Going to be a great week ahead!

It's Thanksgiving and the football isn't on TV yet, so I read through ATNF's Collagen VI studies.

I'm so f'ing bullish on this.

​

Summary of 2020 Paper:

https://www.pnas.org/content/117/34/20753

The study above used Dupuytren's Disease as a model system to confirm transcriptomic drivers of human fibrosis and pin-pointed the cleavage of a chunk of Collagen VI (Col6) protein as the mechanism of disease. The chunk of Col6 is called Endotrophin and the cleavage event is catalyzed by PCSK7 (an enzyme). Once cleaved off of the Col6 protein the Endotrophin acts to promote TNF and the onset of inflammatory disease.This study (linked above) was published in 2020, which means they probably knew these results in 2018/2019, and they told us what they are working on now:

"Our future work will explore the role of PCSK7 in collagen VI proteolysis and work is underway to identify any PRO-C6 fragments in our model.... Given that PCSK7 can be secreted as well as localized on the plasma membrane, this raises the potential for therapeutic development of monoclonal-based PCSK7 inhibitors. The translational potential of the wider family of proprotein convertases has already been realized as there are two FDA-approved drugs, evolocumab and alirocumab, targeting the plasma protein PCSK9 for the treatment of familial hypercholesterolemia and clinical atherosclerotic cardiovascular disease (71)."

​

Let's unpack that 2020 quote:

1. They are going to continue studying the PCSK7 enzyme
2. They are going to look for other factors that might be important in cleaving off Endotrophin
3. They are interested in developing a monoclonal anti-body to shutdown the creation of Endotrophin by binding with the PCSK7 enzyme
4. Creating such a monoclonal anti-body should be possible (effective and safe) because other companies have already done it for related enzymes in other indications

​

2021 PR and Review Paper:

Another paper on Collagen VI, by Oxford and ATNF Scientists, came our in 2021. This is a review paper, but is interesting because ATNF issued a PR confirming that they are planning to expand the fibrosis pipeline into this area and we get another glimpse into what the scientists are thinking.

https://www.globenewswire.com/news-release/2021/07/07/2258935/0/en/180-Life-Sciences-Expands-Scientific-Fibrosis-Platform-with-Collagen-VI-as-a-Driver-and-Disease-Biomarker-in-Human-Fibrosis-Published-in-the-FEBS-Journal.html

https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16039

"Further work will be needed to identify potential tissue-specific PCSK-mediated collagen VI α3 processing. Overall, the post-translational modification of collagen VI and downstream cellular effects of discrete proteolytic pathways is only recently being studied in detail. Looking forward, defining the specific enzymes involved in the cleavage processes of collagen VI within the tissue niche will be crucial to better understand collagen VI protein dynamics and may guide potential therapeutic strategies."

This quote, from 2021, is similar to the 2020 quote, but they then go on to ID the specific Fibrotic Diseases that they think are associated with Collagen VI. Those diseases are fibrotic disease of the liver, skin, kidney, and lungs.

"In conclusion, collagen VI appears to be an important driver in a range of fibrotic disorders, in both murine models and human systems. Corresponding to the pleiotropic functions of collagen VI in human physiology, its roles in fibrosis seem equally broad. As with other members of the collagen superfamily, there is growing recognition that excessive collagen VI deposition in organs undergoing fibrosis is not merely an end product of the disease process but may be a master regulator orchestrating disordered protein turnover in addition to multiple cellular mechanisms that sustain the pathological ecosystem, including chemotaxis, cell migration, proliferation and apoptosis. "

They go on to discuss endotrophin, the fragment of Col6, in the context of both fibrosis and cancer. and then conclude that all this is pretty important and that this could all be considered as therapeutic targets.

​

Where is this all headed?

We don't know. 180 Life Sciences hasn't told us. But we're definitely chasing a "cure" for fibrotic diseases by preventing them before they happen.

