science of cardiamp heart failure cell therapy · 2019-05-02 · cell potency assay should enhance...

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Science of CardiAMP Heart Failure Cell Therapy

5/1/2019 05141-A (MKT) Science of CardiAMP Cell Therapy

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Cautionary Note Regarding Forward-Looking Statements

These slides and any accompanying oral presentation contain forward-looking statements as that term is defined under the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, among other things, references to development plans and timelines for our products, the regulatory pathways for our clinical trials and approvals, and our relative position among competitors with respect to development and commercialization strategies. BioCardia has based these forward-looking statements on its estimates and assumptions and its current expectations and projections about future events. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including the inherent uncertainties associated with clinical trials, regulatory approvals, patient enrollment, the ability to raise the additional funding needed to continue to pursue our business and product development plans and timing of other cardiac cell therapies. In light of these risks, uncertainties and assumptions, actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. BioCardia undertakes no obligation to update publicly or revise any forward-looking statements for any reason after the date of this presentation, to conform these statements to actual results or to changes in BioCardia’s expectations. Certain data in this presentation was obtained from various external sources that neither the Company nor its affiliates, advisers or representatives has verified with independent sources. Accordingly, neither the Company nor any of its affiliates, advisers or representatives makes any representations as to the accuracy or completeness of that data or to update such data after the date of this presentation. Such data involves risks and uncertainties and is subject to change based on various factors. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of the products or services of the Company.

This presentation does not constitute an offer to sell securities including but not limited to within any jurisdiction in which the sale of such securities would be unlawful. This presentation does not constitute a solicitation or offer to sell securities. Such offer and the information set forth herein have not been reviewed, approved or disapproved, nor has the accuracy or adequacy of the information set forth herein been passed upon, by the SEC or any state securities administrator. Any representation to the contrary is a criminal offense.


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Backgroundo What is bone marrow cell therapy?o Cardiac cell therapy mechanisms of actiono Cardiac cell therapy – paracrine effects

Bone marrow cell therapy – Preclinical Experienceo Rats: Paracrine stimulus study - reduces scar and leads to micro vessel formationo Pigs: Dose dependent study - shows higher dose reduces scar and leads to increased microvessel formation

Effective Dosage: o Helix increases efficiency of delivery o Cell Potency Assay should enhance patient responsiveness to therapy

CardiAMP Heart Failure Trialo Clinical background o Phase 1 design & resultso Phase 2 design & resultso Phase 3 design & results

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Science of CardiAMP Cell Therapy - Overview

05141-A (MKT) Science of CardiAMP Cell Therapy

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What is Bone Marrow Cell Therapy?

• Stem cell therapies may offer the potential to treat diseases or conditions for which few treatments exist.

• Sometimes called the body’s “master cells,” stem cells are the cells that develop into blood, brain, bones, and all of the body’s organs.

• They have the potential to repair, restore, replace, and regenerate tissues, and could possibly be used to treat many medical conditions and diseases.

• The hip bone or iliac crest contains a large volume of bone marrow cells that have historically been harvested for bone marrow transplantation and as a source of stem cell therapies.

5/1/2019https://www.fda.gov/forconsumers/consumerupdates/ucm286155.htm

Bone marrow cells include a number of important cell populations that have each been studied for therapeutic benefit for treating the heart and have shown benefit in animal and clinical studies

• Hematopoietic stem and progenitor cells • Mesenchymal stem cells


https://www.fda.gov/forconsumers/consumerupdates/ucm286155.htm

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Cardiac Cell Therapy: Mechanistic Basis for Regeneration

Transplanted bone marrow cells have been hypothesized to benefit the heart through direct and indirect pathways.

Behfar, A. et al. (2014) Nat. Rev. Cardiol. 11: 232–246

Direct Regeneration: Transplanted cells actively home to injury sites and differentiate into new functional tissue to augment organ function. No cell therapy for cardiovascular regeneration in clinical trials is yet believed to integrate into heart tissue permanently. Of note, studies that showed cells did not turn into heart cells also showed some improvements in treated animal hearts.

