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What causes Insufficiency Degenerative Disc Disease? DDD - PowerPoint PPT Presentation

Nov 12, 2023 •220 likes •353 views

The NEXT Treatment for Low Back Pain Tom Hedman, Ph.D. Associate Research Professor Center for Biomedical Engineering and Department of Neurosurgery University of Kentucky Founder, General Partner and Chief Scientific Officer

  1. The NEXT Treatment for Low Back Pain Tom Hedman, Ph.D. Associate Research Professor Center for Biomedical Engineering and Department of Neurosurgery University of Kentucky Founder, General Partner and Chief Scientific Officer – Orthopeutics, LP Founder, Chairman – Intralink Spine, Inc. Founder, Board Member – Equinext, LLC September 2013

  2. Genetics Loss of GAGs/ Hydration Nutritional Deficiency Mechanical What causes Insufficiency Degenerative Disc Disease? DDD

  3. Associated Disc Bulge/ Neural Biomarkers: Compression Joint Instability/ - Disc Bulge Afferent Nerve Strain - Joint Instability - Fissures into outer 30% of AF Fissuring/EP - AF HIZs (T2) Damage - Modic I&II Proinflammatory Cytokine Release adjacent to EP Neo-Innervation Edema Pain Generators Neuropathy

  4. Disc Therapeutic Performance Criteria Factors Underlying Increase retention of GAGs/ hydration? Increase nutritional flow/ permeability? Improve mechanical properties/ durability? Reduce disc bulge? Generators Pain Reduce joint instability? Increase tear resistance? Provide adhesion of adjacent tissues? Ensure minimal toxicity? Criteria Other Useful as an adjunct to surgery? Fast-acting / Long-lasting? Inexpensive?

  5. NEXT - Nonsurgical EXogenous Crosslink Therapy • Injectable Collagen Crosslink augmentation • Genipin -based reagent augments crosslinking of native ECM • Injectable/conservative care/ biomimetic approach • Immediate effect/ long-lasting covalent bonds • Cost effective genipin NEXT TM

  6. Summary of Experimental Results: NEXT… Factors Underlying  Increases retention of GAGs/ hydration (>40%)  Increases nutritional flow/ permeability (100%)  Improves mechanical properties/ durability (>25%)  Reduces disc bulge (>25%) Generators Pain  Reduces joint instability (4-fold)  Increases tear resistance (50%)  Provides adhesion of adjacent tissues (3X)  Exhibits minimal toxicity (sub-cu/neurotox/6-studies) Criteria Other  A good adjunct: Restabilizes post-discectomy  Fast-acting / Long-lasting  Inexpensive (90% reduction in device costs)

  7. References Some of Our 28 Peer-Reviewed Publications Follow-On Work By Others Hedman, T, Saito, H., Vo, C. and Chuang, S-Y, Exogenous Crosslinking Yerramalli CS, Chou AI, Miller GJ, Nicoll SB, Chin KR, Elliott DM, The Increases the Stability of Spinal Motion Segments, Spine 31(15):E480- effect of nucleus pulposus crosslinking and glycosaminoglycan 485, 2006. degradation on disc mechanical function . Biomech.Model.Mechanobiol , Chuang, S-Y , Odono, R.M., Hedman, T.P., Effects of Exogenous 2007;6:13-20. Crosslinking on In Vitro Tensile and Compressive Moduli of Lumbar Intervertebral Discs , Clinical Biomechanics , 22(1):14-20, 2007. Barbir A, Michalek AJ, Abbott RD, Iatridis JC., Effects of enzymatic Chuang, S-Y, Popovich, JM, Lin, L-C, Wang, S-J, Hedman, T, The Effects digestion on compressive properties of rat intervertebral discs, J of Exogenous Crosslinking on Hydration and Fluid Flow in the Biomech . 2010 Apr 19;43(6):1067-73 Intervertebral Disc Subjected to Compressive Creep Loading and Unloading Spine, Spine , 35(24):E1362-6, 2010. Chuang SY, Lin LC, Tsai YC, Wang JL., Exogenous crosslinking recovers Chuang, S-Y, Lin, L-C, Hedman, T.P., The Influence of Exogenous the functional integrity of intervertebral disc secondary to a stab injury., Crosslinking and Compressive Creep Loading on Intradiscal Pressure, J Biomed Mater Res A . 2010 Jan;92(1):297-302. Biomech Model Mechanobiol. 9(5):533-538, 2010 . Fessel G, Wernli J, Li Y, Gerber C, Snedeker JG., Exogenous collagen Slusarewicz, P, Zhu, K, Hedman, T, Kinetic Characterization and cross-linking recovers tendon functional integrity in an experimental Comparison of Various Protein Crosslinking Reagents Suitable for Tissue model of partial tear, J Orthop Res. 2011 Nov 18. doi: Engineering, J Mater Sci Mater Med., 21(4):1175-81, 2010. 10.1002/jor.22014. [Epub ahead of print] Slusarewicz, P., Zhu, K. and Hedman, T., Studies on the degradation of genipin in aqueous solution, Natural Products Communications, Fessel G, Gerber C, Snedeker JG., Potential of collagen cross-linking 5(12):1853-8, 2010. therapies to mediate tendon mechanical properties, J Shoulder Elbow Slusarewicz, P., Zhu, K., Kirking, B., Toungate, J., Hedman, T., Surg. 2012 Feb;21(2):209-17 Optimization of Protein Crosslinking Formulations for the Treatment of Degenerative Disc Disease, Spine, 36(1):E7-13, 2011. Zhu, K, Slusarewicz, P, Hedman, T, Thermal Analysis Reveals Differential Effects of Various Crosslinkers on Bovine Annulus Fibrosis, J Orthop Res. , 29(1):8-13, 2011. Popovich, J.M., Yau, D, Chuang, S-Y, Hedman, T., Exogenous Collagen Crosslinking of the Intervertebral Disc Restores Joint Stability following Lumbar Posterior Decompression Surgery, Spine , 36(12):1-6, 2011 .