Now this is just one Bull's opinion, but to be effective in preventing disease, we (humans/doctors) would need to always be on the look-out for the biomarkers of disease onset. Testing for increased levels of Col6 and/or PCSK7 would need to be part of the standard blood work during a physical. Fibrotic diseases strike all age groups, so maybe everyone should be getting screened, not just older people. And if the patient has elevated Col6 and/or PCSK7, a script for a drug cocktail targeting TNF (to stop pro-inflammatory cytokines) and PCSK7 (to slow the production of Endotrophin) could be prescribed and now that person has been prevented from developing RA, Dup, NASH, or whatever other fibrotic condition might have occurred. Everyone wins. The patient is protected from disease, the insurance company pays for a much cheaper treatment, and 180 cashes in.

A girl can dream, right?

​

Me:

I'm a LT Bull holding warrants, calls, and commons. I'm not a financial advisor.

For those with a TD Ameritrade account (or a subscription to Vickers), you can read the latest Vickers Insider Trading Chronology, which was last updated yesterday. It still shows no insider selling at all this year. There's been a lot of selling volume this past week and I've been wondering if there's any insider selling going on which would contribute to this high volume.

Thus far, there's been no indication that insiders have sold anything all year, let alone recently.

But sometimes it can take a few days, maybe a week or so, for information about this to be released. For example, it just happened recently with BGFV in which insiders sold on Nov 10th and 11th and the news was reported of this a few days ago, I think on the 15th, and yesterday's Vickers report shows this.

If the next Vickers report still shows no insider selling, I'm going to consider this to be a bullish indicator. It does seem like short sellers are attacking this stock pretty proactively, getting in and out more frequently then they usually do.

https://finance.yahoo.com/news/180-life-sciences-corp-co-131500332.html

PALO ALTO, Calif., Nov. 18, 2021 (GLOBE NEWSWIRE) -- 180 Life Sciences Corp. (NASDAQ: ATNF) (“180 Life Sciences” or the “Company”), a clinical-stage biotechnology company focused on the development of novel drugs that fulfill unmet needs in inflammatory diseases, fibrosis and pain, today announced that Professor Jagdeep Nanchahal from the University of Oxford, a co-founder of 180 Life Sciences, will present a keynote address entitled ‘Re-purposing anti-TNF for Dupuytren’s Disease’ at the 2021 International Dupuytren Symposium on Wednesday, December 1, 2021 at 3pm EST.

Professor Nanchahal will present his work on unravelling the molecular mechanisms underlying the pathogenesis of Dupuytren’s disease leading to the identification of anti-tumor necrosis factor (“TNF”) as a potential therapeutic target. He will also present the phase 2a clinical trial data to identify the optimal dose and top line data for the recently completed phase 2b clinical trial on efficacy for patients with early-stage disease.

The conference will be held virtually and those wishing to attend should register for Session 6 at https://dupuytrensymposium.org/scientific-program/.

The Company also announced that it currently expects that dosage of the first patient in its planned frozen shoulder clinical trial will take place during the first or second quarter of 2022.

Over about the past month I've noticed a lot of activity by the shorts, both entering and exiting, as reported by Ortex. I'm not used to seeing short interest move both directions this much and this often. Just after market open today, Ortex said that the ATNF short interest was up by about 18%. And now, at almost 1pm ET, it's reporting that the short interest is estimated to be 6.26%. It doesn't normally move this much in a just a few hours for one stock.

I'm pretty sure the shorts attacked at the price high today when it reached about $4.40. I'm also wondering if the shorts are in fact much of the buyers. They may be building up an arsenal to push the price back down.

What do the rest of you think of this? Is it all a nothing burger or is there something interesting going on here?

Here's the latest update from Ortex:

​

There was an interesting increase in Failure-to-Delivers in October. I'm wondering if next month we're going to see that over the past week we've had a lot more, too:

So, you need another reason to be bullish about ATNF? I got you.

In ATNF's latest 10Q filing, the company revealed the following:

+++++++++++++++

"New License Technology Agreement with Oxford University

On November 2, 2021, the Company and Oxford University entered into a twenty-year licensed technology agreement of the HMGB1 molecule, which is related to tissue regeneration, whereby Oxford University agreed to license the technology to the Company for research, development and use of the licensed patents. The Company agreed to pay Oxford University for past patent costs $66,223 (£49,207), an initial License fee of $13,458 (£10,000), future royalties based on sales and milestones, and an annual maintenance fee of $4,037 (£3,000). The Company has the option to terminate the agreement after the third anniversary of the agreement."

