Presentation on theme: "STRICTLY PRIVATE AND CONFIDENTIAL Implantable, Programmable, Re-fillable Stem Cell Pump + Microcurrent Regenerative Stimulator for treating Heart Failure."— Presentation transcript:
STRICTLY PRIVATE AND CONFIDENTIAL Implantable, Programmable, Re-fillable Stem Cell Pump + Microcurrent Regenerative Stimulator for treating Heart Failure and Limb Salvage 30 th Annual Interventional Cardiology Snowmass 3/3/15
STRICTLY PRIVATE AND CONFIDENTIAL Financial Interest Disclosure: I currently own 54.6% of the issued stock of BioLeonhardt. 30 th Annual Interventional Cardiology Snowmass 3/3/15
STRICTLY PRIVATE AND CONFIDENTIAL 300 YEARS! 142 IS OBSOLETE
STRICTLY PRIVATE AND CONFIDENTIAL Stem Cell Pump + Stimulator STRICTLY PRIVATE AND CONFIDENTIAL 4
Product Development STRICTLY PRIVATE AND CONFIDENTIAL 5
510Kd Microcurrent Stimulators for Healing STRICTLY PRIVATE AND CONFIDENTIAL 6
Goal heart failure = 230 meters improvement in exercise capacity. Reduction from 12 hospital days a year down to < 1. Goal limb salvage – reduce amputation rate and associated mortality by more than 50%.
STRICTLY PRIVATE AND CONFIDENTIAL Myoblast Engraftment Post-Transplantation STRICTLY PRIVATE AND CONFIDENTIAL 8 Contractile muscle tissue growing in the scarred portion of the heart following treatment with myoblast injections.
STRICTLY PRIVATE AND CONFIDENTIAL BioLeonhardt Method PRE-TREATS SCAR – Lays down vascular bed, Mircro RNAs partially converts fibroblasts to muscle, converts resident stem cells to cardiomyocytes, delivers nutrient hydrogel to prepare for cell injections. TREATS SCAR – Recruits via SDF-1 signal and infuses stem cells to scar tissue, proliferates recruited stem cells and resident cardiomyocytes, matures blood vessels, and differentiates cells into contractile muscle fibers. POST TREATS SCAR – Delivers nutrients and growth factors. Maintains blood supply. Release arrhythmia protection proteins. REPEATS ALL THE ABOVE AGAIN AND AGAIN UNTIL SCAR COMPLETELY REGENERATED INTO BEATING PUMPING MUSCLE ONLY THERAPY DESIGNED TO REGENERATE 100% OF HEART SCAR TISSUE BACK TO BEATING PUMPING MUSCLE STRICTLY PRIVATE AND CONFIDENTIAL 9
BioLeonhardt Method Pre-Treat Scar 1. Micro-RNAs (helps converts scar to muscle). 2. Nutrient hydrogel 3. Electrical stimulation releases SDF-1, VEGF, MCP1 + 3. 4. Growth factor infusion ie; VEGF, SDF-1, HGF 5. Granulocyte colony stimulating factor. 6. Endothelial progenitor cells derived from adipose tissue. Treat Scar 1. TANAKA cardiac progenitor cells derived from skeletal muscle as developed in Japan 2. Cardiac stem cells delivered at rim edge of scar. 3. SDF-1 via infusion + microcurrent stimulation. 4. Nutrient hydrogel 5. Electrical stimulation from MyoStim Pacers San Diego. 6. Injection of iPS cells with MicroRNAs. 7. Cardiobridge or Procyrion implantable pump to allow heart to rest during healing process. Post Treat Scar 1. Repeat injections of all of the above. 2. Continued electrical stimulation. 3. Continued delivery of nutrient hydrogel and growth factors. 4. Arrhythmia protection proteins and synchronization signal.
