Checkmate Pharmaceuticals raises $20 million Series A financing for development of TLR9 agonist

Checkmate Pharmaceuticals raised $20 million Series A financing from Sofinnova Ventures and venBio. The company has licensed a virus-like particle platform including a clinical TLR9 agonist known as CYT003 from Cytos Biotechnology.

Checkmate is led by CEO Arthur Krieg, former CSO of Sarepta Therapeutics (SRPT). Krieg only worked at Sarepta for six months. Sarepta never explained the reasons for the abrupt departure of Krieg. Here is the speculation from stockerjocker (@np32817):

It was a failed bid to replace CG (Chris Garabedian) and become CEO. Board stuck with CG. AK (Arthur Krieg) then immediately terminated.

CYT003 is an immune modulator derived from CpG oligonucleotides. Krieg demonstrated that the CpG motifs in bacterial DNA was responsible for B-cell activation in 1995[1]. He led the R&D of agatolimod (PF-3512676, CPG 7909), a TLR9 agonist. However, Pfizer discontinued the Phase III trials of agatolimod in NSCLC[2] and melanoma[3] due to a lack of clinical efficacy.

Cytos has tested CYT003 in hundreds of asthma patients, and it failed to demonstrate clinical efficacy. Krieg believes the drug will enhance the efficacy of checkpoint inhibitors. Checkpoint inhibitors have shown remarkable results in cancers, but they work for only a limited number of patients (about 20%).

Why do so few patients respond to checkpoint inhibitors?
In a patient whose immune system is already activated and poised to kill their tumor, treatment with a checkpoint inhibitor can free the immune system to destroy the tumor. Unfortunately, most patients’ immune systems are not already activated so treatment with a checkpoint inhibitor does not provide any therapeutic benefit and may actually worsen the patient’s condition by causing significant toxicity.
Source: Checkmate Pharmaceuticals website.

Checkmate believes that there is tremendous promise to the combination of CpG DNA and checkpoint inhibitors. CpG DNA activates the anti-tumor T cells, while checkpoint inhibitors block immunoinhibitory signals.

Dynavax Technologies (NASDAQ: DVAX) is combining its TLR9 agonist SD-101 with Merck’s pembrolizumab in Phase I/II trials. In a 21-patient phase I study of tremelimumab plus PF-3512676, two melanoma patients achieved durable partial response[4].

[1] Nature. 1995, 374(6522), 546-549.
[2] J Clin Oncol. 2011, 29(19), 2667-2674.
[3] Cancer. 2009, 115(17), 3944-3954.
[4] Br J Cancer. 2013, 108(10), 1998-2004.

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