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Disclaimer: This is not financial advice. Invest at your own risk.

Cytodyn: LERONLIMAB (Pro140) A hyperbolic shift in pharma.

By: Synthesis:1

My goal for this paper is to discuss the market potential of the drug leronlimab by Cytodyn. I will lay out data showing Leronlimab’s hyperbolic potential. If the company executes correctly it WILL become one of the top 3 revenue pharma’s in the world. I say this very conservatively. I truly believe Cytodyn will become the biggest grossing pharma in the world. This paper is broken up into two sections. Section one is a list of each leronlimab indication assuming 20% of the total market share. In some indications 20% is a very conservative estimate considering some indications are unmet medical needs. So theoretically it should take up 100% market share. With just 2 out of the estimated 30 indications at 20% market share Cytodyn will be a top 5 pharma in the world.

The second section of this paper is a list of the top pharma’s in the world by revenue and some of their top grossing oncology, HIV, and immunology drugs. Most of which I believe Leronlimab will replace or compete with in the future. What you will find in this section is most of these drugs that Leronlimab will compete with have severe life threatening side effects. Leronlimab has little to no side effects in over 1185 patients treated in clinical trials. In some cases for over 5+ years.

Before continuing this paper I strongly suggest everyone go through the new investor presentation Cytodyn published on april 22, 2021 on their website. (link below) https://d1io3yog0oux5.cloudfront.net/_e81da2624f58c3391b29dfa87338ec69/cytodyn/db/193/29 12/pdf/CytoDyn+-+Investor+Presentation_Updated+4-21-2021+%28final%292.pdf

Leronlimab: A monoclonal antibody CCR5 receptor antagonist with around 30 indications. The target of Leronlimab (PRO 140) is the important immunologic receptor CCR5. The CCR5 receptor is a protein located on the surface of a variety of cells including white blood cells and 2

cancer cells. On white blood cells, it serves as a receptor for chemical attractants called chemokines. The CCR5 receptor is also the coreceptor needed for HIV to infect healthy T-cells. Recent research has identified the CCR5 receptor as an important target for many disease processes, including cancer metastasis and certain immunological conditions. Leronlimab is well tolerated with data from over 1185 patients in clinical trials with no major safety concerns with some patients taking Leronlimab weekly for 5+ years in HIV trials.

Leronlimab Indications:

1.HIV combination therapy: (unmet medical need for this population 3, 4 class resistance)

-Patients taking Leronlimab had 81% viral load suppression at 48 weeks compared to recent big pharma drugs approved for this population: 43% after 24 weeks and 45% after 48 weeks. Both drugs have serious side effects, Pfizer's has a blackbox warning. Pfizer's drug requires 30 minute infusions every 2 weeks administered by a healthcare professional. Compared to Leronlimab a 30 second subcutaneous self administered injection once a week with little to no side effects and negligible toxicity.

Status: Phase 3 primary endpoint met. Expecting to re- file BLA in the USA, UK, EU, and Canada in 2021.

2. HIV monotherapy: completed a phase 3 investigative trial- previously completed a successful phase 2 trial. Higher responder rate prompted Cytodyn to file a phase 3 pivotal trial protocol with the FDA as a “switch therapy”

-215 patients reached almost 1 year of suppressed viral load and over 40 patients average 3 years, with 5 patients nearly 6 years. No drug resistance in patients for over 6 years now.

Status: Phase 3, label expansion, protocol submitted to the US FDA; will also be presenting the protocol to EMA, Canada, UK regulatory agencies and pursue approvals. 3

Market potential: this is just in America combined $14 billion yearly

3. HIV Prep: Animal study was very successful for use of Leronlimab in PrEP for one dose per month.

Status: One dose/month. Publication has been submitted to a medical journal and potential Phase 2 may initiate in 2021.

Overall market value: $2.6 billion in 2019. Projected: $3.3 billion by 2029 https://www.globenewswire.com/news-release/2021/03/10/2190440/0/en/Global-Human-Immun odeficiency-Virus-HIV-Therapeutics-Drug-Forecast-and-Market-Analysis-to-2029.html#:~:text=T he%20PrEP%20market%20was%20valued,the%20impact%20of%20generic%20erosion.

Leronlimab market value at 20%: $520 million a year.

Opinion: Leronlimab has the potential to dominate the HIV market if approved for “switch to monotherapy maintenance”. Gilead science dominates the HIV ( pg.20) market currently with 70% of their revenue coming from there HIV products seven of their products have blackbox 4

warnings for safety issues. Their highest grossing HIV medication is Biktarvy, which generates revenues of $7.3 billion yearly. However it has a blackbox safety warning. Biktarvy is a combination of three separate antiretroviral drugs in one pill, taken once a day. That has shown to be effective without resistance for 3 years . They also have majority market share for their PrEP medications. Biktarvy the other Descovy both which you have to take everyday and both having black box safety warnings. Gilead is competing against ViiV (pg.13). A partnership between GSK and Pfizer. Both combo therapies one is an injection that you have to schedule once a month and is administered by a professional (can't miss your injection window possibility of resistance) the other is a combo pill. Both have bad side effects and are about the same effectiveness compared to Gilead's HIV drugs. Doctors favor Gilead's 3 treatment therapy because of the risk of resistance to two treatment therapies. Leronlimab is a self administered subcutaneous injection once a week with little to no side effects. Patients in the monotherapy trial have been taking Leronlimab up to 5+ years without resistance. Also if successful in PrEP Leronlimab is a once a month subcutaneous injection. Compared to a daily pill with bad side effects. Leronlimab is truly a paradigm shift in HIV care. It will be the first monotherapy ever, and the First HIV treatment with no severe side effects and the first self administered shot. Finally the average cost of HIV treatment is $110,000 yearly. Leronlimab costs $70,000 yearly, $40,000 cheaper than the standard of care. It should take 100% of the prep market. If it's successful in clinical trials.

Covid-19 Four Peer reviewed medical publications on leronlimab in covid-19. https://d1io3yog0oux5.cloudfront.net/cytodyn/files/pages/cytodyn/db/256/content/JTAUTO-D-20- 00043_R1+_3__1_.pdf https://www.medrxiv.org/content/10.1101/2020.11.02.20224659v1.full https://www.sciencedirect.com/science/article/pii/S2589909021000174?via%3Dihub https://www.ijidonline.com/article/S1201-9712(20)32305-5/fulltext

Look at presentation on pg.1 for (full covid-19 data sets)

4. Covid-19 severe to critical: (unmet medical need) 2nd phase 3 trial Discussion underway with US FDA- Brazil anvisa, and India. Finale protocol should be accepted by next week (4/27/21).

-Submitting IO (interim order ) to Canada there version of EUA with critical data from the 1st phase 3 trial.

-Under compassionate special permit (csp) in the Philippines, Cytodyn is well positioned to generate revenues. April 15 2021 chiral pharma and Cytodyn signed an exclusive supply and distribution agreement for up to 200,000 vials of leronlimab to the Philippines. Significant 5

pressure from Citizens , media and government officials for the FDA to grant EUA to leronlimab. That could happen any day now.

Overall market value: Unknown depends on demand. (unmet medical need)

Leronlimabs market value: Cytodyn has 1.2 million vials ready for commercial use at $1350 a vial that's $1.62 billion in sales. This is a (estimate) it's a very unpredictable virus with variants. We do know the vaccines will not be effective against variants but Leronlimab is effective against variants because it does not target the spike protein of the virus like the vaccines do. So the market value is really unknown. When approval happens in multiple countries who knows what the demand will be. Cytodyn have committed 200k vials to the Philippines and 500k vials upon EUA in Brazil. Cytodyn manufacturer Samsung biologics could make up to 1 million vials a week if the demand is there.

