A new biotech is coming out of stealth with $16 million to develop cell therapies for solid cancers — an area where scientists have had limited success.
OverT Bio (pronounced “overt,” not “over-T”) launched Monday, founded by New York University professor Neville Sanjana and his former postdoc Mat Legut.
The startup is developing a screening platform which searches for genes that, when overexpressed, could help T cells become better agents against solid tumor cancers. While there have been several cell therapies approved for blood cancers, developing them for solid tumors has proven far more challenging. Only one cell therapy has been approved for a solid tumor cancer: Iovance’s tumor-infiltrating lymphocyte-based therapy Amtagvi, which won FDA approval in February for advanced melanoma.
Neville SanjanaSanjana and Legut met at a conference in Wales in 2017, Legut said, where Sanjana was giving a presentation on his work using CRISPR screening to understand resistance to T cell therapies. He was looking for immunologists to expand his team in New York, and Legut joined him there. They founded OverT in 2022.
The seed round was co-led by ARTIS Ventures and Wing VC, and included Fusion Fund, OMX Ventures, Alexandria Venture Investments, and LGBTQ+-focused venture capital group Gaingels, among other investors.
Screening the genome
Legut and Sanjana exhibited their screening tool in a 2022 Nature paper, pointing out certain genes that can potentially make more potent CAR-T cell therapies when overactivated. In particular, the paper calls out a gene that encodes for the lymphotoxin beta receptor, which is typically not expressed in T cells.
The overexpressed gene “superpowers those T cells versus just regular CAR-T cells,” Sanjana said.
Sanjana had worked on CRISPR screening tools as a postdoc in Feng Zhang’s lab at the Broad Institute of MIT and Harvard, and the gene editing tool was one of the first approaches he and Legut took to develop their screen. “CRISPR cuts genes and can knock them out. But what about the opposite? Can we turn on genes, maybe genes that are never expressed even in T cells, that can kick them into new states?” Sanjana said.
In the hands of Sanjana and Legut, a CRISPR screen that activated genes was not as effective as they had hoped. “That was a great place to start. It turned out to be quite a poor way of engineering T cells for these therapeutic approaches,” Legut said.
So they developed another that would overexpress thousands of genes, each with unique DNA barcodes, to find ones that could stimulate T cell function when activated.
They’re not alone in the approach. Around the same time as the co-founders published their paper, two other research labs published studies on using CRISPR activation screens to identify ways to boost T cell therapies.
OverT Bio is also developing T cell receptors for its cell therapies based on a type of rare immune cell called gamma delta T cells. Gamma delta T cells sit at the crossroads between the initial and secondary responses of the immune system. Unlike typical T cells, they don’t need to be presented with a marker from a foreign substance, such as from a virus or bacteria, to be activated.
OverT Bio’s goal is to have a first development candidate ready for clinical trials by mid-2025, according to Legut. The company currently has 10 employees, Legut said.