The Science, Policy, and Potential of Cell and Gene Therapies

December 4, 2019

Public Briefing

Cell and gene therapies are a promising frontier in biomedical innovation that have the potential to cure deadly and debilitating diseases. Over the past two years, several breakthrough therapies that treat cancers and genetic diseases have been approved by the FDA. Today there are more than 300 cell and gene therapies in development. While proliferation of these treatments may transform clinical outcomes, their high up-front costs and unique composition will likely challenge existing regulatory, financing, and delivery paradigms. During this briefing, panelists discussed factors policymakers must consider in order to support access to safe, effective, and affordable cell and gene therapies.


Rena Conti, Ph.D., Associate Research Director of Biopharma and Public Policy, Boston University Institute for Health System Innovation and Policy

John Glasspool, Senior Advisor, MIT Center for Biomedical Innovation: NEWDIGS, Financing and Reimbursement of Cures in the US (FoCUS) Project

Joanne Kurtzberg, M.D., Director of the Marcus Center for Cellular Cures (MC3), Duke University School of Medicine

Gillian Woollett, D.Phil., M.A., Vice President, Avalere Health

Sarah J. Dash, MPH, President and CEO, Alliance for Health Policy (moderator)



12:00 p.m. – 12:10 p.m.        Welcome and Introductions

Sarah J. Dash, MPH

President and Chief Executive Officer, Alliance for Health Policy, @AllHealthPolicy

Jocelyn Ulrich, MPH

Deputy Vice President of Policy and Research, Pharmaceutical Research and Manufacturers of America, @PhRMA


12:10 p.m. – 12:50 p.m.        Panelist Opening Remarks

Gillian Woollett, D.Phil., M.A.

Principal Research Scientist, Avalere Health, @avalerehealth

Joanne Kurtzberg, M.D.

Director, Marcus Center for Cellular Cures (MC3), Duke University School of Medicine

John Glasspool

Senior Advisor, MIT Center for Biomedical Innovation: NEWDIGS, Financing and Reimbursement of Cures in the US (FoCUS) Project

Rena Conti, Ph.D.

Associate Research Director, Biopharma and Public Policy, Institute for Health System Innovation and Policy, Boston University, @contirena1


12:50 p.m. – 1:30 p.m.          Question and Answer Session

Event Resources

Event Resources

Key Resources (listed chronologically, beginning with the most recent)

“Payer Perspectives on Financing and Reimbursement of One-Time High-Cost Durable Treatments.” MIT NEWDIGS FoCUS Project. October 11, 2019. Available at

“Gene Therapy in 2019: Milestones and Challenges.” Patient-Centered Outcomes Research Institute. July 2019. Available at

“Rebalancing High Prescription Drug Prices with Innovation Incentives.” Conti, R. and David, S. Health Affairs Blog. July 1, 2019. Available at

“MIT Group Brings Together Stakeholders to Brainstorm How to Pay for Curative Therapies Over Time.” Caffrey, M. American Journal of Managed Care. June 18, 2019. Available at

“Projections from the Existing Pipeline of Cell and Gene Therapies: Launches and Patient Numbers.” MIT NEWDIGS FoCUS Project. October 29, 2018. Available at

“Paying for Therapies That Cure: Innovative Solutions Needed.” Dubois, R. STAT. July 25, 2018. Available at

“FDA Prepares for the Next Generation of Regenerative Medicines.” Woollett, G. Avalere. December 14, 2017. Available at

Additional Resources (listed chronologically, beginning with the most recent)

“Making Life Saving Treatments More Affordable.” Jena, A., Kee, A., Baumgardner, J. et al. Harvard Business Review. October 25, 2019. Available at

“FDA’s Framework for Regulating Regenerative Medicine Will Improve Oversight.” Richardson, L. Pew Charitable Trusts. October 17, 2019. Available at

“Gene Therapies’ Accessibility Problem.” Owens, C. Axios. October 2, 2019. Available at

“Our Take: How Insurers are Scrambling to Cover Multimillion-Dollar Gene Therapies.” The Daily Briefing. Advisory Board. September 9, 2019. Available at

“Breakthrough Therapies, Breakthrough Economics in the Era of Cure.” Farnia, S., Mostovoy, L., Flamm, C. et. al. Cell and Gene Therapy Insights. September 4, 2019. Available at

“Putting the Costs and Benefits of New Gene Therapies into Perspective.” Cohen, J., Chambers, J., Silver, M. et al. Health Affairs Blog. September 4, 2019. Available at

