CytoDyn receives FDA clearance for its first non-HIV indication for PRO 140

Phase 2 protocol for a transplantation indication cleared for patient enrollment

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VANCOUVER, Wash.—CytoDyn Inc., a biotechnology company focused on the development of new therapies for combating human immunodeficiency virus (HIV) infection, today announced that it has been cleared by the FDA to conduct a Phase 2 trial for Graft versus Host Disease (GvHD), which is a life-threatening complication for patients undergoing stem cell transplants. CytoDyn currently is conducting a Phase 3 pivotal trial with its lead product candidate, PRO 140, for the treatment of HIV.
The approved GvHD clinical trial is a Phase 2, randomized, double-blind, placebo-controlled, multi-center study. It evaluates the safety and efficacy of PRO 140 for prophylaxis of acute GvHD in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) undergoing allogeneic stem-cell transplantation. The trial is a 100-day study with 60 patients.
Positive results from this study would allow the company to file for a breakthrough designation to expedite the commercialization of PRO 140 for this clinical indication. As previously reported, PRO 140 is considered safe and well tolerated with negligible toxicities or side effects. The company believes that this makes it an ideal candidate for treatment of GvHD, a life-threatening disease for transplant recipients with compromised immune systems.
The company has selected a transplantation indication called GvHD as its first non-HIV clinical indication. The CCR5 receptor, the target for PRO 140, is an important mediator of GvHD, especially in the organ damage that is the usual cause of death. The only approved CCR5 inhibitor, Maraviroc, is currently in a Phase 2 study in GvHD. The company believes that PRO 140 has significant advantages over Maraviroc in more favorable dosing and pharmacokinetics, less toxicity and side effects, and no direct stimulation (agonist activity) of the CCR5 receptor.
PRO 140 is a monoclonal antibody that targets the chemokine receptor, CCR5, expressed on a variety of cells that play a central role in inflammatory responses. PRO 140 binds to this receptor in a way that prevents HIV from using it as an entry gateway, while not activating the immune function of the receptor. The company’s recent data indicate that PRO 140 interferes with (antagonist activity) activation of the receptor by its ligand, named CCL5. The CCL5 is a chemokine mediator which has been shown to be a central figure in many inflammatory disease processes, and blocking its interaction with CCR5 is believed to be of therapeutic benefit.
Dr. Nader Pourhassan, president and CEO, commented:  “We are very pleased to receive FDA clearance for a second, non-HIV, indication for PRO 140. Importantly, this is the first prophylaxis clinical trial with PRO 140 with our drug administered two or three days prior to the stem cell transplantation, then weekly or biweekly thereafter. If successful, the trial is expected to provide additional evidence for clinical applications for PRO 140 outside of HIV where the target of PRO 140 is involved, such as inflammatory conditions, autoimmune diseases and cancer.”
Graft-versus-host disease (GvHD) is a complication that can occur after a stem cell or bone marrow transplant. With GvHD, the newly transplanted donor cells attack the transplant recipient's body. GvHD may occur after a bone marrow or stem cell transplant in which an individual receives bone marrow tissue or cells from an unrelated donor. This type of transplant is called allogeneic. The new, transplanted cells regard the recipient's body as foreign. When this happens, the newly transplanted cells attack the recipient's body. GvHD does not occur when an individual receives his or her own cells during a transplant. Before a transplant, tissue and cells from possible donors are tested to determine how closely they match the person having the transplant. GvHD is less likely to occur, or symptoms will be milder, when the match is close. The chance of GvHD is approximately 30 percent to 40 percent when the donor and recipient are related and approximately 60 percent to 80 percent when the donor and recipient are not related. There are two types of GvHD: acute and chronic. Symptoms in both acute and chronic GvHD range from mild to severe. Acute GvHD usually happens within the first six months after a transplant. Chronic GvHD usually starts more than three months after a transplant and can last a lifetime.
In the United States, in 2011, over 7,500 unrelated donor bone marrow transplants were performed and another 10,000 were conducted outside the U.S.  One-year survival is now approximately 60 percent with the most common causes of death being relapse or GvHD. The market in the U.S. is expected to reach $500 million in the next several years.
CytoDyn is a biotechnology company focused on the clinical development and potential commercialization of humanized monoclonal antibodies for the treatment and prevention of Human Immunodeficiency Virus (HIV) infection. The company has one of the leading monoclonal antibodies under development for HIV infection, PRO 140, which has finished Phase 2 clinical trials with demonstrated antiviral activity in man and is currently in Phase 3. PRO 140 blocks the HIV co-receptor CCR5 on T cells which prevents viral entry. Clinical trial results thus far indicate that PRO 140 does not negatively affect the normal immune functions that are mediated by CCR5. Results from six Phase 1 and Phase 2 human clinical trials have shown that PRO 140 can significantly reduce viral burden in people infected with HIV. A recent Phase 2b clinical trial demonstrated that PRO 140 can prevent viral escape in patients during several weeks of interruption from conventional drug therapy. CytoDyn intends to continue to develop PRO 140 as a therapeutic anti-viral agent in persons infected with HIV.
PRO 140 belongs to a new class of HIV/AIDS therapeutics—viral-entry inhibitors—that are intended to protect healthy cells from viral infection. PRO 140 is a fully humanized IgG4 monoclonal antibody directed against CCR5, a molecular portal that HIV uses to enter T cells. PRO 140 blocks the predominant HIV (R5) subtype entry into T cells by masking this required co-receptor, CCR5.  Importantly PRO 140 does not appear to interfere with the normal function of CCR5 in mediating immune responses. PRO 140 does not have agonist activity towards CCR5 but does have antagonist activity to CCL5 which is a central mediator in inflammatory diseases. PRO 140 has been the subject of seven clinical trials, each demonstrating efficacy by significantly reducing or controlling HIV viral load in human test subjects. PRO 140 has been designated a “fast track” product candidate by the FDA. The PRO 140 antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements as compared to daily drug therapies currently in use.
Source: CytoDyn Inc.

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