AEMD basket oncology trial, patient enrollment process
We participated in a discussion with Aethlon Medical (NASDAQ:AEMD) Interim Chief Executive Officer and Chief Financial Officer James Frakes and Chief Medical Officer Steven LaRosa, MD, last week at the Life Science Investor Forum. We present our takeaways in this note.
The company’s lead asset, the Aethlon Hemopurifier®, is being evaluated as a potential treatment for cancer and life threatening infectious diseases and for use in organ transplantation. The Hemopurifier is an extracorporeal device – in other words, it works outside the body, as illustrated in the figure below. The device is used on existing blood circulatory equipment such as dialysis and CRRT machines that are already installed in hospitals and clinics, making the Hemopurifier essentially a plug & play tool for medical centers.
The device has received FDA Breakthrough Device designation for two independent indications. The Hemopurifier has Breakthrough Device designation for the treatment of people with advanced or metastatic cancer who are either unresponsive to or cannot tolerate standard of care therapy, and with cancer types in which exosomes are indicated in the development or severity of the disease and also for life-threatening viruses that are not addressed with approved therapies.
Currently, the company’s primary focus is on researching the Hemopurifier therapeutic blood filtration system as a potential treatment in oncology. AEMD is launching a basket oncology trial to study the impact of the Hemopurifier in patients with various solid tumors who have stable or progressive disease during anti-PD-1 monotherapy treatment. It is a phase 1 safety, feasibility and dose-finding study. With a basket trial, the company will administer Hemopurifier treatment to patients suffering from various solid tumor types. Checkpoint inhibitors are also used to treat a broad range of tumor types. In fact, checkpoint inhibitors such as Keytruda® have been used to treat 25+ different types of cancer. If the study shows the Hemopurifier to be beneficial in multiple cancer types, the company believes the data will support the broad utility of the device. Moreover, by focusing on multiple cancers and including patients with a variety of solid tumors, the company has also expanded the opportunities for patient enrollment and can build a database to support regulatory approval. Including both Keytruda and Opdivo® is also expected to facilitate patient enrollments. The goal is to build its database in oncology to help with the development of the Hemopurifier as an oncology treatment.
The clinical trials will be conducted in Australia and India. Conducting studies in these two markets helps maximize R&D spending. AEMD expects to realize benefits from attractive economic incentives the Australian government provides for clinical development efforts and lower costs in India, where R&D expenses are substantially lower than in the U.S., according to management, and thereby maximize its R&D dollars. Australia offers an R&D tax incentives rebate program, which enables companies to receive a cash tax rebate of up to 43.5% on clinical trial related R&D costs and is expected to help it reduce costs, lower risk, and accelerate time to market.
Each patient will be its own control, as a patient’s EV level pre- and post HP treatment will be monitored. If there is a quantifiable decrease in EV levels, the Hemopurifier treatment is expected to improve their T-cell’s ability to fight the cancer.
The company has completed substantial preclinical, in vitro and in human analysis of the Hemopurifier. These activities have demonstrated virus and EV (which include exosomes) clearance both in vitro and in patients. AEMD’s recent in vitro binding study indicated positive results supporting that the Hemopurifier removes EVs from plasma and provides pre-clinical evidence to support the planned phase 1 safety, feasibility and dose-finding clinical trials in patients with solid tumors who have stable or progressive disease during anti-PD-1 monotherapy treatment, such as Keytruda® or Opdivo®. EVs are released from the parent cell and tumor cells generally have more mannose compared to healthy cells. EVs have been shown to contribute to metasisis of the malignancy and to suppressing the body’s immune system from helping the body fight disease. If the Hemopurifier can remove a quantifiable amount of EVs, it is expected it can help improve responses to standard-of-care cancer therapy.