“Beyond the Hype: Gene Therapies Require Advanced Capabilities to Succeed After Approval.” PwC Health Research Institute. September 2019. Available at

“State Medicaid Programs Already Have Considerable Flexibility to Adopt Innovative Payment Models for New High-Cost Prescription Drugs.” Edwin, P. Georgetown University Health Policy Institute Center for Children and Families. July 9, 2019. Available at

“Transforming Next-Gen Therapy Supply Chains into Patient-Connected Value Chains.” Srivastava, S., Pernenkil, L., and Mooraj, H. Cell & Gene. June 20, 2019. Available at

“How Will We Pay for the Coming Generation of Potentially Curative Gene Therapies?” Cassidy, B. STAT. June 12, 2019. Available at

“The Death of Jesse Gelsinger, 20 Years Later.” Rinde, M. Science History Institute. June 4, 2019. Available at

“Estimating the Clinical Pipeline of Cell and Gene Therapies and Their Potential Economic Impact on the US Healthcare System.” Quinn, C., Young, C., Thomas, J., et. al. Value in Health.  June 2019. Available at

“Extending VBP Models into Medicaid Drug Purchasing: Challenges and Opportunities.” Dworkowitz, A., Fiori, A. and Bachrach, D. Health Affairs Blog. May 22, 2019. Available at

“Commentary: We Need to Make Sure New Drug Cures Don’t Widen Income Gap for Poor.” Gottlieb, S. CNBC. May 20, 2019. Available at

“CAR-T Payment Challenges Are Only Beginning.” Owens, C. Axios. April 29, 2019. Available at

“Hospitals Are Saving Lives with CAR-T. Getting Paid is Another Story.” Swetlitz, I. STAT. March 12, 2019. Available at

“The Future of Pharmaceuticals in Medicaid.” Dworkowitz, A., Fiori, A., and Robinson, S. Manatt, Phelps & Phillips, LLP. January 23, 2019. Available at

“A New Report Shows Nearly 300 Cell and Gene Therapies in Development.” Powaleny, A. The Catalyst. Pharmaceutical Research and Manufacturers of America. December 6, 2018. Available at

“Affording Miracles: As Biotech Victories in Gene Therapy Excite, Costs Spur Question for New Ways to Pay.” Knox, R. 90.9 WBUR. June 7, 2018. Available at

“Mass Health Leads the Way Towards Addressing Cell and Gene Therapy Reimbursement.” Barker, T. Medicaid and the Law. Foley Hoag LLP. February 3, 2018. Available at

“Advancing Gene Therapies and Curative Health Care Through Value-Based Payment Reform.” Daniel, G., Leschly, N., Marrazzo, J., et al. Health Affairs Blog. October 30, 2017. Available at

“Does the Hype Exceed Reality for Precision Medicine?” Knowledge@Wharton. University of Pennsylvania. April 27, 2017. Available at



Rena Conti Boston University Institute for Health System Innovation and Policy, Associate Research Director of Biopharma and Public Policy

R. John Glasspool MIT Center for Biomedical Innovation: NEWDIGS, Financing and Reimbursement of Cures in the US (FoCUS) Project, Senior Advisor; Anthos Therapeutics, CEO

Joanne Kurtzberg Duke University School of Medicine, Director of the Marcus Center for Cellular Cures (MC3)

Gillian Woollett Avalere Health, Principal Research Scientist


Experts and Analysts

Peter Bach Memorial Sloan Kettering Cancer Center, Director of the Center for Health Policy and Outcomes

Thomas Barker Foley Hoag, LLP, Partner and Co-Chair of Healthcare Practice

Justin Bekelman Penn Center for Cancer Care Innovation at the Abramson Cancer Center, Director; University of Pennsylvania Perelman School of Medicine, Associate Professor

Robert W. Dubois National Pharmaceutical Council, Chief Science Officer & Executive Vice President

Lisa Bo Feng Cystic Fibrosis Foundation, Senior Director of Policy and Advocacy

Jennifer Bright Momentum Health Strategies, Executive Director of Innovation and Value Initiative

Sarah Emond Institute for Clinical and Economic Review, Executive Vice President and Chief Operating Officer

Andrew Hu Patient-Centered Outcomes Research Institute, Director of Policy and Government Relations

Karen Katz MIT Center for Biomedical Innovation: NEWDIGS, Financing and Reimbursement of Cures in the US (FoCUS) Project, Director

Eleanor M. Perfetto National Health Council, Executive Vice President of Strategic Initiatives

