BrainStorm Cell Therapeutics Inc (BCLI)

[midastouch017]

but I’ve been burned here before.

Me too, hence i will be on the watching mode only,
hoping for the best for mankind and those suffering
from this terrible disease!
God Bless!

[murocman]

It’s key whether or not the ADCOM and more importantly the FDA, find all of this public input compelling.

You would think so but there’s a lot of bad history here and the FDA is not an organization that easily admits it was wrong.

If they do reject this, I think there will be people with pitchforks and torches after them.

I’d like to say I’m optimistic, but I’ve been burned here before. Will see what the briefings docs say? May dabble into a small position into the ADCOM.

Murocman

[bubbarayjr]

Fox News: Matt's Mom

https://www.foxnews.com/opinion/mothers-hope-treating-als

[midastouch017]

This week it's an either make
or break for $BCLI.
Fingers crossed.

[Monksdream]

BCLI new 52 week low

[Monksdream]

BCLI new 52 week low

[Fmello]

https://seekingalpha.com/article/4635514-brainstorm-cell-therapeutics-i-anticipate-a-positive-adcom-but-there-are-major-risks?mailingid=32729419&messageid=2800&serial=32729419.506&utm_campaign=rta-stock-article&utm_medium=email&utm_source=seeking_alpha&utm_term=32729419.506

[Fmello]

Here's the pdf file listing those who we KNOW got NurOwn in EAP or Phase 2, with hyperlinks to their Public Statements filed with the FDA as of August 17, 2023.

https://www.facebook.com/groups/NOMOREEXCUSESALS/permalink/1038725100403214/

[Fmello]

[bubbarayjr]

incredible

[Fmello]

Comment from Mira Klingenberg:

Dear Dr. Califf, Dr. Marks and Advisory Committee members:

I am Mira Klingenberg from Marcus, Iowa, and the Mother of Matt Klingenberg of Brandon, South Dakota. Matt has ALS. He was a participant in the NurOwn Phase 3 randomized, controlled trial, then he received 6 doses of NurOwn via an Expanded Access protocol.
Matt’s neurologists are Dr. Anthony Windebank and Dr. Nathan Staff at Mayo Clinic. I am writing today to share the “substantial evidence” proving NurOwn works and to ask the FDA to approve NurOwn with a Phase 4 post-marketing study.

I am a healthcare professional, with my BSN, RN. I spent 35 years in psychiatric nursing, working at the Cherokee Mental Health Institute, a state of Iowa hospital. I cared for the most mentally ill people in the state. This type of nursing required expertise in observational assessment and evaluation, using subjective scales and tools. The evidence that I am sharing with you today is no different than the clinical documentation I provided every day in my nursing career.

I’m also a level-headed Midwestern mom. I have seen many people die, and buried many family and friends. There is no deluding myself about this disease and the ravages it causes. All this is to say, my observations are objective and not optimistic. I know ALS will kill my son. But I also know that NurOwn has improved how he feels and functions, improved his quality of life, and most importantly, given him more time with our family and especially his three young children.

“I know ALS will kill my son.” These are the most painful words I’ve ever uttered or written.

I can’t adequately express the difficulty of this journey, how hard it is for Matt, my sunshine boy; Kelly, his wife, and the kids: Mason, James and Aubrey. Matt faces this path with grace and a sense of humor that sustains all of us. Matt deserves the chance to live longer. Kelly works all day every day without fail or complaint. She deserves the chance to love Matt longer.

I worry about Mason, the oldest, already so responsible. He’s 8 years-old. He helps his Dad and Mom with the work of life because he’s called upon to do so. Because of ALS, his childhood will be cut short. James at 5 years old doesn’t quite know this yet but it’s around the corner. Aubrey sits on Matt’s lap, climbing up without assistance, and kisses him like he is her everything.

The reality of this disease hits like a tsunami. Grief, anger, fear are constant companions now. I find ways to stay afloat. One way is knowing my family needs me and another is the firm belief that NurOwn works and that it will be approved.

Matt’s ALS Diagnosis
At 32 years old, Matt was diagnosed with ALS. His onset was in his upper limbs, on his non-dominant side. The initial symptom prompting medical care was left shoulder fasciculations. My no-nonsense son knew his body and knew something was wrong. He pushed for answers and was diagnosed on March 18, 2018 at the University of Iowa Hospitals. He was diagnosed based upon his fasciculations, his EMG and his abnormal neurological exam. In June of 2018, a second opinion by Dr. Crum at Mayo confirmed ALS. On August 26, 2018, Matt’s ALSFRS was 48/48.

Last week, Matt celebrated his 38th birthday. When he was diagnosed at 32 years old, we didn’t know if we would see these birthdays. Matt is now 5+ years post-diagnosis. He has outlived the average 2-5 year prognosis. We’d like to keep that streak going.

The NurOwn Trial
On September 24, 2018. Matt was evaluated for BrainStorm Cell’s Phase 3 interventional clinical trial of NurOwn at Mayo Clinic. At screening, his ALSFRS was 46/48. He reported to Dr. Staff that, since June, his left arm, thumb and foot were worse. To qualify for the trial, you had to lose at least 1 point/month in the ensuing 12-week run-in phase. Matt met that threshold and was accepted into the trial. His first dose was January 2019.

On July 30, 2019, Matt had his last appointment for the NurOwn trial. His progression halted. He functioned normally, with minor lifestyle changes (electric can opener). We did not tell family or friends of his diagnosis until January 2020. Everyone was shocked as no one could see any impairments. Eighteen months after his diagnosis, Matt had no observable symptoms of ALS.

After the NurOwn Trial
Once the NurOwn trial was over, these are my observations about Matt’s disease manifestation:

Disease was evident by February 2020 – over a year after his last dose in the trial, but much of 2020 Matt was able to live normally with little progression. His bulbar function was normal. He ate, talked, and breathed without difficulty.

His gross and fine motor skills showed limited impairment. His walking was slower and less steady. But, he walked at parks, worked in the garden, held the kids and gave horsey-back rides. At Christmas he sat on the floor and played games with the kids. He worked with tools around the house with his dad. In June 2020, he built a sandbox for the kids, only needing help with the heaviest lifting and screwing boards together after he got tired.

By the end of 2020 and into 2021, progression was steady. Decreased balance. Falling occurred and increased in frequency, typically several times a week. Increasingly unable to use arms, decreased mobility and strength in arms/shoulders. Walking was slower and gait demonstrated further foot drop.

In April 2021, due to declining mobility, he retired from work at just 35 years old and moved his family to South Dakota so his wife Kelly and his children, Mason, James and Aubrey, would be close to Kelly’s parents after he died. Matt supervised the moving, but was unable to lift or carry boxes or items. Dressing and showering were more difficult. Kelly took over more household chores.

Notably, Matt experienced increased pain, cramping and spasticity, as is common with upper motor neuron involvement. It is a fallacy that ALS is painless.

Without NurOwn, the pain increased and progression sped up. Assistive devices such as w/c, scooter, larger eating utensils were used. On the ALSFRS assessment, the areas most affected were the fine and gross motor domains. The bulbar and respiratory domains were mostly unaffected – though his voice was slower with a different cadence.

NurOwn Expanded Access Program: Doses #1 - 3 in 2021
In June 2021, Matt received NurOwn via an expanded access protocol. In this round of EAP, he received 3 doses. Matt immediately noticed his walking improved. He had better balance, with fewer falls. In his statement to the FDA in a Patient Listening Session in October 2021, Matt told them:

After my first injection of NurOwn on June 10th my balance improved immensely. Before that injection I was falling down several times a week and after the injection I stopped falling down.

His fine motor skills improved as well as he was able to open wrappers on chewy bars for he and the kids. He was also able to buckle their car seats again, which meant he could help with getting the kids or car rides. He could also buckle his own seat belt. Overall, he reported “feeling better.”

With the second treatment in August 2021, Matt experienced stabilization and some improvement. He continued to have no difficulties with breathing. This second dose caused a change in his speech. Matt’s voice was stronger with improved cadence. This was noted by myself and others, who commented about his voice.


Matt explained this to the FDA in the October Patient Listening session:

After my second injection I noticed that my voice improved dramatically. Before the injections, my tongue would get very tired during long conversations and now that doesn’t happen.

Matt has stated he hopes his voice goes last, as he wants to be able to talk to the kids until the end. NurOwn helps his voice.

Each dose in EAP helped his gross motor function. The ability to climb stairs is one of the questions in the gross motor skills domain of the ALSFRS. Quite compelling are the two videos from June of 2021 comparing Matt walking up/down the stairs in his home before and after the first NurOwn dose in EAP. The third video shows him descending wooden stairs in July 2021.

In this video, you can see that Matt is able to walk up the patio steps at my home on September 21, 2021 – this is 3.5 years after his ALS diagnosis.

His improvement wasn’t just limited to climbing stairs, but walking as well. Because of how frequently he was falling, previously Matt had been confined to the farmhouse when they visited his wife's grandmother’s property. After receiving NurOwn, Matt was able to walk on the rutted, uneven dirt and gravel road on the family farm. Fearful of him falling, I was one step back and to his left as he walked on the road. But he never tripped or lost his balance.

As Matt told the FDA in October of 2021:

Before the injection, I was confined to the little area in the blue rectangle because it was flat. After the injections, I can travel down the sloped gravel road to the machine shed. This is a huge quality of life win for me because my three children love hanging out in the machine shed and climbing around on the equipment. After the Nurown injection, I get to walk down there and enjoy that
with them.

This regained function is about so much more than just the ability to walk better... it’s about what it enabled Matt to do with the kids. For Matt, this is everything.

Matt started EAP at 37/48 on the ALSFRS. He finished EAP at 38/48.
Recall that his ALSFRS score at trial screening was 46/48, and to qualify for the trial, he had to lose at least 1 point per month during the run-in phase. Thus, from the September 2018 screening to the September 2021 end of EAP – in 36 months – Matt had only lost 8 points of function. Even including the quicker earlier progression during the run-in phase, this is still an overall average of just 0.22 points per month – approximately 20% of an average ALS progression.

Sadly, with no NurOwn doses for 6 months, the steady decline resumed, albeit more gradually than before the trial. Matt needed assistance with walking. He predominantly used the walker, switching intermittently to a wheelchair or scooter. He needed more help with ADL’s such as putting on shirts and shoes.

But, there were still things to celebrate. This video in March 2022 demonstrates Matt’s core strength as he was able to sit up from a lying flat position – without using his hands. And this video shows, as of April 2022, he was still able to walk slowly up the patio stairs.

NurOwn Expanded Access Program: Doses #4 - 6 in 2022
In May 2022, just before Memorial Day, Matt began the second round of EAP. Again NurOwn improved how Matt felt and functioned. After that first dose in May, Matt said to me: “Mom, I feel whole, I feel like my body is working again.” Those are words a mother never forgets.

Matt’s body responds. Within the first day, the symptoms like fasciculations (muscle twitching) are less severe and intense as well as his stiffness and spasticity are less severe and intense with every NurOwn treatment. This is critical as the latter are what causes pain. Matt has a significant amount of pain and although he never complains, the look on his face and his activity level are revealing.

