Angiogenesis inhibitor Puns

I just saw a presentation by Dr. Judah Folkman (Harvard Medical School) from 2004 on angiogenesis inhibitors (Ex: interferon alpha, thalidomide), and they practically sounded like a miracle cure -- no sickness and high success rate.

Why aren't they more widely used? Are there some limitations to their use?

Once there, scroll to p. 52 to begin.

I hope nobody suppressed the invention in order to line their pocketbooks from the sale of less-effective longer-term treatments.

I hope to know how far we are now on angiogenesis inhibition, 18 years later.

My question arises from the transcript of this program: http://www.pbs.org/wgbh/nova/transcripts/2805cancer.html

About 2/3 of the way through, there's discussion of how primary cancerous tumors release an angiogenesis inhibitor to control blood vessel growth in the metastases. I'm a little shaky on the benefit of this to the primary tumor, though, and google yields no helpful results so far. Can anyone satisfy my curiosity?

Thanks, everyone!

25:05 Nader: For the next task of 2022, Cancer Basket Trial. 22 indications. We have lots of patients who talk to Dr. Kelly. Dr. Kelly is involved with a lot of patients who want to get on Leronlimab. Dr. Kelly, tell us a little bit about why we are excited about the Basket Trials.

25: 25 Kelly: We are excited about the Basket Trials. I'll start by saying I just presented at San Antonio Conference December 10th. That was in results wrt mTNBC in combination with carboplatin, CCR5 positive, mTNBC and I tell you, the reason why we are excited about the Basket Trial is that they think that there is a growing acceptance that the Tumor Micro Environment is the next Frontier for Immunotherapy. And I mean this amongst practicing physicians, the academic world, probably as well as big pharma, and I think we are more advanced than this. We've been looking at the mechanism of action in the tumor micro environment and see Leronlimabs impact across multiple different oncologic indications and we also think that we can pair this with a check point inhibitor, chemo, radiation, antibody zero conjugates, as well as maybe even a potential monotherapy in certain patients that don't qualify for other treatments. We think the MOA, with T-Regs. When T-Regs come in, they turn off the immune system. We know that they have a high prevalence of CCR5. We can block that. We can actually maybe leverage the immune system. If we look at macrophage re-polarization, that's another potential opportunity. Our animal studies showed a significant reduction in angiogenesis. I think it was 62% in total vessillary and 80% reduction in small vessel area. But, we know that tumors need a blood supply to grow and if we can help limit that, then we think we can have benefit for patients. And last, we know that normal cells, CCR5 is only present on an immune cell, but we know that when cells under go malignant transformation, that they start sprouting up CCR5, and we believe that is a contributor to metastasis. So we have multiple different mechanisms of action and we continue to find more as we go along that we will be evaluating.

27:15 Nader: Yeah, and BTD that we will be filing, Dr. Nitya Ray did a fantastic job on that. There were some patients with brain metastases. Dr. Ray, explain to us, for a breakthrough designation strategy, are we going to file for brain metastases and perhaps later on, if we do get BTD on the original submissions, maybe we want to ask for Basket Tria

Hello everyone, this is the first issue of my new newsletter, The Biotech Report!

In this issue of The Biotech Report, we will thoroughly examine Akebia Therapeutics: its partnerships, CEO, insider trading patterns, institutional holdings, and financials. Then, we will take a close look at its marketed product in the U.S. - Auryxia. The main focus of this report is the upcoming catalyst for Akebia, the March 22nd 2022 PDUFA action date for vadadustat. We will take a deep-dive to better understand the condition vadadustat targets, the current standard of care, and the patient population. We will then examine how vadadustat works and how it compares to other drugs in the same class. This will allow us to get a better understanding of the landscape and what can happen on March 22nd.

Founded in 2007, Akebia Therapeutics ($AKBA) is a Cambridge-based “fully integrated” biopharmaceutical company with a focus on treating complications of kidney disease. Akebia Therapeutics currently has a market cap of $472.392M.

