Confirmed overall response rate (ORR) of 21% in the Phase 1b dose-escalation stage across all doses, with 1 complete response and 3 partial responses

Confirmed ORR 33% at the highest and recommended Phase 2 dose

Durable and ongoing responses at the time of data analysis, with progression-free survival exceeding 6 months in all 4 responders and 16 months in 2 responders

Shrinkage of injected as well as regional or distant noninjected tumors, supportive of systemic (abscopal) effects

CHICAGO, IL & CAMBRIDGE, MA, USA I November 9, 2020 I Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing proprietary spherical nucleic acid (SNA™) technology, today announced the presentation of updated Phase 1b data from the ongoing Phase 1b/2 clinical trial evaluating intratumoral cavrotolimod (AST-008), the Company’s SNA-enabled TLR9 agonist, in combination with the anti-PD-1 therapies pembrolizumab (KEYTRUDA®) or cemiplimab (LIBTAYO®), in patients with Merkel cell carcinoma, cutaneous squamous cell carcinoma, and other advanced solid tumors (NCT03684785).

The Phase 1b dose-escalation stage was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of cavrotolimod alone and in combination with pembrolizumab, and to identify a recommended Phase 2 dose. Cavrotolimod was dosed intratumorally once weekly for 8 weeks and subsequently once every 3 weeks. Following an initial cavrotolimod monotherapy period, pembrolizumab was initiated at week 3 and dosed in combination with cavrotolimod once every 3 weeks. The Phase 1b stage enrolled patients with locally advanced or metastatic melanoma (n=10), Merkel cell carcinoma (n=5), cutaneous squamous cell carcinoma (n=2), head and neck squamous cell carcinoma (n=2), and leiomyosarcoma (n=1).

Updated data from the Phase 1b stage demonstrated that the combination of cavrotolimod and pembrolizumab continued to be well tolerated, with a confirmed overall response rate (ORR) of 21% (4/19 patients) according to RECIST v1.1 criteria. The combination immunotherapy regimen induced durable and systemic anti-tumor responses in patients with advanced solid tumors who previously progressed on anti-PD-1 therapy. At the time of enrollment in the clinical trial, 85% of patients were experiencing progressive disease despite treatment with PD-1 blockade and 65% of patients had been treated with 2 or more lines of systemic therapy.

Highlights from the Phase 1b Dose-Escalation Stage

– The RECIST-confirmed ORR was 21% (4/19 patients) overall in the Phase 1b dose-escalation stage, reflecting 1 complete response and 3 partial responses.

– In the highest cavrotolimod dose cohort (32 mg), which was selected as the Phase 2 dose, the RECIST-confirmed ORR was 33% (2/6 patients).

– Responses were durable and ongoing at the time of data analysis, with progression-free survival exceeding 6 months in all 4 responders and 16 months in 2 responders.

– 85% of patients overall (17/20 patients) and 75% of responders (3/4) were progressing on anti-PD-1 therapy at the time of trial enrollment.

– Systemic (abscopal) effects were observed, with shrinkage of regional or distant noninjected tumors.

– The majority (98%) of treatment-related adverse events were grade 1 or grade 2. No dose-limiting toxicities and no treatment-related serious adverse events were reported in the Phase 1b stage. The most common adverse events were flu-like symptoms and injection site reactions, consistent with other adverse events experienced with local and systemic immune activation associated with TLR9 agonism.

Details of the poster presentation are as follows:

Title: Safety and preliminary efficacy of intratumoral cavrotolimod (AST-008), a spherical nucleic acid TLR9 agonist, in combination with pembrolizumab in patients with advanced solid tumors

Authors: Steven J. O’Day, Cesar A. Perez, Trisha M. Wise-Draper, Glenn J. Hanna, Shailender Bhatia, Ciara M. Kelly, Theresa M. Medina, Douglas E. Laux, Adil Daud, Sunandana Chandra, Montaser Shaheen, Ling Gao, Melissa A. Burgess, Leonel Hernandez-Aya, Emil M. deGoma, Weston L. Daniel, Douglas E. Feltner, Laurel Sindelar, Robert E. Michel, Alice S. Bexon, Martin Bexon, and Mohammed M. Milhem

Poster/Abstract Number: 423

The abstract and poster will be available on the SITC website once the conference begins on Monday, November 9 at 8:00 a.m. EST. The poster will also be made available on the Exicure website.

Live Q&A will take place Wednesday, November 11 from 5:15–5:45 p.m. EST and Friday, November 13 from 4:40–5:10 p.m. EST.

About Exicure, Inc.

Exicure, Inc. is a clinical-stage biotechnology company developing therapeutics for neurology, immuno-oncology, inflammatory diseases and other genetic disorders based on our proprietary Spherical Nucleic Acid, or SNA technology. Exicure believes that its proprietary SNA architecture has distinct chemical and biological properties that may provide advantages over other nucleic acid therapeutics and may have therapeutic potential to target diseases not typically addressed with other nucleic acid therapeutics. Exicure is in preclinical development of XCUR-FXN an SNA–based therapeutic candidate, for the treatment of Friedreich’s ataxia (FA). Exicure’s therapeutic candidate cavrotolimod is in a Phase 1b/2 trial in patients with advanced solid tumors. Exicure is based in Chicago, IL and in Cambridge, MA.

For more information, visit Exicure’s website at

SOURCE: Exicure