ANI Pharmaceuticals Inc (ANIP) Options

Thanks JTFM for an excellent summary of the bull case.

BB, I feel optimistic about ANIP continuing to beat estimates and raise guidance for the foreseeable future for the following reasons.
- Novitium should keep rolling out generic drugs to outpace erosion from competition.
- The market's under estimate Corti's peak sales
- Zero value has been given to female testosterone, with results pending.
- Zero value has been given ANIP's potential royalty and milestone payments for CG Oncology's Cretostimogene.
- Regarding Cretostimogene and female tetosterone, in 2023, 89% of NDA's were approved cancer. So for future filings.
- Though we don't know the details of the Cold Genesys Biosante deal, at the time Biosante was represented by Oppenheimer Wolff & Donnelly LLP the same law firm that hammered out the GVAX agreement with Aduro Biotech. So at a minimum, I expect a clause in the deal covering royalties during the FDA approval exclusivity period (even after patent expiration), just like they did in the GVAX deal. It the deal gave them 5% on Global sales.
- JP Morgan pegged peak sales at $2.3 billion.
- I read an article where effective cancer drugs reach peak sales within 5 years. Assuming it gets approved , JP Morgan is correct regarding peak sales and ANIP is successful in litigation ANIP could receive $530 million in royalties plus milestone payments between 2026 and 2032. This is most likely in addition to any royalties for other indications if approved.

Lots to be bullish about.

GLTA


[tag]https://www.statista.com/statistics/817552/key-measurements-of-us-cder-drug-approvals/[/url][tag]FDA Approval Rate[/tag]

I would like to thank you gentleman once again. With all the info you place here, makes a shareholder feel very optimistic for the future. 😃

Thanks Silvr, the FDA post the Pre-Notices for Potential Noncompliance in submitting trial results quarterly. ANIP was not in the last batch. I think it should not be much longer before it comes out.

Another ten-year study. Hopefully the Libigel study is next.

50% Reduction in Breast Cancer Incidence

Thanks Silvr

We will get a read out on the CG0070 Phase 2 study with Keytruda at the early June ASCO meeting.

CG0070 ASCO Meeting

They probably already withheld a milestone payment, leading ANIP to request a declaratory judgement.

Researchers from the Baker Heart and Diabetes Institute and Monash University’s Women’s Health Research Program are leading a world first study to see if testosterone therapy can prevent the development of heart failure in postmenopausal women

Can testosterone therapy fight off heart disease in older women?

Silvr, if the CG Oncology agreement is similar the GVAX agreement. I find it hypocritical that CG Oncology is stating that they have no obligation to pay ANIP, especially when their agreement with Kissei Pharmaceuticals has a provision to make royalty payments on the first 12 years of commercialization or patent expiration, which ever is longest.

Kissei paid to us a one-time upfront payment of $10.0 million and, in connection with the entry into the Kissei Agreement, purchased $30.0 million worth of shares of our Series D redeemable convertible preferred stock as part of our Series D financing. Kissei is obligated to make development, regulatory and commercial milestone payments of up to $100.0 million. We have also agreed to pay Kissei a royalty on net sales of Licensed Product outside the Kissei Territory and outside the Lepu Territory (as described below), including on any U.S. sales, in a low-single digit percentage, subject to certain reductions. We are entitled to receive a royalty on net sales of Licensed Product in the Kissei Territory in the mid-twenties percentage, subject to certain capped reductions. Also, Kissei has the right to offset the royalty payments due to us with respect to the cost for the supply of Licensed Product sold by us to Kissei, and to indefinitely carry forward credits for any excess supply amounts paid over royalty amounts owed in a given quarter. We are entitled to receive a specified minimum percentage of royalties on net sales of a given Licensed Product in a given country and a given quarter, unless, if for such Licensed Product in such country and such quarter, Kissei has taken the maximum allowable reductions and the ratio of the cost for the supply of Licensed Product to the sales price for Licensed Product exceeds a low-double digit percentage threshold, then we shall receive no royalties on the net sales of such Licensed Product in such country and such quarter. Kissei’s and our royalty obligations will expire on a Licensed Product-by-Licensed Product and country-by-country basis on the later of twelve years from the date of first commercial sale of such Licensed Product in such country or when there is no longer a valid patent claim covering such Licensed Product in such country.

CG Oncology filing

Silvr, that is a very interesting article. Hopefully peer review will support the assertions. If testosterone levels can help regulate your immune system, it has huge implications and yet another reason to get female product on the market.

