Lyfebulb, the company I co-founded with Dr. Steve Squinto, Venture partner Orbimed and Riccardo Braglia, CEO Helsinn, three years ago, is about to launch an early-stage Diabetes Innovation Venture Fund focused on breakthrough opportunities in autoimmune, insulin-dependent diabetes and other associated autoimmune diseases. Our goals are to deliver a superior return on investment and to remove the burden of autoimmune diabetes.
With Lyfebulb, we have created a community focused on chronic disease, and we are relentless in articulating the voice of the patient to bring forward better products, improve compliance and put pressure on industry to listen to the consumer.
Type 1 diabetes (T1D) is my particular problem, but I am not alone.
There are millions of people like myself, and even more who care about someone who has the disease. Most people have heard about diabetes, but many ask me, “isn’t this just a disease of the Western world, a disease that if we only ate better and exercised more, we would not have to worry about?” Most people perceive diabetes to be a less ”severe” disease than for example cancer.
Here are some facts:
- There are 29M people with diabetes in the US, and another 86M with pre-diabetes, of which 90% are Type 2 Diabetes (T2D), a disease of inflammation and insulin resistance, which initially can be treated with diet, exercise, and oral medications, is often diagnosed mid-life and in people who are overweight. 5-10% are T1D, a disease of the immune system, always requires insulin injections, and is most often diagnosed in young people
- Both T1D and T2D present with elevated blood sugar levels, and are leading causes for blindness, kidney failure, amputations, and increase the risk for stroke and heart disease several-fold, are the 3rd leading cause for death in the US, and accounts for over $250B/year in spending. The burden T1D has on society, is disproportionate to its prevalence vs T2D
How has industry and the public reacted to these data? Well, the large and growing numbers of T2D patients have attracted multinational companies, scientists and media to spend large sums of money and time on solving the T2D problem. The reality is that the numerous drugs available for T2D are both insufficient and ineffective to keep people in range. There is a very large behavioral component to T2D, and without human as well as electronic help, patients do not take their drugs, do not change their diets, and do not exercise more.
In my opinion, in T2D, we should focus more on incentive models to keep T2D patients in control and let the drugs that are on the market become easily accessible and less expensive. This brings about a shift for the pharmaceutical industry, which historically has led with an expensive new drug and cared less about the behavioral programs that must go with them. New models are emerging, with companies such as Fitscript (exercise), Wellth (employer-driven behavior modification) and Fit4D (force amplifying nurses to add the human touch), as well as companies, such as Livongo and Glooko, where the sugar levels are explained to patients and prompts are given so that people have a diabetes guide with them all the time. Community-based support is another way to go, and here OneDropToday has a great model, where the glucose strips are unlimited and the support comes from fellow patients.
For T1D, the body is no longer making insulin. Treatment may improve with behavior modification, but this is far from enough. Although insulin saves lives, it is not a Cure and causes major side effects such as hypoglycemia (low blood sugar), weight gain, and cannot completely remove the risk of late-stage complications such kidney failure and heart disease. No one wants to think about their disease all the time, but for a person with T1D that is the only way to stay in control. Some people argue that this control forces them to change their life for the better, allows them to focus on health, but I don’t think anyone would say no to a break from diabetes management if offered.
Companies such as BetaBionics and Bigfoot, as well as large companies such as JNJ, Dexcom and Medtronic, are working on fully automated systems that combine insulin dosing with glucose measuring, which theoretically could remove some of the burden of disease from patients with T1D and keep them safe. This has been called the “artificial pancreas project”, an effort that has been driven hard by the JDRF, and now has triggered multiple financial rounds and start-ups.
This is great for the T1D space, but it still is not a Cure.
I have already mentioned how the two types of diabetes are different. Now let us compare T1D to other autoimmune diseases, such as celiac disease, Hashimoto’s thyroiditis, Addison’s disease, MS, Rheumatoid Arthritis (RA), and Inflammatory Bowel Disease (IBD). In all these diseases, the immune system attacks part of “self”, i.e., part of the person’s own body, instead of attacking only foreign objects such as virus, bacteria, parasites or even transplants.
The difference between some of the autoimmune diseases, such as RA, IBD and MS, vs T1D, is that they have apparent relapsing remitting symptoms, i.e., the person gets worse and then better again, since the cells that are being attacked manage to regenerate. Over time, there is often a progressive nature to the diseases, but with new drugs, there may be some recovery and even fewer episodes going forward.
