Comment from Nicholas Warack, Esq.

Subject: Docket FDA-2025-P-2109 Dear Commissioner Diamantas, Director Mikhail and Director Comstock Rick, As our nation recently marked its 250th birthday, July 4th held particular significance for the ALS community as one year has now passed without a response to our 309-page Citizens’ Petition filed under 21 CFR § 10.30. Our Petition requested a de novo review of the totality of the new and existing evidence and asked CBER to grant accelerated approval of NurOwn, a mesenchymal stem cell therapy developed by BrainStorm Cell Therapeutics for the treatment of rare disease, ALS aka Lou Gehrig’s disease. While we recognize that CBER needs time to review the new data in our Citizens’ Petition -- including now mature long-term survival, respiratory, and biomarker results from the Expanded Access Program — we write to respectfully request prompt action on our original requests: (a) invite BrainStorm to re-file its BLA so the new evidence can be considered in the proper procedural context; (b) expedite review under the National Priority Voucher Program; and (c) grant accelerated approval with a Phase 4 confirmatory study and mandatory biorepository to advance the science of ALS. Because our request for an urgent review did not prompt a substantive response from former CBER leadership, in this letter, we are elevating several legal issues for your attention. Petitioners assert: 1.Passage of the 180-day statutory time to respond to our Citizens' Petition constitutes an "unreasonable delay" under the Administrative Procedure Act and thus, we request a substantive response that matches the urgency with which ALS is killing people. 2.The totality of evidence – including newly mature long-term survival data, real-world evidence, and objective Neurofilament Light biomarker data that the FDA has never considered — supports accelerated approval of NurOwn. 3.FDA’s prior statutory interpretations will no longer be given deference since the Supreme Court overturned Chevron in Loper Bright Enterprises v. Raimondo; and this alone warrants reconsideration of the NurOwn BLA under proper interpretation of various provisions of the Food Drug & Cosmetics Act. 4.FDA’s failure to approve NurOwn was and would continue to be “arbitrary and capricious,” violating the Administrative Procedure Act. To address these issues, we are now also requesting a public hearing. Petitioners deserve our proverbial day in court. Based on the new and highly probative evidence that the FDA has never considered, our Petition is akin to a motion for new trial. Importantly, the FDA’s prior decision was based solely on the results from a short 28-week Phase 3 trial. It has never considered the new survival data; the 8 years of RWE from the trial, EAP and Right to Try; nor has it ever considered NurOwn for approval under the Accelerated Approval pathway. We are also asking this new FDA Administration to review our Citizens’ Petition as a court would view a motion for mistrial. In the legal memorandum below, you will see ample evidence that demonstrates the arbitrary and capricious nature of CBER’s prior decision, as well as the violation of due process. What you will see illustrated repeatedly throughout the legal memorandum is CBER’s failure to “treat like things alike.” This arbitrary inconsistency related to: its failure to use expedited pathways; the differing legal standards for approval of different therapies; the differing Instructions, Voting Questions and procedures at the advisory committee meeting; and the differing application of congressional intent for terminal diseases with unmet needs. We appreciate the FDA’s renewed commitment to thinking differently and tailoring your regulatory approach to advance therapies for rare diseases with critical unmet needs. Just as the FDA has recently reconsidered other investigational therapies for rare and oncologic diseases, we pray the same regulatory flexibility and reconsideration will be extended to NurOwn for ALS. We recognize that it is highly unusual for the FDA to consider data that is in the exclusive possession of the trial participants themselves. Notably, the drug sponsor and the trial sites do not possess much of the 8+ years of real-world evidence as the informed consents ended when the 28-week Phase 3 trial and Expanded Access Program ended. Accordingly, we are also seeking clarity about how and to whom we can submit real-world evidence/data for a retrospective medical records review -- just as the FDA has done for other investigational therapies for oncologic and rare diseases. Please provide an update on the status of the Citizens’ Petition as soon as possible and consider the urgent need to advance NurOwn’s regulatory pathway. We look forward to discussing this matter further with FDA leadership. With hope, Nicholas J. Warack, Esq.