UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 18, 2019
CALADRIUS BIOSCIENCES, INC.
(Exact Name of Registrant as Specified in Charter)
Delaware (State or Other Jurisdiction of Incorporation) | 001-33650 (Commission File Number) | 22-2343568 (IRS Employer Identification No.) |
110 Allen Road, Second Floor, Basking Ridge, NJ 07920
(Address of Principal Executive Offices)(Zip Code)
(908) 842-0100
Registrant's Telephone Number
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act: | ||
Title of each class | Trading Symbol(s) | Name of each exchange on which registered |
Common Stock, par value $0.001 per share | CLBS | The Nasdaq Capital Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
o Emerging growth company
o If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 7.01 Regulation FD Disclosure.
On November 16, 2019, Caladrius Biosciences, Inc. (the "Company") issued a press release in connection with its presentation at the American Heart Association Scientific Sessions in Philadelphia, PA on the same date. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated into this Item 7.01 by reference.
A copy of a slide presentation that Caladrius Biosciences, Inc. (the "Company") will use at investor and industry conferences and presentations is attached to this Current Report as Exhibit 99.2 and is incorporated herein solely for purposes of this Item 7.01 disclosure.
The information in this Item 7.01, including Exhibit 99.1 and Exhibit 99.2 attached hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section. The information in this Item 7.01, including Exhibit 99.1 and Exhibit 99.2 attached hereto, shall not be incorporated by reference into any registration statement or other document pursuant to the Securities Act of 1933, except as otherwise expressly stated in such filing.
Item 9.01. Financial Statement and Exhibits.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
CALADRIUS BIOSCIENCES, INC.
By: /s/ David J. Mazzo
Name: David J. Mazzo, PhD
Title: President and Chief Executive Officer
Dated: November 18, 2019
Exhibit 99.1
Caladrius Biosciences Reports Positive Results for CLBS16 from the ESCaPE-CMD Trial at American Heart Association Scientific Sessions 2019
Single administration of CLBS16 durably improves heart function and symptoms with no cell-related adverse events
CLBS16 cell therapy shows promise as a significant advancement in treatment of Coronary Microvascular Dysfunction (CMD), a condition that disproportionately afflicts women
PHILADELPHIA (November 16, 2019) - Caladrius Biosciences, Inc. (Nasdaq: CLBS), a late-stage biopharmaceutical company focused on developing treatments for select cardiovascular diseases, along with researchers from Cedars-Sinai (Los Angeles), Mayo Clinic (Rochester, Minn.) and The Christ Hospital (Cincinnati), today presented results from the ESCaPE-CMD trial of Caladrius’s autologous CD34+ cell therapy, CLBS16, at the American Heart Association Scientific Sessions 2019. Data showed highly statistically significant improvement in coronary flow reserve correlating with symptom relief for patients with coronary microvascular dysfunction after a single intracoronary injection of CLBS16. The results for patients who have completed the six-month follow-up to date (17 of 20) were presented, with the results from the remaining patients expected by the end of 2019.
“CLB16 represents a potential breakthrough for the treatment of CMD, a condition that affects millions in the U.S. and that disproportionately afflicts women. This is the first time that a therapy has shown the ability to durably increase coronary flow reserve and potentially reverse CMD after a single dose. These reported results clearly support the premise that manageable cell-based tissue regeneration is possible in patients with CMD,” said David J. Mazzo, Ph.D., President and CEO of Caladrius. “The reported results from the ESCaPE-CMD trial bring us one step closer to realizing the promise of CD34+ cell therapy to augment microvasculature in the heart enabling the restoration of health rather than simply management of disease.”
Trial investigators observed that patients experienced a highly statistically significant (p=0.0087) increase in coronary flow reserve after a single intracoronary administration of CLBS16. The trial also evaluated changes from baseline to six months in chest pain frequency, Canadian Cardiovascular Society angina classification and Seattle Angina Questionnaire scores. A single administration of CLBS16 resulted in statistically significant improvements in all these measures of patient symptoms and function.