5. COVID-LONG HAULERS: (unmet medical need)

Status: Phase 2 results due by july 2021 https://clinicaltrials.gov/ct2/show/record/NCT04678830

Market value: There are projected to be 60 million long haulers at the end of 2021 but know one knows how many there actually will be with variants surfacing around the world. Leronlimab at the moment is the only drug in clinical trials for this indication. The trial is one shot a week for 56 days that is 8 total shots of leronlimab. If each vial is priced at $1350 two shots in each vial. I am trying to be as conservative as possible. Cydy is charging 70,000 a year for their HIV treatment breaks down to one shot a week. There are 52 weeks in a year X that by $1350 equals approximately $70,000 a year. At this price Leronlimab is still half the price of the SOC covid treatments. Each patient using four vials of Leronlimab that's $5400 for a full treatment each patient X that by 60 million people that's $324 billion dollars in sales that's just not realistic. Lets go conservatively 10% of the 60 million people with long haulers get Leronlimab that's $32.4 billion in sales. This will make Cytodyn one of the biggest pharmas in the world. On this one indication alone. https://www.youtube.com/watch?v=_v-bvztZOTo&ab_channel=Covid19LongHaulerClinicDrGayli sNormanAARDS

Opinion: Leronlimab has had the best data in the world for every phase of covid-19 in clinical trials. (mild to moderate) though it didn't hit its primary endpoint it was a (phase 2) trial. The goal is to find an endpoint for a phase 3 trial . It beat the SOC (Remdesivir) in every category. It also showed better data then regeneron and lily's cocktails (both had government contracts) which got approved on easier endpoints then Leronlimab had. Just to put it in perspective these three approved drugs had significantly bigger patient populations in their trials then the Leronlimab trial . Which makes it easier to hit statistical significance especially when you have a weak 6

subjective primary end point like “hospital stay” however the drug wasn’t dropping viral load. The point of a phase 2 trial is to find a primary endpoint for a phase 3 trial so there're many endpoints in a phase 2. Leronlimab hit statistical significance in NEWS2 (secondary endpoint) which is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice, when patients present to, or are being monitored in hospital. Six simple physiological parameters form the basis of the scoring system: (respiratory rate, oxygen saturation, temperature, blood pressure, pulse/heart rate, AVPU response). Cytodyn went to the FDA and asked if they should file for EUA because they hit statistical significance with a small patient population in mild to moderate. Where most patients get better on their own would be a very strong indication that the drug is stopping disease progression so patients don't escalate to severe and critical conditions. The logical approach for a country that wants to stop the mortality in covid-19 would be to stop patients from reaching the point of severe and critical. This NEWS2 statistical significance proved that Leronlimab could do that in covid-19. The FDA told Cytodyn to focus on severe and critical population cd12 trial. So Cytodyn did not end up doing a phase 3 for mild to moderate. Which they could have made their new primary endpoint NEWS2 repeat the same trial with a bigger population and get approval. CD12 was very controversial to some degree. The DSMC at 50% of the trial suggested to stay with the original primary end point and not to add more patients to the trial but they requested another look at 75% full. The trial was double blinded. So Cytodyn couldn't see the data but they would see the total deaths in the trial. All deaths get reported to the FDA. However Cytodyn doesn’t know if it's the Leronlimab arm or placebo was used in that death. By using basic math you can tell if you're trending towards statistical significance because the trial was all cause mortality. The trial had 88 deaths in total which would mean Leronlimab should have hit statistical significance of their primary endpoint. This is where controversy struck in the critical sub population of the trial patients 65+ which have a 80% chance and higher death rate. In this population the Leronlimab arm was shifted 3:1 vs placebo instead of the trial designed 2:1. Leronlimab had a disproportionate number of patients above 65; this skewed the deaths in the trial and gave placebo an unfair advantage. What are the statistical odds of something like this happening in a clinical trial? In my opinion it is statistically impossible. Even more controversial in the trial was the FDA allowed only 2 doses of Leronlimab. When during the trial design protocol process of cd12 the company requested up to 4 doses. Leronlimab only stays in the patient system for about a week. Patients got dosed at day 1 and day 7 the primary endpoint was all cause mortality at day 28. That means the drug was no longer in the system on day 14. The data at day 14 was statically significant p-value of 0.021 and decreased mortality by 82% of patients in critical condition. Also Clinical outcome improvement (based on ordinal scale) with Leronlimab at day 14 was 400% better than placebo arm. Even with the limited 2 doses Leronlimab had a 24% reduction in all cause mortality. All this adversity Leronlimab half dosed and 3:1 verse 2:1 in high risk patients, Leronlimab was still better than any drug tested for covid-19 in severe and critical populations ever recorded in clinical trials. Cytodyn requested an age adjustment for the trial. The FDA rejected giving Cytodyn an age adjustment. AGE adjustments are common practice if a trial is 2:1 and it gets shifted to 3:1 it's a very simple fix. All they do is take some patients out of the official data report. So the trial can be stratified back to 2:1. If the age adjustment happens Leronlimab would have hit statistical significance in the trial and be the first drug in the world to 7

do this with an all cause mortality primary endpoint. The last drug that was given EUA for this population was 2% better than placebo and was allowed an age adjustment. As stated above, Leronlimab at day 28 decreased mortality by 24% compared to 2% and the other drug has a bad safety profile. The 14 day data speaks for itself when the drug is in the system it works. I actually can't comprehend how this drug does not have an EUA yet based on the data and safety profile. However the big opportunity is long haulers. This potentially could be the biggest blockbuster indication of the century. Based on the mild to moderate data collected and the anecdotal testimony of people in the long haulers phase 2 study. Some patients started the trial in wheelchairs and were walking in 6 weeks. The Cytodyn team is confident in approval for this indication. Long haulers will make Cytodyn one of the biggest pharmas in the world and put Leronlimab on the worldwide stage. Every country will need it.

Total leronlimab market potential in covid-19:$34 billion+

Cancers:

Please do not continue this paper until you watch the video link below. It's a video simulating how Leronlimab MOA works to cure cancer: https://www.youtube.com/watch?v=il1ZcW0W5oY&ab_channel=nicehedges

Status: Phase 2 Basket trial for 22 solid cancer tumors underway. To date in this trial there are 9 patients with stage 4 cancer living past 12 months right now also having ZERO CTC(circulating tumor cells) after one year. This is just unheard of. Cytodtyn is applying for breakthrough designation with the FDA. 8

6.Melanoma:

Full market value: $8.19 billion in 2019. Projected: $14.55 billion by 2027. https://www.globenewswire.com/en/news-release/2020/05/25/2038033/0/en/Skin-Cancer-Treat ment-Market-to-Reach-14-55-Billion-by-2027-Increasing-Regulatory-Approvals-Will-Provide-Imp etus-to-Market-Growth-says-Fortune-Business-Insights.html

Leronlimab at 20% market share:$1.6 billion a year.

7.Brain-glioblastoma: treatment option is limited. I am classifying it as a (unmet medical need)

Full market value: projected $2.83 billion in 2021. Projected: $5.64 billion in 2028. 9

https://www.globenewswire.com/news-release/2021/03/15/2192683/0/en/Brain-Tumor-Drugs-M arket-to-Reach-USD-5-64-Billion-by-2028-Surging-R-D-Activities-to-Improve-Treatment-Options -will-Favor-Growth-Fortune-Business-Insights.html

Leronlimab at 20% market share: $560 million a year.

8.Throat:

Full market value: $1.48 billion in 2019. Projected: $3.89 billion by 2025. https://www.industryarc.com/Report/16874/throat-cancer-treatment-market.html

Leronlimab at 20% market share: $280 million a year.

9.Lung:

Full market value: $17.9 billion in 2018. Projected: $26.3 billion by 2023. https://www.bccresearch.com/market-research/pharmaceuticals/lung-cancer-therapeutics-marke ts-report.html#:~:text=The%20global%20market%20for%20lung%20cancer%20grew%20to%20 %2421.9%20billion,totaling%20%2431.8%20billion%20in%202019.

Leronlimab at 20% market share:$3.5 billion a year.

10. Stomach:

Full market value:$2.6 billion in 2018. Projected: $8.2 billion by 2026. https://www.globenewswire.com/news-release/2020/02/11/1982770/0/en/Stomach-Cancer-Gastr ic-Cancer-Treatment-Market-to-Reach-USD-8-20-Billion-by-2026-Rapid-Adoption-of-PD-1-Inhibi tors-for-Treating-Gastric-Cancers-to-Boost-the-Market-Fortune-Business.html

Leronlimab at 20% market share: $520 million a year. 10

11. Colon Carcinoma:

Full market value: $15.3 billion in 2020. Projected: $17.4 billion in 2025. https://www.marketdataforecast.com/market-reports/global-colorectal-cancer-market

Leronlimab at 20% market share:$3.6 billion a year.

12. Breast:

Full market value: $21.58 billion in 2019. Projected: $55.27 billion by 2027. https://www.fortunebusinessinsights.com/industry-reports/breast-cancer-therapeutics-m arket-100163

Leronlimab at 20% market share: $4.3 billion a year.

13. Testicular:

Full market value: $421 million in 2019. https://www.businesswire.com/news/home/20191218005494/en/Global-Testicular-Cancer-Drugs -Market-2019-2023-Evolving-Opportunities-with-Baxter-and-Bristol-Myers-Squibb-Technavio

Leronlimab at 20% market share: $84 million a year.

