developing regenerative therapies that reverse chronic disease · 5/14/2020 · buerger’s...
TRANSCRIPT
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Developing Regenerative Therapies
that Reverse Chronic Disease
David J. Mazzo, PhD
President and Chief Executive Of f icer
May 14, 2020 | Nasdaq: CLBS
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This Investor Presentation contains forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. Forward-looking statements reflect management’s current
expectations, as of the date of this presentation, and involve certain risks and uncertainties. All
statements other than statements of historical fact contained in this Investor Presentation are
forward-looking statements. The Company’s actual results could differ materially from those
anticipated in these forward-looking statements as a result of various factors. Factors that could
cause future results to differ materially from the recent results or those projected in forward-looking
statements include the “Risk Factors” described in the Company’s Annual Report on Form 10-K filed
with the Securities and Exchange Commission (“SEC”) on March 5, 2020 and in the Company’s other
periodic filings with the SEC. The Company’s further development is highly dependent on, among
other things, future medical and research developments and market acceptance, which are outside of
its control. You are cautioned not to place undue reliance on forward-looking statements, which speak
only as of the date of this Investor Presentation. Caladrius does not intend, and disclaims any
obligation, to update or revise any forward-looking information contained in this Investor Presentation
or with respect to the matters described herein.
Forward-looking statement
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▪ Investment case summary
▪ Management team introduction
▪ CD34+ cell therapy platform technology overview
▪ Pipeline description and individual program summaries
▪ Financial overview
▪ Milestone timeline
▪ Conclusion
Presentation contents
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CD34+ cell therapy company with an advanced clinical pipeline with 2 programs
with “breakthrough” designation and 1 targeting COVID-19 induced lung repair
Proprietary field-leading technology in multi-billion dollar global indications
backed by a strong IP portfolio
Multiple potential value creating events in the next 12-18 months based on
milestones across the pipeline (timing subject to COVID-19 pandemic influence)
Seasoned management team with noteworthy domain expertise along with
big pharma and emerging biotech experience
Strong balance sheet; ~$34 million in cash & cash equivalents (April 30, 2020)
with no debt and cash runway projected to fund operations into 2H 2021
Caladrius investment rationale
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Note: Select experience is shown above. For a comprehensive bio, please visit: www.caladrius.com
Caladrius management team
5
David J. Mazzo, PhD
President and
Chief Executive Officer
Douglas Losordo, MD
EVP, Global Head of R&D and
Chief Medical Officer
Joseph Talamo, CPA
Senior VP and
Chief Financial Officer
Todd Girolamo, JD
Senior VP, General Counsel
and Corporate Secretary
John Menditto
Vice President, IR and
Corporate Communications
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Ochsner Health, New OrleansDuke Clinical Research Institute
C. Michael Gibson, MDC. Noel Bairey Merz, MD Timothy Henry, MD
Thomas Povsic, MD, PhD
Scripps Clinic, San Diego
Richard Schatz, MD Christopher White, MD
Cedars-Sinai, Los Angeles Harvard Medical School The Christ Hospital, Cincinnati
Stanford Cardiovascular Institute
Joseph Wu, MD, PhDGoethe University, Frankfurt
Andreas Zeiher, MD
University of Florida, Gainesville
Carl Pepine, MD
Esteemed scientific advisory board
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CD34+ cell therapy
platform technology
overview
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▪ Naturally occurring endothelial progenitor cells
▪ Reestablish blood flow to under-perfused tissues1,2
▪ Possess pre-programmed tissue repair effects mediated by
pro-angiogenic and anti-inflammatory functions3,4
1Mackie, A.R. et al., Tex Heart Inst J 2011, 38(5), 474-4852Kocher, A.A. et al., Nat Med 2001, 440-436
Normal microvasculature
Augmented microvasculature
post-CD34+ cells treatmentCompromised microvasculature
Artery Vein
Capillaries
Artery Vein
Capillaries
Artery Vein
Capillaries
New
Capillaries
CD34+ cells have a well characterized mechanism of action
83Abd-Allah et al., Cytotherapy 2015, 17: 443-534Lo , B.C. et al., Am J Respir Cell Mol Biol 2017, 57: 651-61
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▪ CD34+ cells have been studied clinically in a variety of ischemic disease
indications by numerous investigators across many sites and countries
▪ CD34+ cells repeatedly have shown evidence of vascular repair in
multiple organs
