Mr. Thomas Smeenk reports

HEMOSTEMIX FILES FOR ETHICS APPROVAL OF ITS STUDY OF VASCULAR DEMENTIA

Hemostemix Inc. has filed its Institutional Review Board application for approval of its phase 1 clinical trial titled "Treatment of Vascular Cognitive Impairment and Dementia with Angiogenic Cell Precursors (ACP-01)." The 102-page submission marks a critical milestone in expanding the therapeutic reach of ACP-01.

Plain-language summary

Hemostemix has officially applied for ethics approval to begin a new clinical study testing its stem cell therapy, ACP-01, for people suffering from vascular dementia -- a form of memory loss caused by poor blood flow to the brain. This is an important step toward treating a disease for which no current cure exists.

Significance of the filing

Vascular dementia (VaD) and vascular cognitive impairment (VCID) represent the second most common cause of dementia worldwide, accounting for up to 20 per cent of all cases. With no Food and Drug Administration-approved therapies, VCID remains a major unmet medical need. The IRB submission positions Hemostemix at the forefront of regenerative neuroscience by proposing the first autologous intrathecal stem cell therapy designed to restore brain perfusion and neurovascular integrity in affected patients.

Plain-language summary

Vascular dementia is the second-most common cause of dementia after Alzheimer's. It happens when blood flow problems damage brain tissue. No approved drugs exist to stop or reverse it. Hemostemix's new trial aims to repair blood vessels in the brain using the patient's own stem cells injected safely into the spinal fluid to reach the brain directly.

ACP is safe and effective

ACP-01, a population of angiogenic cell precursors derived from autologous peripheral blood, has demonstrated strong safety and efficacy in clinical trials for refractory angina, ischemic cardiomyopathy, non-ischemic dilated cardiomyopathy and peripheral arterial disease as chronic limb-threatening ischemia. The vascular dementia trial represents the first direct application of ACP-01 to the central nervous system, leveraging its pro-angiogenic, anti-apoptotic and neurotrophic mechanisms.

Plain-language summary

ACP-01 is made from a person's own blood. It has been safely used to increase new blood vessels in the heart and legs of patients with blocked arteries. This new study is the first to see if those same cells can improve blood flow and nerve health in the brain.

Key highlights of the protocol

Study title

Phase 1 Study: Treatment of Vascular Cognitive Impairment and Dementia with Angiogenic Cell Precursors (ACP-01)

Objective

To evaluate the safety, feasibility and preliminary efficacy of intrathecal ACP-01 administration in patients diagnosed with vascular cognitive impairment or vascular dementia

Plain-language summary

The study will test whether it is safe and practical to give patients their own stem cells directly into the spinal fluid, and whether this treatment shows early signs of improving memory and thinking ability and improves their quality of life.

Design:

• Phase 1, multicentre, open-label, non-randomized study;
• 20 to 100 adult participants (ages 50 to 100);
• Intrathecal (lumbar puncture) administration of autologous ACP-01, with optional second dose at three months;
• Follow-up at three, six and 12 months posttreatment.

Plain-language summary

The study will include between 20 and 100 people, aged 50 and older. They will receive an injection of their own stem cells into their spinal fluid. Several will get a second dose three months later to study the effect of one dose verses two doses. The team will then monitor the patients for one year to track safety and changes in brain function and quality of life improvements following one or two treatments.

Primary end points:

• Demonstrate safety and feasibility of intrathecal delivery;
• Establish incidence and tolerability of adverse events.

Secondary end points:

• Improvement in cognition, executive function and quality of life (through MoCA, MCI screen, SF-36 and Barthel Index);
• Change in EEG-based brain network analytic (BNA) patterns;
• MRI-assessed changes in brain perfusion and volume.

Plain-language summary

The main goal is to confirm that the treatment is safe. The study will also look for any signs of better memory, clearer thinking, improved brain activity on EEG tests, healthier blood flow on MRI scans and improved quality of life as measured by how patients feel after the treatment, comparing one versus two treatments.

