Apple Tree Partners (ATP) – a leader in life sciences venture capital – announced the launch of Initial Therapeutics, a biotechnology company created to make medicines that block notoriously difficult-to-drug protein targets with a new mode of action: selective termination of protein synthesis (STOPS). Initial has developed its proprietary STOPS platform to discover new therapeutics based on the recently demonstrated scientific premise that the translation of a specific protein can be selectively interrupted at the moment in which its linear sequence is first produced in the exit tunnel of the ribosome.
Initial was developed by ATP with $75 million in Series A funding and co-founders Jamie H.D. Cate, Ph.D., Professor of Chemistry, Biochemistry, Biophysics, and Structural Biology at the University of California (UC) Berkeley; Brian Paegel, Ph.D., Professor of Pharmaceutical Sciences, Chemistry, and Biomedical Engineering at UC Irvine; and Kevan Shokat, Ph.D., Professor of Cellular and Molecular Pharmacology at UC San Francisco (UCSF) and Chemistry at UC Berkeley.
The groundbreaking structural biology work from the Cate Lab has revealed how protein synthesis can be affected selectively in any phase of translation by interactions of small molecules with a complex that includes the ribosome and the nascent peptide chain of a target protein. And within Initial, this work has been industrialized with custom ribosomal assays scaled to ultra-large library screening using miniaturized microfluidics technology from the Paegel Lab.
Initial is known for designing small molecule therapeutics to modulate the cellular synthesis of known well-validated, high-value targets. And unlike interventions that work with mature proteins, such as targeted protein stabilization and protein degradation, Initial’s strategy circumvents the need to accommodate the cellular activity of the fully formed protein or to structurally solve for docking. Plus preventing protein synthesis may stave off aggregate formations and other disease-related molecular pathologies that are difficult to reverse and in that regard, Initial’s approach could offer therapeutic benefit.
KEY QUOTES:
“Initial grew out of conversations between Jamie, Kevan, Brian, and me about work we had each been doing in these intersecting areas of protein synthesis kinetics, ribosome profiling, rapid chemistry, etc., and how we could collaborate to build something new to expand on the idea of selectively modulating protein translation, which we all saw as potentially transformative. The resulting combination of unmatched expertise and technologies brought by our founders grants Initial unique abilities to prosecute this new approach, and we are very excited about its promise to fight certain cancers and other serious illnesses.”
— Spiros Liras, Ph.D., founding CEO of Initial Therapeutics and a venture partner at ATP
“We started Initial Therapeutics to go after therapeutically important proteins that no one has been able to target successfully. I’m thrilled to see the amazing progress the Initial team has made on that front, with profound implications for the treatment of life-threatening diseases.”
— Dr. Cate
“Where other drug modalities involve recognition of the three-dimensional shape of the protein, Initial’s modality recognizes the primary linear sequence. I see that as a game-changer. Some proteins don’t have ligandable pockets, but a linear sequence, that’s in everything. Initial’s bespoke platform allows us to go into the ribosome, the machinery of mRNA translation, in a selective way that has never before been technically possible.”
— Dr. Shokat
“When the therapeutic approach doesn’t concern mature proteins, the rules of drug discovery change and the universe of what is ‘druggable’ expands significantly.”
— Dr. Paegel
