JDRF Mission Summit 2020

February 4, 2020; La Jolla, CA; Highlights – Draft

Executive Highlights

  • JDRF’s annual Mission Summit just took place – yet again, it was a very exciting two days filled with tremendous learning. What a privilege to be present. In our memory, the world of type 1 has never been as active as it is right now, and JDRF is having absolutely remarkable impact.

  • A discussion on the T1D Fund was a major highlight, featuring a conversation between JDRF CEO Dr. Aaron Kowalski and T1D Fund Executive Chair Sean Doherty. Now just over three years old, the T1D Fund has almost $100 million under management and has made almost $50 million in investments across eighteen companies. Looking ahead at 2020, Mr. Doherty said he expects the fund to make ~$30 million of investments in new companies and follow-on investments in existing companies. Interest in the T1D Fund was especially high as the fund won its first major exit this year with Vertex’s $950 million acquisition of Semma in September. By bringing other, larger firms’ investments in the type 1 space and re-investing returns from its investments, Mr. Doherty made the argument that a $1 million donation to the T1D Fund may actually be leveraged into much more.

  • As always, this meeting brought a distinct focus on the latest regarding progress in type 1 cures development and type 1 prevention/delay. A fascinating breakout session focused on immune therapies touched on the utility of general population screening (especially relevant in light of recently published results from the Fr1da study), the need for continued development of biomarkers in type 1 screening, how JDRF can best communicate scientific findings in this space with regulators, and the potential for pharma in viewing type 1 therapies as possible orphan drug assets. A parallel session on beta cell replacement therapies focused on the potential and challenges in this field, with Novo Nordisk’s CMO Dr. Stephen Gough pointing to encapsulation of beta cells as a specific area for improvement.

  • In the day’s keynote, Harvard’s Dr. Chad Cowan provided a “big waterfront view” of all things related to cell therapies in type 1 diabetes. Dr. Cowan focused his talk specifically on biological immune protection – in other words, manipulating stem cells to forego detection by the body’s immune cells. Dr. Cowan framed this idea by asking the audience, “What if we had ready-made components to transplant into people?” He explained the concept of “cloaked” stem cells that are able to evade and be protected from the immune system and therefore would not require any encapsulation or parallel immunosuppression. Of course, this ideal has not yet been achieved, although several labs are making good progress.

  • We’re always so very lucky to attend this meeting that brings together top physicians, researchers, donors, and industry partners. The learnings are always top notch! Be sure to see our reports from this meeting in year’s past, including 2019, 2018, 2017, and 2016.

Hello from The Lodge at Torrey Pines in La Jolla, CA, where JDRF just held its annual Mission Summit! See our top highlights below.

Top Six Highlights

1. T1D Fund: $100 Million Under Management, $50 Million Invested Across 18 Investments, and “Turbocharging” More Venture Capital Investment in T1D

In a well-attended session just before lunch, JDRF CEO Dr. Aaron Kowalski and T1D Fund Executive Chair Sean Doherty gave an update on the venture philanthropy fund, which Mr. Doherty called “the most impactful venture philanthropy fund in disease right now.” Now more than three years old, the T1D Fund has almost $100 million under management and has made $50 million in investments across eighteen companies. Looking ahead at 2020, Mr. Doherty said he expects the fund to make ~$30 million investments. For comparison, at last year’s JDRF Mission Summit, the Fund had raised $70 million and investments in twelve companies. As a reminder, the Fund invests in three categories: (i) Improving Lives, (ii) Beta Cell Therapies, and (iii) Immune Therapies. It’s worth noting that the T1D Fund’s Portfolio page only lists 15 investments – unlisted are two legacy investments that JDRF had before the Fund’s creation (AnTolRx and Capillary Biomedical) and one investment that has not yet been publicly announced. The three new investments listed on T1D Fund’s website include one immune therapy company (IM Therapeutics), one beta cell therapy company (Veralox), and one improving lives company (Biolinq).