14. Ovarian:

Full market value: $2.9 billion by 2022. https://www.bccresearch.com/market-research/healthcare/therapies-and-diagnostics-for-ovarian -cancer-report.html#:~:text=The%20global%20ovarian%20cancer%20therapeutic,7.1%25%20d uring%202017%2D2022.

Leronlimab at 20% market share: $580 million a year. 11

15. Uterine:

Full market value: $211 million in 2015. Projected: $273.6 million in 2024. https://www.prnewswire.com/news-releases/us-uterine-fibroids-market-worth-us-2736-million-by -the-end-of-2024-rising-prevalence-of-fibroid-to-ensure-uptake-says-tmr-601117275.html

Leronlimab at 20% market share: $42 million a year.

16. Pancreas:

Full market value: $2.41 billion in 2020. Projected: $3.47 billion by 2025. https://www.marketdataforecast.com/market-reports/global-pancreatic-cancer-market

Leronlimab at 20% market share: $482 million a year.

17. Bladder:

Full market value: $240.22 million in 2020. Projected: $320.8 million by 2025. https://www.marketdataforecast.com/market-reports/bladder-cancer-therapeutics-market

Leronlimab at 20% market share: $48 million a year.

18. Sarcoma:

Full market value: $1.2 billion by 2023. https://www.grandviewresearch.com/industry-analysis/sarcoma-drugs-market

Leronlimab at 20% market share: $240 million a year. 12

The global solid tumor cancer treatment market was valued at US$ 121.3 Bn in 2018 and is expected to reach US$ 424.6 Bn by 2027 https://www.researchandmarkets.com/reports/4828522/global-solid-tumor-cancer-treatment-mar ket-size#:~:text=The%20global%20solid%20tumor%20cancer,15.0%25%20from%202019%20t o%202027.

Leronlimab at 20% market share: $24.26 billion a year.

Opinion: CCR5 directs the movement of a t-cell. When a T-cell activates CCR5 it moves. That's what immune cells do tracking down inflammation/infections etc. Cancer cells turn on that same receptor CCR5. When a cancer cell does that it starts moving. This receptor CCR5 normally expressed on T-cells promotes migration to the brain, organs, and tissues. This process is the same for a cancer cell. So CCR5 is necessary for the metastasis of cancer cells. It is the metastasis not the primary tumor that kills 90% of cancer patients. When an immune cell CCR5 is activated and the cell starts moving the first thing it does is turn on calcium signalling. Which is akin to the gas that goes into the car. It is the same process for cancer cells. When Leronlimab is added it blocks the calcium signalling. Metaphorically you block the gas going into the car and it doesn't move. In animal studies Leronlimab was 98% effective in stopping metastasis. I believe Leronlimab will become the biggest cancer drug in the world. Go through all of section 2 almost every single one of these drugs approved for cancer have life threatening side effects and alot of them have to be used in combination with other drugs because of their limited effifancies. Look at Keytruda (pg.20) one of the biggest cancer drugs ever, that works with your immune system to kill cancer cells. A monoclonal antibody like Leronlimab as well. This drug has limited efficacy and terrible side effects and does not have the metastasis MOA that Leronlimab has yet Leronlimab still has the immunomodulation property. The beautiful thing about Leronlimab besides the MOA is it can be used with any cancer treatment chemotherapy, CART, radiation, checkpoint inhibitors because there are no drug interactions and the safety profile of Leronlimab. This is not the case for other cancer treatments due to their terrible side effects. The bar for cancer approval is set very low. Many of these drugs are band aids.. They extend patients' lives to some degree but with terrible side effects and in some cases the drug itself can cause death. All Leronlimab needs to do in clinical trials is show the same efficacy or just a slight improvement and these other cancer drugs already approved will become obsolete because of the safety profile of Leronlimab. When a physician is assessing the risk reward of a treatment for a patient if you have a drug that is just as good as another drug but one of the drugs has terrible side effects the obvious route would be to choose the one with the least side effects. Patient safety is the number one priority. When adding another drug to a cancer treatment for example the patient is on chemo it has brutal side effects. A physician is not going to add another drug if it's going to enhance the side effects to make life even more unbearable and possibly dangerous. Leronlimab can be added because there are little to no side effects. (my hypothesis) considering the immunomodulatory property of Leronlimab who is to say it 13

couldn't counteract some of the negative side effects of chemo or other cancer treatments. Leronlimab is and will be the future of cancer for monotherapy and combination therapy based on its MOA and safety profile. https://www.cytodyn.com/pipeline/cancer

19. Nash: (unmet medical need.)

Status: phase 2 last patient enroll expected to be in 2021.

Full market value: Projected: $84.34 billion in 2029. https://www.globenewswire.com/news-release/2020/07/15/2062580/0/en/Non-Alcoholic-Steatoh epatitis-NASH-Drugs-Market-2020-2029.html

Leronlimab at 20% market share: $16.8 billion a year. 14

20. Multiple sclerosis (MS)

Status: (phase 2) Protocol & IND submission to the FDA (US) by end of 2021.

Full market value: $25 billion in 2019. Projected: $40.66 billion by 2027. 15

https://www.fortunebusinessinsights.com/industry-reports/multiple-sclerosis-drugs-market-10038 6

Leronlimab at 20% market share: $5 billion a year.

21. Stroke:

Full market value: $30.1 billion in 2019. Projected: $65.6 billion by 2030. https://www.globenewswire.com/news-release/2021/02/17/2177365/0/en/Stroke-Diagnostic-and -Therapeutic-Market-Size-to-Worth-Around-USD-65-6-Bn-by-2030.html

Leronlimab at 20% market share: $6.2 billion a year. 16

23. Autoimmune Diseases:

Full market value: $3.98 billion in 2020. Projected: $7.17 billion by 2027. https://www.prnewswire.com/news-releases/autoimmune-disease-diagnostics-market-worth--7-1 7-billion-globally-by-2027-at-8-79-cagr-verified-market-research-301192857.html

Leronlimab at 20% market share: $780 million a year. 17

24. Sepsis:

Full market value: $627.73 million in 2020. Projected: $1.18 billion by 2027. https://www.grandviewresearch.com/press-release/global-sepsis-diagnostics-market

Leronlimab at 20% market share: $125 million a year.

25. Seizures: 18

Full market value: $180.3 million in 2019.

Leronlimab at 20% market share: $36 million a year.

If all indications are approved for Leronlimab: yearly market share: Around $101,741,000,000 billion a year.

You also need to factor in:

-Long haulers (unmet medical need) was only set to 20% market share.

-Oncology was set to only 20% market share.

-Stroke was set to only 20% market share. 19

-HIV was set to american revenue only, not global. The global hiv market was 30.5 billion in 2020.

-Nash (unmet medical need) was only set to 20% market share.

-Covid-19 was set to already produced inventory:

Opinion: The true yearly revenue of Leronlimab is rather unknown; it could be more than I estimated considering some indications that are (unmet medical needs) Leronlimab should take 100% of those markets. Also some indications it might not get approved. Many people speculate a partnership or a buyout in the near future for Cytodyn. Cytodyn CEO is on the record stating If a company wants to buy us out they have to buy all indications for Leronlimab. Well considering all indications approved would be over 100 billion dollars in revenues per year, big pharma simply can't afford Cytodyn. As you will see in section 2 Leronlimab is probably the greatest threat to the top 15 biggest biotechs in the world. Especially Roche/Genentech and Gilead. In conclusion, Leronlimab has a near perfect safety profile. Once the receptor occupancy test is completed (in progress) the FDA will no longer have any more excuses for delay. The safety profile is what really makes Leronlimab impenetrable. Cytodyn owns all the patents for Leronlimab as well. They have no ties to any government agency or government funding/program. They also just raised 50 million dollars in funding. Many small biotects are forced to partner or get bought out by big pharma because they can't handle or do not have the expertise to manufacture on an industrial level. Cytodyn doesn't have that problem; they have a deal with the best manufacturer in the world, Samsung Biologics. They could produce up to 1 million vials of Leronlimab a week. Samsung announced this year they are building a new state of the art $2 billion dollar manufacturing plant. When Leronlimab gets its first EUA approval they will be ready to produce on an industrial level. Leronlimab will have two approvals this year HIV and Covid. I believe when the first EUA happens Cytodyn will be uplisted to Nasdaq. 20

Big Pharma: Section 2

2020 revenue and list of top oncology,Immunology, and hiv product revenues.