Demonstrating the changes in fine motor skills and core strength, this video shows that he was able to bend at the knees to squat a little, lean over, and pick up a leaf with his right hand Matt’s ROM in his upper limbs improved. Compare this video at the hotel in Minnesota the night before the NurOwn dose at Mayo, and this video one week later in his front yard in South Dakota. There is marked improvement. The ability to raise his arms higher and move his arms more freely is important to Matt’s ADLs such as the ability to shower, shave and groom himself. It also made it easier for Matt to hug his kids.

Matt’s upper limb improvements mirror those reported by Nicole Cimbura’s husband, Mike, after he received his one dose of NurOwn in the Phase 2 trial in 2015. It is my understanding this was repeatedly communicated to the FDA at that time. It was also shared by Nicole during the Patient Listening Session with EAP participants and Dr. Wilson Bryan (CBER's OTAT) on October 12, 2021:

Mike was able to raise his arms above his head to wash his hair, shave his own face, put on a tee-shirt over his head, stand up without assistance, walk around a National Park – all abilities he had lost prior to his NurOwn treatment.

And again, this was shared with the FDA in the December 2022 Press Release wherein people in the EAP advised that they had regained the ability to “put our arms over our head, and wash our bodies and hair unassisted.”

With that single EAP dose in May 2022, Matt’s walking, drop foot and balance improved. He relied on assistive walking devices less. Although he had previously used a walker consistently, he was now able to walk without one around the house. Before the NurOwn dose, this May 19th video shows Matt in his Minnesota hotel. His gait is stilted and he is relying upon a walker to walk.

On Memorial Day weekend – after receiving the dose the prior week – Matt walked on the sidewalk and grass independently. The grass is significant as it is tall, “sticky” and makes walking with drop foot even more difficult. You can also see improvements from the May 27th video to the May 29th video, where Kelly, a physical therapist, comments that he’s “walking with his heels down.”

Matt’s improvement was so profound that his two young sons noticed the difference. That weekend, they started by Matt watching the boys and Aubrey race each other on the front lawn. This was followed by 4-year-old James noticing the speed of Matt’s gait in this video:

“DaDa, you walking a lot better... yeah, you walking a lot faster... but I still beat you.”

Both boys join in the pronouncement that they can both beat their Dad in a race. With a hopeful response , Matt tells the boys:

“Well maybe if I can keep getting more medicine, then I’ll beat you guys.”

In response, you can also hear Kelly, a physical therapist, affirming James’ observation and remarking how fast Matt can walk now and that he’s putting his heels down. A few days later in this video on May 29th, 6-year old Mason again proclaims, rather matter of factly:
“DaDa’s walking better!”

Matt’s stabilization was sustained through the next two treatments, with the last dose in September 2022. And the effects of NurOwn endured for a while. Just as he had climbed stairs in September 2021 during the first round of EAP, in January 2023, Matt maintained the ability to walk up basement steps independently, only requesting help for stabilization when he got to the top step where there was no handrail. This was approximately 5 years (58 months) from his date of diagnosis.

NurOwn improves Matt’s Quality of Life
One of the most significant things about Matt’s improvements in and maintenance of functionality are how it impacts his ability to interact with his wife and the kids. This means everything to his quality of life.

What NurOwn has given Matt is immeasurable. These are just some of the memories he has made because of how NurOwn made him “feel and function.” There is nothing more “clinically meaningful” than this.

In January 2022 and 2023, our entire Klingenberg family vacationed together in Florida. In 2022, the kids had their first trip to Disney World. You’ll notice that Matt was still able to stand, and was able to take them on rides. They’ve traveled to historic Mt. Rushmore, were at Clearwater beach in 2023, and to the Omaha zoo in summer 2023. He was there, participating, when his kid’s experienced these new life events.

These photos show you some of the recent memories Matt and Kelly have made with the kids in 2023. “Clinical meaningfulness” isn’t only measured by how long you can stand on your toes, how adeptly you can touch your finger to your thumb or how long you can blow into a spirometer. Each of these pictures is a glimpse into the “clinically memorable” moments that Matt has been making because of NurOwn.

One particularly touching time was during camping weekend. Matt and his three-year-old daughter, Aubrey, have a special bond. Matt is a “Girl Dad.” This video was taken when the family went camping in August of 2021 (after he had received 2 doses of NurOwn in EAP). Functionally, it shows that Matt is walking in a slow saunter with almost no detectable impairments – 3.5 years after diagnosis. Most people who aren’t familiar with this disease would not know that he has ALS.

But more importantly, it shows a father-daughter stroll on a lazy summer vacation ... and Matt making memories with Aubrey.

A year later, on July 28, 2022, we went camping again. In this video are both the good and the bad. The kids love to camp – sleeping in the camper, playing in the water, with bugs, frogs, campfires, s’mores, and so much more. They especially love the “creaky bridge.” Matt was still able to walk on and maneuver the old swaying suspension bridge to throw rocks with the boys – an accomplishment when ALS strips your body of its core muscles and balance.

But, you can also see that Matt has lost function without consistent doses of NurOwn. He can no longer raise his arms to throw the rocks and can only toss them sidearm. And as he walks, you can see that his gait is markedly different than it was on his father-daughter walk with Aubrey one year prior. This summer in 2023, Matt was no longer able to walk on the bridge.

Matt has also been making sports-memories with the kids. When Matt was younger, he was a gifted, four-sport athlete. He played both ways in football, placed 2nd at 145 lbs at the Iowa HS state wrestling tournament, placed 5th two times in the 800 meter run at the Iowa HS state state track meet.

His favorite sport was golfing and he once got a hole in one on our home town golf course.

This photo of Matt is from 2018 - just before his ALS diagnosis. Matt was an outstanding golfer but with upper limb onset, he knew his days of playing 18 holes were over so he sold his clubs in 2019.

While Matt no longer has the upper limb strength or range of motion to hit a drive, in this video from July 30, 2022, you can see Matt standing and putting. Even now Matt is able to give Mason verbal golfing instruction and enjoys being on the golf course with the family.

The Present
Now in July 2023, Matt’s progression has become more rapid. Matt’s voice is more affected: softer, slower, and a little slurry. Today, my Matt is still walking. But, his walking is very slow with right leg immobility at times. He can still get up off the couch, but asks for assistance more frequently. His electric wheelchair is used. The bathroom is remodeled. We know how this is going.

To date, he is not using any assistive breathing devices. This is significant as the collection of the breathing data in the trial was halted due to COVID. It’s an incalculable loss as nearly everyone in the EAP has reported improvements in breathing – even the people who were at the lower end of the ALSFRS scale. Some people had 40% improvements in FVC; others like Matt Bellina stopped using a bipap.

Loss of respiratory function kills people with ALS when their phrenic nerve stops innervating the diaphragm. This improvement, alone, should be enough to support approval as it’s not just “clinically meaningful,” but clinically critical.

Substantial Evidence Proves that NurOwn Works
Our family's request is simple. Please give our son more time. Please approve NurOwn.

NurOwn works for my son. I’ve witnessed his beginning symptoms, when progression halted, when some improvements were seen and felt, when symptoms were alleviated, and also when the normal progression of a 100% fatal disease resumed without NurOwn.

There is “substantial evidence” that NurOwn works, improving how people feel and function. The clinical trial data demonstrated – with just three doses – that NurOwn met its pre-specified secondary endpoint, slowing loss of function.

We believe there is a dose-dependent response. With six non-consecutive doses in EAP, Matt’s experience is even stronger and more sustained than the Phase 3 clinical trial data. NurOwn doesn’t just slow loss of function. In Matt, it halts his progression and helps restore some function. It improves his quality of life.

For those who question whether NurOwn can halt or significantly slow ALS progression, I’d direct your attention to the clinical data published in the Supplement in Muscle and Nerve. Even with a small heterogeneous trial population, the p-value was .022 for people with scores of 34+. Matt was in this population during the Phase 3 trial and again in EAP.

The biomarker data adds to the “substantial evidence” proving NurOwn works. It demonstrates that NurOwn is having a biological impact on the inside, matching Matt’s improvement on the outside. And no one in the placebo arm experienced these positive changes. Plus the biomarker data proves NurOwn is hitting its target engagement across the disease spectrum, not just helping those early in progression. To the best of my knowledge, these multiple CSF biomarker changes are a first in any interventional trial for sporadic forms of ALS.

Accelerated Approval Advances Science & Ensures Humanity
The test for Accelerated Approval is whether surrogate endpoints, like the CSF biomarkers, are reasonably likely to predict a “clinically meaningful” benefit. I will defer to Matt’s neurologists at Mayo to talk about how they correlate with and corroborate the clinical trial data, but I can say that our family is absolutely certain that NurOwn provided Matt with many clinically meaningful benefits. I can also say with absolute certainty that Matt will die more quickly if NurOwn is not approved.

For those who query if we need another trial, that can be accomplished with Accelerated Approval. You can show humanity to my son and the other 32,000 people battling ALS by approving NurOwn, while concurrently conducting a Phase 4 study.

And there is an upside to the scientific community too. Unlike cancer and COVID, where interventional trials enroll thousands, in a rapidly fatal rare disease like ALS, the trial populations are small. No Phase 3 trial with a few hundred could ever provide the treasure trove of CSF biomarker data that could be obtained in a Phase 4 study of thousands.

This is a unique opportunity with a post-marketing study of NurOwn because of its method of delivery. When Matt receives NurOwn via intrathecal injection, Dr. Windebank removes a small amount of CSF to make room for the NurOwn dose. In a Phase 4 study, those CSF samples could populate a biorepository that could empower researchers to transform the science of not only ALS, but other neurodegenerative diseases too. Humanity and science need not be mutually exclusive.

For all these reasons, our family is asking CBER to exercise the same regulatory flexibility as CDER has shown for other ALS therapies. We know NurOwn works, please don’t let a Type II error kill my son.

Matt’s Goal
Because of NurOwn, Matt is still making memories with his family over 5 years post-diagnosis. He is outliving the natural history of this disease.

Matt wants to live long enough for his children to remember him. Even changes of a small magnitude can help him achieve this life goal. There is no scale that can measure what it would mean for his kids to remember their Dad alive.

Please approve NurOwn.
Thank you.

Mira Klingenberg

[murocman]

I don’t know who could possibly read that and not support approval unless they are heartless, and/or without any empathy for other human beings.

That being said, I think approval is maybe 40-60. The amount of animosity that exists within the FDA towards Brainstorm is going to make it very challenging to get this past the finish line.

I sincerely hope they do. This would be an incredible game changer in the ALS battle.

Murocman

[Fmello]

Here is the comment that Matt Bellina's mom uploaded to the FDA:
https://www.regulations.gov/comment/FDA-2023-N-2608-0012

Dear Advisory Committee Members and Food and Drug Administration Staff:

I am writing to appeal to the Advisory Committee to vote to approve NurOwn for the treatment of Amyotrophic Lateral Sclerosis (ALS).

My son Matt Bellina was diagnosed with ALS in April 2014. By Mid-2018 he was wheelchair-bound and using a Trilogy machine (a non-invasive ventilator) during the night to assist with breathing. Matt was struggling to swallow and choking incidents were frequent and terrifying. The length of time it took to definitively diagnose Matt’s ALS precluded him from participation in any clinical trials. The “duration from date of first symptom” trial- participant measure is a common exclusion for people living with ALS.

