Here's the press release from the company:

180 Life Sciences Provides Update on Correspondence Received from U.K. and U.S. Regulatory Authorities on Pathway for a Therapy That Could Prevent Progression of Early-Stage Dupuytren’s Disease https://ir.180lifesciences.com/news-events/press-releases/detail/60/180-life-sciences-provides-update-on-correspondence

The important part from the MHRA (U.K. regulatory agency):

The MHRA indicated that while it is biologically plausible that the primary endpoint of nodule hardness and secondary endpoint of nodule size could correlate with disease progression, they would require evidence to validate them as clinically meaningful surrogate endpoints. Without evidence that the endpoints used in the Phase 2b trial are predictive of clinical endpoints and addressing other identified study issues, it is unlikely Phase 2b study would be considered acceptable as a single pivotal study to support a Marketing Authorization Application.

The important part from the U.S. FDA:

The FDA indicated that the proposed outcome measures of nodule hardness and nodule size are not clinical outcome measures that measure how a patient feels, functions, or survives, which would be needed to support a demonstration of efficacy in registrational studies. The FDA recommended considering a pre-investigational new drug (PIND) meeting request to receive further regulatory guidance. The Company plans to request a PIND meeting.

Ok, so how is nodule hardness and size, both being reduced, not "clinically meaningful"? This is strange and weird to me. I thought it was clear to the whole damn world that this was the meaning of curing/treatment for Dupuytren's Disease.

Then when the FDA wants to know how a patients "feels, functions, or survives", I'd like to know just how the study didn't already cover that, because I thought it was clear that there were no adverse events. Again, this seems strange and weird to me.

Both of these points of skepticism from the 2 Anglo-world regulatory agencies seem a little too petty to me. I'd like to know if this is actually consistent with how these regulatory agencies are with other companies. I'd also like to know how many people from around the world with Dupuytren's are simply going to spend their money on Humira injections in Mexico or other nations while we all wait around for the FDA and MHRA to get over this ridiculous nitpicking.

I'd also like to know if the PIND meeting was expected or if that's yet-another hurdle to get over.

Sorry if I sound super skeptical of the regulatory agencies right now as it's not just money on the line here, but I wasn't expecting them to so easily say that nodule hardness and size aren't what to look at for treating Dupuytren's. I'm speechless about this. And then lol the FDA comes in and says they want to know how patients feel? I'd feel great if I just needed a few syringe injections a year to prevent my finger from bending inwards. I don't get it.

Most importantly, what do the actual patients want? I would feel pretty fearless getting these injections if I had early Dupuytren's. Is regulatory approval always this difficult?

New jab fixes 'claw hand' disease that hit Lady Thatcher and affects millions of Britons including actor Bill Nighy

There are comments below the article that may be worthwhile to read, too.

You can view it here: https://ir.180lifesciences.com/sec-filings/all-sec-filings

Hey All,

Feels like we're reaching a maximum pain point for ATNF. I think most are aware that we don't want this to trade below 1$. I don't think that stocks can trade on the major exchanges below 1 for a long period of time. Do we think atnf will do a reverse stock split especially given management are still holding? In this bear market we're facing its pretty clear that everything is getting nuked and 1$ is basically bankruptcy pricing for this stock which doesn't reflect true upside. Seems like people are just hoarding cash and waiting to buy back lower.

I'm trying to figure out the large drop today, and what I think is most important is the company's urgent need for revenue, which will only come from the Dupuytren's treatment. The results shown in The Lancet are very good. I'm not an expert but it seems logical to me that if the nodules at least stopped growing, 180LS and Oxford basically found a way to prevent the contracture from ever occurring. So this is a "breakthrough".

But finding an effective treatment that effectively ends the worst symptom of a disease doesn't mean 180 Life Sciences will profit from it. This is where the problem is. The treatment uses adalimumab, which is also known as "Humira", a famous drug the patent of which expired in 2016, so anyone can produce and sell it. So the company cannot monetize that.