  8. When is it the right time to use NEXT? Normal Aging, Disc Degeneration / Dehydration Annulus Overload / Nutritional Deficiency Bulges / Fissures / Cracks / Mechanical Insufficiency Disc Collapse / Herniations Nerve Root Compression / Facet Joint Pain *Weber ‘94

  9. The ‘Injectable’ Competition: Can Biologic Treatments Work in the Intervertebral Disc? Intervertebral Disc x Harsh, nutritionally deficient (largely avascular) environment of the disc led to DDD in the first place x “Degenerative discs are not able to support the added nutrient demands from increase in cellular activity or Vertebral Body cell number…” – Jill Urban, PhD (well vascularized) x Biological treatments offer no near- term effect, not appropriate as a stand-alone treatment

  10. NEXT Is the Perfect Adjunct to Cell-Based Therapies  Provides immediate joint stability and resistance to mechanical degradation  Crosslinking increases nutrient permeability for long-term treatment viability

  11. Patent # Principal Claims US 10/230,671 Found in Mechanical degradation, disc, articular cartilage, load condition for allowance supporting collagenous tissue 7,435,722 Scoliosis and permeability, knee meniscus and articular cartilage Patent Portfolio 8,153,600 General deformity: kyphosis, listhesis, post-surgical; listed reagents; for increasing effectiveness of cell or cytokine treatments 8,022,101 Knee meniscus tear resistance; concentrations GP, PA, EDC, LO, TG, non-enzymatics 8,119,599 Tear resistance, prevention of expulsion of nucleus or nucleus implant; disc and knee meniscus, reagent • 10 US and 6 concentrations 8,198,248 Formulation & composition of matter claims; international patents 8,211,938 Treatment of annulus fibrosus against expulsion or extrusion of implanted device or material issued or in condition for 8,283,322 Improved formulation and composition of matter claims allowance 8,450,276 Increasing biological viability for regeneration of spinal discs 12/966,812 Found in Divisional: Mechanical degradation, disc, articular • Additional 25 US and condition for allowance cartilage, load supporting collagenous tissue Foreign international patents Australia 2002335683 Mechanical degradation, disc, articular cartilage, load supporting collagenous tissue pending Canada 2,458,821 Mechanical degradation, disc, articular cartilage, load supporting collagenous tissue Australia 2004268628 Spinal disc, scoliosis, permeability, knee meniscus, articular cartilage Japan 2006-524909 Spinal disc, scoliosis, permeability, knee meniscus, articular cartilage Canada 2,536,415 Crosslinking reagent for treating intervertebral disc disorders Korea Spinal disc, scoliosis, permeability, knee meniscus, articular cartilage

  12. Funding required: $600k or $6million Exit Strategy #1: Early acquisition by spinal device company $600k for 6 mo. FIM clinical trial + License fee, 300-650% ROI within 18 mo. • Malaysian clinical site – Harwant Singh, MD, PhD, Hansen Yuan, MD, Kevin Pauza, MD, Todd Abruzzo, MD, John M Racadio, MD – spine surgeons & interventionalists Available upon request • Elsa Abruzzo, CQE, CQA, RAC, FRAPS, President/CEO ARAC, LLC, Clinical/Regulatory VP • LMH Biotech, Sdn., Bhd., Malaysian Clinical Trials CRO/Partner Exit Strategy #2: Acquisition after US market entry or IPO* $6 million total investment, FIMs + clinicals for CE marking • High profit margin allows for internal funding of US trials from EU/Asia sales Available upon request • Disruptive potential provides incentive to avoid early exit Contact Tom Hedman for more information: thedman@intralinkspine.com

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