Developing ng R Regene nerat ativ ive Therap apie ies that R - - PowerPoint PPT Presentation

Developing ng R Regene nerat ativ ive Therap apie ies that R Reverse Ch Chroni nic D Dis iseas ase

David J

• J. Ma

. Mazzo, PhD hD President and C Chief E f Executive Officer

May 14, 2020 | Nasdaq: CLBS

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

• ther 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

• nly as of the date of this Investor Presentation. Caladrius does not intend, and disclaims any
• bligation, to update or revise any forward-looking information contained in this Investor Presentation
• r with respect to the matters described herein.

Forward rd-lo looking statement

2

• Investment case summary
• Management team introduction
• CD34+ cell therapy platform technology overview
• Pipeline description and individual program summaries
• Financial overview
• Milestone timeline
• Conclusion

Present ntation

• n contents

3

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

Caladri rius investment rationale

4

Note: Select experience is shown above. For a comprehensive bio, please visit: www.caladrius.com

Caladri rius management team

5

Da David J

• J. Mazz

azzo, P PhD D

President and Chief Executive Officer

Douglas Losor

• rdo,
• , M

MD

EVP, Global Head of R&D and Chief Medical Officer

Joseph T h Talamo, C CPA

Senior VP and Chief Financial Officer

Todd Girol

• lamo,
• , J

JD

Senior VP, General Counsel and Corporate Secretary

John M Menditt tto

Vice President, IR and Corporate Communications

Ochsner er Health, N New ew Orlea eans Duke C Clinical Research I Insti titu tute

• C. Michael Gibson, MD
• C. Noel Bairey Merz, MD

Timothy Henry, MD Thomas Povsic, MD, PhD

Scripps Clinic, S San D Diego

Richard Schatz, MD Christopher White, MD

Cedars-Sinai, L Los Angeles Harvard M Medical S School

• ol

The C Christ H Hospita tal, C Cincinnati ti Stanford Cardiovascular I Insti titu tute

Joseph Wu, MD, PhD

Goeth the U Unive versity ty, Frankfurt

Andreas Zeiher, MD

Unive versity of Florida, G Gainesvi ville

Carl Pepine, MD

Esteemed scientific advisory board

6

CD34+ cell therapy platform technology

• verview

• 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

Normal al microvascu culat ature Augmented microvas asculat ature post-CD CD34+ cells treat atment Compromis ised microvas asculat ature

Artery Vein in Capil illaries Artery Vein in Capil illaries Artery Vein in Capil illaries Ne New Capil illaries

CD3 D34+ c 4+ cells ls have a well characterized mechanism of action

8

• 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

CD3 D34+ c 4+ cell th l thera rapy is extensively studied/clinically validated

9

• 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

Caladri rius’ CD34 process is simple/fast/economical/scaled

Shipme ment

Day 1 1 Day 2 2 Day 3 3 or 4 4

Shipme ment

Sample collection

• n via apheresis after CD34+

+ cell d drug ug-in induced mobil iliz izat atio ion Isolat atio ion, conce centrat atio ion and formulat atio ion of CD34+/CX CXCR CR4+ cells Cells returned to same patient by inject ctio ion; site indic icat atio ion dependent

• r
• r

10

U.S. p patent nts grant nted

9 27

Foreig ign p patents grant nted

Fundamental l pro rotection to 2031+

Key Cl Claim aims

• Pharmaceutical composition of non-expanded CD34+/CXCR4+ stem cells
• Therapeutic concentration range
• Stabilizing serum
• Repair of injury caused by vascular insufficiency

Caladri rius’ CD34 technology has robust intellectual property

11

Product Indication Development Stage Commercialization Target1

CLI LI = Critical Limb Ischemia CMD MD = Coronary Microvascular Dysfunction NORDA DA = No Option Refractory Disabling Angina

