Yale Technology Spotlight: Cytosolix
Cytosolix is rewriting the story for oral small molecule cancer drugs - doing one thing the field has never optimized for: exploiting the acidity that all solid tumors generate. Cytosolix has built a proprietary chemistry platform that redesigns known small molecule oncology drugs to accumulate in tumors and stay out of healthy cells. The insight is deceptively simple. Decades of drug discovery assumed cancer cells were only slightly acidic – not enough to take into consideration in drug development. But not only are they acidic, they are 10x more acidic than previously thought at the cell membrane surface where a drug enters a cell. Work in the Engleman Lab at Yale has shown that the tumor cell surface runs close to pH 6, meaning existing oncology drugs have been developed and optimized for the wrong environment, optimizing for uptake at healthy tissue pH, with many drugs, actually favoring uptake by healthy cells.
John Deacon, PhD, developed the TAP platform at Yale as a postdoc in the laboratory of Donald Engelman, the Eugene Higgins Professor of Molecular Biophysics and Biochemistry.
FOUNDED
2023
New Haven, CT
FOUNDERS
John Deacon, PhD — Co-founder, CEO & President; inventor of the TAP platform
Colin Foster, MBA — Co-founder & Executive Chairman; former CEO, Bayer Pharmaceuticals North America; Yale Ventures EIR
TECHNOLOGY
Core Technology: Tumor Activated Permeability (TAP) – pH-dependent small-molecule redesign
Applications: Solid tumors and lymphomas; broadly applicable across small-molecule oncology and as ADC warheads
The Universal Weakness
Unlike all healthy tissues in the body, which are slightly basic, solid tumors run acidic because of their altered metabolism – the Warburg effect – a shift that holds regardless of tumor size, stage, or location. That makes acidity one of the few features every solid tumor shares. The TAP approach turns that acidity into a targeting mechanism: the platform swaps a variable chemical group in a known drug for a weakly acidic "TAP group" tuned to a tumor's pH. The result is a drug that is charged and cell impermeable at the pH in circulation and in healthy tissues, then becomes neutral and penetrates cells selectively in the acidic tumor environment. The TAP drug is a new chemical entity with fresh intellectual property that keeps the original drug's therapeutic activity, while improving its therapeutic index by selectively accumulating in the tumor, widening the therapeutic window and facilitating greater efficacy and safety.
Of more than 180 approved small-molecule oncology drugs, only three are weak acids, and none were designed for tumor pH. Cytosolix's lead program, CYTX-0502, is an androgen receptor inhibitor & degrader built for early-stage prostate cancer where patients currently have no approved drug, because existing therapies carry systemic side effects too harsh for early disease. CYTX-0502 has shown a 14-fold bias for tumor tissue, eliminating both CNS and hormonal dose-limiting toxicities common to all drugs in the class. Two other drugs in the company’s pipeline, CYTX-0438 (CDK9/AURKA) and CYTX-0214 (ATR) are near nomination as candidates for preclinical development and both eliminate the myelosuppression that dose-limits their classes.
In the Founder's Words
"Tumor acidity is a weakness that's been sitting in plain sight, unexploited for decades. We're not inventing new biology, we're finally designing drugs for the environment tumors actually create." – John Deacon, PhD, Co-founder & CEO
Future Outlook
Cytosolix is advancing CYTX-0502 toward the clinic while extending TAP across new targets, ADC payloads, and beyond oncology. The platform is designed as a repeatable engine: take a drug that already works, and aim it.
Learn more: Cytosolix.com