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): August 6, 2015
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.) |
106 Allen Road, 4th 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)) |
Item 2.02. Results of Operations and Financial Condition.
On August 6, 2015, Caladrius Biosciences, Inc. ("Caladrius Biosciences" or the "Company") issued a press release relating to, among other things, the results of the Company's second quarter ended June 30, 2015. A copy of this press release is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated into this Item 2.02 by reference.
In accordance with General Instruction B.2 of Form 8-K, the information in this Item 2.02 of this Current Report on Form 8-K, including Exhibit 99.1, shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such a filing.
Item 7.01 Regulation FD Disclosure.
Caladrius Biosciences, Inc. intends, from time to time, to present and/or distribute to the investment community and utilize at various industry and other conferences a slide presentation. The slide presentation is accessible on the Company's website at www.caladrius.com and is attached hereto as Exhibit 99.2. Caladrius Biosciences undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
In accordance with General Instruction B.2 of Form 8-K, the information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.2, shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended, except as shall be expressly set forth by reference in such a filing.
Forward Looking Statements
This Current Report on Form 8-K, including Exhibits 99.1 and 99.2, contains “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are typically preceded by words such as “believes,” “expects,” “anticipates,” “intends,” “will,” “may,” “should,” or similar expressions, although some forward-looking statements are expressed differently. Forward-looking statements represent the Company's management's judgment regarding future events. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, the Company can give no assurance that such expectations will prove to be correct. All statement other than statements of historical fact included in the Current Report on Form 8-K are forward-looking statements. The Company cannot guarantee the accuracy of the forward-looking statements, and you should be aware that the Company's actual results could differ materially from those contained in the forward-looking statements due to a number of factors, including the statements under "Risk Factors" contained in the Company's reports filed with the Securities and Exchange Commission.
Item 9.01 Financial Statements and Exhibits
(d) Exhibits
Exhibit No. | Description |
99.1 | Press Release dated August 6, 2015* |
99.2 | Power Point Presentation dated August 2015* |
*Exhibits 99.1 & 99.2 are furnished as part of this Current Report on Form 8-K.
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/ Robert S. Vaters | |||
Name: | Robert S. Vaters | |||
Title: | President and CFO | |||
Dated: August 6, 2015
Exhibit 99.1
Caladrius Biosciences, Inc. Announces Second Quarter 2015 Financial Results and Provides Corporate Update
Revenues up 31% from 2Q 2014 and Company Sets Future Direction for its Ischemic Repair Program
NEW YORK, August 6, 2015 (GLOBE NEWSWIRE) - Caladrius Biosciences, Inc. (Nasdaq:CLBS) ("Caladrius" or the "Company"), a company combining a leading cell therapy service provider with a development pipeline including a Phase 3 clinical program in immuno-oncology and a portfolio of projects in immune modulation and ischemic repair, announced today 2015 second quarter results.
The Company reported a 31% increase in revenues from the second quarter of 2014 to the second quarter of 2015. In addition, the Company has decided to explore chronic heart failure and/or critical limb ischemia as targets for further development within its ischemic repair program.
“We are excited and encouraged by strong revenue growth at our wholly-owned subsidiary, PCT,” said Dr. David J. Mazzo, Chief Executive Officer of Caladrius. “Additionally, the Company followed through on its promise to set an optimized pathway forward for our ischemic repair program.”