Morgan Romine Duke Margolis Center for Health Policy, Policy Fellow for Strategic Engagement

Jeremy Sharp Waxman Strategies, Senior Vice President

Zachary Zalewski Avalere Health, Consultant





Anna Abram FDA, Deputy Commissioner for Policy, Planning, Legislation and Analysis

John Coster CMS, Director of Division of Pharmacy at Center for Medicaid and Chip Services

Molly Morein Medicare Payment Advisory Commission, Special Assistant

Matt Salo National Association of Medicaid Directors, Executive Director

Anne Schwartz Medicaid and CHIP Payment and Access Commission, Executive Director

Elad Sharon National Institutes of Health, Senior Investigator in the Investigational Drug Branch of the National Cancer Institute



Jeremy Allen Spark Therapeutics, Inc., Head of Government Affairs

Holly Campbell Pharmaceutical Research and Manufacturers of America, Deputy Vice President of Public Affairs

Erin Darling Merck, Associate Vice President of Federal Policy and Government Relations

Shari Erickson American College of Physicians, Vice President of Government Affairs

Betsy Foss-Campbell American Society of Gene and Cell Therapy, Director of Policy and Advocacy

Janet Lambert Alliance for Regenerative Medicine, CEO

Lisa Mostovoy Blue Cross Blue Shield Association, Executive Director of Clinical Pharmacy Services

Murray Ross Kaiser Permanente, Government Relations & Institute for Health Policy

Heidi Rosvold-Brenholtz Healthy Women, Senior Vice President for Strategic Engagement of Policy and Science

Mark Skinner Institute for Policy Advancement Ltd., President & CEO; Former Head of the National Hemophilia Foundation

Gretchen C. Wartman National Minority Quality Forum, Vice President for Policy and Program

