Checkmate Pharmaceuticals Inc., of Cambridge, Mass., completed an $85 million series C to continue developing CMP-001, a differentiated Toll-like receptor 9 (TLR9) agonist, for treating anti-PD-1-refractory melanoma and to study additional indications that include front-line melanoma and head and neck squamous cell carcinoma.

Privately held Checkmate has competition, as Idera Pharmaceuticals Inc. and Dynavax Technologies Corp. are also using TLR9 agonists to treat anti-PD-1-refractory melanoma. The malignant melanoma therapy market is expected to grow from $3.6 billion in 2018 to about $6.5 billion in 2028 in major markets that include the U.S., the U.K., Japan and most of western Europe, according to DRG. That growth will principally be fueled by label expansions of current therapies, specifically those targeted to PD-1 and BRAF/MEK for use in the adjuvant setting.

Checkmate’s CMP-001 is delivered as a biologic virus-like particle using a CpG-A oligonucleotide as a key component.

Checkmate’s phase Ib trial, CMP-001-001, for treating advanced melanoma began in 2016 and is a multicenter, two-part, open-label study of CMP-001 either as a monotherapy or in combination with Keytruda (pembrolizumab, Merck & Co. Inc.). The primary objective of part one is to determine the recommended phase II dose and schedule of CMP-001 with pembrolizumab. The primary object of part two is to assess CMP-001’s safety profile as a monotherapy. The study’s completion date is set for December.

Last October, Checkmate treated the first patient in its phase Ib/II trial of Bavencio (avelumab, EMD Serono/Pfizer Inc.) in multidrug combinations with CMP-001 in up to 60 patients with squamous cell cancer of the head and neck. It will also evaluate the triplet combination of CMP-001, avelumab and utomilumab (a 4-1BB agonist, Pfizer); and the triplet combination of CMP-001, avelumab and PF-04518600 (an OX40 agonist, Pfizer), in patients with locally advanced squamous cell cancer of the head and neck.

Enter Idera

Exton, Pa.-based Idera’s tilsotolimod, also a TLR9 agonist, received fast track designation and orphan drug designation from the FDA and is being evaluated in multiple tumor types and in combination with multiple checkpoint inhibitors. It is in a phase I trial for treating anti-PD-1-refractory advanced melanoma. The Illuminate-204 study’s top-line data released in late April showed that of 52 patients treated with 8 mg of tilsotolimod in combination with Yervoy (ipilimumab, Bristol Myers Squibb Co.), the median overall survival was 21 months in 49 evaluable patients. The overall response rate was 22.4%, including two complete responses. The disease control rate (stable disease or better) was 71.4% (95% CI: 56.7%-83.4%) and the median duration of response was 11.4 months (95% CI: 3.3 months-NR).

Idera also has the phase III Illuminate-301 study underway, comparing intratumoral tilsotolimod in combination with ipilimumab with ipilimumab alone in about 450 patients with anti-PD-1-refractory advanced melanoma. The primary outcome measure is efficacy measured by overall survival. Key secondary endpoints include durable response rate, time to response, progression-free survival, patient-reported outcomes and safety. The study completion date is estimated to be September 2021.

Dynavax’s entry

Dynavax is conducting a phase Ib/II open-label, multicenter trial evaluating the safety, tolerability, biologic activity and preliminary efficacy of intratumoral SD-101 injections in combination with intravenous pembrolizumab in patients with metastatic melanoma or recurrent or metastatic head and neck squamous cell carcinoma. SD-101 is a second-generation TLR9 agonist CpG-C class oligodeoxynucleotide. In data released in June 2019, Dynavax reported a progression-free survival rate of 18 months in 72% of the patients in the study enrolling those who are naïve to anti-PD-1/PD-L1 treatment.

For the study, SD-101 is administered intratumorally with 8 mg in one lesion or 2 mg in one to four lesions combined with intravenous administration of 200 mg of pembrolizumab. The overall response rate in the SD-101 2-mg/lesion group (76%) was higher than in the SD-101 8-mg/lesion group (49%).

The study was estimated to be completed in February.

Checkmate’s backers

Checkmate’s series C financing was led by Longitude Capital and Novo Holdings, with participation from existing investors Sofinnova Investments, Venbio Partners, F-Prime Capital and Decheng Capital. New investors included Medicxi, Omega Funds, Clough Capital Partners, Sectoral Asset Management and Brightedge, the venture investment fund of the American Cancer Society. Checkmate brought in a $27 million series B in June 2017 and a $20 million series A in August 2015.

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