*Products are distinct and not interchangeable

Caladri rius’ innovative CD34+ cell therapy pipeline*

12

4Q202 2021 Regis istrat atio ion elig igib ible t trial ial (Japan; ongoing) CLB CLBS12 CLI CLI TBD BD Phase 3 3 confirmato tory (USA; initiation pending funding) CLB CLBS14 NORD RDA TBD BD Phase 2 2b (USA; start target 2H 2020) CLB CLBS16 CM CMD TBD BD Phase 2 2 (USA; start target 3Q20) CLB CLBS119

COV OVID-19 19 Lung ung D Dama mage

1 Timing subject to COVID-19 pandemic influence

CLBS11 119

COV OVID-19 Induced L Lung g Damage ge

(USA)

• Human coronavirus disease-19 (COVID-19) is caused by severe acute respiratory

syndrome coronavirus 2 (SARS-CoV-2)

• Evidence suggests1,

1,2, 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

14

• 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 so r solu luti tion: CLBS119

15

SAKIGAKE designated – Japan Advanced Therapeutic Medicinal Product (ATMP) designated - EU

CLBS BS12 12

Critica cal L Limb b Ischemia

(Japan)

• 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)

17

CLI: : higher mortality rate than most cancers

Mustapha, J. A., Katzen, B. T., et al. (2019, May). Endovascular Today, 18(5), 80-82

18

10000 00000 20000 200000 30000 300000 10 10 20 20 30 30 40 40 50 50 60 60 70 70 80 80 90 90 No. . In Incident Ca Cases i in U.S .S. Death th w with thin 5 years ( (%)

CLI

Rutherford (“R (“R”) ”) s scale

R 6 R 6: Functional foot no longer salvageable R 5 R 5: Minor tissue loss non-healing ulcer; focal gangrene with diffuse pedal ischemia R 4 R 4: Debilitating rest pain R 1 R 1-3: : CLI-free

CLBS12 targets patients with R4 R4 or R5 R5 disease

CLI CLI amputation rates increase with disease severity1

19

Post-treatment (week 12) Pre-treatment

Actu tual C l CLI P Pati tient Lase ser r Dopple ler I r Image ~80% of patients achieved sustainable remission within 6 months of a single treatment; durable for at least 4 years

40% 40% 60% 60% 70% 70% 80% 80% 85% 85% 85% 85% 90% 90% 82% 82% 4 8 12 24 52 104 156 208

% o

• f P

Patie ients (CLI + BD) A Achie hievin ing CLI-free S Stat atus

Time ( e (we week eks) s)

Kinoshita et al, Atherosclerosis 224 (2012) 440-445

Si Singl gle treatment of CD34+ cells reversed CLI

20

Probab abil ilit ity o

• f amputat

atio ion-fre free ( (n=28)

14 28 28 42 42 57 57 71

Time ( e (we week eks) s)

CL CLBS BS12 Place cebo 75% 75% 22% 22%

p = = 0 0.01 014

Losordo, D.W. et al, Circulation 2012; 5(6):821-830

106 cells/kg

Sing ingle treatment of CD34+ cells increased amputation-free survival

21

Primar ary E Endpoin int

• Continuous CLI-free (2 consecutive monthly visits, adjudicated independently)

St Study Siz Size

• 30 subjects with no-option CLI + 7 Buerger’s Disease pts.; all R4 or R5;

12 centers in Japan Dose se

• 106 cells/kg (CLBS12) per affected limb (studied in previous trial)

Control/Co Compar arat ator

• Standard of Care: wound care plus drugs approved in Japan
• Including antimicrobials, antiplatelets, anticoagulants and vasodilators

Mode o

• f admin

inis istrat atio ion  Intramuscular, 20 injections in affected lower limb in a single treatment Timin ing/Co 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 12 registration-eligible study (Japan)

22

1Timing impacted by COVID-19 pandemic

Pre re 1 30 30 60 60 90 90 120 120 15 150 180 180 210 24 240 27 270 300 300 330 330 365 365 (end)

Current P Patie ient CLI Stat atus (coho hort c completed; c clin inic ical p primar ary e endpoint m 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 LI-free Continuous C CLI-fr free Rutherford 6 6 Rutherford 4 4 or 5

Ext xtraordinary CLBS12 results in Buerger’s Disease (Japan)

23

Amputation

CLBS16

Coronary M Micr crovascu cular Dysfunct ction

• n

(USA)

Hea Heart d disea ease: still a major unmet medical need globally

Statistics System, 65(4), 1-122.

