Written Public Comment to REGULAR MEETING OF THE INDEPENDENT CITIZENS OVERSIGHT COMMITTEE AND THE APPLICATION REVIEW SUBCOMMITTEE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE Organized Pursuant To The CALIFORNIA STEM CELL RESEARCH AND CURES ACT on Sept. 28, 2023

Written Public Comment to REGULAR MEETING OF THE INDEPENDENT CITIZENS OVERSIGHT COMMITTEE AND THE APPLICATION REVIEW SUBCOMMITTEE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE Organized Pursuant To The CALIFORNIA STEM CELL RESEARCH AND CURES ACT on Sept. 28, 2023

California Institute for Regenerative Medicine (CIRM) was established and has been sustained by California Propositions with taxpayer money to fund human embryonic stem cell (hESC) research. CIRM is compelled by California voters to fund hESC research in order to find treatments or cures for a host of disorders that destroy lives. However, only a very decimal fraction of CIRM funding has really gone to hESC research. As a result, after almost 2 decades later, after 4 or 5 billions of CA taxpayer money later, California still has no clinical-grade hESC lines and banks, no world-class hESC training courses and training centers, no cutting-edge stem cell centers, no highly promising hESC product in clinical trials, no promising treatment or cure for any disorders that destroy lives, though technology has become available. An extremely high percentage of CIRM awards has gone to those with close ties to CIRM President/CEO and ICOC, and almost no CIRM discovery stage awards (DISC) could immediately progress to translational or clinical stages (TRAN or CLIN) to enable broad use, and ultimately, improve patient care. Such conflicts of interest (COI) have been repeatedly demonstrated again and again by every round of CIRM award meetings and press releases. Such COI have been repeatedly demonstrated again and again by millions and millions of taxpayer money awarded by CIRM to their close ties who have ended up producing absolutely nothing, including the $40 millions that CIRM President/CEO promoted and had CIRM give to her mentor’s Company Stem Cell over a decade ago. Many CIRM awards appeared in the top selection lists of CIRM not only are not original, not competitive, lack novelty, but also actually are fraudulent, including > $ 300 millions to induced pluripotent adult/stem cells (iPSC) that are in fact adult cells reprogrammed with oncogenes or cancer cells. Ironically, all CIRM stem cell research leadership awards have gone to cancer cells, mostly to iPSC, but not stem cells; almost all CIRM stem cell research leadership awards were actually struck beforehand in the back room of ISSCR conferences between the Stem Cell Center Directors of CA organizations and their identified CIRM reviewers outside CA and appointed by ICOC. As a result, CIRM has scandalously misappropriated and continues to misappropriate hundreds of millions of CA taxpayer money to make and bank cancer cells (e.g., iPSC) that are falsely called stem cells, to turn the universities of a “Blue” State into the notorious waste hubs of a scarlet “Red” adult stem cell Ponzi scheme of the Bush Administration and the training centers for the next generation of adult stem cell Ponzi scammers, to fuel the political power and public policy shift to the “Red”, including the overturning of Roe v. Wade. Dr. Parsons’ public comments provide an inside view to look into the secrecy of CIRM grants review, see the loopholes of the behind-closed-door practices of CIRM, and understand how their Ponzi schemes or scams could get preferential selections and treatments for public funding, which has resulted in the massive fraud and waste of taxpayer money.

Written Public Comment to REGULAR MEETING OF THE INDEPENDENT CITIZENS OVERSIGHT COMMITTEE AND THE APPLICATION REVIEW SUBCOMMITTEE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE Organized Pursuant To The CALIFORNIA STEM CELL RESEARCH AND CURES ACT on Sept. 28, 2023

Dear ICOC and the Application Review Subcommittee CIRM,

Thanks for the meeting notice and thank you for this opportunity to present my "Public Comment" in writing. I’d like to make a public comment regarding 4 items on your meeting agenda.

1. Consideration of appointment of members to the Grants Working Group

2. Consideration of applications submitted in response to DISC2 23.1 Quest Program Announcement

3. Consideration of proposed ReMIND Concept Plan for Neuropsychiatric Disease

4. Discussion of Personnel [Evaluation of CIRM President/CEO]

Consideration of appointment of members to the Grants Working Group (GWG)

The new appointments of the GWG were identified by Linda Nevin, Senior Science Officer for Grant Review at CIRM, and Hayley Lam, Associate Director, Portfolio Development & Review at CIRM.

We know it is a undeniable scientific fact that induced pluripotent adult/stem cells (iPSC) are adult cells reprogrammed with oncogenes or cancer cells harboring oncogenes, an adult stem cell Ponzi scheme or scam created by the opponents of human embryonic stem cell (hESC) research during the Bush Administration, including the former Presidents of International Society for Stem Cell Research (ISSCR) --- Nobel Prize winner Shinya Yamanaka and Dean of Harvard Medical School George Daley --- as well as the former CEO of Cell Press and Editor-in-Chief of Cell --- UCLA Associate Dean Emilie Marcus who we all still remember was even bidding for CIRM Chair not long ago (please see my website https://sdrmi.org hESC research blogs for more about iPSC Ponzi scheme). We know the Nobel Prize winning iPSC Ponzi scammer Shinya Yamanaka has resided in UCSF, and Linda Nevin, who was a PLOS senior editor with UCSF ties and was responsible for many fraudulent iPSC publications in PLOS, has also abused her CIRM position at the cost of California (CA) taxpayer money to facilitate many CIRM iPSC Ponzi scheme awards to her close ties in CA that Nevin has built an extensive network of connections through her previous favors as the senior editor of PLOS, including many CIRM iPSC Ponzi scheme awards to UCSF, all listed on CIRM website. CIRM President/CEO Maria Millan, CIRM Senior Science Officer Linda Nevin, and their staff are all CA State employees, and have violated CA conflict of interest (COI) law by deliberately soliciting, selecting, assisting the reviews and awards of their close ties, including many fraudulent CIRM iPSC Ponzi scheme awards, and by deliberating blocking hESC research proposals pursuant to the California Stem Cell Research and Cures Act for review and award, all without publicly disclosing their COI.

Such COI have been demonstrated by every round of CIRM meeting and press release, particularly prominent in this round. It is public consensus that hESC research holds huge promise for treating major human diseases that have been challenging to traditional medicine, and provide the only solution and hope for a wide range of incurable or hitherto untreatable diseases. CA taxpayers even passed 2 propositions, Prop. 71 and Prop. 14, to support funding hESC research, CA taxpayers are even willing to pay CIRM Chair and President more than the Governor to support funding hESC research in order to find promising treatments and cures for those life-threatening and devastating diseases. Is that quite odd and self-demonstration of COI that hESC research is completely absent in the selection of CIRM President/CEO Maria Millan, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers? Is that quite odd and self-demonstration of COI that even 4 or 5 definitive fraudulent iPSC Ponzi scheme scandal awards appeared in the top ten selection of CIRM President/CEO Maria Millan, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers? Is that quite odd and self-demonstration of COI that hESC research is not even the programmatic priority of CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers, but iPSC scandal, a scarlet “Red” adult stem Ponzi scheme of the Bush Administration, actually is? Is that quite odd and self-demonstration of COI that the programmatic priorities of CIRM are actually not aligned with the priority of The CALIFORNIA STEM CELL RESEARCH AND CURES ACT; not aligned with highly promising hESC research that millions of people are pinning their hopes on and supported by the voters of a “Blue” State; not aligned with the sciences and facts; but aligned with a scarlet “Red” adult stem Ponzi scheme of the Bush Administration --- the fraudulent the iPSC Ponzi scheme scandal as the Congress calls it “the massive fraud and waste of the Obama Administration”; but aligned with fraudulent scientific programs often appeared on the top funding lists of CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers; but aligned with the COI of the close ties of CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers; but aligned with frauds and wastes?

