Update

Fall 2020

FUNDRAISINGHow You Can Help

A Year Without Events
It was a year where events were cancelled, but our incredible
friends and advocates kept pushing and helping us as much as
they could, always providing inspiration for everything we do.

Please consider making a
tax-deductible donation to thistype 1 diabetes research program.
Every gift makes a difference.
1. To make a secure online donation,
visit www.faustmanlab.org andclick on “Donate.”

Our wall of heroes keeps on growing.

Donor Spotlight: Sue Root
For many years, Sue Root has been one of the Lab’s most ardent supporters.
We asked her to share some of her story.

2. You may make a gift by check(payable to “MassachusettsGeneral Hospital”) and mailit to:Diabetes Clinical Trial
c/o Dr. Denise Faustman

How long have you been supporting the lab? My family and I have been
supporting this research for over 16 years. My first visit to the MGH lab was in
October of 2003. After meeting Dr. Faustman and taking 6 months to investigate
the type 1 diabetes research by reading published papers and contacting
scientists around the globe, I believed that BCG could be the first potential
treatment for someone like my daughter, who at the time had been living withdiabetes for 7 years and was otherwise healthy.

Immunobiology Laboratory

Tell us the story of the fundraising ride to Boston. I wanted to help raiseawareness and, more importantly, funding for the Phase I human trial. Working
together with my good friend Jackie Fusco, who has two children living with
type 1 diabetes, we put together a fundraising event that all of our children
could be a part of. What better way than to bike over 200 miles from CT to theMGH lab? Amazingly, and to our surprise, we raised over $150,000. The successof our first bike ride pushed us to do 3 additional bike rides, which we opened
up to the public to participate. We raised over $1 million to help support thePhase I human trial.

On the memo line, please write:“Faustman T1D research.”

What have you learned along the way? Our daughter, Alex, was diagnosed
with type 1 diabetes the week of her 3rd birthday, back in 1996. She is 26 years
old now, working and living in New York City. Alex was one of the youngest
children to be put on the insulin pump when she was in kindergarten. Although
we are grateful for these devices, about 10 years ago I started witnessing ashift from curative research to management of the disease for those who are
already living with type 1 diabetes, which is why I am so passionate about Dr.
Faustman’s research. I have learned so manythings along the way. I learned how important it
is to educate yourself about scientific research,especially if you are going to take the time tofundraise and donate money to any project.

Sue and Alex Root in 1995.

Why are you still excited? There is so much
more to learn about BCG and the effects it hason the body in regards to autoimmunity. I am
excited for my daughter to participate andreceive the BCG treatment when it is available.
I’m also excited to see the effect of BCG in thepediatric population, especially when given to
those who are recently diagnosed in the hospital.

MGH - East
Building 149, 13th Street, CNY-3601
Charlestown, MA 02129

Thank you for joining us in thefight against diabetes!

For more information, visit
www.faustmanlab.org or email
DiabetesTrial@partners.org.
Find us on Facebook:www.facebook.com/FaustmanLabFollow us on Twitter:
www.twitter.com/FaustmanLabUpdates

from the Faustman Laboratory at Massachusetts General Hospital

Fall 2020

A Note from Dr. Faustman
The year 2020 was eventful

for all of us, and it is one
we certainly will not forget
anytime soon. Despite thepandemic, the lab pushedforward. Patients in thediabetes trials found ways tocome in for trial appointments
and, while the golf events,
bike rides and dozens of otherevents we always look forwardto did not happen, we wereable to stay in touch withthe people who continue tomake these trials possible.

The COVID-19 pandemic
also presented a newopportunity for BCG.
Shortly after the pandemic
emerged, researchers whoare part of our global BCG
working group began looking
again at BCG’s efficacy inpreventing complications
from respiratory infections
overall, as well as the emerging
trend of lower death rates
from COVID-19 in countries
that have BCG vaccination
programs. Several membersof our group have initiated

BCG COVID-19 trials. Our lab,in collaboration with Brigham& Women’s Hospital and theImmune Tolerance Network,will begin a BCG trial that isenrolling 2,800 healthcare
workers at high-risk of
COVID-19 infection.

used for more than 100years. This means we needto fund this not-for-profit
research with donations
from individuals and private
philanthropies. We hope
you will help us move thisimportant work forward.

The Phase II type 1 diabetes
clinical trial continues and wecan look forward to unblinding
the trial and analyzing thedata in about two years. An
Expanded Access protocol andpediatric trial will hopefullylaunch soon.

Please contact the lab if
you have any questions
by emailing
diabetestrial@partners.org.

BCG is considered a “generic”
vaccine because it has beenThank you for your support!
Sincerely,Denise L. Faustman, MD, PhD

UpdateFall 2020www.faustmanlab.org

Updates on BCG for Type 1 Diabetes

Updates from FOCIS Meeting

The 2020 COVID-19 Pandemic and BCG

The Phase II trial continues to progress. All
150 enrolled patients have been followed foralmost three years of the five-year trial. Newtrials are launching (pediatric and expandedaccess protocol) and we have been publishing
new findings on the underlying mechanismsof how BCG alters the immune system. Thisincludes new insights on Myc, a pivotal
transcription factor for four metabolic pathways
that accelerates the utilization of sugar. Thisis the first documentation of BCG induction ofMyc and its association with the correction ofblood sugars as seen in the Phase I trial.

