Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

Codycrusher
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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

Post by Codycrusher »

So Tim, if I may, I have a question and first off, a statement, some investors are thinking on the line.
$TSOI
Jadi Cell for CTE IND! it was accomplished.

Revised catalyst list:
Initiation of Jadi Cell for CTE trial
Initiation of Phase III Jadi Cell for Covid patients trial
StemVacs IND
Quadramune trial results.

I think StemVacs will happen in April but the two Jadi Cell ones could happen this month.

So my question is this, let's say for pure guessing and speculation because this has not happened yet, let's say you got Stemcell IND, would that mean immunotherapy would become an official thing in the Nation and world? Would that make this company the company to have come up and developed the top most BEST treatment for cancer patients everywhere?
2nd question, Do you believe that it is possible to get this stemcell officially finished and approved, on it's way to becoming NATIONWIDE by the end of the year? what is your thoughts because I am looking at the long term potential of this company and share price. I would like to understand and know these timelines a bit better on what you think you could accomplish and what would come out of it if you, said accomplished these said goals, for the future of this company and the nation.
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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

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Dave Lyons describes the benefits he's received from Mesenchymal Stem Cell Therapy

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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

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Clinical Applications of Wharton's Jelly-Derived Mesenchymal Stem Cells

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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

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Adipose Derived MSC Spinal Graft For Post Surgical Low Back Pain

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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

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Q&A with Dr. Duncan Stewart on Biotherapeutics & COVID vaccine manufacturing.

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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

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Joe's experience with Stem Cells at DBC - Pandemic procedures and MSC treatments


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TimGDixon
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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

Post by TimGDixon »

Let me see if i can help you all make better sense of the future here.

CTE IND# 27377 has been issued which now allows us to engage with FDA to work towards approval to proceed. How long this will take i can't say but we are hoping for some accelerated review if possible since we also own rights to the DMF (drug master file) and all that is in that file is applicable to our IND. It is called Right of Reference and its a legal term within FDA framework that says any and all data ever submitted to FDA involving these cells must be applied to our applications for investigation (good or bad). I think when he have our first conf-call with FDA i'll have a better handle on timing and i will let you guys know.

So IND# 27377 is Phase 2 and a successful outcome will allow us to apply for Phase 3 so we still have some ways to go on CTE.

I have no updates on when Phase III Jadi Cell for Covid patients - just know it is in the works.

StemVacs often gets confused with Stem Cells and they are not the same at all. We currently have an IND for Phase 1 in the USA before FDA but sometime back we decided we would repurpose that IND from autologous StemVacs(v1) to allogeneic StemVacs(v2). You have seen multiple press releases about things related to StemVacs involving cell lines and animal models - these are being done to satisfy FDA on additional studies they want to see performed. I think we have enough data for that aspect, however, I want to double down on human data before we file to repurpose. What do i mean by that?

US Law allows biotech company's like TSOI to conduct clinical trials outside the USA without an IND. This is known as a 312.120 "Foreign clinical studies not conducted under an IND." As long as we compile all data, regulatory approvals, and associated reports to document the clinical trial performed on StemVacs in a manner that is compliant with USA FDA Definition of an acceptable Ex-USA Trial as stated in 21 CRF 312.210 they will accept the results as though we did the same thing here under an approved IND. This is about cost savings. 10 patients in the USA phase 1 would likely cost the company $2-2.5 million. I can pull this off in Mexico for probably $300k - at least thats my current budget i need to build.

So once we have this data we will supplement the existing IND with more human data and ask for repurposing. Now you begin to understand why we did a bunch of animal studies using the StemVacs2 product seemingly out of nowhere - its all being done to buttress work we've already done and satisfy the FDA.

Just so you know, i'm not doing any of this with a single doubt in my mind of future success. In Nov 2015 we treated 10 people with StemVacs1 who had life expectancy of 6mos or less (ECOG <6) and in Nov 2018 they were *all* still alive. I do not know what happened after 2018 because the clinic stops collecting data after year 3 - i am hopeful many of them are still alive even though we will likely never know.