1.Johson and Johnson: $56.1 billion

IMMUNOLOGY and ONCOLOGY combined make up 24.64 billion dollars that's almost half their revenue.

Darzalex: $3 billion in sales in 2019 its a monoclonal antibody that helps slow or stop the progression of multiple myeloma. It is not a cure but it can improve the quality of life in most people. The treatment cost 5,850 infusion avg. monthly cost is 11,212$.( Leronlimab is 1400$ a self administered injection or IV )

Effectiveness: salvage therapy demonstrated a 1-year overall survival (OS) rate of 90.9% in patients with multiple myeloma who relapsed following allogeneic stem cell transplantation (SCT) and also failed several posttransplant therapies https://www.targetedonc.com/view/daratumumab-salvage-therapy-effective-in-relapsed-myeloma-foll owing-allogeneic-sct

Side effects: Serious https://www.darzalex.com/darzalex-treatment/side-effects?utm_source=google&utm_medium=cpc&u tm_campaign=GO-USA-ENG-PS-Darzalex-BP-EX-RN-DTC&utm_content=Side+Effects&utm_term= darzalex+side+effects&gclid=Cj0KCQjwpdqDBhCSARIsAEUJ0hOar9320fk-PplaRwtsXAZuVLkH_BY qsOaumut_Cr9Fo7fZ4Rv-5LQaAjDzEALw_wcB&gclsrc=aw.ds#slide-1

Zytiga: $3.5 billion in sales in 2019 a hormone therapy drug. Treatment is prostate cancer.

Effectiveness : Those who took Zytiga had a three-year survival rate of 83%. This means that they lived for three years after they started taking the drug. Those who received standard therapy had a three-year survival rate of 76%. Also in this study, Zytiga lowered the risk of death within three years of starting treatment by 37% “ 21

https://www.medicalnewstoday.com/articles/325694#:~:text=Those%20who%20took%20Zytiga %20had,of%20starting%20treatment%20by%2037%25.

Side effects: Serious https://www.zytiga.com/taking-zytiga/side-effects

2. Pfizer: $51. 75 billion

54% revenue came from international markets

Ibrance: (palbociclib) $4.96 billion in sales in 2019 estimated to do 11.04 billion in sales by 2026. It's a treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.

Effectiveness: Women treated with Ibrance plus Faslodex survived without cancer progression for 9.5 months, compared with 4.6 months for those treated with Faslodex alone. Researchers with the PALOMA3 study enrolled 521 patients with metastatic HR-positive, HER2-negative breast cancer. No cure found yet in this indication.

Together, the combination of IBRANCE and letrozole delayed disease progression for a median time of 24.8 months versus 14.5 months for those that received letrozole and placebo. Patients taking IBRANCE with letrozole reduced their risk of disease progression by 42% compared to those taking letrozole and placebo. https://www.ibrance.com/about-ibrance#how-works

Side effects: Serious life threatening https://www.ibrance.com/about-ibrance#trial-results

Xtandi: $2.7 billion 2019. (Enzalutamide) non steroidal antiandrogen medication used to treat prostate cancer:

Effectiveness: At the interim analysis (after a median follow-up of approximately 22 months), 28 percent of men in the enzalutamide group had died, compared with 35 percent of men in the placebo group. Men who received enzalutamide experienced a 29 percent reduction in the risk of death compared with those who received placebo. Men treated with Xtandi survived for longer before treatment became ineffective and their prostate cancer started to spread. Men treated with Xtandi had a 71% lower risk of metastasis or death than placebo-treated patient 22

https://www.drugs.com/medical-answers/long-xtandi-enzalutamide-work-3554743/#:~:text=Men %20treated%20with%20Xtandi%20survived,death%20than%20placebo%2Dtreated%20patients .

Side effects: Serious life threatening https://www.xtandi.com/side-effects?utm_source=google&utm_medium=cpc&utm_term=enzalut amide%20side%20effects&utm_campaign=gs-branded%20generic&utm_content=gs-enzalutam ide%20side%20effects_ex&gclid=Cj0KCQjwpdqDBhCSARIsAEUJ0hNK_mqM8w-g9-WpYHfp9 X65cfF9EV9DkFZRpMJoyNlqYZGEtSV_2wAaAmV_EALw_wcB&gclsrc=aw.ds

Zirabev: $600 million projected sales by 2021 a monoclonal antibody in combination with carboplatin and paclitaxel, is indicated for the first line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer (NSCLC). ZIRABEV is indicated for the treatment of recurrent glioblastoma (GBM) in adults.

Effectiveness: The cancer improved in 45% of those given Zirabev (162 of 358 patients) and in 45% of those given Avastin (161 of 361). Because Zirabev is a biosimilar medicine, the studies on effectiveness and safety of bevacizumab carried out with Avastin do not all need to be repeated for Zirabev. https://www.ema.europa.eu/en/medicines/human/EPAR/zirabev#:~:text=The%20cancer%20imp roved%20in%2045,to%20be%20repeated%20for%20Zirabev.

Side effects: Serious life threatening https://www.zirabev.com/takingzirabev

Maraviroc: selectively binds to the human chemokine receptor CCR5, which is present on the cell membrane. This binding prevents the interaction of HIV-1 gp 120 with CCR5-tropic HIV-1 and thereby inhibits the virus from entering the cell.

Effectiveness: Individuals with non-R5 viruses were more likely than individuals with R5 viruses to discontinue maraviroc (75% vs 34%, p<0.0001). At 30 months, the estimated rates of virological and immunological success were respectively 89% and 51% in individuals with R5 viruses and 48% and 23% in individuals with non-R5 virus https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144746#:~:text=Individuals% 20with%20non%2DR5%20viruses,individuals%20with%20non%2DR5%20viruses.

Safety: BLACKBOX WARNING https://en.wikipedia.org/wiki/Maraviroc

Study HIV-1 Resistance to Maraviroc Conferred by a CD4 Binding Site Mutation in the Envelope Glycoprotein gp120 https://jvi.asm.org/content/87/2/923#sec-12 23

Orgovyx: $4.2 billion partnering with myovant science. Prostate cancer treatment

Effectiveness: Orgovyx achieved and maintained low enough levels of testosterone (castrate levels), by day 29 through the end of the treatment course. In the 622 patients who received Orgovyx, the castration rate was 96.7%. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-hormone-therap y-treating-advanced-prostate-cancer

Side effects: Serious life threatening https://www.erleada.com/about-erleada/side-effec

3. Roche: $49.23 billion / Genentech bought by roche for $47 billion in 2009.

Avastin: 7 billion chemotherapy and targeting therapy. Used to treat colorectal, lung, glioblastoma, kidney, cervical, and ovarian cancer.

Effectiveness: When combined with standard chemotherapy, Avastin extended the survival of patients with advanced cervical cancer by nearly four months, doctors reported in one trial. However, two other trials found the drug proved of little use in treating newly diagnosed glioblastoma brain tumors.

Side effects: Severe life threatening https://www.avastin.com/patient/mcrc/treatment/possible-side-effects.html

Herceptin: $6.08 billion in sales 2019. A Chemotherapy that can treat breast, stomach, and esophageal cancer.

Effectiveness: Patients treated with Herceptin had a 46% reduced risk of death, a cancer recurrence, cancer in the other breast, or cancer other than breast cancer. At two years, cancer-free survival was improved by 8.4% overall in the patients treated with Herceptin https://www.webmd.com/cancer/cervical-cancer/news/20140219/avastin-shows-mixed-results-a gainst-different-cancers#:~:text=When%20combined%20with%20standard%20chemotherapy,n ewly%20diagnosed%20glioblastoma%20brain%20tumors.

Side effects: Serious life threatening https://www.enhertu.com/en/risks-and-side-effects/?utm_source=google&utm_medium=cpc&ut m_campaign=branded+competitor_2020%3bs%3bph%3bbr%3bonc%3bdtc%3bcom&utm_cont 24

ent=branded+competitors_2020_exact&utm_term=herceptin&gclid=cj0kcqjwpdqdbhcsarisaeuj0 homyzzzf-b8jigs6vb5wmrois9ipb3dmvq76ykschhyfoqga83tpruaaq-dealw_wcb&gclsrc=aw.ds

Rituxan: $6.54 billion in 2019 but due to biosimilars sales are projected to fall. A Monoclonal antibody targets CD20. used to treat certain autoimmune diseases and types of cancer.