Steven Wojcik National Business Group on Health, Vice President of Public Policy



(This is an unedited transcript. For accurate quotes and presentations, please refer to the full-event video.) SARAH DASH:  All right, good afternoon everybody.  Can everybody hear me?  Thank you so much for joining us today for the final event of the Alliance for Health Policy’s 2019 Solving For Health Signature Series, about navigating the frontiers of innovation and value.  I’m Sarah Dash and I’m President and CEO of the Alliance and very pleased to be joined by two Alliance board members today.  John Rother and , thank you for joining us today.   The Alliance is a non-partisan organization dedicated to advancing knowledge and understanding of health policy.  Our Signature Series began almost six months ago with a thought leader discussion that brought together policy experts, providers, advocates, and industry leaders, to reflect on what is most exciting, ground breaking, and challenging for healthcare innovation and value transformation.  Last month we hosted a summit.  Based on what we learned from that discussion, the summit featured sessions about the value of the patient voice, addressing biases and blind spots in the quest for innovation, the intersection of innovation and value, and future policy considerations.   Today’s briefing will explore the science policy and potential of cell and gene therapies.  And I can think of nothing more pertinent to our series on innovation and value than the exciting opportunities and challenges posed by the emergence of these therapies.  In some ways this briefing comes full circle for me as a science student 20 years ago.  We were only beginning to talk about some of the therapies that are on the horizon today, and today we have not just nationally, but really internationally recognized experts who are going to help us better understand the interdependence of these therapies not just on the innovator, science, manufacturers, but also the doctors and nurses who administer the therapies, the hospitals, the payment, and payer systems and there’s probably no other issue in front of us today that really puts quite as fine a point on these — the intersectionality of our healthcare system than we’re about to talk about today.   So in line with our mission to present a 360 degree view of today’s health policy issues, the Alliance is proud for this series to be supported by organizations that represent many facets of the healthcare system.  And you have some of them listed in your packet today.  I would particularly like to thank today our visionary sponsor, Pharma, and our innovator sponsors, Anthem and Ascension, along with a multiple of other supporters from across the spectrum.   So before we get started with the panel and I’ll introduce our panelists in a moment, but I would like to invite Jocelyn Ulrich, who’s Deputy Vice President of Policy and Research at Pharma, to make a few opening remarks.  Thanks, Jocelyn.   JOCELYN ULRICH:  Thank you, Sarah.  And thank you to the Alliance for having me today.   So cell and gene therapies are at the forefront of today’s cutting edge technology and they are truly amazing.  We’re talking about therapies that help our own bodies fight the actual root causes of a disease at the cellular and genetic level.  This is the first time in human history that we’ve been able to do that.  We hear stories about the lives that patients and caregivers can lead because of these new types of treatments, the potential for cures, the potential to give someone their sight back.  This type of innovation can be a game changer for so many patients and their families, and we are just at the beginning of it.  Currently, there are four approved cell and gene therapy products that treat five diseases and nearly 300 additional therapies in development.  These new therapies have the potential to cure previously incurable diseases and to fundamentally alter the trajectory of many other life-threatening conditions.   Take for example, sickle cell disease.  Approximately one hundred thousand Americans have this life-threatening condition that can lead to stroke, difficulty breathing, pulmonary hypertension, and other organ damage.  Today, scientists are exploring new ways to use established medicines and cutting edge technologies such as RNA interference, gene edited stem cell therapy, and gene therapy, to treat this disease.  On therapy currently under development could potentially be a one-time treatment for sickle cell disease.  And this is just one of the nearly 20 sickle cell disease therapies in development, or in FTA review.   The manufacturing process for cell and gene therapies is uniquely complex and defines the product.  Because of this, biopharmaceutical companies are exploring existing and new technologies to more effectively and cost-effectively develop and manufacture these therapies.  And are investing in cutting-edge manufacturing sites to ensure high standards and quality.  Cell and gene therapies truly reflect the scientific advances.  But in many ways, our current healthcare system is not structured to handle them.  Many of these therapies need to be delivered as early as possible to patients to provide maximum clinical benefit, which can be complicated by prior authorization policies.  Insurance plans are struggling to estimate exactly how many patients may need these therapies in a given year.  And current policy proposals such as the Lower Drug Cost Now Act of 2019, also known as HR3, could lead to 56 fewer new medicines coming to market over ten years, according to a recent analysis.  HR3 would have an especially large impact on small emerging biotech firms that rely on venture capital and venue streams from the rest of the industry to finance their R&D investments, and it would most impact areas where the science is toughest such as in Alzheimer’s, ALS and other diseases that could potentially be cured by cell and gene therapies.  Just as our regulatory system is evolving to advance the opportunities offered by these therapies, our payment and coverage system needs to evolve to reflect the value of 21st century science. We need to evolve our healthcare system to one that values treatments based on patient outcomes.  To achieve this, biopharmaceutical companies are increasingly exploring innovative contracting arrangements in which payment and reimbursement for new treatments is tied more closely to health outcomes.  