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CytoDyn’s Data: Approvable Drug Sets Stage For Near-Term Move Upward
Cytodyn's Update Provides A Clear Path Towards Approval With Up-Listing Potential Still In The Cards

• Research supportive of initiating HIV cure clinical trial
• Subpopulation of HIV cancer patients ideal for trial
• Possible label expansion into other disease indications
• Anecdotal data from trial may lead to quicker approval in other indications

CytoDyn Inc. (OTCMKTS: CYDY) announced in a Proactive Investors video a major advancement in HIV whose message may have gotten buried due to a lengthy disclosure about a fake new article that was promulgated by short seller Citron Research.

CytoDyn believes they have a cure for HIV that will work on a subpopulation of patients which may challenge Gilead Sciences (Nasdaq: GILD) and their drug vesatolimod (GD-9620). About a year ago CytoDyn brought Dr. Jona Sacha onboard as senior science advisor to spearhead their HIV cure strategy. Before he was onboarded, he was a key player in CytoDyn’s collaboration with the Thai Red Cross Aids Research Centre to study pre-exposure prophylaxis (PrEP) of leronlimab. Sacha has been busy testing leronlimab in the lab and plans on initiating an emergency IND protocol for two HIV patients that were also afflicted with blood cancer. This type of cancer requires a bone marrow transplant and is an integral part of the cure and represents a novel approach compared to Gilead.  
 

Research Supporting HIV Cure

The first person to be cured of HIV over a decade ago was Timothy Brown who became known as the “Berlin patient.” Brown was afflicted with myeloid leukemia and had radiation to wipe out the rest of his T-cells before the bone marrow transplant. The theory behind Timothy’s Browns HIV cure was that he was given a bone marrow transplant from a donor who had the CCR5 delta 32 mutation. This allowed the production of new T-Cells that didn't contain the CCR5 coreceptor on the cell surface to allow HIV entry. After the transplant his bone marrow was essentially reprogrammed to only make the CCR5 delta 32 T-Cells that had no expression of CCR5 on their cell surface. People that have the CCR5 delta 32 gene do not have CCR5 receptors on their T-Cells and as a result are immune to HIV. Without a host to enter, the HIV in his system eventually worked its way out of the tissues and was eradicated. 

In January 2020, Dr. Sacha indicated that he had an oral presentation at the Keystone Symposia on HIV Pathogenesis and Cure. His paper was titled Antibody-Mediated CCR5 Blockade Recapitulates the CCR5 Deficiency-Mediated Protection from Sexual HIV Acquisition. The conference was cancelled due to COVID-19 but the theory underpinning his presentation seems to be the catalyst for these emergency IND’s. The CEO of CytoDyn, Dr. Pourhassan said
 

“He showed us the data, ….. we believe that leronlimab can mimic the genetic mutation that results in the loss of CCR5, thereby making an HIV cure a possibility for any HIV patient who requires a bone marrow transplant.”

The concept behind CytoDyn’s cure is that the virus will not be able to enter the newly created T-Cells that originated from the bone marrow transplant. In theory, the transplant will occur at the time when the T-Cells are completely destroyed and the cancer is poised to overtake the body. At this tipping point there are no more T-Cells for the virus to infect. The idea behind this cure is that leronlimab will protect these newly formed T-Cells from infection. As long as this is maintained for a reasonable amount of time the HIV reservoirs in the tissue should deplete and eventually lead up to a cure.

Path Toward an HIV Cure

Cytodyn estimated that 10 - 15% of the HIV patients who get cancer will need a bone marrow transplant. Dr. Sacha has identified 2 patients that fit his criteria for this treatment and is in the process of requesting an emergency IND from the FDA. If granted and it works for these patients the company plans on filing Breakthrough Therapy Designation (BTD) for this patient population. At this time it's unclear what clinical outcomes constitute a cure and how long patients will need to be treated with leronlimab before it is withdrawn. There are currently 5 patients that have taken leronlimab for over 5 years and they have not been classified as cured, but an argument could be made that they have been functionally cured since they have no side effects and no rebounding viral load. This approach is radically different from what Gilead has been working on.

Instead of using a combination of cancer and HIV to eradicate the T-Cells before transplantation, Gilead is planning on using its velastamod, which targets toll like receptor TLR7, to force latent HIV from the virus’s immune cell reservoir. Once in the vasculature PGT121 would attach to the virus and clear it from the blood. This methodology is known as a shock and kill tactic and was presented at the 2018 CROI meeting. Unfortunately there hasn't been a lasting response because monkey tests showed that the treated group took 112 days to rebound versus the control which rebounded in 21 days.   

Merck (NYSE: MRK) had a similar plan called “kick and kill” in which it used a cancer drug called Vorinostat as an activating agent to clear the body of its viral reservoir. This approach forces the body's innate immune system into action to kill off what was left in the reservoir. Merck conducted a study of 60 men who recently acquired HIV, and had them start ART and got their viral loads to undetectable levels and then receive the “kick and kill.”This consisted of Vorinostat and an anti-HIV vaccine. Results were very disappointing and showed that there was no impact on the copies per ml compared to ART alone. 

Expansion of Cancer Indication and Graft versus Host Disease (GvHD)

If the FDA approved these emergency IND’s for the HIV cancer cure, it makes a stronger case for approval in other cancer indications. For example, patients with Acute Myeloid Leukemia (AML) typically experience Graft versus Host Disease (GvHD). Leronlimab is also in a clinical trial for GvHD and could represent additional anecdotal data that supports approval. The drug might also lower Circulating Tumor Cells (CTC’s) in the patient's cancer. This too could be more anecdotal data supporting the basket trial in metastatic cancer patients. There is a lot of crossover between diseases because CCR5 is implicated in so many indications, lending credence to a mega platform technology.  

Investment Summary

A cure for HIV has been sought after for decades, and recent studies are demonstrating a greater understanding of CCR5 and the crucial role it plays in disease pathogenesis. This study if successful would be a huge datapoint to support label extension of leronlimab. In all likelihood they would get a BTD. Right now the company has the potential for 3 BTD’s in metastatic Triple Negative Breast Cancer, metastatic cancer, and COVID-19. CytoDyn is expecting its PDUFA date by July 11th. It filed its BLA in April and is widely expected to receive a PDUFA date in August or September because it has fast track and rolling review. The market reaction to this news was underwhelming and clouded by the spectre of fake news and threats of attorney litigation. Gilead has been very quiet about velastamod so it’s conceivable that leronlimab's approval in HIV combination therapy could easily upset the HIV cure leaderboard putting itself on top.