Indirect Regeneration: Transplanted cells secrete stimulatory cytokines to instigate an innate regenerative response from resident stem cells.

5/1/201905141-A (MKT) Science of CardiAMP Cell Therapy

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Cardiac Cell Therapy: Paracrine Stimulus

Cell therapies have been shown to provide paracrine mediators that promote a number of valuable mechanisms of action. Significant compelling preclinical data sets using bone marrow derived cells

Dzau, VJ et al. (2011); J Mol Cell Cardiol. 50(2): 280-289.


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Bone marrow Cells – Preclinical Experience

Small (rats, mice) and large animal (swine, canine) studies support safety and efficacy of bone marrow cells. A few of these are provided.

Takahashi et al. (2006): o Explored paracrine mechanism in ratso BMC media injected after overnight incubation under normoxia and hypoxia

Sun J et al (2009): o Cardiac function enhanced after BMC or BMC medium transplantation in rats

Silva et al. (2011): o Explored dose effect of bone marrow mononuclear cells, delivered via

transendocardial injection in post infarct pig modelo 50, 100, 200 Million BMC injected in infarcted heart

Takahashi M et al. Am J Physiol Heart Circ Physiol (2006);291:H886-H893Sun J et al. Am J Physiol Heart Circ Physiol 2009;296:H43-H50Silva et al. Tex Heart Inst J (2011);38(3):219-24


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Paracrine Stimulus: BMC Media (Normoxia and Hypoxia) led to reduced fibrotic scar and enhanced microvessel density in the infarcted rat

myocardium 28 Days after treatment

Takahashi, M. et al. (2006) Am J Physiol Heart Circ Physiol 291:H886-H893

Bone Marrow Cells – Preclinical Experience (Rat)

Reduced Fibrosis Increased Microvessel Density


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1111

Cardiac Function Enhanced After BMC or BMC Medium Transplantation in Rats

Sun J et al. Am J Physiol Heart Circ Physiol 2009;296:H43-H50


Results of echocardiography showing more rapid loss of function and ventricular dilation in the control group[sham group, n = 6; medium group, n = 9; and bone marrow cell-transplanted (BMC) group, n = 9]

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Dose Dependence: Higher dose of MNC led to less fibrosis and increased microvessel formation in infarcted pig myocardium 60 days after treatment

Silva et al. Tex Heart Inst J (2011);38(3):219-24

Reduced Fibrosis>100 Million BMC resulted in less fibrosis

Increased Capillary Density200 Million BMC (>20 Million BMC/segment) resulted in highest capillary density and least fibrosis

Bone Marrow Cells – Preclinical Experience (Pig)


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CardiAMP Heart Failure Trialo Phase 1 design & resultso Phase 2 design & resultso Phase 3 design & results

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Content Overview – CardiAMP Cell Therapy Science


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Effective Dosage A Pharmacokinetic Approach to Better Understand Pharmacodynamic Responses in Cardiac Cell Therapy Trials

Dose response relationships have been described in some phase I-II clinical trials.

Cross correlation between studies should take into account the myocardial retention (efficiency of the delivery method and absolute dose).

Cross correlations should take into account the release criteria of the cell graft (which requires consensus regarding what qualifies a relevant cell: requirements for identity-purity, functionality, viability of cell graft as verified by flow and/or functional assays).

CD34+ Cells in Clinical Studies

http://www.sec.gov/Archives/edgar/data/320017/000032001713000073/neosteminvestorpresentat.htm

Modified from Altman et al Int.Conf.Cell Ther.Cardiovasc.Dis. 2014 Perin et al, FOCUS-CCTRN Trial, JAMA. 2012; 307(16)Martin-Rendon et al. Eur.Heart J. 2008, 29Lipinsky et al, JACC 2007, 50(18)Losordo et al, Circ Res 2011;109:428–436Perin et al Circ Res 2015

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Effective Dosage: Absolute Dose Delivered & Retained in Myocardium

Effective dosage is the actual cell dose for delivery, corrected by the efficiency of the delivery route (actual dose retained locally in the myocardium).