  • The T1D Fund saw one portfolio company have a big exit this year: Semma Therapeutics was acquired by Vertex Pharmaceuticals for $950 million in September 2019. The Fund made its investment in Semma back in 2017 and the acquisition brought $15 million back to the Fund. We don’t know how much was invested in Semma at the time, but T1D Fund’s average investments are fairly small (around $3 million). As the T1D Fund sits under JDRF’s 501(c)(3) organization, the return from the investment in Semma is simply returned to the Fund for future investment. Thus, Mr. Doherty made the argument that a $1 million donation to the T1D Fund may actually be leveraged into much more.

  • From its inception, the goal of the T1D Fund has been to “turbocharge” investment in T1D by convincing other investors to join the area. Mr. Doherty called the fund “a different tool in the kit” in JDRF’s larger mission to fund cures for diabetes. Ultimately, the goal of the T1D Fund is not to “build an empire,” but to “identify great opportunities and convince other people to come in and invest.” For this reason, most of the fund’s investments are fairly small. However, other VCs and investors trust the T1D Fund’s expertise and experience and are more willing to make investments when a company has a “stamp of approval” from the T1D Fund and JDRF.  

    • As an example of “turbocharging” investment in the T1D space, Mr. Doherty told us a story that he couldn’t have “drawn up any better”: “SQZ Biotechnologies was developing basically a microscopic-sized gun that could shoot any material into a cell without damaging the membrane of the cell itself. The idea was that they could fire materials into a cell to induce intolerance for cancer cells … we learned he was interested in applying that technology to autoimmunity … The Managing Director of the Fund at the time approached [SQZ’s Founder] and months later we became an investor in SQZ and their first autoimmune indication they were targeting. Along with that, their lead investor, Polaris Partners, had never made an investment in type 1 diabetes and suddenly they were interested in and willing to talk about type 1 diabetes. Specifically, one of the managing partners at Polaris went to a Monday meeting at Polaris and another partner introduced them to Pandion, because they’d talked about type 1 before. We went to talk to Pandion. Somewhere like six to eight months later, we became investors in Pandion, and they suddenly became a T1D company. Polaris now has two type 1 programs. Ten months after our Pandion investment, through connections at JDRF, Pandion introduced itself to Astellas, a pharma company based in Japan who had never done anything in type 1 diabetes. Now, they’re an industry partner of Pandion and is developing a tissue targeted immunotherapy for type 1 diabetes.” Wow!

  • Notably, type 1 diabetes and celiac are the only two major autoimmune conditions with zero disease-modifying therapies. For comparison, rheumatoid arthritis and multiple sclerosis have 15 or more disease-modifying therapies! Mr. Doherty cited this fact as one of the most motivating things driving his work at the T1D Fund as they continue to convince other investors to invest in type 1.

New investments since Mission Summit 2019

Company

Opportunity

Area & Rationale

Biolinq

March 2019

Developing a wirelessly-enabled biosensor patch capable of continuously monitoring multiple biomarkers. Initially focused on a minimally-invasive continuous glucose monitor (CGM) for people with diabetes

Area: Improving Lives

Rationale: Accelerating the development of a clinical-stage next gen sensing platform

Veralox Therapeutics

September 2019

Developing a therapeutic to inhibit beta cell stress

Area: Beta Cell Therapies

Rationale: Accelerating the development of early stage therapy for T1D, catalyzing matching participation from other investors