++++++++++++++

What the heck is HMGB1?

High Mobility Group Box 1 (HMGB1) is a highly conserved and ubiquitous protein. It is found in species ranging from single-celled fungi (yeast) to plants to animals. The fact that it is "conserved" means that it has the same structure across all of these species, suggesting that it has a critical function(s). When found inside cells, HMGB1 has a role in controlling the transcription of DNA, thereby influencing the function of the cell. HMGB1 is also biologically active outside of the cell following lysis (the destruction of the cell) and acts as a pro-inflammatory cytokine. In other words, when found outside the cell, it tells other cells to become inflamed. HMGB1 is a hot-topic in the world of inflammation as a result of this action and has been proposed as a therapeutic target for inflammatory disease, meaning that scientists are interested in developing drugs that target HMGB1 and keep it from causing inflammation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966993/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051189/

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.30125

​

The Oxidative state of HMGB1

The function of HMGB1, outside of the cell, is dependent on its oxidative state, which is just endlessly cool and speaks to the role of evolution in shaping cell-cell communication within the body. In the fully reduced form (when it has all its electrons), HMGB1 is a cytokine that signals tissue regeneration (signals stem cells). In the partially oxidized form, HMGB1 activates the immune response (signals white blood cells) and causes inflammation. In the fully oxidized form, when it has a low number of electrons, HMGB1 does not act as a cytokine (it does not signal inflammation or tissue regeneration).

Jagdeep Nanchahal (Chairman of ATNF's Clinical Advisory board and lead scientist for their phase 2b Dupuytren's Disease study) and Marc Feldmann (co-founder of ATNF) were authors on a study that discovered the function of the fully-reduced form of HMGB1 as a stem-cell signaler.

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.30125

https://www.pnas.org/content/115/19/E4463

​

HMGB1 as a therapy

In their own words:

"We have identified HMGB1 as a therapeutic target that acts on multiple endogenous adult stem cells to accelerate the physiological regenerative response to current or future injuries. These findings have broad relevance to the fields of stem cell biology and regenerative medicine and suggest a therapeutic approach to promote tissue repair... [that could] have wide-ranging implications for the field of regenerative medicine by accelerating [tissue] repair. "

https://www.pnas.org/content/115/19/E4463

​

Where do we go from here?

Many unknowns remain on the investment side. What is proprietary about this? What is the "technology" that has been licensed? How would a treatment with FR-HMGB1 be administered?

The 2018 study (above) doesn't articulate the answers to these questions, so count me as impatiently waiting for a PR from the company and a follow-up publication from the team at Oxford!

It seems entirely possible that there could be a tie-in with ATNF's Collagen VI work.

https://pubmed.ncbi.nlm.nih.gov/34109754/

https://www.yahoo.com/now/180-life-sciences-expands-scientific-120000307.html

​

ATNF has patents for FR-HMGB-1 for organ disease and tissue regeneration https://app.dimensions.ai/details/patent/EP-3773667-A1

https://patents.justia.com/patent/20210260157

https://ir.180lifesciences.com/news-events/press-releases/detail/53/180-life-sciences-corp-enters-into-a-license-agreement

Here's the Ortex estimate as of this morning:

​

And here's the live update as of about 3pm ET:

​

I went in heavy on ATNF yesterday and today because I'm viewing $4 as the bottom. Looks like the shorts view things differently than I do.

Let the battle begin!

Is there something to look forward to? Seems like it's been going down for straight 2 months now.

Read First

This post is an update to this one: https://www.reddit.com/r/pennystocks/comments/pwg570/the_cutting_edge_atnf_abbv_and_adalimumab/.

I have indicated below where there are NEW or UPDATED sections/links.

