The Drug-Building Tools Got Ahead of the Targets. Envisagenics and Boehringer Want to Close the Gap With RNA Splicing

Boehringer Ingelheim has signed a multi-year research collaboration and option agreement with Envisagenics to validate cancer targets that come from RNA splicing rather than from genes. The New York company, which announced the deal on September 22, is eligible for more than $1 billion in potential payments, including an upfront payment, research funding, option fees, milestones and royalties.

The deal builds on targets Envisagenics has previously identified  through SpliceCore, its proprietary AI platform. Boehringer will further validate the targets’ therapeutic potential for the treatment of solid tumors across antibody-drug conjugates, T-cell engagers and multispecific antibodies.The pharma company holds an option to exclusively license the targets it selects.

Chief executive officer and co-founder, Maria Luisa Pineda, frames the problem as one of aim rather than engineering.

"The drug-building tools have advanced faster than the discovery of new targets. ADCs, T-cell engagers and multispecific antibodies are among the most promising therapeutic modalities in oncology, yet the field continues to converge on a relatively small set of established tumor antigens. One of the biggest bottlenecks is no longer just how to build the drug, it's where to point it."

Most oncology targets start from a gene that tumors overexpress. Healthy tissue usually expresses the same gene, and that overlap limits how hard a potent payload or an engager can be pushed. Alternative splicing offers a finer cut. One gene can yield several protein isoforms, and cancers often switch on isoforms that normal cells rarely make.

"Splicing-derived targets are particularly compelling for these therapeutic modalities because alternative splicing can generate unique protein sequences expressed on tumor cells but largely absent from healthy tissues. For ADCs and T-cell engagers, that tumor selectivity is critical to the potential for more precisely targeted therapies that minimize effects on healthy tissues and ultimately improve outcomes for patients."

Envisagenics says SpliceCore now covers more than 14 million splicing events, roughly double the 7 million it cited in 2021. Pineda says the gain that matters is resolution rather than size.

"At more than 14 million, spanning 44 tumor types and more than 50,000 patient samples, we can ask much sharper questions. How often does a particular isoform appear across patients? Is it confined to one tumor subtype or shared across many? And, critically, how selectively is it expressed compared with normal tissues?"

The third question is the one that sinks most candidates.

"That last question is where many oncology targets fall short. A more comprehensive dataset helps us eliminate less promising candidates earlier and focus our experimental validation on those with the greatest potential for tumor selectivity."

Envisagenics has partnered before, with Biogen in 2021 and Bristol Myers Squibb in 2022. Pineda says the difference this time is what it brought to the table.

"Our 2022 collaboration with Bristol Myers Squibb demonstrated the potential of SpliceCore® as a platform for discovering novel oncology targets. With Boehringer Ingelheim, we brought forward targets we had already identified and supported with experimental data."

The split of work follows from what each side lacks. Envisagenics can nominate and validate targets, but turning a tumor-specific isoform into an ADC or a T-cell engager takes antibody engineering, manufacturing and clinical capacity that a company its size does not have. Boehringer will lead development and commercialization of therapies against the targets it selects. The deal also fits a pattern at Boehringer, which Fierce Biotech reported has been sourcing oncology targets through outside partners, including AI deals with Immunai, OpenProtein.AI and Owkin.

"Alternative RNA splicing offers access to a largely unexplored target space, and Envisagenics has built a distinctive capability to investigate it," said Mark Petronczki, Global Head of Oncology Research at Boehringer Ingelheim, in the announcement.

The option structure leaves Envisagenics room to keep building. The company spun out of Cold Spring Harbor Laboratory in 2014, and its lead wholly owned program is an antisense oligonucleotide for ALS that it describes as late-stage preclinical.

"Importantly, exclusivity is limited to the specific targets selected by Boehringer, not our platform or broader target portfolio. That allows us to continue building our oncology pipeline and advancing our wholly owned therapeutic programs, including our ASO program in ALS."