Linda Nevin has absolutely no experience and expertise of stem cell research and regenerative medicine, Hayley Lam has very little experience of stem cell research. They both have absolutely no knowledge, skill, and qualification for the jobs of Senior Science Officer for Grant Review at CIRM and Associate Director, Portfolio Development & Review at CIRM. They landed their jobs in CIRM because of their close ties, not because of their experience, expertise, and qualification, as demonstrated by how much grants money they have facilitated to flow into their own close ties, many of which are frauds and wastes, at the cost of CA taxpayers.

To stall CIRM’s bond financing with CA State, to drag ICOC into the iPSC Ponzi scheme scandal as the Congress calls it “the massive fraud and waste of the Obama Administration”, which has resulted in Congressional, HHS, and State investigations, which has resulted in Stanford’s ~$15 million payment to the State that CIRM President/CEO and her mentor Irving Weissman covered up as “loyalty payment”, which has resulted in the resignations of NIH Director Francis Collins and White House science advisor Eric Lander (please see below my previous public comment for more information), Linda Nevin and Hayley Lam even identified their close ties outside California, many iPSC Ponzi scammers, for ICOC to appoint as reviewers to make it even easier for them to select their close ties inside California for CIRM award. Theresa Alenghat, Associate Professor of Cincinnati Children’s Hospital Medical Center, and Christine Kay, Vitreoretinal Surgeon and Director of Electrophysiology and Retinal Genetics, have no stem cell research and regenerative medicine expertise relevant to CIRM’s mission to qualify them as CIRM reviewers. Christopher Mayhew, Director of Pluripotent Stem Cell Facility at Cincinnati Children’s Hospital Medical Center, Takanori Takebe, Associate Professor and Endowed Chair of Organoid Medicine at Cincinnati Children’s Hospital Medical Center, Wenli Yang, Research Assistant Professor of Medicine and Director of the iPSC Core Facility at University of Pennsylvania, and Ting Zhou, Director of SKI Stem Cell Research Facility at Memorial Sloan Kettering Cancer Center, are all iPSC Ponzi scammers, probably those missed by HHS, and have absolutely no scientific integrity to qualify them as CIRM reviewers. ICOC appointing those Linda Nevin and Hayley Lam’s close ties as CIRM reviewers is betrayal to CALIFORNIA STEM CELL RESEARCH AND CURES ACT, is betrayal to CIRM’s mission, is betrayal to the trust of CA taxpayers, is sabotage to CIRM’s bond financing with CA State, is complicity to the iPSC Ponzi scheme scandal as the Congress calls it “the massive fraud and waste of the Obama Administration”, is complicity to the opponents of hESC research, is leniency to those who have committed scientific misconducts, is leniency to frauds and wastes at the cost of CA taxpayer money, is walking into their trap of scandal and corruption prohibited by CA State Law.

Consideration of applications submitted in response to DISC2 23.1 Quest Program Announcement

I’d like ICOC to give me a reasonable, justifiable explanation in public and according to appropriate CA State laws or regulations or CA Props why CIRM could not review my DISC2 application, DISC2-15068, titled “Tackling the Unmet Medical Need of Amyotrophic Lateral Sclerosis Using Human Embryonic Stem Cell (hESC) Derived Neuronal Progenitor Cells”; why human embryonic stem cell (hESC) research proposals/applications like my DISC2-15068 pursuant to the California Stem Cell Research and Cure Act are not even the programmatic priority of CIRM established and funded by the taxpayer money of a “Blue” State, but induced pluripotent adult/stem cell (iPSC) scandals, a scarlet “Red” adult stem cell Ponzi scheme of the Bush Administration as the Congress calls it “the massive fraud and waste of the Obama Administration”, actually are, including DISC2-15010, DISC2-15119, DISC2-14897, DISC2-15137 on the top ten funding list of CIRM DISC2; why hESC research like my DISC2-15068 that CA voters passed 2 propositions to establish The CALIFORNIA STEM CELL RESEARCH AND CURES ACT and fund CIRM to pursue is not even the programmatic priority of CIRM, but fraudulent projects and projects irrelevant to The CALIFORNIA STEM CELL RESEARCH AND CURES ACT and CIRM’s mission, actually are, including DISC2-14935. DISC2-15120, DISC2-14982, DISC2-14907, DISC2-14899, DISC2-14963 on the top ten funding list of CIRM DISC2, and CIRM minority report DISC2-14900, DISC2-15114; why hESC research of The CALIFORNIA STEM CELL RESEARCH AND CURES ACT that CIRM is organized to pursue, crucial to provide the only solutions for a wide range of incurable or hitherto untreatable diseases, is not even the programmatic priority of CIRM, but the frauds and wastes of the close ties of CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, CIRM GWG reviewers, and ICOC members actually are.

DISC2-15068, titled “Tackling the Unmet Medical Need of Amyotrophic Lateral Sclerosis Using Human Embryonic Stem Cell (hESC) Derived Neuronal Progenitor Cells” is a resubmission, and we have addressed all the concerns of previous GWG reviewers. Please see the resubmission statement and CIRM staff email below.

We know ALS is a devastating, fatal, and most costly neuromuscular disease that currently has no cure and no effective treatment to save life. Finding an effective therapeutic approach remains a primary goal for ALS research. Human trials with traditional adult stem cells (e.g., Brainstorm’s MSC, Kadimastem’s astrocytes, Cedars-Sinai’s iPSC [induced pluripotent adult/stem cells] that CIRM have previously funded tens of millions) have failed to demonstrate clinical efficacy/benefit for ALS patients, identifying the urgent need for an effective therapeutic cell source adequate to regenerate the lost nerve tissue and function in ALS. We have built a key innovative PluriXcel-SMI-Neuron platform that enables highly efficient, direct conversion of non-functional human embryonic stem cells (hESC) uniformly into a large supply of high quality human neuronal progenitor cells (Xcel-hNuP) as a novel neuronal regenerative medicine advanced therapy (NRMAT) product to tackle the unmet medical need of ALS [patent: USPTO# 8,716,017]. The goals of this project are to obtain necessary preclinical safety and efficacy data, and determine whether our product is a neuronal lineage-committed prototype with a high likelihood of graft-dependent motor neuron regeneration and no pluripotence- or other cellular impurity-associated safety concerns, thus meriting its advance to CIRM TRAN 1 for immediately progressing to translational stage activities as a therapeutic candidate for ALS. This project presents an innovative, more effective therapeutic solution for ALS, overcoming the major bottleneck in the regenerative medicine market for CNS repair and advancing treatment of CNS disorders. If successful, this platform/product will have broad applications for a wide range of incurable or hitherto untreatable neurological diseases, having tremendous economy and health impact and bringing enormous benefit to CA diverse population. In this resubmission, we have also addressed all the GWG reviewers’ concerns. And the PI’s outstanding contribution to DEI is also well-documented in the resubmission.

