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
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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 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 2.02 Results of Operations and Financial Condition.
The information in Item 7.01 is incorporated by reference.
Item 7.01 Regulation FD Disclosure.
On March 22, 2022, Caladrius Biosciences, Inc. (the "Company") issued a press release in connection with its financial results for the fiscal year ended December 31, 2021. 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.
The Company will conduct a conference call to review its financial results on March 22, 2022 at 4:30 p.m. Eastern Time.
A copy of a slide presentation that 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 Exhibits 99.1 and 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 Exhibits 99.1 and 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.
| Exhibit No. | Description | ||||
| Press release, dated March 22, 2022 | |||||
| Caladrius Biosciences, Inc. Corporate Presentation, March 22, 2022 | |||||
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: March 22, 2022
Exhibit 99.1
Caladrius Biosciences Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Business Update
Conference call begins today at 4:30 p.m. Eastern time
BASKING RIDGE, N.J. (March 22, 2022) – Caladrius Biosciences, Inc. (Nasdaq: CLBS) (“Caladrius” or the “Company”), a clinical-stage biopharmaceutical company dedicated to the development of innovative therapies designed to treat or reverse disease, provides a business update and reports financial results for the three and twelve months ended December 31, 2021.
“Caladrius made significant progress in 2021 that we believe has positioned us well to achieve several important milestones in 2022,” stated David J. Mazzo, Ph.D., President and Chief Executive Officer of Caladrius. “Highlights from 2021 include the initiation of our ongoing Phase 2b FREEDOM Trial of XOWNA® for the treatment of coronary microvascular dysfunction; the appointment of Kristen K. Buck, M.D., as Executive Vice President of Research & Development and Chief Medical Officer; and the strengthening of our balance sheet with approximately $95 million in capital that will serve as a foundation for our next phase of growth. The Company remains focused on refining and executing its development plans in 2022 and is already off to a strong start with the initiation of our Phase 1 study of CLBS201 in diabetic kidney disease where we anticipate the first patient to be treated early in the second quarter. In parallel, the Company continues to identify and evaluate strategic development opportunities with the aim of consummating transactions that will deliver additional value to our shareholders beyond our current development pipeline.”
Product Development and Financing Highlights
HONEDRA® (CLBS12) for the treatment of critical limb ischemia (“CLI”)
HONEDRA® is the Company’s SAKIGAKE-designated product candidate for the treatment of CLI and Buerger’s disease in Japan. As discussed in previous quarters, enrollment in the ongoing registration-eligible trial has been severely impeded by the multiple states of emergency declared by the Japanese government during 2020 and 2021 as a result of the COVID-19 pandemic. This has made even incremental enrollment exceedingly challenging. Since the trial continues to demonstrate positive trends in both safety and efficacy, the key criteria for consideration of conditional approval in Japan under the SAKIGAKE designation, the Company suspended enrollment and turned its focus to securing a Japanese partner either to complete study enrollment of the four remaining patients, if necessary, and/or to explore the possibility of submitting the existing data to the Japanese Regulatory Authorities for registration review. This decision was motivated by the Company’s desire to minimize additional operational and financial burden caused by enrollment delays and the lack of visibility on time to completion of the current study. The Company has had numerous conversations with the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan regarding the best path forward and anticipates having clarity on next steps during the second quarter of 2022.
XOWNA® (CLBS16) for the treatment of coronary microvascular dysfunction (“CMD”)
XOWNA® is an experimental regenerative therapy for the treatment of CMD. It was the subject of a positive Phase 2a study (the “ESCaPE-CMD trial”) reported in 2020 and is currently being evaluated in the U.S. Phase 2b FREEDOM Trial. The FREEDOM Trial is a double-blind, randomized, placebo-controlled study designed to assess the efficacy and safety of delivering autologous CD34+ cells to subjects with CMD and without obstructive coronary artery disease. As previously communicated, enrollment in the FREEDOM Trial initially proceeded as planned with the first patient treated in January 2021, however, the impact of the COVID-19 pandemic in the U.S. has contributed to a general slowing of enrollment that continues to this day. Caladrius has taken steps to accelerate enrollment by expanding the number of participating investigational sites as well as modifying the study protocol to make study inclusion criteria more flexible. At this time, the Company is unable to give guidance on when enrollment will be
completed but expects the study to run into 2023, if continued as planned. Final data from the study is expected approximately six months after last patient/last visit in the study. Caladrius continues to monitor the progress of the study and will consider additional future protocol and/or execution changes, as appropriate, to accelerate completion.