STRICTLY PRIVATE AND CONFIDENTIAL BioLeonhardt Stem Cell Pump + Stimulator STRICTLY PRIVATE AND CONFIDENTIAL 11
STRICTLY PRIVATE AND CONFIDENTIAL Uncle Jim STRICTLY PRIVATE AND CONFIDENTIAL 12 On 16 different CHF drugs Died at age 67 heart failure $8 billion spent on CHF drugs each year Drugs do not work to convert heart scar tissue to muscle.
STRICTLY PRIVATE AND CONFIDENTIAL “Designed to totally heal a severely damaged and failing heart.”
STRICTLY PRIVATE AND CONFIDENTIAL How? 1. Grows new vibrant blood supply. 2 Totally converts scar tissue 100% to beating pumping muscle.
STRICTLY PRIVATE AND CONFIDENTIAL Patented Microcurrent Stimulation causes tissues to produce … 1. SDF-1 expression. 2. VEGF expression. 3. MCP-1 and 3 expression. 4. Hepatocyte Growth factor expression. 4. Healing and pain relief.
STRICTLY PRIVATE AND CONFIDENTIAL Implantable, Programmable, Re-fillable Pump… 1. Delivers MicroRNAs and angiogenic growth factors to pre-treat scar. 2. Repeat delivers muscle building cells. 3. Post cell delivery maintenance. Intended Result = New blood supply network + myocardial scar is 100% converted to beating pumping muscle.
STRICTLY PRIVATE AND CONFIDENTIAL Gladstone Scientists Transform Non-Beating Human Cells into Heart-Muscle Cells - Research findings lay foundation for one day regenerating damaged heart muscle SAN FRANCISCO, CA—August 22, 2013—In the aftermath of a heart attack, cells within the region most affected shut down. They stop beating. And they become entombed in scar tissue. But now, scientists at the Gladstone Institutes have demonstrated that this damage need not be permanent—by finding a way to transform the class of cells that form human scar tissue into those that closely resemble beating heart cells. Last year, these scientists transformed scar-forming heart cells, part of a class of cells known as fibroblasts, into beating heart-muscle cells in live mice. And in the latest issue of Stem Cell Reports, researchers in the laboratory of Gladstone Cardiovascular and Stem Cell Research Direct Deepak Srivastava, MD, reveal that they have done the same to human cells.
STRICTLY PRIVATE AND CONFIDENTIAL MicroRNA regulation of cardiac regeneration miRNAs regulate many processes in cardiac regeneration, including cardiomyocyte proliferation, differentiation, survival, and reprogramming.
STRICTLY PRIVATE AND CONFIDENTIAL Lancet. 2003 Aug 30;362(9385):697-703. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Askari AT1, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS. FINDINGS: 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm2, n=4 per group, p<0.02) resulting in greater left- ventricular mass (1.24 [0.29] vs 1.57 [0.27] g) and better cardiac function (shortening fraction 9.2 [4.9] vs 17.2 [4.2]%, n=8 per group, p<0.05). These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signaling for stem-cell homing is re-established.
STRICTLY PRIVATE AND CONFIDENTIAL Cardiovasc Res. 2011 Aug 1;91(3):402-11. doi: 10.1093/cvr/cvr053. Epub 2011 Feb 22. VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart. Tang JM1, Wang JN, Zhang L, Zheng F, Yang JY, Kong X, Guo LY, Chen L, Huang YZ, Wan Y, Chen SY. The (VEGF)MSC-conditioned medium markedly promoted cardiac stem cell (CSC) migration at least in part via the SDF-1α/CXCR4 pathway and involved binding to VEGFR-1 and VEGFR-3. In vivo, (VEGF)MSC-stimulated SDF-1α expression in infarcted hearts resulted in massive mobilization and homing of bone marrow stem cells and CSC. Moreover, VEGF-induced SDF-1α guided the exogenously introduced CSC in the atrioventricular groove to migrate to the infarcted area, leading to a reduction in infarct size. Functional studies showed that (VEGF)MSC transplantation stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T, CD31, and von Willebrand factor and improved the left ventricular performance\\ CONCLUSION: Exogenously expressed VEGF promotes myocardial repair at least in part through SDF- 1α/CXCR4-mediated recruitment of CSC.
