CytoDyn Stock: Moving Leronlimab Forward On All Fronts (CYDY)

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CytoDyn (OTCQB:CYDY) recently publicized encouraging results from their Part 2 open-label portion of the Phase II NASH clinical trial testing 350 mg weekly dose of Leronlimab, demonstrated an average 80 msec cT1 decrease in half of the patients and a reduction of roughly 50 msec in 80% of patients. According to CytoDyn, these marks hit their endpoints and are statistically significant. These results are just one of several positive updates coming from the company over the past couple of months. CytoDyn is walking into 2022 with numerous prospects in play including HIV programs, metastatic triple-negative breast cancer “mTNBC”, COVID-19 programs, and nonalcoholic steatohepatitis “NASH”. I believe Leronlimab is making a case to be a unique product that can be safely employed in some of the worst chronic and acute diseases and conditions. As a result, I am still bullish on CYDY in both the near term and long term.

I intend to review the company’s recent developments and will discuss why I believe these developments verify Leronlimab’s potential to be an essential therapeutic that has a universal application.

Background on Leronlimab

Leronlimab is a humanized IgG4 mAb that attaches to the CCR5 receptor, which is important in HIV infection, tumor metastases, NASH, and numerous other diseases or conditions. Thus far, Leronlimab has been tested in 16 clinical trials with more than 1,200 patients in several different indications.

Leronlimab achieved its primary endpoints in a pivotal trial for combination therapy with HAART for HIV in patients with multi-drug resistance. For HIV, Leronlimab works as a viral-entry inhibitor by binding to CCR5, as a result, guarding healthy T cells against infection of the HIV “R5” subtype. Leronlimab was able to demonstrate the ability to meaningfully reduce or control HIV viral load in five clinical trials. It is important to note that Leronlimab displayed fewer side effects and less frequent dosing than contemporary HIV therapies. The FDA granted Leronlimab Fast Track designation for combination therapy with HAART for HIV

For cancer, CCR5 is theorized to have a critical part in tumor invasion, metastases, and tumor microenvironment control. By blocking CCR5, Leronlimab could moderate tumor metastases. In mTNBC, Leronlimab eliminated breast cancer metastasis by more than 97% in a murine xenograft model. Accordingly, CytoDyn is running Leronlimab in a Phase II study in mTNBC, and a basket trial of 22 different solid tumor cancers. The FDA granted Leronlimab Fast Track designation for mTNBC.

In infectious diseases, the CCR5 receptor helps modulate immune cell movement to spots of inflammation in the body. This has made Leronlimab a candidate for the treatment of various stages of COVID-19. So far, Leronlimab has completed two clinical trials including a mild-to-moderate trial and severe-to-critical trial. These studies did not meet their primary or secondary endpoints except for the secondary endpoint in the critically ill subpopulation. As a result, the company moved beyond the U.S. and is now running a trial in Brazil with an improved trial structure. In addition, Leronlimab is being tested in a Phase II investigative trial for COVID-19 Long-Haulers. Furthermore, the company has submitted a protocol for Phase III registrational trial for the critically-ill population with the U.S. FDA. Beyond COVID, CytoDyn is planning to evaluate Leronlimab’s effect on myalgic encephalomyelitis/chronic fatigue syndrome, which is found in other viral infections.

CytoDyn is also pushing Leronlimab forward in NASH and its effect on liver steatosis and fibrosis. Pre-clinical studies revealed Leronlimab’s potential to reduce liver fat deposits and reduce liver fibrosis. At this point in time, there are no FDA-approved treatments for NASH, which is found in 3-12% of adults in the United States.

CytoDyn is also looking to pit Leronlimab against neurodegenerative diseases and autoimmune diseases. In total, the company has taken Leronlimab from 1 indication to 32 indications in seven years that total over $100B in market opportunity.

It is important to note that Leronlimab has no strong safety signals recognized in several disease continuums, counting HIV, COVID-19, and oncology. At this point in time, I can’t find another drug that has such broad applications with the same level of safety.

NASH Update

On January 5th, CytoDyn publicized positive results from their Phase II NASH clinical trial. The double-blind Part 1 matched a 700 mg weekly dose verse placebo, whereas Part 2 evaluated a 350 mg weekly dose compared to the same placebo blinded arm.

The primary endpoint was PDFF, which is an MRI-derived biomarker for fatty deposits, while the secondary endpoint was cT1, which displays inflammation and liver fibrosis. Together, they can assess the risk of a patient developing NASH. The Leronlimab 350 mg arm was able to hit its primary endpoint and was statistically significant. Leronlimab came close to hitting its secondary endpoint. The company reported that there were no significant differences in adverse events between Leronlimab and placebo groups. It is important to note that these results were achieved in a 14-week trial, where most NASH trials usually run 24 to 32 weeks in length.

NASH can evolve into liver disease, cirrhosis, and even develop into hepatocellular carcinoma. Despite these risks, there are presently no approved drugs for NASH, so physicians are relying primarily on obesity and Type II diabetes medications to treat or prevent NASH. Unfortunately, patients with advanced fibrosis due to NASH are at an expressively higher risk of developing those advanced symptoms and conditions. The data from the Part 2 portion indicates that Leronlimab could be effective in treating those conditions and become a primary treatment for NASH, which impacts roughly 5% of the world’s population. As a result, I expect Leronlimab to get the FDA’s Breakthrough Therapy Designation and even Accelerated Approval.