25 100 200 300 400 500 600 700 Suicide Kidney failure Influenza and Pneumonia Diabetes Alzheimer's Stroke Lower Respiratory disease Accidents All Cancers Heart Disease

2017 2011

Hea eart D Disease

Number of D

• f Deaths

hs (thou housands)1

As of 2014, 1 in 32 female deaths was from breast cancer, but 1 in 3 was from cardiovascular disease.2

ISCH SCHEMIA T Trial ial3 re results v vali lidate t the he n need f for

• r

tre reatments t tha hat g go

• beyond la

larg rge v vessel l intervention

• ns
• 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 Conclu lusi sion: Interventional heart procedures do no not t reduce the overall rate of heart attack

• r death compared with medicines

and lifestyle changes alone.

• 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,

1,2

• 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

Indication: coronary microvascular dysfunction (CMD)

26

Endpoin ints

• 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 St Study Siz Size

• 20 subjects (U.S. centers - Cedars Sinai, Los Angeles & Mayo Clinic, Rochester)

Dose se

• Up to 300 x 106 CD34+ cells

Mode o

• f admin

inis istrat atio ion

• Single intracoronary infusion

Timin ing/Co Cost

• Positive complete results presented at SCAI Scientific Sessions (May 2020)
• Study funded to completion in current budget projections

(including NIH grant R44HL135889)

ESCaP aPE-CMD: CLBS16 interventional, proof-of-concept trial

27

Coronar ary F Flow R Reser erve 2

CLBS16 16 ESCaPE-CMD results are unique and compelling

28

• 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

Pr Pre-Treatment Af After 6 6 months 2. 2.08 08 2. 2.68 68

p = 0. = 0.00 0045

N=20 N=20 N=1 N=19

29

CLBS16 16 ESCaPE-CMD results are unique and compelling

Higher s scores i indicate improvement1

20 40 60 80 100 Treatme ment S Sat atis isfac factio ion Disease P Perception Phys ysical L Limitation Angin ina S Stabilit lity Ang ngina na F Freque uenc ncy

Seattle A Angin ina Q a Questio ionnair aire S Score2

Baseline 6 months

p = 0. = 0.0117 p = 0. = 0.00 0026 p = 0. = 0.02 0247 p = 0. = 0.0156 p = 0. = 0.00 0005

30

4. 4.42 42 2. 2.02 02 N=20 N=20 N=1 N=19 Pr Pre-Treatment Af After 6 6 months

p = 0. = 0.00 0036

CLBS16 16 ESCaPE-CMD results are unique and compelling

Daily A Angina F Frequency D Decreased a after 6 6 mon

• nths1

CLBS16 16 program status summary

31

• 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

CLBS14

No-Opt ptio ion n Refract ctor

• ry

Disab ablin ing Angin ina

(USA)

Regenerative Medicine Advanced Therapy (RMAT) designated - USA

• 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)

33

• Clinical data from double-blind, randomized, placebo-controlled clinical

trials, including big pharma sponsored Phase 2 and partial Phase 31,

1,2,3, 3,4, 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

Our so r solu luti tion: CLBS14

34

*Change in

in exercise tim ime f from

• m b

baseline a at 6 6 mon

• nths w

wil ill be the P Phas ase 3 prim imar ary endpoi

• int

Ch Chan ange in in Exercise T Tim ime f from B Bas aseline ( (Ph Phas ase 2 2, n=168)

58 58 69 69 14 140 13 139 CLBS14 14 (10 105 cells/k /kg) CLBS14 14 (10 105 cells/k /kg) g) Place cebo Place cebo