Business Highlights
• | First patient dosed in Phase 3 trial (the Intus Study) of CLBS20 for patients with stage III recurrent or stage IV metastatic melanoma; |
• | Receipt of $17.7 million grant award from California Institute for Regenerative Medicine (CIRM) to support the Intus Study, reflecting significant endorsement of the potential of CLBS20 and expected to fund a significant portion of the study; |
• | Research collaboration with the University of Southern California and California Institute of Technology to explore next-generation strategies for the Company’s core cancer technology; |
• | Establishment of a new cardiovascular scientific advisory board; |
• | National Institutes of Health (NIH) grant to fund retinal disease research; |
• | Expansion of relationship between PCT, a Caladrius company, and ImmunoCellular Therapeutics to provide manufacturing for ImmunoCellular’s Phase 3 trial; and |
• | Closing of $28.75 million public offering of common stock which introduced a strong contingent of new institutional investors. |
After a thorough review, the Company has set the future direction for its ischemic repair program. Based on an analysis of the available Phase 2 data from the PreSERVE-AMI trial, an updated commercial assessment considering all major potential relevant cardiovascular indications and consultation with the Company’s new cardiovascular scientific advisory board and the Science and Technology Committee of the Board of Directors, Caladrius has decided that it will not pursue further development of the acute myocardial infarction indication upon completion of the ongoing PreSERVE-AMI Phase 2 clinical study. However, the positive suggestion of safety and therapeutic activity seen to date in the PreSERVE-AMI trial supports the underlying platform technology and enables the Company’s exploration of more commercially viable indications of chronic heart failure and/or critical limb ischemia as targets for further development. The Company will continue to seek partnerships for all the indications in this platform, which will be necessary for Caladrius to proceed to the next steps in clinical development.
2015 Second Quarter Financial Highlights
Total revenue for the quarter was approximately $5.9 million compared to $4.5 million for 2Q 2014, an increase of 31%, which was primarily due to higher reported Clinical Services revenues at PCT. Total non-GAAP Adjusted Revenue, which excludes the impact of deferred revenue adjustments, was approximately $5.0 million for 2Q 2015 compared to $5.3 million for 2Q 2014 (see below for reconciliation).
Research and development expenses were approximately $7.6 million for the quarter compared to $5.8 million for 2Q 2014. The increase was primarily related to an increase in expenses for the Company’s immuno-oncology program, primarily associated with the Intus Phase 3 clinical trial, as well as a minor increase in expenses for the ischemic repair program for a potential critical limb ischemia development program in Japan. These expenses were partially offset by lower continued costs associated with the PreSERVE-AMI Phase 2 clinical trial for the Company’s product candidate CLBS10 and lower expenses associated with the immune modulation program, including our efforts focused on initiating our Phase 2 study of CLBS03 in type 1 diabetes.
Selling, general and administrative expenses were approximately $8.7 million for the quarter compared to $7.4 million for 2Q 2014. The increase is primarily due to higher equity-based compensation in the current quarter compared to 2Q 2014.
Net loss for 2Q 2015 was approximately $17.2 million compared to net loss of $12.8 million for 2Q 2014. Net loss for 2Q 2015 excluding non-cash charges was $26.1 million, compared with $19.4 million for 2Q 2014 (see below for reconciliation).
Net loss for 2Q 2015 included the impact of changes in the Company's ischemic repair program. As a result, the Company determined that IPR&D valued at $9.4 million was fully impaired, and the associated deferred tax liability of $3.7 million was reversed. In addition, the fair value of contingent consideration associated with earn out payments on CLBS10 future revenues was reduced from $5.6 million to $0 as of June 30, 2015. The overall net impact for these changes was a $20,000 increase in net loss.
At June 30, 2015, Caladrius' cash, cash equivalents and marketable securities totaled $39.2 million.
As previously announced, Dr. David J. Mazzo, Chief Executive Officer, and Robert S. Vaters, President and Chief Financial Officer, will discuss results and provide a company update via a webcast and conference call today at 4:30 pm ET. To access the webcast, visit the Investor Relations section of the Company’s website at http://www.caladrius.com/investors/overview/. Alternatively, callers may participate in the conference call by dialing 877-562-4460 or, for international callers, 513-438-4106, and providing conference ID 91597846.
Use of Non-GAAP Financial Measures
The Company uses “Adjusted Revenues” and “Net Loss Excluding Non-Cash Charges” as non-GAAP financial measures in evaluating its performance.