As to QM trial - its going slow you guys - we have enrollees and we have completed cases but its getting more difficult because of vaccines being provided to those front line workers - but nevertheless Mrs Tim (you guys don't know bout Mrs Tim, she's the real brains behind this operation) and Serena continue to enroll people and attempt to contact new potential enrollees.

We have a busy year you guys and remember i have work to do in Idaho this summer and i'll tell you more about that in the future.

Tim

Codycrusher wrote: Fri Mar 05, 2021 5:49 pm So Tim, if I may, I have a question and first off, a statement, some investors are thinking on the line.
$TSOI
Jadi Cell for CTE IND! it was accomplished.

Revised catalyst list:
Initiation of Jadi Cell for CTE trial
Initiation of Phase III Jadi Cell for Covid patients trial
StemVacs IND
Quadramune trial results.

I think StemVacs will happen in April but the two Jadi Cell ones could happen this month.

So my question is this, let's say for pure guessing and speculation because this has not happened yet, let's say you got Stemcell IND, would that mean immunotherapy would become an official thing in the Nation and world? Would that make this company the company to have come up and developed the top most BEST treatment for cancer patients everywhere?
2nd question, Do you believe that it is possible to get this stemcell officially finished and approved, on it's way to becoming NATIONWIDE by the end of the year? what is your thoughts because I am looking at the long term potential of this company and share price. I would like to understand and know these timelines a bit better on what you think you could accomplish and what would come out of it if you, said accomplished these said goals, for the future of this company and the nation.
``
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TimGDixon
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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

Post by TimGDixon »

A little more background on our general plan of investigation. Chronic Traumatic Encephalopathy (CTE) for purposes of our proposed clinical trial will be defined as a major reduction in brain weight, with brains weighing up to 30% less than control brains when “age-matched” by volumetric imaging.

Severe atrophy of the frontal, medial temporal lobes, as well as anterior thalami will be observed, along with atrophy of the white matter tracts. Inclusion into the study will be limited to patients also possessing advanced language deficits, psychotic symptoms which include paranoia, motor deficits, and parkinsonism.

Bobby Duckworth is our dear friend and a significant motivator for me personally - I want you to see what CTE does to a guy who at one time was unstoppable on the field of play - listen to my friend in his own words.



Mesenchymal Stem Cells (MSCs) are potent immunomodulatory cells that recognize sites of injury, limit effector T cell reactions, and stimulate regulatory cell populations (i.e., T-regs) via growth factors, cytokines, and other mediators. Simultaneously, MSCs also stimulate local tissue regeneration via paracrine effects inducing angiogenic, anti-fibrotic and remodeling responses[3]. Consequently, MSCs-based therapy represent a viable treatment option for autoimmune conditions and other inflammatory disorders [4-9], yielding beneficial effects in models of autoimmune Type 1 Diabetes [10-16], Systemic Lupus Erythematosus, Autoimmune Encephalomyelitis [17], Multiple Sclerosis [18, 19], cardiac insufficiency [20, 21], and organ transplantation [22].

JadiCells, which are a type of umbilical cord MSC demonstrated to maintain its expansion capacity over 90 population doublings without cell senescence, while maintaining MSC characteristics and functions [23]. UC-MSC have demonstrated safety and efficacy in clinical trials, and have been safely administered across histocompatibility barriers. UC-MSCs have been recently introduced intravenously in patients with Alzheimer`s Disease [24], and have been approved for testing in patients with Type 1 Diabetes.

In the proposed study we seek to utilize the same dose of JadiCells which were safely administered to 12 advanced COVID-19 patients safely with evidence of efficacy. Specifically, we seek to administer 100 million JadiCells intravenously and assess baseline and 1, 3, and 6 months markers of safety and efficacy.



