Through our broad approach to drugging the immune system, we have generated a robust pipeline focused on bridging innate and adaptive immunity.  Our differentiated antibodies and multispecifics effectively engage T cells, NK cells, and macrophages to promote tumor-specific activation or reverse immune suppression.

Discovery
In-Vitro
In-Vivo
IND Enabling
Studies
Phase 1
T-Cell
Activation
CTX-471 / CD137 agonist
Phase 1

CTX-471 is a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137, also known as 4-1BB, a member of the tumor necrosis factor receptor superfamily.

Preclinical data presented at the 2018 Society for Immunotherapy of Cancer Annual Meeting suggest that CTX has the potential to become a best-in-class CD137 agonist displaying curative monotherapy efficacy against multiple syngeneic tumor models and generation of long-term functional immunological memory. Most notably, CTX-471 is able to induce the complete eradication of large, established tumors where other preclinical CD137 antibodies and antibodies against PD-1, PDL, CTLA, and OX40 have minimal effect. CTX-471 profoundly reprograms the tumor microenvironment, increasing CD8+ T cell infiltration and penetration while reducing T-cell exhaustion. In contrast to other clinical and preclinical CD137 antibodies, CTX-471 shows no evidence of hepatic inflammation and toxicity in both mice and non-human primates, supporting a wide therapeutic window.

We are now enrolling patients in a Phase 1 clinical trial of CTX-471. Visit clinicaltrials.gov for more information.

CTX-471 Combination
IND Enabling Studies

CTX-471 is a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137, also known as 4-1BB, a member of the tumor necrosis factor receptor superfamily.

In preclinical combination sudies, CTX-471 significantly enhances the efficacy of other IO agents including tumor targeting antibodies cetuximab (Erbitux) and trastuzumab (Herceptin), checkpoint inhibitors against PD-1 and PD-L1, and small molecule inhibitors of CXCR2.

Checkpoint Blockade
CTX-8371 / PD-1 x PD-L1
In-Vivo

CTX-8371 is a common light chain-based, bispecific antibody targeting the checkpoint receptor PD-1 and its ligand PD-L1. Discovered via an unbiased screen of bispecifics targeting checkpoint combinations using our StitchMabsTM platform, CTX-8371 enhances T cell activation and tumor cell killing in vitro and in vivo with significantly increased potency compared to Keytruda and other approved PD-1/PDL-1 therapies. Mechanistic studies suggest that the enhanced efficacy is due to a unique ability of this bispecific to drive PD-1 downregulation and degradation in T cells.

NK Cell
Activation
CTX-8573 / NKp30 x BCMA
IND Enabling Studies

CTX-8573 is a first-in-class, common light chain-based NKp30 x BCMA bispecific antibody that targets B-cell maturation antigen (BCMA) positive tumor cells and potently recruits and activates NK and γδ T cells through engagement of the activating receptor NKp30, as well as the activating receptor CD16a through an intact Fc. Compared to monoclonal antibodies that only engage CD16a, the NKp30 bispecific platform increases ADCC potency more than 100-fold, and also maintains activity in the context of CD16a downregulation. This allows the bispecific to productively engage CD16a-low or -negative NK subpopulations that are enriched in certain tumor settings.

Unlike conventional monoclonal antibodies that require high levels of target antigen for efficacy, CTX-8573 potently induces NK cell activation and killing of tumor cells that express high, medium and low levels of BCMA. Importantly, CTX-8573 does not activate NK cells in the absence of BCMA-positive tumor cells, lowering the risk of off-target toxicities. Due to its common light chain-based molecular structure, CTX-8573 is highly manufacturable with expression, purity, stability, and pharmacokinetics essentially identical to a monoclonal antibody.

Preclinical data on the NKp30 x BCMA platform was presented at the 2018 Society for Immunotherapy of Cancer (SITC) annual meeting and the 2019 American Association for Cancer Research annual meeting.

NKp30 x TAA
In-Vitro

The NKp30 bispecific engager platform originally developed for targeting BCMA is a highly modular format that can be extended to other tumor-targeting antibodies against hematological and solid tumor antigens. Using our common light chain discovery platform, Compass scientists have generated NKp30 bispecific engagers targeting diverse indications including NHL and breast cancer, with additional programs for prostate and ovarian cancer in progress. Our lead NKp30 x Her2 bispecific demonstrates enhanced activity compared to trastuzumab (Herceptin) targeting cells with a wide range of Her2 expression.

Checkpoint Blockade
TGFβtrap x TIGIT
In-Vitro

Compass’ TGFβ x TIGIT bispecific is a novel therapy designed to neutralize TGFβ, a highly immunosuppressive cytokine that is overproduced by many tumors, while simultaneously blocking the immune inhibitory receptor TIGIT (T cell immunoreceptor with Ig and ITIM domains) commonly expressed on exhausted T and NK cells. Unlike other TIGIT blockers currently in development, Compass’ TIGIT blocker is a non-depleting, pure antagonistic antibody.

Macrophage
Activation
CTX bispecific
In-Vitro
Checkpoint Blockade
SIRPα and combinations
In-Vivo

CTX-5861 is a fully human SIRPα antibody which binds and blocks all polymorphic alleles of SIRPα. By inhibiting SIRPα engagement with CD47, it prevents the “do not eat me” signal in macrophages, leading to enhanced antibody-mediated phagocytosis (ADCP) of tumor cells. In syngeneic tumor models, CTX-5861 significantly increases the efficacy of tumor-targeting antibodies, checkpoint blockers, and our CD137 agonist CTX-471, without inducing the hematological toxicities (hemagglutination, anemia) observed with CD47-directed therapies.

Partnering philosophy

We are looking for strategic partners to help advance our pipeline of next-generation antibody therapeutics. We are also seeking discovery collaborations around our StitchMabs™, common light chain and Sympleitope™ discovery technologies.

Are you interested in collaborating with us? Contact partners@compasstherapeutics.com.