• | Adjusted Revenues represents GAAP revenues less the impact of the change in unearned revenues. The Company believes that providing this measure to investors provides important supplemental information relating to its performance and permits investors and management to evaluate the impact of the Company’s revenue-generating activities on its cash position. Additionally, the Company believes this information is frequently used by securities analysts, investors and other interested parties in the evaluation of performance. Management uses, and believes that investors benefit from, this non-GAAP financial measure in assessing the Company's revenue-generating activities, as well as in planning, forecasting and analyzing future periods. |
• | Net Loss Excluding Non-Cash Charges represents net loss, less equity-based compensation, depreciation and amortization, impairments of intangible assets, and other non-cash adjustments included in calculating net loss. The Company believes that providing this measure to investors provides important supplemental information relating to its performance and permits investors and management to evaluate the core operating performance and cash utilization of the Company by excluding the use of these non-cash adjustments. Additionally, the Company believes this information is frequently used by securities analysts, investors and other interested parties in the evaluation of performance. Management uses, and believes that investors benefit from, this non-GAAP financial measure in assessing the Company's operating results, as well as in planning, forecasting and analyzing future periods. |
These non-GAAP measures have limitations as an analytical tool, and investors should not consider these measures in isolation, or as a substitute for analysis of the Company's results as reported under generally accepted accounting principles in the United States ("GAAP"). For example, Net Loss Excluding Non-Cash Charges does not reflect the Company's cash expenditures, future requirements for capital expenditures, contractual commitments or cash requirements for working capital needs. Although depreciation and amortization are non-cash charges, the assets being depreciated or amortized often will have to be replaced in the future, and Net Loss Excluding Non-Cash Charges does not reflect any cash requirements for such replacements. Given these limitations, the Company relies primarily on its GAAP results and uses the Net Loss Excluding Non-Cash Charges measure only as a supplemental measure of its financial performance and cash utilization.
GAAP to Non-GAAP Reconciliation | ||||
Adjusted Revenues Reconciliation (unaudited) | ||||
(in millions) | For the three months ended June 30, 2015 | For the three months ended June 30, 2014 | ||
Revenues | $5.9 | $4.5 | ||
Change in Unearned Revenue | (0.9) | 0.8 | ||
Adjusted Revenues | $5.0 | $5.3 | ||
Net Loss Excluding Non-Cash Charges Reconciliation (unaudited) | ||||
(in millions) | For the three months ended June 30, 2015 | For the three months ended June 30, 2014 | ||
Net loss | $(36.4) | $(26.6) | ||
Equity-based compensation | 8.1 | 5.7 | ||
Depreciation and amortization | 1.3 | 1.0 | ||
Changes in acquisition-related contingent consideration | (4.8) | 0.4 | ||
Impairment of intangible assets | 9.4 | 0 | ||
Deferred income taxes | (3.7) | 0.1 | ||
Net Loss Excluding Non-Cash Charges | $(26.1) | $(19.4) | ||
About Caladrius Biosciences
Caladrius Biosciences, Inc. is among the first of a new breed of immunotherapy companies with proven expertise and unique experience in cell process optimization, development, and manufacturing. Caladrius is a company combining a leading cell therapy service provider with a development pipeline including late-stage clinical programs based on proprietary platform technology for immuno-oncology, as well as additional platform technologies for ischemic repair and immunomodulation. This integrated approach supports the industry in bringing significant life-improving medical treatments to market. www.caladrius.com
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. Forward-looking statements include, among others, statements herein with respect to the commercial viability of the chronic heart failure and/or critical limb ischemia indications within the Company’s ischemic repair program and the Company’s seeking of partnerships for its ischemic repair programs. 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 materially differ 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 2, 2015, and in the Company's other periodic filings with the SEC. The Company's further development is highly dependent on future medical and research developments and market acceptance, which is outside of its control.
CONTACT: Caladrius Biosciences, Inc.