Oncology Basket Trial - Safety, Feasibility and Dosing
The company’s trial will analyze whether the Hemopurifier can help decrease the concentration of EVs in cancer patients and thereby improve overall patient outcomes, as noted. The company’s objective in designing the trial was to test the Hemopurifier in a patient population that is already receiving checkpoint inhibitor treatment but could obtain incremental benefit from the Hemopurifier. The company’s hypothesis is that using the Hemopurifier in conjunction with treatment of checkpoint inhibitors can increase the percent of patients who can benefit from combined treatment. The company expects the Hemopurifier, in conjunction with an inhibitor, can help improve overall patient outcomes and demonstrate proof of concept about the device’s benefits in treating solid tumors. The company is optimistic that the trial will show the Hemopurifier’s ability in conjunction with Optivo or Keytruda that block anti-PD1 to improve body’s cancer fighting ability.
In addition to monitoring safety, the study is designed to examine the number of Hemopurifier treatments needed to decrease the concentration of EVs and if these changes in EV concentrations improve the body's own natural ability to attack tumor cells. Participating patients will be assigned to one of three different cohorts: cohort 1 will receive one Hemopurifier treatment during a one-week period, cohort 2 will receive two treatments and cohort 3 will receive three treatments during a one-week period. Analysis of the data generated from this study will be used to inform the design of a subsequent efficacy and safety, Premarket Approval (PMA), study to move toward regulatory approval. Following completion of treatment, the company will continue to follow patient participants.
Sites in Australia and India Moving Forward
AEMD has three sites in Australia that are moving towards patient enrollment. One site, Royal Adelaide, has gone through the entire approval process and is ready for enrollment. Another, Kinara, has gone through the approval process and the AEMD team will make a site initiation visit in the next few weeks. Kinara is expected to be open for enrollment shortly. A third site in Sydney has submitted a request to be added to the study. In India, the company has Medanta Medicity Hospital participating.
Specifically, This month AEMD announced that the Cancer Clinical Trial Unit at Royal Adelaide Hospital was activated to begin screening and enrolling patients in the trial. Last month the Bellberry Human Research Ethics Committee (BHREC) granted full ethics approval to the Pindara Private Hospital for the trial and earlier this week, AEMD announced the site in India. The Medanta Institutional Ethics Committee (MIEC) granted full ethics approval for the clinical trial. Importantly, the Hemopurifier treatments will be performed by Dr. Puneet Sodhi from the Department of Nephrology and, according to AEMD, he has conducted more Hemopurifier treatments than anyone else.
Primary endpoint safety; trial will also assess feasibility, dose-finding
The primary endpoint of the roughly 9-to-18 patient, safety, feasibility and dose-finding trial is safety. The trial will monitor any adverse events and clinically significant changes in lab tests of Hemopurifier treated patients with solid tumors with stable or progressive disease at different treatment intervals following two months of PD-1 antibody, Keytruda® or Opdivo® monotherapy. Patients who do not respond to the PD-1 therapy will be eligible to participate in AEMD’s Hemopurifier study.
We would expect AEMD to announce that the first patient has been treated possibly by year-end 2024 or early 2025. Subsequently, we would expect AEMD to announce that it has received all the data from the first cohort of patients once the data has come through.
Oncology market unfortunately is large
If Aethlon can demonstrate the ability of the Hemopurifier to improve outcomes of cancer patients suffering from a variety of different cancer types, we would anticipate strong commercial prospects for the Hemopurifier. AEMD believes it can generate data to support the Hemopurifier’s ability when combined with checkpoint inhibitor treatment to improve outcomes in multiple tumor types where cancer associated extracellular vesicles, or EVs, may promote immune suppression and resistance to anti-PD-1 antibodies. The Hemopurifier has demonstrated the ability to remove exosomes; management believes the device can be used to affect improved outcomes in a number of cancers.
Unfortunately, the oncology population is large. Some 40% of all cancer patients are eligible for checkpoint inhibitor treatment, according to AEMD, with about two million patients treated annually with Keytruda and an additional patient population with Optivo. However, as noted, currently, only about 30% of cancer patients who receive these treatments for solid tumors have lasting clinical responses. If the Hemopurifier, in conjunction with these treatments, can improve outcomes for a higher percentage of patients, the benefits would be substantial, in our view, as would the expected commercial prospects of the Hemopurifier.
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