Innovative Melanoma Treatment Among NCInnovation's $5.2 Million Research Funding Recipients

NCInnovation recently announced the approval of $5.2 million in research funding for 8 research projects at 7 North Carolina public universities. NCInnovation is a non-profit organization with a mission to support innovative researchers across North Carolina. The 8 projects recently approved include lithium refining, drinking water purification, power grid efficiency, multi-year vaccine development, mosquito-borne infectious disease identification and risk assessment, beehive improvement and monitoring system, neuro drug delivery system, and melanoma research.¹

Rukiyah T. Van Dross-Anderson, PhD, associate professor of pharmacology at East Carolina University, is developing a first-of-its-kind cancer immunotherapy for patients with melanoma to kill the cancer cell and prompt the immune system to seek out and destroy other cancer cells. The molecule, 15-Deoxy, Δ^12,14-Prostamide J₂ (15d-PMJ₂), “elicits death in diverse cancer cell types by targeting different signaling pathways and cellular processes including ER stress, PPARγ, and ROS.”²

In a recent interview, Dermatology Times spoke to Michelle Bolas, executive vice president and chief innovation officer of NCInnovation, and Van Dross-Anderson to discuss the significance of NCInnovations’ funding and the clinical impact of Van Dross-Anderson's research in patients with melanoma who do not respond to currently available treatments.

Q&A With Michelle Bolas

Michelle Bolas

Executive vice president and chief innovation officer

Image credit: NCInnovation

Dermatology Times: Can you please provide an overview of NCInnovation and its mission?

Bolas: NCInnovation is a public private partnership that was formally started with the passing of legislation in 2023 that allows NCInnovation to have use of $500 million out of state reserve for the purpose of programming that is operated on the investment income from that endowment. We have 2 programs, our regional hub programs and our non-dilutive grants to technology development to university researchers, and both are funded out of that investment income run on the endowment. So we started in earnest in 2023 by placing 4 regional hub directors at four initial universities: East Carolina University, Western Carolina University, UNC Charlotte, and North Carolina A&T, and those directors are really seasoned technology commercialization pros who are familiar with what it takes to move applied research from the bench to commercial viability, and have been diligently working with faculty at those 4 institutions, as well as the remainder of the UNC system institutions for the past 8 months. In February of this year, we launched a pilot grants program, and through a very strident process, down selected from an initial cohort of 29 to 8 funded projects, of which Dr. Van Dross-Anderson is one, and announced those projects after our May board meeting where our directors approved that slate and happy to say that as of today, all but one of the funding agreements have been signed, and those dollars will flow shortly to the research institutions and to the researchers that won those awards. So NCInnovation is off and running, and we are just thrilled to have Dr. Van Dross-Anderson as one of the first researchers in our first cohort.

Dermatology Times: What does the in-depth review and selection process include?

Bolas: Our directors are the first point of contact for researchers at the universities really getting to understand where they are in their development pipeline, what kind of work has been done to date, and looking at where they think that technology might be headed in terms of a market fit opportunity. From there, the researchers were encouraged to apply based on whether they meet the basic criteria outlined in our funding authorities. And at that point, the directors really stepped back from the process and NCI developed and executed a multi-tiered external review process. We had an external panel of reviewers from across all sorts of disciplines. Since we are technology agnostic, we needed to have a lot of different types of experience in the mix so that our projects got as much review from experts who have either been on the research side or on the commercialization side of their technologies. That panel was chaired by a very seasoned faculty entrepreneur and someone who has run many, many programs designed to give grants to the technology development process. We also had an external review provided by RTI innovation advisors groups looking at specifically validating the technology readiness level of the projects. We want our technologies to be at least TRL3. Looking at the various ways that that can be validated as well as looking at potential market fit. So is there, based on what we know about the market currently, is there at least a viable runway for this technology given the development pathway that the applicant has laid out. With those two processes completed, then we took the scores and the feedback from that and did an internal review and conducted a consensus conversation with all sets of reviewers so that the scoring that we came out with was finely tuned and well-validated with everyone in the room. We feel good about the 8 projects. I would say that there were about 8 right behind them that were also very good and scored very high, and what we did was collected a lot of feedback from our reviewers, provided that in documentation to the non-selected projects, and then at that point, the directors in the field pick up the relationship again and work with those PIs through those reviewer comments to see what we can do to help continue to develop those projects toward a viable funding inflection.

