March 20, 2023 PAO-03-23-CL-06
Denis Dufrane (DF): While working at the University Hospital San Luc in Brussels, the University Hospital of the Universite Catholique of Louvain, from 2000 to 2015, I focused on building a new strategy for skin and bone tissue reconstruction in worst-case patients. In 2007, we treated many pediatric and adult patients in compassionate use who had required bone resections to remove tumors or because they suffered from congenital diseases associated with bone defects. In this context, my former mentors asked me to develop a new approach to restore large quantities of resected bone.
I applied the expertise in cell therapy that I had initially gained when studying diabetes to test the abilities of different types of cells to generate three-dimensional structures. The precept was that, in order to repair such large bone defects, it is necessary to first mimic the natural physiology of bone formation ex vivo to truly restore the activity of the cells when they are transplanted into patients. The first three years of work in the lab focused on mimicking bone healing physiology in tissue flasks, studying different matrices, mineral composition, and active viable cells. The result was development using a unique approach: a three-dimensional, scaffold-free product.
In 2010, due to the presence of a GMP facility within the university hospital, I was able to establish the first adipose tissue cell bank in Europe, with the goal of advancing this product into clinical trials with patients. Fifteen patients received large bone reconstructions, and five patients received skin reconstructions under compassionate use. The results were successful, and in 2013, on the basis of the patents that were established and these positive achievements, the university asked if I would be interested in licensing the technology to start a company. It was a good opportunity, and we founded Novadip that year.
Series A funding of up to €28 million was raised in 2015. As the Chief Scientific Officer, my added value was to consolidate the platform, design clinical trials, and perform tech transfers into the clinic. Over the next five years, we performed two clinical trials and proposed a new class of products for the treatment of young children with certain congenital diseases and for patients with worst-case bone tumors. In 2022, we raised a Series B of €40 million with international shareholders from the United States, Hong-Kong, and Europe.
Today, Novadip has three products in development: the initial autologous bone product NVD-003, which derived from adipose stem cells currently in phase I/b/IIa trials in the United States and the EU for the treatment of a rare pediatric bone disease called congenital pseudoarthrosis of the tibia (CPT); NVD-X3, an off-the-shelf allogeneic matrix entering phase I/II clinical trials in the EU as a first-line treatment for bone non-union and spinal fusion; and a new class of products based on microRNA to treat solid tumors and metastatic cancers.
DF: For the worst-case patients with critical size tissue reconstruction needs, no evidence-based treatments are currently available. There is a high unmet medical need for these patients, and no true treatment is yet available on the market. Many of these patients –– both young children and adults –– often face years of reconstructive surgery and ultimately amputation. Autologous cell therapies often comprise limited cells and have variable results. Plasma-rich platelets (PRPs) have been used, but clinical evidence of full consolidation is lacking. Drugs, such as bone morphogenic proteins (BMPs), also provide variable results. Novadip has the only product that includes a cell matrix to cure large bone defects, potentially with a single treatment. We believe in the active role that cells play in releasing growth factors to improve bone healing, and that is key to our 3M3 platform.
Our 3MAuto program is geared toward avoiding the need for amputations and restoring normal active mobility in young patients suffering from CPT. NVD-003 has received orphan drug designation in the U.S. and EU and, if approved by the FDA, would not only address a total market opportunity of $500 million but also make Novadip eligible for a priority review voucher worth as much as $100 million in revenue. Our allogeneic, off-the-shelf matrix NVD-X3, which can be stored at room temperature, is easy to use and is intended as a first-line treatment for spine fusion and trauma, which represent a much broader market of $7 billion.
DF: The 3M3 platform is three-dimensional, which is very important. Adipose stem cells are combined with particles, and the cells neosynthesize the matrix to form a bridge between the particles and the cells, leading to spontaneous generation of a three-dimensional graft. The first 3 in 3M3 represents the dimensionality of the product. The three-dimensional structure also creates a predictive loop that causes the cells to secrete growth factors and microRNA. So, the M stands for matrix, mature and microRNA, while the second 3 indicates the three classes of products: autologous, allogeneic, and exosome, the latter of which secretes specific exosomes not only for tissue healing but also as a treatment for solid tumors.
