Cellestia

Pipeline and Science

R&D Programs

Discovery

ADME / PoC

IND Enabling

Phase 1

Phase 2

CB-103 CSL-NICD                              

Solid Tumors and Leukemia

CB-103 CSL-NICD

GvHD in SC Transplant

NextGen  CSL-NICD

Additional AIID indications

Virus Induced Cancers

AML – Oncology

MYB – Oncology

R&D Programs

Discovery

ADME / PoC

IND Enabling

Phase 1

Phase 2

CB-103 CSL-NICD

Solid Tumors and Leukemia

CB-103 CSL-NICD

GvHD in SC Transplant

NextGen CSL-NICD

Additional AIID indications

Virus Induced Cancers

AML – Oncology

MYB – Oncology

The outstanding potency and safety of CB-103 has been confirmed in the Phase 1 clinical trial, showing strong target engagement and downregulation of key target genes. CB-103 has also demonstrated strong clinical benefit for ACC patients achieving long-term disease control. Achieving clinical proof of concept for CB-103 is the foundation to now enter Phase 2 clinical development with treatment of patients with ACC, T-ALL, breast cancer and rare NOTCH positive tumors.

In addition, the company has a rich pipeline of pre-clinical assets, with in vivo proof of concept in relevant animal models, covering a wide range of indications such as oncology, virus-induced cancers, and autoimmune and inflammatory disorders. These achievements put Cellestia on an excellent track to bring first-in-class innovative therapies to patients, addressing currently unmet medical needs across a wide range of indications.

TESTIMONIALS

“Cellestia’s capability to control and modulate gene expression is a big step forward in developing new high potential breakthrough medicines for treatment of cancer and other indications.”

David R. Epstein
Chairman of Cellestia’s Strategic Advisory Boards

Innovative Approach

Cellestia is developing first-in-class therapies to control pathogenic gene expression by selective inhibition of previously undruggable gene transcription factors (GTFs) in the cell nucleus.

Gene transcription is one of the fundamental principles of life, and dysregulation of this process is the core driver of most diseases. Selectively controlling gene expression by directly targeting specific gene transcription factors has been an aim of modern medicine for decades, as it would offer the possibility to modulate a virtually unlimited range of biological processes contributing to disease.

In spite of their enormous therapeutic potential, GTFs have remained undruggable due to lack of small molecule binding pockets and inaccessibility to therapeutic antibodies. However recent advances in structural biology have allowed identification of unique pockets in GTFs amenable to targeting with small molecule drugs.

Cellestia has been at the forefront of identifying and targeting GTFs implicated in human disease, and has brought a first-in-class GTF-targeting drug to the clinic. One key success factor for Cellestia is in its ability to integrate computational power for structure–activity relationship modelling with experience in medicinal chemistry and scientific excellence. These competencies have enabled Cellestia to design, synthesize and evaluate new therapeutics in a very effective rational design process with an outstanding success rate, rapidly creating an attractive portfolio of R&D projects.

“Gene transcription factor inhibitors: a novel class of therapeutics modulating gene expression.”

The importance and oncogenic contribution of the Notch signaling pathway is well recognized, making it a clinically relevant therapeutic target in cancer. In most cancers, oncogenic aberrations of the Notch pathway emerges as the disease evolves into a genetically complex disease, with simultaneous activation of multiple oncogenic pathways.

 

As shown in the graph above CB-103 selectively inhibits CSL-NICD interaction, thereby preventing the assembly of the complex and leading to down-regulation of target gene expression.

Cellestia has fully validated CB-103’s novel mode of action, confirming the exquisitely selective and highly potent control of gene transcription.

Cellestia is developing a novel therapy for currently untreatable cancers.

Our Biomarker Program

As a highly selective targeted therapy, CB-103 is being developed for cancer patients in which aberrant signaling of this mode of action contributes to tumor growth, metastatic spread and eventually multi-drug resistance. Identifying these patients is essential both for running informative clinical trials of CB-103, and, in the future, ensuring that this therapy is only given to patients who will benefit from it. To meet this goal, Cellestia has developed a comprehensive biomarker and diagnostic program that will be used for identification of patients requiring such targeted therapy as well as evaluating pharmacodynamic responses to treatment. This program will finally serve as the basis for companion diagnostic development guiding the use of CB-103 to identify patients who most benefit.