Eric Powers
Manager of Communications and Marketing
Phone: +1-212-584-4173
Email: epowers@caladrius.com
Delivering Personalized Medicine Corporate Presentation NASDAQ: CLBS David J. Mazzo, PhD Chief Executive Officer August 2015
Forward-looking statements This 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. Forward-looking statements include statements herein with respect to the successful execution of the Company's business strategy, the Company's ability to develop and grow its business, the successful development of cellular therapies with respect to the Company's research and development and clinical evaluation efforts in connection with the Company's Immuno-oncology Program, Ischemic Repair Program, Immune Modulation Program and other cell therapies, the future of the regenerative medicine industry and the role of stem cells and cellular therapy in that industry, and the performance and planned expansion of the Company's wholly-owned subsidiary and its center of excellence for cell therapy process development, engineering and manufacturing, PCT. The Company's further development is highly dependent on future medical and research developments and market acceptance, which is outside of its control. The Company's actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see the factors described under the heading, “Item 1A. Risk Factors" in the Company's Annual Report on Form 10-K filed with the SEC on March 2, 2015 and those described in the Company's other periodic filings with the SEC. The Company undertakes no obligation to update or revise any forward-looking statements. 2
Transforming cells into therapies 3
PCT, a Caladrius company: Industry-recognized single source premier cell therapy service provider Caladrius Biosciences’ Center of Excellence for process development, engineering and manufacturing PRODUCT & PROCESS DEVELOPMENT MANUFACTURING CELL & TISSUE PROCESSING LOGISTICS, STORAGE & DISTRIBUTION EXPERT CONSULTATION & REGULATORY SUPPORT ENGINEERING & AUTOMATION 4
Unmatched experience: >100 clients and 30,000 products over 15 years 5
At a glance Unifying platform approach yielding a robust, balanced pipeline targeting critical unmet medical needs Proven internal center of excellence (PCT) with bicoastal facilities innovating discovery, development, manufacturing and delivery of cell-based therapies Highly experienced management and scientific team 6
Experienced executive and scientific team David J. Mazzo, PhD Chief Executive Officer 30+ years’ experience - all aspects of large and emerging global biotech, biopharma company operations, successful international drug development Robert S. Vaters, MBA President and Chief Financial Officer 25+ years’ financial and management experience in a variety of healthcare, biotechnology, biologics, medical device and pharmaceutical companies Douglas W. Losordo, MD Senior VP, Clinical, Medical and Regulatory Affairs and Chief Medical Officer Leader in cell therapy research and development; renowned cardiologist with noteworthy academic and industry credentials Hans Keirstead, PhD Senior VP, Research and Chief Science Officer Internationally known stem cell expert; CEO of California Stem cell prior to acquisition by Caladrius; Founder of Stem Cell Research Center, University of California, Irvine Robert A. Preti, PhD Senior VP, Development and Technical Operations and Chief Technology Officer; President of PCT, a Caladrius company Leading authority on cell-based therapy engineering; unique development and commercialization experience 7
Immune modulation Ischemic repair Immuno- oncology Robust and balanced pipeline Fast Track & Orphan Drug Designations with Special Protocol Assessment Granted PRECLINICAL PHASE 1 PHASE 2 PHASE 3 8 PROGRAM CLBS20: metastatic melanoma (AKA NBS20, USAN = eltrapuldencel-T) CLBS14: CHF CLBS12: CLI PRESERVE-AMI Trial Currently enrolling Seeking partner FDA-cleared protocol, seeking partner CLBS03: Type I diabetes Seeking partner Fully enrolled, ongoing follow-up