I am looking forward to seeing the results from the 700 mg blinded group, which presumably should show even better results. It is important to realize that the majority of NASH therapeutic candidates focus on weight loss and are hoping to have some impact on fibrosis. Whereas, Leronlimab is focusing on the fibrosis of the liver, which not only differentiates it from other NASH candidates but also addresses the main concern of the condition that leads to the worst symptoms. What is more, Leronlimab’s safety profile may give it an advantage over other NASH candidates who may have potential complications caused by the patient’s comorbidities.

HIV Update

Back in December, they filed a request with the FDA for expanded access of Leronlimab for HIV patients. The company still has nearly half of its patients from their Phase III trial still on Leronlimab, so the expanded access will allow CytoDyn to charge for Leronlimab for these patients until it is approved.

CytoDyn is working on resubmitting its BLA for this HIV combination therapy since getting a Refusal to File in July of 2020. In July of 2021, CytoDyn proclaimed they submitted a dose justification report to the FDA, and they anticipate finalizing the submission this quarter.

In addition to the in combination HIV program, CytoDyn is planning to initiate a registration-directed study for monotherapy indication. Data has shown that Leronlimab can maintain a suppressed viral load in R5 HIV patients. Numerous patients from the Phase IIb extension arm have continued to show viral suppression for nearly 7 years and patients from the Phase IIb/III trial are two years and some four years with suppressed viral load.

If all goes well, we should see the PDUFA date by year-end and the company moving forward with their other HIV programs to have follow-up HIV indications.

COVID-19 Updates

Back in December, the company publicized that they submitted a Phase III protocol to the FDA for critically ill patients with COVID-19 pneumonia with the need for invasive mechanical ventilation or extracorporeal membrane oxygenation. If approved, it will be a randomized, double-blind, placebo-controlled trial to assess Leronlimab’s efficacy and safety in combination with standard of care. Patients will be randomized in a 1:1 ratio to be given up to four doses of 700 mg of Leronlimab with the standard of care or placebo.

This would be the company’s second attempt at the severe/critical population in the U.S. after coming up short in their CD12 trial. An analysis of a subgroup of 62 critical patients in the CD12 trial presented an 82% survival benefit at Day 14 with doses on Day 0 and Day 7. After four weeks, the survival benefit dropped from 82% to 30%, which could indicate that Leronlimab was helping them stay alive. So, we should expect additional improvement in survival benefit in this potential study due to the four (2 doses in CD12) weekly doses of Leronlimab provided via IV infusion (Subcutaneous in CD12). The IV dosing should improve bioavailability and peak serum concentration of Leronlimab vs. subcutaneous. Additionally, the IV administration should allow for maximum serum concentration in less than two hours for IV infusion, while it takes two to three days for subcutaneous. What is more, the decision to go with 4 dosages of Leronlimab should also improve outcomes compared to the two doses.

According to the company, the FDA commented “While there are currently fewer U.S. patients hospitalized for COVID-19 daily in the U.S. compared to when you submitted your initial request for an expanded access protocol in August 2021, the CDC reports that 38,332 patients were hospitalized daily in the U.S. during the week of November 7th-13th, 2021. In this context, conducting a clinical trial in the U.S. that could support marketing approval of Leronlimab for the treatment of critically ill patients with COVID-19 appears feasible.” So, it looks as if there is a possibility the FDA is in support of CytoDyn’s efforts.

If everything turns out all right, the company should be conducting two Phase III trials in Brazil while pursuing critically ill and long-haulers in the United States. Ultimately, these trials could produce sufficient data that can be used for a COVID-19 EUA in multiple countries.

Demonstrating Potential

These latest developments show that all of Leronlimab’s potential indications are still in play, with some of them moving closer to approval. Not only is this important for those specific programs, but it also validates Leronlimab’s potential to be operative in the other potential indications. It is possible that Leronlimab could be a “jack of all trades” to be used in, oncology, metabolic diseases, neurodegenerative diseases, and autoimmune diseases. These divisions of medicine have immense market opportunities that have plenty of room for novel therapeutics, especially ones that have amazing safety profiles such as Leronlimab. Keep in mind, that most of these diseases are chronic, so a patient could be on Leronlimab for the rest of their life or until there is another option on the market. In addition, patients with these diseases typically have comorbidity and possibly have one or more of Leronlimab’s target indications. Hopefully, Leronlimab will be eventually seen as the physician’s version of “duct tape” where it is essential to have in the toolbox and is believed to be able to fix everything.

Haunting Downside Risks

As I mentioned in my previous article, CytoDyn has several chronic downside issues such as financials and expected losses. However, I am also considering the company’s record of starting several projects with little-to-show is starting to weigh on investor sentiment, which is evident in the share price performance. It is likely that these downside risks are not going to be remedied in the near term and might have a negative impact on the share price until they are resolved.

My Plan

In light of these developments, I am still committed to my previous game plan of increasing the size and frequency of my buy transactions. I have accepted the possibility of these developments nose-dive and do not assist the share price. However, I believe these developments will create subsequent catalysts that are more potent and could lead to a fundamental change for the company.

My time horizon is still several years out to let the company prove their efforts with Leronlimab will be productive, which could radically change the company’s valuation and improve investor sentiment.

Thank you for reading my research on CytoDyn Inc. If you want to learn even more about my method and how I discover these investment opportunities, please stand by because I am launching On The Pulse Analytics, a subscription marketplace service on Seeking Alpha, in the near future and the initial wave of subscribers will be offered a lifetime discount. Further details are around the corner, so please keep an eye out and read my research.

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