In the fall of 2018 Matt, unable to participate in any active trials, opted to access a promising therapy through an FDA-approved alternative pathway. Matt’s breathing was challenged. He was “huffing” while breathing. The weight of his own lungs made taking a breath a conscious act which he could perform while awake. Matt used a trilogy device (a non-invasive breathing device) to assist in breathing while sleeping. Over the past 10 years I’ve known hundreds of people living and dying of ALS. I knew this “huffing” activity was the sign of a final decline that started the irreversible trajectory to more invasive breathing assistance and death.

Matt is a veteran and under the care of the Philadelphia VA. He petitioned Brainstorm and the Veterans Administration and requested access to NurOwn, they both agreed. The treatment started with a bone marrow aspiration on 11/19/2018 where they gathered his own cells to build the foundation to carry the NurOwn treatment. Matt’s ALSFRS-r score at that time was 21. Six weeks later, on December 27, 2018, Matt received his first NurOwn treatment at the Philadelphia VA Hospital. On that day, after the intrathecal injection, Matt nearly choked to death while eating dinner. This incident is documented in his post-procedure medical records.

Fast-forward one-month, mid-January 2019, Matt stopped choking while eating, he was breathing without mechanical assistance, the “huffing” was gone. He was completely off the trilogy machine. Shortly after, Matt was able to lift his arm and remove his own sunglasses, scratch an itch, touch his children’s faces. His breathing improved, his swallowing improved, and he was able to move in ways he could not before the first injection in December 2018. On 1/25/2019, his ALSFRS-r Score was 23. Two points higher. We knew this was not just a “pause” in progression. Matt went on to have 6 more treatments. By mid-2019 Matt was able to rise and stand without assistance. On 11/1/2019, nearly 1 year after his first treatment, Matt’s ALSFRS-r was 27. 6 points higher than it was prior to treatment.

Matt’s blog post of 3/5/2021 outlines his pre/post NurOwn stats, documented in his VA medical records. a summary of his blog including the dates/stats he posted at the time:

• Bone Marrow aspiration:
11/19/18

• NurOwn Infusion Dates:
12/27/18
2/12/19
4/18/19
7/18/19
9/18/19
11/21/19
8/12/20

• ALSFRS r:
Matt’s Note: “Leading slope from diagnosis to first NurOwn treatment averaged a loss of 0.45 ppm” 11/19/18 – 21
Below is

12/27/18 – 21
1/25/19 – 23
3/15/19 – 26
5/17/19 – 27
8/23/19 – 27
11/1/19 – 27
12/20/19 – 26
3/27/20 – 25
7/31/20 – 24
10/2/20 – 24

• PFT:
Matt’s Note: “ Unfortunately, I have not seen Pulmonary since this whole Covid thing started. I have been doing Virtual clinic, so the last data point is the end of 2019. I have still not gone back on the Trilogy despite being hospitalized with pneumonia for 8 days in February 2020.”

12/19/2019 PFT: FEV1 2.51 (58% pred), FVC 3.21 (60% predicted), FEV/FVC 78%
11/1/2019 PFT: FEV1 2.80 (65% pred), FVC 3.69 (68% predicted), FEV1/FVC 76%
8/23/2019 PFT: FEV1 2.71 (XX% pred), FVC 3.46 (XX% predicted), FEV1/FVC XX%
7/18/2019 PFT: FEV1 2.45 (56% pred), FVC 2.89 (53% predicted), FEV1/FVC 85%
5/17/2019 PFT: FEV1 2.54 (58% pred), FVC 3.84 (71% predicted), FEV1/FVC 66%
3/8/2019 PFT: FEV1 2.79 (XX% pred), FVC 3.85 (XX% predicted), FEV1/FVC 72.5%
2/12/2019 PFT: FEV1 2.55 (59% pred), FVC 3.11 (57% predicted), FEV1/FVC 82%
1/25/2019 PFTs: FEV1 3.12 (72% pred), FVC 3.81 (70% predicted), FEV1/FVC 82%
12/27/2018 PFTs: FEV1 1.83 (42% pred), FVC 2.61 (48% pred), FEV1/FVC 70%

• Elliptical Results:
Matt’s Note: “Unfortunately, also pre-Covid because the Governor of Pennsylvania shut down the facility where I was using the equipment. I have been riding at home with similar results but it is not standardized.”

11/14/2018 Time 40:00 Distance 1.81 miles
4/3/2019 Time 40:00 Distance 3.05 miles
3/16/2019 Time 40:00 Distance 3.11 miles
5/30/2019 Time 40:00 Distance 4.41 miles
7/8/2019 Time 60:00 Distance 5.41 miles
7/24/2019 Time 60:00 Distance 5.63 miles
8/7/2019 Time 60:00 Distance 5.84 miles
9/9/2019 Time 60:00 Distance 6.04 miles
12/2/2019 Time 60:00 Distance 6.11 miles

Matt’s last NurOwn dose was administered nearly 3 years ago on August 12, 2020. In the same order in which the disease progressed the first time, Matt started losing ground. Matt can no longer drive his chair or reach up and touch his children’s faces. He is still breathing on his own and still does not use a trilogy machine. He still takes all nutrition by mouth.

Everything about Matt’s experience with NurOwn supports the published trial data and the reports of other responders in the trial:

1. There is no doubt the treatment had a favorable impact on the progression of Matt’s disease. His ALSFRS- r scores confirm a pre-treatment decline of average 0.45 per month prior to NurOwn then a steady climb from 21 to 27 in the year following.

2. Post NurOwn, with a gap of nine months between dose 6 and dose 7, Matt started to decline in line with the pre-treatment ALSFRS-r slope though he continues to breath and eat with no intervention.

3. NurOwn had an undeniable biological effect on Matt. We believe there was a measurable and sustainable reduction in neurodegeneration, that NurOwn provided neuroprotection and that it reduced neuroinflammation.
We ask the FDA and the Advisory Committee to exercise the regulatory flexibility in the approval of this treatment for all people living with ALS today and for those diagnosed in the future. The NurOwn trial data and our personal experience demonstrate this treatment has a significant, measurable benefit and that it can stop and reverse ALS progression.

We ask the FDA to allow people living with ALS a chance to survive until another treatment is found. NurOwn is a start. The ALS Community deserves to see their disease treated with the same approach as other, now chronic diseases like cancer, HIV, and diabetes. In those diseases patients are receiving therapies that extend their lives while research continues seeking a cure. Since NurOwn is biologic in nature, we ask CBER to apply the same standards of urgency and flexibility as CDER does in the non-biologic space.

We know this treatment worked for my son Matt. It would be a travesty to continue to keep this effective treatment away from him and others, knowing it can stop and reverse the devastating progression of ALS. We can no longer stand by and watch people die when we know there is an effective treatment.

Very Respectfully,

Deborah Bellina ALS Mom

[midastouch017]

BrainStorm Cell Therapeutics Data Show Treatment with NurOwn Significantly Reduces NfL, a Key Biomarker of Neurodegeneration

https://finance.yahoo.com/news/brainstorm-cell-therapeutics-data-show-110000879.html

New data presented this week at Gordon Research Conference

Analysis reinforces NfL levels as predictive of ALS clinical outcomes

NEW YORK, July 7, 2023 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, this week presented new biomarker data from the Phase 3 trial of its late-stage investigational ALS treatment, NurOwn at the 2023 ALS and Related Motor Neuron Diseases Gordon Research Conference. These data show that treatment with NurOwn significantly elevated markers of neuroprotection and lowered markers of neuroinflammation and neurodegeneration, including neurofilament light (NfL) over time compared to placebo in all trial participants.

New data analysis presented this week was motivated by the regulatory precedent set by a recent FDA drug approval in ALS, and the knowledge gained through the regulatory process, suggesting that the blood-based biomarker neurofilament light (NfL) is associated with disease prognosis and progression in patients with ALS and potentially other neurodegenerative diseases. It is believed that reductions in plasma NfL are reasonably likely to predict clinical benefit in ALS.

"It's well known that in ALS, accounting for disease characteristics such as site of onset, time from first symptom to treatment and baseline physical function are important to understanding the treatment effect in clinical trials given the great heterogeneity in the disease, which can influence prognosis," said Stacy Lindborg, PhD, BrainStorm co-CEO and presenter of the poster. "The data we presented at the Gordon Research Conference show that it is equally important to examine biomarker data, particularly neurofilament light, which is a predictor of disease progression. Treatment-driven reductions in NfL are associated with better clinical outcomes in ALS."

About the data analysis

The presentation, titled "CSF biomarkers identified as predictive of clinical outcomes in ALS participants following NurOwn treatment in a phase 3 clinical trial: Reductions in NfL associated with less ALSFRS-R decline", examined biomarkers that were pre-specified in the NurOwn study: 16 pro-inflammatory/anti-inflammatory, eight neurodegeneration, and nine neuroprotection biomarkers. This analysis is the largest biomarker study conducted in people living with ALS. Cerebrospinal fluid was collected for all participants in the trial seven times, per the protocol. The data provide further evidence of the importance of NfL as a prognostic and predictive biomarker. The addition of baseline disease covariates and additional biomarkers to NfL encompassing inflammation and neuroprotection more fully explains the clinical response to NurOwn observed in the trial.

The poster presentation is available on the BrainStorm website, on the Events & Presentations section: https://ir.brainstorm-cell.com/events-and-presentations

Highlights of the biomarker analysis:

Statistical modeling identifies three biomarkers that predict clinical outcomes observed with NurOwn-treatment in the Phase 3 trial (BCT-002), including change in Galectin-1 and baseline biomarkers NfL and LAP/TGFß1, highlighting the importance of three pathways important to ALS in the observed clinical outcomes.

Baseline disease characteristics pre-specified in the primary efficacy model were included as covariates in the statistical analysis of biomarker data, following 2023 FDA guidance and ALS industry standard. These covariates were all found to be important in the analysis of clinical outcomes (p<.001, each covariate), in addition to biomarker data.

Accounting for baseline disease covariates, NurOwn treated participants had reduced NfL values from baseline to week 20 compared to placebo (p<0.05).

NfL baseline levels were prognostic of ALS disease progression, confirming results from other ALS trials. Participants with greater decline from baseline at week 28 as measured by ALSFRS-R total score, had higher baseline NfL values, r=-0.33, p=0.0064.

Causal Inference using a natural disease progression model showed a relationship between reductions due to NurOwn in NfL changes from baseline and ALSFRS-R changes from baseline. The correlation between NurOwn-driven changes at the final measure in NfL (week 20) and ALSFRS-R (week 28), after adjusting for the predicted changes due to natural disease progression, was r=-0.365, p=0.087. This analysis was conducted in participants who had all ALSFRS-R items >1 at baseline.

[midastouch017]

Evaluating Brainstorm's 'Hail Mary' For ALS Treatment

Jun. 09, 2023 4:39 PM ETBrainstorm Cell Therapeutics Inc. (BCLI)9 Comments

Stephen Ayers

Summary
Brainstorm Cell Therapeutics faces uncertainty in the approval process for its NurOwn treatment for neurodegenerative diseases, with a pivotal ADCOM meeting scheduled for September 27, 2023.
The company's corrected data from Phase 3 trials show promising results in certain subgroups, but the lack of statistically significant results across the broader trial population presents challenges for approval.
Brainstorm's financials reveal a decreasing cash balance, which may require the company to seek additional capital soon, adding to the investment risk profile.