Exploratory end points:

• Biomarker response (IL-6, CRP and neurofilament light chain);
• Correlation of EEG and cognitive test improvement;
• Dose-response evaluation between one versus two ACP-01 treatments.

Plain-language summary

Researchers will also look at blood and spinal fluid markers that show inflammation or nerve damage, to see which patients respond best and whether two treatments work better than one.

Scientific rationale

ACP-01 cells express CXCR4, enabling homing to ischemic brain tissue through the CXCL12 chemokine gradient, and release VEGF, angiogenin and IL-8 (CXCL8) -- potent mediators of angiogenesis and neuroprotection. Of particular interest, IL-8 activates nuclear factor-kappaB (NF-kappaB), a transcription factor known as the learning molecule essential for synaptic plasticity, dendritic formation and long-term memory consolidation.

By restoring microvascular circulation, stabilizing the blood-brain barrier and promoting neuronal survival, ACP-01 may address the vascular basis of cognitive decline.

Plain-language summary

Since the cells, ACP-01, are the patient's own cells, they leverage the body's natural signalling processes to navigate to damaged areas in the brain, release growth factors that help repair blood vessels and protect nerve cells. They also switch on a key protein in the brain -- called NFKB (NF-kappaB). NFKB helps build and maintain memory. In short, ACP-01 could help the brain heal itself, improve blood flow where the brain signals it needs new circulation most, and improve memory and the ability to learn.

Mechanism of delivery

Unlike prior intravenous stem cell trials that suffered from limited brain penetration, Hemostemix's protocol utilizes direct intrathecal delivery -- bypassing the blood-brain barrier and exposing cerebrospinal fluid directly to the therapeutic cells.

Plain-language summary

Instead of giving the cells through a vein (where most stem cells get trapped in the lungs), this method injects them into the spinal fluid, a fluid that surrounds the brain and spinal cord. That way, the cells reach the brain more directly and can start repairing tissue sooner.

Safety oversight

All procedures are conducted in an outpatient setting under the supervision of licensed neurosurgeons. The protocol includes comprehensive safety monitoring under the oversight of a data safety monitoring board.

Plain-language summary

The study will be done by qualified neurosurgeons in a clinical setting. An independent safety board will watch over every patient's experience to ensure the treatment is handled safely and ethically.

Executive commentary

"Filing our vascular dementia phase 1 protocol represents a major step forward in applying ACP-01's regenerative power to one of medicine's most intractable conditions," said Thomas Smeenk, president and chief executive officer, Hemostemix. "We have already demonstrated the safety and efficacy of ACP-01 in the heart and limb. This next trial extends our platform to the brain where vascular repair may restore blood flow, memory and cognition itself. We know ACP-01 worked for Mrs. L for 10 years, who was treated for vascular dementia. This study will demonstrate its broad application is warranted," Mr. Smeenk said.

About Hemostemix Inc.

Hemostemix is an autologous stem cell therapy platform company, founded in 2003. A winner of the World Economic Forum technology pioneer award, the company has developed, has patented, is scaling and is selling autologous (patient's own) blood-based stem cell therapy, VesCell (ACP-01). Hemostemix has completed seven clinical studies of 318 subjects and published its results in 11 peer-reviewed publications. ACP-01 is safe, clinically relevant and statistically significant as a treatment for peripheral arterial disease, chronic limb threatening ischemia, non-ischemic dilated cardiomyopathy, ischemic cardiomyopathy, congestive heart failure and angina. Hemostemix completed its phase 2 clinical trial for chronic limb threatening ischemia and published its results in the Journal of Biomedical Research & Environmental Science. As compared with a five-year mortality rate of 60 per cent in the CLTI patient population, the University of British Columbia and the University of Toronto reported to the 41st meeting of vascular surgeons: 0 per cent mortality, cessation of pain and wound healing in 83 per cent of patients followed for up to 4.5 years as a midpoint result.

We seek Safe Harbor.