▪ Consistent and compelling results of rigorous clinical studies comprising
>1,000 patients have been published in peer reviewed journals1,2,3,4
▪ Single treatment has elicited durable therapeutic effect
▪ No cell-related adverse events reported to date
1 Povsic, T. et al. JACC Cardiovasc Interv, 2016, 9 (15) 1576-15852 Losordo, D.W. et al. Circ Cardiovasc Interv, 2012; 5:821–830
3 Velagapudi P, et al, Cardiovas Revasc Med, 2018, 20(3):215-2194 Henry T.D., et al, European Heart Jour 2018, 2208–2216
CD34+ cell therapy is extensively studied/clinically validated
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▪ Drug induced mobilization eliminates need for surgical bone marrow aspiration
▪ No genetic manipulation or ex vivo expansion of cells
▪ Four days or less from donation to treatment
▪ Cost-of-goods an order of magnitude less expensive than CAR-T therapies
Caladrius’ CD34 process is simple/fast/economical/scaled
Shipment
Day 1 Day 2 Day 3 or 4
Shipment
Sample collection via apheresis after CD34+
cell drug-induced mobilization
Isolation, concentration and
formulation of CD34+/CXCR4+ cells
Cells returned to same patient by
injection; site indication dependent
or
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U.S. patents
granted
9 27Foreign patents
granted
Fundamental protection to 2031+
Key Claims
▪ Pharmaceutical composition of non-expanded CD34+/CXCR4+ stem cells
▪ Therapeutic concentration range
▪ Stabilizing serum
▪ Repair of injury caused by vascular insufficiency
Caladrius’ CD34 technology has robust intellectual property
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CLI = Critical Limb Ischemia
CMD = Coronary Microvascular Dysfunction
NORDA = No Option Refractory Disabling Angina
*Products are distinct and not interchangeable
Caladrius’ innovative CD34+ cell therapy pipeline*
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1 Timing subject to COVID-19 pandemic influence
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CLBS119COVID-19 Induced Lung
Damage(USA)
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▪ Human coronavirus disease-19 (COVID-19) is caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2)
▪ Evidence suggests1,2,3 that severe lung damage due to COVID-19 leads to long term
disability and possibly death as a result of inflammation and vascular damage
▪ Early data shows that almost all patients who survive COVID-19 pneumonia have
some level of lung damage visible in CT scans taken before hospital discharge4
▪ Prior data from the SARS epidemic suggest that CD34+ cells in the lung could be a
target of SARS-CoV-2 infection and that destruction of lung CD34+ progenitors could
account for the inability of patients with severe lung damage to recover fully5
Indication: COVID-19 induced lung damage
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1 Varga Z, et al., Lancet. 2020;395(10234):1417‐14182 Lo., et al, Am J Respir Cell Mol Biol, 2017. 57(6): p. 651-6613 Abd-Allah SH., et al, Cytotherapy, 2015. 17(4): p. 443-453
4 Yuhui Wang, et al, Radiology, March 19, 20205 Chen Y, et al. J Exp Med. 2007;204(11):2529‐2536.
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▪ The FDA has authorized Caladrius’ IND for the study of CLBS119, a CD34+ cell
therapy for the repair of COVID-19 induced lung damage
▪ CLBS119 will be studied in a Phase 2 open-label proof-of-concept clinical trial to
evaluate the safety and efficacy of autologous peripheral blood derived CD34+ cells
delivered by intravenous infusion
▪ Efficacy endpoints include clinical measures such as biomarkers of inflammation,
pulmonary function testing and resolution of lung infiltrates
▪ Safety endpoints include examination of adverse events, laboratory investigations,
physical examinations, vital signs and occurrence of death
▪ Study initiation target: 3Q20
Our solution: CLBS119
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SAKIGAKE designated – Japan
Advanced Therapeutic Medicinal
Product (ATMP) designated - EU
CLBS12Critical Limb Ischemia
(Japan)
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▪ Severe arterial obstruction impeding blood flow in the lower extremities
▪ Often found as a co-morbidity in diabetes patients
▪ Includes severe rest pain and non-healing ulcers
▪ Buerger’s disease (inflammation in small and medium arteries) also causes CLI;
exacerbated by a history of heavy smoking
▪ Patients with no-option CLI have persistent symptoms even after bypass surgery,
angioplasty, stenting and available pharmacotherapy
▪ CLI patients are at high risk of amputation and increased risk of death
▪ Multi-billion dollar global commercial opportunity
Indication: critical limb ischemia (CLI)
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CLI: higher mortality rate than most cancers
Mustapha, J. A., Katzen, B. T., et al. (2019, May). Endovascular Today, 18(5), 80-82 18
0 100000 200000 300000
0
10
20
30
40
50
60
70
80
90
No. Incident Cases in U.S.