“Coronary microvascular dysfunction is becoming increasingly recognized as a major health problem that disproportionately affects women. Unfortunately, there are no currently available therapies that directly target this condition. The reported data from this study provide objective evidence that CD34+ cell therapy results in long-lasting improvement in microvascular function, something that has not been shown with any other therapy to date,” said Timothy D. Henry, M.D., Medical Director of the Carl and Edyth Lindner Center for Research at The Christ Hospital Health Network. “The CLBS16 program has demonstrated real promise and I am looking forward to seeing Caladrius further develop this new therapeutic option for CMD patients.”
The ESCaPE-CMD 1 trial is an interventional, proof-of-concept study designed to evaluate the effect of Caladrius’s autologous CD34+ cell therapy (CLBS16) on CMD symptoms and indicators while also evaluating treatment
1Funding for the Phase 2 ESCaPE-CMD study came, in part, from a $1.9 million grant from the National Institutes of Health under award number R44 HL135889. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
tolerance. The key endpoint was measurement of the change from baseline of coronary flow reserve, a direct measure of microvascular function, at six months following a single injection of CLBS16. The trial completed enrollment of the targeted 20 patients in May of 2019. The study’s three principal investigators are Dr. C. Noel Bairey Merz, Cedars-Sinai, Dr. Timothy D. Henry, The Christ Hospital, and Dr. Amir Lerman, Mayo Clinic. All patients received a single infusion of their own GCSF-mobilized CD34+ cells formulated as CLBS16.
“CMD patients often are frustrated and in despair due to unresolved symptoms even after exhausting all other available therapies. These data indicate that the naturally-occurring CD34+ repair cell could provide a durable improvement in symptoms and reduced risk of adverse cardiovascular outcomes,” said Douglas W. Losordo, M.D., FACC, FAHA, Chief Medical Officer at Caladrius. “We are extremely encouraged by these results from the trial and look forward to advancing the development of CLBS16 expeditiously with the goal of one day soon helping the large and underserved population of patients suffering from CMD.”
Results from the six-month follow-up of the remaining treated patients will be available by year-end 2019.
About Coronary Microvascular Dysfunction
Coronary microvascular dysfunction is a type of non-obstructive coronary artery disease that causes decreased blood flow to the heart muscle that affects approximately 8.3 million2,3 people in the U.S. With common symptoms such as recurring, debilitating chest pain, tiredness, and shortness of breath, many CMD patients are undiagnosed because of the absence of large vessel obstruction. Due to a misunderstanding of the disease, patients, the majority of whom are women, often go years without proper treatment. When a diagnosis of CMD is missed, patients are untreated and remain at high risk of heart attack and/or cardiovascular-related death.
About Caladrius Biosciences
Caladrius is a late-stage therapeutics development biopharmaceutical company pioneering advancements of cell therapies for select cardiovascular and autoimmune diseases. Our leadership team collectively has decades of biopharmaceutical development experience and world-recognized scientific achievement in the fields of cardiovascular and autoimmune disease, among other areas. Our current product candidates include three developmental treatments for cardiovascular diseases based on our CD34+ cell therapy platform: CLBS12, recipient of a SAKIGAKE designation in Japan and advanced therapy medicinal product classification (ATMP) in Europe, eligible for early conditional approval for the treatment of critical limb ischemia in Japan based on an ongoing clinical trial; CLBS16, subject of the proof-of-concept ESCaPE-CMD clinical trial in the U.S.A. for the treatment of coronary microvascular dysfunction; and CLBS14, a Phase 3 ready clinical program in no option refractory disabling angina and recipient of a RMAT designation in the U.S.A. For more information on the company, please visit www.caladrius.com
Safe Harbor for Forward Looking Statements
This press release 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 press release, and involve certain risks and uncertainties. All statements other than statements of historical fact contained in this press release are forward-looking statements including, without limitation, all statements related to any expectations of revenues, expenses, cash flows, earnings or losses from operations, cash required to maintain current and planned operations, capital or other financial items; any statements of the plans, strategies and objectives of management for future operations; any plans or expectations with respect to product research, development and commercialization, including regulatory approvals; any other statements of expectations, plans, intentions or beliefs; and any statements of assumptions underlying any of the foregoing. Without limiting the foregoing, the words “plan,” “project,” “forecast,” “outlook,” “intend,” “may,” “will,” “expect,” “likely,” “believe,” “could,” “anticipate,” “estimate,” “continue” or similar expressions or other variations or comparable terminology are intended to identify such forward-looking statements, although some forward-looking statements
2Mittal, S.R.; Indian Heart Journal, Volume 66, 2014, Pages 678-681
3Cleveland Clinic/AHA (American Heart Association)
are expressed differently. 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 14, 2019 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 Press Release. Caladrius does not intend, and disclaims any obligation, to update or revise any forward-looking information contained in this Press Release or with respect to the matters described herein.