*6 m

months: 12 m 12 months:

p=0. =0.014 p=0. =0.017

se sec se sec se sec se sec

CL CLBS14 single treatment significantly improved exercise time

35

CLBS14 14 (10 105 cells/k /kg) Place cebo CLBS14 14 (10 105 cells/k /kg) Place cebo 13 13.8 8 8.8 8.7 15 15.3

p=0.042 0421 p=0. =0.0109

6 months: 12 m 12 months:

Reduction

• n i

in Weekly ly A Angina F Frequency f from B Baseli line ( (Phase 2 2, n=168)

CLBS14 single treatment significantly reduced angina frequency

36

24 24 12 12

10 10%

p = 0. = 0.00 0065

Ti Time ( (mo months)

Mor Mortality ( (Pha hase 2 2, , n=168)

(10 105 cells/k /kg) g) CL CLBS BS14 Place cebo 2.5% 5%

CLBS14 single treatment significantly improved survival

37

Primar ary E Endpoin int

• Change in exercise time from baseline at month 6 (studied in Phase 2)

Timin ing

• 39 months from first-patient-in to top-line data; interim analysis after 50% of

patients complete 6-month follow-up St Study Siz Size

• ~400 subjects (~200 active, ~150 placebo, ~50 SOC with cross-over to open

label treatment at 6 months) Dose se

• 105 cells/kg body weight (studied in Phase 2)

Control/Co Compar arat ator

• Placebo control (blinded)
• Standard-of-care (unblinded)

Mode o

• f admin

inis istrat atio ion

• Intramyocardial injection guided by mapping catheter (NOGA)

Timin ing/Co 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.)

38

Pro rogram 2020 2021

Caladri rius timeline of key development milestones*

39

CLBS119

FD FDA a auth thorized I IND f for CLBS119 s 119 study

(COVID-19 lung damage)

Init itiat iatio ion o

• f Phase 2

2 Trial al Targe get t – 3Q 3Q 2020 2020

*Tim imin ing s subje ject t to COVID-19 p pandemic i influenc nce

CLBS14 14

(NORDA)

Confir irmat atory P Phase 3 3 Init itia iatio ion T Target: T TBD (pending funding)

CLBS12 12

(CLI)

Target E Enro rollme llment Completi tion b by End o

• f 1Q

1Q 2020 2020 Earli liest st p possi sible le a appro roval l in J Japan 2H 2H 2021 2021 J-NDA R Rolli lling S Submissi ssion Init itiat iatio ion T Target – 2H 2H 2020 2020 Top-line D Data ta T Targe get t – End 2020 2020/Early 2021 2021

CLBS16 16

(CMD)

Present Fu t Full E ESCaPE-CMD MD Data – 2Q 2Q 202 2020 Init itiat iatio ion o

• f Phase 2

2 Trial al Targe get t – Mid id-2020 2020

Caladri rius key financial information

40

Cash sh & & Investm stments: s: As s of A Apri ril 30, 30, 2020 20201 ~$34 million Three M Months hs Ended March 3 h 31, 2 2020 O Operating C Cash h Burn: $4.2 million Cash R Run unway Base sed o

• n C

Curr urrent Pla lan: 2H 2021 Debt as o s of A Apri ril 30, 30, 2020 2020: $0 Common S

• n Shares Outstand

nding ng: As s of A Apri ril 30, 30, 2020 20202 12.8 million shares Options Outstanding a as o s of M March 31, 2020 2020: Exerci cise P e Price: ce: $3.01 - $4. $4.00 = 532, = 532,000 00 shar hares Exerci cise P e Price: ce: > $4. > $4.00 = = 748, 48,000 00 shar hares 1.3 million shares Warrants Outstanding a as o s of A Apri ril 30, 30, 2020 20203: Exerci cise P e Price: ce: $2.25 1.1 million shares

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

Caladri rius investment rationale

41

May 14, 2020 | Nasdaq: CLBS

Investor Relat atio ions C Contact act: John D. Menditto Tel: (908) 842-0084 jmenditto@caladrius.com

Thank nk y you! u!