IM Therapeutics

October 2019

Precision medicine platform developing small molecules blockers of autoimmunity

Area: Immunotherapies

Rationale: Advancing second generation of genetically targeted blockers

2. T1D Fund Companies Provention, Pandion, and Biolinq Discuss Strategy, Pipelines, Effect of T1D Fund, and More

In the Mission Summit’s final breakout session, T1D Fund Managing Directors Steven St. Peter and Katie Ellias hosted a panel with Provention CEO Ashleigh Palmer, Pandion CSO Jo Viney, and Biolinq CEO Jared Tangney. The panel was very interactive, with lots of audience members excitedly chiming in with questions for the company leaders throughout. Interest was perhaps highest in San Diego-based CGM company Biolinq, especially after Mr. Tangney held up a version of Biolinq’s CGM, a thin and attractive, bright blue, hexagon-shaped device with no needles. Right after his introduction, an audience member asked about the cost and reimbursement for the device. The fully-disposable patch will have Bluetooth connection and is intended to be priced as “one of the lowest-priced devices out there.” Mr. Tangney talked about some of the benefits of being a later-stage player in the CGM field, including the ability to use existing reimbursement structures and to learn from Abbott and Dexcom on the importance of manufacturing scalability and securing partnerships with pump companies. When asked about accuracy, Mr. Tangney stated that Biolinq was aiming to meet iCGM special controls. In terms of timeline, the company has a “few more trials this year” and plans to complete a pivotal trial with FDA submission by the “end of next year.” As a needle-free device, Mr. Tangney said the user experience would be Biolinq’s key differentiator – he compared the device’s insertion process to putting on a Band-Aid. T1D Fund made its investment in Biolinq earlier this year, as part of $15 million Series A. The fund’s investment was a big vote of confidence, as the T1D Fund is known for its experts and diligence on its investments, and the CGM landscape is littered with discontinued projects (see out full CGM landscape here). Additionally, Mr. Tangney thanked JDRF for its work with the FDA in creating the iCGM classification and defining the regulatory pathway for CGMs.

  • Coming off of promising type 1 prevention data presented at ADA 2019, interest was also high in Provention and its gregarious CEO, Ashleigh Palmer. The phase 2 trial for teplizumab showed reductions in cumulative diabetes onset (72% vs. 43%, HR=0.41, p=0.006) and time to diagnosis (48 months vs. 24 months) compared to placebo. Provention owns the development rights for teplizumab, and the FDA has granted it Breakthrough Therapy designation. Of note, Provention is also the only public company in T1D Fund’s portfolio, having gone public in July 2018. While IPOs often mark a reduction in VC influence over a company, Mr. Palmer said JDRF’s support was even more critical as his company matured – we certainly agree with this, given the goal of developing a therapy with landmark results that still carry a lot of associated challenges. In order to “chart the uncharted” territory of type 1 diabetes prevention, JDRF’s patient, clinician, and provider network and expertise will be invaluable.

  • Pandion, one of T1D Fund’s immunotherapy investments, was represented by Chief Scientific Officer Jo Viney. As T1D Fund Executive Chair Sean Doherty alluded to earlier in the day, Pandion did not start with any diabetes-related projects. Instead, the company was focused on bowel, skin, and kidney diseases. After meeting some scientists from JDRF’s research team and T1D Fund portfolio company SQZ Biotechnologies, Pandion secured an investment from T1D Fund and began a full-fledged type 1 diabetes program. In November, Japanese pharmaceutical company Astellas, announced a diabetes collaboration with Pandion, with up to $795 million in milestone payments.

3. Immune Therapy Breakout: Panelists Speak on General Population Level Screenings, Biomarker Development, Communicating w/ Regulators, and Orphan Drug Opportunities in Type 1

JDRF’s Dr. Jessica Dunne led a fantastic breakout session on immune therapies, bringing together important figures from academia (Cardiff University’s Dr. Colin Dayan and Katholieke Universiteit Leuven’s Dr. Chantal Mathieu), industry (BI’s Dr. Mario Ehlers), and regulatory expertise (JDRF’s Ms. Campbell Hutton). Wide-ranging discussion touched on general population screening, challenges in connecting scientific progress to regulatory bodies, barriers to pharma investment, and much more – see below for some of the top takeaway’s from the panel discussion.