Media Contact:
W2O Group
Alana Rockland
Phone: +1-301-537-5392
Email: arockland@w2ogroup.com
Investors Contact:
Caladrius Biosciences, Inc.
John Menditto
Vice President, Investor Relations and Corporate Communications
Phone: +1-908-842-0084
Email: jmenditto@caladrius.com
# # #
Advancing Restorative Therapies to Treat Ischemic Disease David J. Mazzo, PhD President and Chief Executive Officer November 2019 | Nasdaq: CLBS
Forward-looking statement 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 14, 2019, as subsequently amended on March 19, 2019, 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. 2
Presentation contents . Investment case summary . Management team introduction . CD34+ cell therapy platform technology overview . Pipeline description and individual program summaries . Financial overview . Milestone timeline . Conclusion 3
Caladrius investment case summary CD34+ cell therapy platform company with an advanced clinical pipeline with two programs with cell therapy “breakthrough” designation 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 months based on development milestones across the pipeline Seasoned management team with noteworthy domain expertise along with big pharma and emerging biotech experience Strong balance sheet; $29.2 million in cash (September 30, 2019) with no debt and cash runway projected into 2021 4
Caladrius management team David J. Mazzo, PhD Douglas Losordo, Joseph Talamo, Todd Girolamo, JD John Menditto President and MD CPA Senior VP, General Counsel Vice President, IR and and Corporate Secretary Corporate Communications Chief Executive Officer EVP, Global Head of R&D Senior VP and and Chief Medical Officer Chief Financial Officer Note: Select experience is shown above. For a comprehensive bio, please visit: www.caladrius.com 5
Esteemed cardiovascular disease scientific advisory board C. Noel Bairey Merz, MD C. Michael Gibson, MD Timothy Henry, MD Cedars-Sinai, Los Angeles Harvard Medical School The Christ Hospital, Cincinnati Thomas Povsic, MD, PhD Richard Schatz, MD Christopher White, MD Duke Clinical Research Institute Scripps Clinic, San Diego Ochsner Health, New Orleans Joseph Wu, MD, PhD Andreas Zeiher, MD Zan Fleming, MD Stanford Cardiovascular Institute Goethe University, Frankfurt Executive Chairman, Kinexum 6
CD34+ cell therapy platform technology overview
CD34+ cells have a well characterized mechanism of action Augmented microvasculature post-CD34+ cells treatment Normal microvasculature Compromised microvasculature Capillaries Capillaries Capillaries New Capillaries Artery Vein Artery Vein Artery Vein . Naturally occurring vascular repair (endothelial progenitor) cell . Provokes restorative angiogenesis of the microvasculature . CD34+ cells reestablish blood flow to under-perfused tissues1,2 1Mackie, A.R. et al., Tex Heart Inst J 2011, 38(5), 474-485 8 2Kocher, A.A. et al., Nat Med 2001, 440-436
CD34+ cell therapy is extensively studied/clinically validated. CD34+ cells were clinically studied in multiple ischemic disease indications by numerous investigators across many sites and countries . 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 3 Povsic, T. et al. JACC Cardiovasc Interv, 2016, 9 (15) 1576- Velagapudi P, et al, Cardiovas Revasc Med, 2018, 20(3):215- 9 1585 219 2 Losordo, D.W. et al. Circ Cardiovasc Interv, 2012; 5:821–830 4 Henry T.D., et al, European Heart Jour 2018, 2208–2216
