Regeneron Acquires Checkmate for $250 Million, Gets TLR9 Agonist

On April 19, REGENERON and Checkmate jointly announced that the two companies have signed a definitive agreement under which Regeneron will acquire Checkmate common stock at an all-cash price of $10.50 per share, with a proposed total equity value of Checkmate of approximately $2.50. One hundred million U.S. dollars.

Affected by the news, Checkmate shares soared 329%.

Checkmate's lead investigational candidate, Vidutolimod, is a CpG-A oligodeoxynucleotide toll-like receptor 9 (TLR9) agonist delivered via virus-like particles (VLPs).

Vidutolimod acts through two complementary mechanisms to drive robust systemic T cell antitumor responses. First, VLPs activate the body to mount an immune response, so that the antibodies produced deliver VLPs to plasmacytoid dendritic cells (pDCs) and to other immune cells via FcR-specific receptors. This provides the pDC with an initial stimulatory signal and brings CpG-A to TLR9 (CpG DNA receptor) within the pDC. Second, the manner in which CpG-A stimulates TLR9 induces significantly higher levels of type I interferons (IFN-α, etc.) in pDCs compared to other innate immune activators, resulting in a stronger T cell antitumor response.

Several approaches are currently being developed to fight cancer by activating the immune system, such as TLR7, TLR8 and/or TLR9 agonists, as well as activators of the STING pathway and oncolytic viruses. The immunological effects of vidutolimod are unique for two reasons: First, biological VLPs delivering CpG-A enhance the immune response by stimulating the production of antibodies that promote uptake of the VLPs themselves and provide additional pDC activation, leading to more potent Systemic antitumor T cell responses.

Second, CpG-A self-assembles into a structure known as a G-quad helix, which mimics the replicative form of viruses and retroviruses, and has the advantage compared to other TLR activators that use nuclease-resistant phosphorothioate backbones A native DNA backbone that can be cleaved during TLR9 activation, thereby inducing higher amounts of type I interferons (IFNs). Type I IFNs are important for generating strong antitumor immune responses.

In contrast to oncolytic viruses, vidutolimod does not infect human cells and is therefore not blocked by antiviral antibodies, but enhanced by these antibodies. Oncolytic viruses are inhibited by a strong type I IFN response, but vidutolimod is designed to induce this response.

In patients with melanoma whose tumors had progressed after prior PD-1 inhibitor therapy, vidutolimod monotherapy induced and expanded antitumor T cells and induced tumor regression by intratumoral administration. In the Phase Ib program, the ORR of vidutolimod in combination with K drug was 27.6%, and the ORR of monotherapy was 22.5%.

Vidutolimod is currently being developed in combination with other drugs to treat melanoma, non-melanoma skin cancer and head and neck cancer.