Radius Fractures

At six months post-grafting surgery with NVDX3, x-rays demonstrate that 90% of patients have reached, or are steadily progressing towards, complete bone healing Derived from Novadip’s 3M 3 stem cell platform, NVDX3, a unique ‘off-the-shelf allogeneic matrix product to cure common but challenging orthopedic conditions, has potential to replace existing allogeneic bone substitutes to heal fractures MONT SAINT-GUIBERT, Belgium I October 17, 2024 I Novadip Biosciences, a clinical stage biotechnology company specializing in regenerative medicine, today announces positive interim results from its first-in-human clinical trial, NVDX3-CLN01, assessing the safety and efficacy of NVDX3 to heal distal radius fractures in adults. Originating from Novadip’s 3M 3 platform, NVDX3 is an allogeneic bone grafting material created from human osteogenic adipose tissue-derived mesenchymal stem cells (ASCs). It is formulated as a lyophilized powder intended to be used as an ‘off-the-shelf’ implant to induce bone formation between two bone segments in both orthotopic and heterotopic environments. NVDX3 is a new class of regenerative tissue products that accelerates bone healing in a single treatment for patients at high risk of nonunion due to co-morbidities (ageing, diabetes, obesity, smoking and other conditions) and medication use. NVDX3-CLN01 (NCT05987033) is a single-arm, open-label clinical trial designed to assess the safety and preliminary efficacy of NVDX3 in adults with distal radius fractures, involving the wrist joint with multiple bone fragments. Ten participants, aged 28 to 84 years old, were treated. Radiologically, 90% of patients have achieved, or are on-track to achieve, complete bone healing. All but one are progressing as expected clinically. There is no apparent impact of age or sex on the efficacy of NVDX3, despite the complexity of fractures treated. There have also been no safety concerns arising from this study. “The interim results of this first clinical trial mirror the safety and efficacy of NVDX3 demonstrated in our nonclinical program. NVDX3 is the first and only bone graft product following a Biologics License Application (BLA) pathway.Based on these preliminary data, NVDX3 has the potential to address the high unmet needs of patients with bone defects who, due to co-morbidity factors, experience delayed bone formation or nonunion,” said Denis Dufrane, MD, PhD, CEO of Novadip Biosciences. “We will share the results of this trauma study with the US FDA as part of our IND submission to support the further clinical development of NVDX3 as we explore its potential for the treatment of complex cervical spine fusion.” “We need more options to improve outcomes in bone healing, particularly for patients with co-morbidities like advanced age, diabetes and smoking,” said Philipp Leucht, MD, PhD, Vice Chair of Research, Department of Orthopedic Surgery at NYU Grossman School of Medicine. “These interim results suggest that NVDX3 may have the potential to address this unmet need.” The 12-month results of NVDX3-CLN01 are expected at the end of 2024. In parallel to NVDX3-CLN01, Novadip is investigating the safety and preliminary efficacy of NVDX3 as a bone graft to achieve spine fusion in the lumbar spine in trial NVDX3-CL02 (NCT05961956). One-year results from this trial are expected in March 2025. In addition to its allogeneic program with NVDX3, the clinical development of the company’s lead autologous program, NVD003, will soon be entering phase 3 for the treatment of congenital pseudarthrosis of the tibia, a rare pediatric disease that often leads to amputation. Planning for a pivotal phase 3 trial and BLA submission is underway. About Novadip’s 3M 3 platform The 3M 3 platform drives multiple classes of product candidates, with an initial focus on autologous cell therapies for critical size tissue reconstruction and allogeneic therapeutics in development for prevalent bone grafting procedures and solid tumors. The platform consists of a 3-dimensional, scaffold-free, extracellular matrix (ECM) utilizing differentiated adipose-derived stem cells (ASCs), to generate highly specific growth factors and miRNAs to restore the physiology of natural healing. The components of the 3M 3 include a matrix with ASCs to deliver growth factors/miRNA, the mature implant mimicking the physiology of natural healing. About Novadip Biosciences Novadip is a Belgium-based clinical stage biotech company aiming at advancing the standard of care in bone and tissue regenerative medicine. Based on the scientific discoveries of founder Prof. Dr. Denis Dufrane, MD, PhD, the company is developing its unique 3M³ tissue regeneration technology platform, which has the potential to generate an array of candidates that utilize adipose-derived stem cells to mimic the physiology of natural tissue healing, and hard and soft tissue reconstruction, for patients with limited or no treatment options. Novadip is a spin-off company from the Université Catholique de Louvain (UCLouvain) and St. Luc University Hospital. www.novadip.com SOURCE: Novadip Biosciences

