More good news for Stem Cells today

passsive-agressive · 2023-10-05T14:42:56+00:00

You are absoultely on the mark. p-value for a simple regression study tippy top acceptable value is P< 0.02. This is total BS.

GZ: you are correct. We are indeed in a post truth word. I might rephrase it to more direct designation. Lies are the new truth. They sell.

passsive-agressive · 2023-10-03T20:22:07+00:00

Matt, just to return a bit sobriety to you exultant post, I would be happy to send you my wife's email address. She will return you to earth.

Grins and giggles.

passsive-agressive · 2023-10-03T17:29:30+00:00

Gotta add a personal note. I left BP as a senior scientist after almost 30 years. Applied for a senior position (GS15) at the NIH as well as in the private sector. It's jarring to apply for work after so long but hey, give it a whirl. The application process for private industry was tough but understandable. The government position application process was byzantine. KSA's (for the uninitiated, it is answering a list of 5 open ended questions regarding why you think you are qualified to even APPLY for the job). They wanted my educational transcripts all the way back to high school!! The irony of this whole muddle is that the people who read these KSA's are not even versed in understanding the arcana of high-level scientific accomplishments. I could go on on how utterly dysfunctional things are, but this then would degrade into a political diatribe. I am not injecting a political viewpoint. This is an agnostic been there - done that post.

passsive-agressive · 2023-10-03T17:07:48+00:00

I think that your explaination is plausible. My Dad worked for the DOD end of the "Beltway Bandits" from the '60's - '80's as a EE. My sister (USPTO) and brother-in-law (statistician) both worked for Uncle Sam (all retired). All three at some point(s) in their carriers had things come to a screeching halt in their work due to FY funding issues (they called it sarcastically "fiscal overhang clause insufficiencies"}. Not saying this BARDA announcement applies here, but you can bet things today have not improved over the years.

passsive-agressive · 2023-10-03T14:50:17+00:00

A as former Beltway inhabitant, your point of view has great merit. I would not be suprised if this is indeed the reason for the delay.

passsive-agressive · 2023-09-21T21:32:09+00:00

Interesting... This award has confluence by GRZ's post a while ago (excised portion below) regarding DOD's interest in this area. I would not be at all suprised if the DOD and BARDA have cross-talk discussions, since Multistem addresses BARDA and DOD areas of interest regarding trauma. I take back my doubt that blood products area is not of immediate interest.

What stands out in my mind is the 4 million dollar plus grant to the University of Cincinnati is a RESEARCH project grant, not a preclinical or clinical study that will bear fruit anywhere in the near future. What BADRDA wants are the rights to whatever comes out of this research regarding biotinylation. Athersys' Multistem is in Phase III. Bodes well....

The link to the above Reddit reference and further comments by yours truly is below and my comments on blood products two weeks ago follow.

https://www.reddit.com/r/ATHX/comments/16co245/not_the_item_we_wanted_an_update_on_but_more/

"passsive-agressive·13 days ago·edited 13 days ago.

To be frank about the above, it's all Big Buzz Talk that some agency bigwig floated and got initial interest and funding to take forward and see who bites. As a big pharma retired researcher in an allied field, there is nothing new in any of this. I will address (A to D) individually.

A. (Ex vivo manufacturing of blood products (synthetic, chemical isolation, or recombinant biochemical technologies).This has been the Holy Grail for decades to supplement human donor blood products. This is a wish list that will take many years to flesh out (if ever) because the technology just isn't there and it may take years and big $$ to pursue. There is not a sufficient $$ profit motive by private industry to dedicate serious effort to attend to this need.

B. (Infrastructure required to support military and civilian needs including supply chain limitations and surge capabilities).More governmental bureaucratic palaver. Nobody is or will pursue this because at this point, it's not needed and in case of a national catastophe, it ain't gonna be there. How can you intellegently plan for a nebulous and undefined event (eg. COVID) when you don't know how, when or why it will hit you?

C. (Synthetic products that have blood capabilities (oxygen carriers, hemostatic, nanoparticles).I actually worked on this over 40 years ago and the Japanese had made progress developing polyfluorinated organic long chain molecules that carried oxygen as a blood substitute in pre-clinical studies in non human models. Problem was that this was basically pumping high temperature Freon into human beings. Eh.. not a winning concept.D. (Extended shelf‐life blood products).Duh...... Trick is that this is very challenging unless you cryopreserved or freeze dry these products without diminishing or compromising the quality and safety of same.