Effectiveness: rituximab or rituximab with chemotherapy is often used (56). Unlike reported for DLBCL and FL, rituximab combined with chemotherapy has not yet been demonstrated to improve survival, while rituximab monotherapy is reported to achieve a 69% 7-year PFS (56) https://www.frontiersin.org/articles/10.3389/fonc.2018.00163/full

Side effects: Serious life threatening https://www.ruxience.com/taking-ruxience?gclid=Cj0KCQjwse-DBhC7ARIsAI8YcWJuHTF4st9H UXQTlb5mK13ovzceUOGR-dPGza-RP7IHyizjoQ3L_tYaAvh5EALw_wcB&gclsrc=aw.ds

Side effects: Serious https://www.perjeta.com/?c=per-16e8fec5ef8&gclid=Cj0KCQjwse-DBhC7ARIsAI8YcWLFxNqAG _n2TnEvS7VX0GuEw3l8nDWaKNU8vErPYW1i-RT5W6RBQg0aArgJEALw_wcB&gclsrc=aw.ds

Genentech:

Pertuzumab: $2.8 billion a year-a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2- positive breast cancer.

Effectiveness: The results indicated that patients who received the addition of Perjeta to Herceptin/docetaxel lived longer without their cancer getting worse. The initial report demonstrated a median progression-free survival in the Perjeta group of 18.5 months compared to 12.4 months in the placebo group .

Side effects: Serious https://www.perjeta.com/patient/safety.html?c=per-16e8fec5ef8&gclid=Cj0KCQjwgtWDBhDZARI sADEKwgM85ZBypGevSwzED04NX5Nuot-TWoaqnz1duYieajbr-53KTKQMDJsaAkb4EALw_wc B&gclsrc=aw.ds

Trastuzumab emtansine: $1.0 billion yearly used to treat breast cancer is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the cytotoxic agent DM1. 25

Effectiveness: Trastuzumab after Chemotherapy Is Effective in HER2-Positive Breast Cancer. Treatment with trastuzumab (Herceptin®) for 1 year following standard chemotherapy improved disease-free survival in women with HER2-positive early breast cancer https://www.cancer.gov/types/breast/research/trastuzumab-after-chemo

Side effects: Serious life threatening https://www.kadcyla.com/

Atezolizumab: $800 million yearly. A monoclonal antibody medication used to treat, non-small cell lung cancer, triple negative breast cancer, small cell lung cancer. targets the PD-1/PD-L1 pathway (proteins found on the body’s immune cells and some cancer cells). By blocking these interactions, Tecentriq may help the body’s immune system fight cancer cells by reactivating the T-cells.

Effectiveness: (Small lung cancer) Median overall survival for those who took the Tecentriq combination was 12.3 months, compared to 10.3 months among those who took the chemotherapy drugs and a placebo. https://www.drugs.com/medical-answers/effective-atezolizumab-tecentriq-3552927/

Side effects: severe life threatening https://www.gene.com/patients/medicines/tecentriq

Kadcyla: $1 billion in 2019. Is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab covalently linked to the cytotoxic agent DM1.The drug works by inhibiting HER2 receptor signalling.

Effectiveness: Overall 77% of patients who received Herceptin compared to 88.3% of patients who received Kadcyla were alive without evidence of cancer progression 3 years from treatment. This represents an absolute increased improvement of 11% for patients treated with kadcyla. https://news.cancerconnect.com/breast-cancer/kadcyla-t-dm1-significantly-improves-treatment-o f-her-2-breast-cancers-7Vqhw73EB0ukbC5NazRjOA#:~:text=Overall%2077%25%20of%20patie nts%20who,for%20patients%20treated%20with%20Kadcyla.

Side effects: BLACK BOX WARNING https://www.gene.com/patients/medicines/kadcyla

Tecentriq: $800 million in 2019. A monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer, triple-negative breast cancer, small cell lung cancer, and hepatocellular carcinoma. 26

Effectiveness: https://www.drugs.com/medical-answers/effective-atezolizumab-tecentriq-3552927/#:~:text=Tec entriq%20effectiveness%20for%20small%20cell%20lung%20cancer&text=Median%20overall% 20survival%20for%20those,chemotherapy%20drugs%20and%20a%20placebo.

Side effects: Severe life threatening. https://www.gene.com/patients/medicines/tecentriq

Perjeta: $2.8 billion in 2019. A monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it is also used in the same combination as a neoadjuvant in early HER2-positive breast cancer.

Effectiveness: The disease-free survival rate was higher than expected in both groups: 94.1% of the women in the Perjeta treatment group were alive with no cancer recurrence. 93.2% of the women in the standard treatment group were alive with no cancer recurrence. https://www.breastcancer.org/research-news/herceptin-w-perjeta-better-than-alone-for-some#:~: text=The%20disease%2Dfree%20survival%20rate,alive%20with%20no%20cancer%20recurren ce

4.Novartis: $47.45 Billion

Gleevec: $4.7 billion before US patent expiration in 2016. A tyrosine kinase inhibitor Is used to treat certain types of cancer (such as acute lymphoblastic leukemia, chronic myeloid leukemia, gastrointestinal stromal tumors, and myelodysplastic/myeloproliferative diseases). It works by slowing or stopping the growth of cancer cells.

Effectiveness: In a seven-year clinical study, the survival rate for adults who took Gleevec for newly diagnosed Ph+ CML was 86.4%. This means that 86.4% of the adults survived for seven years after they started taking Gleevec. This was compared to 83.3% of people who took standard chemotherapy drugs. https://www.medicalnewstoday.com/articles/gleevec

Side effects: Serious https://www.medicalnewstoday.com/articles/gleevec

Afinitor: $1.5 billion yearly since its approval. A chemotherapy It can treat cancer of the kidney, pancreas, breast, and brain. It can also be used along with other medications to prevent rejection of a transplanted kidney or liver. 27

Effectiveness: In the randomized, advanced, hormone receptor-positive, HER2-negative breast cancer study, the incidence of deaths due to any cause within 28 days of the last AFINITOR dose was 6% in patients ≥65 years of age compared with 2% in patients <65 years of age. Novartis's Afinitor (everolimus), deters cancer growth but doesn't shrink tumors, and it prolongs patient survival only a few months. https://www.hcp.novartis.com/products/afinitor/metastatic-breast-cancer/efficacy/#:~:text=In%20t he%20randomized%2C%20advanced%2C%20hormone,patients%20%3C65%20years%20of% 20age.

Side effects: Serious https://www.hcp.novartis.com/products/afinitor/?site=AFE-1224238GK100003&utm_source=goo gle&utm_medium=cpc&utm_campaign=2020_afinitor_gateway_hcp_branded_home_phrase%3 Bs%3Bph%3Bbr%3Bonc%3Bhcp%3Bbr&utm_content=afe-1224238&utm_term=afinitor&omap_ code=AFE-1224238&gclid=Cj0KCQjw1PSDBhDbARIsAPeTqrdbkKJY5_Ehj-Ev-RXxlJnlVi1vZG NkmL1QXykFUDtVh2bcDsRP93saAqSOEALw_wcB&gclsrc=aw.ds#important-safety-info Gilenya: $3 billion 2020. Immunosuppressive drug. It can treat flare-ups of multiple sclerosis (MS)

Effectiveness: Gilenya is a more effective (category 1.2) DMD; in clinical trials people taking Gilenya had about 50% fewer relapses than people taking placebo. In clinical trials, MRI scans showed that people taking Gilenya had fewer, smaller or no new areas of active MS (lesions). https://mstrust.org.uk/a-z/gilenya-fingolimod#:~:text=Gilenya%20is%20a%20more%20effective, of%20active%20MS%20(lesions).

Side effects: Serious https://mstrust.org.uk/a-z/gilenya-fingolimod#:~:text=Gilenya%20is%20a%20more%20effective, of%20active%20MS%20(lesions).

Novartis has acquired GlaxoSmithKline’s (GSK) oncology products and certain related assets. The company has also been granted rights of first negotiation over the co-development or commercialization of GSK’s current and future oncology research and development pipeline, excluding the oncology vaccines.

5. Merck: $46.84 billion by far Mercks biggest product and the biggest cancer drug in the world.

11% year on year increase in revenue international sales led by china grew 47% and there blockbuster cancer drug KEYTRUDA: grew 55% 28

Keytruda: $14.1 billion in 2020. A humanized monoclonal antibody used in cancer immunotherapy. This includes treating melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, and stomach cancer. It is given by slow injection into a vein. https://www.youtube.com/watch?v=R0ccmAXq4RU&ab_channel=LighterSideofCancer

Effectiveness:The average overall survival duration among Keytruda treated patients is now 26.3 months compared to 14.2 months for those treated with chemotherapy. The 36-month overall survival is 43.7% for Keytruda compared to 24.9% for chemotherapy. https://news.cancerconnect.com/lung-cancer/keytruda-doubles-survival-compared-to-chemother apy-treatment-of-nsclc-gTmT5kobzkeSTjd4_iwDQw#:~:text=The%20average%20overall%20sur vival%20duration,compared%20to%2024.9%25%20for%20chemotherapy.