It is public consensus that hESC research holds huge promise for treating major human diseases that have been challenging to traditional medicine, and provide the only solution and hope for a wide range of incurable or hitherto untreatable diseases. CA taxpayers even passed 2 propositions, Prop. 71 and Prop. 14, to support funding hESC research, CA taxpayers are even willing to pay CIRM Chair and President more than the Governor to support funding hESC research in order to find promising treatments and cures for those life-threatening and devastating diseases. Is that quite odd and self-demonstration of COI that hESC research is completely absent in the selection of CIRM President/CEO Maria Millan, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers? Is that quite odd and self-demonstration of COI that even 4 or 5 definitive fraudulent iPSC Ponzi scheme scandal awards appeared in the top ten selection of CIRM President/CEO Maria Millan, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers? Is that quite odd and self-demonstration of COI that hESC research is not even the programmatic priority of CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers, but iPSC scandal, a scarlet “Red” adult stem Ponzi scheme of the Bush Administration, actually is? Is that quite odd and self-demonstration of COI that the programmatic priorities of CIRM are actually not aligned with the priority of The CALIFORNIA STEM CELL RESEARCH AND CURES ACT; not aligned with highly promising hESC research that millions of people are pinning their hopes on and supported by the voters of a “Blue” State; not aligned with the sciences and facts; but aligned with a scarlet “Red” adult stem Ponzi scheme of the Bush Administration --- the fraudulent the iPSC Ponzi scheme scandal as the Congress calls it “the massive fraud and waste of the Obama Administration”; but aligned with fraudulent scientific programs often appeared on the top funding lists of CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers; but aligned with the COI of the close ties of CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM GWG reviewers; but aligned with frauds and wastes?

Even CIRM presentation shows that CIRM DISC2 is to promote stem cell and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care, that could immediately progress to CIRM TRAN1, none of the top ten selection of CIRM President/CEO Maria Millan and CIRM Senior Science Officer Linda Nevin could be translated to enable broad use and ultimately, improve patient care, or could immediately progress to CIRM TRAN1.

In stunning contrast to the discriminative and unfair treatment behind closed doors to the highly promising hESC research proposals of women and minority PI like me, CIRM President/CEO Maria Millan, CIRM Senior Science Offices Linda Nevin, and GWG reviewers even selected a iPSC Ponzi scheme project DISC2-15010 “C9orf72 repeat expansion-tuned allelic suppression by CRISPRi as an ALS therapy”, and a Minority Report for DISC2-15114 “Development of a VAV2 antisense oligonucleotide (ASO) treatment for ALS”, for ICOC approval for funding. It is common scientific knowledge that ALS is not caused by genes, and gene therapy for ALS is a very distant, often failed, option for anyone to pursue. C9orf72 of DISC2-15010 has only been studied in fly, mouse, and iPSC (the basis in wrong, e.g., iPSC are not stem cells but cancer cells harboring oncogenes, the iPSC results and data of C9orf72 of DISC2-15010 are definitely falsified or fabricated), has never been studied in humans, and whether C9orf72 plays any role in ALS remains unknown. Also, studies show C9orf72 is not an essential component that mediates neuronal survival, and crucially, none of the mouse C9orf72 knockouts recapitulate ALS, suggesting that C9orf72 loss of function is insufficient to precipitate ALS disease. There is also absolutely zero data to show the VAV2 ASO of DISC2-15114 has anything to do with ALS and could provide any treatment for ALS at all. Even CIRM presentation shows that CIRM DISC2 should demonstrate disease modifying activity and CIRM GWG review should be scientifically rigorous. Both C9orf72 of DISC2-15010 and VAV2 ASO of DISC2-15114 are fraudulent against scientific evidence, against scientific data, against scientific vigor. Neither C9orf72 of DISC2-15010 nor VAV2 ASO of DISC2-15114 could demonstrate any disease modifying activity, could enable board use & improve patient care, could immediately progress to CIRM TRAN1 as our hESC product of DISC2-15068 can. Neither C9orf72 of DISC2-15010 nor VAV2 ASO of DISC2-15114 could restore motor neuron tissue and function in ALS patients as our hESC product of DISC2-15068 can. Neither C9orf72 of DISC2-15010 nor VAV2 ASO of DISC2-15114 have any technology, patent, or scientific publication to show they could translate it to humans as our hESC product of DISC2-15068 can. Neither C9orf72 of DISC2-15010 nor VAV2 ASO of DISC2-15114 are scientifically rigorous as our hESC product of DISC2-15068 is. How could such fraudulent C9orf72 of DISC2-15010 and VAV2 ASO of DISC2-15114 Ponzi schemes or scams get preferential selection, treatment, biased scores of 84 or 85 over our highly promising hESC research project for CIRM funding by CIRM President/CEO Maria Millan and CIRM Senior Science Officer Linda Nevin, and GWG reviewers at the cost of taxpayer money? Those iPSC Ponzi scammer professors they identified with close ties to themselves for ICOC appointing as CIRM GWG reviewers may partially explain. To add insult to injury for CIRM President/officer/staff and GWG’s discriminative and unfair treatment behind closed doors to the highly promising hESC research proposals of women and minority PI like me, CIRM GWG reviewers even select a fraudulent VAV2 ASO of DISC2-15114 against scientific evidence, against scientific data, against scientific vigor, against scientific integrity for a minority report to deliberately defraud the investing public and taxpayers. CIRM minority report is supposed for an extraordinary therapeutic opportunity such as the hESC breakthrough medical innovation of our DISC2-15068 would be able to provide for ALS patients, not for GWG reviewers to sneak in their COI and fraudulent projects against common scientific knowledge and against all scientific evidence to publicly sham ICOC and sabotage CIRM’s bond financing with the State.

Even though CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM Associate Director, Portfolio Development & Review Hayley Lam, have no or little experience and expertise of stem cell research and regenerative medicine, have no or little knowledge, skill, or qualification for their jobs, only know how to select fraudulent projects against scientific data and scientific vigor for their close ties, do not know how to select highly promising hESC research proposals pursuant To The CALIFORNIA STEM CELL RESEARCH AND CURES ACT, the public is not blind. Everyone can see that their selection contains only iPSC scandal, a scarlet “Red” adult stem cell Ponzi scheme of the Bush administration, including C9orf72 of DISC2-15010, DISC2-15119 “Drug discovery for gastrointestinal motility disorders using hPSC-derived enteric ganglioids”, DISC2-14897 “Assessing the Functional, Immunologic and Microbiologic Characteristics of Human Livers Created in Chimeric Pigs”, DISC2-15137 “Inhibitory interneurons derived from human induced pluripotent stem cells to treat stroke and other scams”, but have absolutely no highly promising hESC research projects that would bring enormous benefit to CA diverse population, help gain voter and CA State support for bond financing and funding, and help gain voter support for future Proposition. CIRM President/CEO Maria Millan, CIRM General Counsel Rafael Aguirre-Sacasa, CIRM Senior Science Officer Linda Nevin, and CIRM Associate Director, Portfolio Development & Review Hayley Lam, are publicly shaming ICOC with their deliberate act to defraud the investing public and taxpayers and with their purposely self-demonstration of COI to serve their close ties under the public eyes as CA State employees.