Unifying root approach across platforms Ischemic repair Immuno- oncology Immune modulation 9
Immune modulation Ischemic repair Immuno- oncology Robust and balanced pipeline Fast Track & Orphan Drug Designations with Special Protocol Assessment Granted PRECLINICAL PHASE 1 PHASE 2 PHASE 3 1 0 PROGRAM CLBS20: metastatic melanoma (AKA NBS20, USAN = eltrapuldencel-T) CLBS14: CHF CLBS12: CLI PRESERVE-AMI Trial Currently enrolling Seeking partner FDA-cleared protocol, seeking partner CLBS03: Type I diabetes Seeking partner Fully enrolled, ongoing follow-up
Immuno-oncology: Turning cancer against itself Metastatic melanoma: CLBS20 (AKA NBS20, USAN = eltrapuldencel-T) • Fast Track & Orphan Drug designations • Special Protocol Assessment • ATMP (EMA) • $17.7 million CIRM grant award 11
Stage III recurrent/stage lV metastatic melanoma 1. American Cancer Society, 2014 SEER 2. For Stage IV metastatic melanoma - AJCC Cancer Staging 2010 (based on 17 academic centers) (Five-year data for recently approved melanoma immunotherapies is not yet reflected) 3. GBI Research – 2013 PREVALENCE AND UNMET MEDICAL NEED ~20,000 estimated new cases per year in U.S.1 ~10,000 deaths per year in U.S.1 ~15% five-year survival rate2 ~$1 billion U.S. market size3 Distant metastases commonly in brain, lung, liver, small bowel, lymph nodes, bone, and cutaneous and soft tissue NUMEROUS NON-SYNONYMOUS INTER-PATIENT MUTATIONS • Unique patient-specific antigenic fingerprints • Ideal target for autologous immunotherapy 12
0 10 20 30 40 50 60 70 80 Medi an O ve ra ll Su rvi va l ( m o n th s) Lower End 95% CI median overall survival Upper End 95% CI upper CI not estimable Confidence intervals not reported CLBS20 Phase 2 data suggests superior survival ipilimumab (BMS) dacarbazine (generic) vemurafenib (Roche) pembrolizumab (Merck) nivolumab (BMS) Interleukin-2 (Prometheus) Tumor Infilt. Lymphocytes (Lion – P2) talimogene laherparepvec (Amgen) Pooled CLBS20 stage IV Pooled CLBS20 recurrent stage III Sourced from published materials 13
CLBS20: Uniquely targets cancer-initiating cells (CICs) Process times are approximate Surgical excision CIC isolation Expansion and irradiation (7-14 weeks) Incubate together and quality control (2-3 weeks) Subcutaneous injection (weekly for 3 wks and monthly for 5 mos) Leukapheresis Monocyte isolation Dendritic cell (DC) production (6 days) 14
0% 20% 40% 60% 80% Control Group Irradiated Tumor Cells Treatment Group 0% 20% 40% 60% 80% 100% 0 10 20 30 40 50 60 Pe rc en t Su rviv in g Months Phase 2: two trials; consistent, compelling data Dillman, et al. Journal Immunotherapy 2012 Historical control for distant metastases 2-YEAR OVERALL SURVIVAL 42 patient randomized P2 trial p = 0.007; Hazard ratio = 0.27 Treatment considered safe and generally well tolerated ― Minor local injection site reactions 72% 31% N=24 N=18 50% observed 5-year survival rate Treatment considered safe and generally well tolerated ― Minor local injection site reactions Dillman, et al. Cancer Biother Radiopharm 2009 Historical control: Balch J Clin Oncol 2009 N=54 5-YEAR OVERALL SURVIVAL 54 patient single arm P2 trial 2 Y ea rs 73% Treatment 10% 25% Historical control for distant metastases 50% 15
The Intus study: Phase 3 with SPA and orphan drug and fast track designations DESIGN • Randomized (2:1), double blind, placebo controlled trial • Stage III recurrent or stage IV metastatic melanoma • Single trial for registration assuming positive outcome ENDPOINT • Overall survival POWERING • 80% power to detect 37.5% reduction in risk of death RELATION TO STANDARD THERAPIES • Adjunctive • Clinical practice based trial STUDY SIZE • Planned 250 eligible patients • Approximately 50 sites (U.S., Canada, Australia, New Zealand, considering E.U.) TREATMENT • CLBS20: Autologous DC loaded with antigens from autologous CICs, in GM-CSF CONTROL • Autologous monocytes in GM-CSF 16
