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

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 437^th 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, 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 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 43^rd 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.

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 437^th 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: [email protected].

On November 10, 2022, Brainstorm Cell Therapeutics (Nasdaq: 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.

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.

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.

SOURCE I Am ALS