In the clinical trial, half the patients treated with KEYTRUDA were alive without their cancer spreading, growing, or getting worse at 7.1 months compared to 6.4 months for patients treated with chemotherapy. https://www.keytruda.com/non-small-cell-lung-cancer/monotherapy-clinical-trial-results/#:~:text=I n%20the%20clinical%20trial%2C%20half,for%20patients%20treated%20with%20chemotherapy .

Side effects: Serious Life threatening. https://www.fda.gov/media/89934/download

Below is a list of clinical trials merck is conducting. Most of the trials include keytruda. Merck is betting big on this 1 drug for many cancer indications. https://merckoncologyclinicaltrials.com/en-us/patient?utm_source=google&utm_medium=cpc&ut m_term=keytruda%20drug&utm_campaign=Google_14-MK-005-0026_Keynote-Programmatic_ General&utm_content=ad4&gclid=Cj0KCQjw9_mDBhCGARIsAN3PaFM1l7332YLOOwoQ1N_8 59gRvvh9NyJSUZ3pv8HlIR-FNotJJm02g1caAvMREALw_wcB

Isentress: $1.4 billion in 2017. Hiv treatment used with other antiretrovirals. by interfering with an enzyme needed by HIV called integrase. Using Isentress greatly reduces HIV's ability to infect cells and make copies of itself.

Effectiveness: https://www.isentress.com/what-is-isentress/?src=google&med=cpc&camp=Isentress_Isentress _BRND_NA_ENGM_BMM_TEXT_MULTI&adgrp=Isentress+General&kw=%2Bisentress&gclid= CjwKCAjwmv-DBhAMEiwA7xYrd8ULWy8hTJ0ZJYtjEocTuOwEE97ew4Kc3ftsDv-SRmofM8Aw5 kU91RoCwYMQAvD_BwE&gclsrc=aw.ds

Side effects: Serious Life threatening. https://www.isentress.com/side-effects/ 29

6. GlaxoSmithKline: $44.27 billion

In 2019 GSK acquired Tesaro an oncology company for 5.1 billion with one approved indication for ovarian cancer the drug is called zejula and it's currently being investigated for lung, breast and prostate cancer.

Side effects: Serious Life threatening. https://www.zejula.com/en/why-zejula/side-effects-and-safety

Cabenuva injection: approved 2021 a long-acting, complete HIV regimen you get once every month. Before you start you have to take about a month of “once daily starter pills” you have to schedule a once a month appointment to have your injection given by a trained professional. Its called a “target treatment date” you have to meet that date each month to stay “undetectable'' flexible treatment window from 7 days before to 7 days after your target treatment date. The Cabenuva injection contains two active ingredients cabotegravir and Janssen’s rilpivirine and has previously proven as effective as standard daily pills that have three active ingredients, when given monthly. The FDA declined to approve the injection in 2019 because of questionable manufacturing. https://www.reuters.com/article/us-gsk-viiv-fda/u-s-fda-approves-gsk-units-long-acting-hiv-injecti on-idUSKBN29Q31M

Effectiveness: In another study published in The Lancet, researchers found that, after 48 weeks, Cabenuva injectable treatment was equally effective (“noninferior”) at keeping a person's viral load undetectable when administered every eight weeks as it was every four weeks. https://www.thebody.com/health/hiv-cabenuva

Side effects: Serious https://www.cabenuva.com/about/what-is-cabenuva/?gclid=Cj0KCQjw9_mDBhCGARIsAN3PaF O6K9Rmvf7PmHFz1yimWO0UwecRs_n_TpQ1bOjVdIY0CSvOW3eSl84aAgEWEALw_wcB&gcl src=aw.ds

Dovato and Juluca: $869 million in 2020. It is to treat HIV among those new to antiretroviral (ARV) therapy whose virus does not have mutations associated with either of the drugs in the combination tablet. Dovato and Juluca are based on the integrase inhibitor dolutegravir (sold separately as Tivicay). The lamivudine component of Dovato belongs to the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) class of ARVs while the rilpivirine component of Juluca is a non-nucleoside reverse transcriptase inhibitor.

Effectiveness: suppressed HIV as effectively as a three drug regimen. https://www.poz.com/article/viivs-2drug-regimen-par-3drug-combo 30

Side effects: Serious https://www.dovato.com/dovato-side-effects/

Triumeq: $2.3 billion. is a complete HIV treatment—taken once daily, with or without food, day or night—and is widely used. Clinical trials have found it to be highly effective and generally well tolerated, though some users have reported difficulty falling asleep and/or staying asleep.

Effectiveness: https://us.triumeq.com/index/

Side effects: Serious https://us.triumeq.com/risks-and-side-effects-of-triumeq/

Tivicay: $1.5 billion in 2020. is an antiretroviral medication used, together with other medication, to treat HIV/AIDS https://www.firstwordpharma.com/node/1719681

Effectiveness: Nineteen months after starting Tivicay, 89 percent (79) of the cohort members were still on the drug; all of them had a fully suppressed viral load. Ten people stopped taking the drug a median three months after starting. Half (5) of those who stopped taking Tivicay had a fully suppressed viral load at the time.

Side effects : Serious https://us.tivicay.com/risks-and-side-effects/#

Oncology programs are small but glaxio is investing a lot of money into expanding that field. Article below describes there pipeline and vision: https://xconomy.com/national/2020/06/12/glaxosmithkline-keeps-oncology-2-0-growth-plans-on-t rack/

7. Sanofi: $40.46 billion

Jevtana: $582 million in 2019 Chemotherapy It can treat prostate cancer.

Effectiveness: JEVTANA was shown to be effective in a clinical study with 755 men who: Had prostate cancer that spread to other parts of the body. Were no longer responding to medical or surgical treatment to lower testosterone. Had previously been treated with a chemotherapy called docetaxel. 15.1 months with jevtana vs. 12.7 months with mitoxantrone https://www.jevtana.com/study-results#:~:text=JEVTANA%20was%20shown%20to%20be,with %20a%20chemotherapy%20called%20docetaxel

Side effects: Serious Life threatening 31

https://www.jevtana.com/study-results#:~:text=JEVTANA%20was%20shown%20to%20be,with %20a%20chemotherapy%20called%20docetaxel

Taxotere: $3 billion in 2017. Chemotherapy It can treat breast, lung, prostate, stomach, and head and neck cancer. Classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."

Effectiveness: https://news.cancerconnect.com/breast-cancer/taxotere-effective-in-early-breast-cancer-i_e4X8 Qvu0Cb-h4_LgVSGg#:~:text=Five%2Dyear%20cancer%2Dfree%20survival,among%20women %20treated%20with%20AC. a meta-analysis performed on seven clinical trials in patients with advanced non-small cell lung cancer showed that patients receiving Taxotere(R) (docetaxel) Injection Concentrate had demonstrated overall survival and less febrile neutropenia than those treated with vinca-alkaloid (vinorelbine or vindesine) regimens. The trials used Taxotere(R) and vinca-alkaloids alone or in combination as first-line therapy for advanced non-small cell lung cancer. http://www.news.sanofi.us/press-releases?item=118396

Side effects: Severe life threatening https://www.drugwatch.com/taxotere/side-effects/

Sarclisa: $43 million in 2020. A monoclonal antibody that binds to the CD38 receptor on multiple myeloma cells. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells.

Effectiveness: Sarclisa in combination with pomalidomide and dexamethasone (pom-dex) significantly reduced the risk of disease progression or death by 40% compared to pom-dex alone in a pivotal trial. http://www.news.sanofi.us/2020-03-02-FDA-approves-Sarclisa-R-isatuximab-irfc-for-patients-wit h-relapsed-refractory-multiple-myeloma

Side effects: Serious https://www.sarclisa.com/possible-side-effects

8. Abbvie: $32.26 billion

Humira: $19.83 billion in 2020. A monoclonal antibody It can treat arthritis, plaque psoriasis, ankylosing spondylitis, Crohn's disease, and ulcerative colitis. 32

Effectiveness: Humira is FDA-approved to treat moderate to severe rheumatoid arthritis that’s active in adults. “Active” means that you have symptoms. The goal of Humira is to significantly ease signs and symptoms of RA and help limit joint damage and improve mobility.