17 1Q 2015 Screening Initiated 4Q 2017 Interim Results after 99 Deaths 2Q 2015 First Patient Randomized 2Q 2018 Projected BLA Submission based on successful interim analysis 2Q 2019 Final Study Results 4Q 2019 Projected BLA Submission 4Q 2016 Enrollment Completed 2015 2016 2017 2018 2019 Study continues to 162 deaths Total trial cost to earliest projected BLA: ~$45 million Timeline to BLA
Potential application for multiple solid tumor types Multi-billion dollar lifecycle opportunity LUNG CANCER (Feasibility of cell lines from biopsies initiated) COLON CANCER (Feasibility of cell lines planned) OVARIAN CANCER (US FDA-cleared phase 2 protocol, cell line feasibility established) HEPATOCELLULAR CARCINOMA (LIVER) (8 HCC patients with HBV treated, no toxicity) GLIOBLASTOMA MULTIFORME (BRAIN) (Feasibility under investigation) 18 RENAL CELL CARCINOMA (KIDNEY) (9 RCC patients treated)
Immune modulation Ischemic repair Immuno- oncology Robust and balanced pipeline Fast Track & Orphan Drug Designations with Special Protocol Assessment Granted PRECLINICAL PHASE 1 PHASE 2 PHASE 3 1 9 PROGRAM CLBS20: metastatic melanoma (AKA NBS20, USAN = eltrapuldencel-T) CLBS14: CHF CLBS12: CLI PRESERVE-AMI Trial Currently enrolling Seeking partner FDA-cleared protocol, seeking partner CLBS03: Type I diabetes Seeking partner Fully enrolled, ongoing follow-up
Ischemic repair Critical Limb Ischemia: CLBS12 Chronic Heart Failure: CLBS14 20
Ischemic repair: Leveraging the body’s natural repair mechanism to develop new blood vessels CD34/CXCR4 from peripheral blood • Ischemic events – caused by restriction of blood to tissue, e.g., stroke, acute myocardial infarction and claudication • Results of ischemia include chronic heart failure, critical limb ischemia and more • CD34+ cells have been shown to induce the development of new blood vessels, preventing tissue death by improving blood flow Critical limb ischemia 21 CD34 cell therapy promoting angiogenesis CD34/CXCR4 Post acute myocardial infarction CD34/CXCR4 from bone marrow
PreSERVE study: enrolled Phase 2 study in follow-up 22 DESIGN • Randomized (1:1), Phase 2, double blind, placebo controlled trial • Post-AMI (STEMI) patients PRIMARY ENDPOINTS AND KEY SECONDARY ENDPOINT • Change in cardiac perfusion from baseline to 6 months (exploratory endpoint) • Incidence rates of Serious Adverse Events (SAEs) and Major Adverse Cardiac Events (MACE) (FDA guidance-driven endpoint) • LVEF change from baseline to 6 months (FDA guidance-driven endpoint) KEY INCLUSION CRITERIA • Confirmation of ST Elevation MI • Ejection fraction < 48% at day 4 by CMR • State-of-the-art care post stenting STUDY SIZE • 161 patients, 60 centers in United States TREATMENT • Single dose via infarct related artery with minimum dose ≥10M (million) ±20% CD34+ cells. • Actual dose determined by intrinsic number of cells in marrow and processing success rate CONTROL • Placebo infusion
PreSERVE interim conclusions emphasize cell dose-dependent trends* CD34 cell dose-dependent trend in reduction of MACE — Signal for a mortality benefit (12 month data) Signal for reduction in frequency of SAEs in higher dose groups (12 month data) CD34 cell dose-dependent trend in improvement of left ventricular ejection fraction and reduction in infarct size No correlation between exploratory endpoint of perfusion and treatment Favorable trends in clinical events encourage continued development for platform *Based on data collected at 6 months except where noted 23