Caladrius CD34 process is simple/fast/scalable/economicalSample collection via apheresis Isolation, concentration and Cells returned to same patient by after 5 days of GCSF formulation of CD34+/CXCR4+ injection; site indication mobilization cells dependent Day 1 Day 2 Day 3 or 4 Shipment Shipment or . GCSF 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 10 therapies
Caladrius CD34 technology has robust intellectual property Fundamental protection to 2031+ 9 23 U.S. patents Foreign patents granted granted Key Claims . Pharmaceutical composition of non-expanded CD34+/CXCR4+ stem cells . Therapeutic concentration range . Stabilizing serum . Repair of injury caused by vascular insufficiency 11
Caladrius innovative CD34+ cell therapy pipeline* Commercialization Product Indication Development Stage Target CLBS12 CLI Registration eligible Phase 2 (Japan; ongoing) 2021 CLBS16 CMD Proof-of-concept (USA; ongoing) TBD Phase 3 confirmatory (USA; initiation pending CLBS14 NORDA TBD funding) CLI = Critical Limb Ischemia *Products are distinct and not CMD = Coronary Microvascular Dysfunction NORDA = No Option Refractory Disabling Angina interchangeable 12
CLBS12 Critical Limb Ischemia (Japan) SAKIGAKE designated – Japan Advanced Therapeutic Medicinal Product (ATMP) designated - EU
Indication: Critical Limb Ischemia (CLI) . 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 14
CLI: higher mortality rate than most cancers 90 80 70 60 50 Death within 5 40 years (%) 30 20 10 0 0 100000 200000 300000 No. Incident Cases in U.S. Mustapha, J. A., Katzen, B. T., et al. (2019, May). Endovascular Today, 18(5), 80-82 15
CLI amputation rates increase with disease severity1 Rutherford (“R”) scale R 6: Functional foot no longer salvageable R 5: Minor tissue loss non-healing ulcer; focal gangrene with diffuse pedal ischemia CLBS12 targets patients with R4 or R5 R 4: Debilitating rest pain disease R 1-3: CLI-free 1 Reinecke H., European Heart Journal, 2015 Apr 14;36(15):932-8 16
Single treatment of CD34+ cells reversed CLI Actual CLI Patient Laser Doppler Image % of Patients (CLI + BD) Achieving CLI-free Status 90% Pre-treatment Post-treatment (week 12) 85% 85% 80% 82% 70% 60% 40% 0 4 8 12 24 52 104 156 208 Time (weeks) ~80% of patients achieved sustainable remission within 6 months of a single treatment; durable for at least 4 years Kinoshita et al, Atherosclerosis 224 (2012) 440-445 17
Single treatment of CD34+ cells increased amputation-free survival Probability of amputation-free (n=28) CLBS12 75 % 106 cells/kg p = 0.014 Placebo 22 % 0 14 28 42 57 71 Time (weeks) Losordo, D.W. et al, Circulation 2012; 5(6):821- 18 830
CLBS12 registration-eligible study (Japan) . Continuous CLI-free (2 consecutive monthly visits, adjudicated Primary Endpoint independently) . 30 subjects with no-option CLI + 5 Buerger’s Disease pts.; all R4 or R5; Study Size 12 centers in Japan Dose . 106 cells/kg (CLBS12) per affected limb (studied in previous trial) . Standard of Care: wound care plus drugs approved in Japan Control/Comparator . Including antimicrobials, antiplatelets, anticoagulants and vasodilators Mode of administration . Intramuscular, 20 injections in affected lower limb in a single treatment . Results expected by year end 2020; earliest possible commercialization Timing/Costs 2021 . Study funded to completion in current budget projections 19
