A biomarker-defined synthetic metabolic lethality program.
Mito Laboratories is developing a precision metabolic oncology strategy focused on glycolytic, LDHA-high / PDK1-high pancreatic tumors. Our lead program is designed around simultaneous inhibition of lactate dehydrogenase (LDH), pyruvate dehydrogenase kinase 1 (PDK1), and anti-apoptotic Bcl-2 family proteins to drive mitochondrial stress and tumor-selective apoptosis.
Lead program overview
The lead program is anchored in a defined metabolic phenotype. Dual metabolic inhibition (LDH + PDK1) is intended to force oxidative flux and mitochondrial stress in glycolytic PDAC cells. Concurrent pan–anti-apoptotic Bcl-2 family inhibition is designed to exploit stress-induced vulnerability and trigger non-linear apoptotic activation. A key development objective is a dose-sparing rationale for BH3 mimetic exposure under metabolic stress.
Indication
Pancreatic ductal adenocarcinoma (PDAC)
Selection
Glycolytic tumors with elevated LDHA and PDK1 expression
Intervention
Simultaneous LDH + PDK1 + pan–Bcl-2 family inhibition
Development stages
The timeline below is illustrative. Specific naming and staging will be refined as preclinical data mature.
Stage 1 — Biomarker & model definition
Identify and stratify PDAC models by LDHA / PDK1 expression, establish subtype-relevant panels, and define practical biomarker readouts for selection.
Stage 2 — Triple synergy validation
Demonstrate simultaneous triple-combination synergy in vitro, quantify mitochondrial stress (ROS, membrane potential) and apoptotic activation (caspase, MOMP), and confirm subtype selectivity.
Stage 3 — In vivo proof-of-concept
Establish efficacy signals in PDAC models and evaluate the dose-sparing hypothesis for the BH3 mimetic component under metabolic stress.
Target modules
Our lead program is built around three mechanistic modules. Over time, Mito Laboratories intends to develop proprietary assets within each module, while remaining disciplined and milestone-led at seed stage.
LDH module
Inhibit lactate dehydrogenase to constrain glycolytic throughput and redox recycling in glycolytic PDAC.
PDK1 module
Inhibit pyruvate dehydrogenase kinase 1 to increase mitochondrial flux and amplify oxidative stress under glycolytic dependency.
Pan–Bcl-2 family module
Inhibit anti-apoptotic Bcl-2 family signaling to release mitochondrial apoptosis under metabolic stress, with a goal of dose-sparing apoptotic activation.
IP and asset strategy
Mito Laboratories is pursuing a two-layer strategy:
- Layer 1 (platform IP): biomarker-defined simultaneous triple inhibition in LDHA-high / PDK1-high PDAC, including mechanistic claims and dose-sparing rationale.
- Layer 2 (asset creation): staged proprietary inhibitor discovery across LDH, PDK1, and pan–Bcl-2 family modules as capital and data maturity increase.
Seed-stage milestones
- Subtype stratification: define LDHA-high / PDK1-high selection criteria and validate in PDAC model panels.
- Synergy quantification: demonstrate non-linear triple-combination synergy with formal scoring (e.g., Bliss/Loewe).
- Mechanistic validation: confirm mitochondrial stress (ROS, membrane potential) and apoptotic execution (caspase/MOMP).
- Dose-sparing signal: show reduced BH3 mimetic exposure required for apoptosis under LDH + PDK1 metabolic stress.
- IP expansion: file and expand provisional claims anchored to biomarker definition and mechanistic readouts.
Partnering & collaboration
We welcome introductions to translational oncology groups, metabolism labs, and experienced development partners supporting PDAC model selection, biomarker validation, and preclinical execution.