CHS-114 shown to have an acceptable safety profile with no dose-limiting toxicities (DLTs) in heavily pretreated patients with solid tumors

Selective depletion of peripheral CCR8+ regulatory T cells (Tregs) was observed and depletion was maintained over the dosing interval, establishing proof of mechanism

Preclinical data and preliminary clinical results support further evaluation of CHS-114 in combination with the anti-programmed cell death protein 1 (PD-1) antibody, toripalimab-tpzi, and other immuno-oncology (IO) agents

REDWOOD CITY, Calif., May 23, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today announced clinical data from the CHS-114, single agent dose escalation stage of its Phase 1 study at the ASCO Annual Meeting, taking place May 31 to June 4, 2024, at McCormick Place in Chicago. CHS-114 is a novel afucosylated human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that selectively and potently targets human CCR8 with no off-target binding. CCR8 is a G protein-coupled receptor (GPCR) that shows preferential expression on tumor resident Treg cells and has promise as a drug target for selectively targeting immune suppression in the tumor microenvironment (TME) without broadly depleting Treg cells, which has the known unwanted side effect of autoimmune activation.

“The Phase 1 preliminary dose escalation results are an important milestone as we progress our innovative I-O pipeline. We are very pleased with the safety profile, the predictable dose proportional pharmacokinetic profile, and the selective depletion of peripheral CCR8+ Tregs that were observed,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “By targeting CCR8, we believe CHS-114 has the potential to overcome Treg immune suppression in the TME and allows T cell recruitment, which turns cold tumors hot and enhances anti-tumor activity when combined with I-O agents. The data support further evaluation of CHS-114 in combination treatment with our anti-PD-1 antibody, toripalimab, and other I-O agents.”

CCR8 is a chemokine receptor predominantly expressed by tumor infiltrating Tregs that suppress the body’s natural anti-cancer immune response. Targeting CCR8 is a promising potential therapeutic strategy designed to selectively deplete intratumoral CCR8+ Tregs, reshape the tumor microenvironment by alleviating local immunosuppression, and enhance anti-tumor immune response when combined with I-O agents. Data presented at ASCO demonstrate proof of mechanism for selective depletion of CCR8+ Tregs and an acceptable safety profile to date.

Poster presentation:

Abstract # 2664: Preliminary Results of a Phase 1, First-in-human, Dose Escalation Study of the Anti-CCR8 Cytolytic Antibody, CHS-114 (formerly SRF114) in Patients with Advanced Solid Tumors.
Poster Session: Developmental Therapeutics - Immunotherapy
Date and Time: Saturday, June 1, 2024, 9:00 a.m. – 12:00 p.m. Central Daylight Time

Poster presentation data are summarized as follows:

• CHS-114 has demonstrated an acceptable safety profile in 20 evaluable, heavily pre-treated patients with advanced solid tumors, with no DLTs reported to date. Treatment emergent adverse events (TEAEs) were generally low grade. One patient experienced a treatment-related serious adverse event (SAE) of Grade 2 colitis. There were no treatment related adverse events (AEs) leading to discontinuation or death.
• CHS-114 PK exposure was approximately dose proportional, and the elimination appeared linear with a half-life of about 10 days (range 9-17 days).
• Depletion of peripheral CCR8+ Treg cells was observed and depletion was maintained over the dosing interval, establishing proof of mechanism.
• Preliminary results and acceptable safety profile support further evaluation of CHS-114 in combination treatment with toripalimab and other I-O agents. In 19 patients evaluable for response, no objective responses were yet noted, while the stable disease rate was 47%.

About the Phase 1 trial (NCT05635643):

SRF114-101 is a Phase 1, First-In-Human, open-label, dose escalation study, evaluating CHS-114 as a single agent and in combination with toripalimab. The study enrolled patients with advanced solid tumors who received more than one line of prior treatment (75% had more than three prior lines). Stage 1a of the study included CHS-114 administered intravenously (IV) on day one of each Q3W cycle as part of single-agent dose escalation and employed the Bayesian optimal interval (BOIN) design, including accelerated titration and 3+3 run-in. Stage 1b will enroll an additional five patients with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) at each of two dose levels.

Primary endpoints: rate of DLTs and TEAEs, with the overarching objective of determining two recommended doses for expansion (RDE).

Key secondary endpoints: objective response rate (ORR) based on Investigator review per RECIST v1.1, pharmacokinetics, pharmacodynamic assessments (changes in FOXP3 expression within tumor tissue –Stage 1b).

Exploratory pharmacodynamic endpoint: Changes in frequency of CCR8-expressing immune cell subsets in the periphery.

About CHS-114

CHS-114, a human, afucosylated anti-CCR8 monoclonal antibody, is designed to selectively target human CCR8 and preferentially deplete CCR8+ Tregs within the tumor microenvironment, while preserving effector T (Teff) cells in tumors or Tregs in normal tissue. In preclinical studies, CHS-114 induced antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) to deplete tumoral CCR8+ Tregs. In addition, treatment with CHS-114 alone reduced tumor growth in murine models, and enhanced antitumor activity was observed in combination with anti-PD-1 treatment. CHS-114 is currently being evaluated in a Phase 1 clinical trial (NCT05635643) as a monotherapy and in combination with toripalimab in advanced solid tumors, including head and neck cancer. As reported in June 2023, early evidence of biological effect has been seen with CCR8+ Tregs depletion in blood following treatment with CHS-114, with no effect observed on non-CCR8+ Tregs.

About Coherus BioSciences 

Coherus is a commercial-stage biopharmaceutical company focused on researching, developing, and commercializing innovative therapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline expected to synergize with its proven commercial capabilities in oncology. 

Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust antitumor immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel IL-27 antagonistic antibody currently being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors. CHS-1000 is a preclinical candidate targeting immune-suppressive mechanisms via the novel pathway ILT4, with a response from the FDA on Coherus’ IND filing expected in the second quarter of 2024.

Coherus markets LOQTORZI^® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, UDENYCA^® (pegfilgrastim-cbqv), a biosimilar of Neulasta^®, and YUSIMRY^® (adalimumab-aqvh), a biosimilar of Humira^®.

Neulasta^® is a registered trademark of Amgen, Inc.
Humira^® is a registered trademark of AbbVie Inc.

Forward-Looking Statements

Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Coherus’ ability to identify synergies between its I-O pipeline and its commercial capabilities; Coherus’ expectation for the timing of the FDA’s response for its IND for CHS-1000; Coherus’ expectation that CHS-114 has the potential to overcome Treg immune suppression in the TME; and Coherus’ expectations that its immunotherapy candidates will enhance outcomes for patients with cancer.

Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance, or achievements to differ significantly from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the preclinical and clinical drug development process; risks related to Coherus’ existing and potential collaboration partners; risks of Coherus’ competitive position; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus’ regulatory filings; the risks of competition; the risk that Coherus is unable to complete commercial transactions; and the risks and uncertainties of possible litigation. All forward-looking statements contained in this press release speak only as of the date of this press release. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2024 filed with the Securities and Exchange Commission on May 9, 2024, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission.

UDENYCA^®, YUSIMRY^® and LOQTORZI^®, whether or not appearing in large print or with the trademark symbol, are trademarks of Coherus, its affiliates, related companies or its licensors or joint venture partners unless otherwise noted. Trademarks and trade names of other companies appearing in this press release are, to the knowledge of Coherus, the property of their respective owners.

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