Significant Unmet Need for CLI and CHF NO-OPTION CRITICAL LIMB ISCHEMIA • If options for surgical or endovascular therapies are exhausted, patients only receive pain management, wound care or amputation • Even with surgical options over 50% lead to amputation or death within one year1 • Prevalence (Japan): 21K CLI no-option patients2 • Incidence (Japan): ~2K – 8K per year3 24 CHRONIC HEART FAILURE • Heart failure is the only major cardiovascular disorder still on the rise with incidence of CHF doubling with each decade of life • Most Class III patients are hospitalized two to three times per year4 • Prevalence (U.S.): 5M heart failure patients5 • Incidence (U.S.): ~550K per year5 1. TASC II Guidelines, Huron Primary Research (Sept-Oct/2014); 2. ; 3. Source: Nihon GekaGakkaiZasshi. 2007 Jul;108(4):171-5, Am FamPhysician. 1999 Apr 1;59(7):1899-1908; TASC II Guidelines, Huron Primary Research (Sept-Oct/2014); 4. ; 5;
25 CLBS12 CLI Japan Program Update Objective: file J-IND approval and consummate partnership to allow for clinical study execution Could take advantage of new Japanese regulatory path to early conditional approval Clinical background: Previous studies of autologous CD34+ cells in no-option CLI patients in Japan and U.S. (combined total, N=56) • Conclusions from 2 previous studies in Japan: • Study 1: CD34 cell injection was safe and led to improvement in all clinical parameters • Study 2: CD34 cell injection was safe and led to improvement in CLI-free status as well as other clinical parameters • Conclusion from previous study in U.S.: • CD34 cell injection was safe and led to improved amputation free survival Study 1: Kawamoto A et al. Stem Cells 2009; Study 2: Fujita Y et al. Circ J 2014; Study 3: Losordo et al. Circ Cardiovasc Interv 2012.
Phase 2 study in Japan, targeting conditional approval Study designed in consultation with PMDA 26 DESCRIPTION • Prospective, open label controlled, randomized, multicenter study in patients with no-option CLI DOSAGE • Up to 106 autologous G-CSF-mobilized peripheral blood-derived CD34+ cells/kg per affected limb STUDY SIZE • 35 subjects PRIMARY ENDPOINT • Time to continuous CLI free status DOSAGE FORM • Solution/suspension; injectable DOSAGE FREQUENCY • Once MODE OF ADMINISTRATION • Intramuscular CONTROL/COMPARATOR • SOC pharmacotherapy with drugs approved in Japan (e.g., antiplatelets, anticoagulants, and vasodilators) • The choice of pharmacotherapy will be made by the investigators
Potential application across several indications Multi-billion dollar lifecycle opportunity STROKE CLAUDICATION 27 N-STEMI REFRACTORY ANGINA SYNDROME X Platform supported by independent preclinical and early clinical data, as well as positive suggestion of safety and therapeutic activity seen to date in the PreSERVE-AMI trial
Immune modulation Ischemic repair Immuno- oncology Robust and balanced pipeline Fast Track & Orphan Drug Designations with Special Protocol Assessment Granted PRECLINICAL PHASE 1 PHASE 2 PHASE 3 2 8 PROGRAM CLBS20: metastatic melanoma (AKA NBS20, USAN = eltrapuldencel-T) CLBS14: CHF CLBS12: CLI PRESERVE-AMI Trial Currently enrolling Seeking partner FDA-cleared protocol, seeking partner CLBS03: Type I diabetes Seeking partner Fully enrolled, ongoing follow-up
Immune Modulation Diabetes Mellitus Type-1 (T1D): CLBS03 29
30 T Regulatory Cells (Tregs) : restoring immune balance and function NORMAL IMMUNE SYSTEM: IMMUNE BALANCE INFUSION of TREGs BALANCE REGAINED AUTOIMMUNITY: IMMUNE IMBALANCE T regulatory cells T effector cells Natural polyclonal T regulatory cells SIMPLE PROCESS WITH PROTECTED INTELLECTUAL PROPERTY
