Eli Lilly and Co. has signed another billion-dollar deal, this time with Boston-based Ascidian Therapeutics Inc., a company that is barely four years old and one that is focused on treating human diseases by rewriting RNA. “Our technology, we call it RNA exon editing,” said Ascidian’s Chief Scientific Officer Robert Bell. “It edits RNA, not DNA … but it does so at the kilobase scale.” The company’s exon editors repair genetic instructions that cause disease and are designed to address large genes or those with high mutational variance. The RNA is rewritten using the cell’s natural RNA splicing machinery. The genome is not modified, nor are foreign enzymes introduced, and the work is done fully in vivo, within a single adeno-associated virus. In return for receiving exclusive, target-specific rights to Ascidian’s RNA exon editing technology for undisclosed kidney disease targets, Indianapolis-based Lilly will pay Ascidian up to $1.9 billion in an up-front payment, development and commercial milestone payments, and tiered royalties on global commercial sales.

Cytomx, Regeneron expand bispecifics deal to potential $4B

Cytomx Therapeutics Inc. and Regeneron Pharmaceuticals Inc., which inked a bispecifics-focused collaboration worth up to $2 billion in 2022, agreed to broaden their efforts in an expanded deal that provides Cytomx with additional funding up front as it advances its promising colorectal cancer candidate, varsetatug masetecan (Varseta-M). As with the initial agreement, the up-front payment is modest, with Cytomx set to receive a $37 million target selection payment for two additional programs to be selected. Beyond that, Regeneron gains an option to choose up to six more future targets. If it opts for the full package, the target nomination, R&D, regulatory and sales-based milestones to Cytomx under the newly expanded collaboration could total up to about $4 billion.

Pancreatic space heating up with news from Revolution, others

After Revolution Medicines Inc.’s headline-making pancreatic cancer splash at the American Society of Clinical Oncology meeting in Chicago – along with other recent updates in the space – investors as well as patients are looking at the indication with renewed hope. Redwood City, Calif.-based Revolution provided details from the phase III RASolute 302 study with its pan-RAS inhibitor daraxonrasib previously treated, metastatic pancreatic ductal adenocarcinoma. Players with dispatches lately include Can-Fite Biopharma Ltd., Ideaya Biosciences Inc. (collaborating with Roche AG), and Immuneering Corp.

Rubio reopening door with Gavi

Nearly a year after Health and Human Services Secretary Robert Kennedy announced that the U.S. was cutting off funding for Gavi, a global vaccine alliance, Secretary of State Marco Rubio said his department is reengaging with the organization in light of the ongoing Ebola outbreak in central Africa. Rubio’s comments before the Senate Foreign Relations Committee yesterday provided no details of what that engagement might look like, but Rubio acknowledged such a step contradicts Kennedy’s vaccine stance, which led to him slamming the door on the alliance last year.

Mammogen raises $30M for blood-based breast cancer detection assay

Mammogen Inc. raised $30 million in equity financing in a series A round to support the clinical advancement and commercialization of its RNA-powered molecular diagnostics platform. The company’s lead product is Gentru-breast, a blood-based assay designed to detect molecular signatures associated with breast cancer from a simple blood draw. Mammogen hopes that the test will help with the earlier detection of breast cancer, particularly for women with dense breast tissue, where traditional screening approaches, such as mammograms and ultrasound scans, can face meaningful limitations.

Nature: Single cell sequencing links non-coding loci to genes

Genome-wide association studies (GWAS) have identified multiple loci associated with complex diseases, but these are mostly on regulatory genes in the non-coding part of the genome, and it has proved difficult to identify the effector genes that they control. Now, researchers in the U.K. have shown how single cell sequencing at scale can be used to precisely link non-coding GWAS loci to specific protein coding genes and cell types. They demonstrate this by pinpointing effector genes at more than half of the 321 loci associated with inflammatory bowel disease risk, and propose their approach provides a framework for interpreting non-coding loci in other complex diseases. “Genome-wide association studies have told us where in the genome IBD risk resides, but this study tells us which genes these risk variants disrupt and in which cell types this occurs,” said Carl Anderson, co-author of a paper in Nature describing the research.

CRISPR-based approach fights pathogenic E. coli

Escherichia coli is both a ubiquitous commensal in the human gut and, sometimes, an opportunistic pathogen causing severe intestinal and extraintestinal infections. Shiga toxin-producing E. coli (STEC) represents a public health threat that can lead to serious problems, such as bloody diarrhea and hemolytic uremic syndrome (HUS) in children in up to 10%-15% of cases. STEC produce two types of toxins, Stx1 and Stx2, with Stx2 causing most of HUS cases and E. coli O157:H7 being the most common serotype involved in human disease. Antibiotics that normally combat diarrhea are not recommended for STEC infections and patients are usually treated only for symptomatology. Now, French researchers from Eligo Bioscience SA and their collaborators have published a paper on a CRISPR-based antimicrobial approach, EB-003, aimed for cleavage of the Shiga toxin gene targeting >99% of the stx gene variants in O157. The killing ability of EB-003 was tested in a clinically relevant panel of E. coli O157 strains, as well as its ability to prevent Shiga toxin release. Investigators designed EB-003, a CRISPR-Cas12-based approach to efficiently kill O157 STEC strains without toxin release by targeting the stx genes.

Also in the news

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