Side effects: Serious life threatening. https://www.humira.com/global/safety-side-effects

Humira is responsible for 58% of abbvies revenue in 2019

Lupron: $750 million in 2019. Hormone Associated Therapy and Sex hormone suppression It can treat endometriosis, uterine fibroids, and premature puberty. It can also treat prostate cancer.

Effectiveness: Lupron is not a cure for prostate cancer. Rather, it works to slow down the growth and spread of the cancer. https://www.healthline.com/health/prostate-cancer/lupron-for-prostate-cancer#side-effects

Side effects: Serious https://www.webmd.com/drugs/2/drug-6888/lupron-subcutaneous/details

9. Takeda: $30.52 billion

Ninlaro: $721 million in 2019. Is a second-generation proteasome inhibitor in the same class of drugs as Velcade. an oral targeted therapy anticancer drug that is used in combination with lenalidomide (Revlimid) and dexamethasone to treat multiple myeloma.

Effectiveness: Ninlaro group had a 78% positive response rate compared to 72% for the placebo group. https://www.drugs.com/medical-answers/effective-ninlaro-ixazomib-3537220/

Safety: Serious https://www.ninlarohcp.com/discontinuation-rates

Cometriq: $226.9 million in 2020. A medication used to treat medullary thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma. It is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, and also inhibits AXL and RET.

Effectiveness: significantly prolonged PFS vs placebo (p<0.0001) Placebo 4 months cometriq 11.2 months. https://www.cometriq.com/hcp/clinical/progression-free 33

Side effects : Severe life threatening https://www.cometriq.com/hcp/clinical/safety-profile

10. Shanghai pharmaceuticals: 26.69 billion

11. Bayer: $26.59 billion

Stivarga: $116 million in 2020. is an oral multikinase inhibitor used to treat cancer of the colon and rectum. It is also used to treat liver cancer and a certain cancer of the digestive system (gastrointestinal stromal tumor). It works by slowing or stopping the growth of cancer cells.

Effectiveness: Stivarga prolonged life and delayed tumor growth. Patients in the Stivarga group lived a median of 6.4 months, compared to 5 months for patients in the placebo group. Patients in the Stivarga group also experienced a delay in cancer growth compared to placebo. https://news.cancerconnect.com/colon-cancer/stivarga-treatment-for-metastatic-colorectal-canc er-A9hyH-Kk0kSMKux1LbgwjA#:~:text=The%20results%20indicated%20that%20Stivarga,canc er%20growth%20compared%20to%20placebo.

Side effects: Serious life threatening https://www.stivarga-us.com/understanding-side-effects/

Nexavar:$706 million in 2019. Chemotherapy It can treat kidney, liver, and thyroid cancer.

Effectiveness: NEXAVAR will not cure your cancer, but it has been shown to slow or temporarily stop the growth or spread of certain cancer cells. This is called stable disease. https://www.nexavar-us.com/understanding-nexavar/?p=liver/

Side effects : Serious life threatening. https://www.nexavar-us.com/understanding-nexavar/?p=liver/

12. Bristol Myers Squibb: $26.15 billion

Orencia: $3 billion in 2019. A immunomodulator used to treat autoimmune diseases like rheumatoid arthritis, by interfering with the immune activity of T cells. It is a modified antibody 34

Effectiveness: Of those taking Orencia, 62% of people had at least a 20% reduction in their RA symptoms after 3 months of treatment. Of those taking a placebo (treatment with no active drug) with methotrexate, 37% had the same result https://www.medicalnewstoday.com/articles/326618#:~:text=Effectiveness%20for%20rheumatoi d%20arthritis&text=Of%20those%20taking%20Orencia%2C%2062,37%25%20had%20the%20 same%20result.

Side effects: Serious life threatening https://www.orencia.com/?cid=sem_692732&gclid=Cj0KCQjw9_mDBhCGARIsAN3PaFNEIPcx9 JuZPm4ysB3qgDIu9hMUYf9SLLx7Ez9px5qtHQgfhdM1aEAaAt-iEALw_wcB&gclsrc=aw.ds

Revlimid: $9.3 billion in 2019. Chemotherapy It can treat myelodysplastic syndrome (MDS), multiple myeloma, and mantle cell lymphoma (MCL)

Effectiveness: Results showed that patients receiving Revlimid lived 39 months without their disease worsening, compared with 20 months for the observation arm. This translated into a 54% reduction in the risk of disease progression or death https://myelomaresearchnews.com/2019/01/18/revlimid-maintenance-delays-myeloma-progressi on-death/#:~:text=Results%20showed%20that%20patients%20receiving,of%20disease%20pro gression%20or%20death. https://www.revlimid.com/about-revlimid

Side effects : Serious life threatening https://www.revlimid.com/serious-side-effects

13. AstraZeneca: $23.57 billion

Tagrisso: $4.3 billion in 2020. is a tyrosine kinase inhibitor, which acts by blocking the activity of the epidermal growth factor receptor (EGFR). Used to treat non-small-cell lung carcinomas with specific mutations. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor.

Effectiveness: Tagrisso improved overall survival duration compared to Tarceva and Iressa. Median overall survival was 38.6 months compared to 31.8 months with first generation EGFR-TKIs. More than half (54%) of Tagrisso treated patients were alive at three years compared to 44% for Tarceva or Iressa https://news.cancerconnect.com/lung-cancer/tagrisso-standard-of-care-for-egfr-non-small-cell-lu ng-cancer-SqpYQoN28UGjQT-qHHTdaQ#:~:text=Tagrisso%20improved%20overall%20survival %20duration,44%25%20for%20Tarceva%20or%20Iressa. 35

Side effects: Serious life threatening https://www.tagrisso.com/after-surgery/about-tagrisso/safety.html

Imfinzi: $2.04 billion in 2020. A human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 with the PD-1. Durvalumab is known as a checkpoint inhibitor drug.

Effectiveness: Imfinzi demonstrated unprecedented survival in unresectable, Stage III non-small cell lung cancer with an estimated 50% of patients surviving four years. https://www.astrazeneca.com/media-centre/press-releases/2020/imfinzi-demonstrated-unpreced ented-survival-in-unresectable-stage-III-nsclc.html

Side effects: Serious life threatening https://www.imfinzihcp.com/non-small-cell-lung-cancer/stage-3/durvalumab-nsclc-side-effects.ht ml?source=imz_n_h_9&umedium=cpc&uadpub=google&ucampaign=2019imfinzihcpnsclcbrand ed_safety_hcp&ucreative=branded_safety_ex&uplace=imfinzisafety&outcome=hcp&cmpid=1&g clid=CjwKCAjwmv-DBhAMEiwA7xYrd6s1pGfxne5B15eHH2UulBGrX8VF7XCasNUhCvOdJjVab 9lRBXfZjxoCEdwQAvD_BwE&gclsrc=aw.ds#isi

Casodex: $13.4 billion in 2018. Hormone Associated Therapy and Hormone based chemotherapy It can treat prostate cancer when used along with other medications.

Effectiveness: Bicalutamide along with the luteinizing hormone-releasing hormone may help stop the growth and spread of cancer cells but does not cure prostate cancer.After 160 weeks, 47.3% of the men who took Casodex were still alive, compared with 42.5% of the men who took flutamide.

Side effects: Serious https://www.medicalnewstoday.com/articles/326940#uses

Enhertu: $336 billion in 2020. Can be used to treat people diagnosed with metastatic HER2-positive breast cancer that has been previously treated with at least two anti-HER2 medicines. Enhertu also can be used to treat HER2-positive breast cancer that can't be removed with surgery. The IHC test uses a chemical dye to stain the HER2 proteins.

Effectiveness: One clinical study involved women with HER2+ breast cancer that couldn’t be surgically removed or was metastatic. All of the women with metastatic breast cancer had received two or more previous HER2 treatments. 4.3% of women taking Enhertu had a complete response to the drug. (A complete response is when tests show no more cancer in your blood.)56% of women taking Enhertu had a partial response to the drug. (A partial 36

response means the amount of cancer in your body has decreased.)For at least half of the women taking Enhertu, their response to the drug lasted 14.8 months or more before their cancer got worse.Enhertu wasn’t compared with any other drugs or a placebo in this study. https://www.medicalnewstoday.com/articles/enhertu#uses

Side effects: Serious life threatening https://www.enhertu.com/en/risks-and-side-effects/?utm_source=google&utm_medium=cpc&ut m_campaign=branded+side+effects_2020%3bs%3bph%3bbr%3bonc%3bdtc%3bbr&utm_conte nt=side+effects_2020_exact&utm_term=enhertu+side+effects&gclid=cjwkcajwmv-dbhameiwa7x yrd-bclsinwfcf8uluymihvlqst3wfblc_pavc7pzqy0fqkq8d5g5kehocn4wqavd_bwe&gclsrc=aw.ds

Lynparza: $1.2 billion in 2020. is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase, an enzyme involved in DNA repair.