Dermatology Times: How is NCInnovation helping to make research like Dr. Van Dross-Anderson's more accessible?

Bolas: I think that this project is such a great example of why NCI is necessary in North Carolina and how we're working. I first met Dr. Van Dross-Anderson at my very first visit to ECU well over 18 months ago, and she presented as an example, she had taken the technology very, very far with the available grants for her particular area of work and was really close to facing a decision point as to whether or not she was going to be able to go forward with the development of this technology given the very limited amount of funding for this next phase. In particular, in North Carolina, where we have a lot of our biosciences work and life sciences work really clustered in RTP, it's especially difficult or challenging for researchers who are at regional institutions who have very well-developed expertise in a particular area, but perhaps their institution isn't as well known in that area to compete with the funding that is available in RTP. I was very interested in seeing how her project scored in the review process, and it scored very high. There was a lot of discussion around, in particular, her ability through the funding that NCI has provided, to make it to a viable stage and potentially to be classified as an orphan disease, is an area where there's a particular interest in the investment market right now. She had really done the work to dial in what she could do with this funding, and where that would leave her relative to those next commercial inflection points that are so critical in developing a therapeutic of this kind. Our job is to help ensure that she's successful over the next two years, as she's completing this round of work, and by the end of it, is well positioned from a commercial viability standpoint.

Dermatology Times: Do you have any closing thoughts about NCInnovation?

Bolas: Like many other areas of university work, the developing technologies and the technology transfer pipeline are very complex and not as well understood. I think that we get a lot of questions around why are we targeting this funding toward the university researcher and not potentially a startup company or something that is on the on the commercial side, and I think that the role that NCI is able to play is so unique in this point where many, many projects will remain on the shelf. I know that sounds trite or worn, but it is true. "Die on the vine. Shelved research." It simply means that the kind of funding available to develop the technology and not add on to the research portfolio is very, very limited, and especially in the life sciences and biosciences where this work falls. It's not an insignificant amount of funding that's needed. This is an over $800,000 award for this work. The limitation on the funding, the need to continue to do this work within the university where there are resources and the benefits accrue to the researcher and to the university, is a critical piece. And if we can get this right, not only in the life sciences, but across many sectors, we are going to be able to increase the volume and the quality of the innovations that are entering the commercial arena in North Carolina, and I think that's a game changer, especially at the regional level.

Q&A With Rukiyah T. Van Dross-Anderson, PhD

Rukiyah T. Van Dross-Anderson, PhD

Image credit: East Carolina University

Dermatology Times: Can you please provide an overview of your research that has received funding from NCInnovation?

Van Dross-Anderson: My lab group has worked to patent a novel molecule that we have tested in different settings to determine if it is effective against cancer. We've conducted several studies, both in culture cells and in mice, to determine if this agent could kill cancer. What we found is that our molecule, which we call PMJ, for short, but our molecule, has the ability to kill melanoma cells, and it also kills those melanoma cells in small animals. And so, this is really important, because melanoma is a type of cancer. It's a skin cancer, and unfortunately, it is the deadliest skin cancer when individuals typically have it, and it is diagnosed at a late stage, some of the treatments that are available are effective against it, but there are half of the people who try the drugs that are commercially available, and those drugs don't work. So, what we sought to do is to develop an agent that could potentially be combined with those drugs that are already on the market to make them even better. And so that is our goal, to try to make those drugs better and potentially use it as a drug for stage 3 and stage 4 melanoma, which is an advanced stage melanoma, as well as unresectable melanoma, which cannot be removed. So those are our intended uses for our drug.

Dermatology Times: What is unique about PMJ compared to already available treatments for advanced melanoma?

Van Dross-Anderson: Our drug is unique because it does 2 things. First, it kills the cancer cells. And the second thing that it does is it recruits immune cells to the tumor. Now, it recruits a specific type of immune cell, which is called a CD8+ T cells, and these cells have the ability to kill cancer cells. So not only is the drug killing cancer cells, but it's activating immune cells that can also kill the cancer cell. And so, that combination is important, and there are other commercially available products that can do it, but unfortunately, those products are oncolytic viruses. They're great agents, but the safety of that agent is not quite there, because it's a herpes virus, and what happens is that patients can wind up with herpes virus infections. So, our drug offers similar activity, but it's safe because it's a small molecule and it is not virus material. So, we're offering a safe alternative to an approach that has been found to be effective, particularly when combined with drugs that are already on the market.