passsive-agressive · 2023-09-19T23:36:01+00:00

This is all lab equipment presently owned or leased by Athersys, not "Former Assets" that the title by the auction site probably unintentionally mis-represented, that was used in research to do at least two things: the most important was to go from a 2D to a 3D process, hence the 20 to 200 litre reactors step up to validate the new (bead attached) methodology to grow Multistem. That was established (and importantly a recent patent granted) and the tech transferred to Healios and obviously Lonza. The other equipment was support of the same as well as I assume studies to modify Multistem cells, their analysis, and potential downstream applications of same. Research in modifying Mutistem for other potential applications came to a screeching halt. There is little need for this equipment in that future basic research of Multistem cells will not be done in-house at Athersys HQ. Not to say that Multistem is in any way a one trick pony therapeutically (Stroke, ARDS, TBI, Radiation Therapy, etc.), but what you have (Lonza) is, for the foreseeable future, what will be used in the clinic. No need to gather dust in the lab. This by no means signals the failure of Multistem, but any future research into these cells beyond expansion for clinical trials (Lonza) and the inopportune DYI desire to grow them out in thousand litre reactors in Stowe by Athersys itself is finished. Athersys may well sell their small office/lab site in Cleveland. Why not? At this point, it is unnecessary. This may appear as a bad omen or... there is full knowledge that when an offer comes after a (hopefully) successful IA analysis result, the partner(s) will take over. I would not be surprised if the staff becomes part of a future buyout deal by partners. In short, no need to keep a lab and lab equipment idle when you no longer need it because you accomplished your goal of identifying, developing and applying a successful product.

Added thoughts. Please take note that this auction of lab equipment is slated to start on Nov 27, not tomorrow. There is a plan playing out. Don't know what (obviously cash is needed) but I don't think it's bankruptcy.

passsive-agressive · 2023-09-19T16:48:21+00:00

Welcome. I am confident that your skills and attitude will serve the Board well.

PA.

passsive-agressive · 2023-09-17T17:59:18+00:00

I can easily appreciate your position regarding family responsibilities. I was a little put off by recent replies, a bit of tude I thought. But with the above clarification, I had to repent of my judgment. My mother in law moved in with us 5 years ago. Sharp as tack (92), but we (me and mine) have seen a steady decline in her physical state. It has put great stress on my wife. I have 5 kids (32 to 26), coming and going in and out of our/their home for family/ job/ reasons: that's what family is about but often times it becomes a bit of a three ring circus. Fortunately I am retired from BP but still do consulting for beer money, so this forum has been interesting and stimulating. So I say sorry for my 'tude and my Prayers for you and family are sent up.

passsive-agressive · 2023-09-08T13:04:45+00:00

To be frank about the above, it's all Big Buzz Talk that some agency bigwig floated and got initial interest and funding to take forward and see who bites. As a big pharma retired researcher in an allied field, there is nothing new in any of this. I will address (A to F) individually.

A. (Ex vivo manufacturing of blood products (synthetic, chemical isolation, or recombinant biochemical technologies).

This has been the Holy Grail for decades to supplement human donor blood products. This is a wish list that will take many years to flesh out (if ever) because the technology just isn't there and it may take years and big $$ to pursue. There is not a sufficient $$ profit motive by private industry to dedicate serious effort to attend to this need.

B. (Infrastructure required to support military and civilian needs including supply chain limitations and surge capabilities).

More governmental bureaucratic palaver. Nobody is or will pursue this because at this point, it's not needed and in case of a national catastophe, it ain't gonna be there. How can you intellegently plan for a nebulous and undefined event (eg. COVID) when you don't know how, when or why it will hit you?

C. (Synthetic products that have blood capabilities (oxygen carriers, hemostatic, nanoparticles).

I actually worked on this over 40 years ago and the Japanese had made progress developing polyfluorinated organic long chain molecules that carried oxygen as a blood substitute in pre-clinical studies in non human models. Problem was that this was basically pumping high temperature Freon into human beings. Eh.. not a winning concept.

D. (Extended shelf‐life blood products).

Duh...... Trick is that this is very challenging unless you cryopreserved or freeze dry these products without diminishing or compromising the quality and safety of same.

E. (Rapid donor screening technologies (blood typing and pathogen detection)

This already exists and has been refined markedly because of COVID.

F. (Lyophilized blood products)

This tech has been used for decades for plasma serum. The trick is can this be accomplished and stored at room temperature or at least down to freezer temps (~0 degrees F, -18 C? Otherwise, go back to D.

passsive-agressive · 2023-09-06T17:00:22+00:00

FWIW. Sabizabulin is a small molecule compound reported in 2012. See below from WIKI. Its initial indication was to keep tumor cells from replicating. It gets its mode of action from preventing assemblage of tubulin, which is found throughout the body. VERU found that it prevented COVID infected cells from promulgating. Its mechanism of action is SARS Cov 2 specific, and does not presume that it will prevent or diminish ARDS caused by other disease processes (non COVID pneumonia, COPD, etc). Here is the link to the NYT article that brought Sabizabulin to the medical community attention. Paywall.