Introduction
Brainstorm Cell Therapeutics (NASDAQ:BCLI) is a clinical-stage biotechnology company focused on the development and delivery of advanced autologous cell therapies aimed at neurodegenerative diseases. The firm's unique cell therapy platform, NurOwn, fosters the growth of autologous bone marrow-derived mesenchymal stem cells to produce an abundance of neurotrophic factors. These elements contribute to regulating neuroinflammatory and neurodegenerative processes, promoting neuron survival, and enhancing neurological functionality. Diseases targeted include Amyotrophic Lateral Sclerosis (ALS), Progressive Multiple Sclerosis (PMS), and Alzheimer’s disease (AD), among other neurodegenerative conditions.

In 2022, the company applied for a Biologics License (BLA) for NurOwn, intended for ALS treatment, but encountered a setback when the FDA issued a Refuse To File (RTF) letter due to questions about the clinical trial's efficacy and Chemistry, Manufacturing, and Controls [CMC] processes. In response, Brainstorm held a Type A meeting to address these concerns and subsequently requested to 'File over Protest,' which opened a quicker route to an Advisory Committee [ADCOM] meeting now planned for September 27, 2023.

Following these steps, Brainstorm updated and resubmitted their BLA in March 2023. At the present moment, the FDA is in the process of actively examining the BLA for NurOwn with an action date of December 8, 2023.

This article explores Brainstorm's journey with its cell therapy product, NurOwn, focusing on its FDA review process, financial standing, and the implications for investors amid the ongoing regulatory and clinical uncertainties.

Q1 2023 Financials
Let's first review the company's most recent financial report. As of March 31, 2023, Brainstorm's cash, cash equivalents, and short-term bank deposits amounted to approximately $2.2 million, down from $3 million at the close of December 2022. The company's research and development expenses for the first quarter of 2023 rose slightly to around $2.9 million from $2.6 million in the same period of 2022. In contrast, general and administrative expenses decreased to about $2.2 million from $2.9 million year over year. Overall, Brainstorm experienced a net loss of about $5.1 million in Q1 2023, a slight improvement from the $5.4 million net loss in Q1 2022. The net loss per share also reduced marginally, from $0.15 in Q1 2022 to $0.14 in Q1 2023.

Chart
Data by YCharts
NurOwn Faces Uncertain Approval Prospects in ALS Treatment Journey
The development journey of NurOwn has progressed through a series of clinical trials across prominent U.S. medical centers and the Hadassah Medical Center in Jerusalem, Israel. Initial trials showed promising signs regarding its tolerability and preliminary effectiveness, setting the stage for more rigorous testing.

In a subsequent Phase 2 study conducted in the U.S., NurOwn underwent a double-blind, placebo-controlled trial involving 48 patients. The results not only reinforced the treatment's tolerability but also revealed clinically meaningful benefits. Most notably, patients who received NurOwn showed higher response rates in the ALS functional rating scale over 24 weeks.

Following this, Phase 3 trials were launched with the aim of generating supportive data for a BLA in the U.S. These trials focused on rapidly progressing ALS patients and maintained the consistent finding that NurOwn was well-tolerated. However, they did not produce statistically significant results. Despite this, the FDA allowed the company to proceed with their BLA submission, suggesting room for further exploration.

Significant updates regarding the Phase 3 trial data arrived when the company rectified some initial data. The corrected data from their Phase 3 clinical trial strengthened their original conclusions and indicated a statistically significant treatment difference in a critical secondary endpoint. Additionally, the corrected analysis highlighted considerable benefits for all subgroups with ALSFRS-R baseline scores between 26 and 35 post-treatment with NurOwn.

This data correction shed new light on the Phase 3 trial results of NurOwn. While initial data released in December 2021 did not show statistically significant results, a correction in August 2022 introduced a significant pivot. In the adjusted data, a significant treatment difference became evident for a key secondary endpoint - the average change from the baseline in the ALS functional rating scale (ALSFRS-R) - within a pre-specified subgroup of participants with a baseline score of at least 35. This crucial change was attributed to a correction in the efficacy model utilized in the original analysis. When the pre-specified model was employed in the revised analysis, marked improvements surfaced in all patient subgroups with ALSFRS-R baseline scores between 26 to 35 after NurOwn treatment.

The reevaluated data provides promising signals. The significant improvement in a key secondary endpoint, alongside evidence of beneficial effects on diverse patient subgroups, hints at the potential effectiveness of NurOwn. However, the lack of statistically significant results in the wider Phase 3 trial population might present hurdles in the approval process. Additionally, the reliance on subgroup analyses when assessing significant clinical improvements could potentially stem from sophisticated numerical crunching, rather than being indicative of an authentic, reproducible trend.

The chances of NurOwn receiving approval remain uncertain. The promising subgroup data and solid safety profile might be enough to gain approval under specific circumstances, yet the absence of statistically significant results in primary endpoints in the larger population presents a formidable challenge. Furthermore, the approval process depends significantly on the company's dialogue with the FDA. In 2021, the FDA did not see the data as sufficient evidence to back a BLA but did not discourage a future submission either. This implies that while approval is not assured, there may be scope for negotiation and potential submission of further data to bolster the application. Nonetheless, the final verdict lies in the hands of the regulatory authorities, who navigate the complex and often unpredictable world of drug approval.

Brainstorm Pursues FDA Approval through 'File Over Protest' Protocol
"File Over Protest" is a process within the U.S. Food and Drug Administration's (FDA) drug approval protocols that Brainstorm has chosen to follow for the review of their Biologics License Application (BLA) for NurOwn. This procedure allows a pharmaceutical company to insist that the FDA reviews an application that was initially refused, as was the case with Brainstorm's BLA.

The FDA initially refused to file Brainstorm's application as it believed the application lacked the necessary data to establish NurOwn's safety and efficacy. However, through the "File Over Protest" process, Brainstorm maintains that the existing data is sufficient and demands that the FDA review it.

Choosing to "File Over Protest" is not a decision Brainstorm would have taken lightly. Such a choice could potentially create tension between Brainstorm and the FDA and could lead to a more stringent review process. Furthermore, even though Brainstorm has chosen to "File Over Protest," this does not guarantee approval for NurOwn. The treatment still needs to meet the FDA's rigorous standards for safety and efficacy.

My Analysis & Recommendation
Investors in Brainstorm should prepare for a significant amount of uncertainty. The fate of NurOwn is at a critical juncture with the ADCOM meeting on September 27, 2023, looming in the near future. The FDA's review of the new and corrected data from Brainstorm's Phase 3 trials will be instrumental in defining the future of the drug. Any indications regarding the FDA's position towards the company's addressed CMC issues and corrected trial efficacy data will be crucial.

While there is always a degree of uncertainty surrounding drug approvals, Brainstorm's situation is particularly precarious. I believe the company's decision to 'File over Protest' can be seen as a desperate 'Hail Mary' attempt to push NurOwn over the regulatory finish line. This move could lead to a more stringent and critical review process, which could potentially complicate Brainstorm's interactions with the FDA in the future. Moreover, the lack of statistically significant results in the broader patient population casts a shadow over the promising results seen in specific subgroups.

Brainstorm's financial position further exacerbates these concerns. With a cash balance of approximately $2.2 million as of March 31, 2023, and quarterly expenditures exceeding this amount, the company may need to secure additional capital in the immediate future. Whether through debt, issuing more equity, or forging partnerships, these actions could dilute the value of existing shares and stress the company's financial health.

While the potential breakthrough that NurOwn represents in the treatment of neurodegenerative diseases cannot be denied, the combination of regulatory and financial hurdles paints a risky investment landscape. The optimism stemming from the corrected trial data and the potential of the company's unique cell therapy platform needs to be tempered by the harsh realities of the approval process and the company's precarious financial position.

Given these uncertainties, the current recommendation for Brainstorm is a "Sell". The need for additional capital, coupled with the 'Hail Mary' nature of their 'File over Protest' action and uncertain approval odds, creates a high-risk scenario for investors. Therefore, despite the potentially transformative nature of NurOwn, investors might want to exit at this stage until there is more clarity on the FDA's stance and the company's financial outlook.

Risks to Thesis

There are several potential risks involved that could significantly impact my ‘Sell’ recommendation.

Regulatory Approval: A primary risk is the potential for unexpected positive regulatory outcomes. If the FDA accepts the resubmitted BLA and ultimately approves NurOwn, the company's stock value could significantly rise.

Subgroup Efficacy: The company has noted a significant treatment difference in specific subgroups of ALS patients, as per the corrected trial data. If future data continues to support these results, it could increase the chances of approval, which might boost the company's valuation.

Successful Financing: Currently, Brainstorm's cash position is a concern. However, if the company manages to secure substantial funding without significant dilution of shares, it could enhance the financial outlook and strengthen the company's position, potentially leading to a rise in the stock price.

Strategic Partnerships: Brainstorm may also form strategic partnerships or collaborations that could provide additional financial support, resources, and credibility, potentially increasing the company's valuation.

Promising Future Pipeline: While the current focus is on NurOwn, Brainstorm might have other promising candidates in their pipeline. Future successes in the development of these candidates could increase the company's worth.

Market Sentiment: Investor sentiment can often defy fundamental analysis. If investor sentiment becomes overwhelmingly positive, the stock price could rise, regardless of the current uncertainties.

[midastouch017]

BrainStorm Cell Therapeutics Announces FDA Advisory Committee Meeting to Review NurOwn® Biologics License Application Scheduled for September 27, 2023

https://finance.yahoo.com/news/brainstorm-cell-therapeutics-announces-fda-100000203.html

PDUFA target action date set to occur by December 8, 2023

NEW YORK, June 6, 2023 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced that the U.S. Food and Drug Administration (FDA) will convene a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee (ADCOM) to review the Biologics License Application (BLA) for NurOwn®, its investigational mesenchymal stem cell therapy for the treatment of amyotrophic lateral sclerosis (ALS). The advisory committee meeting has been scheduled for September 27, 2023, and will be available for live streaming. In addition, BrainStorm's BLA for NurOwn has a Prescription Drug User Fee Act (PDUFA) action date targeted to occur by December 8, 2023.

"We are encouraged by the regulatory flexibility that the FDA has shown over the last year in ALS broadly, and with respect to NurOwn in particular, and believe an Advisory Committee meeting is good for patients," said Chaim Lebovits, BrainStorm President & CEO. "We are of course deeply committed to the scientific and regulatory process, which includes continuing research to confirm the results of the NurOwn clinical program and are working with ALS experts in designing a rigorous clinical study to answer important questions about this therapy and inform further research on ALS."

Stacy Lindborg, Ph.D., BrainStorm co-CEO, commented: "We welcome the opportunity to present our data at the forthcoming ADCOM. We remain confident in NurOwn and believe our data support regulatory approval. As is the case with most ALS research, our clinical program generated complex results, which deserve a thoughtful and holistic review by scientists, ALS experts, FDA reviewers, advocates, and patients. We believe this approach honors the needs of those living with ALS and offers the greatest promise for BrainStorm to fulfill our commitment to the ALS community."