Regarding monetizing Libigel, we should find out when the results are published. Though the way greedy pharma companies try to weasel out of their agreements does create a concern (e.g, Cabaret and CG Oncology).

That would be great and ahead of any final FDA approval. They probably owe us some milestone payments too.

Thank you JTFM. It would be great to see the Libigel study published. There is certainly a lot of activity in this space. I just hope some of it translates into money in our pocket.

Here's another article.

Long Covid

Here are a couple of parts I like:

The work has yet to undergo peer review, the typical process by which scientific studies are vetted, but I’m highlighting it now given the enormity of need in long COVID — recent data from the Centers for Disease Control and Prevention showed some 8.8 million people in the U.S. were living with the condition in 2022 — and this team’s track record in conducting high quality research.[/I]

]We can’t let the opportunity go to waste. For too long, sex hormone differences have been seen as an inconvenient liability in clinical trials rather than a variable worth considering. Until recently, many drugs were only studied in male mice (lest the results be muddied by fluctuating female hormones) and even human tests skewed toward men.

Meanwhile, chronic conditions like ME/CFS (commonly known as chronic fatigue syndrome), Lyme’s disease and now long COVID, tend to be more common or more severe in women. Time and again, those women’s symptoms are dismissed as psychological rather than physical.

This latest study illuminates our limited knowledge about the role of hormones in chronic disease and should be a clarion call for more work in long COVID and beyond. That can help "start to right the wrongs of this sort of sexism and ableism in women’s health,” says David Putrino, director of rehabilitation innovation for the Mount Sinai Health System, who helped lead the study

Silvr, ANIP commenced an action on June 10, 2019, seeking a declaratory judgment to determine the parties' rights and obligations under the Tripartite Agreement, Escrow Agreement and Assignment Agreement against Cabaret. The decision in ANIP's favor was rendered April 26, 2020. If the CG Oncology matter follows a similar timeline, we will hopefully get a decision in January 2025.

ANI Pharm., Inc. v. Cabaret Biotech Ltd.

A third Female TRT related article in the Journal of Urology May 1, 2024 edition.

MP47-19 EFFICACY AND SAFETY PROFILE OF TRANSDERMAL TESTOSTERONE FOR HYPOACTIVE SEXUAL DESIRE DISORDER: A SYSTEMATIC REVIEW AND META-ANALYSIS

Maybe next month addition of Journal or Urology publishes the Libigel trial study results.

Journal of Urology put out another article regarding TRT and HSDD titled MP47-04 EXAMINING THE TRENDS IN TESTOSTERONE THERAPY FOR WOMEN WITH HYPOACTIVE SEXUAL DESIRE DISORDER

RESULTS:
We identified 33418 females diagnosed with HSDD at a mean age of 44.2±10.8 years. 850 females received TTh: 378 received 1 prescription, 195 received 2-3, 161 received 4-9, and 116 received more than 10. 461 females received prescriptions for injectable testosterone, 257 for topical, and 119 for pellets. 162 females were co-prescribed estrogen. A positive quadratic trend in prevalence of TTh for HSDD is observed across all age groups until September 1, 2015, after which there is an observable decrease in prevalence compared to the expected forecast (Figure 1). A positive linear trend in prevalence emerged from this point onwards. The slope of this linear trend is 0.0005 for the overall population (p

Another study supporting TRT for women. According to PD52-06 TESTOSTERONE THERAPY IN WOMEN IS NOT ASSOCIATED WITH INCREASED CARDIOVASCULAR RISK—A US CLAIMS DATABASE ANALYSIS

Method
A large electronic medical record and claims database, TriNetX Diamond Network, was queried to identify adult women with >3 testosterone prescriptions within a year for our study cohort. Our control cohort excluded women with testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts were propensity-matched and excluded women with prior heart failure, unstable angina, intersex surgery female to male, personal history of sex reassignment, or gender identity disorders. We assessed the association of TTh to MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within three years of initiating TTh. Age-based sub-analysis (18-55-year-old and 56+ year-old) was also conducted.

The following table shows great promise especially when looking at Breast Cancer reduction.



Journal of Urology article

Thanks auh2oman.

Thanks for the GVAX info Silvr, as demonstrated by their litigation against CG Oncology, at least they will defend their stake in IP, even if they won't articulate it openly.

From Pharmaceutical Technology ...

https://www.pharmaceutical-technology.com/data-insights/ani-pharmaceuticals-gets-grant-for-powder-for-oral-suspension-with-hydrochlorothiazide-for-hypertension-treatment/

I finished looking at the current status of Biosante GVAX patents. Healthtree is the sole assignee for two of them and shares assignment with Bristol Meyers for a third. Aduro (Chinook) is still listed for others and CG oncology for one as well.

