Unshackling TP53 in leukaemia with a novel combo; Merus receives funds for cancer research pact; Vera Therapeutics bags $80M; Gritstone appends COVID-19 to the pipeline.

Posted on Jan 21, 2021 by Delveinsight

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Unshackling the TP53 in leukaemia with a novel combination approach.

Drugs that target the cancer-promoting proteins MDM2 and BET have been attempted in acute myeloid leukaemia (AML) and have not been all that effective on their own. However, they might be useful if they were combined.  

Researchers at the Sanford Burnham Prebys Medical Discovery Institute and the University of Glasgow have early proof a combination strategy may work in AML.

Combining MDM2 and BET inhibitors enhanced the eradication of AML cell lines in lab studies and were more effective than solo treatment in killing cancer in mouse models. The researchers stated in the journal Nature Communications. The combination appears to work by activation of the tumour-suppressing protein p53, they announced. 

A senior author Peter Adams, PhD, a professor at Sanford Burnham Prebys said in a statement that the results were astonishing because previous research had shown that each drug on its own had modest benefit against AML. The new research provides a scientific rationale to advance clinical studies of the drug combination in patients with AML.

The gene TP53 produces the protein p53, a known tumour suppressor. TP53 is frequently mutated across various cancers, so targeting the gene is a popular pursuit in oncology research.

Eli Lilly gives a huge amount in biobucks to Merus for next-gen cancer research pact.

Eli Lilly, via its Loxo Oncology biotech unit, is enlisting to a three-therapy pact with Merus concentrated on T-cell redirecting bispecific antibody work.

Netherlands-based Merus receives USD 40 million upfront and a USD 20 million equity investment from the Big Pharma and USD 1.6 billion in total for three drugs.

These will come out of Merus’ so-called Biclonics platform that develops CD3-engaging, T-cell redirecting bispecific antibody therapies.

Jacob Van Naarden, M.D., chief operating officer of Loxo Oncology, said that CD3-engaging bispecific antibodies are soon becoming one of the most transformative immune-modulating modalities used for cancer treatment.  

Merus is working on its internal pipeline zeroing in on zenocutuzumab (also called MCLA-128), targeting fusions comprising the gene NRG1 that can drive the growth of many different types of cancers.

Vera Therapeutics bags USD 80 Million for trials. 

Vera Therapeutics has raised USD 80 million to take a drug licensed from Merck KGaA into a phase 2b kidney disease clinical trial. The drug, atacicept, has flunked multiple autoimmune clinical trials, but Vera contemplates that it is a prospect in IgA nephropathy.

Atacicept is a recombinant fusion protein made to prohibit B cells selectively. Merck, which initially worked with ZymoGenetics on the candidate, recognised the mechanism of action as a good fit for autoimmune diseases, leading it to run clinical trials in multiple sclerosis, optic neuritis, rheumatoid arthritis and systemic lupus erythematosus (SLE).

The drug failed to improve results in most of those diseases. A phase 2 SLE clinical trial, which lost its primary endpoint, showed improved outcomes in a pre-specified subgroup analysis. 

Data in another indication underpin Vera’s interest in atacicept. In 2017, Merck, having seen atacicept fall short in other diseases, began a phase 2 trial to evaluate the drug in 16 patients with the kidney disease IgA nephropathy.

A 24-week interim analysis published last year linked atacicept to a dose-dependent drop in serum immunoglobulins and improved the urine protein-creatinine ratio. While small, the clinical trial provided early proof of concept that atacicept may improve patients’ outcomes with IgA nephropathy. There is no treatment for the disease. 

Gritstone appends COVID-19 to the pipeline with the NIAID-supported vaccine.

Gritstone Oncology, the biotech company, working on cancer vaccines based on traditional infectious disease immunology, works on a vaccine against SARS-CoV-2. This virus causes COVID-19, which could also work against other viruses in this family in a future pandemic.

The company is making the vaccine alongside the Bill & Melinda Gates Foundation that proffered a grant to fund preclinical work, and the National Institute of Allergy and Infectious Diseases, which will perform a phase 1 study via the Infectious Diseases Clinical Research Consortium.

The vaccine is based on Gritstone’s EDGE technology that utilises machine learning to predict antigens presented by tumour cells or cells infected by a virus that the immune system can see, and work out of the La Jolla Institute of Immunology, which has researched hundreds of patients recovering from COVID-19. 

Under a licensing pact with La Jolla, Gritstone has access to epitopes of the SARS-CoV-2 virus, a part of the virus to which antibodies bind, identified in its studies.

Besides potentially provoking a more robust immune response than the first generation of COVID-19 vaccines does, a new vaccine focused at targets beyond the spike protein could prove useful in the face of new variants of the SARS-CoV-2 virus.

Like the first generation of COVID-19 vaccines, the candidate of Gritstone aims the spike protein of the new coronavirus. However, it also includes other targets that could help boost T-cell immunity.

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