STRICTLY PRIVATE AND CONFIDENTIAL Circulation. 2004 Nov 23;110(21):3300-5. Epub 2004 Nov 8. Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Abbott JD1, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ.
STRICTLY PRIVATE AND CONFIDENTIAL Hepatocyte growth factor modification enhances the anti-arrhythmic properties of human bone marrow- derived mesenchymal stem cells. Zhang J1, Wang LL1, Du W1, Yu YC2, Ju WZ1, Man YL1, Li XR1, Chen Y1, Wang ZD1, Gu WJ1, Zhang FX1, Wang H3, Wu CT3, Cao KJ1. The HGF-MSC group displayed the highest vessel density and Cx43 expression levels, and the lowest levels of apoptosis, and tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) expression. Moreover, the HGF-MSC group exhibited a decrease in the number of sympathetic nerve fibers, substantial decreases in the low frequency and the low-/high- frequency ratio and increases in the root mean square of successive differences (rMSSD) and the percentage of successive normal sinus R-R intervals longer than 50 ms (pNN50), compared with the other two groups. Finally, the HGF-MSC group displayed the lowest susceptibility to developing VA. CONCLUSION: HGF-MSCs displayed potent antiarrhythmic effects, reducing the risk for VA. PLoS One. 2014; 9(10): e111246.
STRICTLY PRIVATE AND CONFIDENTIAL PLoS One. 2008 Mar 12;3(3):e1789. doi: 10.1371/journal.pone.0001789. Cardiomyocyte formation by skeletal muscle-derived multi-myogenic stem cells after transplantation into infarcted myocardium. Tamaki T, Akatsuka A, Okada Y, Uchiyama Y, Tono K, Wada M, Hoshi A, Iwaguro H, Iwasaki H, Oyamada A, Asahara T. Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, Isehara, Kanagawa, Japan. email@example.com@is.icc.u-tokai.ac.jp METHODS AND RESULTS: Transplanted Sk-34 cells were incorporated into infarcted portions of recipient muscles and contributed to cardiac reconstitution. Significant improvement in left ventricular function, as evaluated by transthoracic echocardiography and micro-tip conductance catheter, was also observed. CONCLUSIONS AND SIGNIFICANCE: Skeletal muscle-derived multipotent Sk-34 cells that can give rise to skeletal and smooth muscle cells as reported previously, also give rise to cardiac muscle cells as multi-myogenic stem cells, and thus are a potential source for practical cellular cardiomyoplasty.
STRICTLY PRIVATE AND CONFIDENTIAL Clinical Trials STRICTLY PRIVATE AND CONFIDENTIAL 24
STRICTLY PRIVATE AND CONFIDENTIAL 400 pts Enrolled in Myoblast Cell Trials for Heart Failure Since 2000 84% of pts improved in treated group. Only 16% of control or placebo pts improved. 69% of control and placebo pts worsened compared to 16% in treated group. Improvement = 6 min. walk, QOL, Dobutamine Stress Echo, PV Loops, Hospital Days or Heart Failure Class Phase I Lancet, JACC, Phase II EuroIntervention,Phase III American Heart Journal. STRICTLY PRIVATE AND CONFIDENTIAL 25
STRICTLY PRIVATE AND CONFIDENTIAL Reverse remodeling with myoblast transplantation STRICTLY PRIVATE AND CONFIDENTIAL 26
STRICTLY PRIVATE AND CONFIDENTIAL PV Loops Study Myoblast Transplantation - Serruys et al European Heart Journal STRICTLY PRIVATE AND CONFIDENTIAL 27
STRICTLY PRIVATE AND CONFIDENTIAL Dobutamine Stress Echo Observed Improvement Myoblast Transplantation STRICTLY PRIVATE AND CONFIDENTIAL 28
