Curative by Design™

tumor cells with target

Our guiding principle to create maximum
impact is to tackle the most limiting
challenge first because it will matter most.

 

Verik aims for a direct shot at
tumor regeneration.

We believe that adoptive cell therapy can cure solid tumor cancer and that it shouldn't rely on chance.

What distinguishes Verik is the deliberate targeting of the essentials of tumor regeneration as a way of eliminating cancer.

 

When we began our work, some in oncology questioned whether cancer even regenerated. Tumor antigens for T cells were scarce (and still are), and the few that were tested clinically in a
T cell therapy were largely ineffective and sometimes dangerous. We believed that the days of thinking of a tumor as a mass of cells dividing uncontrollably or that any difference from normal could make an effective tumor target had to come to an end.

 

Verik committed to using its knowledge and skills to find ways to target the regeneration-capable component of solid tumors. It required dealing with the tumor's biology first.

 

Eliminating the regenerative response is essential. Here's why:

small tumor cell clusters within tissue

Relapse is still the most common result of even the most effective targeted therapies. The use of immune checkpoint inhibitors is calling attention to the biology of recurrence through the observations of hyperprogression1.  This closer look at tumor behavior is raising awareness that something more is at work when the tumor shrinks and that ultimately, it can create both good and bad outcomes. Progression and hyperprogression can be understood, if not predicted, by how normal regeneration is stimulated and controlled2.

 

Ideally, concerns about a therapy’s impact on tumor regeneration should extend to the manipulation of enabling (auxiliary) factors such as inflammation, myeloid cell differentiation or tissue remodeling within the tumor–all related to normal mechanisms of wound healing with regeneration as a partner.

 

Thus, no matter what is done to target the bulk of a tumor or manipulate the tumor microenvironment, we believe that directly eliminating the regeneration-capable component will define the outcome for a majority of patients. Whether the most dangerous cells within a shrunken tumor are dormant for a time or active within days, the patient is not yet cured without elimination of this cellular component.

 

1. Champiat, S. et al. Clin Cancer Res 23:1920 (2017); Kato, S. et al. Clin Cancer Res 23;4242.

2. Parenteau N. et al. (2004) Cur. Topics Dev. Biol. Academic Press, New York. 64:101.

Formulating a direct attack on tumor regeneration

Regenerative Nexus

A regenerative nexus represents a core aspect of tissue regeneration. Nexuses must work in concert to maintain a capacity for regeneration, and, in the case of cancer, its ability to persist and return.

network shows a nexus

Targetable Change

A cancer-specific protein change that governs a nexus, creates a High Curative Potential (HCP) Target.

 

The nature of an HCP Protein Target means it is likely to be retained as the cancer advances and is also likely to be shared between cancer patients. This creates the possibility of serving a broad population of  patients with a reliably potent T cell therapy.

network with asterick marking HCP target

Navigating the complex biology in and around tumor regeneration requires several biological considerations:

•Regeneration is influenced by injury, inflammation, vascularization, tissue remodeling, and fibrosis–all part of a wound response and all active in advanced cancer. Their impact on regeneration is influential yet indirect. Therefore, targeting these processes would be indirect. We needed to tease out targets that would lead directly to the regeneration-capable cells.

•Targeting ”driver” mutations (a mutation that confers a growth advantage) would get us closer to maximizing curative potential. However, some driver mutations would still be auxiliary actors to the regenerative process; for example, protein changes that better enable cancer to spread. An enabling ”driver mutation“ would have a lower impact on curative potential. We needed protein targets that would have a direct effect on regenerative processes.

 

We worked to reconcile data on development, regeneration, and stem cell manipulation. Our hypothesis was that certain subcellular functions, patterns, and pathways would emerge as essential to regeneration. This led us to know where to look for cancer-specific changes that would make these ”essentials” targetable. Verik developed  SeleCTR (Selection of Curative T-cell Receptors) algorithms to identify High Curative Potential proteins and find T cell epitopes within the proteins. The SeleCTR platform has led to multiple proprietary High Curative Potential targets as well as patented and patent-pending sequences for the selection of T cell receptors that can create High Curative Potential T cell therapy.

Independent clinical studies have reported the retention of shared HCP target gene expression in patients with metastatic disease.

Using a Verik target will better ensure that persistence and progression within a tumor will not occur.   More on Verik Targets

Diving deeper into functional tumor regeneration

”Is it possible that the quest to treat cancer has also stalled because we haven't even found the right kind of cell?”

SIDDHARTHA MUKHERJEE, The Cancer Sleeper Cell by E, The New York Times, October 29, 2010

 

 

Although genetic tumor data are steadily increasing, useful data on tumor regeneration are lacking. Regeneration-capable tumor cells are not easy to identify as they will not always fit the academic definition of a cancer stem cell. Depending on conditions, they may be either active or dormant. They will not necessarily express surface proteins that scientists have relied on for the identification of normal as well as cancer stem cells. How the regeneration-capable component manifests within the tumor is a function of the collective biology of the tumor cell population and cues from its milieu. It is a concept we learned from normal epithelial regeneration. Verik developed a patented in vitro method that can stimulate the regenerative component within a tumor biopsy so one can identify it, functionally isolate it, and characterize tumor regeneration without needing to assume marker expression that might be misleading.

 

© 2019 Verik Bio, Inc