we’re looking at those platforms — is because we’re considering combinations. Particularly for some of the more difficult to treat cancers, it’s hard to imagine that a mono-targeted, mono-cell therapy is going to cure a patient.
However, if we project over the next decade, the possibility of using an NK or a macrophage approach to first target a tumor and make it more amenable to a CAR-T approach becomes very real. Since we have these different effector cells that work through various mechanisms of action, we should consider ways to maximize their individual properties by combining them.
The focus of the company is absolutely on cell and gene therapies and is currently solely focused on oncology, but, as we grow, I’m sure there will be plenty of opportunities to expand to other diseases.
I foresee the need for a gene-editing technology as an inevitability, and this will open up a number of options for modifying our cell therapies. Imagine using a gene-editing tool and viral vectors or nonviral delivery to actually make those cells in vivo — in the patient rather than processing cell therapies ex vivo in a GMP facility. While that’s still outside of our realm, and I think, leans a bit toward what is currently “science-fiction,” it’s something that we’re watching closely for the future.
MN: I’m excited to watch how the field of allogenic CAR-Ts advances. I think the autologous approach is not something that should be abandoned, though scaling that is a clear challenge. I think one thing we’re very interested in — and this is a key component of the AMP+ model — is finding technologies that we believe will allow us to do that in a more intelligent way.
The allogenic or universal donor off-the-shelf approach is obviously intriguing, whether that’s through donor-derived T cells, other effector cells, or IPSC-derived effector cells.
Personally, one of the challenges I see with gene and cell therapy is the cost, which is fundamentally unsustainable. These million-dollar gene therapies are not how we’re going to make an impact in the field over the next 50 years –– there has to be a better solution.
MN: Yes, talent is a big challenge. We’re very lucky to be based in Research Triangle Park (RTP), North Carolina, which is very well well-situated for talent, especially in manufacturing. RTP has become a real hotbed for cell and gene therapy manufacturing — it feels like every week another company is announcing that they’re moving here.
We’re also lucky here with so many amazing local universities, between UNC Chapel Hill, NC State, North Carolina Central, and Duke. We’ve got really a tremendous talent pool. We’re also open to partnering with local universities and community colleges to develop training programs to help build that next level of workforce.
Having said all that, one thing that I’ve always found is successful is recognizing that tangential experience and backgrounds can be really important to thinking outside of the box; for example, people with backgrounds in autoimmunity can be great sources of insights and new ideas on how to engineer effector cells.
MN: I hope by then that cell therapies will have moved up in the lines of treatment where appropriate. I’d also love to see that they’re more accessible in local clinics. A few short years ago, you had to go to a major medical center to get CAR-T, but that’s starting to branch out more. In the future, I’d expect it to be possible in local and even rural clinics, though that will either require an off-the-shelf option or serious advances in manufacturing and almost point-of-care manufacturing, which I imagine will happen beyond the coming decade.
In terms of gene therapies, I think it will be a similar situation. In probably well-past 10 years, I’d love to see gene therapies moving out of rare and ultra-rare disorders. While I don’t know that gene therapy will ever be the right source for common maladies, there are so many genetic diseases that can be potentially solved and cured by gene therapies.
Fundamentally, I hope Inceptor Bio will have treated hundreds and hundreds of patients in trials — and I hope that there will be hundreds more lined up.
MN: I think it’s coming up with manufacturing solutions that allow us to address some of the fundamental problems with cell therapy. Beyond that, I hope we have the ability to generate cells in vivo. I want to be part of building something that makes certain technology irrelevant because there’s a much better solution.
Mike Nicholson, Ph.D., serves as Chief Scientific Officer for Inceptor Bio, LLC. Prior to joining Inceptor Bio, Dr. Nicholson was Vice President of Operations at BioAgilytix, where he led the organization’s Gene and Cell Therapy bioanalytical services. Before that, Dr. Nicholson spent nearly 13 years at Precision BioSciences, where he held several leadership roles including Vice President of R&D, Senior Vice President of Research, and Chief People Officer. Dr. Nicholson earned his BS in chemistry from SUNY College at Brockport and his Ph.D. in molecular biology and genetics from the Johns Hopkins University School of Medicine.