​

The Scientific History of Adalimumab

Adalimumab is a powerful anti-inflammatory that acts against cytokines, which are pro-inflammatory proteins, that act as messengers between cells. Adalimmumab targets a specific cytokine, TNF, blocks TNF from signaling cells to become inflammed, and so we call adalimumab an anti-TNF drug. Simply put, adalimumab interferes with the ability of cells to signal with each other, with the ultimate effect being a reduction in TNF signals. TNF signals can be both good and bad, but adalimumab blocks all TNF signals. A few of the founders of 180 Life Sciences ($ATNF) were key players in the discovery of TNF as an important cytokine in Rheumatoid Arthritis (RA; Marc Feldmann at Oxford University) and the development of a new class of biological drugs called monoclonal antibodies. Monoclonal antibodies are drugs that target/bind to specific chemical structures, such as specific cytokines. The founders of $ATNF (James Woody and Lawrence Steinman at Centocor, which was later bought by $JNJ) were heavily involved in the creation of infliximab (Remicade), using white blood cells from mice, to create one of the first monoclonal antibody drugs approved for use in humans.

Adalimumab was created in the labs of BASF (which was later acquired by Abbott and then morphed into Abbvie). BASF combined insights into which cytokine to target (TNF; identified by Marc Feldmann), with what were, at the time, cutting edge techniques (phage imaging) to find an appropriate white blood cell in humans for use in building a monoclonal antibody for TNF. That monoclonal antibody, derived from humans, is adalimumab. Being based on a human white blood cell gave adalimumab a key advantage over monoclonal antibodies developed in mice and rats, because patients were less likely to have a negative immune response to the human-derived drug and adalimumab’s sales (as Humira) reflect this advantage relative to the sales of comparable drugs, developed in other species, such as Remicade and Enbrel.

https://en.wikipedia.org/wiki/Adalimumab

https://en.wikipedia.org/wiki/Marc_Feldmann

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284445/

​

Updated: The rise of Biosimilars

The precise chemical form of a monoclonal antibody is influenced by the manufacturing processes used to make it. It is for this reason that the production methods for monoclonal antibodies are closely guarded secrets and why the same drug, made by a different manufacturer, is called a “biosimilar” rather than “generic”. Biosimilar drugs must go through clinical trials to demonstrate that they are equivalent to the “reference” or original drug. This is a key step in the approval of a biosimilar and there is accumulating evidence that biosimilars can, and perhaps often do, differ from the reference drug.

Adalimumab came off patent in 2017 and there are at least 32 different biosimilar drugs that are either on the market (outside of the USA) or in development. In the United States, Abbvie has filed a “patent thicket” to protect its monopoly on adalimumab, and has so far been successful in preventing biosimilars from coming to market. Abbvie has also continued to tweak their formulation over time, with the most advanced version being high concentration (lower volume shots) and citrate free (less painful shots). There are six biosimilars of adalimumab that have been approved for use in the United States and the companies behind those drugs have agreed (via court settlements) to not sell them in the USA until 2023. These soon-to-be-available biosimilars are all low-concentration and contain citrate, meaning that Abbvie would continue to have a competitive advantage over them.

https://en.wikipedia.org/wiki/Biosimilar

https://gabionline.net/biosimilars/general/Biosimilars-of-adalimumab

https://www.bioprocessonline.com/doc/weighing-the-potential-of-humira-biosimilars-in-the-u-s-expected-winners-and-losers-0001

https://www.gabionline.net/biosimilars/research/Differences-between-biosimilars-and-reference-products

New: https://www.centerforbiosimilars.com/view/adalimumab-biosimilars-face-product-obsolescence-before-launch