The 2020 annual meeting of the Federation ofClinical Immunology Societies (FOCIS) was heldin October as a virtual event. The lab presented
two key updates on the BCG clinical trial program.
The first was new data on the role of BCG inglucose utilization in type 1 and type 2 diabetes.
The second presentation was an update on how
BCG alters the function of a key subset of immune
cells called regulatory T cells (Tregs). Tregs havebeen identified as key to changing the underlying
immune defect associated with type 1 diabetes.

It has been known for many years that BCG
appears to protect recipients from a variety ofnon-tuberculosis-related infections, including
respiratory infections, as seen in global studies.
Further, multiple studies suggest that the impactof COVID-19 is more severe—with more illness
and more death—in countries that do not
routinely administer the BCG vaccination to their
populations. The positive effect of BCG is moststriking in countries who administer the Tokyo
strain of BCG (the strain MGH is using in thediabetes trials). BCG is now being investigatedin multiple global trials using different strains.
Historically, vaccine design has involved theidentification of a specific antigen that generates
long-term, infection-specific immune responses
and protection from the same disease-causing
agent later. This is the approach taken by most of
the COVID-19 vaccine programs. BCG is anotherapproach, aimed at boosting the immune system
to fight infection by triggering a form of boosted
immune memory, called innate immunity, which
can arm cells against a broad range of infectious
diseases. BCG has the added advantage of being
very safe and available in many places, and holds
the potential to prevent complications from thecurrent pandemic. Type 1 diabetes subjects in ourtrials may have added benefits from BCG.

Key Facts - Phase IIb Clinical Trial• Double-blinded, placebo-controlled• 150 patients enrolled (100 BCG and 50 placebo)• All are patients with established type 1 diabetes(not a new-onset trial)• Six doses of BCG over five years• Expected to unblind in 2023

Value of BCG
As more clinical data emerges on the potentialof BCG, groups have started to calculate thevalue BCG could create if approved for type 1diabetes. Boundless Impact, an independent
research organization focused on assessing
new technologies, looked at multiple factors
including:• Quality Adjusted Life Years• Average Annual Cost of Care Per Patient• Invasiveness• Severe Complications
In all major categories, Boundless Impact foundconsiderable value to health systems and patients.
A full copy of the report is available on our web
site, www.faustmanlab.org.

Our FOCIS abstracts:• Correction of Underlying Lymphoid Glucose
Utilization Defects with the BCG Microorganism:
Implications for Type 1 and Type 2 Diabetes
through Quantitative Method Development• Beneficial Effects of BCG Vaccinations inLong-Term Type 1 Diabetes: Updated Clinical
Trial Data and Epigenetic Impact on Foxp3
Treg Methylation

About BCG
BCG is a live, attenuated bacterial vaccine derived
from Mycobacterium bovis. Introduced in 1921,
BCG has historically been given to protect against
tuberculosis and it is generally considered tobe extremely safe. BCG is on the World HealthOrganization’s Model List of Essential Medicines
for adults and children and is given to roughly 100
million children per year globally. Over the lasttwenty years, a growing group of researchers andclinicians have begun to explore the “off target”
effects of BCG for diseases including type 1 diabetes,
multiple sclerosis, allergy, fibromyalgia, Alzheimer’sand respiratory infections, including COVID-19.

BCG-JAPAN Vaccination toPrevent COVID-19 and Other
Viral Respiratory Infections
in Healthcare Workers
This Boston-based trial is funded by theNational Institutes of Health and will test if
one dose of BCG-Japan can protect healthcare
workers at high risk for SARS-CoV-2 infection
from COVID-19 and other viral respiratory
illnesses. A total of 2,800 patients will beenrolled across multiple sites in collaboration
with the Immune Tolerance Network andBrigham & Women’s Hospital. Dr. Faustman
and Dr. Baden are co-principal investigatorson the trial. This is the only major COVID-19
trial using BCG-Japan.

The Fourth International BCGand Autoimmunity Conference
In the Fall of 2019, the BCG Working Group(www.bcgworkinggroup.org) convened ourfourth conference in Barcelona. The meeting
happened well before the start of COVID-19,
but the participants in our conferences andbooks have been laying the groundwork fortrials like the new BCG/COVID-19 clinical
trials for several years. Our group has become
the leading voice for the off-target effectsof BCG and the potential on autoimmune
diseases such as Type 1 diabetes. Peter Aaby
and Christine Stabell Benn did pivotal earlytrials showing BCG protected infants from
respiratory infections and have started aCOVID-19 trial in Denmark. Mihai Netea(Holland), Nigel Curtis (Australia) andGobardhan Das (India) among others are all
conducting major trials of BCG for COVID-19
protection.