Response to therapy (pharmacodynamics) may be better understood by tracking the effective dosage (myocardial retention) at a specified time post delivery (pharmacokinetics) by a standardized test.

Modified from Altman et al International Conference on Cell Therapy for Cardiovascular Disease 2014.

Study Total Cell Dose% CD34

Reported/ Estimated

CD34 Counts

Estimated Retention

(%)

Calculated Effective CD34+ Dosage

REPAIR AMI 20061 236,000,000 1.5%* 3,540,000 1% 35,400BM CMI 20092 98,000,000 2.4% 2,352,000 6% 141,120

ACT34-CMI 20113 7,000,000 100% 7,000,000 6% 420,000TABMMI 20114 100,000,000 1.9% 1,900,000 18% 342,000FOCUS 20115 30,000,000 1.5% 450,000 6% 27,000FOCUS 20126 100,000,000 2.6% 2,600,000 6% 156,000TACHFT 20137 200,000,000 1.9% 3,800,000 18% 684,000

*CD34+/CD45+ population reported1.Schachinger V, et al.N Engl J Med 2006.2.van Ramshorst J, et al. JAMA 2009,.3.Losordo DW, et al Circ Res 2011. 4.de la Fuente LM, EuroIntervention 2011.5.Perin EC, et al. Am Heart J 2011.6.Perin EC, et al. JAMA 2012.7.Heldman AW, et al. JAMA 2014.


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Intramyocardial Cell Delivery with Helix/Morph Delivery System

The CardiAMP cells are intramyocardially injected using the Helix percutaneous delivery system (10 injections of 0.5 cc)

Clip courtesy of Dr. Todd Brinton, Stanford University


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CardiAMP Cell Therapy Delivery Approach

MorphGuide

Enhanced Navigation

ContrastConfidence in Engagement

Helical NeedleStability in the heart


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Qualitative Assessment of CardiAMP Cell Delivery Approaches: Transendocardial (Helix), Transepicardial, and Coronary Artery Delivery

Mitsutake Y,, et al. Improvement of local cell delivery using Helix Transendocardial Delivery Catheter in a porcine heart. Int Heart J. 2017.

.1 1

1 PET imaging of cells in swine model with external calibration (1) shows superior myocardial retention with Helix delivery.

Transendocardial Helix Transepicardial Intracoronary Artery


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Quantitative Assessment of CardiAMP Cell Delivery Approaches: Transendocardial (Helix), Transepicardial, and Coronary Artery Delivery

Helical shaped needle in Helix/Morph delivery device results in superior myocardial retention and higher effective dose of delivered BM MNC.

In CardiAMP HF trial, patients receive a target dose of 200 Mill MNC with expected CD34+ effective dose approximately that of ACT34-CMI 2011, due to efficiency of delivery and patient selection.

3x

Mitsutake Y,, et al. Int Heart J. 2017.

Increased Efficiency of Delivery Increases Effective Dosage


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CardiAMP Potency Assay bone marrow biomarker panel analysis at core lab:

Personalized approach to autologous cell therapy:— Reduces problematic patient-to-patient variation in bone marrow cells— Significantly lowers cost of therapy by enabling point of care treatment and excluding

patients from therapy not likely to respond— Attractive to patients, physicians and payors

Additional Screening with CardiAMP Cell Potency Assay

Anticipated to select 70% most likely to respond based on

therapeutic potentialof their bone marrow


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Biomarkers identified in previous BioCardia trials and scientific literature have shown to correlate independently to the efficacy of CV cell therapy

Proprietary biomarker analysis at central core lab to assess the presence of minimal bone marrow requirements to promote myocardial repair in the bone marrow sample taken days before the treatment procedure

Central core flow cytometry and cell biology labs at Baylor University, Houston

Biobanking of blood and bone marrow samples for in depth analysis

One of the markers is the CD34+ cell titer in the bone marrow

Modified from Wong et al : International Conference on Cell Therapy for Cardiovascular Disease 2014

0

400

800

1200

Repair AMI2006

Late TimeAMI 2011

TimeAMI2012

FOCUS HF2011

BM CMI2009

PreserveAMI 2014

FOCUS HF2012

ACT34 CMI2011

CardiAMPHF Ph I 2011

CardiAMPHF Ph II

2013

CardiAMPHF Ph III

CD34

cel

l dos

age

(000

s)

Estimated effective CD34+ cell dosage from leading trials

Positive trial

CardiAMP assay threshold in HF

Negative trial



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This data is part of a campaign intended to impact cellularity focus of BMA draws.