STRICTLY PRIVATE AND CONFIDENTIAL MARVEL Phase II/III Randomized Double Blinded, Placebo Controlled – American Heart Journal October 2011 Mean Change in 6-Minute Walk Distance (meters) STRICTLY PRIVATE AND CONFIDENTIAL 29 Bioheart MyoCell myoblasts one half hour session of 16 injections low dose 400 million cells, high dose 800 million cells. Placebo received optimal CHF drugs. 95.7 meters improvement over placebo. Phase II/III MARVEL Part I study - 33 Leading U.S. Heart Failure Centers Enrolled in Study. Am Heart J. 2011 Oct;162(4):654- 662.e1. doi: 10.1016/j.ahj.2011.07.020
STRICTLY PRIVATE AND CONFIDENTIAL Supporting Pre-Clinical Studies STRICTLY PRIVATE AND CONFIDENTIAL 30
STRICTLY PRIVATE AND CONFIDENTIAL Over 80 published papers supporting: Ability to regenerate damaged muscle Homing stem cells to target Differentiating stem cells to muscle Growing a new mature non-leaky blood vessel supply Benefits of repeat delivery Benefits of combined therapy Supporting Data STRICTLY PRIVATE AND CONFIDENTIAL 31
STRICTLY PRIVATE AND CONFIDENTIAL Repeat injections even more improvement European Heart Journal (2010) 31, 1013–1021 doi:10.1093 Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction Felipe Prosper et al. A significantly greater increase in the DLVEF was detected in animals that received three doses vs. a single dose of SkM. A correlation between the total number of transplanted cells and the improvement in LVEF and DLVEF was found (P, 0.05). Skeletal myoblast transplant was associated with an increase in tissue vasculogenesis and decreased fibrosis (collagen vascular fraction) and these effects were greater in animals receiving three doses of cells.
STRICTLY PRIVATE AND CONFIDENTIAL Repeat Delivery of Cells Brings More Improvement STRICTLY PRIVATE AND CONFIDENTIAL 33 We have calculated that it would take 36 needle catheter procedures to fully recover an average post-heart attack scar completely and reliably. The BioLeonhardt device replaces the need for 36 separate cath lab interventions. European Heart Journal (2010) 31, 1013–1021 doi:10.1093 Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction Felipe Prosper et al.
STRICTLY PRIVATE AND CONFIDENTIAL SDF-1 + Myoblasts Pre-Clinical Study Presented @ 7 th Cardiovascular Cell Therapy Meeting Columbia 2008 Modified Adult Stem Cells – Myoblasts SDF-1 – Pre-Clinical Study Cleveland Clinic 2007 - Dr. Marc Penn > Sham 10 percent decline. > Myoblasts alone 27% improvement cardiac function. > SDF-1 modified myoblasts 54% improvement cardiac function Dr. Marc Penn from Cleveland Clinic presented pre-clinical data demonstrating that adult muscle stem cells (myoblasts) modified to overexpress SDF-1 (stromalderived factor-1) are able to achieve significant improvements in the pumping ability of the heart. Myoblasts alone in his study provided a 27 percent improvement of the pumping ability of the damaged animal hearts he treated, while SDF-1 modified myoblasts provided a 54 percent improvement. STRICTLY PRIVATE AND CONFIDENTIAL 34
STRICTLY PRIVATE AND CONFIDENTIAL SDF-1 Expression from Heart Decreases After MI STRICTLY PRIVATE AND CONFIDENTIAL 35 Following MI, myocardial release of SDF-1a is reduced. Boyle et al. Journal of Translational Medicine 2011 9:150 doi:10.1186/1479-5876-9-150 Transmyocardial gradient = coronary sinus level - coronary artery level; stable = stable coronary artery disease; UAP = unstable angina pectoris; MI = myocardial infarction.