CLBS201 for the treatment of diabetic kidney disease (“DKD”)
Progressive kidney failure is associated with attrition of the microcirculation of the kidney. Pre-clinical studies in kidney disease and injury models have demonstrated that protection or replenishment of the microcirculation results in improved kidney function. Based on these observations, the Company recently initiated a Phase 1, open-label, proof-of-concept trial evaluating CLBS201, a CD34+ regenerative cell therapy investigational product for intra-renal artery administration in patients with DKD. Although still in the pre-dialysis stage of kidney disease, the selected patients will exhibit rapidly progressing stage 3b disease. The protocol provides for a staggered, sequentially dosed cohort of six patients overseen by an independent Data Safety Monitoring Board (DSMB) with the objective of determining the tolerance of intra-renal cell therapy injection in DKD patients as well as the ability of CLBS201 to regenerate kidney function. A key read-out of data will occur at the 6-month follow-up visit for all patients. As previously announced, the Company anticipates the first patient to be treated in this study early in the second quarter of 2022 with top-line data from all subjects expected by the first quarter of 2023.
Fourth Quarter and Full Year 2021 Financial Highlights
Research and development expenses for the fourth quarter of 2021 were $4.2 million, a 43% increase compared with $2.9 million for the fourth quarter of 2020, and $17.7 million for the year ended December 31, 2021 compared to $9.3 million for the year ended December 31, 2020, representing an increase of approximately 91%. Research and development activities in both the current year and prior year periods focused on the advancement of our ischemic repair platform and related to:
•Expenses associated with efforts to continue execution and acceleration of enrollment of the FREEDOM Trial;
•Expenses associated with the planning, preparation and initiation of the Phase 1 proof-of-concept trial for CLBS201 as a treatment for DKD; and
•Ongoing expenses for HONEDRA® in CLI and Buerger’s disease in Japan associated with maintenance of manufacturing facility and personnel qualification as well as Contract Research Organization engagement despite no subject treatment execution due to the COVID-19 imposed state of emergency in Japan.
General and administrative expenses, which focus on general corporate related activities, were $2.7 million for the three months ended December 31, 2021, representing an increase of 6% compared to $2.5 million for the three months ended December 31, 2020, and $11.4 million for the year ended December 31, 2021, representing an increase of 15% compared to $9.9 million for the year ended December 31, 2020. This increase was primarily due to an increase in directors and officers liability insurance premiums and strategic consulting expenses.
Overall, net losses were $27.5 million and $8.1 million for the years ended December 31, 2021, and 2020, respectively.
Balance Sheet Highlights
As of December 31, 2021, we had cash, cash equivalents and marketable securities of approximately $95.0 million. Based on existing development programs, the Company projects that its current cash balance will fund operations for the next several years. Based on this favorable cash position, the Company will continue its concerted efforts to identify and acquire additional development assets to diversify its portfolio of product candidates and to enhance the opportunity for shareholder value creation.
Conference Call
Caladrius will hold a live conference call today March 22, 2022, at 4:30 p.m. (ET) to discuss financial results, provide a business update and answer questions. To join the conference call, please refer to the dial-in information provided below. A live webcast of the call will also be available under the Investors & News section of the Caladrius website (https://ir.caladrius.com/) and will be available for replay for 90 days after the conclusion of the call.
Dial-in information:
Conference ID: 5066195
U.S. Toll-Free: 866-595-8403
International: 706-758-9979
Please dial-in 10 minutes before the start of the conference call.
For those unable to participate on the live conference call, an audio replay will be available that day starting at 7:30 p.m. (ET) until March 29, 2022, by dialing 855-859-2056 (U.S. Toll-Free) or 404-537-3406 (International) and by entering the replay passcode: 5066195.
About Caladrius Biosciences
Caladrius Biosciences, Inc. is a clinical-stage biopharmaceutical company dedicated to the development of innovative therapies designed to treat or reverse disease. We currently are developing first-in-class autologous cell therapy products based on the finely tuned mechanisms for self-repair that exist in the human body. Our technology leverages and enables these mechanisms in the form of specific cells, using formulations and modes of delivery unique to each medical indication.