  • Dr. Dunne kicked the panel off by referencing results from the recently published JDRF-funded Fr1da study (see link for extensive interview with Dr. Dunne). As a reminder, the trial demonstrated the benefits of general population screening for type 1 diabetes among children with pre-symptomatic type 1, with rates of DKA lowered considerably with implementation of screening (<5% in the study vs. 20% nationally in Germany, where the study took place). In discussing these results and general thoughts regarding population wide screening in type 1 diabetes, Dr. Mathieu noted that “our Achilles heel in the screening of the general population at the moment is that we don’t have anything to really offer for prevention nor intervention to these people.” Indeed, one of the hopes with this general screening approach is that earlier diagnoses would be coupled with better enrollment of therapy trials that could eventually lead to more treatment options down the line. Moreover, recent breakthroughs in the field – such as positive results of teplizumab in type 1 prevention – could significantly contribute here. Dr. Mathieu also underscored the need for better communication strategies and biomarkers in diagnosis. Dr. Mathieu urged JDRF to “please continue to support research in developing better biomarkers” for diagnosis, which she sees as absolutely necessary in ultimately improving diagnosis of type 1 diabetes.

    • Dr. Dayan added that one of his greatest takeaways from the Fr1da study was the similar rates of type 1 progression in people with and without relatives with type 1, given the presence of multiple autoantibodies. Dr. Dayan stressed, during screening, that focusing on individuals with type 1 relatives will end up missing around 85% of total cases, and that this should not be the sole focus given the relatively similar rates of progression between those with and without type 1 relatives. Dr. Dayan explained that he found this similarity to be striking, as he and the rest of the field normally believes that rates of progression to type 1 would be higher in people with type 1 relatives. In other words, while people with relatives with type 1 are at higher relative risk of having type 1 themselves, the actual rate of progression to type 1 diabetes given the presence of autoantibodies in these two populations is similar. This finding that progression is “just as aggressive in the general population” has important implications for screening initiatives, target populations, and potential therapy development.

    • Dr. Dayan further provided context on the important distinction between interventions designed before and after type 1 onset. He explained that “from a pure endocrinology view, you only need a little bit of insulin production to not have diabetes. From a clinical view, if you don’t have the disease, you don’t need insulin, and you can’t go into hypoglycemia and won’t have DKA. This is a much better place to be. A lot of companies are saying that this [type 1 prevention] is an easier place to register new drugs as well. In prevention, payers will pay for more drugs versus than in new onset indications, where you are not actually reversing the disease all together.” Dr. Dayan’s point underscores just how much of a breakthrough positive results from the teplizumab type 1 prevention trial were, as it showed for the first time that intervention with a drug could delay the onset of type 1. We’ll be interested to see whether Dr. Dayan’s prediction of payer enthusiasm for these types of drugs proves to be true; nonetheless, it’s clear that this will be an important first step to more development in the field now that the concept has been proven.

  • On the regulatory front, Ms. Campbell Hutton explained the work that JDRF is undertaking to connect the latest scientific progress in the field with FDA. Ms. Hutton noted that “all of this progress in the past decade since the FDA last provided its guidance document on prevention and new-onset therapies needs to be communicated. One of the ways that JDRF can work with the community is to bring that science to FDA and make sure that all the learnings that have happened influence how they are thinking about therapies in type 1 diabetes. For example, a year ago we hosted a symposium with FDA staff to present that science and have an open discussion with them. We need to make sure that the FDA staff working in this space understand all of this progress and understand type 1 diabetes.” We were a bit surprised to hear that FDA only last provided a guidance document in the type 1 prevention space a decade ago, and wonder whether any future updates are immediately imminent (especially considering the momentum behind teplizumab, which could become the first drug with an indication to delay type 1 onset).