And research is showing that these types of contracts can reduce health system and out-of-pocket costs and improve patient access and health outcomes at the same time.  And just as there won’t be a one-size-fits-all gene and cell therapies, there’s not a one-size-fits-all approach to payment.  Policymakers, biopharmaceutical companies, and payers, are exploring a range of creative options that include extended payment plans and annual subscription plans.  Together, we can develop a policy environment that ensures timely patient access, manages short-term affordability, and continues to foster the development of these lifesaving treatments.   I’m excited to hear from today’s panelists about how we can address some of these challenges and look forward to a rich and informative discussion.  Thank you very much.   SARAH DASH:  Thank you, Jocelyn.  All right, well now we get to the fun part, we get to introduce our panelists and get into the weeds on this really important conversation.  You can join on Twitter if you’re interested at the hashtag #allhealthlive.  And please be thinking about questions that you want to ask.  We’ll be coming around to collect them on the green paper that you all have on your tables.   So very pleased now to introduced our panelists and you can find their full bios in your packets.  First, we’ll hear from Gillian Woollett, who is a principle research scientist at Avalere Health, where she leads the FDA practice.  She is a train immunologist and previously held positions at Engle and Novitt Bio and Pharma.  She has her doctorate in Immunology from University of Oxford, and degrees in biochemistry from the University of Cambridge.   Next, we will hear from Dr. Joanne Kurtzberg, who is a faculty member at the Duke University School of Medicine, where she serves as Director of the Marcus Center for Cellular Cures, the Pediatric Blood and Marrow Transplant Program, and the Carolina’s Cord Blood Bank.  She is also the co-director of the Stem Cell Laboratory at Duke.  She’s an internationally renowned expert in pediatric hematology and oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation and novel applications of cord blood in the emerging fields of cellular therapies and regenerative medicine and she’s going to bring us into what it means to actually translate from the bench to the bedside, if you will.   Next, we’re pleased to welcome John Glasspool.  Mr. Glasspool is a senior advisor to the Massachusetts Institute of Technology Center for Biomedical Innovation, NEWDIGS initiative, and the Financing and Reimbursement of Cures in the U.S. Project, or FoCUS.  He’s also the CEO of Anthos Therapeutics.   And finally, we have with us Dr. Rena Conti, who is the Associate Research Director of Bio Pharma and Public Policy for the Boston University Institute for Health System Innovation and Policy.  She also an Associate Professor at the Boston University Questrom School of Business.  Dr. Conti is a health economist whose research focuses on the organization, financing, and regulation of medical care and she has written extensively on the pricing demand and supply of prescription drugs.   And I really want to thank our friends from Boston for making it down following a snowstorm particularly.  So with that being said, very pleased now to turn the conversation over to Gillian Woollett.   GILLIAN WOOLLETT:   Delighted to be here.  Most of  you all know Avalere for reimbursement commercialization.  We also do have a practice with a bunch of molecular biologists and immunologists and PhD types that have approached the different form of evidence in the sense of what FDA generally is looking for.  But for the purposes of this discussion, I’m going to go very broad, very general.   Some of you will appreciate Colman’s mustard.  It’s that lethally hot stuff and you always put a really big splodge on the plate, but you don’t eat it.  And they always argue that Colman’s made their money by the mustard left on the plate.  Everybody had the mustard available, but the point being that just as with some medicines you have a lot of people treated that leverage the cost, but their response may be different.  Our ability to focus who gets a treatment in the first place as our colleague from Pharma introduced, is critically important, but obviously it changes the economics.  So the traditional return on investment for a small molecule drug, if you’re treating for blood pressure, what I tend to call, unfortunately, the popular diseases, you have a broader return on investment available to you.  Biologics were already breaking this model with the specificity of monoclonal antibodies where you had a tighter diagnosis perhaps of the disease, and then cell and gene therapy, which has been a dream for years, ever since we knew the structure of DNA in ’52.  Cell and gene therapy are really focusing on treating the right person at the right time.  So if we look at the complexity, we have the small molecule drugs, obviously, small.  We have the biologics, which can be quite big, that Y shape, your traditional monoclonal antibody, and then soup, as I call it, which characteristically was not well defined.  Goes back to 1796 and the small pox vaccine, but now may include some of these cells, and they may be living entities in and of themselves, which is then a supply chain issue.   So yes, complexity is a challenge, but the specificity ultimately determines the economics and historically, and still, much many of us have high blood pressure, but historically most therapies target a disease rather than a person.  And the great news is, we’re getting to the point we can target the person.  Obviously, biologics are an increasing part of the U.S. pipeline and the reason I flag this one is you look at the number in the pipeline and the number of approvals and we’ve got a ratio of about 100 to 1. It’s about a century to approve at FDA what’s already in the pipeline.  So maybe we’re putting some things into people too soon, or maybe we need to look at our regulatory model, but either way, I think that ratio needs to change.  But the expansion of these specialty meds continues to increase.  That’s good; the promise is there.  But it’s going to add to the visibility of the cost in cell and gene therapy even more so.  We’ve already, even without the specificity, the acute, astute specificity, got a move from (indiscernible) to smaller populations that get benefit from each drug.  