References
1. Iacono, D., et al., Early-Onset Dementia in War Veterans: Brain Polypathology and Clinicopathologic Complexity. J Neuropathol Exp Neurol, 2020. 79(2): p. 144-162.
2. Li, Y., et al., Low-Level Primary Blast Induces Neuroinflammation and Neurodegeneration in Rats. Mil Med, 2019. 184(Suppl 1): p. 265-272.
3. Caplan, A.I. and D. Correa, The MSC: an injury drugstore. Cell Stem Cell, 2011. 9(1): p. 11-5.
4. Ge, W., et al., Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression. Transplantation, 2010. 90(12): p. 1312-20.
5. Bartholomew, A., et al., Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Experimental hematology, 2002. 30(1): p. 42-8.
6. Casiraghi, F., et al., Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. Journal of immunology, 2008. 181(6): p. 3933-46.
7. Ge, W., et al., Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2009. 9(8): p. 1760-72.
8. Uccelli, A., A. Laroni, and M.S. Freedman, Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet neurology, 2011. 10(7): p. 649-56.
9. Ge, W., et al., Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance. Am J Transplant, 2009. 9(8): p. 1760-72.
10. Perez-Simon, J.A., et al., Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica, 2011. 96(7): p. 1072-6.
11. Garcia-Olmo, D., et al., A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum, 2005. 48(7): p. 1416-23.
12. Sun, L., et al., Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells, 2009. 27(6): p. 1421-32.
13. Dhere, T., et al., The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn's disease - a phase 1 trial with three doses. Aliment Pharmacol Ther, 2016. 44(5): p. 471-81.
14. Carlsson, P.O., et al., Preserved beta-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes, 2015. 64(2): p. 587-92.
15. Cai, J., et al., Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion. Diabetes Care, 2016. 39(1): p. 149-57.
16. Hu, J., et al., Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocr J, 2013. 60(3): p. 347-57.
17. Morando, S., et al., The therapeutic effect of mesenchymal stem cell transplantation in experimental autoimmune encephalomyelitis is mediated by peripheral and central mechanisms. Stem cell research & therapy, 2012. 3(1): p. 3.
18. Hedayatpour, A., et al., Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone model of multiple sclerosis. Cell journal, 2013. 15(2): p. 142-51.
19. Al Jumah, M.A. and M.H. Abumaree, The immunomodulatory and neuroprotective effects of mesenchymal stem cells (MSCs) in experimental autoimmune encephalomyelitis (EAE): a model of multiple sclerosis (MS). Int J Mol Sci, 2012. 13(7): p. 9298-331.
20. Bartolucci, J., et al., Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). Circ Res, 2017. 121(10): p. 1192-1204.
21. Tuma, J., et al., RESCUE-HF Trial: Retrograde Delivery of Allogeneic Umbilical Cord Lining Subepithelial Cells in Patients With Heart Failure. Cell Transplant, 2016. 25(9): p. 1713-1721.
22. Franquesa, M., et al., Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Fourth Meeting: lessons learned from first clinical trials. Transplantation, 2013. 96(3): p. 234-8.
23. Patel AN, V.V., Raveloo P, Bull DA, Mesenchymal Stem Cell Population Isoalted From the Subepithelial Layer of Umbilical Cord Tissue. Cell Transplantation, 2013: p. 513-519.
24. Baumel, B. A Phase I, Prospective, Open-label Trial to Evaluate the Safety, Tolerability and Exploratory Outcomes of Multiple Allogeneic Human Mesenchymal Stem Cells (HMSC) Infusions in Patients With Mild to Moderate Alzheimer's Disease. [cited 2020 March 9].
retsehc
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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

Post by retsehc »

Thanks, Tim, for the clarity regarding Jadi Cell, StemVacs and Quadramune. Great post! Have you all ever considered posting one of those pretty graphical pipelines just to give people a quick sense of all you just described? Helps people to easily keep up with the process.
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TimGDixon
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Re: Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Chronic Traumatic Encephalopathy

Post by TimGDixon »

Yeah we could probably create something like that. I'll see what i can come up with.
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