Also, is that against CA State laws or regulations for CIRM President, staff, general counsels, and panelists to be involved in CIRM grants review or selection process without publicly disclosing their COI or their personal, professional, and financial ties to the grants they selected for review and awards, and without giving them proper scientific review trainings to avoid or mitigate COI, biases, and integrity breaches? Such behind closed door practices of COI, biases, and systemic racism by CIRM President, staff, general counsel, and panelists have not only betrayed the trust of CA taxpayers to CIRM and stalled stem cell research, but also resulted in CIRM scandalously misappropriating and continuing to misappropriate hundreds of millions of CA taxpayer money to make and bank cancer cells (e.g., induced pluripotent adult/stem cells [iPSC]) that are falsely called stem cells, to turn the universities of a “Blue” State into the notorious waste hubs of a scarlet “Red” adult stem cell Ponzi scheme (iPSC) of the Bush Administration and the training centers for the next generation of adult stem cell Ponzi scammers in higher education, to fuel the political power and public policy shift to the “Red”, including the overturning of Roe v. Wade. For example, in last round of CIRM DISC0, CIRM President, staff, general counsels, and panelists would not even select my proposal for review, DISC0-14415, titled “Human Embryonic Stem Cells (hESC) as a Model System to Unveil Polycomb (PcG) and Trithorax (TrxG) Antagonism in Human Embryonic Neurogenesis” to bridge knowledge gap in human CNS development and facilitate rapid progress on tackling neuro diseases, instead, CIRM ICOC gave or approved 5 or 6 iPSC Ponzi scheme awards to UC and Stanford Universities with close COI ties to CIRM President, staff, general counsels, and panelists, against CIRM’s own COI policy.

Are you resubmitting a substantially similar proposal that addresses GWG reviewer comments on a previous CIRM application? X Yes.

We appreciate the GWG reviewer comments, which enable dramatic improvements of this application, including: ALS currently has no effective treatments and this would represent a major advance, methods and information obtained from this proposal is likely to be valuable to other similar diseases and indications, the strength of the proposal is the technology to generate a relatively pure population of motor neurons, these will be very useful for ALS and other research, the project plan has a well-developed plan to account for race, ethnicity, sex and gender diversity. To address the GWG reviewer concerns:

The GWG reviewers were concerned about the feasibility of implanting motor neurons and motor neuron replacement therapy for ALS. We totally agree with the GWG reviewers, previous studies show poor survival/integration of motor neurons or stem cell-derived motor neurons following transplantation. To address those problems or GWG reviewer concerns, this proposal uses the highly neurogenic hESC-derived human neuronal progenitor cells (hNuP) in large quantity, not the motor neurons as assumed by the GWG reviewers, to tackle ALS, a devastating, fatal, and most costly neuromuscular disease with no cure and no effective treatment to halt or reverse the disease’s progression. To avoid confusion, we have deleted the term of “motor neuron replacement therapy” from this revised proposal.

We have secured patent (USPTO # 8,716,017) for the proposed studies and further development and commercialization of relevant hESC-derived products and technologies. To clarify our product’s unique advantages over existing products, our Nurr1+/Nestin- hESC-derived hNuP is a novel stem cell product that yields exclusively neurons, is highly neurogenic in vitro and in vivo, and contains no residual pluripotent cells and other cellular impurities of safety concerns, distinctly different from the prototypical epithelial-like Nurr1-/Nestin+ hESC/hiPSC-derived hNSC that differentiate into a heterogeneous population of mixed cell types containing undifferentiated hNSC, neurons (~6%), astrocytes, and oligodendrocytes, and yield motor neurons at a low prevalence following engraftment, not only insufficient for motor neuron regeneration, but also accompanied by high incidents of teratoma and/or neoplasm formation, raising considerable safety concerns. So far, there is no other technology that can turn pluripotent stem cells into a large supply of neuronal cells at the pluripotent stage in such high efficiency or enables well-controlled neuronal lineage-specific differentiation direct from the pluripotent state of hESC, therefore, this approach is a big breakthrough, providing advantages of safety, efficacy, and large-scale production or scalability over other approaches for successful clinical trials, and overcomes a current major bottleneck for CNS repair or regeneration and advancing treatment of CNS disorders.

This is a CIRM DISC2 proposal, as defined by CIRM, the purpose of DISC2 is to promote discovery of promising new stem cell-based and/or gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care. The goals of this project are to obtain necessary preclinical safety and efficacy data, and determine whether our product is a neuronal lineage-committed prototype with a high likelihood of graft-dependent motor neuron regeneration and no pluripotence- or other cellular impurity-associated safety concerns, thus meriting its advance to CIRM TRAN 1 for immediately progressing to translational stage activities as a therapeutic candidate for ALS. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms. Finding an effective therapeutic approach remains a primary goal for ALS research. Human trials with traditional stem cells (e.g., Brainstorm’s MSC, Kadimastem’s astrocytes) have failed to demonstrate clinical efficacy/benefit for ALS patients, identifying the urgent need for an effective therapeutic cell source adequate to regenerate the lost nerve tissue and function in ALS. If successful, this platform/product will have broad applications for a wide range of incurable or hitherto untreatable neurological diseases, having tremendous economy and health impact and bringing enormous benefit to CA diverse population. Therefore, the benefit to complete the proposed studies outweighs any potential risks or concerns of the GWG reviewers.

To address the GWG reviewer concerns about the hostile or toxic environment of ALS, we propose the initial transplantation be done in pre-symptomatic rats to allow the transplanted cells survive, integrate, differentiate into motor neurons, to increase the likelihood of survival and motor neuron regeneration or repair. Multicomponent combined approaches, such as co-transplanting support cells that can provide secreted trophic factors and remyelination will be examined as stated in the alternative approaches.

From: Liz Noblin <lnoblin@cirm.ca.gov>
Sent: Friday, July 14, 2023 11:06 AM
Cc: Scott Tocher <stocher@cirm.ca.gov>; Discovery Mailbox <Discovery@cirm.ca.gov>; Claudette Mandac <cmandac@cirm.ca.gov>
Subject: CIRM DISC2 Positive Selection Outcome

Dear DISC2 Applicant,

Thank you for submitting your application under the California Institute for Regenerative Medicine’s (CIRM) DISC2 Quest Program.

When the total number of submitted applications exceeds the capacity of a CIRM Grants Working Group (GWG) panel to review in a single session, GWG panelists screen the applications and select a subset to advance to full review. The CIRM staff and President examine non-selected applications to determine if any others merit full review based on programmatic priorities, and the remainder are not considered further. This process is described in the DISC2 Program Announcement, on page 11.

In this DISC2 competition, 89 eligible applications were submitted and 46 advanced to GWG review. Unfortunately, your application was not among those selected for review. CIRM’s consideration of your application has concluded, and no further action will be taken or is required of you.