1st US patient treated with an autologous cell-based product (NVD-003) in a rare pediatric disease Full enrollment of patients on track for year-end completion in allogeneic cell-derived product (NVD-X3) trial in patients with a distal radius fracture following trauma MONT SAINT-GUIBERT, Belgium, Dec. 5, 2023 /PRNewswire/ -- Novadip Biosciences SA ("Novadip" or "the Company"), a clinical-stage biopharmaceutical company developing a new class of regenerative tissue products to accelerate healing of large bone defects and injuries in a single treatment, today announced that the first US patient has been implanted with its investigational tissue regeneration product, NVD-003, in its Phase 1b/2a clinical trial in Congenital Pseudarthrosis of Tibia (CPT), a rare pediatric bone condition. An autologous therapy derived from a patient's own adipose stem cells (ASC), NVD-003 has the potential to accelerate healthy bone formation, restore mobility and avoid the need for amputation in children with CPT. "This is an exciting moment to be able to treat one of our patients with NVD-003," said Philip K. McClure, MD, FAAOS, Director of the International Center for Limb Lengthening, Baltimore, Maryland and the principal investigator in the US on this trial. "Three months after we collected the patient's adipose tissue in here in Baltimore, the NVD-003 graft, which was then manufactured in Belgium, was sent to us for implantation. With NVD-003, there's hope that the standard use of invasive iliac crest bone grafting, which can be very painful and lead to complications such as infection, bleeding and large scar formation, can be avoided. This is particularly important for patients who have had previous surgeries on the pelvis, making graft harvest of higher risk." According to Novadip, this Phase 1b/2a trial has now reached full enrolment; 3 patients have been enrolled in Belgium, of whom 2 have already been grafted with NVD-003 by Professor Pierre-Louis Docquier, MD, PhD, a specialist in pediatric surgery at the University Hospital Saint-Luc in Brussels. The company is actively planning the pivotal trial to support NVD-003's approval by the US Food and Drug Administration (FDA). Novadip also provided an update on NVD-X3, their allogeneic off the shelf matrix product, which entered clinical development this past summer with two parallel Phase 1b/2a EU clinical trials. Enrolment in the first trial, for the treatment of a distal radius fracture following trauma, is near completion with 9 of 10 patients already treated. In addition, the first patient has been treated in the second trial investigating NVD-X3 in spine fusion. "We are very pleased with the speed of recruitment in our first clinical trial with NVD-X3," said Judy Ashworth, MD, Novadip's CMO. "As we now begin to prepare our Investigational New Drug Application to submit to the FDA, we're anxious to advance NVD-X3 into an aggressive phase 2 program in the US with trials beginning in early 2025." "We are excited by the progress of both of our programs in Europe and in US," said Denis Dufrane, MD, PhD, CEO, and founder of Novadip Biosciences. "We have demonstrated our capacity to manage multiple clinical trials in parallel as well as the robustness of our manufacturing platform for two different classes of cell-based and cell-derived products with the aim to deliver the best therapeutic agents to the patients. Novadip is now a clinical advanced company." About NVD-003 and CPT Congenital pseudarthrosis of the tibia, or CPT, is a devastating diagnosis. Impacting patients in just .5-3.5 in 150,000[1][2][3] live births, the condition is very rare and debilitating. Treatment of CPT is difficult and once a fracture occurs, subsequent fractures are likely. Children with CPT can face impaired mobility, years of corrective surgeries to try to repair and stabilize the bone, it is not uncommon for patients to ultimately undergo amputation of the limb. Novadip is developing NVD-003, an autologous therapy derived from adipose