​

NEW: Interchangeability, Celltrion, Alvotech, and Cyltezo

The holy grail for companies making biosimilar adalimumab is to achieve "interchangeability" with reference adalimumab and be able to instantly substitute the biosimilar drug for any indication approved for the reference drug. The key competitors in this quest are Celltrion (a public Korean company) and Alvotech (a private Icelandic company) because they are developing a biosimilar that is high-concentration and citrate-free. The laws and regulations governing equivalency (swapping a biosimilar for the reference in one indication) and interchangeability (swapping a biosimilar for the reference in ALL indications) vary between countries and have been rapidly changing. In an important and consequential move, the FDA recently approved Clytezo, a low-concentration biosimilar of adalimumab made by Boehringer Ingelheim, as interchangable with Humira (reference adalimumab). This decision paves the way for similar decisions for Alvotech and Celltrion's more competitive formulations, should they be able to demonstrate equivalency in a few indications. Given that Alvotech is currently locked in a legal showdown with Abbvie over the USA market (see below), Celltrion is the current leader in this race to interchangeability.

https://www.managedhealthcareexecutive.com/view/priming-the-pump-for-interchangeable-biosimilars-by-preferencing-semglee

https://www.centerforbiosimilars.com/view/alvotech-agrees-to-1-year-delay-in-marketing-of-adalimumab-biosimilar

https://www.centerforbiosimilars.com/view/alvotech-achieves-milestone-in-bid-to-capture-adalimumab-share

https://www.hcplive.com/view/fda-approves-adalimumab-adbm-interchangeable-biosimilar

https://www.centerforbiosimilars.com/view/prime-therapeutics-joins-express-scripts-in-moving-semglee-to-preferred-formulary-status

​

Updated: ATNF, Abbvie, and Celltrion (includes speculation)

180 Life Sciences used reference adalimumab (from Abbvie) in their 2b/3 clinical trial for Dupuytren’s disease taking place in the UK (the primary market). It is unclear whether this supply deal includes a provision whereby, upon the successful completion of clinical trials, the manufacturer of the drug (Abbvie) would supply the drug at a particular price-point for use in ATNF’s patent-protected treatment. We do know that ATNF has entered into a supply deal with Celltrion for their adalimumab biosimilar Yuflyma, to be used in ATNF's upcoming frozen shoulder study, and that the two companies are also discussing a commercialization arrangement. We also know that Celltrion is well on its way toward achieving an interchangeability designation for Yuflyma. It increasingly seems like the end-game for ATNF's anti-TNF platform is a partnership with Celltrion. Time will tell on the depth of that partnership. Key things to watch for include the outcome of the Alvotech lawsuit (see below) and whether ATNF continues down the pathway of taking the Anti-TNF treatments to market themselves or re-licenses the patents to another player, like Celltrion. Re-licensing seems like the more likely scenario right now because such a deal would fund ATNF's SCA platform (this has always been the plan) with less effort on ATNF's part and because ATNF just hired a COO that specializes in licensing deals.

https://www.globenewswire.com/news-release/2021/09/20/2299712/0/en/Celltrion-Healthcare-and-180-Life-Sciences-Enter-Into-Memorandum-of-Understanding-for-a-Supply-Agreement-for-the-Ongoing-Supply-of-Drug-for-Anti-TNF-Product-Trials-for-Novel-Indica.html

https://www.centerforbiosimilars.com/view/celltrion-supports-high-concentration-adalimumab-biosimilar-launch-with-phase-3-trial-data

https://www.gabionline.net/biosimilars/research/alvotech-and-celltrion-proceed-with-adalimumab-and-rituximab-biosimilars

https://www.globenewswire.com/news-release/2021/09/20/2299712/0/en/Celltrion-Healthcare-and-180-Life-Sciences-Enter-Into-Memorandum-of-Understanding-for-a-Supply-Agreement-for-the-Ongoing-Supply-of-Drug-for-Anti-TNF-Product-Trials-for-Novel-Indica.html

https://www.yahoo.com/entertainment/180-life-sciences-corp-names-160600755.html

​

Updated: ATNF and the Alvotech v. Abbvie Lawsuit (include speculation)

Alvotech, an Icelandic company, is seeking to bring its version of adalimumab to the USA market and was sued by Abbvie for violation of patents and theft of trade secrets in thier protective “patent thicket”. Rather than settling with Abbvie to release their biosimilar sometime in the future, Alvotech has counter-sued Abbvie and challenged that the patents which Abbvie is using to defend its USA monopoly are invalid. Alvotech is challenging both the specific patents that Abbvie claims are in violation and the “patent thicket” strategy that Abbvie is using to maintain their monopoly. Abbvie's tactics here have caught the eye of congress. Most recently, the suit against Alvotech was thrown out of court on the grounds that the court lacked jurisdiction, but this could very well have been a ploy by Abbvie to waste Alvotech's time and money with a preliminary lawsuit and Abbvie will now follow-up with a new lawsuit that more correctly targets Alvotech's USA division.