About NurOwn®

The NurOwn® technology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are harvested from each person with ALS and are manufactured using an innovative and proprietary process to secrete neurotrophic factors to target specific neurodegenerative diseases. The lead program for NurOwn is for the treatment of ALS, which is under FDA review. BrainStorm's long-term commitment to ALS is demonstrated in preclinical research and a series of clinical studies, all of which have been published in peer-reviewed journals.

The Phase 3 pivotal trial NurOwn did not reach statistical significance on the primary or secondary endpoints, likely due to a "floor effect," which confounds measurement of disease progression in patients with more advanced disease. A thorough analysis of NurOwn Phase 3 data shows evidence of clinically meaningful effectiveness in ALS participants who have not progressed to advanced levels of disease progression. In a pre-specified group of participants with an ALSFRS-R score ³35, there was larger treatment effect across all endpoints with NurOwn compared to placebo, which aligned with historical trials and the study power assumptions. With a statistically significant difference on a key endpoint (change from baseline in ALSFRS-R). Additionally, a post-hoc sensitivity analysis of patients across threshold of >26 through ≥35 on the ALSFRS-R highlighted that NurOwn-treated patients retain, on average, two points of function more compared to placebo - clinically meaningful preservation and important for quality of life for a person living with ALS and their loved ones.

NurOwn's clinical program also included the largest cerebrospinal fluid (CSF) biomarker study ever done in ALS, strong and consistent biomarker data, which are predictive of clinical response in the trial, span pathways that are important to ALS (neuroinflammation, neurodegeneration, neuroprotection), and align with NurOwn's mechanism of action. Biomarker data in all trial participants showed consistent biological patterns of NurOwn reducing markers of inflammation and neurodegeneration, and increasing neuroprotective markers relative to placebo. Biomarker patterns were consistent across all NurOwn-participants, including in those with Advanced ALS disease where clinical scales, such as the ALS Functional Rating Scale, have demonstrated measurement challenges. Three CSF biomarkers were predictive of clinical outcomes in NurOwn-treated participants– neurofilament light (NfL), galectin-1, latency associated peptide of TGF-beta1 (LAP or TGF-b).

The NurOwn clinical program has generated valuable insights into the pathology of ALS, as well as disease progression and treatment. Since the initial Phase 3 readout, BrainStorm has shared the full dataset through rigorous peer-reviewed analysis, including: quantification of Floor Effect, which had been noted but never before explored in depth; evaluation of multiple pre-specified biomarkers, collected at seven different points across 20 weeks during the trial, allowing a longitudinal view; and analysis of genetic data, which represents one of the first ALS trials to prospectively invoke pharmacogenomic analysis of clinical outcome, offering great promise for the development of future treatments for ALS.

BrainStorm previously announced the FDA intention to hold an ADCOM meeting to review NurOwn for the treatment of ALS. The company filed a BLA for NurOwn on September 9, 2022, and received a Refusal to File (RTF) letter from FDA on November 8, 2022. Following a Type A meeting and subsequent discussions with the FDA, BrainStorm requested that CBER utilize the FDA's "File Over Protest" procedure, which offers the shortest amount of time to complete the regulatory process. The BLA active review was resumed on February 7, 2023.

[midastouch017]

Our valuation remains at $20 per share.

It will finally end up at $40 or $0.5 hence $20 average
as per evaluation.

[Fmello]

From Zacks:

The FDA’s decision to grant an AdCom for NurOwn is indicative of the agency’s flexibility regarding therapies for terminal illnesses such as ALS, particularly when there are so few treatment options available to patients. We have the utmost confidence in BrainStorm’s management team as they prepare to present their case for NurOwn’s approval.

In addition, it’s encouraging to see that KOL’s such as Dr. Heiman-Patterson support the idea that the floor effect can influence outcomes in ALS trials, something that will undoubtedly be discussed during the AdCom.

We anticipate the announcement of the AdCom and PDUFA dates sometime in the near future. Our valuation remains at $20 per share.

[Fmello]

https://www.neurologylive.com/view/critical-importance-fda-adcomm-meeting-als-therapy-nurown?fbclid=IwAR1jotHV1fAxK93A48M8EL3uKz1GeE56-W5OXfcVc6UMSoi6zcw0BRsOFBA

[Fmello]

BCLI stock rose 80.33% in five days!
Can't wait to see what happens next week.

[Fmello]

https://seekingalpha.com/article/4591218-brainstorm-upcoming-adcom-meeting-for-nurown-for-als-could-be-start-of-major-turnaround?utm_source=stck.pro&utm_medium=referral

[Fmello]

https://www.cgtlive.com/view/stacy-lindborg-phd-upcoming-fda-advisory-committee-meeting-nurown-als

[Fmello]

From Michelle Lorenz post on No More Excuses:

"Feb 23rd is 30 biz days since the Type A meeting between the FDA & Brainstorm re #NurOwn. This is the deadline or the FDA giving Brainstorm the meeting minutes. Hopefully we will hear news within a few days after that."

[Fmello]

I just read this post on the No More Excuses Facebook page from Michelle Lorenz:

"The FDA has 30 days (we suspect biz days) to share meeting minutes with brainstorm, which would mean Feb 23rd-ish. Then brainstorm has a few days to disclose under sec law."

[Fmello]

No clue. Hope it turns around by the closing bell.

[Robinsold]

Started the day up... whats going on

[Fmello]

Ouch...down -18.89% do far today.

[bubbarayjr]

Nice movement this week, hope it's due to leakage...

[Fmello]

We're up +$1.18 (77.63%) in the past 5 days. I'd like to see the same progress over the next 52 weeks.

[midastouch017]

Stock manipulation.

[Fmello]

Up 46.58% over the past 5 days.

[Fmello]

Biotech Showcase

https://event.webcasts.com/starthere.jsp?ei=1591565&tp_key=3794c48ea7

[Fmello]

Brainstorm Cell Therapeutics (BCLI) Receives a Buy from Maxim Group

https://www.tipranks.com/news/blurbs/brainstorm-cell-therapeutics-bcli-receives-a-buy-from-maxim-group-2?mod=mw_quote_news

In a report released yesterday, Jason McCarthy from Maxim Group maintained a Buy rating on Brainstorm Cell Therapeutics (BCLI – Research Report), with a price target of $5.00. The company’s shares opened today at $1.65

[Fmello]

BrainStorm Preps for Type A NurOwn Meeting, Shakes Up C-Suite

https://www.biospace.com/article/brainstorm-preps-for-type-a-nurown-meeting-shakes-up-c-suite-for-success-/

BrainStorm Cell Therapeutics concluded 2022 on a cautiously optimistic note as the FDA granted a Type A meeting to discuss the refuse to file letter it served the Israel and New York-based biotech in November for its ALS hopeful, NurOwn.

The meeting is scheduled to take place on Jan. 11th.

BrainStorm is seeking an advisory committee meeting. For context, ALS competitor Amylyx’s Relyvrio (formerly AMX0035) enjoyed the benefit of not one, but two adcomms prior to its September approval.

BrainStorm believes an adcomm would “serve as an important part of the review process and…provide an open forum for BrainStorm, together with medical experts, statisticians, patients and other members of the ALS community to discuss the body of clinical evidence supporting NurOwn,” Chaim Lebovits, BrainStorm CEO, said in a statement.

The clinical profile of NurOwn, a therapy made up of autologous mesenchymal stem cells (MSC) and neurotrophic factors (NTF), is what appears to be in question at the FDA.

Highlights from the nearly three-year regulatory saga include:

• A high placebo response: In the Phase III trial, NurOwn hit the primary treatment response endpoint, with 34.7% of therapy recipients seeing an improvement of 1.5 points per month. However, the placebo response of 27.7% exceeded those of others observed in contemporary ALS trials.
• A pre-specified subgroup of patients with early-stage disease achieved a meaningful response (34.6%) across all primary and secondary endpoints. This was compared to 15.6% in the placebo group.
• A correction posted by BrainStorm in August to the initial trial results published in Muscle and Nerve. The adjustment resulted in a statistically significant treatment difference of 2 points in average change from baseline on the ALSFRS-R scale.

Despite hopes that the correction would buttress NurOwn’s case, the FDA appeared not to agree, handing down an RTF letter for NurOwn in this indication. The therapy is also being assessed in a Phase II trial in progressive multiple sclerosis.

In the company’s Q3 earnings call, Lebovits said it was clear the regulator still sought “substantial evidence defined by statistically significant results as measured by the endpoints of the Phase III trial.”

The RTF sparked frustration from some patient advocacy groups like Stevens Nation, which stated the FDA’s position “ignores the vast evidence of efficacy and denies both the company's and patients' rights of due process.” The group further stated it believes the RTF does not adhere to FDA's own guidance.

In 2019, the FDA implemented the Guidance Document for ALS, which emphasized the regulator’s willingness to "exercise regulatory flexibility" for the "critical unmet need" in ALS.

The FDA doubled down on that commitment in June 2022, when it released the “Action Plan for Rare Neurodegenerative Diseases, Including ALS.”

The five-year strategy aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments. The FDA called it a blueprint for how the agency would “move forward aggressively” to this end.

C-suite Shuffle

On Wednesday, BrainStorm made a series of C-suite moves in what could be a show of confidence in NurOwn’s ability to prevail.

The company announced the promotion of Stacy Lindborg, to the role of co-chief executive officer. Lindborg, currently EVP and chief development officer, will share the CEO responsibilities with Lebovits.

Current president and CMO Ralph Kern will retire from these positions and transition to BrainStorm’s Scientific Advisory Board. Lebovits will re-assume the president title. In an e-mail to BioSpace, BrainStorm confirmed Kern will be in attendance at the Type A meeting.

Lindborg’s promotion “is part of a broader strategic initiative to build out our leadership team and position BrainStorm for success,” Lebovits said in a prepared statement.

He added that Lindborg’s track record in late-stage clinical development and commercial strategy means she is “exceptionally well qualified to guide BrainStorm” as it prepares to enter the next phase as a company.

At Biogen, Lindborg contributed to the approval of spinal muscular atrophy therapy Spinraza as vice president, analytics and data science. She followed this up with a stint as Head of R&D strategy at Eli Lilly.

In a prepared statement Wednesday, Lindborg said she would “relentlessly focus on the regulatory process to secure a path with FDA with the goal to make NurOwn available for ALS patients.”

[Fmello]

https://www.pbs.org/newshour/show/former-obama-staffer-fights-to-raise-als-awareness-after-devastating-diagnosis?fbclid=IwAR1BBiqNxlCkAnLf64F_30Ge3O10scVA8bLUa7CM3mT7dEVHfYTnfAC1Ec0

[Fmello]

That's definitely good news. Hopefully they can set up an ADCOM meeting soon after.

[midastouch017]

BrainStorm Cell Therapeutics Announces Type A Meeting with FDA Granted for NurOwn®

https://finance.yahoo.com/news/brainstorm-cell-therapeutics-announces-type-110000672.html


NEW YORK, Dec. 27, 2022 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted a Type A meeting to discuss the contents of a refusal to file letter previously issued regarding the company's New Biologics License Application (BLA) for NurOwn® for the treatment of ALS. The Type A Meeting has been scheduled to occur on January 11, 2023.