Effectiveness: Overall Lynparza treatment was well tolerated and 72% of Lynparza treated patients responded to treatment compared to 51% of those receiving chemotherapy. The time until cancer progression was 13.4 months with Lynparza compared to 9.2 months with chemotherapy. https://news.cancerconnect.com/ovarian-cancer/lynparza-delays-progression-significantly-prolo ngs-survival-in-ovarian-cancer-JvlGAtB8ZEuJiyVQWcfu0w#:~:text=Overall%20Lynparza%20tre atment%20was%20well,to%209.2%20months%20with%20chemotherapy.

Side effects: Serious https://www.lynparza.com/side-effects.html#:~:text=IMPORTANT%20SAFETY%20INFORMATI ON,-MDS%20or%20AML&text=If%20you%20develop%20MDS%20or%20AML%2C%20your%2 0healthcare%20provider%20will,fever%2C%20cough%2C%20or%20wheezing.

14. Amgen: $23.36 billion

Kanjinti: bio similar to Herceptin.

Kyprolis: $654 million in 2019. A type of chemotherapy drug and a second-generation proteasome inhibitor. Kyprolis is used to treat multiple myeloma, which is a type of hematological malignancy, or blood cancer, that affects plasma cells

Effectiveness: Results from an early study in newly diagnosed patients suggest that the combination of Kyprolis, Revlimid, and low-dose dexamethasone is highly effective, with 98% of patients responding to treatment and 42% achieving a stringent complete response 37

Side effects: Serious https://www.kyprolis-hcp.com/dkd-safety/

15. Gilead Sciences: $22.45 billion ( nearly 70% was derived from its HIV division.)

Biktarvy: $7.3 billion in 2020. is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains 50 mg bictegravir, 200 mg emtricitabine, and 25 mg tenofovir alafenamide. One pill a day.

Effectiveness: The three-year results from both Biktarvy studies provide further evidence that it is potent and effective, enabling people living with HIV to maintain an undetectable viral load over the long term. https://www.gilead.com/news-and-press/press-room/press-releases/2019/11/gileads-biktarvy-ma intained-high-efficacy-with-no-cases-of-treatment-emergent-resistance-through-three-years-in-p hase-3-hiv-clinical-trials#:~:text=%E2%80%9CThe%20three%2Dyear%20results%20from,load %20over%20the%20long%20term.%E2%80%9D

Side effects: BLACKBOX WARNING. https://www.biktarvyhcp.com/important-safety-information?utm_source=google&utm_medium=c pc&utm_campaign=USA_GO_SEM_B_EX_Biktarvy-HCP-Branded-Standard&utm_content=Saf ety+Information&utm_term=Biktarvy+safety&gclid=CjwKCAjwmv-DBhAMEiwA7xYrd8n-PDbzhJ abym7j4lnnRm_JQXUel9vLevR58QlR_d_PEoFZXEzIQBoCvqMQAvD_BwE&gclsrc=aw.ds

Atripla: $501 million in 2019. 3 medicines in 1 pill. It is a combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate. It can treat HIV, the infection that causes AIDS. It doesn't cure HIV or AIDS, but combinations of drugs that treat HIV infection may slow the disease progress and prolong life.

Effectiveness: The study showed that switching to Atripla was as effective as remaining on the previous treatment combination. After 48 weeks, 89% of the patients taking Atripla (181 out of 203) and 88% of those remaining on previous treatment (85 out of 97) had viral loads below 200 copies/ml. https://www.ema.europa.eu/en/documents/overview/atripla-epar-medicine-overview_en.pdf

Side effects: BLACKBOX WARNING. https://www.gilead.com/-/media/files/pdfs/medicines/hiv/atripla/atripla_patient_pi.pdf?la=en

Complera: A fixed-dose co-formulation of three anti-HIV drugs: tenofovir, FTC and rilpivirine. Complera can be used by itself as combination therapy for people with HIV who have not taken anti-HIV drugs in the past and who have HIV that is not resistant to any of the drugs in Complera 38

Effectiveness: https://www.rxlist.com/complera-drug.htm#indications

Side effects : BLACKBOX WARNING. https://www.rxlist.com/complera-drug.htm#indications

Truvada: $718 million in 2020. used to treat human immunodeficiency virus (HIV) and hepatitis B virus infection. Truvada is now being used to prevent HIV infection. When you take Truvada to prevent HIV infection, doctors refer to this use as “pre-exposure prophylaxis” or “PrEP”.

Effectiveness: Truvada for PrEP provides 92%-99% reduction in HIV risk for HIV-negative individuals who take the pills every day as directed. If a daily dose is missed, the level of HIV protection may decrease. It only works if you take it. People who use PrEP correctly and consistently have higher levels of protection against HIV. https://prepfacts.org/prep/the-basics/

Side effects : BLACKBOX WARNING. https://www.truvada.com/truvada-safety/important-safety-information

Descovy: first half of 2020 year over year sales $700 million. The selling point it’s safety profile is better than truvada. new PREP. Is Descovy or Truvada better? Descovy and Truvada are both effective drugs for HIV treatment and PrEP. Descovy does not impair kidney function or decrease bone density as much as Truvada. However, Truvada is an older drug with more data to support its use in some cases.

Side effects : BLACKBOX WARNING. https://www.descovy.com/hcp/safety-tolerability/warnings-precautions#:~:text=Important%20Saf ety%20Information,-BOXED%20WARNING%3A%20POST&text=Do%20not%20initiate%20DES COVY%20in,of%20renal%2Drelated%20adverse%20reactions.

Genvoya: $3.98 billion in 2019. 4 treatments in 1 pill. elvitegravir 150 mg/cobicistat 150 mg/ emtricitabine 200 mg/tenofovir alafenamide 10 mg

Effectiveness: https://www.medicalnewstoday.com/articles/genvoya#:~:text=Genvoya%20has%20been%20sho wn%20to,after%2048%20weeks%20of%20treatment.

Side effects : BLACKBOX WARNING. https://www.gilead.com/-/media/files/pdfs/medicines/hiv/genvoya/genvoya_pi.pdf 39

Odefsey: $1.67 billion in 2020. Used to treat patients who have not received HIV-1 medicines in the past and who have an amount of HIV-1 in their blood (this is called “viral load”) that is no more than 100,000 copies/mL

Effectiveness: https://www.healio.com/news/infectious-disease/20160302/fda-approves-odefsey-for-treatment- of-hiv

Side effects : BLACKBOX WARNING. https://www.gilead.com/-/media/0b3fb330330e40c89d759a19a48894e9.ashx

Veklury: (Remdesivir) $2.8 billion in 2020. acts to inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which is essential for viral replication—and thus creation of virions that circulate in the body.

Effectiveness: This is a very controversial medication. There have been many studies showing its non efficacy in Covid19 considering the subjective primary end-point and showing the drug is not dropping viral load. I leave this up to the reader to investigate but it is considered SOC.

Safety: Serious https://www.veklury.com/important-safety-information/

Trodelvy: $49 million in 2020. is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate used for the treatment of metastatic triple-negative breast cancer and metastatic urothelial cancer.

Effectiveness: In addition to producing an overall response rate of 34% another 11% of patients had stable disease (SD) for 6 months or more resulting in an overall disease control rate of 45% Average overall survival was 12.7 months. https://news.cancerconnect.com/triple-negative-breast-cancer/trodelvy-sacituzumab-govetecan-t reatment-for-triple-negative-breast-cancer-eTmDeLEQg0CiRHzLsosLPQ#:~:text=In%20addition %20to%20producing%20an,%2C%20anemia%2C%20fatigue%20and%20vomiting.

Side effects: Severe life threatening https://www.trodelvyhcp.com/hcp/mTNBC/safety?gclid=CjwKCAjwmv-DBhAMEiwA7xYrd0j8tVo0 vaSD0H0UjSPyexD_UU6UqziieZldLB3RV2piJBG-nLzeYhoCO_8QAvD_BwE&gclsrc=aw.ds 40 41