JDRF RESEARCH UPDATE Daniel Finan, Ph.D. Research Director March 10, 2018
PRESENTER Daniel Finan Biomedical engineer B.S. Chemical Engineering University of Colorado, 2003 Ph.D. Chemical Engineering UC Santa Barbara, 2008 10+ years in T1D research Algorithms for Artificial Pancreas (AP) applications New to JDRF Started in September 2017 Focus on AP, Metabolic Control (MC) The Plan for a World without T1D 1
STATE OF T1D CARE 2
STATE OF T1D CARE Technology of the Past 3
Percentage of people not meeting target HbA1c levels Percentage of people reporting one or more events in prior 3 months STATE OF T1D CARE We Aren t There Yet Most people with T1D do not reach blood-glucose control targets Life-threatening complications levels (like severe hypoglycemia and diabetic ketoacidosis [DKA]) are much too common 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 77% 78% 83% 86% 70% 71% 9% 8% 7% 6% 5% 4% 3% 2% 1% Severe hypoglycemia 6% 5% 4% 4% 3% 2% DKA 6% 5% 8% 8% 2% 1% 0% 2-5 6-12 13-17 18-25 26-49 50+ Age (years) 0% 2-5 6-12 13-17 18-25 26-49 50+ Age (years) Diabetes Care 38 (6), 971-978 (2015) 4
OUR PLAN AND IMPACT 5
OUR PLAN Our Vision and Mission OUR VISION A world without type 1 diabetes OUR MISSION Accelerating life-changing breakthroughs to cure, prevent and treat type 1 diabetes and its complications 6
JDRF RESEARCH PORTFOLIO Our Clinical Goals CURE PREVENT TREAT Restore normal glucose control Prevent long-term complications Prevent autoimmune attack so people never develop T1D Preserve beta cell function and prevent insulin dependence in early-stage T1D Improve glucose control Simplify T1D management Decrease daily burden of T1D Prevent long-term complications 7
JDRF RESEARCH PROGRAMS 8
JDRF RESEARCH Advancing Multiple Program Areas ARTIFICIAL PANCREAS METABOLIC CONTROL COMPLICATIONS BETA CELL REPLACEMENT REGENERATION AND IMMUNE THERAPIES PREVENTION 9
JDRF RESEARCH Advancing Multiple Program Areas PREVENTION METABOLIC CONTROL REGENERATION/ IMMUNE ARTIFICIAL PANCREAS BETA CELL REPLACEMENT Time Adapted from Eisenbarth 10
Prevention Prevent or delay insulin dependence Multiple potential prevention strategies are in clinical testing for T1D, including the use of oral insulin to delay onset of T1D in people at high risk, and various others are at earlier stages of development. 11
PREVENTION Screening can Identify People at Risk 12
Restoration REGENERATION Promote survival and/or regrowth of the body s own beta cells JDRF-funded studies are making significant progress toward developing novel drugs and identifying existing drugs that may be effective in enhancing beta cell survival and regeneration. 13
Restoration IMMUNE Prevention THERAPIES Prevent or stop the immune system attack on insulin-producing beta cells in the pancreas Multiple potential immune therapies are undergoing clinical testing in T1D. JDRF is also supporting earlier-stage development of promising new and next-generation approaches. 14
Beta Cell Replacement Deliver insulin independence without broad immune suppression JDRF-funded researchers demonstrated that transplantation of donor islets could temporarily reverse disease in people with T1D, and this procedure is approved and reimbursed outside the US in people with T1D who have serious hypoglycemia unawareness. 15
BETA CELL REPLACEMENT Cell Replacement is Effective in T1D BG before islet transplant BG after islet transplant...but is not currently available to everyone Limitations: Relies on donor islets which are too scarce Requires broad immune suppression which has unwanted effects JDRF strategies to overcome: Unlimited sources of insulin-producing cells Delivery systems that keep cells alive and functional without broad immune suppression Ali Naji, University of Pennsylvania 16
Complications Preserve kidney function and eyesight through early intervention JDRF is leading the effort to identify biomarkers measurable signs of biological processes of early-stage T1D to enable both the development of early intervention therapies and better designed clinical trials. 17
Metabolic Control Improve glycemic control and restore the body s overall biochemical balance without increasing disease burden 18
GLUCOSE CONTROL Glucose-Responsive Insulins Glucose-responsive insulins will circulate through the bloodstream, turning on when they are needed and turning off when they are not GLUCOSE INSULIN Blood-glucose levels: low Insulin: inactive Blood-glucose levels: high Insulin: active Active insulin can unlock the cells of the body This allows glucose to enter and be used as fuel PREVENT HIGHS AND LOWS SIGNIFICANTLY REDUCE BURDEN 19
Artificial Pancreas Enable more effective and improved glucose control with significantly less burden 20
ARTIFICIAL PANCREAS A Decade of Progress in AP Systems FULL AUTOMATION 21
ARTIFICIAL PANCREAS Many Reasons to Celebrate First hybrid closed-loop system approved More AP systems are coming These systems improve outcomes Hemoglobin A1c Hypoglycemia Quality of life Benefits of expanded use of technology in special populations Coverage for continuous glucose monitors (CGMs) is expanding First CGM approved for making decisions about insulin dosing I am thinking about diabetes 50% less of the time, which enables me to focus on what I want to do in life. Kady Helme AP Trial Participant 22
ARTIFICIAL PANCREAS Three Goals for AP Systems 23
ARTIFICIAL PANCREAS Enhancing Glucose Control Additional inputs Faster insulins & other drugs Advanced algorithms 24
ARTIFICIAL PANCREAS Reducing Burden Advanced infusion sets Extended wear Integrated CGM Increased automation Miniaturization 25