"We look forward to the Type A meeting which will provide an opportunity to discuss the path forward for NurOwn in ALS, including a possible Advisory Committee Meeting," said Chaim Lebovits, Chief Executive Officer of BrainStorm. "We believe that an Advisory Committee Meeting would serve as an important part of the review process and would provide an open forum for BrainStorm, together with medical experts, statisticians, patients and other members of the ALS community to discuss the body of clinical evidence supporting NurOwn. We intend to provide a further update once we have received the minutes from the meeting, or when we have more clarity on the next steps in the approval process."

About the Phase 3 Trial of NurOwn in ALS

BrainStorm previously completed a Phase 3 trial in approximately 200 participants with ALS (Cudkowicz et al., 2022 Muscle and Nerve). In an attempt to examine a real-world population, the study enrolled people with more advanced disease than other late-stage ALS trials. In fact, more than a third of these participants with advanced disease entered the trial with one or more dimensions of physical function (e.g., dressing/hygiene, cutting food, walking) starting at the lowest possible score of 0 on the ALSFRS-R; thereby preventing the measurement of further deterioration. A pre-specified subgroup of participants, with baseline ALSFRS-R ≥35, which controls for this 'scale effect' showed a trend to a meaningful increase in the clinical response with NurOwn compared to placebo. The secondary endpoint, average ALSFRS-R change from baseline to 28 weeks in this subgroup, was statistically significant (p=0.050, Muscle and Nerve Supplemental File and Muscle and Nerve Erratum). In addition, post-hoc sensitivity analyses were presented in November 2022 (21st Annual NEALS Meeting 2022) which also showed a statistical trend towards a clinically meaningful treatment effect with NurOwn across subgroups, and one that is consistent with the pre-specified subgroup of participants with less advanced ALS at baseline. Finally, biomarker data in all trial participants also showed consistent patterns of NurOwn reducing markers of inflammation and neurodegeneration, and increasing neuroprotective and anti-inflammatory markers relative to placebo, further supporting the notion that trial participants taking NurOwn are indeed experiencing a positive biological effect (ALS ONE Research Symposia 2022).

[Fmello]

BrainStorm Cell Therapeutics Submits Type A Meeting Request to U.S. Food and Drug Administration

https://seekingalpha.com/pr/19051717-brainstorm-cell-therapeutics-submits-type-meeting-request-to-u-s-food-and-drug-administration

Meeting expected to occur within 30 days of the FDA's receipt of the meeting request

NEW YORK, Dec. 12, 2022 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced that the company has submitted a Type A Meeting Request to the U.S. Food and Drug Administration (FDA) to discuss the contents of a refusal to file letter previously issued by the FDA regarding the company's New Biologics License Application (BLA) for NurOwn® for the treatment of ALS. The Type A Meeting is expected to occur within 30 days of the FDA's receipt of the meeting request.

As previously reported, the contents of the refusal to file letter focus on topics related to chemistry, manufacturing, and controls (CMC), as well as clinical data and statistics. As part of the Type A Meeting, BrainStorm intends to discuss a path to an FDA Advisory Committee Meeting.

"Participating in a Type A meeting will be an important next step towards enabling NurOwn's advancement through the regulatory process," said Chaim Lebovits, Chief Executive Officer of BrainStorm. "The extensive briefing package submitted with our request contains a comprehensive strategy to fully address the CMC matters raised in the refusal to file letter. We anticipate achieving quick alignment with the FDA on the CMC strategy and expect that its execution will be straightforward. We therefore anticipate a Type A meeting focused primarily on discussing how we can secure an Advisory Committee Meeting, which we believe will be a critical step on NurOwn's path towards approval as an ALS therapy."

About the Phase 3 Trial of NurOwn in ALS

BrainStorm previously completed a Phase 3 trial in approximately 200 participants with ALS (Cudkowicz et al., 2022 Muscle and Nerve). In an attempt to examine a real-world population, the study enrolled people with more advanced disease than other late-stage ALS trials. In fact, more than a third of these participants with advanced disease entered the trial with one or more dimensions of physical function (e.g., dressing/hygiene, cutting food, walking) starting at the lowest possible score of 0 on the ALSFRS-R; thereby preventing the measurement of further deterioration. A pre-specified subgroup of participants, with baseline ALSFRS-R ≥35, which controls for this "scale effect" showed a trend to a meaningful increase in the clinical response with NurOwn compared to placebo. The secondary endpoint, average ALSFRS-R change from baseline to 28 weeks in this subgroup, was statistically significant (p=0.050, Muscle and Nerve Supplemental File and Muscle and Nerve Erratum). In addition, post-hoc sensitivity analyses were presented in November 2022 (21st Annual NEALS Meeting 2022) which also showed a statistical trend towards a clinically meaningful treatment effect with NurOwn across subgroups, and one that is consistent with the pre-specified subgroup of participants with less advanced ALS at baseline. Finally, biomarker data in all trial participants also showed consistent patterns of NurOwn reducing markers of inflammation and neurodegeneration, and increasing neuroprotective and anti-inflammatory markers relative to placebo, further supporting the notion that trial participants taking NurOwn are indeed experiencing a positive biological effect (ALS ONE Research Symposia 2022).

[Fmello]

West Virginia man battling ALS hoping FDA reverses decision on drug treatment

https://www.wowktv.com/news/local/west-virginia-man-battling-als-hoping-fda-reverses-decision-on-drug-treatment/

[Fmello]

How Matt Feels & Functions w #ALS,
which kills most in 3-5 yrs

2018 Dx
2019 #NurOwn trial - stabilized
20-21 Declined
2021 EAP - stabilized. Climbing stairs
21-22 Declined
2022 EAP - stabilized. #Walking w walker@FDACBER Act Urgently & let Matt Testify
Matt Knows #NurOwnWorks pic.twitter.com/ONv2DMFbdO

— AZ Latina ☮️🌊🟦 (@aVoice4ALS) December 6, 2022

[condoe3]

No annual shareholder meeting date has been released for 2022, what's up with that ?

[Fmello]

https://www.facebook.com/michelle.lorenz.395/videos/826580615242103?idorvanity=156722665270133

[Fmello]

Dramatic letter from Esteban Bulrich to Joe Biden for the United States to approve a drug against ALS

https://nationworldnews.com/dramatic-letter-from-esteban-bulrich-to-joe-biden-for-the-united-states-to-approve-a-drug-against-als/

The former senator called on the FDA to exercise “the broadest regulatory flexibility” with regard to a stem cell treatment called NurOwn for his disease.

Esteban Bulrich sent him one Carta and Joe Biden Asking for approval from the President of the United States and the US Food and Drug Administration (FDA) a Amyotrophic Lateral Sclerosis (ALS) Treatment,

Former MLA sent letter 500 patients signed with the disease he is also suffering from And asked that the powerful drug control body act with “wide flexibility” to give the green light to the treatment, which is, according to the description, “therapy with mesenchymal stem cells”.

“I want to let you know that we are going to be sending a letter to the President of the United States, the Director of the FDA, the Chairmen of the Senate Health Committee and the National Health Service requesting their approval. NooronBulrich wrote on his Twitter account.

“It’s a treat that even Demonstrated in trials that it can reverse the effects of disease, The letter has been signed by some 500 ALS patients in Argentina, but to increase the impact we want to add patients from across the region,” said the former national education minister, who revealed in April 2021 that he was suffering from ALS.

On 21 September, the leader of the Juntos por el Cambio was discharged after spending three weeks in hospital in Australia, where he had been admitted due to pneumonia.

A month earlier he was present at a concert by the group Coldplay at River Stadium.

What the letter Esteban Bulrich will send to Joe Biden says
At the beginning of the letter, Stephen Bulrich described it as “immediate”. FDA required to give green light to mesenchymal stem cell therapy, NurOwn.

“It is my honor to address you On behalf of over 1,500 ALS patientsand their families and loved ones in Latin America who need your assistance with an urgent matter related to FDA approval mesenchymal stem cell therapy It’s called NurOne,” Bulrich said.

After reviewing and noting the features of the disease “there is no cure”showed him “Disappointment” By 6-4 vote against approval of AMX0035, a drug to slow the progression of ALS. This treatment was approved by Canada and the former senator himself requested it before the ANMAT last June.

I’ve seen enough faces of despair and sadness in my family and friends to know that no one may live to see the ALS patient die slowly but steadily“, Bulrich added with the obvious play, for whom FDA approval would have been a strong signal to the rest of the country.

He then added that he understands the complex web of research and approvals that companies and the FDA go through before giving their approval for a treatment.

“But Mr. President, I think I speak for the majority of ALS patients when I say that we will happily waive any claims to gain access to a medicine that could potentially cure us,” Bulrich said,

And it was again hard and concrete: this is what you have to understand, Today our best scenario is a few more months, We are willing to experiment for ourselves, but also for our family and friends.”

“We expect the FDA to operate with broad regulatory flexibility. We expect the FDA to do so.” Hear from the best scientific mindsThe former Mauricio Macri government official insisted before saying goodbye to Biden.

NurOwn, developed by BrainStorm Cell Therapeutics, is a bone marrow stem cell therapy. According to a publication of the Argentine ELA Association, treatment did not reach statistically significant results and did not pass the Phase 3 study in November 2020.

Although this achieved a 35% response in treated patients, they were not significantly higher than the placebo sample’s record (28%).

Last August, the BrainStorm company announced that it had reviewed the studies and would submit a “biologics license application to the FDA.”

[Fmello]

My son also. He did not progress for 14 months while in the trial. His progression began 2 months after his last injection.
So upsetting to know there is treatments, but we can't have them.
Doors have to be opened, and it can begin NOW!

— Smithstrongmom (@Smithstrongmom1) May 28, 2020

[Fmello]

Fort Smith man losing hope after FDA denies potential ALS treatment

https://www.newsbreak.com/news/2835324206088/fort-smith-man-losing-hope-after-fda-denies-potential-als-treatment

[Fmello]

I Am ALS and Veterans with ALS send an Open Letter to FDA Requesting an Advisory Committee Meeting to Discuss NurOwn

https://seekingalpha.com/pr/19033407-i-als-and-veterans-als-send-open-letter-to-fda-requesting-advisory-committee-meeting-to

Veterans have a Significantly Increased Risk of 100% Fatal ALS, Caused by their Service for our Country

FDA Advisory Committee Meeting is Essential to Allow Veterans' Voices to be Heard about Need for Access to a Medical Arsenal including NurOwn

WASHINGTON, Nov. 23, 2022 /PRNewswire/ -- To the Honorable Dr. Robert Califf and Dr. Peter Marks:

We represent Veterans with ALS who support Brainstorm Cell Therapeutics' request for the FDA to hold a public Advisory Committee meeting ("AdCom") to engage in scientific discourse about the "clinically meaningful" evidence supporting FDA's approval of a mesenchymal stem cell therapy, NurOwn.

When we volunteered to serve, we swore an oath to protect our country against all enemies. We knew a day may come when we could be fighting for our lives. We never imagined that day would be once we returned home safely. Our enemy is now ALS.

ALS is universally fatal. One in six people who dies of ALS is a Veteran. According to a VA Report, 1,055 Veterans die of ALS each year. Since 9/11, three times more Veterans have lost their lives to ALS than those lost in combat in Iraq and Afghanistan combined.

In 2008, the VA recognized ALS as a presumptive, compensatory illness (a 100% service-connected disability) thanks to the leadership and Congressional testimony of Brigadier General Thomas Mikolajcik ("General Mik"), Commander of the 437th Airlift Wing at the Charleston AFB.