This investment is always full of surprises which is why it has maintained my interest for so long. Here's the latest one. The GVAX trademark is now owned by "Healthtree Inc".

GVAX.com

I can't make heads or tails out of why this "foundation" would own this. However, when you look at the contact info you get directed here:

Meridian Therapeutics

Two of the principals of this company (Borrello and Noonan) are actually the researchers at Johns Hopkins investigating GVAX for multiple myeloma. It is the best testimony that they are now personally involved in its commercialization.

Maybe someday ANIP will get around and share our potential royalty pipeline.

Healhtree Inc is also listed as the assignee now for one of the Biosante patents (US7901902B2) for pancreatic cancer. Don't know the significance of this either.

Thank you JTFM. With the reported continued category expansion, this means that our product must be taking share from them and then capturing all of the category growth. Great news.

According to Mallinckrodt's 2023 Earnings Report, Acthar sales dropped from $140.9 million in Q4 2022 to $104.4 million in Q4 2023. Within two years ANIP has captured approx. 28.5% of the market, and is poised to keep growing market share.

Mallinckrodt expects fiscal 2024 Acthar Gel net revenue to decline in the low single digits, compared with fiscal 2023. This represents significant progress toward net revenue stabilization for the brand. In addition, Mallinckrodt expects Acthar Gel net sales performance to improve over the course of fiscal 2024, as prescribing momentum within the category continues to grow.

Mallinckrodt plc Reports Fourth Quarter and Fiscal Year 2023 Financial Results

Looks like Sovuna is starting to make the preferred tier of some formularies

Western Sky Community care Preferred Drug List

Silvr, according to the FDA Fast Track process they could have a rolling review.

Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA

Fast track.

I imagine they can file later this year and provide the final readout during the review period.

Thanks again JTFM. Hopefully they did use the same royalty term definition in the CG0070 agreement. That "or" statement could end up having a lot of value. It is sad that we are paying a high royalty to Merck for a decades-old Cortrophin Gel, but CG Oncology is apparently unwilling to do the same.

There will be a 12-month readout on the pivotal phase 3 study coming up in May. I like the comment from their president that “we are excited to share encouraging 12-month Phase 3 monotherapy results from the BOND-003 study at AUA 2024". Any idea when they would begin the FDA approval process? Can they use the 12 month results or do they have to wait until the trial officially finishes next year?

Urology Conference

Silvr, ANIP will have to add it in their filing and I expect they will face question. Though they may be limited in what they will release regarding their legal strategy. It is hard to know what their potential argument might be without seeing the details of the agreement. As I understand it, the Supreme Court has ruled long ago on not being able to collect royalties when the patent expires in the US (1964 decision in Brulotte v. Thys Co.) and Kimble v. Marvel Entertainment, LLC . But neither speak to the lengthy process to commercialize drugs and the effect of conditions outside patent expiration, such as FDA's regulatory 7-year exclusivity period. Interestingly, should it ever stretch out this far, Justices Alito, Roberts and Thomas opinions lead me to believe that they would lean towards backing ANIP's position (assuming a similar agreement to GVAX).

I believe North is more versed in the nuances surrounding patents patents, and may be able to better inform us.

I imagine the terms for CG0070 would be similar to the agreement with Aduro for the GVAX portfolio. If so, it looks like ANIP might have a compelling argument, even if the patents have expired.

1.57 “Royalty Term” shall mean, with respect to each GVAX Product, the period commencing on the Closing Date and continuing on a country-by-country, and product-by-product basis until the later of either (a) the expiration date of the last to expire of the Purchased Patent Rights covering the GVAX Product or any other applicable governmental or regulatory exclusivity period, including orphan drug exclusivity following approval (in either case, the “Regulatory End Date”), or (b) the seventh (7th) anniversary of the First Commercial Sale of such GVAX Product in that country; provided, however, that (i) if Net Sales in such country for any twelve-month period ending on the same month and day as the Regulatory End Date (a “Measurement Year”) but following the Regulatory End Date are less than 80% of the Net Sales in such country for the Measurement Year with the highest Net Sales during the Royalty Term, then the Royalty Term for such country shall expire as of the last day of the most recently completed Measurement Year; and (ii) if Net Sales in such country for any Measurement Year are less than 90% of the Net Sales in such country for the immediately preceding Measurement Year then the Royalty Term for such country shall expire as of the last day of the most recently completed Measurement Year.

