March 6, 2024 LAM Science Research Update

Great. So,

all right. Good evening and welcome everyone. It's so lovely to see you all

everyone. It's so lovely to see you all here. On behalf of the Lamb Foundation,

here. On behalf of the Lamb Foundation, it is my pleasure to welcome you to this evening's Lamposium in Your Living Room educational webinar series. My name is Cindy Beasley and I am the director of

education and advocacy for the foundation and I will be your moderator this evening. So before we begin, I

this evening. So before we begin, I would like to take a moment to thank our generous sponsor, the National Disease Research Interchange or NDRI. NDRI's

partnership with the Lamb Foundation and Lamb Patients has pushed forward the science of lamb through their coordination of lamb tissue procurement at the time of transplant. We appreciate

their ongoing support of our research efforts and our educational programs. Now, speaking of research, most of you will have received an email survey in

your inbox today regarding Lamb Prep, the Lamb patient needs assessment and research priorities survey. This survey

was developed based on input from numerous Lamb patient focus groups.

Filling out this survey will be invaluable for setting the priorities of Lamb research moving forward. So, we

thank you for your participation. Now,

there's a couple of quick technical items. Microphones will be muted and the chat box disabled throughout the presentations. At the conclusion of the

presentations. At the conclusion of the presentations, we will open the chat box for Q&A. Now, following Q&A, we will

for Q&A. Now, following Q&A, we will move into a patient and family group discussion. Now, we're going to try

discussion. Now, we're going to try something a little different this evening because we're going to use breakout rooms to try to facilitate smaller group discussions. I encourage

you to stay logged on for this opportunity to connect with fellow Lamb community members from across the globe.

So, we've got a great program for you this evening as we welcome our new scientific director Dr. Ver Kimskaya along with lamb specialist and lamb

clinic medical co-director Dr. Rob Kutooff. We will begin with Dr. Kimskaya

Kutooff. We will begin with Dr. Kimskaya and our lamb research update. So, many

of you know Dr. from Skaya because of her long association with the Lamb Foundation and the best way I can describe her is that she is a trailblazer. In 2008, she was tenured

trailblazer. In 2008, she was tenured and appointed as the first female professor of medicine at the University of Pennsylvania School of Medicine. Her

pioneering research on lamb paved the way for the FDA approval of rapamyosin as a new treatment for lamb and TS. We

are fortunate to have her leadership in moving land science forward towards a cure. So at this point we will turn this

cure. So at this point we will turn this over to Dr. Krkaya.

>> Good evening. Thank you Cindy for introduction.

Uh it's a great pleasure today tonight to speak to you uh lamb patients. I'm

very proud to be in this unique position.

>> Uh over 20 years ago I started my um research career working in lamb research and I couldn't imagine that I will be

speaking now as a scientific director of the lamb foundation.

Over 20 years ago, I was very interested to def to find the focus of my research which could save patients life and uh I

was studying path day which called mtorque path day and here's u the image of that and that path specific was in a

key regulation of cell growth and proliferation. Then I learned about this

proliferation. Then I learned about this rare disease lamb which affects only women of childbearing age. I um sent email to Sue Barnes which at that time

she was uh scientific and found she was director founder of the lamb foundation.

And then um few days later I receive um phone call from Frank McCormack which was absolutely fascinating for me because I was just young investigator

starting my lab at Penn and Frank told me that at that time Dr. uh Lisa Hans discover the function of

the gene but I mean the genetic um base of the disease but it wasn't clear what that gene does and uh we were very lucky

at that time to uh uncover the function of TSC2 and this is the only big scientific image what I

show uh which demonstrate how rapomyosin work And how we discover the function.

This is lamb cells which grow really fast and then we usein of label at that

time uh to to really um grow inhibit growth of uh lum

cells. And um just to explain in a

cells. And um just to explain in a little bit more simple terms of all these graphs and dots and uh bands what

is mtor mtor it works like printing machine and in lamb uh loss of uh function of tsc2 leads to it continuous

work of this machine which call mtor and then it's like print and press as I said so what was able Rapomyosin do is

repay inhibit this growth but the problem what we see in clinic and Rob will tell later and you many of you know that it doesn't

completely block that growth of the lamb cells and there is a like second arm of the press can uh keep printing so uh

moving fast forward current time last year it was um uh advances were make to uh discover new

uh drug which called bisteric inhibitor.