Death within
5 years (%)
CLI
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Rutherford (“R”) scale
R 6: Functional foot no longer salvageable
R 5: Minor tissue loss non-healing ulcer;
focal gangrene with diffuse pedal ischemia
R 4: Debilitating rest pain
R 1-3: CLI-free
CLBS12 targets patients
with R4 or R5 disease
1 Reinecke H., European Heart Journal, 2015 Apr 14;36(15):932-8
CLI amputation rates increase with disease severity1
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Post-treatment (week 12) Pre-treatment
Actual CLI Patient Laser Doppler Image
~80% of patients achieved sustainable remission within
6 months of a single treatment; durable for at least 4 years
40%
60%
70%
80%85% 85%
90%
82%
0 4 8 12 24 52 104 156 208
% of Patients (CLI + BD) Achieving CLI-free Status
Time (weeks)
Kinoshita et al, Atherosclerosis 224 (2012) 440-445
Single treatment of CD34+ cells reversed CLI
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Probability of amputation-free (n=28)
0 14 28 42 57 71
Time (weeks)
CLBS12
Placebo
75%
22%
p = 0.014
Losordo, D.W. et al, Circulation 2012; 5(6):821-830
106 cells/kg
Single treatment of CD34+ cells increased amputation-free survival
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Primary Endpoint ▪ Continuous CLI-free (2 consecutive monthly visits, adjudicated independently)
Study Size▪ 30 subjects with no-option CLI + 7 Buerger’s Disease pts.; all R4 or R5;
12 centers in Japan
Dose ▪ 106 cells/kg (CLBS12) per affected limb (studied in previous trial)
Control/Comparator▪ Standard of Care: wound care plus drugs approved in Japan
• Including antimicrobials, antiplatelets, anticoagulants and vasodilators
Mode of administration ▪ Intramuscular, 20 injections in affected lower limb in a single treatment
Timing/Costs
▪ Enrollment completion/results targeted 2H 2020/2H 2021, respectively1
▪ Earliest possible commercialization late 2021 or during 20221
▪ Study funded to completion in current budget projections
CLBS12 registration-eligible study (Japan)
221Timing impacted by COVID-19 pandemic
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Pre 1 30 60 90 120 150 180 210 240 270 300 330 365(end)
Current Patient CLI Status (cohort completed; clinical primary endpoint met)
▪ Natural evolution of Buerger’s Disease is continual deterioration for all patients
▪ Surgery is not viable and existing pharmacotherapies do not prevent amputation1
▪ CLBS12 treatment resulted in 57% of patients achieving a positive outcome
CLI-free Continuous CLI-freeRutherford 6Rutherford 4 or 5
1 Cacione DG, et al, Pharm. treatment of Buerger’s Disease, Cochrane Database of Systematic Reviews, 2016, (3) CD011033
Extraordinary CLBS12 results in Buerger’s Disease (Japan)
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Amputation
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CLBS16Coronary Microvascular
Dysfunction(USA)
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Heart disease: still a major unmet medical need globally
1 Centers for Disease Control and Prevention as cited in McKay, Betsy. "Heart-Failure Deaths Rise, Contributing to Worsening Life Expectancy." The Wall Street Journal, 30 Oct. 2019, Link to article.2 Kochanek, KD., et al. (2016). Deaths: final data for 2014. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital
Statistics System, 65(4), 1-122. 3 ISCHEMIA Study Results, AHA Scientific Sessions November 2019. https://ischemiatrial.org/ischemia-study-results#slides
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0 100 200 300 400 500 600 700
Suicide
Kidney failure
Influenza and Pneumonia
Diabetes
Alzheimer's
Stroke
Lower Respiratory disease
Accidents
All Cancers
Heart Disease
2017 2011
Heart Disease
Number of Deaths (thousands)1
As of 2014, 1 in 32 female
deaths was from breast
cancer, but 1 in 3 was from
cardiovascular disease.2
ISCHEMIA Trial3 results validate the need for
treatments that go beyond large vessel
interventions
▪ The International Study of Comparative Health
Effectiveness with Medical and Invasive
Approaches (ISCHEMIA) was funded by the
National Heart, Lung, and Blood Institute
▪ The study enrolled 5,179 patients at 320 sites
in 37 countries
Conclusion:
Interventional heart procedures do not
reduce the overall rate of heart attack
or death compared with medicines
and lifestyle changes alone.