The Company’s current product candidates include: XOWNA® (CLBS16), the subject of both a recently completed positive Phase 2a study and an ongoing Phase 2b study (www.freedom-trial.com) in the U.S. for the treatment of coronary microvascular dysfunction (“CMD”); CLBS12 (HONEDRA® in Japan), recipient of a SAKIGAKE designation in Japan and eligible for early conditional approval for the treatment of critical limb ischemia (“CLI”) and Buerger’s disease based on the results of an ongoing clinical trial; and CLBS201, designed to assess the safety and efficacy of CD34+ cell therapy as a treatment for diabetic kidney disease (“DKD”). 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, 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; market and other conditions; any plans or expectations with respect to product research, development and commercialization, including regulatory approvals; any plans or expectations to complete strategic transactions to diversify our pipeline of development product candidates; 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 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 22, 2022, 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, except as required by law.
Contact:
Investors:
Caladrius Biosciences, Inc.
John Menditto
Vice President, Investor Relations and Corporate Communications
Phone: 908-842-0084
Email: jmenditto@caladrius.com
- Tables to Follow -
Caladrius Biosciences, Inc.
Selected Financial Data
(in thousands, except per share data)
| Three Months Ended December 31, | Twelve Months Ended December 31, | |||||||||||||||||||||||||
| 2021 | 2020 | 2021 | 2020 | |||||||||||||||||||||||
| (in thousands, except per share data) | (unaudited) | (unaudited) | ||||||||||||||||||||||||
| Statement of Operations Data: | ||||||||||||||||||||||||||
| Research and development | $ | 4,150 | $ | 2,907 | $ | 17,680 | $ | 9,253 | ||||||||||||||||||
| General and administrative | 2,699 | 2,539 | 11,370 | 9,892 | ||||||||||||||||||||||
| Total operating expenses | 6,849 | 5,446 | 29,050 | 19,145 | ||||||||||||||||||||||
| Operating loss | (6,849) | (5,446) | (29,050) | (19,145) | ||||||||||||||||||||||
| Investment income, net | 40 | 15 | 151 | 132 | ||||||||||||||||||||||
| Other expense, net | 15 | — | (75) | — | ||||||||||||||||||||||
| Net loss before benefit from income taxes and noncontrolling interests | (6,794) | (5,431) | (28,974) | (19,013) | ||||||||||||||||||||||
| Benefit from income taxes | — | — | (1,508) | (10,872) | ||||||||||||||||||||||
| Net loss | (6,794) | (5,431) | (27,466) | (8,141) | ||||||||||||||||||||||
| Less - net (loss) income attributable to noncontrolling interests | — | (1) | — | 9 | ||||||||||||||||||||||
| Net loss attributable to Caladrius Biosciences, Inc. common shareholders | $ | (6,794) | $ | (5,430) | $ | (27,466) | $ | (8,150) | ||||||||||||||||||
| Basic and diluted loss per share attributable to Caladrius Biosciences, Inc. common shareholders | $ | (0.11) | $ | (0.28) | $ | (0.50) | $ | (0.53) | ||||||||||||||||||
| Weighted average common shares outstanding | 59,775 | 19,396 | 55,313 | 15,440 | ||||||||||||||||||||||
| December 31, 2021 | December 31, 2020 | |||||||||||||||||||||||||
| Balance Sheet Data: | ||||||||||||||||||||||||||
| Cash, cash equivalents and marketable securities | $94,970 | $34,573 | ||||||||||||||||||||||||
| Total assets | 97,008 | 36,002 | ||||||||||||||||||||||||
| Total liabilities | 5,008 | 3,760 | ||||||||||||||||||||||||
| Total equity | 92,000 | 32,242 | ||||||||||||||||||||||||
# # #
David J. Mazzo, PhD President & Chief Executive Of ficer M a rc h 2 2 , 2 0 22| N a s d a q : C L B S Developing Innovative Therapies that Treat or Reverse Disease Exhibit 99.2
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 22, 2022, 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 2