Unwilling to let Veterans' suffering continue to be ignored, General Mik "vowed to keep speaking" until he no longer could. We too vow to keep speaking and demand that our country give us a right to be heard at an AdCom – where regulators, researchers and patients can have a scientific discourse about a therapy that could impact Veterans' lives, and the lives of our fellow Americans with ALS.

In the military, when confronting an enemy, we meet with the best military minds. We gather all the intelligence. We listen to competing voices. We debate the best tactics and strategies. We always strive to equip our men and women with every possible weapon in the arsenal to enable them to complete the mission … to beat the enemy. In the military, if we make mistakes, people die.

In our battle today, the enemy is ALS. Our country has failed its mission since Lou Gehrig died 81 years ago.
As such, we expect the FDA to act with the broadest of regulatory flexibility. We expect the FDA to hear the opinions of the best scientific minds … to listen to the neurologists who have witnessed how the enemy responds to NurOwn … to consider competing voices … to learn from ALS biomarker specialists … and to equip people with ALS with the best weapons in the arsenal.

We further expect the FDA to act with the same urgency as the military does after a terrorist attack on our country because the ALS attack is swift and relentless, causing irreparable destruction. If the FDA delays or denies the approval of a therapy like NurOwn that slows and halts progression in some people with a vastly heterogeneous disease like ALS, another generation of Americans will be deprived of a chance to fight for our lives.

Veterans with ALS have a unique stake in the fight for a NurOwn AdCom. First, we sacrificed our lives for every citizen's right of due process. It is the antithesis of all we fought for if we, now, were denied that same right.

Second, as General Mik reminded Congress (CACOX), it is our country's moral obligation to equip Veterans with ALS with every possible weapon in the "medical arsenal." We expect the FDA to honor this moral obligation and consider all the evidence that NurOwn could be a weapon that will allow us to live to fight another day.

Third, as Veterans, we have watched our brother, Navy (NVYAF) pilot Matt Bellina benefit from NurOwn. Matt was serving as an EA-6B Prowler pilot when he was diagnosed with ALS in 2014. But with the help of the VA and Brainstorm, Matt received 7 doses of NurOwn. Matt is living proof of NurOwn's efficacy:

I have regained the ability to stand on my own without assistance. My lung capacity is 37% higher than it was before my first injection, so I no longer need the assistance of a breathing machine. I have gained enough mobility in my arms to scratch my face and even take my glasses off. All of these are improvements from where I was before the treatment.

Most importantly, Matt has been able to continue making memories with his wife and three boys. He has earned the right to tell his story and share his "clinically meaningful" evidence at an AdCom.

The risk of ALS among Veterans is on the rise. In 2007 when General Mik testified, that risk was recognized as 1.6 times higher for Veterans than civilians. The risk to those deployed in the Gulf War doubled. Some battalions were hard hit. For example, Eric Payonk served in the 43rd Air Defense Artillery Regiment. He is one of two men in his regiment -– that he knows of -- who got ALS.

A recent study in Military Medicine uncovered more daunting statistics. Among post 9/11 Veterans, the risk is skyrocketing to nearly 4 times higher than the civilian population. And the study recognizes that these post 9/11 Veterans are experiencing ALS onset at much younger ages – just like Prowler pilot Matt Bellina who was medically retired at just 32 years old. In 2007, General Mik warned that this would happen:

We are currently exposing hundreds of thousands more service members to the elevated risk of this disease. There will be young men, women and families celebrating a return from Iraq and Afghanistan alive, who have no idea that they may soon be facing a certain death from ALS. We will have to answer to those families when they ask what their government has been doing to prepare for this onslaught.

That onslaught is tragic in human lives lost, but costly in military assets as well. Those with a 10 times higher risk are the military's most highly trained people: pilots and tactical operations officers. Exemplifying the real-life implications of this marked rise in ALS: General Mik died of ALS in 2010. Less than a decade later, three other young C-130 pilots -- in his same squadron from Charleston AFB -- also died of ALS.

Living daily with the inhumanity of this disease, General Mik challenged Congress and our country to step up its commitment to Veterans:

If these soldiers were dying in the field rather than quietly at home… we would leave no stone unturned. We would use the best existing resources to make sure they had whatever they needed to survive… to ensure that no man or woman is left behind.

The first step in giving us whatever we need to survive is giving us a chance to be heard. As we are confronting the battle for our lives, it would be an affront to all that we sacrificed to deny us a voice in the dialogue about what weapons will be in our medical arsenal.
Please do not abandon us on this ALS battlefield.

About the Veterans with ALS
Veterans who are currently battling amyotrophic lateral sclerosis and insist upon the FDA recognizing our due process rights to be heard at an Advisory Committee meeting:

• Chris Mulholland (64). USMC (Ret.) 1977-2000. VFW National Deputy Chief of Staff. Deployed for combat tours in Iraq and Beirut. Deployed to Kuwait, Egypt, Haiti, Panama, Turkey, Morocco, and Japan. Stationed at Camp Lejeune. Diagnosed with ALS in 2020 (VISN 6).

• Juan Reyes (55). USAF (Ret.) 1986-2007. Served in Operation Desert Storm, Operation Enduring Freedom, Operation Enduring Hope. Deployed to Saudi Arabia, Africa, Spain, Bulgaria, Germany & UK. Diagnosed with ALS in 2015 (VISN 17).

• Mary Porter, DO (52). USA 2006-2015. Served in Operation Iraqi Freedom. Diagnosed with ALS in 2019 (VISN 20).

• Kate Peters (39). USMC 2007-2015, USN (Medically Ret.) 2015-2020. Served in Operation Iraqi Freedom. Diagnosed with ALS in 2020 (VISN 21).

• Guillermo Garcia (47). USN 1993-1997. Deployed in Persian Gulf. Diagnosed with ALS in 2015 (VISN 17).

• Eric Payonk (55). USA 1987-1991. Served in Operation Desert Storm.
Diagnosed with ALS in 2018 (VISN 17).

• John McCormack (56). USAF 1984-1988. Deployed to UK. Diagnosed with ALS in 2022 (VISN 23).

• Nick Sloan (45). USMC 1997-2005. Deployed to Japan and Cuba. Diagnosed with ALS in 2020 (VISN 17).

• Matthew Wild (49). USMC 1992-1996. Deployed to Japan, South Korea & Thailand. Diagnosed with ALS in 2015 (VISN 20).

• Tony DiBenedetto (62). USA (Medically Ret.) 1988-2013. Served in Operation Desert Storm, Operation Desert Shield, Operation Just Cause, Operation Enduring Freedom. Deployed to Iraq, Afghanistan, Panama. Diagnosed with ALS in 2013 (VISN 21).

• Gregory Vanison (42). USMC & USA (Medically Ret.) 2001–2021. Operation Iraqi Freedom and Operation Enduring Freedom. Diagnosed with ALS in 2019 (VISN 16).

• Jim Clingman (78). USN 1965-1969. Vietnam. Diagnosed with ALS in 2013 (VISN 7).

• Shelly Hoover, EdD (57). USN 1983-1988. Head of I AM ALS Veterans Team. Diagnosed with ALS in 2013 (VISN 6).

• Matt Bellina (39). USN (Medically Ret.), 2005-2015. Served in Operation Enduring Freedom. Deployed to Africa & Korean Peninsula. Diagnosed with ALS in 2014 (VISN 4).

• Christina Mikolajcik in memory of her father, Brig. Gen. Tom Mikolajcik, USAF (Ret.), 1969-1996. Former Commander of 437th Airlift Wing at Charleston AFB with 4,000 flight hours. USAF Director of Transportation at the Pentagon. Served in Vietnam, Cold War & Operation Restore Hope. Deployed to Germany & throughout Europe, Central Africa (Somalia), and South America. Diagnosed with ALS in 2003. (VISN 7).
Died waiting for a medical arsenal on April 17, 2010.

You can reach any of these people mentioned in this open letter to the FDA by contacting Shelly Hoover, the leader of the I AM ALS Veterans team at: [e-mail].

About the FDA's Refusal to File Letter regarding NurOwn
On November 10, 2022, Brainstorm Cell Therapeutics (BCLI) announced that the U.S. Food and Drug Administration issued a Refusal to File ("RTF") letter for its investigational biologic treatment, a mesenchymal stem cell therapy called NurOwn. On November 14, 2022, in its Quarterly call, Brainstorm advised that the FDA's main reason for the RTF letter was NurOwn's failure to meet the substantial evidence standard. Brainstorm plans to request a Type A meeting with the FDA to discuss a path forward and the balance of evidence that it believes supports approval.

About the Military Medicine Study & VA Directive on ALS
The study in Military Medicine was published in October 2019. It examined the records of 1,149,620 Veterans who received care in the VHA in fiscal years 2002-2015. It analyzed data from VHA inpatient, outpatient, and pharmacy records, as well as Veterans Benefits Administration data to identify potential cases of ALS. The study was completed by researchers at the University of Texas Health Science Center San Antonio, the University of Utah, the Bedford VA Medical Center, and the DOD's Human Research Protection Office.

The study suggests the need for evaluating the occupational exposures these personnel are exposed to, such as ionizing radiation, ozone, jet emissions in the pathogenesis of ALS. Researchers commonly recognize that toxins in diesel fuel, including hexane and benzene, are associated with ALS. Other studies from the Army Research Institute have examined pesticides and permethrin-treated uniforms and their association with neurodegenerative diseases. Lead and other heavy metal exposures also play a role in ALS pathogenesis, making Burn Pit exposures a likely suspect of the increased number of Veterans dying of ALS.

VHA Directive 1101.07 outlines the ALS System of Care for Veterans. According to a 2006 study by the Institute of Medicine, the authors estimated an annual incidence of 4.5 per 100,000, yielding an estimated annual incidence of 1,055 Veterans who died after valiantly serving their country.

About Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis ("ALS") is a progressively paralyzing and universally fatal neurodegenerative disease. It results from the death of motor neurons in the brain and the spinal cord that lose their ability to send signals to the voluntary muscles. When ALS starts, people may only experience muscle twitches, weakness, unexplained tripping or slurring of words. As it progresses, people with ALS lose all ability to move, speak, eat, swallow, and eventually breathe. Average life expectancy for people with ALS is three to five years from the time of symptom onset, but life expectancy varies with 50% of the population dying within two years. According to the CDC's ALS Registry, approximately 6,000 people each year die of ALS.

[Fmello]

Stevens Nation Responds to FDA's Refusal to File Letter, NurOwn Recipients Call for Advisory Committee Meeting

https://www.biospace.com/article/releases/stevens-nation-responds-to-fda-s-refusal-to-file-letter-nurown-recipients-call-for-advisory-committee-meeting/?fbclid=IwAR2iG67LyxK2h8-k2qNvl4MRittIKFmOoOOOley1u5pkWXckuwvJ3gNNwbA

Published: Nov 22, 2022

• FDA Decision Does Not Adhere to Administration's Own Guidance and Ignores Evidence of NurOwn's Effectiveness

• Advisory Committee Meeting is Needed to Allow Patient Voices to be Heard and to Provide Transparent Consideration of NurOwn's Impact

WASHINGTON, Nov. 21, 2022 /PRNewswire/ -- Brainstorm Cell Therapeutics is seeking FDA approval of its mesenchymal stem cell therapy called NurOwn for the treatment of ALS. In response to the FDA's Refusal to File letter, and as people who participated in the NurOwn trials and its Expanded Access program ("EAP"), we support Brainstorm's efforts to seek an Advisory Committee ("AdCom") meeting.