Akebia Therapeutics merged in 2018 with Keryx Pharmaceuticals, another biotech focusing on kidney disease complications. The merger was a smart move because Keryx Pharmaceuticals already had a marketed product, Auryxia (ferric citrate). Auryxia is indicated for the control of serum phosphorus levels in adult patients with Chronic Kidney Disease (CKD) on dialysis, and the treatment of iron deficiency anemia in adult patients with CKD not on dialysis.

The merger gives Akebia Therapeutics access to Keryx Pharmaceuticals’ commercial capabilities and expertise in the kidney disease complications space, which will be a significant advantage if the company’s New Drug Application (NDA) for vadadustat is approved.

Vadadustat is an investigational oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that is awaiting FDA approval for the treatment of anemia due to CKD in dialysis dependent and non-dialysis dependent adult patients. If approved by the FDA, vadadustat would be a first-in-class drug in the U.S..

Vadadustat is already approved in Japan and is being commercialized by Akebia’s partner Mitsubishi Tanabe Pharma Corporation (MTPC).

The filing for the vadadustat NDA was accepted in June 2021, and the FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of March 29, 2022.

Partnerships

Mitsubishi Tanabe Pharma Corporation (MTPC) is not the only company that Akebia has entered a partnership with.

In 2016, Akebi

As far as HHC research goes, it’s nearly non-existent. However, both natural and synthetic cannabinoids have been found to suppress tumor growth in numerous different animal studies. One study in particular examined the angiogenic effects of several hexahydrocannabinol analogs to see how they can be used in cancer therapies.

As per the study: “Two analogs LYR-7 [(9S)-3,6,6,9-tetramethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-1-ol] and LYR-8 [(1-((9S)-1-hydroxy-6,6,9-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-2-yl)ethanone)] were selected based on their anti-angiogenic activity and lack of binding affinity for cannabinoid receptors. Both LYR-7 and LYR-8 inhibited VEGF-induced proliferation, migration, and capillary-like tube formation of HUVECs in a concentration-dependent manner.”

“The inhibitory effect of the compounds on cell proliferation was more selective in endothelial cells than in breast cancer cells (MCF-7 and tamoxifen-resistant MCF-7). We also noted effective inhibition of VEGF-induced new blood vessel formation by the compounds in the in vivo chick chorioallantoic membrane (CAM) assay. Furthermore, both LYR analogs potently inhibited VEGF production and NF-κB transcriptional activity in cancer cells.”

“Additionally, LYR-7 or LYR-8 strongly inhibited breast cancer cell-induced angiogenesis and tumor growth. Together, these results suggest that novel synthetic hexahydrocannabinol analogs, LYR-7 and LYR-8, inhibit tumor growth by targeting VEGF-mediated angiogenesis signaling in endothelial cells and suppressing VEGF production and cancer cell growth.”

Simply put, these compounds block the growth of the blood vessels that feed tumors, rather than blocking growth of the tumor itself. So, it basically works as an angiogenesis inhibitor that starves any tumors.

“Abstract

We have previously proposed that catabolic fibroblasts generate mitochondrial fuels (such as ketone bodies) to promote the anabolic growth of human cancer cells and their metastasic dissemination. We have termed this new paradigm “two-compartment tumor metabolism.” Here, we further tested this hypothesis by using a genetic approach. For this purpose, we generated hTERT-immortalized fibroblasts overexpressing the rate-limiting enzymes that promote ketone body production, namely BDH1 and HMGCS2. Similarly, we generated MDA-MB-231 human breast cancer cells overexpressing the key enzyme(s) that allow ketone body re-utilization, OXCT1/2 and ACAT1/2. Interestingly, our results directly show that ketogenic fibroblasts are catabolic and undergo autophagy, with a loss of caveolin-1 (Cav-1) protein expression. Moreover, ketogenic fibroblasts increase the mitochondrial mass and growth of adjacent breast cancer cells. However, most importantly, ketogenic fibroblasts also effectively promote tumor growth, without a significant increase in tumor angiogenesis. Finally, MDA-MB-231 cells overexpressing the enzyme(s) required for ketone re-utilization show dramatic increases in tumor growth and metastatic capacity. Our data provide the necessary genetic evidence that ketone body production and re-utilization drive tumor progression and metastasis. As such, ketone inhibitors should be designed as novel therapeutics to effectively treat advanced cancer patients, with tumor recurrence and metastatic disease. In summary, ketone bodies behave as onco-metabolites, and we directly show that the enzymes HMGCS2, ACAT1/2 and OXCT1/2 are bona fide metabolic oncogenes.”