CD34+ cell therapy platform yielding a multi-product development pipeline with 2 clinical programs having regenerative medicine “breakthrough” designation Proprietary field-leading technology in lucrative global indications backed by a strong IP portfolio Potential value creating events in the next 12-24 months based on milestones across the pipeline Seasoned management with noteworthy domain expertise along with big pharma and emerging biotech experience Strong balance sheet [$95 million cash & investments (end 2021) - no debt]; projected to fund operations (current development portfolio) for several years Caladrius investment highlights 3
CD34+ Cell Therapy Technology Overview
Naturally occurring endothelial progenitor cells that re-establish blood flow to under-perfused tissues1,2 Possess pre-programmed pro-angiogenic and anti-inflammatory tissue repair properties3,4 1Mackie, A.R. et al., Tex Heart Inst J 2011, 38(5), 474-485 2Kocher, A.A. et al., Nat Med 2001, 440-436 53Abd-Allah et al., Cytotherapy 2015, 17: 443-53 4Lo , B.C. et al., Am J Respir Cell Mol Biol 2017, 57: 651-61 CD34+ cells have a well characterized mechanism of action
CD34+ cells have been studied clinically in a variety of ischemic disease indications by numerous investigators across many sites and countries CD34+ cells repeatedly demonstrated vascular repair in multiple organs Consistent and compelling results of rigorous clinical studies comprising >1,000 patients have been published in peer reviewed journals1-4 Single treatments elicited durable therapeutic effects Treatment generally well-tolerated 1 Povsic, T. et al. JACC Cardiovasc Interv, 2016, 9 (15) 1576-1585 2 Losordo, D.W. et al. Circ Cardiovasc Interv, 2012; 5:821–830 3 Velagapudi P, et al, Cardiovas Revasc Med, 2018, 20(3):215-219 4 Henry T.D., et al, European Heart Jour 2018, 2208–2216 CD34+ autologous cell therapy is extensively studied/clinically validated 6
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 Caladrius’ autologous CD34+ cell process is rapid/economical/scaled 7
U.S. patents granted 9 28 Foreign patents granted Patent protection to 2031+ Key Patent Claims Pharmaceutical composition of non-expanded CD34+/CXCR4+ cells Therapeutic concentration range Stabilizing serum Repair of injury caused by vascular insufficiency Caladrius’ autologous CD34 technology has robust intellectual property 8
PRODUCT/INDICATION DEVELOPMENT STAGE XOWNA® (CLBS16) CORONARY MICROVASCULAR DYSFUNCTION FREEDOM PHASE 2B TRIAL (USA; ONGOING) Caladrius’ innovative autologous CD34+ cell therapy pipeline1,2 1 Products are distinct and not interchangeable 2 All timing subject to COVID-19 pandemic influence 9 HONEDRA® (CLBS12) *SAKIGAKE DESIGNATED (JAPAN) CRITICAL LIMB ISCHEMIA + BUERGER’S DISEASE REGISTRATION ELIGIBLE TRIAL (JAPAN; ONGOING) CLBS201 DIABETIC KIDNEY DISEASE PHASE 1 (USA; ONGOING)
XOWNA® (CLBS16) Coronary Microvascular Dysfunction (USA)
Deficient heart microvasculature without large vessel obstructive disease Causes frequent, debilitating chest pain; not treatable by stents or bypass; responds poorly or not at all to available pharmacotherapies Afflicts women more frequently (2:1 to 3:1), especially younger women1,2 Results in poor prognosis for patients3 Significantly elevated risk of all-cause mortality4 Clinically diagnosed based on symptoms and demonstrated absence of large vessel obstructive disease Quantitatively diagnosed using Coronary Flow Reserve (CFR)5 and image-techniques (cPET and cMRI) 1 Coronary Microvascular Disease. (2015, July 31). In American Heart Association 2 R. David Anderson, John W. Petersen, Puja K. Mehta, et al., Journal of Interventional Cardiology, 2019: 8 3 Loffler and Bourque, Curr Cardiol Rep. 2016 Jan; 18(1): 1 4 Kenkre, T.S. et al., Circ: CV Qual & Outcomes 2017, 10(12) 1-9 5 Collins, P., British heart journal (1993) 69(4), 279–281 Indication: Coronary microvascular dysfunction (CMD) 11