stem cells as a potential single treatment to save limbs and restore mobility in patients with congenital pseudoarthrosis of the tibia (CPT) and other rare pediatric bone disorders. About NVD-X3 for Spinal Fusion and Bone Non-Union Applications The risk of bone non-union following fracture is greater than 50% across all bones due to fracture severity, co-morbidities (diabetes, obesity, smoking and other conditions) and medication use[1]. Additionally, more than 600,000 spine fusion procedures are performed annually. Together, these indications represent a peak sales opportunity for Novadip of $2.2 billion. Novadip's lead allogeneic product, NVD-X3, employs a matrix containing multiple bioactive factors that induce accelerated tissue healing. Designed as an "off-the-shelf" product, NVD-X3 can be shipped and stored at room temperature and offers superior intraoperative handling characteristics. A favorable COGS profile supports broad distribution and expanded patient access. Preclinical studies demonstrate that NVD-X3 offers superior bioactivity without the undesirable bone formation/resorption and inflammation observed with currently marketed bone engraftment products. About Novadip Biosciences Novadip Biosciences is a clinical stage biopharmaceutical company leveraging its proprietary tissue regeneration technology platform 3M³ to generate multiple product candidates to address tissue reconstruction for patients who have limited or no treatment options. The 3M3 platform involves use of 3-dimensional extracellular matrix and adipose-derived stem cells to deliver highly specific growth factors and miRNAs to mimic the physiology of natural healing to create a range of products that address specific challenges in tissue regeneration. Novadip's initial focus is on reconstruction of critical size bone defects. The company is also applying its 3M3 platform to develop truly novel off-the-shelf/allogeneic therapies addressing more prevalent tissue defects and miRNA/exosome products for broader indications. Visit for more information. 1. Khan T, Bone Joint J. 2013, PMID: 23908415 2. Heikkinen ES, Acta Orthop Scand. 1999, PMID: 10429605 3. Hefti F, J Pediatr Orthop B. 2000, PMID: 10647103 Logo: Media & Investors Inquiries Denis Dufrane Direct: +32 10 77 92 20 Mobile: +32 477 42 00 34 [email protected] SOURCE Novadip

This Grant will Fund the Company’s Translational Research Activities Through the Completion of a Pilot Clinical Trial. LOWELL, Mass.--(BUSINESS WIRE)-- RevBio, Inc., announced that it has been awarded a grant from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), through its Commercialization Readiness Program of up to $3.4 million over the next three years (1SB1AG085803-01). This grant will enable the company to finish its late-stage product development activities and conduct a clinical trial to demonstrate the safety and efficacy of the product in comparison to the current standard of care. This press release features multimedia. View the full release here: RevBio has conducted a pivotal sheep study to assess safety and efficacy of TETRANITE using a wedge ostectomy fracture model in the distal femur. The sheep were assessed after 4, 12, 26 and 52 weeks post-op for biomechanical and histological outcome measures. (Photo: Business Wire) The research funded by this grant will focus on the ability for the patented TETRANITE® technology to fill gaps in bone, fixate bone fragments, and accelerate healing through its osteoconductive capabilities for fractures in the extremities. TETRANITE will be used both as an interoperative fixation aid and as an adjunct to traditional hardware fixation to provide immediate load sharing between bone and metal plate and screw systems. By providing additional stability, TETRANITE will help achieve better healing and prevent complications and revision surgeries. It can also be injected percutaneously as a minimally invasive stand-alone method of fixation to surgically treat fractures without the need for conventional open reduction internal fixation (ORIF). This grant will expand upon the pre-clinical research funded by a previous $2 million SBIR Phase II grant from the National Institute on Aging (R44AG060881-02). “Our pre-clinical studies have demonstrated that TETRANITE is able to redistribute most of the load from plates and screws thereby reducing the likelihood of hardware failure and delayed healing,” said Brittany McDonough, RevBio’s R&D Program Manager, who has led the development of the fracture fixation product. “This adhesive material also