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Pioneering Medicine to Preserve Kidney Health
John B Wirthlin.Founder/Chief Operating Officer
November, 2014
© AlloCure 2014615 Arapeen Dr. Salt Lake City, Utah 84108 Phone (801) 583 8450
The Problem: Acute Kidney Injury (AKI)
• AKI occurs in the hospital, often in but not limited to, the intensive care unit setting
• Characterized by a rapid decline in kidney function, most often in patients with acute insults on top of underlying co-morbidities
• Risk factors include CKD, hypertension, diabetes and age
• There is no approved therapeutic solution other than patient support
3
Common Contributors to AKI CABG and valve replacement surgery with
cardiopulmonary bypass as well as complex surgical procedures in numerous clinical settings
Contrast imaging agents and nephrotoxic drugs
Sepsis and hypotension
Consequences
Extended ICU and hospital stay
Increased need for short and often long term dialysis
Progression of CKD, including ESRD
Treatment of AKI is a Critical Unmet Medical Need
4
Lewington et al Raising awareness of acute kidney injury: a global perspective of a silent killer Kidney International. 2013 84, 457-467
Unfortunately, Single Metabolic Pathway Interdictions in AKI Have Been Unsuccessful
• Natriuretic peptides
• N-acetylcysteine
• Low dose dopamine
• IGF-1
• rHuEPO
5
The AlloCure Solution: AC607 Bone Marrow Derived Mesenchymal Stem Cells
SDF-1
VEGF, HGF,IGF, PGE2
Humphreys and Bonventre. Ann. Rev. Med. 2008. 59:325–39
• AC607 transiently resides in the injured kidney and delivers VEGF, HGF, IGF, PGE2 and other mediators that treat AKI via multiple processes (local, transient, poly-pharmacy effect):
Anti-apoptotic Mitogenic Anti-inflammatory Angiogenic
• AC607 does not divide and repopulate the injured kidney
• Immune privileged- no donor matching
6
AC607 Phase 1 Trial in Cardiac Surgery Completed
• 16 subjects scheduled for elective CABG and/or valve replacement and at high risk for AKI
• Following surgery, AC607 administered via catheter into the suprarenal aorta
• Primary endpoint was safety; additional endpoints evaluating kidney function including assessment of AKI and post operative course 3 year follow up complete; AC607 was safe and well tolerated No SAEs related to study drug
• Historical control data were examined to enable a preliminary assessment of efficacy
7
Incidence of AKI, Hospital Readmission Rates and Length of Stay Lower in AC607 Subjects Vs. Historical Controls*
8
RIFLE (%) AKIN (%) Readmission Rate (%) Hospital Length of Stay (Days)
0
5
10
15
20
25
30
Phase 1 Subjects (n=16) Matched Controls (n=64)
*matched for age, risk factors, surgical characteristics
Doty et al., Abstract. Am Soc Neph Kidney Week, 2011. Phil, PA.
AlloCure Developed a Robust Manufacturing Process for AC607
9
MSC Isolation
Multiple Cell
Factories
MSC Expansion MSC Harvest & Vialing
MediaMedia Cell Factory
Healthy Donor Bone
Marrow
Healthy Donor Bone
Marrow
Cell Factory
Culture
Multiple Cell
Factories
ExpansionConcentrate & Wash
Fill & FinishAC607 Doses
MasterCell Bank
AC607Production
• Closed system for culturing and downstream processing • Free of animal derived raw materials• Fully compliant and tested in accordance FDA guidelines
AC607 Proof of Concept Phase 2 Trial: ACT-AKI
Design Parameters
Design Randomized, double-blind, multi-center, placebo-controlled, two arm study
Sample Size N = 200
Primary Endpoint Time to kidney recovery
Secondary Endpoints Composite of incidence of dialysis and mortality, safety
Exploratory Endpoints Length of stay (ICU and hospital), hospital readmission rates, short and long term measures of kidney function
AC607
n = 100
Placebo
3 Month Evaluation Period Long Term Follow-up
n = 100
⁄ ⁄
⁄ ⁄
Study Population: Subjects undergoing CABG and/or valve
surgery with a 0.5 mg/dL rise in SCr within 48 hours
of surgery
10
11
ACT-AKI Phase 2 Trial Update
• AlloCure recently completed the data analysis from its phase 2 trial
• The clinical data was not strong enough to justify further clinical development of AC607
• Final clinical results will be presented at the American Society of Nephrology next week
12
AlloCure Accomplishments
• Raised $45MM from top tier VCs and corporate partners
• Approval of the first IND using stem cells to treat AKI
• Awarded Fast Track designation by the FDA
• Conducted one of the largest trials in AKI
• Advanced the science of stem cells
• Developed a next generation robust manufacturing process
• Contributed to the clinical knowledge of AKI
13
Lessons Learned
• Attracting Capital
• Capital Efficient Organization
• Agile Clinical Development
14
Attracting Capital
• Approached investors who had experience with stem cells
• Specifically tailored the message
• Show progress in hitting milestones during the funding negotiation
• Tranching
15
Capital Efficient Organization: Keep it Lean
•Employees• Hire individuals who can do more than one job function• High emotional intelligence
• Outsource high cost functions: • Human Resources• Accounting • IT• Clinical operations• Manufacturing
16
Agile Clinical Development
• Early and rapid response to change• High functioning executive team
• Creative problem solving • Clear communication • Trustful execution
• Develop a culture of excellence• Work environment that is exciting, challenging and fun • Employees who are dedicated to reaching the goal • Commitment to “do whatever it takes”