~112 million people globally are affected by angina1 ~8.3 million people in the U.S. suffering from coronary artery disease (CAD)2 10% - 30% of angina patients have no significant CAD on invasive coronary angiography3,4 50% - 65% of patients with angina without obstructive CAD are believed to have CMD5 CMD represents a large unmet medical need 12 1 Kunadian V, et al. European Heart Journal. 2020; 0:1-21 2 Cleveland Clinic/AHA (American Heart Association) 3 Farrehi PM, et al. Am J Manag Care. 2002;8:643–648 4 Bradley SM, et al. J Am Coll Cardiol. 2014;63:417–426 5 Marinescu MA, et al. JACC Cardiovasc Imaging. 2015;8:210-220 6 Tunstall-Pedoe H. (ed.) WHO, Geneva, 2003, pp. 244, Swiss Fr 45, ISBN: 92-4-156223-4. Applicable CMD population in the U.S. potentially treatable by XOWNA® ranges from ~415,000 to ~1.6 million patients6
Endpoints Therapeutic effect and the evaluation of adverse events; including changes from baseline to 6 months for coronary flow reserve, angina frequency, CCS angina class, quality of life 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 Objective Demonstrate proof-of-concept of CD34+ cell therapy in CMD patients Data reported at AHA 2019 and SCAI 2020 ESCaPE-CMD: Phase 2a interventional, proof-of-concept trial completed 13
ESCaPE-CMD: Durable, physiologic coronary vasculature improvement 14 1 Murthy et al, Circulation, 2014 2 Henry, T. D., Bairey Merz, C. N., et al. (2022). Cardiovascular interventions. Coronary Flow Reserve 1 2.08 2.68 p = 0.0045 N=20 Pre-Treatment After 6 months N=19 Key Points: Evaluated subjects with CFR ≤2.5 (diagnosed as CMD) CFR = 2 correlates with a 3-4x increase in major adverse cardiac events (MACE) at 3 years1 A single intracoronary XOWNA® infusion significantly increased CFR to normal values (i.e., ≥2.5) for at least 6 months (period of patient follow-up) First therapy to potentially reverse CMD Treatment generally well-tolerated Intracoronary XOWNA® infusion may ultimately correlate with a reduction in MACE
15 1 Henry, D. T., SCAI 2020 Scientific Sessions 2 Spertus, J.A. et al, JACC Vol. 25, No. 2 February 1995: 333-341 3 Henry, T. D., Bairey Merz, C. N., et al. (2022). Cardiovascular interventions. 0 20 40 60 80 100 Treatment Satisfaction Disease Perception Physical Limitation Angina Stability Angina Frequency Seattle Angina Questionnaire Score1 Baseline 6 months Higher scores indicate improvement2 p = 0.0026 p = 0.0247 p = 0.0156 p = 0.0005 Daily Angina Frequency 2 4.42 2.02 N=20 Pre-Treatment After 6 months p = 0.0036 N=19 ESCaPE-CMD: Durable, symptomatic anginal relief p = 0.0117
Endpoints Change from baseline in angina frequency [Baseline to 3 and 6 months] Change from baseline in total exercise time [Baseline to 6 months] Change from baseline in health-related quality of life [Baseline to 3 and 6 months] Change from baseline in peak coronary flow reserve [Baseline to 6 months] Study Size 105 subjects (~15 sites in the USA) Dose 1 x 106 to 300 x 106 CD34+ cells (XOWNA®) or placebo Mode of Administration Single intracoronary infusion Objective Confirm ESCaPE-CMD safety and efficacy results in a controlled trial (possible basis for RMAT application) Estimate effect size for endpoint(s) likely required in a registration trial Characterize patient flow and diagnoses using “real world” criteria FREEDOM trial: Phase 2b double-blind, placebo-controlled 16
SAKIGAKE designated – Japan Orphan Drug designated (Buerger’s disease) - USA Advanced Therapeutic Medicinal Product (ATMP) designated – EU HONEDRA® Critical Limb Ischemia (Japan) (CLBS12)
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 (BD = inflammation in small and medium arteries) a form of CLI associated with a history of heavy smoking (orphan population) 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 death Multi-hundred-million-dollar opportunity in Japan Indication: Critical limb ischemia (CLI) 18
CLI: Higher mortality incidence than most cancers Mustapha, J. A., Katzen, B. T., et al. (2019, May). Endovascular Today, 18(5), 80-82 19 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