And this means collectively there’s an issue on our pipeline, and we’ve got competition coming with biosimilars for biologics, but it’s being very slow and then here was an observation made by Scott Gottleib as commissioner that — to the individual patient, of course, the improvements are profound, but as measured in GDP, everybody knows the ratio of spending in unsustainable.  So this choices to who gets treated becomes critical.  And the R&D per product is unchanged, but there’s fewer able to benefit.  So the access is an exquisitely important question.   Here we’ve got a rough summary of how the cell therapies may be autologous, they may be self-cells or in my case, I can borrow from my identical twin, but most of you don’t have one.  You have to donate your own cells to yourself to be altered in some way, given back to you, and then we have the (indiscernible) which is donor essentially in the same manner that you have for tissue transplants.  And you get a certain scale up after the manipulation and then administration to the patients.  Now, what’s important here is of course the setting of care is a very complicated situation too.  This is not a pill that you can just take.  This is the aspect of available, suitable appropriate settings for care, is massively important.  And then with the gene therapies, you have the viral vectors that again, gives the corrected gene to the patient and you hope to restore function.  As a regulatory measure, sponsors choose the pathways, but we have two statutes that govern FDA’s authority and then it’s a biologics license application under the Public Health Service Act, as to how these products get approved and this is through the Center for Biologics Evaluation and Research at FDA.  This is the center that also deals with blood, blood products, and historically dealt with the recombinant products, but those are now the center of drugs.  And philosophically this is important in how both as a statutory authority and also how the people available for review approach the approval of these products.  It is not a trivial exercise and it takes a lot of expertise and a lot of working together between the sponsor and the agency to enable a product to be marketed and everything about a drug becomes a hundred-fold for a biologic and becomes a thousand-fold for cell and gene therapy in terms of complexity supply chain and how it gets managed.   Here, as alluded to again, are the four approvals.  We have the two cell therapies at the top and then we have a couple of gene therapies at the bottom.  These are just the beginning, but it’s also evident obviously with the numbers at the bottom of each, that the cost per patient can be quite significant.   Then at FDA there’s the regenerative medicine advanced therapy, better easier said as RMAT designation.  It was created in 21st Century Cures Act.  And there’s certain criteria that allows sponsors to engage in the program, but that ends.  These are not alternatives, the drug has certain specific aspects to it.  It’s intended to treat, modify, reverse, or cure serious or life threatening disease or condition.  This is important:  As we get going into gene therapies, it would be — or cell therapies, it’s naïve to say everything is going to be a cure.  Just because in theory, in principle, it can be does not mean that the first generation will be.  There’s a lot of learning to be done collectively, individually.  So apart from some of the antibiotics, I don’t think we’ve ever had the first gen being instantly perfect and being what we need.  So — and then there’s also this need for preliminary clinical evidence showing that it has this potential to address the unmet medical needs.  So there’s a lot of steps before you get into the RMAT program, but it does enable access to a lot more support from the FDA and also the priority review and certain other programs.  I do have a caution here that by making every drug special, we’re leaving out potentially, if we’re not careful, those drugs for popular diseases, but clearly some of these are very high touch and they need the FDA engagement throughout the process.  However, FDA already has 800 active INDs on file for cell and gene therapies and it’s high touch resource intensive for FDA.  So as we look to say, re-upping of the user fees, we can expect some attention on the resources required by the agency to do the review.   They also have at FDA a number of other levers to accelerate review beyond just standard and priority.  Here we’ve indicated fast track breakthrough and RMAT, so for sponsors it’s very, very important to talk to the agency, work out what they may be eligible for, and make the most of these programs.   And then here we have the pipeline of those products that have the expedited designation and the FDA is saying they expect they’ll receive over 200 INDs per year for cell and gene therapy by 2020, that’s next year.  Shocking though that might be.  And approve ten to twenty per year by 2025.  So this is a head’s up as to these economic demands on the system, whichever part of the system you are, as to how we’re going to manage what should be, will be, ultimately phenomenal therapies, even if the first ones aren’t perfect.  So that’s an introduction to cell and gene.   SARAH DASH:  Thanks so much, Gillian.  Joanne?   JOANNE KURTZBERG:  So I’m a pediatric physician and hematologist/oncologist.  I forgot my instructions about the red light.  And I am really speaking from personal experience about cell therapy programs that we are bringing forward in children with brain diseases.   I want to make a few points though.  You’ve heard already that these therapies are — really can be cells, tissues, and genes.  That their potential is enormous to help exciting – with exciting new therapies for unproven applications and unmet medical needs.  They are very unique because as Gillian said, they are not pills.  There’s manufacturing, there’s packaging, there’s distribution.  And everything about them is really different than drugs and I will give you an example.  We have a cell therapy study in orthopedics and knee arthritis and we had to send frozen cells to an orthopedic clinic.  Orthopedic clinics really don’t know how to handle frozen cells.  Don’t have the freezes for frozen cells.  Don’t know how to thaw the frozen cells.  