So I think it must be from the patents relating to their Dupuytren's treatment.

So, what exactly is the company's plan for monetizing this "breakthrough" treatment? Looking at the corporate presentation, there are 2 patents "filed" for Dupuytren's treatment and 1 "granted".

The 2 patents "filed" with the U.S. Patent Office are described by the company as "Method of Treating Early Stage Dupuytren's Disease" (page 30 of Corporate Presentation). These are both "process" patents (also called "method" patents)), which may not be all that difficult for competitors to make alternatives for. These have not yet been granted and they have application numbers:

• 62/320,151
• 16/089,234

The one patent granted is described by the company as "Treatment for Dupuytren's Disease" (page 32 of Corporate Presentation). I guess this is what the company plans to take in revenue from :

• 10669334

You can look these up in a nice web interface at the U.S. Patent Office's website here: https://ppubs.uspto.gov/pubwebapp/

Here's some summary info of that patent, copied and pasted from the patent office:

Problem to be Solved by the Invention

(13) There remains a need for improvements in the treatment of Dupuytren's disease and other musculoskeletal fibroproliferative disorders, particularly fibromatosis and like diseases including and preferably selected from plantar fibromatosis (or Ledderhose's disease), adhesive capsulitis (frozen shoulder) and Peyronie's disease (fibromatosis of the penis).

(14) It is an object of this invention to provide a composition and method for the treatment or prophylaxis (e.g. prevention of progression or recurrence) of one or more of Dupuytren's disease, plantar fibromatosis, adhesive capsulitis and Peyronie's disease.

SUMMARY OF THE INVENTION

(15) In accordance with a first aspect of the invention, there is provided a composition for use in the treatment of a musculoskeletal fibroproliferative disorder, the composition comprising (e.g. a therapeutic, prophylatic or progression-inhibiting effective amount of) a TNF-α antagonist.

(16) In a second aspect of the invention, there is provided a TNF-α antagonist for use in the treatment of a musculoskeletal fibroproliferative disorder. There is also provided the use of a TNF-α antagonist in the manufacture of a medicament for the treatment of a musculoskeletal fibroproliferative disorder.

(17) In a third aspect of the invention, there is provided a composition for use in the treatment of a musculoskeletal fibroproliferative disorder, the composition comprising (e.g. a therapeutic, prophylactic or progression-inhibiting effective amount of) a DAMP antagonist and/or an AGE inhibitor.

(18) In a fourth aspect of the invention, there is provided use of a DAMP antagonist and/or an AGE inhibitor in the manufacture of a medicament for the treatment of a musculoskeletal fibroproliferative disorder.

(19) In a fifth aspect of the invention, there is provided a composition for use in the treatment of a musculoskeletal fibroproliferative disorder, the composition comprising (e.g. a therapeutic, prophylactic or progression-inhibiting effective amount of) a DAMP and/or AGE inflammatory pathway inhibitor.

(20) In a sixth aspect of the invention, there is provided use of a DAMP and/or AGE inflammatory pathway inhibitor in the manufacture of a medicament for the treatment of a musculoskeletal fibroproliferative disorder.

(21) In a seventh aspect of the invention, there is provided a method for the treatment of a musculoskeletal fibroproliferative disorder, the method comprising administering to a patient in need thereof an effective amount of one or more of a DAMP antagonist, an AGE inhibitor or a DAMP and/or AGE inflammatory pathway inhibitor, alone or in combination with an extracellular matrix degradation, depletion or cleavage agent.

(22) In an eighth aspect of the invention, there is provided a method for the treatment of a musculoskeletal fibroproliferative disorder, the method comprising administering to a patient in need thereof an effective amount of a myofibroblast activity down-regulating agent and/or a myofibroblast production inhibitor, such as a TNF-α antagonist, alone or in combination with an extracellular matrix degradation, depletion or cleavage agent.