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Some centers are believed to do large volume aspirations which result in poor cellularity of the BM aspirate. Potential value of CPA is exclusion of such (large volume) sampling.


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CardiAMP Procedure: Cell Processing

Woodell-May JE et al, BioResearch Open Access (2015), Vol 41, 417-424

• Isolation and approx. 7-10x concentration of nucleated BM fraction at point-of-care• Isolation of 60 cc of BM aspirate able to create target dose of 200 Mill BM MNC• Minimal processing believed to preserve cell viability

Cell poor plasma

Nucleated cellconcentrate

Red blood cells


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Perin, EC et al. JAMA 2012, 307(16), pg. 418

Clinical Background2012 Closest Work to CardiAMP

Relevant Conclusions:• Every 3% higher level of CD34 cells was associated with on average a 3.0% greater

absolute unit increase in LVEF in multiple variable model that included age and treatment as predictor variables [95% CI, 0.14-5.98]; (P = 0.04)

• An analogous computation for CD133 cells (range, 0.1% - 3.6%; SD =0.62) revealed that every 3% higher level of CD133 cells was associated with on average a 5.9% greater absolute unit increase in LVEF [95% CI, 0.36% = 7.77%]; P = 0.04.)


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Clinical Background2018 Meta Analysis Update - Highlights

•Mortality rate in patients - with BM MNC therapy was significantly lower (15.4%; RR 0.38) on meta analysis of 21 randomized trials in 1010 pts)

• Cell therapy was associated with a reduction in non-fatal MI (RR 0.40) and arrhythmias (RR 0.46) over long term follow-up.

• Periprocedural adverse events associated w cell/placebo injection procedure were infrequent.

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Fisher SA et al., Heart. 2018 Jan;104(1):8-10.


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CardiAMP HF Phase I Trial Design and Results

20 Ischemic Heart Failure Patients LVEF

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CardiAMP HF: Phase 2 Trial DesignTransendocardial Autologous Cells in Heart Failure Trial (TAC-HFT), NCT00768066

34 Ischemic Heart Failure Patients LVEF

30*NS: not significant

SecondaryEfficacy

Endpoints

Active(Mean)

Placebo(Mean)

Treat. Difference

FavorsCardiAMP Therapy

P-value

6 minute walk (meters)N=28, Mean ± St Dev

+14.3 ± 59.6

-42.0± 18.1 +56.3

0.049

MLHF quality of life (pts)N= 29, Mean ± St Dev

-7.7± 17.8

+9.7± 24.8 -17.4

0.038

Maximum Oxygen Use (mL/kg·min) +0.16 -0.870 +1.03

0.321NS*

NYHA HF Class -0.42 -0.25 -0.17 0.638

NS

LV End Systolic Volume (ml) +3.2 +47.2 -44

0.129NS

LV End Diastolic Volume (ml) +4.5 +51.2 -46.7

0.149NS

LV Ejection Fraction (%) +0.97 -2.38 +3.35 0.252

NS

TAC-HFT BMC were results superior to TAC-HFT MSC Primary safety endpoint was met: no treatment-emergent MACE at 30 days pp No death or MACE in BMC treatment group at one year follow-up All secondary efficacy endpoints at one year follow-up favor cell therapy (below) Multiple endpoints that are statistically significant and clinically meaningful

Johnston P. , AHA 2018.Wong Po Foo et al, World Congress of Regenerative Medicine, 2015.Heldman A et al, JAMA 2013.

