Evelo (EVLO) announced on December 9th that the company is developing a new modality of orally delivered medicines which act in the small intestine with systemic effects, today announced that it is prioritizing EDP1908 as its lead clinical candidate in oncology given its superior preclinical activity over EDP1503. The Company will halt patient recruitment in the Phase 1/2 clinical trial of EDP1503 and will wind down the study.
The Company also announced that additional interim clinical data from its Phase 1/2 open-label study evaluating EDP1503 in combination with pembrolizumab in patients with triple-negative breast cancer (TNBC) were presented today in a poster session at the San Antonio Breast Cancer Symposium (SABCS) 2020 Virtual Meeting. The presentation showed that as of a cutoff date of October 30, 2020, EDP1503 was well-tolerated, with an overall response rate (ORR) of 17 percent and a disease control rate (DCR) of 25% in the 12 patients who received the higher dose of EDP1503. These results suggest that the small intestinal axis, SINTAX™, has the potential to be targeted with oral, gut-restricted medicines
In the preclinical study presented at SITC, tumor-bearing mice were treated with ascending doses of either oral EDP1908 or the parental microbial strain of EDP1908, or with anti-PD-1. Treatment with EDP1908 resulted in superior tumor growth control versus either the parent microbial strain or anti-PD-1 therapy, with an observed dose-dependent reduction in tumor growth. The effects were at least comparable to those reported in the literature for intra-tumorally administered immune stimulators.
Treatment with EDP1908 significantly reduced tumor growth in syngeneic mice compared to vehicle, and activated IFNγ-positive cytolytic and helper lymphocytes, dendritic cells, and interferon gamma-induced protein 10 (IP-10) in the tumor microenvironment. Fluorescent biodistribution analysis showed that EDP1908 was not detected outside the gastrointestinal tract. These data suggest that EDP1908 activated innate immunity locally on host immune cells in the gut and triggered distal immune responses within the tumor microenvironment, with no apparent adverse safety or tolerability issues.
Interim Data Presented at SABCS from the Phase 1/2 Clinical Trial of EDP1503 in Combination with Pembrolizumab
As of the data cutoff date of October 30, 2020, 15 patients had been treated across two EDP1503 doses, including three patients treated with low dose EDP1503 (two capsules twice daily (BID)) and 12 patients treated with high dose EDP1503 (four capsules BID). 27 percent of patients had received prior anti-PD-(L)1 therapy.
Interim Safety Results
As of the cutoff date, the combination of EDP1503 and pembrolizumab was generally well-tolerated with the majority of treatment-related adverse events (AEs) reported by investigators being Grade 1 or 2. Across all grades, treatment-related AEs reported by investigators most commonly included abdominal distension (20%), decreased appetite (20%), diarrhea (13%), flatulence (13%), nausea (13%), pruritis (13%) and rash maculo-papular (13%). Investigators reported a single treatment-related Grade 3 AE in one patient (diarrhea). No treatment-related Grade 4 or 5 AEs or serious AEs were reported, and one patient discontinued EDP1503 due to a treatment-related AE.
Interim Efficacy Results
Fifteen patients were evaluable for response assessment as of the cutoff date, as measured using the Response Evaluation Criteria in Solid Tumors (RECIST). Among all 15 patients treated, the ORR was 13 percent, and the DCR was 20 percent. In patients receiving high dose EDP1503 therapy (n=12), the ORR was 17 percent and the DCR was 25 percent, with partial responses observed in two patients and stable disease observed in one patient. One patient who had relapsed on prior therapy with an anti-PD-L1 inhibitor combination had a partial response to the EDP1503 and pembrolizumab combination treatment. The patient was on treatment for 10.5 months and had no measurable disease visible on their latest PET scan as of the data cutoff date.