Press

Publications

American College of Rheumatology (ACR) | November 03 - 08, 2017
San Diego CA

  • Results from a 52 Week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis
    Abstract - Slides
  • Radiographic Outcomes Were Associated with Pain and Function Responses: Post-Hoc Analysis of Results from a Phase 2 Study of a Small Molecule Wnt Pathway Inhibitor, SM04690, for Knee Osteoarthritis Treatment
    Abstract - Poster
  • Reducing Heterogeneity in OA Clinical Trials: Data from a Phase 2 Study of SM04690, a Novel, Intra-Articular, Wnt Pathway
    Inhibitor in Knee Osteoarthritis
    Abstract - Poster

Orthopaedic Research Society (ORS) Southern California Regional Symposium | September 25, 2017
Los Angeles, CA

  • Cartilage Regeneration in a Rat Model of Knee OA by SM04690, a Potential Disease Modifying Wnt Pathway Inhibitor
    Abstract - Poster
  • Interim Results from a 52 week Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis
    Abstract - Poster

Osteoarthritis and Cartilage | September 15, 2017

  • A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee

    Osteoarthritis and Cartilage. doi: 10.1016/j.joca.2017.08.015


    V. Deshmukh, H. Hu, C. Barroga, C. Bossard, S. KC, L. Dellamary, J. Stewart, K. Chiu, M. Ibanez, M. Pedraza, T. Seo, L. Do, S. Cho, J. Cahiwat, B. Tam, J.R.S. Tambiah, J. Hood, N.E. Lane, Y. Yazici

    Article

Gordon Research Conference: Wnt Signaling | August 06 - 11, 2017
Stowe, VT

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Poster - Slides

Osteoarthritis and Cartilage | July 13, 2017

  • A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study

    Osteoarthritis and Cartilage, 25(10), 1598-1606. doi:10.1016/j.joca.2017.07.006


    Y. Yazici, T.E. McAlindon, R. Fleischmann, A. Gibofsky, N.E. Lane, A.J. Kivitz, N. Skrepnik, E. Armas, C.J. Swearingen, A. DiFrancesco, J.R.S. Tambiah, J. Hood, M.C. Hochberg

    Article

International Cartilage Repair Society Heritage Summit | June 29 - Jul 01, 2017
Gothenburg, Sweden

  • Cartilage Regeneration in a Rat Model of Knee OA by SM04690, a Potential Disease Modifying Wnt Pathway Inhibitor
    Abstract - Poster

European League Against Rheumatism (EULAR) | June 14 - 17, 2017
Madrid, Spain

  • Anti-inflammatory Properties of SM04690, a Small Molecule Inhibitor of the Wnt Pathway as a Potential Treatment for Knee Osteoarthritis
    Abstract - Poster
  • Clinical Outcomes from a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Injectable, Wnt Pathway Inhibitor (SM04690) for the Treatment of Knee Osteoarthritis: Week 26 Interim Analysis
    Abstract - Poster
  • Radiographic Outcomes from a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee: Week 26 Interim Analysis
    Abstract - Slides

International Society for Pharmacoeconomics and Outcomes (ISPOR) | May 20 - 24, 2017
Boston, MA

  • A Statistical Analysis Plan to Understand Osteoarthritis Patient Journey by Linking Medicare Claims Across Care Delivery Settings
    Abstract - Poster
  • Health Care Resource Use of Medicare Beneficiaries With Primary Osteoarthritis (OA) Of The Knee – A Claims Data Analysis
    Abstract - Poster

Musculoskeletal Regenerative Medicine and Biology: From Development to Regeneration | May 04 - 06, 2017
St. Louis, MO

  • Discovery of a Small Molecule Wnt Pathway Inhibitor (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Poster

Osteoarthritis Research Society International (OARSI) | April 27 - 30, 2017
Las Vegas, NV

  • Anti-inflammatory Properties of SM04690, a Small Molecule Inhibitor of the Wnt Pathway as a Potential Treatment for Knee Osteoarthritis
    Abstract - Poster

World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases | March 23 - 26, 2017
Florence, Italy

  • Discovery of a Small Molecule Wnt Pathway Inhibitor (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Orthopaedic Research Society (ORS) | March 19 - 22, 2017
San Diego, CA

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Poster

Musculoskeletal Development and Regeneration Conference (MDRC) | February 24 - 27, 2017
Cancun, Mexico

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

American College of Rheumatology (ACR) | November 11 - 16, 2016
Washington D.C.

  • Radiographic Outcomes from a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee
    Abstract - Poster
  • A Small Molecule, SM04690, Has Inhibitory Effects on the Wnt Pathway and Inflammation in Vitro, with Potential Implications for the Treatment of Osteoarthritis
    Abstract - Poster
  • Analysis of Pain and Function Components in Omeract-Oarsi Strict Responders from a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee
    Abstract - Poster

International Cartilage Repair Society 2016 World Congress (ICRS) | September 24 - 27, 2016
Sorrento, Italy

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Royal Society of Medicine's 13th Medical Innovations Summit | September 17, 2016
London, United Kingdom

  • Samumed's Regenerative Medicine Platform
    Slides

European League Against Rheumatism (EULAR) | June 08 - 11, 2016
London, United Kingdom

  • Safety, Clinical and Imaging Outcomes of a Novel, Intra-Articular, Injectable, Wnt Inhbitor (SM04690) in the Treatment of Osteoarthritis of the Knee: Exploratory Analysis of Results from a 24 week, Randomized, Double-Blind, Placebo-Controlled Phase 1 Study
    Abstract - Poster
  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Osteoarthritis Research Society International (OARSI) | March 31 - Apr 03, 2016
Amsterdam, Netherlands