We believe the FDA's position ignores the vast evidence of efficacy and denies both the company's and patients' rights of due process. Further, we believe that the letter does not adhere to FDA's own guidance. An AdCom will allow the full array of data to be examined and will give voice to trial participants, the drug sponsor, investigating neurologists and treating clinicians. We must insist that the FDA allow testimony about the "clinically meaningful" changes that occurred when we received NurOwn.

In its quarterly call, Brainstorm outlined the FDA's position in the Refusal to File letter. The FDA concluded there is not "substantial evidence" of efficacy because the Phase III study did not meet its primary endpoint. However, the Phase III trial did meet a pre-specified secondary endpoint in a subgroup of patients with less advanced ALS.

For over five years, the ALS community fought for the adoption of an FDA Guidance Document for ALS, which was implemented in 2019. It provides that evidence of a treatment effect can be assessed by "less decline, stabilization or improvement" in function. Further, objective findings of "even of a small magnitude" can demonstrate efficacy.

Two of the most critical commitments made in that Guidance Document were: (1) the FDA's willingness to "exercise regulatory flexibility" for the "critical unmet need" in ALS; and (2) the willingness to consider "patient reported outcomes" as evidence of efficacy.

The FDA evaluates whether substantial evidence of efficacy exists by asking whether a therapy provides a "clinically meaningful" impact. In essence, how does a therapy make a person "feel and function?" The best people to attest to how NurOwn made them "feel and function" are the people who received NurOwn. Indeed, in a patient listening session in 2019 with the leadership of CDER and CBER, the FDA promised the ALS community: "if it helps you function, and you can prove it, we'll approve it!"

We are asking the FDA to let us prove it.

After receiving NurOwn, each of us halted our ALS decline and improved in some areas of function. The following are some of our changes in daily activities that prove NurOwn works.

• walk without a walker, walk longer distances, walk in sand or farm field
• rise out of a chair unassisted and get up off the floor unassisted
• climb up and down stairs
• climb up into a four-wheel drive vehicle
• decreased or halted fasciculations
• improved balance and less falls when walking
• put our arms over our heads and wash our bodies and hair unassisted
• use the bathroom or hold a urinal
• open water bottles, pill bottles and food jars
• hold a pen to write
• use a cell phone to text and type
• speak more clearly without needing a caregiver to translate
• pull the throttle on a lawnmower and push the lawnmower to mow the grass
• grip a glass and lift it to drink
• operate a wheelchair with one finger
• throw a ball to the dogs or throw rocks with the kids
• swallow dense foods like fried chicken, rice, sushi
• speak for longer periods of time between use of bipap
• breathe stronger as evidenced by improved FVC

Because of these improvements in function after receiving NurOwn, we were able to make memories with our families by going on camping trips, weeklong vacations to Disneyworld, attending our children's graduations, celebrating birthdays and anniversaries, and watching our children being born.

We further believe that the FDA cannot make any assessment of whether a therapy has a "clinically meaningful" impact without allowing scientific discourse and hearing opinions from the world's most esteemed ALS neurologists who were principal investigators in the trials and EAP. With decades of expertise with ALS, they are the only people in the world who have seen the clinical and biomarker data -- as well as observed our function in clinics. Many of our neurologists have publicly and privately expressed the belief that NurOwn works. Any scientific discourse about whether NurOwn works must include the scientists who know it best.

Moreover, several of us also would like to offer opinions from other health care professionals such as unaffiliated neurologists, pulmonologists, and physical therapists, who can attest to the changes they observed in clinic visits.

For example, Paula Smith is the mother of Josh Smith. She stated:

My son Josh is 33 years old. He was in the NurOwn trial and both EAPs. Josh was diagnosed in March of 2019, and he is still walking, talking, eating, and breathing. During the EAP, my son's pulmonologist documented a 41% improvement in his breathing function. Our outside doctors can't believe the changes in my son.

Combined with the many patient reported outcomes like this, the "totality of the evidence" in the trials and EAP proves NurOwn had a clinical and biological effect. We are asking the FDA to exercise its promised regulatory flexibility. We are asking for an opportunity to share our evidence at an Advisory Committee meeting. We are proof that NurOwn works. Please don't let us die waiting.

About the NurOwn trial and EAP participants
Collectively, we are the patients and family members of patients who participated in the NurOwn trials and Expanded Access. One of us participated in the NurOwn Phase II trial in 2015, which now has been unblinded. The balance of us participated in the Phase III trial from 2017-2019, which has not yet been unblinded; however, each of us received doses of NurOwn in the Expanded Access Program in 2021 and 2022.

• Eric Stevens (33). California. Expanded Access at UC Irvine.
Symptom onset in March 2019. Diagnosed with ALS in September 2019.

• Matt Klingenberg (37). South Dakota. Expanded Access at Mayo.
Symptom onset in November 2017. Diagnosed with ALS in March 2018.

• Josh Smith (33). Pennsylvania. Expanded Access at UMass.
Symptom onset in June 2018. Diagnosed with ALS in March of 2019.

• Phil Green (52). California. Expanded Access at UC Irvine.
Symptom onset in June 2017. Diagnosed with ALS in August of 2018.

• Roberto Muggli (47). Costa Rica and Minnesota. Expanded Access at Mayo.
Symptom onset in Spring of 2017. Diagnosed with ALS in December 2017.

• Kylan Morris for her mother, Sandy Morris. California. Expanded Access at CPMC. Symptom onset Aug 2017. Diagnosed with ALS in January 2018.
Died waiting at 56 years old in 2022.

• Nicole Cimbura for her husband, Mike Cimbura. Colorado. Phase II trial at Mayo. Symptom onset in May 2014. Diagnosed with ALS in January 2015.
Died waiting at 53 years old in 2019.

About the FDA's Refusal to File Letter regarding NurOwn

On November 10, 2022, Brainstorm Cell Therapeutics announced that the U.S. Food and Drug Administration issued a Refusal to File ("RTF") letter for its investigational biologic treatment, a mesenchymal stem cell therapy called NurOwn. On November 14, 2022, in its quarterly call, Brainstorm provided more insight into the FDA's reasons for the RTF letter and its plan to request a Type A meeting with the FDA to discuss a path forward for its therapy.

[Fmello]

Any idea what caused this huge spike to the stock price? Did Brainstorm get their ADCOM meeting?

The stock is currently up a whopping 27% so far today.

[Fmello]

BrainStorm Vows to Push for Adcomm Meeting on NurOwn in ALS

https://www.biospace.com/article/brainstorm-vows-to-push-for-an-adcomm-meeting-on-nurown-in-als/

After receiving a Refusal to File (RTF) Letter regarding a BLA for NurOwn in ALS, BrainStorm Cell Therapeutics emphasized its commitment to seek an advisory committee meeting through a Type A meeting with the FDA.

On its Q3 earnings call Monday, the BrainStorm brass, which included Chief Executive Officer Chaim Lebovits, President and CMO Ralph Kern, M.D. and EVP and Chief Development Officer Stacy Lindborg, Ph.D., expressed their collective belief that current data from the Phase III trial should be sufficient for a BLA.

While Lebovits called the RTF letter “a big bump in the road”, the executives maintained a positive forward-looking note throughout the call.

Lebovits stated two primary issues outlined in the RTF: the first, in clinical and statistics; the second in chemistry, manufacturing and Controls (CMC).

BrainStorm spent the majority of the call focused on the former, with Lebovits saying it was clear that the regulator still sought “substantial evidence defined by statistically significant results as measured by the endpoints of the Phase III trial."

NurOwn, which is comprised of autologous mesenchymal stem cells (MSCs) and neurotrophic factors (NTFs), failed to meet statistically significant efficacy endpoints in a Phase III trial where it was being assessed to treat ALS. Top-line results of the trial were first reported in November 2020.

“We also believe there needs to be flexibility and urgency in the review of drugs for ALS,” Lebovits continued. “We believe it is more than reasonable to expect that the FDA will allow an open and fair hearing in a public venue.”

Lindborg highlighted analyses of the Phase III data presented at the 5th Annual ALS One Research Symposium in October and the 21st Annual NEALS Meeting in early November.

“Consistent patterns were observed across biomarkers in subgroups,” she said. Specifically, BrainStorm “observed decreases in pro neuroinflammatory and neurodegenerative markers and increases in neuroprotective and anti-inflammatory markers,” in participants treated with NurOwn compared to placebo.

Lindborg emphasized that the analyses showed NurOwn had a biological effect in all trial participants “regardless of the level of disease progression at baseline.”

BrainStorm ran into challenges with the so-called “floor effect” in this trial. At NEALS, Lindborg presented data from a sensitivity analysis looking at the total score threshold and item level threshold.

The results showed that “after controlling for the impact of the ALSFRS-R floor effect, all participants treated with NurOwn had a higher rate of clinical response and less function loss across 20 weeks compared to placebo,” Lindborg said.

BrainStorm plans to discuss these recent analyses with the FDA during the Type A meeting.

Lindborg added that a confirmatory trial could be an end result of a Type A meeting.

Kern said the regulatory process allowed Amylyx’s Relyvrio, which included two separate adcomm meetings, to underscore the importance of having an open discussion with clinicians and statisticians.

Kern also highlighted the “quite negative views on Relyvrio’s data” expressed in FDA guidance documents prior to its ultimate approval.

“We feel strongly that having an opportunity to have our BLA filed so that we can discuss our data in an adcomm is in the best interest of the ALS community,” Kern said.

Lindborg added that there are processes in place where an RTF letter can move to a BLA acceptance with an adcomm meeting to follow, saying there is precedent for such a move.

ALS Community Reacts

Reaction from the ALS community was swift, with many patients and advocates expressing their disappointment with the RTF.

“It is important for FDA to allow due process and for a public adcomm for NurOwn so the full data set can be shared and scientifically debated,” said Nicole Cimbura, co-lead for the I AM ALS legislative affairs team whose husband succumbed to the disease, in a statement to BioSpace. “In a disease like ALS that is 100% fatal and so heterogenous, a therapy that works even for a subset [of patients] must move forward.”

In a call with BioSpace Thursday, Dr. Merit Cudkowicz, chief of neurology at Massachusetts General Hospital and trial co-investigator, suggested there may be a difference in thinking between the Center for Drug Evaluation and Research (CDER), which reviewed Relyvrio, and the Center for Biologics Evaluation and Research (CBER), which is responsible for reviewing NurOwn.

Cimbura also mentioned this potential difference, saying, “It is concerning that CBER seems to have different views of regulatory flexibility and is behind CDER. Equity between FDA review divisions is integral to the process and confidence in the system.”

Cimbura added that Monday's transparency regarding the RTF from BrainStorm was important.

"BrainStorm and the FDA CBER need to work on the ALS Clock," she said.

[Fmello]

Mike Hensen & Michelle Lorenz going LIVE @ 5:30pm central time to talk about FDA's heartbreaking decision not to consider NurOwn BLA. Go to the No More Excuses ALS Facebook Group to watch.

https://www.facebook.com/groups/NOMOREEXCUSESALS/