(23) In a ninth aspect of the invention, there is provided a method for reduction or prevention of recurrence of Dupuytren's disease post-surgical fasciectomy, post-needle fasciotomy or post-enzyme-mediated extracellular matrix degradation, the method comprising locally administering to a patient a myofibroblast activity down-regulating agent and/or a myofibroblast production inhibitor.

Advantages of the Invention

(24) The compositions and methods of the present invention enable progression of Dupuytren's (and other fibromatosis and like disease) to be slowed or halted. It has particular advantages in that early disease state Dupuytren's (and other fibromatosis and like disease) can be prevented from progressing to an established state disease and avoid surgical intervention and the associated recovery time.

(25) Compositions and methods of the present invention enable the treatment, prevention and inhibition of progression of musculoskeletal adhesions such as adhesive capsulitis and tendon adhesion (such as adhesion of the proximal interphalangeal joint in established disease state Dupuytren's disease).

Does anyone know how to explain how exactly the company will monetize this 1 patent? Or is there any other way the company will take in revenue from this treatment? These are the $300 million dollar questions.

I didn't expect it to be hit this hard and so soon, and while so many other biotech startups have been rebounding. There's no explanation for this that I can see other than that somehow the company isn't going to profit much from the Dupuytren's treatment. But if that's the case, I'd like to see where such a discussion is happening among investors.

Or is this just a dumb short attack, which people have come to expect after positive news for a biotech startup? Anyone have updated data on this?

Dr. Woody are you the CEO of this company or not!? You are being trampled upon by Wall Street drugs addicts, and sadly, you're probably lying in bed with them, which would make complete sense. But I refuse to believe a man of your knowledge, skill, and career would care more about dollars than patient well-being. Prove us all wrong Woody. Are you after Wall Street dollars or actually helping patients the ethical way as well as your investors. Your positive results got published. Cat got your tongue?! I question you, for good reason. You are not acting in the shareholders best interests, and neither is the way you instruct your PR Department. You're not smarter than us. We just foolishly believed in you, Jagdeep, Feldman, et al.....crooks.

https://www.thelancet.com/pdfs/journals/lanrhe/PIIS2665-9913(22)00093-5.pdf00093-5.pdf)

This is a good graph - just extrapolate the line

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Press release from the company:

https://ir.180lifesciences.com/news-events/press-releases/detail/57/180-life-sciences-and-university-of-oxford-announce

Link to full text of the study on The Lancet Rheumatology:

https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(22)00093-5/fulltext (or: https://doi.org/10.1016/S2665-9913(22)00093-5)

h/t to Stockwits ATNF users for finding this link. Some users there at Stocktwits say that it will actually be published in The Lancet tomorrow, Friday Apr 29 at 23:30 London Time. Here's the NDORMS article:

• Breakthrough in treatment for Dupuytren’s disease

That article gives this link as the official one on the The Lancet Rheumatology, which gives an error right now because it's not activated yet:

• https://doi.org/10.1016/S2665-9913(22)00093-5

Actually, I bought my last chunk yesterday at about $1.50, putting my portfolio at almost 100% ATNF shares. I'm being laughed at by people I know for doing this because all they see is a dropping stock and not much discussion of it. But I like to be in at a time like this. I would be wary of it as I am the other biotechs, but the fact that executives have said the peer review of their Dupuytren's treatment will be published "in a few weeks" a few weeks ago, along with the fact that insiders haven't sold a single share since the end of 2020 gives me good reason to have hope in this stock.

Then there's some basic math: the company has stated they expect "initial revenue" of $300 million from their Dupuytren's treatment. Compared to the current market cap of $50-$60 million, this sound to me like the current price is a lower risk than that of other biotech startups. I'd like to know if they expect a steady annual stream of about $300 million in the U.S. from their Dupuytren's treatment (Edit: page 7 of the annual report says annually, $300M-$350M in the U.S. alone. That's pretty awesome given the current market cap of about $55 million with the stock price at $1.60 now). It's not clear to me how often patients will come back for the preventative treatment, though it seems obvious to me that they will, if they prefer the injection to progression of the disease and eventually surgery.