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3507492/

I am long on ATNF and there are some key details I’ve uncovered in my due diligence which might not be immediately apparent to a newcomer to this ticker. Company is targeting inflammation pain and fibrosis which are related in fascinating ways at a cellular level it takes a Phd to actually understand. But we can recognize genius and invest in it.

1. Candlepower

Just listening to CEO Jim Woody or cofounder and largest stockholder Sir Marc Feldmann at Oxford it is clear to me from the succinct masterfully detailed responses to questions we have extraordinarily intelligent principals in management. Ultimately your investment is a wager in whose smarter. I don’t think this is a close call comparing ATNF principals to shorts.

But realize the not invented here syndrome almost blocked the most successful class of drugs ever created. Yes it’s true it doesn’t just live at your organization please read what Dr Feldmann wrote years later;

“We believe that having two research leaders with similar interests and overlapping expertise and many talented Research Fellows, support staff, and well-equipped laboratories with long-term funding, was very important in the efficient progress of this research project toward the clinic. We were not aware at the time that our efforts would lead to the first effective use of molecular biological techniques to define an inflammatory therapeutic target and the first use of modern biological therapeutics (mAbs and receptor fusion proteins) for long-term treatment of a large number of patients.

Having defined TNF as a therapeutic target in preclinical experiments, we were very keen to test our novel, but for many a heretical, idea that a single cytokine could drive a multicytokine, multicellular chronic disease. Arising from the work of Anthony Cerami, Bruce Beutler, and Kevin Tracey (13, 14), many companies had produced anti-TNF inhibitors, both mAbs and TNFR fusion proteins, for the treatment of sepsis, but without success when applied in clinical trials. We were fortunately able to interest an ex-colleague, James N. Woody, Chief Scientist at Centocor (Malvern, PA), a company specializing in mAbs, to work with us in RA clinical trials. John Ghrayeb at Centocor had chimerized (made three-fourths human by using molecular biology techniques to graft human Fc and part of Fab onto a mouse Ab) a mouse anti-TNF monoclonal generated by Jan Vilcek (15). This therapeutic, cA2, was later known as infliximab (Remicade, Centocor).”

https://l

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Posted On: 09/29/2021 3:06:53 PM

Posted By: z_smith01

2021-09-29 Emerging Growth Conference Notes

Rough Notes

Slide

Slide

Slide

What do we think about Biz Plan

“Or is it just fake”

Gave $6M back to NIH

Did Mono, to change HIV paradigm

That was our business plan that we went and executed

Biz Plan going forward

Cancer

We generated that result

Some people take 10yrs to generate those results

If we stop right now, minimum 400% better than SOC

People who analyze our data: ~“Don’t see how you don’t get BTD”

Had brain metastisis in 6 pts

Data was good for those pts as well

Unmet medical need + efficacy

Efficacy requires 5 pts in Clinical Trial; we have 10 pts now

Then try PDL inhibitors after getting BTD

Go small, unmet medical need, then go after other things

SK:

BTD—can reduce 2.5-3.5yrs

patient testimony

Pancreatic cancer

1st dose LL 7/27

8/3

8/19

8/26

9/9

Tumors shrunk 4.8 to 3.