Diabetes Mellitus Type-1 (T1D): an autoimmune disease 1. Hamman RF, et al. Diabetes Care. 2014; Sosenko JM, et al. Diabetes Care. 2008; Palmer JP. Diabetes/metabolism research and reviews. 2009 2. The DIAMOND Project Group. Diabetic Medicine. 2006;23:857-866. PREVALENCE AND UNMET MEDICAL NEED • 18,000 children under 20 in U.S. with new onset T1D per year1 • 3% annual growth rate worldwide2 • No curative treatments for T1D, only lifelong insulin therapy • Diabetes is leading cause of: • kidney failure • new cases of adult blindness • non-traumatic lower-limb amputations Beta Cells T Regulatory Cell T Effector Cell- Mediated Killing of Beta Cells T Effector Cell T Regulatory Cell Defense of Beta Cells 31
Treg cell therapy appears durable in humans1 1. Gitelman et al, American Diabetes Association Abstract, 2014 2. Dr. Jeffrey Bluestone Lab PI Jeffrey Bluestone, PhD, of UCSF – leader in field of Tregs DESIGN U.S. UCSF/Yale open label Phase 1 study, 4-dose escalation cohorts PATIENTS 14 adult patients with established T1D RESULTS • Preliminary data indicates safety and tolerability • Established manufacturing feasibility • Implied sustainability of effect • Infused Tregs were stable and detected in peripheral circulation for 1 year2 % of ad m inis te re d T re g s (i so tope la b eled) out of to tal T re g p op u lat io n Days Post Infusion Each Line Corresponds to an Individual Subject 180 90 0 14 28 365 Administered Treg persistence2 32
0 0.2 0.4 0.6 0.8 1 1.2 Day O Month 4 One Year 0% 20% 40% 60% 80% 100% Control Group Treatment Group Treg cell therapy preserves beta cell function in children1 33 Marek-Trzonkowska, N t al. Clinical Immunology 2014 1. Children aged 5-18 administered 1 (10 or 20 mil cells/kg) or 2 doses (total 30 mil cells/kg) of Tregs REMISSION RATE AT 12 MONTHS FASTING C-PEPTIDE LEVELS C -p e p tide ( n g /m l) 67% 20% Mean Treatment Mean Control Complete insulin independence Remission No Remission N=12 N=10
The Trutina study: Phase 2 in adolescents with T1D1 34 DESIGN • Double blind, placebo controlled, randomized (1:1:1) • Adolescent patients with recent onset T1D ages 12 to 18 PRIMARY ENDPOINT • Preservation of C-peptide at 52 weeks in comparison to placebo POWERING • 80% power to detect 50% attenuation in fasting c-peptide levels STUDY SIZE • 18 patient cohort with early interim safety analysis, total of 111 patients to be enrolled • ~11 U.S. sites TREATMENT • CLBS03: Dose cohorts of 10 or 20 million cells/kg CONTROL • Placebo infusion 1. Study cleared by FDA to proceed based on efficacy data in children establishing prospect of direct benefit
Trutina study: Efficient asset de-risking study design 35 18 51 Initial 18 patients evaluated for safety through 3-6 months (~$3 million cost to these results) PATIENT ENROLLMENT Interim blinded analysis when ~50% of subjects complete 12-month follow up Expected cost of trial: ~$22.5 million 111
Potential application across multiple autoimmune and allergic diseases Multi-billion dollar lifecycle opportunity 36 STEROID RESISTANT ASTHMA MULTIPLE SCLEROSIS (MS) CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INFLAMMATORY BOWEL DISEASE GRAFT VS. HOST DISEASE RHEUMATOID ARTHRITIS LUPUS
Investment summary Lead immuno-oncology program (Phase 3 study in metastatic melanoma) with Fast Track and Orphan Drug designations and a SPA Additional platforms for autoimmune disorders (FDA-cleared Phase 2 study in adolescents with type I diabetes) and multiple cardiovascular indications Internal center of excellence (PCT) with bicoastal facilities and proven capabilities innovating discovery, development, manufacturing and delivery of cell-based therapies Highly experienced management and scientific team 37
Delivering Personalized Medicine NASDAQ: CLBS Contact: Eric Powers, Manager of Communications & Marketing Phone: 212.584.4173 Email: epowers@caladrius.com Web: www.caladrius.com