CardiAMP HF Phase 2 Placebo Controlled Randomized Trial Results


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CardiAMP Phase 2 Placebo Controlled Randomized Trial Results

Improved functional capacity

Treatment vs. placebo: +56.3 m, (p=0.049, at 12 mo FU)

Improved Quality of Life

Treatment vs. placebo: -17.4 pts, (p=0.038, at 12 mo FU)

• Primary safety endpoint: No treatment emergent SAE at 30 days follow up• Secondary efficacy endpoints show that placebo patients deteriorate while

treated patients improve.

Minnesota Living with Heart Failure Questionnaire

Six Minute Walk Distance

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Johnston P, AHJ, 2018Wong Po Foo et al, World Congress of Regenerative Medicine, 2015.Heldman A et al, JAMA 2013.


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CardiAMP HF Phase 2 Efficacy Results in Six Minute WalkRelative to CRT and Entresto heart failure therapies

CRT = Cardiac Resynchronization Therapy or Biventricular Pacing, a $3Bn US Market

50% of patients in CardiAMP placebo controlled Phase II already had AICD or CRT devices

6MWD has been used for approval in PAH, and CRT

This data is from trials used for CRT product registration

1 CRT, Miracle-ICD, JAMA, 20032 Cells, REVASCOR, Circ Res 20053 CRT, Contak CD, JACC, 20034 CRT, PAVE, JCE 20055 CRT, Miracle, Circ, 20036 CRT, Path CHF, JACC, 20027 Cells, CardiAMP, JAMA 2013, WCRM 20158 CRT, Mustic, JACC, 20029 Entresto Paradigm HF, NEJM 2014


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Novel aspects of CardiAMP program High effective dose of stem cells

due to delivery efficiency Cell Potency Assay Point of Care Device Efficient procedure of 60-90 min

CardiAMP Pivotal Phase III Heart Failure Trial Update and Data


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CardiAMP Heart Failure Trial is an Investigational Device Trial

Intended to provide the primary data to support safety and efficacy to support a marketing application of the CardiAMP Cell Therapy System.


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CardiAMP Heart Failure Update and Data

Patient meets initial Medical History eligibility

requirements for Inclusion/Exclusion Criteria

Obtain Informed Consent

Screening tests complete and acceptable?

Randomization

TreatmentSubjects treated with

CardiAMP cell therapy

Sham Control ProcedureSubjects not treated with CardiAMP cell therapy

Primary Endpoint at 12 Month Follow-upAdditional 24 Month Follow-up

Primary Endpoint: 6 MW DistanceSecondary Hierarchical Endpoints: Survival (non-inferiority), Freedom from

MACE (non-inferiority), MLWHF, Time to MACE, Survival

Yes

No

Yes

Yes

NoPatient not

enrolled into study

No

Study Design: Prospective, multi-centered, 3:2 randomized, controlled, double-blinded phase III clinical trial to assess CardiAMP cell therapy in 260 patients with post-infarction heart failure.

Treatment Group: 160 Subjects treated with autologous BM MNC using the CardiAMP cell therapy and optimal medical therapy

Sham Control Group: 100 Subjects treated with optimal medical therapy

Roll-in Phase: Maximum of 10 subjects

Total Number of Patients: 260 subjects

Changes from Phase II:• NYHA Class I patients are not included• Inclusion of Cell Potency Assay

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CardiAMP Heart Failure Trial, NCT02438306, IDE Trial for Premarket Approval

Raval A et al. The CardiAMP Heart Failure trial:, AM Heart Journal, April 2018.