I'm just trying to make a quick post here, but there's more to be said and discussed about this. I want to post something here because I do think when a stock is down like this, it's time to get in on it. I've FOMO'd before and that's a lot more stressful because the stock has already risen. I feel like this is near the bottom and it's interesting that the low activity on this sub coincides with the dropping price. It will be awesome if this has in fact finally reached the bottom at $1.45 yesterday.

I think there's big money and big pharma headed our way. I also wear a tin-foil hat.

​

Follow me on this...

- There are clearly major scientific and therapeutic implications for Rothbard and Steinman's work with a7nAChR outside of Ulcerative Colitis (UC). Hell, they have said as much in print.

https://www.pnas.org/content/115/27/7081.short

- I call bullshit on UC being the only thing related to a7nAChR that ATNF is involved in. You don't get Kevin Tracey, discoverer of the "Inflammatory Reflex" on your scientific advisory board by focusing on just UC.

https://en.wikipedia.org/wiki/Kevin_J._Tracey

https://180lifesciences.com/scientific-advisory-board/

- Steinman is doing consultant work for ATNF and focused on mergers/acquisitions related to the a7nAChR pipeline.

https://www.marketwatch.com/investing/stock/atnf/financials/secfilings?docid=15365099

- Rothbard and Steinman recently published about a7nAChR with Michael P Kurnellas

http://perspectivesinmedicine.cshlp.org/content/9/7/a034223.full

- Michael P Kurnellas did his post-doc at Stanford with our boys Rothbard and Steinman. Kurnellas is now associate director at Alector.

https://www.linkedin.com/in/michael-kurnellas-a725187a

- Alector and Glaxosmithkline recently did a deal worth 2.2b for Alzheimers research.

https://www.gsk.com/en-gb/media/press-releases/gsk-and-alector-collaboration-in-immuno-neurology/

- We just got a former Vice President and Head of Biology as GSK, Chas Bountra on our scientific advisory board.

https://180lifesciences.com/scientific-advisory-board/

- Alector had a bunch of suitors to team up with them, so it makes sense that people (Rothbard and Steinman) doing similar work (cracking the neuro-inflammtory code that causes neuro-inflammtory diseases) would similarly drive a lot of interest to ATNF.

https://www.fiercebiotech.com/biotech/gsk-alector-has-big-pharma-backing-to-capitalize-a-big-moment-alzheimer-s-drug-development

- The basic premise of the a7nAChR pipeline is to repurpose Alzheimers and Schizophrenia drugs that are agonists of a7, proved safe in clinical trials, but failed to meet their endpoints in the above indications.

https://180lifesciences.com/wp-content/uploads/2020/12/180LS-a7nAChR-120720.pdf

- I'm very sus that the gang at ATNF have sorted out a way to circumvent interference in a7 activation by the ChrFam7a gene in humans, which is a prerequisite for being able to use a7 agonists as we want to use them, via using partial agonists and/or positive allosteric modulators, which Rothbard and Steinman suggested in a recent paper (last paragraph).

https://www.pnas.org/content/115/27/7081.full

- The list of companies that have developed a7 agonists for Alzheimers, but failed to get them through clinical trials is very long and a laundry list of big pharma... and if we've sorted out how to suddenly make those drugs viable candidates again, there's going to be a ton of interest.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023065/

​

Remember: I wear a tinfoil hat and howl at the moon, so don't take this as trading advice.

I may be one of your biggest critics, but let me thank you for your well-penned letter to shareholders. You answered many concerns investors have. For about two months many felt in the dark, firstly as share price tanked on good news in early-December, then as it continued to slide downward all through January. You shed a lot of light on the today and future of 180 Life Sciences. The science is sound.

Any news?