So I mean, just putting all of that in place took a whole lot of training, teaching, buying of new equipment, and different kinds of expertise than is in their typical wheelhouse.  And I think these therapies are going to dramatically change the current healthcare system both in delivery, but there are big gaps in the current workforce, particularly in manufacturing under GMP, that really need to be addressed in our whole educational system.  There’s different techniques for storing the products that are not in the bandwidth of a typical pharmacy.  And administration as I alluded to, requires very different expertise when you’re talking about cells or genes or tissues.   So I work in the Marcus Center for Cellular Cures, which is a translationally focused, scientifically-based center in an academic center.  And we are developing cell-based therapies to treat brain diseases and our goal is to develop the therapies and rapidly translate them from the laboratory to the clinic and to the patient.  To do this, we’re like a mini biotech in an academic center, which is an oxymoron in itself.  But somehow we’ve managed to do that.  And so we have a center that has its own research and development and discovery lab.  A FDA licensed public cord blood bank called the Carolinas Cord Blood Bank, which has 45,000 cord blood units, which were donated by moms to be stored and used for the cell therapy and transplantation.  A DMP cell manufacturing lab, clinical trials group, a regulatory group, administrative group, and a physician group.  And we are using cord blood, cord tissue, and cord blood derived cell products under IND to study indications in babies with birth asphyxia, children with cerebral palsy and autism, adults with acute ischemic stroke, children with leukodystrophies, and adults with osteoarthritis to the knee.  And I don’t have time to go into all of those but I just wanted you to see kind of the scope of what we’re doing and where we’re coming from.   So one of our major focuses is using cord blood cells as therapies and the FDA approval for cord blood is for hematopoietic stem cell transplantation, as a cell that can rescue bone marrow after myeloablative therapy, but that property is covered by a cell in the circle at the top called a blood stem cell, which is about .001 percent of the cells in a bag of cord blood.  Everybody always says cord blood is a bag of stem cells, and it really is not a bag of stem cells.  But it turns out there are a lot of other interesting and potentially therapeutic cells in cord blood, including lymphocytes which people are now developing into third party immunotherapies and the monocytes which are on the bottom, which is what I’m going to concentrate on today.  So cord blood monocytes are different than adult monocytes, so if you take my blood and try to get it to do what cord blood can do, it will not work.  And that’s what the graphs on the bottom of the slideshow on the right, but on the upper three panels, you can see normal brain tissue and culture — this is mouse brain tissue, and in the middle, injured brain tissue.  And then on the right, injured brain tissue that was co-incubated with cord blood monocytes and it’s rescued from what was hypoxic injury.  And we use this kind of data to develop a rational to put in an IND to try cord blood cells in babies with birth asphyxia and adults with acute ischemic stroke and kids with cerebral palsy.  We also grow a cell from cord blood, we call it DuOC, which stands for Duke o cell.  Which is swimming around on that slide, but which is a monocyte derived product we grow in the DMP lab over three weeks in culture and which is capable of re-myelinating brain in a number of experimental systems and that has important applications for treating de-myelinating diseases and also for treating children of leukodystrophies.  And on the bottom panel you can see on the left, that the cell has re-myelinated brain in a mouse that was injured by something called cuprizone and that the myelin is of normal integrity.   So one of the things I’ve concentrated on in my life is treating children of rare leukodystrophies.  When you talk about personalized medicine, these are very rare, but fatal diseases that affect infants and young children and — which we showed about 20 years ago could be affected in a positive way by (indiscernible) stem cell transportation with cord blood.  On the right, you see a little girl who has Krabbe disease.  She had an older sister who died.  She was transplanted with cord blood when she was 19 days old.  And she is a healthy 15 year old.  On the right, you see a little girl who also had a sibling who died who was transplanted at 21 days of age and who is alive and doing pretty well, but has trouble walking.  And you can see in the middle, MRIs that show fiber tracking of their cortical spinal tracks, which are the nerves that go from the brain to the legs and the little girl on the left has normal tracks, and the little girl on the right has an abnormal track and these were done when these kids were two days old.  So what that says is even by two days of age, it’s too late to fix everything in some kids and so we developed a therapy where those DuOK cells are now being given to children with leukodystrophies a month after a transplant in the spinal fluid, to see if it will help rescue the damaged areas of brain more rapidly.  And we’ve treated 27 children and have good safety results, but know that we need to do a trial without transplant to see if there’s efficacy, and we’re planning to do that on adults with MS.   We’ve also studied cord blood not with a transplant, but as an infusion like a smart drug.  So we put the cells in the blood and they do their thing in the body and we’re not 100 percent in control of they do.  But they’re smart enough to know, and this just shows you data from a published study in cerebral palsy where we were able to show that cord blood improved motor function in kids with CP.  That’s in the middle. And on the bottom, where you see pictures of all those brain lines, that shows that cord blood cells improved, or increased motor tracks in the brain, in the children whose motor function improved after the cord blood infusion.  To do those scans, each scan is four terabytes of information.  Each child had two scans.  This is composite of all those kids pre and post, so super computers had to analyze that data.  The children had to go into MRIs for an hour to be studied twice.  