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▪ Deficient heart microvasculature without obstructive vessel disease
▪ Causes frequent, debilitating chest pain that is not treatable by stents or bypass;
responds poorly or not at all to available medications
▪ Afflicts women more frequently, especially younger women1,2
▪ Results in poor prognosis for patients with the condition3
▪ Significantly elevated risk of all-cause mortality in women4
▪ Quantitatively diagnosed using Coronary Flow Reserve (CFR)
▪ CFR is the ratio of maximal to resting coronary blood flow5
▪ Multi-billion dollar global commercial opportunity
1 Coronary Microvascular Disease. (2015, July 31). In American Heart Association2 R. David Anderson, John W. Petersen, Puja K. Mehta, et al., Journal of Interventional Cardiology, 2019: 83 Loffler and Bourque, Curr Cardiol Rep. 2016 Jan; 18(1): 1
4 Kenkre, T.S. et al., Circ: CV Qual & Outcomes 2017, 10(12) 1-95 Collins, P., British heart journal (1993) 69(4), 279–281
Indication: coronary microvascular dysfunction (CMD)
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Endpoints
▪ Therapeutic effect and the evaluation of adverse events; including changes
from baseline to 6 months for coronary flow reserve, endothelial-dependent
microvascular function, time to angina; other CV metrics
Study Size ▪ 20 subjects (U.S. centers - Cedars Sinai, Los Angeles & Mayo Clinic, Rochester)
Dose ▪ Up to 300 x 106 CD34+ cells
Mode of administration ▪ Single intracoronary infusion
Timing/Cost
▪ Positive complete results presented at SCAI Scientific Sessions (May 2020)
▪ Study funded to completion in current budget projections
(including NIH grant R44HL135889)
ESCaPE-CMD: CLBS16 interventional, proof-of-concept trial
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Coronary Flow Reserve 2
CLBS16 ESCaPE-CMD results are unique and compelling
281 Murthy et al, Circulation, 20142 Henry, D. T., SCAI 2020 Scientific Sessions
▪ CFR≤2.5 indicates CMD
▪ CFR of 2 equates to a 3-4 fold
increase of MACE at 3 years1
▪ CFR≥2.5 is in “normal” range
▪ Results after a single intracoronary
administration of CLBS16
Pre-Treatment After 6 months
2.08
2.68
p = 0.0045
N=20 N=19
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CLBS16 ESCaPE-CMD results are unique and compelling
1Spertus, J.A. et al, JACC Vol. 25, No. 2 February 1995: 333-3412 Henry, D. T., SCAI 2020 Scientific Sessions
Higher scores indicate improvement1
0 20 40 60 80 100
Treatment Satisfaction
Disease Perception
Physical Limitation
Angina Stability
Angina Frequency
Seattle Angina Questionnaire Score2
Baseline 6 months
p = 0.0117
p = 0.0026
p = 0.0247
p = 0.0156
p = 0.0005
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301Henry, D. T., SCAI 2020 Scientific Sessions
4.42
2.02
N=20 N=19
Pre-Treatment After 6 months
p = 0.0036
CLBS16 ESCaPE-CMD results are unique and compelling
Daily Angina Frequency Decreased after 6 months1
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CLBS16 program status summary
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▪ Statistically significant improvement in heart function and symptoms
▪ First therapy to show the ability to durably increase CFR and potentially reverse
CMD after a single administration
▪ No evidence of cell related adverse events
▪ Expected to lead to a decreased risk of adverse cardiovascular outcomes,
including CV-related death, associated with CMD
▪ Supports microvascular repair mechanism of CD34+ cells across all indications
▪ Represents a potential breakthrough for the treatment of CMD, a condition that
affects millions in the U.S. and that disproportionately afflicts women
▪ Next step in development (Phase 2b) targeted for 2H 2020
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CLBS14No-Option Refractory
Disabling Angina(USA)
Regenerative Medicine Advanced
Therapy (RMAT) designated - USA
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▪ Recurring angina results from chronically impaired cardiac blood supply
▪ The condition persists even after bypass surgery, angioplasty, stenting
and available pharmacotherapy; no current treatment options
▪ NORDA patients experience very frequent disabling chest pain at rest or
with minimal activity
▪ Cardiac microcirculation deficiency is the remaining treatment target
▪ Multi-billion dollar global commercial opportunity
Indication: no-option refractory disabling angina (NORDA)
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▪ Clinical data from double-blind, randomized, placebo-controlled clinical
trials, including big pharma sponsored Phase 2 and partial Phase 31,2,3,4,5
▪ Published results demonstrate:
▪ Statistically significant improvement in exercise capacity