CIRM ensures and verifies that each application is read by at least three panelists during this screening process. To make screening manageable for reviewers, CIRM does not require that reviewers provide any written critique or scoring at the screening stage. As a result, we cannot provide feedback on your application. Review Summaries for those applications that did proceed to GWG review will be posted on CIRM’s website in September and will be available via the following link: https://www.cirm.ca.gov/about-cirm/funding-opportunities-discovery-stage-research. Scroll down to ‘Foundation Application Review Summaries'.

Please continue to check our website for new announcements and funding opportunities. You may also email discovery@cirm.ca.gov to discuss projects that could be the subject of a future Discovery stage application.

I’m sorry to not have better news this time.

Kind regards,

Liz Noblin, PhD (she/her/hers)
Senior Science Officer, Portfolio Development and Review
California Institute for Regenerative Medicine (CIRM)
Phone: 510-775-0431 | lnoblin@cirm.ca.gov

Consideration of proposed ReMIND Concept Plan for Neuropsychiatric Disease

What activities will CIRM fund

Derivation of new induced pluripotent stem cell lines to address specific project needs, especially those derived from ancestral backgrounds currently underrepresented in research studies.

As I have commented before in Larry Goldstein’s Neurotask force meetings that Larry Goldstein considered as public comment he usually would like to ignore, not bring up for discussion, or not post, the neurons derived from iPSC shown by psychiatry professors, like Christine Cheng of UCSD, do not even look like neurons, only very weakly express one single neuron marker, it is very questionable what kind of insight or useful knowledge could be generated from iPSC, considering iPSC is in fact adult cells reprogrammed with oncogenes or cancer cells harboring oncogenes, a scarlet “Red” adult stem cell Ponzi scheme of the Bush administration. Also, most neuropsychiatric diseases have no tissue or functional losses, and are not caused by genes, for the few that may have genetic causes, it is not caused by a single gene, but by a very complex aggregated effect of many genes, which would be very challenging for any gene therapy or genetic studies. Therefore, neuropsychiatric disease may not be a good fit for cell and gene therapy, while many neurological diseases are, such as stroke, Parkinson’s disease (PD), Alzheimer disease (AD), spinal cord injury (SCI), traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA). It would not help CIRM bond financing with CA State to prioritize non-life-threatening neuropsychiatric diseases that only affect a very small population of people, while completely ignore those life-threatening devastating neuro diseases like stroke, like ALS, like PD that affect millions and cost trillions, that CA voters passed 2 propositions to establish The CALIFORNIA STEM CELL RESEARCH AND CURES ACT and fund CIRM to pursue. It could actually hurt CIRM bond financing with CA State to prioritize iPSC scandal, a scarlet “Red” adult stem cell Ponzi scheme of the Bush administration as the Congress calls it “the massive fraud and waste of the Obama Administration”, to derail the “Blue” State officials’ policy and agenda, while completely ignore hESC research pursuant to The CALIFORNIA STEM CELL RESEARCH AND CURES ACT passed by a “Blue” State and aligned with the “Blue” State officials’ policy and agenda. Given Larry Goldstein’s extensive connections to those iPSC neuropsychiatric professors who would benefit from the proposed ReMIND Concept Plan for Neuropsychiatric Disease, it is not without doubt about his real intention to compel ICOC to pass his plan that only prioritizes Neuropsychiatric Disease but completely ignores the priority of The CALIFORNIA STEM CELL RESEARCH AND CURES ACT and hESC research that CIRM is compelled by CA voters to pursue, and it is very questionable whether his proposed ReMIND Concept Plan for Neuropsychiatric Disease is actually rooted in COI.

Discussion of Personnel [Evaluation of CIRM President/CEO]

Public Comment to REGULAR MEETING OF THE GOVERNANCE SUBCOMMITTEE OF THE INDEPENDENT CITIZENS OVERSIGHT COMMITTEE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE Organized Pursuant to The CALIFORNIA STEM CELL RESEARCH AND CURES ACT on Sept. 14, 2023

Dear ICOC and Governance Subcommittee of ICOC CIRM,

Thanks for the meeting notice for Evaluation of CIRM President/CEO. I’d like to make a public comment regarding the discriminative and unfair treatment by CIRM President/CEO Maria Millan behind closed doors to my human embryonic stem cell (hESC) research applications pursuant to the California Stem Cell Research and Cures Act, such as repeatedly not selecting my hESC research proposals based on our breakthrough medical innovations (patents: USPTO# 9,428,731. USPTO# 8,716,017) for GWG review, including multiple resubmissions; unreasonably requiring the applicant like me to demonstrate conflicts of interest (COI) before appeal in front of ICOC without even revealing to the applicant who are the reviewers; intentionally marginalizing the applicant like me from underserved and underrepresented racial/ethnic communities that have neither representation in ICOC nor ally in GWG; and even retaliation that is not tolerated by any Federal and State Laws or by any organization that complies with Federal and State Laws.

The successful derivation of hESC lines from the in vitro fertilization (IVF) leftover embryos is considered as one of the major breakthroughs of the 20th century life sciences. Pluripotent hESC can maintain long-term, stable growth and differentiate into clinically-relevant lineages, providing an inexhaustible source of replacement cells for human tissue and function restoration. It is public consensus that hESC research holds huge promise for treating major human diseases that have been challenging to traditional medicine, such as a wide range of incurable or hitherto untreatable neurological and heart diseases, including heart disease and failure, stroke, Parkinson’s disease (PD), Alzheimer disease (AD), spinal cord injury (SCI), traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA). The estimated costs are over $2 trillions annually. Millions of people are pinning their hopes on hESC research. Despite these devastating and life-threatening diseases are leading causes of death or permanent disability, yet, there is no effective treatment or drug available. The limit capacity of cardiomyocytes (the mature contracting heart muscle cells) of the heart as well as neuron circuitries of the brain/spinal-cord for self-repair constitutes a significant challenge to traditional medicine for tissue and function restoration in seeking cures for those serious diseases and conditions. To date, the need to restore vital tissue and function for a wide range of incurable or hitherto untreatable neurological and heart diseases remains a daunting challenge to the conventional mode of drug development.

Although stem cell therapy represents a promising regenerative medicine approach closest to provide a cure for those diseases, demonstrating stem cell production at the scale and product purity adequate to heal the damaged or lost tissues that have naturally limited capacity for repair, such as the human heart and brain, has been a big challenge for traditional adult stem cell sources or products, including so-called induced pluripotent adult/stem cells (iPSC) that are in fact adult cells reprogrammed with oncogenes or cancer cells harboring oncogenes, and another adult stem cell Ponzi scheme or scam (please see https://www.sdrmi.org hESC research blogs for more about iPSC Ponzi scheme). As neurological and cardiovascular diseases incur exorbitant costs on the healthcare system worldwide, there is a strong focus on translating hESC research innovations to provide potentially life-saving treatments or cures for these major health problems.

