Discoveries & Innovation: New Oncology Target Shows Promise
A new class of drug, dubbed 5D4 and considered a TopBP1 inhibitor, shows the potential to halt breast and ovarian cancer in mouse models. Results were even better when paired with Pfizer’s existing Talzenna, a poly ADP-ribose polymerase (PARP) 1/2 inhibitor called talazoparib. TopBP1 is a protein researchers have considered important in cancer development, including the overdevelopment of MYC protein, which is often present in the worst outcomes in breast, blood, lung and other types of cancer. Traditionally, it has been a difficult protein to inhibit with drugs, but researchers at Baylor College of Medicine are changing that.
After testing thousands of proteins that could target the needed area of the TopBP1, the team tested 5D4 in mice. They found that the drug reduced tumor growth in both of the models compared to controls. This was also the case for a second, more aggressive model of breast cancer with a high level of MYC overexpression.
“It’s very exciting to have found a TopBP1 inhibitor that really stops cancer growth in cells and in animal models in the lab,” Fang-Tsyr Lin, MD, PhD, first and co-corresponding author, said in a statement. Research is going to continue to determine the feasibility of human trials.
Therapeutic Talk: Gene Mutation Breakthrough
Prime Medicine has successfully reversed a gene mutation involved in a rare liver disease in chimpanzees, taking steps towards bringing the innovation to humans. Researchers at Prime were able to prove that a single dose of their gene editing therapy could repair the gene associated with glycogen storage disease 1b in up to 83% of target cells in the livers of primates. The company estimates that a 10% correction rate is required for therapeutic benefit in humans.
“[We] are highly encouraged by the efficient and precise corrections we have observed across in vitro evaluations, in vivo rodent studies, and now, nonhuman primate studies (NHP) studies,” Jeremy Duffield, MD, PhD, Chief Scientific Officer at Prime Medicine, said in a press release. “Importantly, we continue to observe minimal to no detectable off-target edits with our Prime Editors, providing further confidence in the precision of this technology.”
The company relies on its Prime Editing guide RNAs, or pegRNAs, to find a mutated sequence and alter it, thereby correcting the pathology that stems from it in a process more precise than CRISPR. Clinical trials and data analysis from the effect in primates will continue to inform the potential impact on humans with the same and similar genetic diseases.
FDA Update
The FDA approved Bristol Myers Squibb’s Opdivo (nivolumab) for expanded use as an adjuvant treatment of completely resected Stage IIB/C melanoma in patients 12 years and older. Nivolumab is appropriate for adults and pediatric patients in monthly doses until disease progression or unacceptable toxicity for up to one year.
Agamree (vamorolone) has been approved by the FDA to treat Duchenne muscular dystrophy (DMD). Santhera Pharmaceuticals received approval for the dissociative steroid with the effects of steroid treatment minus deleterious side effects, which they hope can work for multiple indications into the future, such as asthma, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other rare diseases besides DMD.
