Mechanism of Action

In Hot Pursuit to Solve Immunotherapy’s Biggest Challenge

Converting Immunologically “Cold” Tumors to “Hot”
Recent advances in cancer immunotherapy are providing new treatment options and better outcomes for people living with cancer. Immunotherapy treatments, such as immune checkpoint inhibitors, work by releasing the brakes on the immune system and allowing special immune cells, known as T cells, to produce a self-sustaining attack on a tumor. However, checkpoint inhibitors are generally only effective in hot tumors which contain T cells. Most people living with cancer have cold tumors, without T cells, and do not respond to this immunotherapy.

Checkmate Pharmaceuticals’ mission is to tackle one of the greatest challenges for physicians and patients in cancer immunotherapy: converting immunologically cold tumors to hot. The unique mechanism of action of our lead compound, CMP-001, along with its delivery as a Virus-like Particle, or VLP, has been shown to reverse cold tumors, making them “hot” or susceptible to immunotherapy treatment with checkpoint inhibitors.

CMP-001 initiates local and systemic immune responses to fight cancer, potentially improving outcomes for people whose tumors are non-responsive to immunotherapies. CMP-001 is being investigated in patients with various types of cancer, including melanoma, lung, and head and neck, whose tumors have proven to be resistant to checkpoint inhibitors. It is also under investigation for certain types of cancer that are particularly resistant to immunotherapy, such as colorectal cancer.

While immunotherapies represent one of the most significant breakthroughs in cancer therapy over the last decade, approximately 70-80% of cancers are resistant to immunotherapeutic agents and fail to respond to therapy.
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Tumor recruits immature pDC.
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Immature pDC maintain immune-suppressed cold tumor microenvironment; immunotherapies are less likely to be effective.
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CMP-001 administration marshals the immune system to convert the tumor microenvironment from cold to hot.
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Activated pDC then mounts an anti-cancer immune response via the production of type 1 IFN and chemokines; T cells are recruited into the newly hot tumor microenvironment.
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T cells specific to the tumor neoantigens mediate a local and systemic.

Making Immunotherapy Work Harder

For decades, it has been known that certain immune cells called cytotoxic T lymphocytes (CTLs) can destroy cancer cells, yet they fail to play this key role in many patients suffering from cancer. Tumors produce “immune checkpoint proteins” that suppress the cancer fighting activity of CTLs. This discovery led to a new class of therapeutics called checkpoint inhibitors. While these therapies are a significant advance, they fail to work on many types of cancer.

The efficacy of checkpoint inhibitors may be dramatically increased by combining them with an immune activator to stimulate T cells. Many different immune activators have been tested and the Toll-like receptor 9 (TLR9) agonist CpG-A oligonucleotides, like CMP-001, have been found to be the strongest at stimulating anti-tumor CTLs. The unique combination CMP-001 with checkpoint inhibitor therapy may result in increased clinical benefit and provide new treatment options for patients with cancer.

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