The difficulty of crossing “the valley of death” in drug development is the pounding consequence of a vast amount of Federal and private investments only go to maintain the status quo of mainstream biomedical research in the non-human model organisms or systems that do not reflect the complexity of humans, thus have little implications for the prevention and treatment of human diseases. Without a readily accessible and effective human model system to unlock the mysteries of human development and disorders, the road of desperately seeking cures has become all but a dead end to real world remedy. Due to the restriction on human embryonic and fetal materials available for study, there is a fundamental gap in our knowledge regarding the molecular networks and pathways underlying human embryogenesis. Derivation of hESC provides powerful in vitro model systems to remove limitations at the cellular or biological systems levels that stymie progress towards developing tools and platforms that can apply to a broad range of diseases.

My breakthrough hESC innovations render neuronal/cardiac lineage-specific conversion directly from the pluripotent state of hESC by small molecule induction, which opens the door for human neural/cardiac tissue/organ engineering/regeneration and investigating molecular human embryonic development using powerful in vitro model systems. My innovative achievements in hESC research have demonstrated the direct pharmacologic utility and capacity of hESC therapy derivatives for human CNS and myocardium regeneration, which not only constitutes clinically representative progresses in both human neuronal and cardiac therapeutic products, but also offers manufacturing innovation for production scale-up and creation of replacement tissue/organ products. My breakthrough medical innovations present hESC as a novel, advanced therapeutic strategy for a wide range of incurable or hitherto untreatable neurological and heart diseases, having tremendous impact on economy, health, future medicine, and patient care.

As we know, Prop.14 designates $1.5 billions on neuro disease research, to find treatments or cures for a host of neurological disorders that destroy lives. CIRM Chair is paid ~$650,000 annually, CIRM President/CEO alike, by CA taxpayers, probably even more than the Governor, to do this job. CIRM Chair, CIRM President/CEO alike, is entrusted by CA taxpayers to fund highly promising hESC research, to establish cutting-edge, world-class stem cell centers in CA, to find treatments or cures for a host of disorders that destroy lives. However, there are stunning discrepancies and double-standards between CIRM public grants review/funding policies of ICOC and behind-closed-door practices of CIRM President/CEO. For examples, in public, ICOC board member Larry Goldstein has so far organized probably 6 or 7 Neuro-task force meetings to tackle neuro diseases; but behind-closed-doors, CIRM President/CEO, staff, general counsels, and panelists would not even bring my highly promising hESC research proposals to tackle such devastating, life-threatening, most costly, incurable or hitherto untreatable neuro diseases like ALS for a fair review. In public, CIRM loudly promotes and values diversity, equity, and inclusion (DEI); but behind-closed-doors, CIRM President/CEO, staff, general counsels, and panelists actually exercise their systemic racism to intentionally marginalize or even block highly promising hESC research proposals tackling unmet medical needs from underrepresented minority/woman PI like me for review. As a result, CIRM has scandalously misappropriated > $300 millions of CA taxpayer money, and continues to misappropriate hundreds of millions of CA taxpayer money to make and bank cancer cells (e.g., induced pluripotent adult/stem cells [iPSC]) that are falsely called stem cells; to turn the universities of a “Blue” State into the notorious waste hubs of a scarlet “Red” adult stem cell Ponzi scheme (iPSC) of the Bush Administration and the training centers for the next generation of adult stem cell Ponzi scammers in higher education; to fuel the political power and public policy shift to the “Red”, including the overturning of Roe v. Wade. In contrast, although the technology has become available, CIRM has not even given a penny of CA taxpayer money for CA to establish clinical-grade high quality human embryonic stem cell (hESC – the real pluripotent stem cell) lines and banks that are in urgent need for patients.

It is common knowledge for anyone with a doctor degree in science or medicine (PhD or MD), such as CIRM President/CEO, that induced pluripotent adult/stem cells (iPSC) contain oncogenes, have oncogenic potential, are in fact cancer cells, but not stem cells. CIRM President/CEO knows or has the full knowledge that iPSC are cancer cells and harmful to patients, but has still knowingly misled the investing public and taxpayers, and deliberately defrauded the investing public and taxpayers by misappropriating >$300 million of the taxpayer money of a “Blue” State to a scarlet “Red” adult stem cell Ponzi scheme of the Bush administration – iPSC the fake stem cells. To prove that CIRM President/CEO absolutely knows iPSC is a scientific Ponzi scheme or adult stem cell scam and deliberately defrauds the investing public and taxpayers by misappropriating over $300 million of CA taxpayer money to iPSC, CIRM President/CEO even awarded DISC0-13806, titled “Development of universal off-the-shelf iPSC derived dendritic cells for use as patient specific anti-tumor vaccine”, to UCSF to use iPSC to make anti-tumor vaccine. You can only use cancer cells, not stem cells, to make anti-tumor vaccine; or you could only use stem cells to make anti-stem-cell vaccine to kill patients if iPSC were really stem cells.

As a matter of fact, CIRM President/CEO and her mentor Irving Weissman of Stanford University even covered up Stanford University’s payment of ~$15 million to the State in January 2022 for their involvement in iPSC Ponzi scheme as the “loyalty payment” (only a small fraction of the iPSC awards from CIRM), without informing the public, without even informing CIRM oversight ICOC, then gave Stanford University back right away by awarding ~$12 million to an adult stem cell scam for a safety trial as her loyalty payment or personal favor to Stanford University. After CIRM former General Counsel resigned for the mishap in Stanford’s “loyalty payment”, CIRM President/CEO even hired a new General Counsel from a iPSC Company of Stanford University with inherent COI to hESC research and CIRM’s mission Organized Pursuant to The CALIFORNIA STEM CELL RESEARCH AND CURES ACT. CIRM President/CEO has an iPSC person who or whose Company has received millions of CIRM funding for iPSC to serve as its General Counsel is self-demonstration of COI to hESC research that CIRM is organized to pursue, and her cover up has resulted in CIRM continuing misappropriation of hundreds of millions of CA taxpayer money to iPSC Ponzi scheme projects with close ties to CIRM President/CEO, all listed on CIRM website.

The Program Announcement (PA) of CIRM DISC0 specifies that DISC0 should address a key knowledge gap in humans and facilitate translational research and therapy development. However, CIRM President/CEO even defied CIRM DISC0 program announcement by denying fair review of our hESC research proposals, including DISC0-13729 and resubmission DISC0-14415, Project Title: “Human Embryonic Stem Cells (hESC) as a Model System to Unveil Polycomb (PcG) and Trithorax (TrxG) Antagonism in Human Embryonic Neurogenesis”, that is essential to bridge the knowledge gap in human CNS development using a much-needed hESC model system we hold patents and facilitate rapid progress on tackling a wide range of neuro diseases that affect millions and cost trillions. Instead, CIRM President/CEO has selected exclusively round and round of iPSC Ponzi scheme awards with close ties to herself for ICOC approval against CIRM’s own COI policy, and even defied CIRM’s own program announcement (PA) of DISC0, as demonstrated by that none of the iPSC Ponzi scheme awards selected by CIRM President/CEO even address any knowledge gap at all. In fact, most of CIRM awards selected by CIRM President/CEO are not original, not competitive, and lack novelty. For example, one CIRM DISC0 award actually is for Oct-4, a transcription factor that has already been overwhelmingly studied before, what more do we really need to know about Oct-4? Why would this university professor’s Oct-4 project that do not even respond to CIRM DISC0 program announcement at all (e.g., address a knowledge gap in humans and provide useful information for treating diseases) score > 85 and even got ICOC approval for funding, while CIRM President/CEO would not even pick my hESC research project that responded to CIRM DISC0 program announcement to address the key knowledge gap in human development and facilitate rapid progress on tackling a wide range of neuro diseases that affect millions and cost trillions for GWG review?