STRICTLY PRIVATE AND CONFIDENTIAL SDF-1 Expression from Heart Decreases from Coronary Artery Disease STRICTLY PRIVATE AND CONFIDENTIAL 36 SDF-1a release from the human heart. In humans, SDF-1a is constitutively released from hearts with normal coronary arteries. However, following MI, myocardial release of SDF-1a is reduced. This is consistent with the murine mRNA expression pattern. SDF-1a release is suppressed in all stages of coronary artery disease, suggesting that coronary artery disease, rather than the tissue damage from MI, is responsible for the suppression of SDF-1a release. Transmyocardial gradient = coronary sinus level - coronary artery level; stable = stable coronary artery disease; UAP = unstable angina pectoris; MI = myocardial infarction. Boyle et al. Journal of Translational Medicine 2011 9:150 doi:10.1186/1479-5876-9-150
STRICTLY PRIVATE AND CONFIDENTIAL BioLeonhardt's Patented Microcurrent Signal Produces Over 230% increase in New Blood Vessels – Circulation. 1999 May 25;99(20):2682-7. STRICTLY PRIVATE AND CONFIDENTIAL 37 Also VEGF mRNA (angiogenic new blood vessel creating protein) increased 450% in smooth muscle and 480% in skeletal muscle.
STRICTLY PRIVATE AND CONFIDENTIAL Microcurrent Causes Stimulated Tissues to Release Stem Cell Homing Factor SDF-1 STRICTLY PRIVATE AND CONFIDENTIAL 38
STRICTLY PRIVATE AND CONFIDENTIAL Hydrogel Infusion to Aide New Muscle Formation PLoS One. 2012; 7(12): e51991. Published online 2012 Dec 20. doi: 10.1371/journal.pone.0051991 Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction Eva Mathieu,1,2 Guillaume Lamirault,1,2,3 Claire Toquet,3,4 Pierre Lhommet,1,2 Emilie Rederstorff,2,5 Sophie Sourice,2,5 Kevin Biteau,1,2 Philippe Hulin,2,6 Virginie Forest,1,2 Pierre Weiss,2,3,5 Jérôme Guicheux,#2,5 and Patricia Lemarchand#1,2,3,* Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. STRICTLY PRIVATE AND CONFIDENTIAL 39
STRICTLY PRIVATE AND CONFIDENTIAL Mixed Compositions of Cells + Genes + Hydrogel STRICTLY PRIVATE AND CONFIDENTIAL 40 Mixed compositions work better than cells or genes alone. The BioLeonhardt device is designed for sustained delivery of multi-stage multiple composition therapies
STRICTLY PRIVATE AND CONFIDENTIAL Heart Failure Treatment Competitive TherapyExercise Improvement Method BioLeonhardt: Stem Cell Pump Stimulator 230 meters* (*expected) Implantable pump + regenerative microcurrent stimulator Mesoblast: Capricor, Cardio-3, Bioheart, Osiris – cell injections one time 53 to 91.7 metersOne time injection of cells into myocardium Medtronic, St. Jude, Boston Scientific Guidant: Sorin, BioTronik CRT Pacers 16 to 20 metersPacing healthy heart tissue to increase output CHF DrugsMinus 4 meters decline Reduce symptoms only. Dilates blood vessels. Reduces water retention. STRICTLY PRIVATE AND CONFIDENTIAL 41
STRICTLY PRIVATE AND CONFIDENTIAL How the Technology Works Therapeutic stem cells and growth factors are delivered in stages over time via an implantable pump and microcurrent stimulation Our cells and growth factors are able to grow new blood vessels and new tissue including muscle where needed and applicable In the case of heart muscle regeneration we gradually grow more and more strips of new contractile muscle in the previous heart scar tissue over time In the case of limb salvage we accelerate healing of the diabetic foot ulcer first than gradually increase the long term blood supply to the lower limb by the creation of a vibrant new blood supply system – biological bypass STRICTLY PRIVATE AND CONFIDENTIAL 42
STRICTLY PRIVATE AND CONFIDENTIAL Heart Failure and Diabetes Two Leading Healthcare Problems in the USA Today No therapy is able to regenerate post heart attacked scarred hearts completely and reliably. Heart failure is the leading economic drain on Medicare costing more than $31 billion annually. No therapy reliably regenerates failing limbs with a sustainable solution. In 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs; at least 33% of these costs were linked to the treatment of foot ulcers. More than $31 billion is spent annually on heart failure STRICTLY PRIVATE AND CONFIDENTIAL 43
