San Diego cancer upstarts Oncternal and Tokalas announce merger

Two biotech startups, Oncternal and Tokalas, have unveiled a merger today that will see the pair combine their research efforts on new experimental cancer drugs under one umbrella group, with pre-existing U.S. university deals also in the loop.

The companies--which are both based in the San Diego area--will bring together all of their assets, R&D programs and operations under the Oncternal Therapeutics name. Financial details have not been disclosed.

The new biotech’s president and CEO will be Dr. James Breitmeyer--an oncologist with more than 25 years in the industry who has led efforts resulting in approval of 8 U.S. or international product approvals, and was most recently president of Bavarian Nordic.

The board of directors will be chaired by Dave Johnson, the man who led Netherlands-based biotech Acerta to be majority owned by AstraZeneca ($AZN) in a deal worth up to $7 billion. The other initial board members will be David Hale, Cam Garner, Scott Glenn, and Breitmeyer--who have been involved in founding and/or developing more than 30 life sciences companies.

The combined company will have two clinical-stage oncology products with potential across a range of cancer indications.

This includes cirmtuzumab, a first-in-class anti-ROR1 monoclonal antibody, currently in a Phase I trial for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). 

Cirmtuzumab was developed by Dr. Thomas Kipps at the Moores Cancer Center of UC San Diego, who conducted research to characterize the function and expression of ROR1--which may identify cancer stem cells in a number of hematologic malignancies and solid tumors.

Dr. Kipps is currently the Evelyn and Edwin Tasch Chair in Cancer Research, Distinguished Professor UC San Diego, and deputy director, research operations, Moores Cancer Center. Cirmtuzumab was initially developed at UC San Diego by Dr. Kipps with funding from the US National Institutes of Health, the California Institute for Regenerative Medicines, and the Blood Cancer Research Fund. 

Oncternal and UC San Diego are currently planning studies in CLL, breast cancer and mantle cell lymphoma later this year. Oncternal also has rights to develop antibody-drug conjugates (ADCs), genetically modified effector immune cells, such as chimeric antigen receptor T-cells (CAR-T), and bispecific antibodies related to ROR1.

The candidate is a humanized IgG1 monoclonal antibody that was designed and developed to bind with high affinity to a biologically important epitope on the extracellular domain of ROR1. Binding of cirmtuzumab to ROR1 on tumor cells inhibits Wnt5a signalling, a pathway that is important for tumor-cell proliferation, migration, and survival. Blockade of this Wnt5a signaling leads to tumor cell death by apoptosis.

Receptor-tyrosine kinase-like orphan receptor 1--also known as ROR1--is a type 1 transmembrane protein that is expressed on the plasma membrane with an extracellular domain that is essential for ligand binding and signal transduction.

High-level expression of ROR1 has been found in many cancers but the highest and most consistent expression of the ROR1 protein is in mantle cell lymphoma, where virtually all patient samples express ROR1, and CLL, and 95% express ROR1 on the cell surface, according to the biotech.

ROR1 is also expressed at high frequency in many solid tumors, including lung and ovarian cancers, as well as triple-negative breast cancer.

And then there is TK216, a first-in-class small molecule ets-family transcription factor inhibitor, which is about to enter human testing for patients with Ewing sarcoma. 

TK216 is based upon the discoveries of Jeffrey Toretsky at Georgetown University, who conducted initial research on the ets-family oncogenic translocations that cause or drive tumor growth in a number of solid and hematologic malignancies. Oncternal and Georgetown are also planning clinical studies in Ewing sarcoma, glioblastoma and prostate cancer in the next year.

"We are merging two San Diego companies developing clinical-stage therapeutic candidates against novel and important cancer targets, creating an exciting new oncology company with a clinical-stage pipeline spanning multiple technologies and cancer indications," said Dr. Breitmeyer in a release.

"Common regulatory and development strategies result in significant synergies for the combined company. Our highly experienced management team will lead Oncternal forward and rapidly advance our two products, cirmtuzumab and TK216, into additional clinical trials for some of the most devastating and underserved forms of cancer."

- check out the release