CIRM President/CEO knows that the breakthrough medical innovations of hESC research would provide potential life-saving treatments and cures for a wide range of incurable or hitherto untreatable diseases, including heart disease and failure, stroke, Parkinson’s disease, Amyotrophic lateral sclerosis (ALS), Spinal muscular atrophy (SMA), Alzheimer disease, spinal cord injury (SPI), traumatic brain injury (TBI), and neurodegenerative diseases that affect millions and cost trillions, but has still deliberately defrauded the investing public and taxpayers by denying fair review and funding of such hESC research projects critical to our nation’s health.

For example, we know ALS is a devastating, fatal, and most costly neuromuscular disease that currently has no cure and no effective treatment to save life. Finding an effective therapeutic approach remains a primary goal for ALS research. Human trials with traditional adult stem cells (e.g., Brainstorm’s MSC, Kadimastem’s astrocytes) have failed to demonstrate clinical efficacy/benefit for ALS patients, identifying the urgent need for an effective therapeutic cell source adequate to regenerate the lost nerve tissue and function in ALS. We have built a key innovative PluriXcel-SMI-Neuron platform that enables highly efficient, direct conversion of non-functional hESC uniformly into a large supply of high quality human neuronal progenitor cells (Xcel-hNuP) as a novel neuronal regenerative medicine advanced therapy (NRMAT) product to tackle the unmet medical need of ALS [patent: USPTO# 8,716,017]. However, CIRM President/CEO even denied fair review and funding of such highly promising hESC research proposals that we responded to CIRM program announcement of DISC2, including DISC2-13125, titled “The Pluripotent Human Embryonic Stem Cell-based Innovative Platform Enabling Regenerative Medicine Advanced Therapy for Amyotrophic Lateral Sclerosis [ALS])”, and resubmission DISC2-15068, titled “Tackling the Unmet Medical Need of Amyotrophic Lateral Sclerosis Using Human Embryonic Stem Cell Derived Neuronal Progenitor Cells”, that provides currently only available effective therapeutic stem cell source we’ve developed and hold patents/IP for the unmet medical need of ALS patients. The goals of our ALS project are to obtain necessary preclinical safety and efficacy data, and determine whether our product is a neuronal lineage-committed prototype with a high likelihood of graft-dependent motor neuron regeneration and no pluripotence- or other cellular impurity-associated safety concerns, thus meriting its advance to CIRM TRAN 1 for immediately progressing to translational stage activities as a therapeutic candidate for ALS, which are highly responsive to the program announcement of CIRM DISC2. Our ALS project presents an innovative, more effective therapeutic solution for ALS, overcoming the major bottleneck in the regenerative medicine market for CNS repair and advancing treatment of CNS disorders. If successful, this platform/product will have broad applications for a wide range of incurable or hitherto untreatable neurological diseases, having tremendous economy and health impact and bringing enormous benefit to CA diverse population. In this resubmission, we have also addressed all the GWG reviewers’ concerns. And the PI’s outstanding contribution to DEI is also well-documented in the resubmission.

In contrast, CIRM President/CEO knows that iPSC are cancer cells and harmful to patients, but has still knowingly misled and deliberately defrauded CA taxpayers by awarding ~$12 millions to Cedar Sinai/UCLA for an iPSC clinical trial to harm ALS patients with cancers and knowingly waste CA taxpayer investment.

We hold IP/Patents for our hESC projects we have responded to CIRM program announcements, and patent is undeniably the gold standard of innovation, originality, competitive advantage. Almost no CIRM awards picked by CIRM President/CEO even hold any technology innovation or patent at all. However, CIRM GWG reviewers even deemed my project DISC2-14071 that we hold IP/Patent, titled “Dopaminergic regeneration of a novel nuclear Nurr1-positive neuronal progenitor derived from human embryonic stem cells (hESC) by small molecule induction”, “not original, not competitive, little innovation, lacks novelty” while they also recognized we in fact hold the patent --- the gold standard of innovation, originality, and competitive advantage, with such very conflicted GWG review comments, apparently biased review, and unfair score of 20. The therapeutic candidate of my application, Xcel-hNuP, is a novel, nuclear-localized Nurr1-positive (Nurr1+), Nestin-negative (Nestin-), human dopaminergic (DA) neuronal progenitor derived from pluripotent human embryonic stem cells (hESC) by small molecule induction (SMI). So far, there is no other candidate or similar project that can turn pluripotent stem cells into a large supply of Nurr1-positive neuronal cells at the pluripotent stage in such high efficiency or enables well-controlled neuronal lineage-specific differentiation direct from the pluripotent state of hESC, and no other cells or candidates that are nuclear Nurr-1 positive and can regenerate damaged or lost DA neurons in PD, therefore, the approach of my DA proposal is a big breakthrough, providing advantages of safety, efficacy, and large-scale production or scalability over other approaches for successful clinical trials, and overcomes a current bottleneck for CNS repair or regeneration. The neuronal lineage specific transcription factor Nurr-1 is essential for maintenance of maturing and adult midbrain DA neurons, or an essential marker for DA progenitor cells or DA neurons. The DA01 of Bluerock Therapeutic/UCI/UCLA/Salk/UCSD does not even have nuclear-localized Nurr-1 (see Piao et al., Cell Stem Cell 2021;28:217-229), suggesting DA01 of Bluerock Therapeutics with connections to UCI/UCLA/Salk/UCSD and big Pharms, like Bayer, is actually not a DA progenitor, will certainly fail in their clinical trial. Bluerock Therapeutic has been eyeing the therapeutic candidate of my application for years, even published our large primate PD model study data from the therapeutic candidate of my application in their Nature paper without our knowing and permission (see Kirks et al., Nature 2011;480:547-551) until they retracted those data later on to avoid the consequence of scientific misconduct. We all know the Parkinson's disease (PD) therapeutic market is huge. With such huge financial interest, COI is sadly unavoidable when those members in GWG, who have direct or indirect connection to Bluerock Therapeutic, UCI/UCLA/Salk/UCSD, and big Pharms like Bayer, have a real or apparent motivation or financial interest in blocking funding of our true DA neuronal progenitor of this application for advancing breakthrough hESC research such that the members who have direct or indirect connection to Bluerock Therapeutic/UCI/UCLA/Salk/UCSD/Bayer or their allies are in a position to gain financially, professionally or personally from “the new candidates being tested in clinic or other similar project already ongoing” of GWG members or their allies/associates by deliberately giving a negative evaluation and biased score of this grant proposal.