STRICTLY PRIVATE AND CONFIDENTIAL Bio-Leonhardt’s Solution Implantable, Programmable, Refillable Stem Cell Pump + Stimulator: Designed to fully regrow new muscle in heart scar tissue completely over time with a proprietary multi-stage therapeutic protocol. –Goal is to cut more than half the $30 billion in annual expenditures for heart failure in the USA. When implanted in the upper thigh muscle designed to revive completely a failing limb by renewing vibrant sustainable blood flow to the lower limbs by growing new blood vessels. –Goal is to reduce the cost of care for diabetic foot ulcers in the USA by over $20 billion annually. STRICTLY PRIVATE AND CONFIDENTIAL 44
STRICTLY PRIVATE AND CONFIDENTIAL Competitor Superiority Competitive TherapiesBioLeonhardt Solutions Heart Treatment Other therapies for the heart either only treated the good tissue and did nothing for the scar or if treating the scar had limited effect with a one time 30 minute treatment without supporting factors. Our method for heart regeneration of 1. Pre-treating scar. 2. Treating scar and 3. Post treating scar follows the tried and true methods used in good farming of crops. We are essentially growing a crop of new muscle in scar tissue supported by fertilizers (growth Limp Salvage Treatment Other therapies for limb salvage either just healed temporarily the ulcer without addressing the underlying problem of lack of blood flow or attempted to address blood flow with a single by- pass vessel which was incomplete. Our method for limb salvage delivers healing and blood vessel growing proteins over time that provide a more sustainable recovery of the limb. STRICTLY PRIVATE AND CONFIDENTIAL 45
STRICTLY PRIVATE AND CONFIDENTIAL Limb Salvage Treatment STRICTLY PRIVATE AND CONFIDENTIAL 46 Problem Patients with critical limb ischemia (CLI) have a considerably bad prognosis, with 40% of patients progressing to major amputation within 6 months and most patients losing their limbs eventually if no attempt at revascularization is performed. 29 million Americans suffer of CLI. Critical limb ischemia is found in 12% of the U.S. adult population = 29 million people. Its clinical presentation varies from no symptoms to intermittent claudication, atypical leg pain, rest pain, ischemic ulcers, or gangrene. Those with critical limb ischemia have a high incidence of cardiovascular comorbidities that reflect a significant systemic atherosclerotic burden; they have increased functional impairment and increased rates of functional decline compared with persons without critical limb ischemia. Interventions for critical limb ischemia and the impact of major amputation have a significant social and economic impact. At 1 year, 25% of patients will be dead, 30% will have undergone amputation, and only 45% will remain alive with both limbs. At 5 years with current available treatments, more than 60% of patients with critical limb ischemia will be dead.
STRICTLY PRIVATE AND CONFIDENTIAL #1 - Microcurrent electro-acupuncture 3X a week for 45 minutes in clinic. #2 - Microcurrent bandages every 3 days. #3 - Microcurrent home treatment. #4 - Adipose derived cell injections. #5 - Temporary circulatory assist pumps. #6 - Athrectomy with EndoCell. #7 - Implantable pump + stimulator. BioLeonhardt MyoStim Limb Salvage Protocol STRICTLY PRIVATE AND CONFIDENTIAL 47
STRICTLY PRIVATE AND CONFIDENTIAL 510Kd Microcurrent Stimulators for Healing STRICTLY PRIVATE AND CONFIDENTIAL 48
STRICTLY PRIVATE AND CONFIDENTIAL Limb Salvage/Diabetic Foot Ulcer Treatment STRICTLY PRIVATE AND CONFIDENTIAL 49 Solution BioLeonhardt MyoStim has a full armentarium of products for CLI associated limb salvage starting with our microcurrent stimulation devices and for advanced patients an implantable, refillable, programmable pump + stimulator placed in their thigh muscle for long term limb recovery.