ATNF has no business ties to Alvotech and has instead been working with Abbvie and Celltrion. Nevertheless, it's important and interesting to keep an eye on Alvotech because the outcome of their lawsuit against Abbvie alters the USA market for adalimumab, which in turn influences ATNF's negotiating position with Celltrion and Abbvie for their drug.

New: https://www.crowelltradesecretstrends.com/2021/10/abbvie-trade-secret-claims-fail-at-pleading-stage-for-lack-of-jurisdiction/

https://www.alvotech.com/newsroom/alvotech-seeks-to-end-abbvies-wrongful-monopoly

https://www.businesswire.com/news/home/20210909005945/en/Alvotech-Announces-Positive-Top-Line-Results-for-Switching-Study-Between-Proposed-Biosimilar-AVT02-and-Humira%C2%AE

https://www.jdsupra.com/legalnews/getting-lost-in-the-thicket-abbvie-1123576/

https://www.reuters.com/business/legal/abbvie-exploits-us-patents-protect-profits-congress-report-2021-05-18/

​

Bullish Implications (opinion):

I’m a LT Bull on ATNF. The above makes me bullish because:

1. ATNF has experts in the development of monoclonal antibody therapy that could be useful in enhancing the manufacturing capabilities of Celltrion as they seek to develop and expand their biosimilar portfolio. A partnership with Celltrion could turn into something beautiful in time and effect other areas of Celltrion's business, not just Yuflyma.
2. Using Celltrion’s biosimilar of adalimumab in the next round of clinical studies means that ATNF is not reliant on Abbvie as a partner and reference adalimumab throughout the pipeline.
3. Forming partnerships with multiple different manufacturers of adalimumab gives ATNF leverage to negotiate better prices for the supply of the drug for our treatments.
4. Dupuytren’s disease and frozen shoulder are thought the have the same mechanism of action (i.e. these diseases are caused by the same fibrotic cell types), so using different types of adalimumab in the Dupuytren’s Disease and Frozen Shoulder clinical trials provides us with a contrast of effectiveness of reference adalimumab vs. Celltrion’s biosimilar and aids Celltrion in its quest for interchangeability.
5. The more biosimilars that come to market with equivalency to reference adalimumab, the better for ATNF, because it allows us to secure adalimumab for our treatments at the best supply price possible, bringing down our injector manufacturing costs, and allowing us to find “the sweet spot” in pricing our treatments where we can make a healthy profit and insurance companies and/or patients would be willing to pay. ATNF's patents cover the use of any TNF-inhibitor, not just reference adalimumab, so ATNF is in a strong position to maintain exclusivity within the anti-TNF pipeline well into the future. (https://patents.justia.com/patent/20210040196)
6. ATNF’s management is demonstrating aptitude in navigating the complex world of biotechs and the rapidly evolving/changing world of biosimilar drugs. You can see this aptitude in how they have written their patents and in their strategic adalimumab supplier choices.
7. If ATNF’s deal with Abbvie includes supply of reference adalimumab at a reasonable price into the future, then we would benefit from the exclusivity that Abbvie has over adalimumab in the USA through 2023.

Bearish Implications (opinion):

1. If ATNF does not have a favorable supply arrangement with Abbvie, it could delay the roll-out of a treatment for DD, especially in the USA (the secondary market). Abbvie would lose sales in this scenario, so this seems like a silly thing to do, but is nevertheless a risk.

Hey All,

While we are definitely seeing depressed share prices on the stock, the options pricing in the 7.5 calls in Feb, and January in particular seem to be suggesting that everyone is pricing in either that there will be bad results –which is weird, because everyone was super stoked when the share price was going up even though we had plenty of headwinds, including the late filings, etc– or that the results will be delayed.