Extraordinary CLBS12 results in Buerger’s Disease (Japan) Current Patient CLI Status (n=6; study on-going) (Follow-up ongoing) (Follow-up ongoing) A Pre 1 30 60 90 120 150 180 210 240 270 300 330 365 Time (days) Continuous CLI- Rutherford 4 or 5 Rutherford 6 CLI-free Amputation (A) free . Natural evolution of Buerger’s Disease is continual deterioration for all patients . Surgery is not viable and existing pharmacotherapies do not prevent amputation1 . To date, CLBS12 treatment has resulted in 50% of patients achieving a positive outcome 1 Cacione DG, et al, Pharm. treatment of Buerger’s Disease, Cochrane Database of Systematic Reviews, 2016, (3) CD011033 20
CLBS16 Coronary Microvascular Dysfunction (USA)
Heart disease: No. 1 cause of death in the U.S. and growing Number of deaths by leading causes Thousands 2011 2017 700 600 500 400 300 200 100 0 HeartHeart Disease Cancer AccidentsLower Respiratory disease Stroke Alzheimer's Diabetes Influenza and PneumoniaKidney failure Suicide Disease Source: Centers for Disease Control and Prevention as cited in McKay, Betsy. "Heart-Failure Deaths Rise, Contributing to Worsening Life 22 Expectancy." The Wall Street Journal, 30 Oct. 2019, www.wsj.com/articles/heart-failure-deaths-rise-contributing-to-worsening-life-expectancy- 11572411901.
Indication: Coronary Microvascular Dysfunction (CMD) . 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 Association 2 4 R. David Anderson, John W. Petersen, Puja K. Mehta, et al., Journal of Interventional Cardiology, Kenkre, T.S. et al., Circ: CV Qual & Outcomes 2017, 10(12) 1-9 23 2019: 8 5 Collins, P., British heart journal (1993) 69(4), 279–281 3 Loffler and Bourque, Curr Cardiol Rep. 2016 Jan; 18(1): 1
ESCaPE-CMD: CLBS16 interventional, proof-of-concept trial . Therapeutic effect and the evaluation of adverse events; including changes Endpoints from baseline to 6 months for coronary flow reserve, endothelial-dependent microvascular function, time to angina; other CV metrics . 20 subjects (U.S. centers - Cedars Sinai, Los Angeles & Mayo Clinic, Study Size Rochester) Dose . Up to 300 x 106 CD34+ cells Mode of administration . Single intracoronary infusion . Positive results reported at AHA on Nov. 16, 2019 (17/20 subjects) . Full results expected by early 1Q 2020 Timing/Cost . Study funded to completion in current budget projections (including NIH grant) 24
CLBS16 ESCaPE-CMD results are unique and compelling Coronary Flow Reserve (17/20 subjects reporting) p = 0.0087 . CFR≤2.5 indicates CMD 2.61 2.08 . CFR≥2.5 is in “normal” range . Results after a single intracoronary administration N=20 N=17 of CLBS16 Pre-Treatment After 6 months Bairey Merz, C. N., AHA 2019 Scientific Sessions 25
CLBS16 ESCaPE-CMD results are unique and compelling Seattle Angina Questionnaire Score (17/20 subjects reporting) Baseline 6 months Angina Frequency p = 0.0143 Angina Stability p = 0.0425 Physical Limitation p = 0.002 Disease Perception p = 0.0005 Treatment Satisfaction p = 0.0044 0 20 40 60 80 100 26
ESCaPE-CMD CLBS16 reported results summary . 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 27
CLBS14 No Option Refractory Disabling Angina (USA) Regenerative Medicine Advanced Therapy (RMAT) designated - USA
Indication: No Option Refractory Disabling Angina (NORDA). 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 29