  • Dr. Ehlers commented on industry challenges in type 1 prevention/new-onset therapies, highlighting a shift in pharma perspectives that have further incentivized orphan diseases. He commented that there are “significant challenges” in this space, and that type 1 is a fascinating disease because although the prevalence in the US is quite large (<1.25 million w/ most estimates), incidence rates are quite small (~30k/year). Because of this low incidence, the target population for prevention/new-onset drugs is actually rather small and would be categorized as an orphan disease to regulators. On the other hand, if a pharma company could develop an approach that can restore islet function beyond newly diagnosed diabetes, then the target population could be quite broad. Nonetheless, in the new-onset space, Dr. Ehlers explained that there is “accelerating interest” here as pharma is “shifting more toward orphan diseases as part of a general cultural shift.” Our sense is that ROI projections in the orphan drug landscape may be favorably shifting for pharma companies as a result of broader pricing structures in the field. Dr. Ehlers predicts that type 1 diabetes will benefit from this shift as more investment is made in the space as a result. We note that Novo Nordisk has pursued an Orphan Drug designation from FDA for its combo therapy of anti-IL-21 and liraglutide in newly diagnosed type 1 diabetes, following positive results that were announced in August 2019.

    • Dr. Ehlers explained one common barrier in the development of type 1 drugs: “pharma is generally reluctant to use an untested drug in type 1 diabetes before you’ve obtained evidence it works generally in autoimmunity first in another disease. We need that evidence before justifying going into type 1. In the pharma world, everything revolves around patent life. This becomes a problem if your first indication for a drug is not the one that you really want to eventually pursue.” We were disappointed to hear that this type of logistical barrier with patent intentions may be stalling progress in the field – what creative ways might patent law and regulatory agencies pursue to ameliorate this issue?

4. Beta Cell Therapy Breakout: Novo Nordisk Points to Better Encapsulation Device as Area of Greatest Need; Dr. Bruce Schneider Provides Regulatory Insight on Various Cell Replacement Categories

  • Novo Nordisk’s Dr. Steven Gough (Global Chief Medical Officer) provided some key insights into how Novo Nordisk is approaching cell therapies in type 1 diabetes. He highlighted the company’s ongoing partnership with UCSF to create cell banks to address multiple disease areas, but with a focus on type 1 diabetes as a first step. In terms of where the field is going in the next five-to-ten years, Dr. Gough noted that the first step will be in encapsulating pluripotent stem cells as a type 1 therapy. Currently, the challenge with this approach is in the actual encapsulation of these cells and ensuring they are properly vascularized and being oxygenated enough (Dr. Gough, when asked by Dr. Dutta about how JDRF can best help in this overall field, named working on improved encapsulation devices as the area of greatest need). In the longer term, Dr. Gough pointed to efforts Novo Nordisk is undertaking to “hide” stem cells and make them invisible to the immune system through gene editing of HLA molecules. The biggest challenge with this approach is ensuring that these edited cells do not themselves become cancerous as a result of their introduced immune-evasive abilities. To work around this problem, Dr. Gough detailed how Novo Nordisk is programming “suicide genes” in these cells so that in case something does go wrong and these cells do become cancerous, they can still be induced to kill themselves and be taken out. We’re curious as to what this inducer of cell death may be and how this might work as part of a patient’s or hospital’s regimen. Would patients need to be checked regularly for potential tumorous growth, or concomitantly take another “cancer-suppressing” therapy?

    • At JPM 2020, Novo Nordisk emphasized that it feels “extremely confident” in its technological knowledge and believes that the company can produces stem cells of “the highest standards that are fit for the market.” CSO Dr. Mads Thomsen quipped at JPM that “I often use the analogy that we’ve actually been producing FDA-compliant, GLP-grade mammalian cells since the 1980s … The only difference now is that we’re using 30+ years of mammalian cell cultivation and nursing in a way where we don’t use the proteins excreted from the cells but the cells themselves, so it’s a wonderful exploitation of the technology that’s been developed in the company for decades.” Excitingly, JPM 2020 slides showed that the company hopes to trial its type 1 stem cells in humans for the first time in 2H21, right around the 100-year anniversary mark of insulin.

