MULTIPRONGED CELL THERAPIES FOR A MULTIFACETED DISEASE

Tumors are a complex, heterogeneous environment comprised of many different cells expressing many different molecules on their surface, called “antigens”.  Antigens that are specific to cancer cells can be used to generate immunotherapies that target and kill tumors.  Marker’s unique MultiTAA technology differs significantly from today’s leading cell therapies, which are genetically engineered to recognize a single portion (or epitope) of a single tumor-associated antigen.  This approach is expensive and difficult to scale and has limited patient benefit because these engineered therapies comprise a uniform T cell population of a single specificity.

Marker’s unique manufacturing process selectively expands a range of naturally occurring, often extremely rare tumor-specific T cells present in patients’ blood that are able to recognize unique epitopes of up to five different tumor-associated antigens.  The result is a remarkably robust mixture of T cells that can target a broad repertoire of cancer cells within a single tumor.  A typical patient dose consists of approximately 4,000 unique anti-tumor T cell types, which when reintroduced into the patient, are able to kill heterogeneous tumor targets more effectively than single-antigen specific approaches.  This reduces the likelihood of tumor “escape” and increases the durability of a patient’s response to therapy.

DEMONSTRATED CLINICAL AND SAFETY BENEFITS

In completed and ongoing studies in lymphoma, the response rate to Marker’s cell therapy is high (~50-60% complete response, or CR, rate), and these responses appear to be highly durable, as no complete responders have subsequently relapsed – with some patients continuing to be relapse-free beyond two years.  This observation is important because in reported CAR-T studies in similar indications, 30% or more of patients with CR typically relapse within one year.

In addition, patients treated with Marker’s therapies have shown consistent evidence of “epitope spreading”, meaning that in addition to the tumor antigen-specific T cells contained in Marker’s infused product, patients’ T cells that recognize additional tumor-associated antigens also expand and contribute to a lasting anti-tumor effect.  This phenomenon is potentially important for driving a durable response because it further expands the range of tumor cells that are targeted by the immune system beyond those recognized by the infused product.

Importantly, Marker’s T cell therapies expand and activate a patient’s T cells without genetic modification or the need for lymphodepletion prior to infusion.  This is believed to provide substantial health and safety benefits. To date, Markers’s MultiTAA therapies have caused no cases of cytokine release syndrome or related serious adverse events, versus up to a 95% incidence rate of grade III or higher adverse events in recent CAR-T studies.

EASE & SIMPLICITY OF MANUFACTURING – AT A FRACTION OF THE COST

Marker’s MultiTAA platform selects for and expands patient tumor-specific T cells by directly presenting a proprietary blend of tumor-associated antigens and cytokines in vitro, bypassing the need for expensive, time-consuming, and complex genetic modification.

Additionally, the innovative G-Rex® cell culture platform further reduces the cost and complexity of manufacturing of this individualized cell therapy by providing a simple and scalable solution to individualized cell culture.

Blood is first drawn from a patient or a stem cell donor in the same manner as a blood donation in an outpatient setting, without the need for a lengthy and potentially painful apheresis procedure.  The immune cells are isolated and cultured together, in two separate steps, with a proprietary blend of tumor-associated antigens, cytokines and antigen presenting cells in G-Rex® culture devices in standard incubators. The resulting MultiTAA product is a diverse mix of helper (CD4) and cytotoxic (CD8) T cells that recognize the tumor-specific antigens that Marker targets.  Because Marker’s proprietary peptide mix is designed in an overlapping sequence structure, Marker is able to isolate, activate and expand any T cell specific for any segment of each antigen it targets in the unique genetic background of every patient.

Once cell manufacturing is complete, the product is tested for identity, sterility, and safety before it is released for infusion into a patient. Subsequent to release of the final patient product, the cells are frozen and transported to the site where the cells will be administered. The standard dose for patients with lymphoma, AML or myeloma ranges 10-40 million cells per adult patient, which is considerably fewer than today’s cell therapies.

Due to the relatively small cell dose volumes and outstanding safety profile of Marker’s therapies, cells can be infused within minutes instead of hours at an outpatient center without the need for hospitalization and overnight monitoring. Patients are monitored for any immediate infusion-related reaction but are usually discharged within two hours.