Our solution: CLBS14 . 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. 4 Povsic, T. J. et al, European Heart Journal, 2018 39(23), 2208-2216 2 Losordo, D.W., et al, Circ Res 2011, 109(4): 428-36 5 Velagapudi P, et al, Cardiovas Revasc Med, 2018, 20(3):215-219 3 Povsic, T.J., et al, JACC Cardiovasc Interv, 2016 9(15): 1576- 30 85
CLBS14 single treatment significantly improved exercise time Change in Exercise Time from Baseline (Phase 2, n=168) *6 months: CLBS14 (105 cells/kg) 139 sec p=0.014 Placebo 69 sec 12 months: CLBS14 (105 cells/kg) 140 sec p=0.017 Placebo 58 sec *Change in exercise time from baseline at 6 months will be the Phase 3 primary endpoint 31
CLBS14 single treatment significantly reduced angina frequency Reduction in Weekly Angina Frequency from Baseline (Phase 2, n=168) 6 months: CLBS14 (105 cells/kg) 13.8 p=0.0421 Placebo 8.8 12 months: CLBS14 (105 cells/kg) 15.3 p=0.0109 Placebo 8.7 32
CLBS14 single treatment significantly improved survival Mortality (Phase 2, n=168) Placebo 10 % p = 0.0065 CLBS14 2.5% (105 cells/kg) 012 24 Time (months) 33
CLBS14 Phase 3 confirmatory registration study (U.S.) Primary Endpoint . Change in exercise time from baseline at month 6 (studied in Phase 2) . 39 months from first-patient-in to top-line data; interim analysis after 50% Timing of patients complete 6-month follow-up . ~400 subjects (~200 active, ~150 placebo, ~50 SOC with cross-over to Study Size open label treatment at 6 months) Dose . 105 cells/kg body weight (studied in Phase 2) . Placebo control (blinded) Control/Comparator . Standard-of-care (unblinded) Mode of administration . Intramyocardial injection guided by mapping catheter (NOGA) . External costs: ~$70 million over a 3-4 years period Timing/Costs . Target initiation: Upon acquisition of sufficient capital that provides confidence that the study could be funded through completion 34
Caladrius timeline of key development milestones Program 2019 2020 Target Enrollment Registration Eligible Completion by Top-line Data Target – End of 1Q 2020 End of 2020 CLBS1 2 (CLI) Phase 2 Clinical Trial AHA Presentation of Complete Top-line Data Initiation of Phase 2 Trial Enrollment Completed Results of 17/20 Subjects by Early 1Q 2020 Target – Mid-2020 CLBS1 6 (CMD) Phase 3 Clinical Operationally Phase 3 Development Plan Ready – CMC and Confirmatory Phase 3 Initiation Target: TBD* Finalized with FDA ClinOps CLBS1 Complete 4 Projected (NORDA) d *Pending funding 35
Caladrius key financial information Cash & Investments as of September 30, 2019: $29.2 million Nine Months Ended September 30, 2019 Operating Cash $14.7 million Burn: Cash Runway Based on Current Plan: Through 1Q 2021 Debt: $0 Common Shares Outstanding as of September 30, 2019: 10.4 million shares Options Outstanding as of September 30, 2019: Exercise Price < $5.00 = 647,000 shares 1.1 million shares Exercise Price > $5.00 = 448,000 shares 36
Caladrius investment case summary CD34+ cell therapy platform company with an advanced clinical pipeline with two programs with cell therapy “breakthrough” designation 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 months based on development milestones across the pipeline Seasoned management team with noteworthy domain expertise along with big pharma and emerging biotech experience Strong balance sheet; $29.2 million in cash (September 30, 2019) with no debt and cash runway projected into 2021 3 7
Thank you! Investor Relations Contact: John D. Menditto Tel: (908) 842-0084 Email: jmenditto@caladrius.com November 2019 | Nasdaq: CLBS