    • In the audience, former JDRF CEO Derek Rapp asked Dr. Gough how long the cells have to be viable in Novo Nordisk’s device for it to be acceptable for use. Dr. Gough responded, saying “I’m not sure I can really answer that question. When you start on this path, you’re hoping you can restore some function and that it would last forever. It depends what it looks like, I suppose it would also depend on what it would look like from a pricing model and how it would be reimbursed. That has to work, if I’m guessing we want something that’s in there for a minimum of a year and maybe longer. I’m probably sticking my neck out here. Shorter of that, it depends on what it is and where you place it. These are not for life and will need to be implanted again and again – however, we don’t want that to be on a very regular basis.”

  • Dr. Bruce Schneider touched on how regulatory agencies are considering cell therapies in type 1, leveraging his previous experience working at FDA. He explained that there are currently four classes of products for cell replacements that FDA considers in diabetes, with the pathways for approval being “essentially the same” for each:

    • Allogenic islets – these have been tried for over a few decades in type 1, and there is an abundance of data characterizing their safety and efficacy profiles. The pathway for this therapy is clear, but the main problem is that there is not a large enough supply of allogenic islets.

    • Xenoislets – this is the transplant of pig islets into humans. Dr. Scheider explained that the main problem with this method being a fear of xenobiotic adverse events due to immune system rejection. The pathway to approval for xenoislets would be similar to allogenic islets, provided that xenoislets are shown to have a favorable safety/efficacy profile.

    • Human embryonic stem cell derived islets – trials for this method are currently in progress, and the field generally has a “good idea” of safety concerns and efficacy. Oxygenation and survival of these islets remain a challenge within encapsulated devices, as Dr. Schneider described how often these implants get “gobbed up and the cells choke to death” because of a lack of oxygen.

    • Induced pluripotent stem cell derived islets – Dr. Schneider characterized this class as having “vast potential” and noted that FDA has not yet created safety guidelines or a guidance for these potential products. One of the biggest challenges for iPSC derived islets (versus human embryonic stem cells) is the issue of genomic stability, which may be challenging for regulators to assess.

  • University of Miami’s Dr. Alice Tomei spoke on the potential for 3D printing in the beta cell space. She noted that the actual technology of 3D printing is now nearly 40 years old and was originally developed for the printing of plastic parts. It has recently become a focus for the first of tissue engineering given its ability to structure matter in a detailed manner. A shift has occurred from structuring non-living matter (such as plastic) to now applying this concept to living matter and trying to mimic the architecture of the body and of the pancreas more specifically. The important components when trying to do so are ensuring proper vascular architecture and close proximity of the beta cells so that they are able to actually sense blood glucose levels. She broadly explained that there is a general optimism for how this technology may work for type 1 diabetes because of the overall success the field has seen in 3D printing various body parts.

    • Dr. Dutta asked Dr. Tomei specifically where these 3D printed products might actually be placed in the body and whether there are multiple potential placements that would work. Dr. Tomei responded by saying that “from the beta cell side, we want to make sure that they are happy and provided with nutrients from the preformed vascular beds or because they are put in a site rich with vascular beds. The cells also need to be able to respond to the glucose environment, similar to the native pancreas. We have to consider safety first as well. Everything you’re doing has to be while considering possible side effects. One site we have particular interest in is islet transplantation in the portal vein that goes into the liver. This has promising data and has been shown to improve quality of life for patients; however, it does require immunosuppression and it is non-retrievable. Looking ahead, we want to make sure that the site is localized and retrievable.”

5. Glucose Control and Complications Panel Focuses on SGLT-2s in Type 1s and Psychosocial Issues as Flashpoints for Treating Diabetes Better

Though the tagline for JDRF’s 2020 Mission Summit was “Laser-Focused on Cures,” one valuable breakout session was dedicated to treating diabetes better. Dr. Jeremy Pettus (University of California, San Diego) spent time highlighting the fact that people with type 1 diabetes who achieve an A1c target <7% still have a two-fold risk for cardiovascular disease. According to Dr. Pettus, the high levels of subcutaneous insulin used by type 1s may potentially explain this increased cardiovascular risk. Thus, Dr. Pettus and others on the panel (Dr. Jill Weissberg-Benchell (Lurie Children’s Hospital), Ms. Cynthia Rice (JDRF), and Dr. Andrew Rakeman (JDRF)) spent time talking about treating type 1 diabetes beyond simply high blood sugars. Dr. Pettus specifically brought up the potential for using SGLT-2 inhibitors in people with type 1, as the drugs could have an effect beyond lowering blood sugar, namely cardiovascular and renal protection. This is particularly true in light of Dr. Pettus’ statement that he believes people with type 1 will likely be more successful taking less insulin, as long as hyperglycemia can be avoided – he believes that more insulin will be more inflammatory, as we understand it.

