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Dear Cure JM Families, Friends, and Supporters,
Allow me to open by apologizing for the lengthy year-end message that follows. As I thought about the opportunities ahead of us over the next few years, I feel it’s essential to provide the “big picture” overview of 2025 research priorities—a look at where we are and where we are going.
The three reasons why 2025 will be our most important year yet:
1.) Drugs known as “JAK inhibitors” present the greatest potential for newer and better treatments with fewer side effects. There are several promising JAKs under study, and others are in such early development they are yet to be named.
2.) CAR-T therapy may well stop JM in its tracks. Early results are more than encouraging. Clinical trials are enrolling.
3.) Partnerships with pharmaceutical companies—both big pharma and smaller biotech companies—are critical in order to ensure that JM is embraced as a target in industry trials and that newer and better therapies are available in the marketplace.
Let’s take a look at these three critical initiatives and what the opportunities mean for Cure JM in 2025.
First, JAK inhibitors: 60 patients with juvenile myositis have been treated with JAK inhibitors. These are drugs known by names you might recognize: baricitinib, ruxolitinib, and tofacitinib, to name a few. Of these 60 JM patients, 36 had chronic muscle weakness, and all 60 exhibited skin disease. After JAK treatments, 30 of the 36 patients with muscle disease (83%) saw moderate to significant improvement. Of the 60 patients with ongoing skin symptoms, 57 (95%) saw moderate to significant improvement after JAK treatments.
All four treated JM patients with interstitial lung disease saw improvements in lung function. Equally, if not more impressive, 31 out of 33 adult Dermatomyositis (DM) patients with interstitial lung disease have seen improvements in lung function after JAK treatments.
Patients with calcinosis also reported notable improvements.
These conclusions are reported by Drs. Julie Paik and Lisa Christopher-Stine from the Johns Hopkins Myositis Center note the need for clinical trials to confirm the extraordinary findings of their study.
Indeed, several clinical trials are now underway, the most important of which may be for the inhibitor deucravacitinib. The trial is being run by Dr. Andy Mammen of Johns Hopkins and the NIH, who is also a member of Cure JM’s Medical Advisory Board.
I have now been involved in the business side of drug development for well over 20 years. I’m not a scientist, but I do know encouraging evidence when I see it, and this is compelling evidence.
In simplest terms, juvenile myositis is an “interferonopathy,” meaning that the interferon protein is overexpressed in muscle, skin, and other organs due to dysregulation of signaling pathways.
While interferon is supposed to send signals to the body to inhibit inflammation—the normal immune response—the overactivation of interferon pathways actually results in the opposite. The overexpression triggers an autoimmune response that results in muscle, skin, and vascular inflammation—all hallmarks of JM. JAK inhibitors block the pathway, resulting in no—or at least less—protein overexpression and notable patient improvement.
In 2025, Cure JM will continue to be focused on JAK development.
Second, CAR-T therapy: I’ve shared the promise of CAR-T therapies recently, but the enthusiasm of the scientific community is worthy of an updated review. Along with JAKs, CAR-T represents a potential revolution of treatment protocols, especially for those JM patients—children and adolescents—with chronic disease that is unresponsive to traditional treatments. In short, CAR-T may be for JM kids (and adults) who will never reach remission with current therapies.
CAR-T works by re-engineering a JM patient’s T-cells in the blood (the good cells) to seek and destroy the aberrant B-cells. These B-cells produce autoantibodies that mistakenly attack the body’s own tissues and organs. Autoantibodies lead to inflammation in JM.
Early CAR-T results in JM adults and adolescents who have not responded to standard treatments are astounding. By any measure, skin and muscle inflammation has receded, muscle strength has increased, vascular symptoms have improved, and calcinosis has reduced. CAR-T patients with related inflammatory myopathies such as lupus reached medical remission and are now sustained for over three years.
Of course, we don’t yet know how long remission will last or if the B-cells, as they repopulate, will remain normal or revert to producing autoantibodies that contribute to the disease. We will know more as we track CAR-T patients over time. What I can say is, so far, so good.
Cure JM is partnering with Cabaletta Bio to conduct a clinical trial in adolescents and adults with JM in 2025. Cabaletta has what we believe to be a superior therapy process for JM, although other companies are also pursuing CAR-T options for autoimmune diseases. Over the next 12-24 months, we will undoubtedly see enormous progress as Cabaletta and other therapy providers move through clinical trials and ultimately to the FDA for approval. Executives at Cabaletta Bio have told me that they expect JM will be the first disease for which they will seek regulatory approval.
Third, partnering with Big Pharma and the biotech industry. Had you asked me a few years ago about the prospect of partnering with pharma, I would have been less than optimistic. But we kept knocking on the door, and over time, the pharmaceutical industry began to pay more attention to autoimmune diseases, including rare ones like JM. This is encouraging because most Cure-JM-funded research is academic research, and often, there is no clear path to move a clinical discovery to the market.
That is changing. For example, pharma giant Bristol Meyers Squibb (BMS) supported the JM clinical trial for the drug abatacept that was conducted at the Cure JM Center of Excellence at George Washington University. The drug deucravacitinib is also a BMS product, and BMS has supported our basic research in deucravacitinib efficacy in JM at SUNY Binghamton.
Octapharma sponsored a clinical trial in myositis for their IVIG product, Octagam 10, which resulted in FDA approval of Octagam 10 for adult DM. A follow-up trial in juvenile myositis is now under consideration.
Century Therapeutics is currently enrolling JM patients in their NK or natural killer cell trial. Similar to CAR-T, the NK process uses a patient’s own natural killer cells to deplete the aberrant B-cell population.
Pfizer’s subsidiary, Proviant Therapeutics, is sponsoring a myositis clinical trial for the drug brepocitinib, a next-generation JAK/TYK2 inhibitor. Pfizer also owns tofacitinib—you know it as Xeljanz—which has found its way into pediatric rheumatology as an effective alternative treatment in JM.
As we close 2024 and look to a bold new year, I am reminded of just how much progress we have made over the past 21 years since Cure JM was founded. There was quite literally nothing on the treatment horizon when our small group of volunteers gathered at Tom and Shari Hume’s home in 2003. Twenty years may seem like a long time, but in research years, it is a nanosecond. The polio vaccine was in development for over four decades.
What I have learned in my 20-plus years of research leadership is that it takes “patient” investing in basic research to get to a stage where Cure JM finds itself today—a stage where newer and better treatments are coming online, often as a result of research grants made years ago. Drug development is a marathon, not a sprint. As long as we can put one foot in front of the other, we will reach the finish line.
We could never have made this progress without you. Cure JM’s current grant obligations total $4.2 million. Over the past several weeks, we’ve made $400,000 in grant payments and will commit another $400,000 in the first months of 2025.
Fortunately, our financial position is solid, even though the higher costs of supporting clinical trials will draw down our reserves. Your support of Cure JM’s Holiday Challenge campaign will ensure we have the financial resources to take advantage of every opportunity within the priorities I’ve described here. If you have made your 2024 contribution to the Holiday Challenge, please accept my sincere thanks.
If you have yet to do so, I hope you will act now to help ensure we leave no stone unturned.
With appreciation for all you do,
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