…

2.5 to 2.2cm

Pancreas 4.6 to 1.5cm

NP:

Main primary tumor shrunk 25% in two weeks of being on LL

SK:

Thinks this is because of blocking angiogenesis

Slide

SK was one who said we should try LL in COVID

Heavy lifting was done by SH

If we had changed PE, would have had EUA by now

Did we drop the ball, CRO, … doesn’t matter now

Slide

Slide

If had 70pts, would have met PE (if this was PE)

Expect to get to interim this year (CD16)

Slide

Next indication that Biz Plan allowed us to have

NP was against LH

CR said he could enroll it this year

Then NP said, let’s do it

PE was not met, at p=0.05 (only 0.27) across 24 symptoms

SK: Post Viral syndromes

LH 233M COVID infections

20-60M for LHs

Perfect way to pivot into Post Viral Syndrome

Trying to crack the code in this arena

Some pts got out of wheelchairs on LL

Now want to get back on LL

Have protocol to FDA

FDA is giving guidelines

Hope to have protocol resolved in the next couple weeks

Slide

Orders are flowing in

$2-3M in sales without approval

Slide

New Biz Plan was created and executed in record time

Will get update on CD16 tomorrow

This is a world class CRO (not like previous CRO)

Slide

CR said he could enroll NASH trial in this year

Believe best enrollment ever

SK:

Over $21B

I don't want to step on anybody's toes here, but the amount of non-dad jokes here in this subreddit really annoys me. First of all, dad jokes CAN be NSFW, it clearly says so in the sub rules. Secondly, it doesn't automatically make it a dad joke if it's from a conversation between you and your child. Most importantly, the jokes that your CHILDREN tell YOU are not dad jokes. The point of a dad joke is that it's so cheesy only a dad who's trying to be funny would make such a joke. That's it. They are stupid plays on words, lame puns and so on. There has to be a clever pun or wordplay for it to be considered a dad joke.

Again, to all the fellow dads, I apologise if I'm sounding too harsh. But I just needed to get it off my chest.

At least, if I'm interpreting this correctly. It doesn't talk about Emgality, but the paper is on CGRP levels in COVID patients. The conclusion is:

> The lower levels of CGRP should negatively impact the respiratory physiology of COVID-19 patients due to vasoconstriction, improper angiogenesis, less epithelial repair, and faulty immune response. Therefore, restoring CGRP levels in these patients may represent a novel therapeutic approach for COVID-19.

Does this mean that people using CGRP-inhibitors could potentially have worse cases of COVID if they catch it? Please tell me I'm misinterpreting this somehow. I have a migraine right now so I'm having difficulty thinking straight. It's possible that that doesn't follow since maybe our CGRP levels are elevated, and inhibitors we take always restore them to normal rather than making them extra low, but I don't know for sure if that is the case.

Do your worst!

Multiple IPs
https://patents.justia.com/assignee/regen-biopharma-inc

and more to come

IP for which a Notice of Allowance has been granted. A Notice of Allowance is notification by the USPTO to the applicant that the USPTO intends to issue a patent
ANTIGEN SPECIFIC MRNA CELLULAR CANCER VACCINES
Antigen specific cancer vaccines in which immunogenic epitopes are produced intracellularly by administration of modified mRNA encoding said immunogenic epitopes. In one embodiment of the invention, said modified mRNA encodes peptides derived from the protein survivin. By directly inducing gene expression of the antigens to which an immune response is desired, immunogenic peptides are generated intracellularly, thus allowing for a wider repertoire of epitopes to be presented to the adaptive immune system, which augments likelihood of successful induction of immunity.
Application Number: 15/162,370

IP for which Patent Protection has expired due to non payment of fees for which revival is in process:

METHOD OF CANCER TREATMENT USING SIRNA SILENCING
Comprises administering to a subject one or more siRNA constructs capable of inhibiting the expression of an immunosuppressive molecule. The invention also provides siRNA constructs and compositions.
Patent No: 83897086