Although JDRF and other patient advocacy groups have not yet been successful in working together toward a common goal in 2019 surrounding approval of SGLT-2s for type 1 (the FDA panel voted 14-2 against approval for BI/Lilly on November 13, 2019, and issued a CRL against approval for Lexicon’s sotagliflozin in type 1 on March 22, 2019, and another CRL against approval for AZ’s dapagliflozin on July 15, 2019), we were glad to hear this was a priority and still believe FDA approval could be possible – we believe it will benefit from collective action. Notably, Dr. Pettus also noted that obesity is increasingly affecting the general societal population broadly, but also people with type 1 diabetes. Dr. Rakeman chipped in also, noting that for JDRF, “treating diabetes better” was as equal a priority as curing diabetes. On the advocacy front, moving forward, JDRF has taken a “multi-prong” approach on SGLT-2s in type 1s, looking at both scientific and education initiatives to reduce DKA incidence (there is lots of valuable work going on in the EU on this front) and meeting with the FDA to get the drug class approved for type 1s. JDRF’s Cynthia Rice highlighted how broad the coalition JDRF is building is: “We’re enlisting clinical organizations, members of Congress, the people with diabetes community, private sector, and constantly getting allies.”

  • The only psychologist at JDRF’s sessions, Dr. Weissberg-Benchell’s presence highlighted JDRF’s growing investment in the psychosocial aspects of diabetes care. Dr. Weissberg-Benchell is highlighted in JDRF’s video series “Psychology and T1D,” which contains videos like “Why is Type 1 Diabetes Stressful?” and “Building Resilience with Type 1 Diabetes” – the entire series is very worth watching. Dr. Weissberg-Benchell focused on the existence of “amazing” treatments for people with anxiety and depression, contrasting it with the inaccessibility of these treatments due to insurance coverage or simply patient knowledge. With JDRF, Dr. Weissberg-Benchell is looking to increase visibility and accessibility to treatments for psychosocial issues. She recently received a very prestigious grant from JDRF and as they emerge, we look very forward to hearing the results of this work by this important scholar.

    • In a powerful moment, one parent of a type 1 shared a personal story of the “doom and gloom” surrounding attitudes for type 1s. Overhearing his son’s conversation in the back of a golf cart, the parent shared some phrases from his son’s conversation with a friend: “my life’s going to be shorter,” “my children will have diabetes,” etc. To this, Dr. Weissberg-Benchell emphasized the importance of having people around as a support system, while Dr. Pettus noted that complications are no longer a “forgone conclusion” and that type 1s with low A1cs actually have the same life expectancy as people without diabetes. However, this information, according to the parent, needs to be shared more widely to people with diabetes.

6. Keynote Address: Dr. Chad Cowan on Cell Therapies and Potential of “Cloaked” Cells in Type 1 and Beyond

Harvard’s Dr. Chad Cowan provided a “big waterfront view” of all things related to cell therapies in type 1 diabetes. Dr. Cowan focused his talk specifically on biological immune protection – in other words, manipulating stem cells to forego detection by the body’s immune cells. Dr. Cowan framed this idea by asking the audience, “What if we had ready-made components to transplant into people?” He explained the concept of “cloaked” stem cells that are able to evade and be protected from the immune system and therefore would not require any encapsulation or parallel immunosuppression. Of course, this ideal has not yet been achieved, although several labs are making good progress. The immense challenge of this problem lies in the fact that the immune system itself is “devilishly tricky,” in Dr. Cowan’s own words. His lab has pushed forward on a two pronged approach that involves both immune evasion and immune protection. Evasion has proven to be an easier task, as it involved taking down the “billboard” HLA system.