Dermatology Times: What inspired your research to develop this one-of-a-kind molecule for melanoma?

Van Dross-Anderson: My inspiration comes from my family and my family history with cancer. Unfortunately, I have a very strong family history of cancer, and both my parents died from very aggressive forms of cancer, and so as a way to honor their memory, I formed a company called Claradele, which is named after my father, whose name is Clarence, and my mother, whose middle name is Adele, so we put Clare and Adele together to make Claradele. This company was founded in order to develop drugs that can not only help the patient to survive longer, but through my own experience, we also know that not only are the patients going through a traumatic situation, but families are going through traumatic situations as well, trying to care for and have hope for people who have these diseases which oftentimes are not curable. And so that was my inspiration. I've always been a cancer researcher, but just that experience has inspired me to try to take this a step further. As an academician, my goal has always been to study cancer and to understand it, but this experience took it to the next level, where now I want to produce something that can help people to not go through this experience, the patient and the family. That is the inspiration for taking this drug from the benchtop to now trying to move it to the commercial space.

Dermatology Times: What would you want dermatology clinicians to know right now about your research and the potential of PMJ?

Van Dross-Anderson: At this point, we are conducting studies where we're doing head-to-head comparisons of our agent with commercially available agents, and we're combining our agent with some commercially available agents, all in melanoma. And the data is looking great. We're still performing those studies. We're looking at not only the efficacy of the drug, but we're also looking at the safety, because that's one of the more important things. We can develop lots of different drugs, but if they're not safe, then that is not going to achieve what we hope to achieve, and that is not only longer lives for cancer patients, but also better quality of life. We don't want to develop something that may be toxic to those patients. So that is what we're working on right now. And as I mentioned, the data looks very promising.

Dermatology Times: How is NCInnovation helping to propel your research?

Van Dross-Anderson: It has been extremely helpful. Because, as Michelle mentioned, there are not that many opportunities to move the research from the benchtop work to the commercial space. There are STTR SBIR grants, which are helpful. They can help you to make that transition, but for many of the studies that we're currently needing to complete, there are very few sources of funding, and so this has been a tremendous help to us. Our goal is to use the funding to perform those studies required by the FDA, because that will be the next hurdle we must meet. There are a series of studies that must be completed, and this grant will help us achieve that goal. And I'd like to mention those studies that need to be done to satisfy the FDA, they are incredibly expensive. And because there are few sources of funding that we can use to achieve that, this really helps, and particularly in this current climate, the investment climate right now is not good. These funds have come at a perfect time where investors are not really wanting to invest in projects that take a bit of time to see the return on the investment. This has been a wonderful opportunity for us to continue to move forward so that we can start our studies where we will be working with patients.

Dermatology Times: Do you have any closing thoughts about NCInnovation or your research?

Van Dross-Anderson: The funding of NCI is really a game changer. As I mentioned, there are few sources of funding that are available. So, this is helpful to allow us to move forward, and so we will be able to achieve those studies needed for the FDA, but at the same time, we're going to be stimulating the economy of North Carolina, and that is unique. In the work that we're going to be doing, we're going to be working with companies that are based right here in North Carolina. The work will be done here. So, not only is this funding helping us, but it's going to help many different companies doing regulatory work. At least for our project, we need regulatory work done, and we're going to be working with companies that are right here. We're going to be providing new income for North Carolina residents, people who work in these firms, and help to ensure that these firms stay in business. The economy is not just bad right now for the investors, but also a lot of the companies, which are called CROs, contract research organizations, a lot of them are really struggling right now because of the lack of investment in these types of things at this current time. So, a lot of people are going to benefit from this NCI funding, not just us. There will be a slew of people who will benefit from this money, and we are just so proud and honored that we were selected as one of the first recipients. And we are so honored and happy to be a part of this initiative.

References

1. NCInnovation approves $5 million to support eight university research projects. News release. NCInnovation. May 16, 2024. Accessed July 18, 2024. https://ncinnovation.org/media/ncinnovation-approves-5-million-to-support-eight-university-research-projects/
2. Ladin DA, Nelson MM, Cota E, et al. Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore. Oncotarget. 2022;13:1380-1396. Published 2022 Dec 29. doi:10.18632/oncotarget.28334