IP for which a Notice of Allowance was granted but classified as abandoned by the USPTO. Revival in progress.
UNIVERSAL DONOR CHECKPOINT INHIBITOR SILENCED/GENE EDITED CORD BLOOD KILLER CELLS
Compositions of matters, cells, and treatment protocols useful for induction of anticancer responses in a patient suffering from cancer. In one embodiment the invention provides the use of NR2F6 silencing or gene editing in cord blood cells possessing anti-tumor activity in order to induce potentiated killer cells suitable for therapeutic use. In one embodiment said allogeneic cord blood killer cells are administered to initiate a cascade of antitumor immune responses, with initially responses mediated by allogeneic killer cells, and followed by endogenous immune responses.
Application Number: 15/494,358

AND THERE ARE THESE:
Active Patent Applications:

ENHANCED DENDRITIC CELL IMMUNE ACTIVATION BY COMBINED INHIBITION OF NR2F6 WITH CANNIBIDIOL;
Application Number 17035955.

REDUCTION OF POST-SURGERY CANCER METASTASIS BY COMBINATION OF CANNABIDIOL AND NR2F6 INHIBITION.

I'm surprised it hasn't decade.

For context I'm a Refuse Driver (Garbage man) & today I was on food waste. After I'd tipped I was checking the wagon for any defects when I spotted a lone pea balanced on the lifts.

I said "hey look, an escaPEA"

No one near me but it didn't half make me laugh for a good hour or so!

Edit: I can't believe how much this has blown up. Thank you everyone I've had a blast reading through the replies 😂

It really does, I swear!

They’re on standbi

Pilot on me!!

Nothing, he was gladiator.

I am still hesitating in using nicotine as a nootropic, I talk about the negatives and benefits in this post to make a final judgement.

Nicotine and acetylcholine system

Nicotine acts as a nicotinic acetylcholine receptor (nAchr) agonist, meaning it enhances the cholinergic/acetylcholine system. Different nAchr types exists and can act in different ways.

Agonizing nicotine receptors acts on following neurotransmitters in order of magnitude; Increases acetylcholine, dopamine, GABA, serotonin, norepinephrine, endocannabinoids.

Nicotine has lots of cognitive enhancing properties but tolerance and addiction develops fast to it, the question is if a net benefit exist?

NICOTINE AND TOLERANCE

Using Nicotine only once every three days is enough to create tolerance.

Brain returning to complete normal can last years but withdrawal symptoms only last 2-4weeks.

Nicotinic Acetylcholine, dopamine and glutamate/NMDA systems can get down-regulated.

Dopamine and most acetylcholine upregulation is quickly reversible and lasts the above mentioned time of withdrawal, restoring most cognitive functions, but glutamate/NMDA and some cholinergic signaling down-regulation are difficultly reversible potentially reducing synaptic plasticity for a longer period of time.

Short-term tolerance:

“Nicotine withdrawal is associated with deficits in neuro-cognitive function including sustained attention, working memory, and response inhibition.”

-> Some individuals are able show low to no deficits on working memory and sustained attention during withdrawal.

-> Studies are done in smokers, while tobacco smoke also contains MAO inhibitors next to nicotine, decreasing cognition during withdrawal even more compared to only nicotine.

Long-term risks of permanent tolerance, especially problematic if nicotine started during adolescence(10-25):

"Researchers believe that long-term nicotine may cause long-lasting changes in the nervous system by, in part, disabling nicotinic cholinergic signaling."

“In the adult rodent brain, weeks after nicotine levels have subsided, nAChR levels in the PFC return to baseline levels. In contrast, at this stage, mGluR2 levels have reduced significantly below baseline levels, thereby altering mGluR2 signaling during short-term plasticity and hampering attention performance. This reduction in mGluR2 signaling underlies the reduced attention performance observed in animals after nicotine exposure during adolescence.”

“Nicotine exposur

Hello everyone, this is the first issue of The Biotech Report!

In this issue of The Biotech Report, we will thoroughly examine Akebia Therapeutics: its partnerships, CEO, insider trading patterns, institutional holdings, and financials. Then, we will take a close look at its marketed product in the U.S. - Auryxia. The main focus of this report is the upcoming catalyst for Akebia, the March 22nd 2022 PDUFA action date for vadadustat. We will take a deep-dive to better understand the condition vadadustat targets, the current standard of care, and the patient population. We will then examine how vadadustat works and how it compares to other drugs in the same class. This will allow us to get a better understanding of the landscape and what can happen on March 22nd.

