CytoDyn Announces Strong Preclinical Results Using PRO 140 in Human Colon Carcinoma

CytoDyn Inc. recently announced that PRO 140 (leronlimab) has been shown effective at inhibiting the growth of a human colon carcinoma cell line (SW480) in a prominent mouse model. The results were statistically significant and provide the basis for filing an Investigative New Drug (IND) application with the US FDA for a clinical trial in colon carcinoma patients.

Two different strains of immunoincompetent mice were used to grow SW480 human tumor cells and different doses of PRO 140 were used in these studies. The SW480 cell line was derived from a patient with colon adenocarcinoma and, like many human cancers, was CCR5-positive. PRO 140 extended the life of treated mice and decreased tumor growth compared to control mice by greater than 50%, which was statistically significant. These results were dose dependent and were repeated in separate experiments. Current ongoing preclinical studies are defining the mechanisms involved in the anti-tumor efficacy of PRO 140.

“We have been conducting these preclinical studies over the past year to better document the activity of PRO 140 against CCR5-expressing human tumors,” said Nader Pourhassan, PhD, CytoDyn President and Chief Executive Officer. “We believe that CCR5 is a crucial receptor in the growth and invasiveness of human malignancies, and these studies support that premise. Along with our recent announcement regarding the potential of PRO 140 in metastatic breast cancer, we believe these results in colon cancer further support that PRO 140, if approved, may offer an important potential therapeutic option for patients with breast and colon cancer. We now plan to file an IND within the next few weeks to begin studies of PRO 140 for the treatment of colon carcinoma. We will also continue to explore the biological pathways involving CCR5 to identify other potential therapeutic opportunities for PRO 140.”

CytoDyn also noted that upon the closing of its proposed acquisition of ProstaGene, Richard G. Pestell, PhD, MD, Chief Executive Officer of ProstaGene and President of the Pennsylvania Cancer and Regenerative Medicine Research Center, is expected to be appointed CytoDyn’s Chief Medical Officer.

“We look forward to Dr. Pestell joining our team and leveraging his decades of research with the CCR5 receptor as we further explore opportunities for PRO 140 in cancer, immunology, and autoimmune disorders,” added Dr. Pourhassan.

PRO 140 is a humanized IgG4 monoclonal antibody that blocks CCR5, a cellular receptor that plays multiple roles with implications in HIV infection, tumor metastasis, and immune signaling.

In the setting of HIV/AIDS, PRO 140 belongs to a new class of therapeutics called viral-entry inhibitors; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. At the same time, PRO 140 does not appear to interfere with the normal function of CCR5 in mediating immune responses. 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 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 compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 plays a central role in tumor invasion and metastasis and that an increased CCR5 is an indicator of disease status in several cancers. Moreover, researchers have shown that drugs that block CCR5, including PRO 140, can block tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. CytoDyn is conducting additional research with PRO 140 in the cancer setting and plans to initiate Phase 2 human clinical trials when appropriate.

The CCR5 receptor also plays a central role in modulating immune cell trafficking to sites of inflammation and it is crucial for the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others have shown that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with PRO 140 to further support the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD and that blocking this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to PRO 140 for the prevention of graft-versus-host disease (GvHD).

CytoDyn is a biotechnology company focused on the clinical development and potential commercialization of humanized monoclonal antibodies for the treatment and prevention of HIV infection. The Company has one of the leading monoclonal antibodies under development for HIV infection, PRO 140, which has completed Phase 2 clinical trials with demonstrated antiviral activity in humans and is currently in Phase 3 development. 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 seven 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 months 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 and to pursue non-HIV, inflammatory indications where CCR5 and its ligand CCL5 may be involved. For more information, visit http://www.cytodyn.com.