ARTIFICIAL PANCREAS Expanding Access and Adoption Targeted subpopulations Barriers to adoption Open-protocol AP systems 26
Medtronic 670G World s 1 st Hybrid Closed Loop AP System Indications for 14+ years old Contra-indication: <7 year old, or <8 units of insulin/day Hybrid closed loop = automated basal rates Still need to bolus for meals Take care with intense exercise, corrections for stress response, etc. Uses new Guardian CGM (AKA Enlite 3), 7 days use, 2 cals/day BG target is fixed at 120 or 150 mg/dl Does not include any Share type ability Soft launching Spring 2017, full launch May- October in US Pricing expected to comparable to 630G ($7-8,000)
670G Pivotal Trial Data 3 months Open-loop Closed-loop
AP Systems in Development: Current Status 2016 2017 2018 2019 Medtronic (Hybrid) Pivotal U.S. Launch Tandem (PLGS) Pivotal Insulet (Hybrid) Pre-Pivotal Pivotal Bigfoot (Hybrid) Pre-Pivotal Pivotal Beta Bionics (Hybrid) Bridge Pivotal
Current/Near-Future Research Priorities Develop user-centric innovations Incorporate additional signals/inputs into AP algorithms/systems Push beyond rapid-acting SC-only systems New insulins, e.g., fiasp Adjunct drugs, e.g., pramlintide Alternate delivery routes, e.g., intraperitoneal Explore the feasibility of open-protocol systems Other priorities Continue to encourage development of new CGM systems and insulin pumps Technology, cost, size Develop extended-wear infusion sets Insulin co-formulations Ultra-concentrated insulins
User-Centric Innovations Miniaturized integrated single-port patch AP System Electroosmotic pumping technology Safety valves and flow sensor Smartphone interface and cloud connectivity Designed for manufacturability Existing patch pump approaching launch Miniaturized integrated dual-port patch AP System Electroosmotic pumping technology MEMS-based check valves BLE connectivity for handheld controller Miniaturized, flexible, bandage-like patch pump Electrolysis-based pumping technology Safety valves and flow sensor BLE connectivity and Android App interface Designed for manufacturability
Additional Signals Goal Enable more robust glucose control under a wider range of conditions Exercise Physiological stress Environmental conditions Enable a reduction in user interaction and/or more user-friendly interaction
Beyond Rapid-Acting SC-Only Systems: Insulin + Pramlintide Goals Deliver pramlintide (with insulin) to slow gastric emptying, helping to enable fully automated control Reduce (or hopefully eliminate) need to inform controller of meals Insulin only Insulin + pramlintide Source: Sherr et al. Diabetes Care. 2016.
Beyond Rapid-Acting SC-Only Systems: Intraperitoneal Delivery Goals Enable physiological PK/PD more conducive to achieving robust glucose control (without hypos) Reduce frequencies of consumables refills/replacements Lower on-body burden by eliminating need to delivery insulin SC Source: Dassau et al. Diabetes Obes Metab. 2017.
Open-Protocol Systems VISION Accelerate the delivery to market of systems that use openly published, well-known, secure data protocols (like Bluetooth LE) to facilitate communication with, and control of, CGMs and insulin pumps by third-party cell phone-based apps or other devices Enable interoperability of diabetes devices Harness innovation of the doit-yourself (DIY) community
Open-Protocol Systems: A Three-Pronged Initiative Technical Aspects Technical solutions are available and well-understood Request for proposals (RFP) hopes to address some of these issues Regulatory Pathway FDA is involved and has been working on interoperability of devices Liability Community must work together to determine solution ensuring transparency and fairness We are not in this alone! We will enlist the FDA, the DIY community, leadership of device manufacturers, and legal counsel to understand how this dream can become a reality.
Open-Protocol Systems: In the News The initiative has been received positively by the community, garnering attention from various news outlets and DIY/#WeAreNotWaiting websites.
JDRF Partnerships in Artificial Pancreas R&D
GET INVOLVED! 39
GET INVOLVED! Participate in a Clinical Trial Participating in a clinical trial is a great way to contribute to research You can do your part by volunteering Use JDRF s Clinical Trials Connection (CTC) tool to find trials that need volunteers Visit jdrf.org/ctc 40
GET INVOLVED! Network for Pancreatic Organ Donors with Diabetes (npod) Provides pancreatic tissues from donors for use in research New insights into the causes, onset and progression of T1D New avenues for investigation You can help! Become an organ donor organdonor.gov Sign an npod Organ Donor Card www.jdrfnpod.org 41
THANK YOU! 42
Gaps Outcomes Glucose control is still suboptimal. Rapid-acting SC insulin (only) different/better insulins/drugs/delivery routes CGM (only) additional signals Burden Current AP systems carry a significant burden for the user. Interactions with medical devices app-based device interactions Constant maintenance longer-lasting components Bulky devices miniaturized devices Frequent decision-making infrequent/no decision-making Access and Adoption Certain subpopulations still do not have access to these systems, e.g., the very young, seniors, pregnant women. Moreover, adoptions remains relatively low in those who do have access. Current access expanded access through specialized clinical studies Current adoption increased adoption through innovation, lower costs, enhanced demonstration of improved outcomes