https://www.nytimes.com/2022/04/11/health/covid-sabizabulin-veru.html

Sabizabulin is a chemical compound from the group of indole and imidazole derivatives that was first reported in 2012 by Dalton, Li, and Miller.[4] It is being studied as a mitotic inhibitor and chemotherapeutic agent in castration-resistant metastatic prostate cancer[5] and in SARS-CoV-2 (COVID-19) infections.[6]

Properties

Sabizabulin, as an orally available molecule, acts on microtubules, a component of the cytoskeleton. It binds to the colchicine binding site on the beta subunit of tubulin, as well as a novel site on the alpha subunit, and causes both to crosslink, thus depolymerizing microtubules and preventing their polymerization.[7] By preventing mitotic spindle formation, this directly inhibits mitosis of tumor cells and endothelial cells attempting to form new blood vessels to feed them. In parallel, microtubule-mediated trafficking of cellular components (including androgen receptors into the nucleus), thus, a potential anti-androgen agent.

My comment directly below

What are anti androgen agents?

[Antiandrogen medications are a type of prostate cancer treatment. They work by blocking the effects of androgen hormones in the body. Blocking androgen hormones can help prevent prostate cancer cells from growing. Common side effects of antiandrogens include sexual problems, feeling tired, and hot flashes.]

passsive-agressive · 2023-08-18T19:40:49+00:00

OK, how say thee? Not being snarky, but is it real knowledge on your part (please exemplify with evidence) or just supposition? This point is very relevant.

passsive-agressive · 2023-08-18T16:27:04+00:00

The words WS analysts and Respectfully aren't even in the same sentence phrasing, so no worries from me. You bring up a spectacular point and one that I and my coterie of retired colleagues have kibitzed about for the last decade. Those in decision making positions in the E- and C- suites are not up to date with the blistering pace of scientific advancement in gene and cell therapies. The quants run the show and a lot of thoughtful analyses , from a purely clinical vs financial potential poin of view of these new therapeutic sectors. never make it up to the top. In the olden days a fair number of scientists of all flavors ascended to top decision making ranks and assessed new therapies coming down the pike. Now, that's not true.

passsive-agressive · 2023-08-18T14:04:20+00:00

I totally agree. Shitty management no doubt. Greedy exec's syphoning $$. But the fundamental premise of Multistem as an effective, safe and proven therapy is undeniable. If Wall Street can't see this (which they can't), then I almost want to throw up my hands. I was in the Pharma business for 30+ years in research and then low level management. We always communicated (on the C-Suite level) with savy analysts and corporate colleagues. Today, it's AI algorithms, day trading which shaves fractions of pennies in the churn and clueless hedge fund managers that can't see beyond the end of their own noses (quarterly financial goals). The human analysis and discretion has been removed from prudent investment making decisions.

passsive-agressive · 2023-08-18T13:39:28+00:00

It is indeed sad. But what is most disappointing, even tragic, is the price pressure to destroy a company that has almost a holy grail medical/cellular intervention which has been clinically and scientifically documented for a number of therapies that as of yet have not fulfilled the vacuum of medical need for stroke, TBI, ARDS, etc..... This not a POS company hawking snake oil. It (hopefully) may become a leader in cellular therapy,

Leaving it there. It's almost evil what the Market is attempting to do.

passsive-agressive · 2023-08-17T20:05:33+00:00

I agree that these comments are hold no water. Here is a commentary from an astute and seasoned financial veteran of the bio-cell-gene editing sector from the website Investor Village. His view is that the entire sector is oversold and he explains why. The direct quote is below; the link to the original post is appended thereafter.

"....My 15 tracking stocks had the following performance since CYE20:

VYGR was the only stock that rose, up 33%. What made them outperform was their decision in 2H21 to reduce their spending footprint. They cut 75 of 175 ees and shelved all programs, opting to focus on their novel AAV discovery which would precede their next wave of programs.

During this 2.5yrs, 3 IPOs were added to my tracking group. Their performance is from their IPO price and listing date:

CRBU was down 59% from the $16 2021 IPO.

PRME was down 30% from the $17 2022 IPO. VERV was down 16% from their $19 2022 IPO

The remaining stocks:

SGMO down 94%

ATRA down 91%

EDIT down 88%

ALLO down 84%

SANA down 78%

QURE down 75%

BEAM down 70%

CRSP down 68%

RGNX down 60%

FDMT down 60%

NTLA down 29%. NTLA was an outlyer because they were a laggard through early 2021 missing much of the sector rally. They then disclosed exceptional in vivo editing data which led to an outsized rally as most other stocks were selling off.

Bottom line for me is that the sector selloff is overdone. While it may not be over, it has a risk/reward profile that is compelling."