HONEDRA® targets patients with R4 or R5 disease 1 Reinecke H., European Heart Journal, 2015 Apr 14;36(15):932-8 HONEDRA® targets patients based on the Rutherford Scale 20 CLI amputation rates increase with increasing Rutherford score (disease severity)1 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: Mild to severe claudication
Single treatment of CD34+ cells reversed CLI (Phase 2 data) 21 Post-treatment (week 12) Pre-treatment Actual CLI Patient Laser Doppler Image 0 14 28 42 57 71 Time (weeks) CLBS12 Placebo 75% 22% p = 0.014 106 cells/kg Probability of Amputation-Free Survival (USA; n=28)2 ~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 Time (weeks) % of Patients (CLI + BD) Achieving CLI-free Status (Japan; n=27)1 1 Kinoshita et al, Atherosclerosis 224 (2012) 440-445 2 Losordo, D.W. et al, Circulation 2012; 5(6):821-830
Primary Endpoint Time to continuous CLI-free (2 consecutive monthly visits, adjudicated independently) Target Study Size 35 (30 subjects with no-option CLI + 5 Buerger’s disease pts.); all Rutherford category 4 or 5; recruited across 12 centers in Japan Dose Up to 106 cells/kg of HONEDRA® (CLBS12) 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 Objective Demonstrate a trend toward efficacy and acceptable safety to qualify for consideration of early conditional approval under Japan’s Regenerative Medicine Development Guidelines HONEDRA® registration-eligible study (CLBS12-P01, Japan) 22
Proportion of CLBS12-treated subjects reaching CONTINUOUS CLI-free status MORE THAN DOUBLE control arm Proportion of CLBS12-treated subjects reaching FIRST CLI-free status MORE THAN DOUBLE control arm CLBS12-P01 “full analysis set” efficacy trends positively 23FAS: Full Analysis Set as defined by Japanese Regulators (PMDA) ASO Control CLBS12(ASO+BD) Proportion of Subjects Reaching Pr op or tio n of S ub je ct s R ea ch in g C O N TI N 0. 0 0. 2 0. 4 0. 6 0. 8 1. 0 14.3% 40.0% (N=14) (N=15) ASO Control CLBS12(ASO+BD) Proportion of Subjects Reach Pr op or tio n of S ub je ct s R ea ch in g FI R ST C 0. 0 0. 2 0. 4 0. 6 0. 8 1. 0 21.4% 46.7% (N=14) (N=15)
CLBS12-P01 efficacy trends positively for both ASO and BD individually 24FAS: Full Analysis Set as defined by Japanese Regulators (PMDA) Efficacy trends are consistent across both populations ASO Control ASO CLBS12 BD CLBS12 CLBS12(ASO+BD) Proportion of Subjects Reaching Pr op or tio n of S ub je ct s R ea ch in g C on tin u 0. 0 0. 2 0. 4 0. 6 0. 8 1. 0 14.3% 33.3% 50.0% 40.0% (N=14) (N=9) (N=6) (N=15) ASO Control ASO CLBS12 BD CLBS12 CLBS12(ASO+BD) Proportion of Subjects Reach Pr op or tio n of S ub je ct s R ea ch in g Fi rs t C L 0. 0 0. 2 0. 4 0. 6 0. 8 1. 0 21.4% 44.4% 50.0% 46.7% (N=14) (N=9) (N=6) (N=15)
HONEDRA® study enrollment was significantly curtailed by the impact of COVID-19 (States of Emergency in Japan between ~ February 2020 and October 2021) Total enrolled to date: 33 (26 no-option CLI pts. + 7 Buerger’s disease pts.) Combined CLI and BD interim data suggest trend toward efficacy and acceptable safety Further enrollment paused as a result of substantial continued operational & financial burden due to enrollment delays and unpredictability of completion timing Priority for Caladrius in Japan is securing a local partner to explore submitting the existing data to the Pharmaceuticals & Medical Devices Agency (PMDA) under the SAKIGAKE designation 25 HONEDRA® development next steps
CLBS201 Diabetic Kidney Disease (USA)
Advancing age is a risk factor for chronic kidney disease (CKD). Type 2 diabetes and hypertension are common comorbidities 1 in 3 adults are type 2 diabetic and 1 in 5 adults are hypertensive1 Chronic kidney disease: Risk factors and comorbidities 1 Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2019. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2019. 0% 10% 20% 30% 40% Hispanics Non-Hispanic Asians Non-Hispanic Blacks Non-Hispanic Whites Women Men 65+ 45-64 18-44 CKD Among U.S. Adults (>18 years old) 0% 5% 10% 15% 20% 25% 30% 35% 40% Unknown Causes Other Causes Glomerulonephritis High Blood Pressure Diabetes CKD Comorbidities 27
