Merck KGaA and Nordic Bioscience in osteoarthritis breakthrough

November 4, 2017

ACR Abstract #1L

Phase II Trial of Sprifermin for Osteoarthritis

Disease Modification Meets Primary Endpoint, Nordic Bioscience A/S and Merck Presents Late Breaking Clinical Data

- Late-breaking presentation at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting (ACR/AHRP) provides data on cartilage thickness in patients with knee osteoarthritis

Herlev, Denmark, November 4, 2017 – Nordic Bioscience A/S, a leading niche CRO specialized in pre-clinical and clinical research in osteoarthritis (OA), today announced results of the two-year primary analysis of FORWARD, a five-year, multicenter Phase II study of sprifermin in patients with knee OA, conducted by Nordic Bioscience and Merck. The results show an increase in cartilage thickness with sprifermin in patients with knee OA, and underscore the commitment of both companies to discover and deliver transformative treatments to patients suffering from osteoarthritis, an area with high unmet need.

“We are excited about these data which show sprifermin may increase cartilage thickness in patients with knee osteoarthritis. This is truly a leap forward in osteoarthritis which hopefully will benefit many patients,” said Morten Karsdal, CEO of Nordic Bioscience A/S. “Our decision to engage in the partnership with Merck on this project was guided by positive signals from our proprietary biomarkers and biological disease models designed to improve innovation and lower risk of development, and our clinical team performed the enrollment of study subjects ahead of schedule and ensured high data quality.”

The study of 549 patients met its primary endpoint, demonstrating a statistically significant, dose-dependent increase in MRI total femorotibial joint cartilage thickness from baseline in each of the two sprifermin groups receiving the highest doses as compared with the placebo group after the two-year treatment period (+0.03 mm with 100µg sprifermin every six months vs. -0.02 mm with placebo, p<0.001; +0.02 mm with 100µg sprifermin every twelve months vs. -0.02 mm with placebo, p<0.001, respectively). Demonstration of an increase in cartilage thickness as opposed to a delay in decreasing cartilage thickness has not been previously reported. The correlation of these changes with clinical endpoints is being evaluated.

"Osteoarthritis of the knee can make it challenging for sufferers to perform everyday activities, such as walking or climbing stairs, and there is a high unmet need for disease-modifying treatment options,” said Dr. Marc C. Hochberg, primary investigator of the FORWARD study and Division Head, Rheumatology and Clinical Immunology, University of Maryland School of Medicine. “These data suggest sprifermin may not only prevent decline in cartilage thickness compared with placebo, but may also increase cartilage thickness in patients with knee osteoarthritis."

Secondary endpoints included changes in cartilage thickness as measured by MRI in the medial and lateral compartments, as well as changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score over two years. Statistically significant treatment effects of increased cartilage thickness were observed in the medial and lateral femorotibial compartments, including the central medial and central lateral regions, in the highest sprifermin dose group. Total WOMAC scores decreased (indicating less symptoms) by approximately 50 percent compared to baseline in all treatment groups, including placebo.

There was no detectable systemic exposure following the intra-articular injections of sprifermin. Treatment-emergent adverse events were balanced between treatment groups, with musculoskeletal and connective tissue disorders being the most common.

The results will be presented in a late-breaking oral presentation, “Efficacy and Safety of Intra-Articular Sprifermin in Symptomatic Radiographic Knee

Osteoarthritis: Results of the 2-Year Primary Analysis from a 5-Year Randomised, Placebo-Controlled, Phase II Study” at the 2017 ACR/ARHP Annual Meeting in San Diego, U.S., on Tuesday, November 7, at 4:30 p.m. PT, by the authors Hochberg M, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, Bihlet AR, Byrjalsen I, Andersen JR, Eckstein F.

Nordic Bioscience A/S is presenting a total of 12 abstracts at ACR, highlighting the momentum of its various programs in rheumatology.

For more information about the data presented, please visit the ACR/ARHP website

About Sprifermin

Sprifermin is in clinical development to investigate its potential as a treatment for osteoarthritis (OA) in the knee. It is a truncated recombinant human FGF-18 protein thought to induce chondrocyte proliferation and increased extra-cellular matrix (ECM) production, with the potential of promoting cartilage growth and repair. Sprifermin is currently in Phase II studies.

About Osteoarthritis

There are approximately 237 million people worldwide living with symptomatic and activity-limiting OA, the third most rapidly rising condition associated with disability globally. By the end stage of the disease, total knee replacement is often necessary. OA is likely to be the number one cause of total hip and knee replacement in the US. Currently there are no approved drugs for preventing or slowing disease progression.

About Nordic Bioscience

Nordic Bioscience is dedicated to preclinical and clinical drug development, and specialized in precision medicine using unique biomarker technologies. Nordic Bioscience engage with biotech and pharmaceutical clients to identify projects most suitable for clinical development by utilizing a proprietary biomarker technology.

Nordic Bioscience has more than 25 years’ experience in biomarker development and clinical trials and has particularly acquired extensive expertise in rheumatology. Combining experience in preclinical and clinical research enables a faster and smarter detection of signals of the potential clinical viability of drug candidates.

About Merck

Merck is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2016, Merck generated sales of € 15.0 billion in 66 countries.

Founded in 1668, Merck is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. The company holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

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