  • Regarding immune protection, Dr. Cowan talked to over 100 leading immunologists on the best way to do this and received 100 different answers. The best answer he received was from one researcher who pointed to the “paradox of pregnancy” as a clue to how stem cells could be engineered to be protected from immune response. In pregnancy, a special interface exists between fetus and the mother that tells the mother’s immune system that “everything is okay,” despite the fact that novel molecules from the fetus are present and could be recognized as foreign to the mother’s own body. Identifying the molecules that are responsible for telling the mother’s immune system that “everything is okay” has proven to be one way to help with immune protection regarding stem cells for various therapeutic uses. Dr. Cowan’s lab has now successfully made these “cloaked cells” and is currently testing them in immune competent mice. The hope with these cells down the line is that they will be an “off the shelf” quality controlled product that is compatible with any patient and able to be produced in large quantitates and stored and distributed at any given moments. Such cells could not only be used for diabetes, but a whole host of other disease states that benefit from cell therapy (see slide below).

  • Dr. Cowan began the talk on a lighter note, explaining his career path and the effect that Dr. Doug Melton had on him and how the acclaimed researcher “captured [his] imagination” back in 2001. Dr. Cowan’s research journey began with work in cell therapies, when halfway through his PhD, the discovery of human embryonic stem cells occurred. He became “entranced” by the idea of using these cells to understand human development, and traveled around the world and visited all the various labs that were using this novel tool. In the process, he met Dr. Melton, who was working on potentially using hESCs to make insulin – it was his single minded mission, given that his own daughter and son were both diagnosed with type 1. Broadly speaking, Dr. Melton had two big ideas at the time: (i) take beta cells from people with diabetes and understand the root cause of the disease; and (ii) take a diabetic beta cell, correct it, and then transplant it back.  These ideas had a huge influence on Dr. Cowan’s research path.


Questions and Answers

Dr. Aaron Kowalski: Can you talk about the concern when “cloaking cells” and the risk for cancer?

Dr. Cowan: That’s a great question. Some of these molecules that protect cells from the immune system are also involved in cancer. The same things that are protecting the cells by having them evade the immune system might also be making them one step to becoming cancerous. There is however no evidence that these cells cause cancer in the first place – there are not too many cases where beta cells themselves are the cause of cancer. The way I like to think of this is if you would do this for your child or loved one – do you feel safe? With the right experimentation, the right set of studies, we can get to the point where you might get to that point where you do feel safe. But it does take time. People are doing these studies now and we are going to get a ton of information. It is possible engineering “kill switches” into the cells and make them sensitive to certain drugs, such that if something went wrong, we would give the patient these drugs and it would eliminate the cells.

Q: Given the speed of gene editing and cloaking vs. encapsulation, it seems like cloaking is moving so quickly and we know the foreign body response issues with encapsulation – why even bother with encapsulation at this point?

Dr. Kowalski: I’m a big believer in lots of shots on goal. We still don’t know everything we need to know concerning doses and quantity of cells. If the trials that Semma are doing, where they put in a functional dose and it lasts for a year, work, then we are going to learn a ton.

Q: Where else is JDRF funding this type of work?

Dr. Kowalski: Cell replacement is a top priority of ours. Some of you may have heard me give this anecdote before, about James Shapiro in Canada. He was a pioneer of islet transplantation. He said to me, “I know JDRF isn’t focused on this anymore, but remember that it does work.” He went on to tell me that he has patients off of insulin with normal blood sugars for 17 years. This can work – these cells can cure type 1 diabetes. We thought when we did that in the 90s that it would be scalable and cure everyone. Two big issues of course are cell sources and protection.

 

--by Martin Kurian, Albert Cai, and Kelly Close