Design of Phase III Pivotal Trial


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CardiAMP Heart Failure Trial: Screening

• New York Heart Association (NYHA) Class II or III• Diagnosis of chronic left ventricular dysfunction, due to previous myocardial

infarction (TTE)• Left ventricular ejection fraction of 20 - 40% as determined by 2D/3D

echocardiogram, and not in the setting of a recent ischemic event• No recent MI within last 6 months• Previous treatment with thrombolytic therapy, coronary artery bypass surgery, or

percutaneous coronary revascularization• On stable evidence-based medical and device therapy for heart failure, per the

2013 ACC/AHA Heart Failure guidelines, for at least 3M prior to randomization– Optimal pharmacotherapy (BB, ARB/ACE-I, diuretics, aldosteron.inh.)– Cardiac resynchronization therapy (CRT/ CRT-D) if appropriate

• CRT or CRT-D implanted at least 3M prior to randomization• Eligible or anticipated to be eligible for CRT or CRT-D > 6M

• Cell Potency Assay Score of 3, as determined by the Cell Analysis Core Lab

Key Inclusion Criteria


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• Bronchospastic lung disease, orthopedic, muscular, or neurologic conditions that could limit the ability to perform the 6MWD Test

• Performance in 6 MWD test at baseline is 450 m• Need for coronary artery revascularization. (PCI/CABG should occur at least 3

months prior to randomization)

• Severe mitral, tricuspid or aortic regurgitation (≥3+) • Presence of aortic stenosis (≥3+, AVA < 1.5 cm2)• Mechanical aortic valve or heart constrictive device

• A life-threatening arrhythmia• Complete heart block or QTc interval >550 ms• AICD firing in the past 60 days prior to the procedure

• Peripheral artery disease involving the aorta or iliofemoral system that impacts the feasibility or safety of the study intervention.

Key Exclusion Criteria



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Baseline Screening


• Informed consent• Medical history (including current medication and recent adverse events)• Physical examination• NYHA HF functional class• Minnesota Living with Heart Failure Questionnaire• 6 minute walking test • 12-Lead ECG• 24 hour holter monitor or ICD interrogation• Blood and urine analysis

• Echocardiogram (contrast enhanced)• Cell Potency Assay of Bone Marrow (5ml)

Clinical chemistry NT-proBNPHematology (w differential) Troponin, CKMBPregnancy test Serology for HBV, HCV, HTLVUrinalysis


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The CardiAMP Heart Failure Trial: Efficacy Outcomes from Roll-In Phase

Peter V. Johnston1, Henricus J. Duckers2, Amish N. Raval3, Thomas D. Cook3, Jay H. Traverse4,

William T. Abraham5, Peter A. Altman2, Carl J. Pepine6

1. Johns Hopkins University, Baltimore, MD, 2.Biocardia, Inc, San Carlos, CA, 3. University of Wisconsin, Madison, WI, 4. Minneapolis Heart Institute, Minneapolis, MN, 5.

Ohio State University, Columbus, OH, 6. University of Florida, Gainesville, FL


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Clinical Results: Roll-in Phase (primary endpoint)

✳P=0,36✳P=0,01✳P=0,21 ✳P=0,36✳P=0,01✳P=0,21

Mean +/-SEM; n=10 at all time points

In 8 out of 10 patients, the 6 minute walking performance improved at 12 months

+33.7

+47.8

+58.1

+46.4

0

20

40

60

80

100

3 months 6 months 9 months 12 months

Δ6M

WD

(m)

✳p=0,36✳p=0,21 ✳p=0,36

p=0.21

*p=0.01

p=0.36p=0.06

Change in 6MWD Relative to Baseline

TAC HFT +14.3 m#

#Wong Po Foo et al, World Congress of Regenerative Medicine 2015.## Slide modified from Johnston et al, rapid communications, AHA meeting 2018

▲ 22%


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Clinical Results: Roll-in Phase – NYHA HF Class and Quality of Life

✳P=0,20 ✳P=0,21 ✳P=0,93

▼ 31%

MLH

FQ s

core TAC HFT -7.7

p=0.20 p=0.21 p=0.93 p=0.33*p=0.015 *p=0.037 p=0.194 p=0.183

Distribution of NYHA HF class (left), n=10 for NYHA HF Class at 3 & 6 mos, n=9 at 9 & 12 mosQuality of Life (right; MLHFQ), Mean +/-SEM; n=10 for all time points.