provides a resorbable scaffold for the regeneration of bone which accelerates healing within the first few weeks following a traumatic injury.” Upper and lower extremity injuries equate to more than 40% of the approximate 2.1 million fragility fractures which occur each year in the United States.1,2 This number is expected to triple by 2040 as the population ages.3,4 External fixation, percutaneous pinning with K-wires, and conventional ORIF procedures that involve the use of plates and screws are interventions that are currently being used to treat these extremity fractures.5 However, despite advances in surgical technique and implant design, nonunion, malunion, and hardware failure continue to remain a significant cause of revision surgeries in the elderly.6 Complication rates as high as 36% have been reported and involve the onset of carpal tunnel syndrome, complex regional pain syndrome, tendon irritation and rupture, and deep infection.7,8 These complications can lead to difficulty performing basic daily tasks, loss of independence, reduction in quality of life, and increased mortality.9,10 “Fractures are often comminuted, and it is difficult to get the pieces back together and so having an adhesive would really help achieve an anatomic reduction,” said Michael J. Weaver, MD, Chief of Orthopaedic Trauma at Brigham & Women’s Hospital, and member of RevBio’s Orthopaedic Scientific Advisory Board. “This material is mechanically strong to allow early weight bearing which is something we cannot do currently in peri-articular fractures treated with metal implants. Having a material that can both augment fixation to prevent hardware failure and facilitate healing will fundamentally improve how our patients do.” Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Numbers 1SB1AG085803-01 and R44AG060881-02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About RevBio, Inc. RevBio, Inc., is a clinical stage medical device company engaged in the development and commercialization of a patented, synthetic, injectable, self-setting, and osteoconductive bone adhesive biomaterial called TETRANITE®. The company is developing a pipeline of products based on this technology for use in the dental, cranial, and broader orthopaedic markets as well as applications in the animal health market. RevBio's Tetranite technology is not yet approved for commercial use. _____________________________ 1 2 3 Watts, Nelson B., et al. "National Osteoporosis Foundation 2008 Clinician's Guide to Prevention and Treatment of Osteoporosis and the World Health Organization Fracture Risk Assessment Tool (FRAX): what they mean to the bone densitometrist and bone technologist." Journal of clinical densitometry: the official journal of the International Society for Clinical Densitometry 11.4 (2008): 473-477. 4 Burge, Russel, et al. "Incidence and economic burden of osteoporosis‐related fractures in the United States, 2005–2025." Journal of bone and mineral research 22.3 (2007): 465-475. 5 Grewal R, MacDermid JC, King GJ, Faber KJ. Open reduction internal fixation versus percutaneous pinning with external fixation of distal radius fractures: a prospective, randomized clinical trial. J Hand Surg Am. 2011 Dec;36(12):1899-906. doi: 10.1016/j.jhsa.2011.09.015. Epub 2011 Nov 3. PMID: 22051229. 6 Kloen, Peter, Geert A. Buijze, and David Ring. "Management of forearm nonunions: current concepts." Strategies in trauma and limb reconstruction 7 (2012): 1-11. 7 Thorninger, Rikke, Mette Lund Madsen, Daniel Wæver, Lars Carl Borris, and Jan Hendrik Duedal Rölfing. "Complications of volar locking plating of distal radius fractures in 576 patients with 3.2 years follow-up." Injury 48, no. 6 (2017): 1104-1109. 8 Watts, Nelson B., et al. "National Osteoporosis Foundation 2008 Clinician's Guide to Prevention and Treatment of Osteoporosis and the World Health Organization Fracture Risk Assessment Tool (FRAX): what they mean to the bone densitometrist and bone technologist." Journal of clinical densitometry: the official journal of the International Society for Clinical Densitometry 11.4 (2008): 473-477. 9 Marchewka, Jakub, Jacek Głodzik, Wojciech Marchewka, and Edward Golec. "Higher Mortality in Men Compared with Women following Distal Radius Fracture in Population Aged 50 Years or Above: Are Common Distal Radius Fracture Classifications Useful in Predicting Mortality?" BioMed research international 2019 (2019). 10 Nellans, Kate W., Evan Kowalski, and Kevin C. Chung. "The epidemiology of distal radius fractures." Hand clinics 28, no. 2 (2012): 113-125.