To prevent the applicant from appealing the GWG biased and flawed review in front of ICOC, CIRM President/CEO even required the applicant like me to demonstrate COI without revealing to the applicant who were the reviewers. However, CIRM President/CEO and General Counsel completely denied any COI for appeal even after we had clearly demonstrated COI in our appeal letter, including “the extremely high percentage of CIRM awards with close ties to themselves, dominated by men, including Alysson Muotri of UCSD, Marius Wernig of Stanford University, Joseph Wu of Sanford University; the extremely low percentage of CIRM DISC2 awards able to progress to CIRM TRAN that our hESC research proposals would make a difference; the GWG reviewer’s own disingenuous comments against scientific evidence, against scientific data, against USPTO’s gold standard by biasing towards their candidates and their similar projects with close ties and biasing against my proposal are evidence or demonstration that COI exists when a Working Group member has a real or apparent interest in blocking funding of this application to advance breakthrough hESC research such that the member is in a position to gain financially, professionally or personally from a negative evaluation and biased score of this grant proposal; although the GWG reviewers remain confidential, it is not too hard to tell most of the GWG reviewers are opponents of hESC research by their comments to promote iPSC Ponzi scheme or adult stem cell scam and their negative comments and unfair scores to hESC research; the well-known fact that CIRM has misappropriated >$300 millions to iPSC Ponzi scheme or scam created by the opponents of hESC research who have direct or indirect connection to ICOC or GWG; CIRM President/CEO, some GWG reviewers, and some ICOC member’s close ties to iPSC Ponzi scammers and opponents of hESC research like George Daley, Alysson Muotri, Marius Wernig; >$300 millions of misappropriation of the taxpayer money of a “Blue” state to iPSC Ponzi scheme or scam have largely benefited those iPSC professors or the opponents of hESC research financially and professionally, and financially fueled and professionally catapulted those opponents of hESC research to their high-ranking and well-paid positions in prestigious universities, despite all those iPSC professors have failed to get any of their iPSC products through any safety trial after billions of public funding spent by them; those iPSC professors or opponents of hESC research who used their high-ranking and well-paid positions they obtained through misappropriation of NIH/CIRM funding to their Ponzi schemes to stonewall public funding for hESC research and medical breakthroughs, to prosecute the proponents/advocates of hESC research, especially discriminative to those underserved and underrepresented minority and women like me, to give women and minority like me working in hESC research field a difficult time in job searching, in career advance, in research, in grant application, in publication, in securing patent, in securing lab, in gaining equitable access and recognition, in advocating hESC research for patients as I have personally experienced over the last decade; CIRM has given not even a penny of CA taxpayer money to breakthrough hESC research that would benefit millions of people in CA, bring billions of health care benefits to CA, help gain voter and CA State support for bond financing and funding, and help gain voter support for future Proposition; without doubt, such demonstrable COI by GWG reviewers as defined by CIRM GWG COI policy had a negative impact on the review process and resulted in a flawed review of this application”.

Ironically, CIRM President/CEO and General Counsel even demonstrated COI themselves after they had completely denied any COI for our appeal in front of ICOC by having ICOC approving funding for Ryne Bio’s CLIN1-14300, titled “Allogeneic iPSC derived Dopaminergic [DA] Drug Product for Parkinson's disease [PD]”, which has severely compromised the scientific integrity of CIRM. Part of our large primate study data of the hESC therapeutic product of my hESC proposal CIRM DISC2-14071 have been held by my former mentor, Jean Loring of Scripps Research Institute, the founder of Aspen Neurosciences. Both Aspen Neurosciences and Ryne Bio have absolutely no patent, no technology, no scientific publication to show they could turn iPSC into DA neurons, and Aspen Neurosciences and Ryne Bio have identical iPSC product with different names. I personally prepared those cells, hESC product of DISC2-14071, for the monkey study, not iPSC product of Jean Loring/Aspen Neuroscinece/Ryne Bio, and Jean Loring absolutely knows that and she also knows it is scientific misconduct to use animal study data of hESC for iPSC (do you think why she has never really done anything herself for over a decade?). And Jean Loring’s student --- Ryne Bio’s founder --- was never involved in the large primate study, and has committed serious scientific misconduct to use our hESC animal data in his iPSC proposal and CIRM award to scam CA taxpayer money with the intention to continue to lie to FDA, with the complicit of CIRM GWG reviewers and ICOC. It is serious COI for CIRM President/CEO and General Counsel to award Ryne Bio’s iPSC using our hESC animal data they had no part of it while denying any COI and appeal for us who actually did the study and own the patent. It is also systemic racism for CIRM President/CEO and General Counsel to marginalize a woman like me from underserved and underrepresented racial/ethnic communities with flawed review and biased score of 20 to her hESC research proposal with hESC breakthrough innovations supported by USPTO patents while giving the iPSC Ponzi scheme or scam of the founder of Ryne Bio, a white man, score of > 85 and even award not supported by any technology, IP, or patent at all.

CIRM President/CEO knows that iPSC are cancer cells and harmful to patients, but has still knowingly misled and deliberately defrauded CA taxpayers by awarding $46 millions to its COMPASS program, also known as shared iPSC labs, to train the next generation of adult stem cell Ponzi scammers in higher education. Almost all the PIs on CIRM COMPASS programs are known iPSC Ponzi scammers, including Alysson Muotri of UCSD, Brian Cummings of UCI, and Lily Chen of San Francisco State University. None of the CIRM COMPASS education training awards has the personnel and expertise of stem cell research and regenerative medicine to provide stem cell course/training and mentorship for students or trainees. In contrast, CIRM President/CEO has not even given a penny of CA taxpayer money for shared hESC labs to train the next generation of stem cell researchers.

CIRM President/CEO’s discriminative and unfair treatment behind closed doors to women and minority PI like me is in stunning contrast to her service for her close ties in public, such as she has frequently gone to ICOC to request 9 or 10 clinical trial awards, ~$10 – 20 M each, exclusively for Stanford University and her close ties with >$150 millions of CA taxpayer money, such as she has even defied CIRM program announcements not to select highly promising hESC research proposals that have patents, are original, competitive, novel, could immediately progress to translational stage for CIRM TRAN and CLIN programs, but only select her close ties for CIRM awards that are not original, not competitive, lack novelty, and even fraudulent like Oct-4 project, like >$100 M to iPSC Ponzi scheme or scam projects in Stanford University. As a result, almost no CIRM DISC2 could progress to CIRM TRAN and CLIN. As a result, none of those multi-million dollar awards that CIRM President/CEO has presented to ICOC for funding have generated anything beneficial or benefited any Californian or any patient, except that her service has largely enriched her close ties financially and professionally. For example, the $40 millions of CA taxpayer money that CIRM President/CEO promoted and had CIRM give to her mentor’s Company Stem Cell has produced absolutely nothing over a decade later. As a result, under her leadership, after 4 or 5 billions of CA taxpayer money later, California still has no clinical-grade hESC lines and banks, no world-class hESC training courses and training centers, no cutting-edge stem cell centers, no highly promising hESC product in clinical trials, no promising treatment or cure for any disorders that destroy lives, though technology has become available. Her performance as CIRM President/CEO has compromised the integrity of CIRM Organized Pursuant to The CALIFORNIA STEM CELL RESEARCH AND CURES ACT. Her performance as CIRM President/CEO has raised a major question regarding the credibility of CIRM Organized Pursuant to The CALIFORNIA STEM CELL RESEARCH AND CURES ACT. Her performance as CIRM President/CEO has completely shaken the public’s confidence in her ability to lead CIRM Organized Pursuant to The CALIFORNIA STEM CELL RESEARCH AND CURES ACT.