CKD: Multiple stages progressing toward kidney failure 1 2020 Dallas Nephrology Associates 2 Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System—United States. The stages of CKD are determined by glomerular filtration rate (GFR)1 GFR is measured to determine how well the kidneys are filtering blood As kidney function worsens, the level of creatinine increases and GFR decreases In 2015-2016, 14%-15% of U.S. adults had evidence of CKD stages 1-4; of these, ~15 to 18 million had evidence of CKD stage 3 or 42 28 STAGE 4 Severe loss of function STAGE 5 Kidney failure STAGE 3B Moderate to Severe loss of function STAGE 1 Normal function STAGE 2 Mild loss of function STAGE 3A Mild to Moderate loss of function
CKD is often associated with progressive microvasculature damage and loss1,2 Preclinical studies show that microcirculation replenishment improves kidney function CD34+ cells are promoters of new capillary growth, improving the microvasculature Therapies currently available and/or expected to be available over the next 5–10 years will slow the progression of CKD/diabetic kidney disease (DKD) An effective regenerative DKD therapy (i.e., one that reverses the course of the disease) could represent a medical and pharmacoeconomic breakthrough 1 Chade AR. (2017) Small Vessels, Big Role: Renal Microcirculation and Progression of Renal Injury. Hypertension; 69(4):551-563. 2 Zuk, Anna & Bonventre, Joseph. (2016). Annual Review of Medicine. 67. 293-307. 10.1146/annurev-med-050214-013407. 29 Development rationale for CLBS201 CLBS201 clinical strategy To demonstrate that CD34+ cell therapy (mobilization, donation and administration) can be tolerated by patients with CKD with Type 2 Diabetes To demonstrate that regeneration of the kidney microcirculation using CD34+ cell therapy improves kidney function
CLBS201: Planned Phase 1 proof-of-concept study 30 Endpoints Change in eGFR compared to baseline, assessed at 6 months Change in Urine albumin-to-creatinine ratio (UACR) and urine protein-to-creatinine ratio (UPCR) from baseline to 3 and 6 months Study Size 6 patients (1 sentinel - unilateral inj., 1 sentinel - bilateral inj., 4 bilateral inj. patients) Dose 1 x 106 – 300 x 106 cells administered as a one-time infusion Patient Population Stage 3b DKD Design Open-label Mode of Administration Intra-arterial injection into one or both renal arteries Timing Top-line data target for all subjects: 1Q2023
Caladrius key financial information 31 Cash & Investments: As of December 31, 2021 $95.0 million Full year ended December 31, 2021 Operating Cash Burn1: $23.7 million Cash Runway Based on Current Plan: Sufficient capital to fund operations beyond multiple key data readouts (>2024) Debt as of December 31, 2021: $0 Common Shares Outstanding: As of December 31, 2021 59.8 million shares Options Outstanding as of December 31, 2021: Exercise Price: $1.28 - $3.28 = 1,474,300 shares Exercise Price: > $3.28 = 657,600 shares 2.1 million shares Warrants Outstanding as of December 31, 2021 : Weighted Average Exercise Price: $2.84 21.4 million shares 1 Excludes $1.4 million in net proceeds from sale of New Jersey NOLs
CD34+ cell therapy platform yielding a multi-product development pipeline with 2 clinical programs having regenerative medicine “breakthrough” designation Proprietary field-leading technology in lucrative global indications backed by a strong IP portfolio Potential value creating events in the next 12-24 months based on milestones across the pipeline Seasoned management with noteworthy domain expertise along with big pharma and emerging biotech experience Strong balance sheet [$95 million cash & investments (end 2021) - no debt]; projected to fund operations (current development portfolio) for several years Caladrius investment highlights 32
Developing Innovative Therapies that Treat or Reverse Disease Investor Relations Contact: John D. Menditto Tel: (908) 842-0084 jmenditto@caladrius.com M a rc h 2 2 , 2 0 22| N a s d a q : C L B S