STRICTLY PRIVATE AND CONFIDENTIAL Microcurrent Electro-acupuncture for Limb Salvage STRICTLY PRIVATE AND CONFIDENTIAL 50
STRICTLY PRIVATE AND CONFIDENTIAL Microcurrent Electro-acupuncture for Limb Salvage STRICTLY PRIVATE AND CONFIDENTIAL 51
STRICTLY PRIVATE AND CONFIDENTIAL Micorocurrent Electroacupuncture for Limb Salvage STRICTLY PRIVATE AND CONFIDENTIAL 52
STRICTLY PRIVATE AND CONFIDENTIAL The future is now: wireless micro current directed stem cell regeneration STRICTLY PRIVATE AND CONFIDENTIAL 53
STRICTLY PRIVATE AND CONFIDENTIAL WIRELESS MICROCURRENT HEALING
STRICTLY PRIVATE AND CONFIDENTIAL Paper on Wireless Micro Current Stimulation STRICTLY PRIVATE AND CONFIDENTIAL 55
STRICTLY PRIVATE AND CONFIDENTIAL Microcurrent Treatment 95% Reduction of Wound Scar Size @ 8 Weeks 47 Patient Clinical Study – Germany & Switzerland – Published International Wound Journal ISSN 1742-4801 2014
STRICTLY PRIVATE AND CONFIDENTIAL Wireless Microcurrent Healing STRICTLY PRIVATE AND CONFIDENTIAL 57
STRICTLY PRIVATE AND CONFIDENTIAL Limb Salvage Treatment STRICTLY PRIVATE AND CONFIDENTIAL 58 Bioheart Reports Positive Results for Adipose Derived Stem Cells in Critical Limb Ischemia - See more at: http://globenewswire.com/news- release/2011/01/10/437455/210672/en/Bioheart-Reports-Positive-Results-for- Adipose-Derived-Stem-Cells-in-Critical-Limb- Ischemia.html#sthash.MorzTSj3.dpufhttp://globenewswire.com/news- release/2011/01/10/437455/210672/en/Bioheart-Reports-Positive-Results-for- Adipose-Derived-Stem-Cells-in-Critical-Limb- Ischemia.html#sthash.MorzTSj3.dpuf SUNRISE, Fla., Jan. 10, 2011 (GLOBE NEWSWIRE) -- Bioheart, Inc. (OTCBB:BHRT) announced positive efficacy data has been reported from the registry study of bone marrow and adipose derived stem cells for the treatment of end stage critical limb ischemia with wounds. Vaclav Prochazka MD, PhD, MSc., of University Hospital Ostrava, Czech Republic presented data at the American Academy of Anti-Aging Medicine Conference in Las Vegas last month.
STRICTLY PRIVATE AND CONFIDENTIAL Adipose Stem Cell Collection Kit Produced according to cGMP Each Laboratory Kit includes: –A vial of lyophilized “Adipolase” which consists of a clinical grade collagenase –consumables necessary to isolate regenerative stem cells
STRICTLY PRIVATE AND CONFIDENTIAL Limb Salvage Treatment STRICTLY PRIVATE AND CONFIDENTIAL 61 Bioheart Reports Positive Results for Adipose Derived Stem Cells in Critical Limb Ischemia –. Vaclav Prochazka MD, PhD, MSc., of University Hospital Ostrava, Czech Republic – "We are very pleased with the preliminary results of adipose derived cells. This is a continuation of our research of bone marrow derived stem cells. Our results have been published this month in Cell Transplantation," said Dr. Prochazka. - The study focuses on end stage patients with severe wounds. Endpoints include elimination of major amputation risk, ankle brachial index, toe pressure, transcutaneous oxygen pressure, and quality of life. Seventy-five percent of patients presented with healing and pain reduction while only twenty-five percent of the patients required major limb amputation due to disease progression. Autologous adipose tissue derived stem cells (ADSCs) can help to produce angiogenesis or formation of new blood vessels as well as assist in the healing process. There were no reported deaths or severe adverse events demonstrating the safety of the products.