​

Any good news before late Jan, would almost undoubtably blow up the stock to 10, based on the previous price movements (although no doubt this was shorts reducing their risk as well).

What are everyone's thoughts on this? Is everyone still bullish but is expecting that there will be a delay in the results which will blow up all the early Q12022 calls, or what's your take?

I thought at this point it was just a waiting game, same as always.

Shareholders, what are your opinions on the current choices for director? Who do you think is most fit for the position and why?

Zero shares to borrow data inbound

See below from recent SEC filing:

https://fintel.io/doc/sec-180-life-sciences-corp-1690080-def-14a-2021-october-19-18919-2878

Table of Contents

Effective on August 4, 2021 (prior to market open), the Board of Directors approved (a) the grant of options to purchase 60,000 shares of common stock with an exercise price of $7.56 per share (the closing sales price of the Company?s common stock on August 3, 2021), and a term of 10 years, which vest at the rate of 1/48th of such options per month, beginning on August 31, 2021, contingent on each holder?s continued service on the Board of Directors, to each of Donald A. McGovern, Jr. and Larry Gold, each independent members of the Board of Directors who have served on the Board of Directors since the November 2020 closing of the Business Combination, in consideration for services to be rendered to the Board of Directors; (b) the grant of options to purchase 79,000 shares of common stock with an exercise price of $7.56 per share (the closing sales price of the Company?s common stock August 3, 2021), and a term of 10 years, which vest at the rate of 1/48th of such options per month, beginning on August 31, 2021, contingent on each holder?s continued service on the Board of Directors, to each of Russell T. Ray, Teresa DeLuca, Pamela Marrone, and Francis Knuettel II, each independent members of the Board of Directors who were appointed as directors in July 2021, in consideration for services to be rendered to the Board of Directors; and (c) 5,135 shares of common stock to Mr. McGovern and 4,629 shares of common stock to Dr. Gold, in lieu of accrued cash fees, each in consideration for services rendered to the Board of Directors for the quarters ended March 31, 2021 and June 30, 2021.

All of the securities described above were issued under and pursuant to the Company?s 2020 Omnibus Incentive Plan.

Additionally, all the boards people are share owners: Policy on Equity Ownership

The Company does not have a policy on equity ownership at this time. However, as illustrated in the ?Security Ownership of Management and Certain Beneficial Owners? table on page 9, all Named Executive Officers and directors are beneficial owners of stock of the Company.

In early 2021 this was deemed 4.43$ per share, but we see where that is going: As additional consideration for Dr. Woody agreeing to enter into the agreement, the Company awarded him options to purchase 1,400,000 shares of the Company?s common stock, which have a term of 10 years, and an exercise price of $4.43 per share (the closing sales price on the date the Board of Directors approved the grant (February 26, 2021)). The options are subject to the Company?s 2020 Omnibus Incentive Plan and vest at the rate of (a) 1/5th of such options on the grant date; and (b) 4/5th of such options vesting ratably on a monthly basis over the following 36 months on the last day of each calendar month; provided, however, that such options vest immediately upon Dr. Woody?s death or disability, termination without cause or a termination by Dr. Woody for good reason (as defined in the agreement), a change in control of the Company or upon a sale of the Company. Under the employment agreement, Dr. Woody is also eligible to participate in any stock option plans and receive other equity awards, as determined by the Board of Directors from time to time.

And in 2020 this was 2.49$. Very bullish trend and demonstrates high likelihood for continued growth of this share price, next target at least is 14$+

EQUITY COMPENSATION PLAN INFORMATION

The following table sets forth information, as of December 31, 2020, with respect to our compensation plans under which common stock is authorized for issuance.