7 out of 10 patients improved at 12 month follow-up (QoL)#Wong Po Foo et al, World Congress of Regenerative Medicine 2015.## Slide modified from Johnston et al, rapid communications, AHA meeting 2018


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Clinical Results: Roll-in Phase – LV Function at 12 months

LVEF

(%)

+1.0

+4.1

0

2

4

6

8

Baseline 6 Months 12 Months

28.9 29.1

32.9

20

25

30

35


Cha

nge

in L

VEF

(%)

Global LV Function Change in LV Function

Mean +/-SEM; n=10 vs. 9 vs. 9; Transthoracic echocardiograms assessed by blinded readers in Echo Core Lab (Yale School of Medicine)

# Slide modified from Johnston et al, rapid communications, AHA meeting 2018

p=0.49

p=0.18

In 7 out of 10 patients, the global LV ejection fraction improved at 12 month follow-up


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Akinetic Wall Segments Change in Akinetic Wall Segments

• Mean +/-SEM; n=10; Transthoracic Echocardiograms assessed by blinded readers in Echo Core Lab (Yale School of Medicine)

• Pre-specified 2º Endpoint: Recruitment of myocardial segments

In 8 out of 10 patients treated with CardiAMP Cell Therapy, the total number of akinetic myocardial segments were significantly decreased at 12 month follow-up

Akin

etic

Seg

men

ts

6.1

5.04.2

0

2

4

6

8


ΔAk

inet

ic S

egm

ents -1.1

-1.9

-4

-3

-2

-1

0


p=0.08

*p=0.04


Decrease in Akinetic Wall Segments (myocardial recruitment)


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Improvement in Wall Motion Score

• Mean +/-SEM; n=10; Transthoracic Echocardiograms assessed by blinded readers in Echo Core Lab (Yale School of Medicine)

• Pre-specified 2º Endpoint: Recruitment of myocardial segments


Total Wall Motion Change in Wall Motion ScoreM

ean

Wal

l Mot

ion

Scor

e

36.533.5

30.6

0

10

20

30

40


-3.0

-5.9

-10

-8

-6

-4

-2

0


ΔWal

l Mot

ion

Scor

e

**p=0.01

**p=0.01

In all 10 out of 10 patients treated with CardiAMP Cell Therapy, the (Total) Wall Motion Score was significantly improved at 12 month follow-up


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Safety• No SAEs or unanticipated events at first 30 days after therapeutic

procedure• Minor AEs managed and resolved within 30 days

The (blinded) DSMB convened at Sept 20th 2017 to review the interim DSMB report.

There were NO safety concerns:

“The committee found the data to be reassuring, also relating to the low biomarker elevation findings. The committee recommends enrollment to continue into the Pivotal Phase.”

CardiAMP Heart Failure Trial – (S)AEs in first 10 patients (roll-in phase)


AEs, SAEs and DRAEs

Final AE BMA CardiAMP CSHelix inj.

IDSpecifyTime intervalOutcomeSeverityNeedleprocedureCardiAMP Procedure Day Kit (CPDK) RelationshipIf NOT related to any of the above, or unknown: SpecifyIf Other, specify:Serious Adverse EventIf Yes, reason (check all that apply)AE additional information

101-001Pain or Discomfort at Bone Marrow Harvest SitePost CardiAMP, prior to dischargeResolvedModerateDefinitelyUnrelatedUnrelatedUnrelatedNo

201-001Bruise right posterior thighPost hospital dischargeResolvedMildProbablyUnrelatedUnrelatedUnrelatedNoThe patients wife emailed the PI to say he had a bruise on the back of his right leg. It's very painful, not warm to touch and no lumps. The PI called the patient, he had not hit or injured the knee and did not have a good explanation for the bruise. He had no swelling of the leg distal to the bruise. It did not affect his ability to walk. Recommended by the PI to elevate the leg when he was sitting or laying down and try a cold compress.. If no improvement over the next 24-48 hours, contact us.