So that inhibitor RMC55552 blocks not only one arm but also blocks two arms. And then in models in

preclinical study it was shown that the the drug has potential for inhibiting very effectively MTOR path but those are

models were in cancer and we don't know how they work could work uh for lamb but uh currently there is a clinical trial

and here is information on the screen where um test this drug is tested for toxicity and tolerability.

Once we have that information, we could um explore opportunities where we could move uh forward or not. So that's a uh

update, brief update, current update, an exciting thing. Also, Lamb Foundation is

exciting thing. Also, Lamb Foundation is uh really dedicated for many many years, for all years to support research and

advance research. So here is a current

advance research. So here is a current uh 2024 awardee of research uh three of them. The first doctor

hyberg broham she received this award uh to study uh lamb lung and how that lamb cells really communicate with other

cells in the lung and destroy the lung.

So she trying to understand how holistically that little cells which called lemon we are familiar they really interact with other and lead to

destruction. So she will be using very

destruction. So she will be using very advanced and unique technique uh which became available only in the last few

years. So um this study by uh Becken

years. So um this study by uh Becken Hmer Bromp will also um definitely will show how lamb cell interact with immune

cells and two other award of for this year focusing on investigation how lamb cells escape

detection and killing by immune system.

Uh so uh Dr. tongue uh will investigate uh how uh immune system could be targeted or uh changed uh that be more

effective with targeting and killing cells and Dr. uh Wanka uh will investigate how why macrofagages are not

really um promote this immune immune response which could help kill themselves. So this is current

themselves. So this is current directions which is uh very exciting and promising

also um we um we would like to move towards new

clinical trials and uh but the biggest limitation is how we could really assess uh patients response to the drug for

example and for that reason We uh organized the group. We had actually a meeting this morning with Dr. Hanska,

Mccormack, Asam, Zidi and Steve Hams and u me. Uh we are trying to brainstorm how

u me. Uh we are trying to brainstorm how we could define those little messengers.

What is biomarkers? My markers are the messengers in the blood which could be detected in a patients who just started

>> or maybe how this patients will respond to therapy. Uh and another big question

to therapy. Uh and another big question this biomarker could help us uh will my disease progress. So this is very

disease progress. So this is very challenging and very important directions which we are currently brainstorming the best minds what we have among others just small group and

uh this task force really working tirelessly to understand and develop this direction which will help us to move uh forward.

Um so this is my concluding uh slides because I I just would like to have a brief conversation with you um on

updates. uh and uh so when we started

updates. uh and uh so when we started over 20 years ago trying to find the treatment for lamb lamb patients

which I met and first of them was medalyn which I met on my way to the my first lymposium which is unforgettable

experience for me who are scientists and meeting the patients who really um really opened my eyes on the needs of

the patients and how critical it is. And

at that time we had really very daunting task to really understand disease, find the function and try to stop um develop

or find new first treatment. And uh at that time the question patient was asked if when I diagnosed

uh can I see my children graduated from school and that time the ali mentality

was discovery just discovery that's what we u move forward al work and now over

20 years later we have um we have a progress and lamb foundation makes significant progress which is serve as a model to many rare diseases. But now

Allet task I would say we move into the second phase in our uh challenge finding and paving way towards the cure

uh to how we could understand other more important tasks. For example, we still

important tasks. For example, we still don't don't have understanding how we could tackle a female specific targeting why disease affects only women and

that's one of the key priorities which is now on a uh list of uh most um focus

for science and urgent understanding how patients young patients who have lamb can have quality of life. How how could

they uh women in their prime could have family and that science now challenged this question.

Also women with flame who already have family and children challenge uh issue

of uh quality of life and scientifically the question what I see is how we could stabilize lung function from decline if

not reverse. So that question is very

not reverse. So that question is very big scientifically and very very important for patients. So to conclude I

would like to assure you that every day lamb foundation lamb researchers and clinicians working tirelessly

to find better way to treat and find the path to find new treatment for lamb. And

um we all together in this mission lamb patients clinicians scientists and the foundation and I'm very very proud to be

in this position and have your trust and support moving forward. Thank you.

>> Thank you so much Vera. We are so thrilled and happy to have you leading the helm and pushing us through and providing a roadmap for research. So,

thank you so much.