In T1D, the beta cells seem to be completely lost and except for a period in the early stages of T1D, often described as the honeymoon, one can never get off insulin. New studies, including those of JDRF’s nPOD project (led by Mark Atkinson), for example, have shown that we may have been wrong in many of our beliefs about the disease. For example, the amount of loss at diagnosis is much more variable than one thought. It is still difficult to show the dynamic nature of the disease since biopsies of the pancreas are not done readily.
What is next, I believe there are at least 3 main scenarios for T1D, where we could complement insulin therapy, even if we cannot Cure the disease immediately. A prerequisite for these scenarios is the earlier diagnosis of T1D. It is already possible to measure autoantibodies in healthy individuals and accurately diagnose beta-cell autoimmunity. It is possible to predict the decline of beta-cells and give us a timeline for the full-blown disease. In certain geographies, this method is already in place, for example in Southern Sweden led by Professor Ake Lernmark, Lund, and through TrialNet in the United States, led by Professor Carla Greenbaum in Seattle. Screening school children for beta cell autoantibodies has began in Colorado. The aim is to diagnose T1D at an early stage to have a better chance to develop preventive measures.
- Supplementing beta-cells with either embryonic stem cells, adult stem cells or transdifferentiated cells (autologous cells that have been converted to beta cells in the laboratory). The proof of concept has been shown through transplantation of cadaveric beta cells and pancreata, which renders the patient free of insulin. That option is not a viable one for all people, due to the requirement of immune suppressants, limited supply of beta-cells and pancreata. However, there are a number of laboratories and companies working on alternatives: Viacyte being the leader in embryonic stem cells, with academics such as Professors Doug Melton (Harvard), Bob Langer (MIT) and Camillo Ricordi (Miami) following. Orgenesis (ORGS) is a public company that is about to test its transdifferentiated (liver) cells in clinical trials.
- Addressing the immune system through combination therapies that halt the attack before a majority of cells are gone. This pathway can also be used in established diabetes to allow for lower insulin doses and thus an easier managed disease through reduced glucose volatility. There have been some failures here, but the field has moved forward through these experiences. Thought leaders include Professor Jeff Bluestone, UCSF, Professor Kevan Herold, Yale, and Professors Lernmark and Atkinson. Interesting approaches also include Dr. Alan Lewis’ DiaVacs and Professor Santamaria’s Parvus. We should learn from oncology and not be afraid of combination therapies!
- Through above mentioned studies of nPOD pancreas, it has been shown that beta-cells might be subject to waves of immune attack (much like other autoimmune diseases), with the time of diagnosis being a period of pronounced destruction. Beyond nPOD, studies of human islets suggest that regeneration of beta cells appears possible, in that at least three drugs have been found capable of inducing such actions. Professors Mathias Hebrok, USCF, Klaus Kaestner, U Penn, and Doug Melton have all ventured into this space.
Taken together, novel understanding of the disease pathology and the comparison to other autoimmune disease, suggest with earlier intervention and the right drugs (or cell therapy), we may be able to prevent the absolute dependency on insulin and even Cure T1D, and insulin-dependent T2D.
An absolute must, is to continuously improve our understanding of the human immune system. We need to explain why and how our immune system gets the signal to attack our own beta cells. It will be necessary to study people not rodents. This is where disease foundations such as the JDRF and government (the NIH) are doing incredible funding work.
I have a personal interest in making sure that we find a Cure for this disease in the not too distant future.
I had a pancreas transplant that “Cured” my T1D in 2010, and since then I have not dosed insulin. However, I am on very toxic immune suppressant drugs that have already caused several serious infections, they render me more vulnerable to certain kinds of cancer, and they cause minor side effects such as hypertension and nausea. I do not ever want to go back on insulin, but the prognosis for my transplanted pancreas is uncertain. At some point, my autoimmune disease will break through and kill my new cells. I also risk rejecting my pancreas since my body does not fully accept it as my “own”. The very drugs that reduce my immune response to this organ are also very toxic to my pancreas and each year, it develops more scar tissue.
I won’t give up until there is a Cure. I have seen what diabetes can do to people – as a medical doctor I have taken care of patients with wounds that won’t heal, eyes that do not see, and kidneys that require dialysis. I have seen young and old people who are depressed due to the constant monitoring and the loss of control and I have known people who died from the disease.
This is why we have decided to create a new kind of Venture Fund – T1D Capital – focused on T1D but solutions will be applicable in associated autoimmune diseases and insulin-dependent T2D. We will identify, invest in, and manage companies that are in the regenerative medicine and immunology space that will deliver breakthrough solutions for people like myself and so many others.