301-001ecchymosisPost hospital dischargeResolvedMildProbablyUnrelatedUnrelatedProbablyNo

401-002Elevated GlucoseAfter procedure BMA, before CardiAMPOngoingModerateUnrelatedUnrelatedUnrelatedUnrelatedPre-existing conditionNo

501-002Increase frequency of PVC'sPost CardiAMP, prior to dischargeOngoingMildUnrelatedUnrelatedPossiblyUnrelatedNo

601-002Pain or Discomfort at Bone Marrow Harvest SitePost CardiAMP, prior to dischargeOngoingMildDefinitelyUnrelatedUnrelatedUnrelatedNo

701-003Infection otherPost hospital dischargeResolvedMildUnrelatedUnrelatedUnrelatedUnrelatedIntercurrent conditionNo

801-005Heparin induced thrombocytopenia (HIT)Post hospital dischargeOngoingMildUnrelatedUnrelatedUnrelatedUnrelatedConcomitant medicationNoPatient to monitor his BP at home.

903-002tendonitis flare upPost hospital dischargeOngoingModerateUnrelatedUnrelatedUnrelatedUnrelatedOtherflare of pre-existing epicondyle tendonitisNorec'd "cortisone shot" for L lower arm tendonitis

wearing compression band

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Thank you

5/1/2019

Slide Number 1Slide Number 2Science of CardiAMP Cell Therapy - OverviewWhat is Bone Marrow Cell Therapy?Cardiac Cell Therapy: Mechanistic Basis for RegenerationCardiac Cell Therapy: Paracrine Stimulus Science of CardiAMP Cell Therapy - OverviewBone marrow Cells – Preclinical ExperienceSlide Number 9Bone marrow Cells – Preclinical ExperienceSlide Number 11Bone marrow Cells – Preclinical ExperienceSlide Number 13Content Overview – CardiAMP Cell Therapy ScienceEffective Dosage A Pharmacokinetic Approach to Better Understand Pharmacodynamic Responses in Cardiac Cell Therapy Trials�Effective Dosage: Absolute Dose Delivered & Retained in MyocardiumIntramyocardial Cell Delivery with Helix/Morph Delivery SystemCardiAMP Cell Therapy Delivery Approach Qualitative Assessment of CardiAMP Cell Delivery Approaches: �Transendocardial (Helix), Transepicardial, and Coronary Artery DeliveryQuantitative Assessment of CardiAMP Cell Delivery Approaches: �Transendocardial (Helix), Transepicardial, and Coronary Artery DeliverySlide Number 21Slide Number 22Additional Screening with CardiAMP Cell Potency Assay ��CardiAMP Procedure: Cell ProcessingScience of CardiAMP Cell Therapy - OverviewClinical Background�2012 Closest Work to CardiAMPClinical Background�2018 Meta Analysis Update - HighlightsSlide Number 28Slide Number 29Slide Number 30CardiAMP Phase 2 Placebo Controlled Randomized Trial ResultsCardiAMP HF Phase 2 Efficacy Results in Six Minute Walk�Relative to CRT and Entresto heart failure therapiesCardiAMP Pivotal Phase III Heart Failure Trial Update and DataSlide Number 34CardiAMP Heart Failure Update and DataSlide Number 36Slide Number 37Slide Number 38The CardiAMP Heart Failure Trial: Efficacy Outcomes from Roll-In Phase��Peter V. Johnston1, Henricus J. Duckers2, �Amish N. Raval3, Thomas D. Cook3, Jay H. Traverse4, �William T. Abraham5, Peter A. Altman2, Carl J. Pepine6��1. Johns Hopkins University, Baltimore, MD, 2.Biocardia, Inc, San Carlos, CA, �3. University of Wisconsin, Madison, WI, 4. Minneapolis Heart Institute, Minneapolis, MN, 5. Ohio State University, Columbus, OH, 6. University of Florida, Gainesville, FL�Slide Number 40Slide Number 41Slide Number 42Decrease in Akinetic Wall Segments (myocardial recruitment)Improvement in Wall Motion ScoreCardiAMP Heart Failure Trial – (S)AEs in first 10 patients �(roll-in phase)Slide Number 46

science of cardiamp heart failure cell therapy · 2019-05-02 · cell potency assay should enhance...

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