4.1.4 GVAX-Other Product Royalty Payments. In further consideration of the Purchased Assets, and subject to the other terms of this Agreement (including the remainder of this Section 4), (a) commencing on the date of the First Commercial Sale of each GVAX-Other Product sold by Buyer and/or its Affiliates in each country in the Territory and continuing for the duration of the Royalty Term in such country, Buyer shall pay to Seller a royalty equal to [ * ] of Net Sales of any GVAX-Other Product sold by Buyer and/or its Affiliates in such country in the Territory; and (b) Buyer shall pay to Seller a one time milestone payment in the following amounts upon reaching the corresponding milestones for each GVAX-Other Product reaching such milestone, as follows:

(a) [ * ] upon [ * ];

(b) [ * ] upon [ * ];

(c) [ * ] upon [ * ]; and

(d) [ * ] upon [ * ].



Key definitions:
1.25 “GVAX-Other Field” shall mean any therapy relating to the treatment of cancer in humans, outside of the GVAX-Pancreas Field and the GVAX-Prostate Field, utilizing the Purchased Technology.

1.26 “GVAX-Other Product” shall mean (a) any product or service of Buyer or its Affiliates or Sublicensees, the manufacture, use, sale or performance of which infringes any Valid Claim included in the Purchased Patent Rights (excluding the GVAX-Pancreas Patent Rights and the GVAX-Prostate Patent Rights) in the GVAX-Other Field, (b) any product or service developed in whole or in part through the use of a process that is covered by a Valid Claim included in the Purchased Patent Rights (excluding the GVAX-Pancreas Patent Rights and the GVAX-Prostate Patent Rights) in the GVAX-Other Field, or (c) any product in the GVAX-Other Field not covered by (a) or (b) but that is developed and/or manufactured as a result of the use of the Purchased Technology.

Biosante Aduro Agreement

Thanks JTFM. What a payday that would be. We better get some questions on this at the next conference call.

Goldman Sachs estimates Cretostimogene's peak sales at $2.4 billion. If ANIP is successful, 5% would add $120 million in royalties per year.

Goldman Sachs starts CG Oncology stock with neutral rating, $42 price target

Though peak sales for Cretostimogene grenadenorepvec has not been identified. It is possible they are looking at peak sales of $3 billion
CG Oncology's Lead Bladder Cancer Drug Offers A Strong Potential Revenue Stream With Buyout Optionality authore dy IPO Kitchen on Seeking Alpha states the following:

While I am unable to find a peak sales estimate for cretostimogene, before Sesen Bio halted the development of Vicineum following a CRL from the FDA in 2021 due to concerns about elevated liver toxicity, the company estimated global peak sales of $3 billion for the drug for the same high-risk BCG-unresponsive NMIBC indication.

North, Biosante speaks about the deal in their filings

Oncolytic Virus Technology. On November 15, 2010, we entered into an assignment and technology transfer agreement with Cold Genesys, Inc. pursuant to which we sold to Cold Genesys exclusive, worldwide rights to develop and commercialize our oncolytic virus technology. The oncolytic virus technology uses replication-competent adenoviruses derived from Adenovirus type 5, a common “cold” virus that replicate in and selectively kill tumor cells. The replication of the virus is controlled by replacing the promoter of a gene required for replication with a promoter that is preferentially expressed only in tumor cells. Furthermore, the virus may optionally include a gene encoding a cytokine, which enhances immune stimulation to the tumor, thereby providing a dual mechanism of action for killing targeted cancer cells by direct cell lysis as well as via cellular and humoral immune responses to the tumor. The oncolytic virus technology includes CG0070, a replication-competent adenovirus that has completed a Phase I clinical trial for treatment of superficial bladder cancer. In exchange for the technology, we received a 19.9 percent ownership position in Cold Genesys and a $95,000 upfront cash payment and are eligible to receive future milestone and royalty payments.

Biosante 10-k for 2010

Here is the press release when the original deal was done.

Cold Genesys Deal

Were there any previous CG Oncology 10Qs or other SEC filings referring to that agreement?