DF: Clearly, 2023 and 2024 will be key for Novadip. We have already closed two trials in the autologous program. We are now in phase I/II trials for CPT in young patients at the Baltimore Limb Institute with Dr. McClure, a leading orthopedic surgery center in the United States, and in Brussels at the Catholic University of Louvain with Professor Pierre-Louis Docquier, who has already used our therapeutic candidates in a number of patients in compassionate use and clinical trials). We are enrolling four young patients that require complete regeneration of part of their tibias in a trial for the adipose tissue treatment for humans, and we expect the patients to start therapy in 2023.
We also started two additional trials for the off-the-shelf product NVD-X3, which will each enroll 10 patients in bone non-union from trauma and 10 patients for spinal injury.
In 2024, we expect to get 1-year clinical data from these three trials to prepare the next financing round and bring the autologous and the allogeneic products closer to the market.
DF: With respect to our current 3MAuto and 3MAllo programs, we have well-defined pathways for both bone and skin regeneration indications. In the skin applications, the autologous product can be used for large critical size tissue reconstruction after burns or surgical resection (i.e., in the case of melanoma), while the off-the-shelf product can be used for chronic non-healing wounds. We also have the program in for solid tumors, which we expect to move into the clinic by the end of 2024 or early 2025.
DF: Initially, the company was founded with one product in mind: the 3MAuto therapy. With this product, distribution will be fairly controlled because the indication is ultra-rare. We have the GMP facility in Belgium and can receive adipose tissue from around the world and ship product everywhere around the globe.
For the 3MAllo off the shelf products, however, the goal is to produce and distribute millions of doses. We have demonstrated that we can achieve an acceptably low COGs (cost of goods) to make this therapy available on demand. Our next step is to gather sufficient evidence of clinical efficacy to support a deal with a strategic partner to help us to reach the market.
Novadip is a well-established company with a strong technology platform that offers multiple product opportunities in a range of indications where there is an unmet need and considerable market opportunity. We are positioned to bring the autologous product, NVD-003, to market on our own but will look for one or more strategic partners to take the off-the-shelf product, NVD-X3, through late-stage development and commercialization. We are also considering a possible IPO. In the next year, we will have steady clinical news to report, which will help generate more business opportunities and greater potential to get our product to patients.
DF: As a small company, we have a U.S. investor –– New Science Venture –– as the lead investor of our Series A funding round. The Series B round in 2020 was also led by a U.S. company and now is co-led by investors from Europe and Hong Kong as well. We also have Belgian funds, but we see our market as being largely in the United States.
It is also important that Novadip is fully supported by our board and investors with respect to positioning the company for the next funding round. In addition, we have a dedicated senior management team and have made steady progress in establishing clinical proof of concept, mapping a path to market, and expanding our drug development portfolio.
DF: The biggest trend in regenerative medicine over the last 20 years has been that the field is always just about to turn the corner. Fortunately, that is changing. The first wave of regenerative cell therapies came in 2000 with treatments for heart and bone conditions. They didn’t always end up as major successes, but the second wave of chimeric antigen receptor (CAR)-T cell therapies for cancer has been significant in that respect. Today, there are many additional cell types available –– such as induced pluripotent stem cells –– that are making standardization of the allogeneic approach possible, which is enabling a reduction in the cost of goods and should drive yet another wave of cell-based therapies.
Within this context, Novadip is well positioned to commercialize both autologous and allogeneic products. The allogeneic product is of particular interest because it is a matrix, not a cell-based product, and will find applications over the next three years as treatments for musculoskeletal diseases. Indeed, we are confident that cell-free approach will be the clinical strategy of choice in the future, and Novadip offers a unique, cell-free solution for tissue reconstruction that will help drive this paradigm shift in the field of regenerative medicine.
Dr. Denis Dufrane co-founded Novadip in 2013 and joined the company as Chief Scientific Officer in 2015. Prior to joining Novadip on a full-time basis, he was head of both the Musculoskeletal Tissue Bank and the Tissue/Cells Therapy Centre at St. Luc University Hospital. Previously, he was head of the Endocrine Cell Therapy Unit at St. Luc University Hospital. Dr. Dufrane has been a member of the Belgium Superior Health Council since 2014. Dr. Dufrane received his medical degree and his doctorate in biomedical sciences (orientation: cell therapy) from Université Catholique de Louvain.