  • OMERACT-OARSI ‘Strict Responders’ Analysis from Results of a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study of a Novel, Intra-Articular, Injectable Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee
    Abstract - Poster
  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04690) as a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

American College of Rheumatology (ACR) | November 06 - Oct 11, 2015
San Francisco, CA

  • Safety, Efficacy and Biomarker Outcomes of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee: Interim, Exploratory Analysis of Results from a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study
    Abstract - Poster
  • Magnetic Resonance Imaging Outcomes Using an Intra-Articular Injection (SM04690) in the Treatment of Osteoarthritis of the Knee: Interim, Exploratory Analysis of Results from a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study
    Abstract - Poster
  • Discovery of an Intra-Articular Injection Small Molecule Inhibitor of the Wnt Pathway (SM04690) As a Potential Disease Modifying Treatment for Knee Osteoarthritis
    Abstract - Slides

Overview: Osteoarthritis

Knee Osteoarthritis

Arthritis is the most common cause of disability among adults, and OA is the most common type of arthritis, accounting for much of this burden.1

  • The global prevalence of symptomatic knee OA has been estimated to be 3.8% (4.8% for females and 2.8% for males).2
  • According to a 2005 estimate, 9.3 million (4.9%) of US adults ages 26 and older had symptomatic knee OA.1 The overall number of US adults affected by OA in any joint has increased during recent decades, from 21 million adults in 1995 to 27 million in 2005, primarily due to an aging population and an ever-increasing prevalence of obesity.1
  • The combination of direct medical costs, pain and suffering, and loss of workplace productivity elevates OA to a major socioeconomic problem for health systems, the economy, and suffering patients.3

OA is characterized by the destruction of articular cartilage and structural changes in bone, which contribute to pain and loss of joint function.4 The Wnt signaling pathway plays a central role in the processes that control whether resident stem cells in the joint become cartilage-forming cells (chondrocytes) or bone-forming cells (osteoblasts).5,6

  • In OA joints, elevated Wnt activity has been shown to cause these stem cells to become osteoblasts instead of chondrocytes, and to cause the production of proteases that degrade cartilage.7,8,9
  • Inhibition of Wnt signaling in OA joints may drive stem cells to become chondrocytes and block protease-mediated cartilage degradation, thus resulting in cartilage regeneration.7,10
  • Therapies that target the Wnt pathway may therefore have potential in treating OA.7

Hip Osteoarthritis

Osteoarthritis has a significant economic impact due to the effects of disability, comorbid disease, and the expense of treatment.11 The global prevalence of symptomatic hip OA is 0.85% (0.98% for females and 0.70% for males).2 

  • Hip OA becomes more common with advancing age, reaching an annual incidence rate of 37/1000-person-years in a cohort over 45 years old.12 
  • Hip osteoarthritis can be disabling to the point of requiring total joint replacement, and it is estimated there will be 572,000 total hip arthroplasties per year in the US by 2030.13

Shoulder Osteoarthritis

The shoulder is the third most common large joint to be affected by OA and the fourth most commonly replaced joint.14 

  • The number of shoulder replacements has been increasing in volume, from 25,180 in 2002 to 67,189 in 2011.15 The prevalence of shoulder OA is 32.8% of adults over 60 years old.16 
  • The burden of disease perceived by shoulder OA patients is similar to other chronic diseases such as congestive heart failure, diabetes, and acute myocardial infarction.15 
  • The loss of shoulder function can lead to depression, anxiety, activity limitations, and job performance problems.17

References

    1. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum. 2008;58:26-35.
    2. Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73:1323-30.
    3. Wier LM, Levit K, Stranges E, et al. HCUP facts and figures: statistics on hospital based care in the United States, 2008. Rockville, MD: Agency for Healthcare Research and Quality, 2010. http://www.hcup-us.ahrq.gov/reports/factsandfigures/2008/pdfs/FF_report_2008.pdf.
    4. Glyn-Jones S, Palmer AJR, Agricola R, et al. Osteoarthritis. Lancet. 2015;386:376-87.
    5. Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science. 2014;346:1248012.
    6. Blom AB, Brockbank SM, Van Lent PL, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: Prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 2009;60:501-12.
    7. Monteagudo S, Lories RJ. Cushioning the Cartilage: a canonical Wnt restricting matter. Nature Reviews: Rheumatology. 2017 epub ahead of print.
    8. Gelse K, Ekici AB, Cipa F, et al. Molecular differentiation between osteophytic and articular cartilage – clues for a transient and permanent chondrocyte phenotype. Osteoarthritis Cartilage. 2012;20:162-71.
    9. Corr M. Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. Nat Clin Pract Rheumatol. 2008;4:550-6.
    10. Zimmerman ZF, Moon RT, Chien AJ. Targeting Wnt pathways in disease. Cold Spring Harb Perspect Biol. 2012;4(11), a008086.
    11. Bitton, R. The economic burden of osteoarthritis. Am J Manag Care. 2009;15(8 Suppl); S230-5.
    12. Moss AS, Murphy LB, Helmick CG, et al. Annual incidence rates of hip symptoms and three hip OA outcomes from a US population-based cohort study: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage. 2016;1518-27.
    13. Kurtz S, Ong K, Lau E, et al. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007;89(4):780-5.
    14. Gross CE, Van Thiel GS, Verma NN. Epidemiology and etiologies of glenohumeral arthritis. 2012.
    15. Padegimas EM, Maltenfort M, Lazarus MD, et al. Clin Orthop Relat Res. 2015; 473:1860-7.
    16. Chillemi C & Franceschini V. Shoulder osteoarthritis. Arthritis. 2013;370231.
    17. Memel DS, Kirwan JR, Sharp DJ, Hehir M. General practitioners miss disability and anxiety as well as depression in their patients with osteoarthritis. Br J Gen Pract. 2000;50(457):645-8.