By Josh Bilenker, M.D., Co-Founder and CEO, Treeline
Treeline was founded with an ambitious vision – to create the next great enduring biopharma by pursuing carefully selected targets with the best available technology. That meant taking on the challenge of building an integrated team across disciplines—lab based and computational—working together, under the same roof. It also meant building a deep preclinical pipeline with flexibility to vet projects thoroughly before committing them to the clinic and to deprioritize struggling projects.
The scale of our ambition required an honest conversation with many of the best investors in the life sciences. We posited that the financing strategy would become the business strategy. If we were financed milestone to milestone, the most common model for our industry, two things were likely to happen. One, we’d make choices—both technical and strategic—to always make it to the next milestone. And two, we’d focus primarily on our lead program. Instead, we asked them to help us build a team capable of repeated invention and to resource multiple programs with complementary time horizons, technical risks and patient populations.
Our investors responded. As of this writing, we’ve raised approximately $1.1 billion in capital. It has carried us for the last 4.5 years and will continue to do so for many more. We have three internally discovered programs tracking to Phase 1 data in 2026, and three more internally discovered programs entering IND (Investigational New Drug) enablement soon thereafter. Currently on ClinicalTrials.gov we have postings for a BCL6 degrader (TLN-121) and an in-licensed EZH2 inhibitor (TLN-254), with plans to post our pan-KRAS inhibitor (TLN-372) this Fall. We are currently working on a fourth IND for submission early next year.
True to thesis, we’ve also killed programs. We’ve abandoned programs because we couldn’t find good chemistry hits, because we had negative or mixed data in efficacy models, because there weren’t good efficacy models, because we didn’t achieve adequate
ADME, because we had lingering concerns around safety, and because other companies got there first with great data. Having the luxury of moving on from programs is probably the greatest gift our funding mandate has given us.
Our pipeline is best understood through the lens of two concepts—
ligandability and
therapeutic index. Ligandability refers to binding a target protein with a drug. It implies that we know where to bind the protein for functional effect, that we can measure this event in orthogonal assays, and that we can visualize how our drug binds the target. For novel targets, establishing ligandability requires years of upfront protein science, assay development and screening work. Our pipeline includes programs that are, to our knowledge, the first to establish ligandability. We have other programs that were structurally enabled from the outset. Unsurprisingly, the latter category gets to the clinic first, as is the case with our first INDs.
Whether previously liganded or not, all our programs must compete based on therapeutic index (TI). TI is a pharmacology (ADME), safety and efficacy concept wrapped into one. It also blends target-driven factors and drug design features. Can I hit my target hard and get away with it? TI is the space between the beneficial dose and the un-tolerated dose. Wider TI is always better because there’s so much variability among patients and disease manifestations. With a wide TI, it is possible to deliver dose intensity for the outlier patients while maintaining a compelling benefit-risk profile for all of the patients. We generally avoid targets where you have to squint your way to a thesis on TI.
“Ligandability” and “therapeutic index” aren’t great elevator pitches. In a break with industry tradition, Treeline was not built around a platform or therapeutic area. We’re target pickers, assay scientists, drug engineers, computer scientists, and operations and clinical-regulatory professionals who’ve joined forces to solve hard problems together. Like the journey from drug discovery to FDA approval, we’re complex.
Whatever the organizing story, all biotech and pharma companies are eventually measured the same way—on their clinical data. Clinical data capture patient impact and get drugs approved. They are also the best way to judge the thousands of hard scientific, technology and strategic business choices that preceded them.
When study patients enroll in a clinical trial and undergo informed consent, they learn not to expect a personal health benefit from participating. They are choosing to help others with the same disease, while maybe holding out a little hope for themselves. At Treeline, we feel an enormous responsibility to these courageous people. To our study patients we say: our medicines, still in the making, represent our best work. We hope they are worthy of your hope and sacrifice.
You can learn more about our first clinical programs on our Medicines page
here. You can also read about our new, Series A extension financing in the press bulletin
here.