Silvr, I see that the royalties are for 5% of worldwide net sales. From CG Oncology's 10-K

Legal proceedings, government investigations and enforcement actions can be expensive and time-consuming. For example, on March 4, 2024, a complaint was filed in the Superior Court of the State of Delaware by ANI Pharmaceuticals, Inc. naming us as defendant, seeking a declaratory judgement that a provision in an assignment and technology transfer agreement between us and ANI (formerly BioSante Pharmaceuticals, Inc.), dated November 15, 2010, obligates us to pay ANI 5% of worldwide net sales of cretostimogene. While we believe the allegations are without merit and intend to vigorously defend this matter, such litigation could result in substantial costs and divert our management’s attention from other business concerns, cause us reputational damage, negatively affect our stock price and result in monetary damages and future royalty obligations, if and to the extent cretostimogene receives regulatory approval. An adverse outcome resulting from any legal proceedings, investigations or enforcement actions could result in significant damages awards, fines, penalties, exclusion from the federal healthcare programs, healthcare debarment, injunctive relief, product recalls, reputational damage and modifications of our business practices, which could have a material adverse effect on our business, financial condition, results of operations and prospects. Even if such a proceeding, investigation or enforcement action is ultimately decided in our favor, the investigation and defense thereof could require substantial financial and management resources.

A settlement won't come cheap.

Thanks Silvr, it blow my mind how they think they can weasel out of royalties. Though they have gotten additional patents more recently, it hard to believe that royalties are not owed, at least on the first 7 years of exclusivity. If they had not entered into the deal they would have nothing. I might be wrong here, but this looks like a potential breach of contract or intent to breach contract. I don't if this could bring the validity of their newer patents into questions, especially in a prior art argument. I think you see CG Oncology end up settling out of court. Especially if they are looking to be bought out.

Thanks auh2oman, early reports coming out of the hearing make it look like the SC is likely to rule in favor ANIP another drug companies favor.

Thanks Silvr. Interesting trial. I note that Kevin Nead the large dementia study has a history of studies linking lowering testosterone to delayed onset of dementia. I think the large study will give an optimal testosterone range help delay dementia. It should benefit both testoterone replacement and reduction therapies.

Make em pay (from the CG Oncology 10K)...

On March 4, 2024, a complaint was filed against us in the Superior Court of the State of Delaware by ANI Pharmaceuticals, Inc. seeking a declaratory judgement that an assignment and technology transfer agreement between us and ANI, dated November 15, 2010, obligates us to pay ANI a royalty on certain "net sales" of cretostimogene. We dispute the allegations and intend to vigorously defend this matter.

Thanks auh2oman.

Today's Oral Argument at The Supreme Court ...

Although it pertains to the drug, Mifepristone, one of the two medications used in chemical abortions. The other is
Misoprostol, which ANI manufactures. Could have an impact. Below is an article from Axios discussing the case:

https://www.axios.com/2024/03/26/supreme-court-abortion-pill-case-fda

Thanks for the update JTFM. Maybe the old adage about a watched pot not boiling applies here. We know this is too big of an opportunity to not do something about it and our product is in the driver's seat. MVP Capital has stuck around too which may be an indicator.

Here's a related trial that is scheduled to be completed early next year.

Evanthea Trial

If you check out the investigators, they are all touting precision and functional medicine in their individual practices. I did not look at every one of them, but the few I did all used testosterone in their practice for women.

Looks like it is taking longer to recruit 700,000 participants for the M. D. Anderson Cancer Center Study tilted "Evaluation of Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes"

Anticipated completion has been change from November 1, 2023 to November 30, 2025.

The Q1medicare website is very informative. A check of coverage for Corti and Acthar shows that on average Corti price is approx. $10,000 cheaper than Acthar. Additionally, it looks like coverage is currently concentrated along the east coast and some larger cities, showing much room for growth, over time.

Correction. When I initially searched Acthar on the Q1Medicare it did not produce result. I just tried it again and now shows that H.P. Acthar is covered by 0 PDPs and 80 MAPDs.

Apologies for any confusion.

Wow, at 7-20K per unit, that is a lot of zeros for a market opportunity. Current sales then have only captured a small fraction of this.

Silver, in 2015, when ANIP announced the deal for Corti they identified a patient population of approximately 4 million. I believe this represented the number of patients, who are refractory to standard of care treatments across all indications. Gouty Arthritis flares would represent 90,000 of the 4 million patients. Obviously working with Veeva has accelerated identifying potential patients who could benefit from Corti.

JMHO

Another great dig JTFM. This bodes very well for us given, from your findings, Medicare represented such a large portion of the category peak sales.

Another great find JTFM. I thought Acthar Gel had broader approved indications, but as your reference shows, we actually have more. I agree with you then that more should be said about our addressable market.

On a positive note, ANIP is chasing some of these indications now which bodes well then for continued category expansion. It is curious that "pulmonology' does not appear to be on the list of indications, but was the one of the first pilot programs they launched ahead of gouty arthritis. Must be a larger market opportunity which makes an even stronger bull case.