STRICTLY PRIVATE AND CONFIDENTIAL 4 Month Follow-up 16 Patients treated for Critical Limb Ischemia 4 patients – MLA (Major Limb Amputation for disease progression (25%) 12 patients – Healing Progression/Pain reduction (75%) Ø Death Ø SAE or Liposuction AE Ø Lost or withdrawn from study
STRICTLY PRIVATE AND CONFIDENTIAL D-0D-10 D-14 D-30 D-60
STRICTLY PRIVATE AND CONFIDENTIAL Procyrion Temporary Aortic Placed Circulatory Assist STRICTLY PRIVATE AND CONFIDENTIAL 64
STRICTLY PRIVATE AND CONFIDENTIAL Cardiobridge Circulatory Assist Pump STRICTLY PRIVATE AND CONFIDENTIAL 65
STRICTLY PRIVATE AND CONFIDENTIAL Athrectomy Followed by Endothelium Adventia Re-lining with Injected EPC’s STRICTLY PRIVATE AND CONFIDENTIAL 66
STRICTLY PRIVATE AND CONFIDENTIAL Patents STRICTLY PRIVATE AND CONFIDENTIAL 67
STRICTLY PRIVATE AND CONFIDENTIAL Pioneering Patent Claims Only signal able to convert stem cells to beating heart muscle – Leonhardt et al. Only electrical signaling to trigger stem cell homing to target tissue – Leonhardt et al. Only electrical signaling to create mature blood vessel supply – Kanno, Chachques, Leonhardt. Pending: Only combo repeat delivery implantable, refillable programmable pump + REGENERATION stimulator Multi-stage combination therapy for heart failure reversal Wireless regeneration of organs Arrhythmia reduction microcurrent therapies – HGF. STRICTLY PRIVATE AND CONFIDENTIAL 68
STRICTLY PRIVATE AND CONFIDENTIAL Pioneering Patent Claims STRICTLY PRIVATE AND CONFIDENTIAL 69 Pioneering patents claims = 1. Recruits stem cells to any target location with control. 2. Converts stem cells to beating heart muscle. 3. Ensures new muscle beats in synchrony with host. 4. Grows new blood supply.
STRICTLY PRIVATE AND CONFIDENTIAL Aortic Aneurysm Repair with Microcurrent – Reinforce Necks For Stent Graft Landing + Fully Repair Small Aneurysms STRICTLY PRIVATE AND CONFIDENTIAL 70
STRICTLY PRIVATE AND CONFIDENTIAL The Future Is Now! STRICTLY PRIVATE AND CONFIDENTIAL 71
STRICTLY PRIVATE AND CONFIDENTIAL Summary Heart Failure Recovery 1. One time session delivery of cells is not enough. Repeat delivery is needed. 2. SDF-1 is key to both arteriogenesis and myogenesis. 3. Our pump+stimulator over a course of year is designed to completely recover myocardial scar tissue into beating heart muscle with a vibrant blood supply and to reverse re-model a failing heart. Additional studies are required to prove.
STRICTLY PRIVATE AND CONFIDENTIAL Summary Limb Salvage 1. A multi-stage aggressive approach is needed to reduce rate of amputation and mortality associated with critical limb ischemia. 2. The BioLeonhardt approach of microcurrent + stem cells + circulatory assist pump + athrectomy with endothelium repair + implantable refillable pump warrants further study.