▪ Statistically significant reduction in angina
▪ Statistically significant reduction in mortality
▪ Pristine cell safety profile
1 Losordo, D.W., et al, Circulation 2007, 115(25): 3165-72.2 Losordo, D.W., et al, Circ Res 2011, 109(4): 428-363 Povsic, T.J., et al, JACC Cardiovasc Interv, 2016 9(15): 1576-85
Our solution: CLBS14
4 Povsic, T. J. et al, European Heart Journal, 2018 39(23), 2208-22165 Velagapudi P, et al, Cardiovas Revasc Med, 2018, 20(3):215-219
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*Change in exercise time from baseline at 6 months will be the Phase 3 primary endpoint
Change in Exercise Time from Baseline (Phase 2, n=168)
58
69
140
139CLBS14 (105 cells/kg)
CLBS14 (105 cells/kg)
Placebo
Placebo
*6 months:
12 months:
p=0.014
p=0.017
sec
sec
sec
sec
CLBS14 single treatment significantly improved exercise time
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CLBS14 (105 cells/kg)
Placebo
CLBS14 (105 cells/kg)
Placebo
13.8
8.8
8.7
15.3
p=0.0421
p=0.0109
6 months:
12 months:
Reduction in Weekly Angina Frequency from Baseline (Phase 2, n=168)
CLBS14 single treatment significantly reduced angina frequency
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0 2412
10%
p = 0.0065
Time (months)
Mortality (Phase 2, n=168)
(105 cells/kg)
CLBS14
Placebo
2.5%
CLBS14 single treatment significantly improved survival
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Primary Endpoint ▪ Change in exercise time from baseline at month 6 (studied in Phase 2)
Timing▪ 39 months from first-patient-in to top-line data; interim analysis after 50% of
patients complete 6-month follow-up
Study Size▪ ~400 subjects (~200 active, ~150 placebo, ~50 SOC with cross-over to open
label treatment at 6 months)
Dose ▪ 105 cells/kg body weight (studied in Phase 2)
Control/Comparator▪ Placebo control (blinded)
▪ Standard-of-care (unblinded)
Mode of administration ▪ Intramyocardial injection guided by mapping catheter (NOGA)
Timing/Costs
▪ External costs: ~$70 million over a 3-4 years period
▪ Target initiation: Upon acquisition of sufficient capital that provides
confidence that the study could be funded through completion
CLBS14 Phase 3 confirmatory registration study (U.S.)
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Program 2020 2021
Caladrius timeline of key development milestones*
39
CLBS119
FDA authorized IND for
CLBS119 study
(COVID-19 lung damage)
Initiation of Phase 2 Trial
Target – 3Q 2020
*Timing subject to COVID-19 pandemic influence
CLBS14(NORDA)
Confirmatory Phase 3 Initiation Target: TBD
(pending funding)
CLBS12(CLI)
Target Enrollment
Completion by
End of 1Q 2020
Earliest possible approval
in Japan 2H 2021
J-NDA Rolling Submission
Initiation Target –
2H 2020
Top-line Data Target –
End 2020/Early 2021
CLBS16(CMD)
Present Full ESCaPE-CMD
Data – 2Q 2020
Initiation of Phase 2 Trial
Target – Mid-2020
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Caladrius key financial information
40
Cash & Investments:
As of April 30, 20201 ~$34 million
Three Months Ended March 31, 2020 Operating Cash Burn: $4.2 million
Cash Runway Based on Current Plan: 2H 2021
Debt as of April 30, 2020: $0
Common Shares Outstanding:
As of April 30, 20202 12.8 million shares
Options Outstanding as of March 31, 2020:
Exercise Price: $3.01 - $4.00 = 532,000 shares
Exercise Price: > $4.00 = 748,000 shares
1.3 million shares
Warrants Outstanding as of April 30, 20203 :
Exercise Price: $2.251.1 million shares
1 Includes $10.9 million in net proceeds from sale of New Jersey NOLs in April 2020, and $4.5 million in net proceeds from registered direct offering in April 20202 Includes 2.2 million shares issued in April 2020 registered direct offering3 Represents warrants issued in April 2020 private placement
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CD34+ cell therapy company with an advanced clinical pipeline with 2 programs
with “breakthrough” designation and 1 targeting COVID-19 induced lung repair
Proprietary field-leading technology in multi-billion dollar global indications
backed by a strong IP portfolio
Multiple potential value creating events in the next 12-18 months based on
milestones across the pipeline (timing subject to COVID-19 pandemic influence)
Seasoned management team with noteworthy domain expertise along with
big pharma and emerging biotech experience
Strong balance sheet; ~$34 million in cash & cash equivalents (April 30, 2020)
with no debt and cash runway projected to fund operations into 2H 2021
Caladrius investment rationale
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May 14, 2020 | Nasdaq: CLBS
Investor Re lations Contact:
John D. Menditto
Tel : (908) 842-0084
Thank you!