Founded in 2007, Akebia Therapeutics ($AKBA) is a Cambridge-based “fully integrated” biopharmaceutical company with a focus on treating complications of kidney disease. Akebia Therapeutics currently has a market cap of $472.392M.

Akebia Therapeutics merged in 2018 with Keryx Pharmaceuticals, another biotech focusing on kidney disease complications. The merger was a smart move because Keryx Pharmaceuticals already had a marketed product, Auryxia (ferric citrate). Auryxia is indicated for the control of serum phosphorus levels in adult patients with Chronic Kidney Disease (CKD) on dialysis, and the treatment of iron deficiency anemia in adult patients with CKD not on dialysis.

The merger gives Akebia Therapeutics access to Keryx Pharmaceuticals’ commercial capabilities and expertise in the kidney disease complications space, which will be a significant advantage if the company’s New Drug Application (NDA) for vadadustat is approved.

Vadadustat is an investigational oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that is awaiting FDA approval for the treatment of anemia due to CKD in dialysis dependent and non-dialysis dependent adult patients. If approved by the FDA, vadadustat would be a first-in-class drug in the U.S..

Vadadustat is already approved in Japan and is being commercialized by Akebia’s partner Mitsubishi Tanabe Pharma Corporation (MTPC).

The filing for the vadadustat NDA was accepted in June 2021, and the FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of March 29, 2022.

Partnerships

Mitsubishi Tanabe Pharma Corporation (MTPC) is not the only company that Akebia has entered a partnership with.

In 2016, Akebia entered a collab

Hello everyone, this is the first issue of The Biotech Report!

In this issue of The Biotech Report, we will thoroughly examine Akebia Therapeutics: its partnerships, CEO, insider trading patterns, institutional holdings, and financials. Then, we will take a close look at its marketed product in the U.S. - Auryxia. The main focus of this report is the upcoming catalyst for Akebia, the March 22nd 2022 PDUFA action date for vadadustat. We will take a deep-dive to better understand the condition vadadustat targets, the current standard of care, and the patient population. We will then examine how vadadustat works and how it compares to other drugs in the same class. This will allow us to get a better understanding of the landscape and what can happen on March 22nd.

Founded in 2007, Akebia Therapeutics ($AKBA) is a Cambridge-based “fully integrated” biopharmaceutical company with a focus on treating complications of kidney disease. Akebia Therapeutics currently has a market cap of $472.392M.

Akebia Therapeutics merged in 2018 with Keryx Pharmaceuticals, another biotech focusing on kidney disease complications. The merger was a smart move because Keryx Pharmaceuticals already had a marketed product, Auryxia (ferric citrate). Auryxia is indicated for the control of serum phosphorus levels in adult patients with Chronic Kidney Disease (CKD) on dialysis, and the treatment of iron deficiency anemia in adult patients with CKD not on dialysis.

The merger gives Akebia Therapeutics access to Keryx Pharmaceuticals’ commercial capabilities and expertise in the kidney disease complications space, which will be a significant advantage if the company’s New Drug Application (NDA) for vadadustat is approved.

Vadadustat is an investigational oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that is awaiting FDA approval for the treatment of anemia due to CKD in dialysis dependent and non-dialysis dependent adult patients. If approved by the FDA, vadadustat would be a first-in-class drug in the U.S..

Vadadustat is already approved in Japan and is being commercialized by Akebia’s partner Mitsubishi Tanabe Pharma Corporation (MTPC).

The filing for the vadadustat NDA was accepted in June 2021, and the FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of March 29, 2022.

Partnerships

Mitsubishi Tanabe Pharma Corporation (MTPC) is not the only company that Akebia has entered a partnership with.

In 2016, Akebia entered a collabo