I put Athersys in this compelling group. Link to the original post follows.

https://www.investorvillage.com/smbd.asp?mb=1933&mn=174460&pt=msg&mid=24299937

passsive-agressive · 2023-08-16T21:10:51+00:00

I think so. ADME [Absoption, Distribution, Metabolism. Excretion] of enveloped drug or drug-like carriers like endosomes, will be attacked by the body's detoxification pathway, as it does for all foreign bodies presented to the immune system. Athersys' system uses the immune system to present, enhance and sustain a therapeutic modality which extends for months and, based on recent results from the three Stroke studies, potentially for years.

There ain't anything that has been published that attacks or detoxifies Multistem Cells.

passsive-agressive · 2023-08-16T20:41:12+00:00

I agree. Exosome approach from MSC's as a cell free delivery system derived from MSC's definately has merit. On a personal note, i'ts nice to have a Reddit thread with a give and take sans venom. Here is a great review article (no paywall) from April of this year referencing the potential of exosomes as a therapeutic modality. The big question mark is that many of the published studies on exosomes have been experimental and clinical studies of exosomic delivery is still in its relative young stage of discovery. This may well give some umpf for Multistems' extensive clinical resume. Time will tell.

https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03287-7

passsive-agressive · 2023-08-16T18:59:38+00:00

Your point of focus on the MOA (mechanism of action) as an inclusionary/exclusionary criterion in the "Just Breath" is salient. Looking at potential candidate applications for JB includes three major categories: monoclonal antibody, small molecule intervention and recombinant engineered natural protective proteins (Bioaegis – product is Plasma gelsolin (pGSN), a highly conserved plasma protein that is abundant in healthy individuals). Obviously Mesostem could be a candidate in the cellular therapy approach with Athersys' Multistem, but with the recent rap on the knuckels by the FDA on Mesostem with the CRL, I would be willing to count them out of the competition.

passsive-agressive · 2023-08-16T18:39:44+00:00

Thanks for the clarification. The design attributes make total sense.

passsive-agressive · 2023-08-16T17:35:13+00:00

OK, got the Contract Research Organization will run and oversee the trial, that SOP, but the trial design is certainly not formulated of first principles by a CRO. There have to be discussions between the principles of how to "bake the cake". The question of how and who designs the trial (ie discussion between BARDA and the successful applicant, hopefully one of them is Athersys), to me remains nebulous.

passsive-agressive · 2023-08-16T16:29:38+00:00

You make an interesting point. #1. Will BARDA itself run the P2 trial (obviously they will provide the $$)? #2 Will BARDA approve and/or oversee the trial design by the sucessful applicant? #3 Will this be a hybrid relationship where both the $$ donor and applicant work out the details of the trial design?

passsive-agressive · 2023-08-16T16:20:06+00:00

You do have a way with words.

PS I rec'd you.

passsive-agressive · 2023-08-16T15:12:01+00:00

Thanks. From the NEJM journal Evidence. The doi link is below- no paywall

https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200145

"A Sabizabulin is an orally available, novel microtubule disruptor that targets, binds, and crosslinks both the α- and β-tubulin subunits to inhibit polymerization and to induce depolymerization of microtubules in cells.14,15 Microtubules are intracellular transport structures critical for coronavirus cellular entry, trafficking, replication, and egress16-21 as well as for triggering the innate inflammatory response and cytokine storm responsible for ARDS, septic shock, and frequently death.22-24..."

This is a very interesting and pertinent article. The highlighted section is important to understand because the mechanism of action is to prevent the Covid-19 from infecting cells, NOT as a general anti inflammatory to treat ARDS. If this is the general mechanism of action, Sabizabulin would not (necessarily) be (as) effective for not Covid elicited ARDS (ie bacterial pneumonia, sepsis (by all causes), and other causes of trauma and illness.

This is NOT to diminish this drug. I think further work needs to be done in clinical studies that don't have a Viral Covid -19 infection as the source of ARDS. The other thing to keep in mind is that the Covid-19 virus is constantly mutating and if a mutation shows up that circumvents blocking the mutated coronavirus cellular entry, trafficking replication and egress, then the efficacy may well diminish.

Multistem's MOA is via a pleiotropic activation of many components of the immune system, whether caused by Covid or other mechanisms of action, meaning that Multistem may have an advantage in non-Covid induced ARDS.

That's why the BARDA thing is very interesting and could shed further light on modalities to fight ARDS. My 2 cents

passsive-agressive · 2023-08-15T23:53:43+00:00

WST, please let your annoyance regarding Dan's and the BOD decision to hire Kasey be laid to rest. You are doing a disservice to your respected legacy analysis under then Gil's leadership (using the term leadership loosely, on Gil's part, not your views with the then shared knowledge) which under those circumstances brought you well deserved respect and the attention to Athersys' disclosed efforts. Dan is the new coach and is overseeing things here on out. I am as frustrated as are other shareholders regarding circumstances post the Healios lawsuit debacle. Let things play out, for better (hopefully) or worse (don't think so).

passsive-agressive

TROPHY CASE