So I mean, there’s a lot of complexity just to get the kind of data that might convince the FDA that this is a reasonable therapy to move forward.  So here’s a good example, the little — this little boy who was a responder on treatment and we filmed all the children and had them independently evaluated, but he’s walking with a walker, he has braces, he can’t walk independently at study baseline.  But on the bottom, one year later, you can see that he doesn’t have the walker, he doesn’t need the braces, he can walk independently.  That is more than a child would be able to do in a year with straight CP if they didn’t have an intervention that made a difference.  But it’s — in growing kids who develop anyway, it’s more complex to show a benefit than just saying, oh, he improved in a year.   We also are looking at cord tissue therapies, so this from the umbilical cord itself, not the blood inside.  And we’re able to show in preparation for studies in kids with autism that cord tissue, MSCs, which stands for Mesenchymal stromal cells which can be grown from the cord in six weeks in culture in a GMP lab.  Can calm down inflammation of what are called microglia, which are known to be inflamed in kids with autism.  Autism now affects one in 59 children in the U.S. and it’s increasing in incidents and severity.  The (indiscernible) is in the hundreds of billions and there is no FDA approved therapy to treat the core symptoms of autism.  We published a study where we showed that giving infusions of autologous cord blood to kids with autism improved in the red on the right — decreased symptoms of autism and improved their behavior.  This is open-label phase one, so it has to be studied in a randomized placebo controlled phase two.  But if cord blood can help, then you could say, well this is autologous, how many families actually store their own kids’ cord blood?  And frankly, I work with cord blood and I think if this is going to be a viable therapy, we have to make it work with donor cells, which can be manufactured more easily, more effectively, and maybe better.  So we’ve done this study, it will be published soon.  Testing whether donor cells or the child’s own cells compared to placebo made a difference.  And one thing that we learned is that we need objective end points, not just, unfortunately, a parent saying their child is better.  And so we are looking at one example, which I show here, called eye tracking, which tracks how a child looks at a video, which is different in autistic kids, than in typically developing kids.  But these objective end points are hard to find, hard to validate, expensive to implement, but really important to prove or disprove the therapy.   So because we’re academic and because we have small labs and because we want to help children and because we don’t want the cost to be super high, to do this, 50 percent of the kids we see on Medicaid, we are looking at market sizes and trying to figure out how to optimize and scale up manufacturing.  But for example, if we use cord tissue, and we’re treating kids with CP, we have about 800,000 doses to make.  If we’re treating kids with autism we have 3.5 million doses to make.  Stroke, 6 million.  Osteoarthritis in knee, 30 million.  I have a little lab and one cord tissue can make a thousand doses.  So you — and that takes six weeks.  So you can kind of do the math.  But if we outsource it and upscale it, it will end up being hundreds of thousands of dollars, when it really can cost tens of thousands of dollars a dose.   So just to sum up and I didn’t really have a lot of time to show you all the data, but we have encouraging early phase data to say that cord blood and cord tissue cells can help children with various types of brain injuries, but we have to do phase three well-designed studies to confirm efficacy and then to obtain regulatory approvals.  Those are long, expensive, and big processes.  But these therapies have the potential to treat diseases with unmet needs, and to change human lives.  And when you make a child better — when you make that child be able to walk alone, it impacts the rest of his whole life.  So it’s not just that one thing that makes him better.  But clinical trials are very expensive and NIH doesn’t typically fund the level of phase three that need to be done.  Complex end points require novel clinical trial designs.  Point of care delivery has to be addressed and the workforce and the competencies to do that have to be developed.  And we have to harmonize the FDA regulations and point of care cell therapies, because some of the lines in the sand on specifications really don’t make any sense.  So thank you.   SARAH DASH:  Wow, thank you, Joanne.  I know we’ll have lots of questions.  We’ll turn to John next.   JOHN GLASSPOOL:  Thanks very much.  I’m going to really pick up from where Gillian and Joanne have been talking and talk about, as we move more to the — if these therapies are so successful.  How I came to be involved in FoCUS was I was the head of corporate strategy for a biopharmaceutical company was so — such a believer in this technology, that essentially said, well, if this technology is going to work the way we think it’s going to work, then we need to change the healthcare system to support that.  Because the science is exciting, the benefit was clear, we knew that it would actually take quite some changes within the system in order to get these products used.  So the FoCUS project is really about the financing reimbursement of cures.  I think Gillian mentioned the point of whether these things are really cures. The key to me is the difference with these therapies are that they are durable.  And their durability as in there’s an initial treatment, would then follow in benefits, is what makes them very different from other drugs in the system and I’ll highlight that.  The FoCUS project itself is very much a mixture of all stakeholders involved in the delivery of healthcare.  So it obviously is drug developers, but it’s also the payers, the providers, the regulators, and the goal of the key overall is to make sure these innovative cures are accessible to patients.  So patient access is the guiding star of the whole project, but the fact is that we believe it needs to be sustainable to all the stakeholders.  So if patient access is going to be achieved, whatever system changes we come up with need to support all parts of the stakeholder system.