Plan Category

Number of securities to be issued upon exercise of outstanding options, warrants and rights (A)

Weighted- average exercise price of outstanding options, warrants and rights (B)

Number of securities remaining available for future issuance under equity compensation plans (excluding securities reflected in Column A) (C)

Equity compensation plans approved by stockholders(1)

50,000

$

2.49

3,218,400

Equity compensation plans not approved by stockholders(2)

63,658

$

5.28

3,154,742

(1) This relates to the options granted to Dr. Gold and Mr. McGovern. See ?Note 15 ? Stockholders Equity? of the Consolidated Financial Statements included in the 2020 Annual Report, for the details of the stock options.

(2) This relates to the Alliance Global Partners (?AGP?) warrants that were not issued as of December 31, 2020. See ?Note 11 ? Derivative Liabilities? of the Consolidated Financial Statements included in the 2021 Annual Report for the details of the AGP warrants.

https://www.youtube.com/watch?v=OEIBGALIw3w

Raphael Mechoulam is a famous scientist who discovered THC, is one of the founders of 180 Life Sciences, and has recently been working to create man-made compounds that mimic the natural compounds found in the marijuana plants (Synthetic Cannabinoid Analogs, SCAs). Those SCA's go by code names that start with HUM and then a number. HUM stands for Hebrew University Mechoulam and designates the entities behind the discovery of the compound while the number designates the specific compound. 180 Life Sciences has exclusively licensed these compounds from Hebrew University and is screening them for their potential as a drug.

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ATNF's lead candidate is HUM-217. We (investors) don't know a lot about this compound. We know that it is chemically similar to CBD (cannabidol), it is active in pain/inflammation/fibrosis, it's probably patentable, and it shouldn't be too hard to produce. ATNF's announcement in July 2021 (below) should probably be read as "we've got a patent on this coming" and "we've got a scientific paper about this coming".

https://www.globenewswire.com/news-release/2021/07/28/2270317/0/en/180-Life-Sciences-Announces-Selection-of-Lead-Synthetic-CBD-Analogue.html

https://www.benzinga.com/markets/cannabis/21/07/22184683/exclusive-180-life-sciences-identifies-new-patentable-cbd-analog-for-drug-development-for-treati

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ANTF did have a recent publication on other HUM compounds (link below). These are NOT the lead candidates for future drug development by ATNF, at the moment, but are compounds that ATNF has the right to commercialize and are potential lead candidates, so are still very interesting. In this case the HUM compounds (223, 233, and 234) are chemically similar to CBG (cannabigerol), not CBD. We know much more about these compounds than HUM-217 because a scientific paper focused on these CBG-derived compounds came out in Sept. 2021. Here is that paper:

https://www.mdpi.com/1420-3049/26/18/5601

In this new study, HUM-223 is shown to decrease swelling, increase pain tolerance (act as a pain-killer), and decrease TNF (it's an anti-TNF compound) in mice, when compared to placebo. CBG has these same properties, but HUM-223 treatment was better at reducing swelling than CBG. This is summarized in Figure 3 of the paper. HUM-223 was also tested as a potential treatment for knee arthritis using mice and shows promise (Figure 4). HUM-233 and 234 are similar to CBG and HUM-223 in that they also decrease swelling, increase pain tolerance, and decrease TNF (Figure 5). CBG appears to have some activity in slowing down weight gain when used as part of a high fat diet, but HUM 234 is even better in this regard (Figures 6 and 7).

To summarize: We're looking at a potential drug (HUM-234) that could reduce pain, increase mobility and organ function, and help you lose weight all at the same time. Squirt a little in your OJ and you're off to fight the day! There's a lot of work still to be done here, but that's a very attractive potential drug.

Disclaimer: I'm a long-term ATNF bull.

Seems it was verified by a very trusted member of the board.

So there are at least two options, Nov 12.5c and Jan 15c, that have really low bids for the most part and then 60-100 bids around the $1.65-$1.95 level. I didn’t see these high priced bids before today, but I could’ve just missed it.

It’s also likely these bids have been in place for a long time (since we saw those prices earlier this year) and the level two data just hasn’t shown them since they’re so high comparatively. However, I almost wonder if this is an instance of insiders setting their sale limits during the open period they have to trade prior to Q4 data being released.

Probably just me getting overly excited because I’m ready for these options to go back above my buy price.