01
Read the damage
Map the repair failure, DNA-copying stress, or treatment escape state that makes this tumor different.
SYNLETH · SYNTHETIC-LETHALITY ONCOLOGY
Discovery begins where repair ends.
SynLeth reads the DNA-repair weakness inside a tumor, finds the backup it can no longer live without, and uses that biology to decide what chemistry to build.
01 · Read the weaknessWhat is broken or overloaded in the tumor
02 · Expose the dependenceWhat the cancer now needs to survive
03 · Build against itChemistry and experiments shaped by both
Tumor DNA becomes the design brief
THE SYNLETH THESIS
The tumor's broken repair system tells us what to build.
SynLeth begins one layer upstream of molecule design: with the biological failure that makes a target matter. The tumor state defines the dependency. The dependency defines the chemistry.
02
Find the lifeline
Identify the remaining repair or cell-division machinery the cancer now leans on to survive.
03
Set the chemical brief
Define where a molecule should bind, what it must avoid, and which properties matter for this target.
04
Build the chemistry
Create distinct, makeable molecules around that brief and narrow them by fit, selectivity, novelty, and drug-like behavior.
05
Design the truth test
Choose the molecules, tumor models, controls, and molecular readouts that can confirm—or overturn—the idea.
Broken repair creates the opening. Dependency directs the chemistry. Measurement decides what survives.
The tumor starts the campaign
SynLeth begins with a specific DNA failure or stress state—not a fashionable target or an undifferentiated cancer market.
Biology changes the molecule
The tumor dependency sets how the target should be hit, what selectivity matters, and which chemical designs are worth making.
A biomarker cannot rescue bad chemistry
A molecule must earn its place on chemistry and target evidence before tumor biology determines where it should be tested.
Failure is part of the design
Each program enters the lab with confirmation tests, related proteins to check, matched controls, and stop rules that can expose a false idea.
From weakness to chemistry
Follow one scientific thread from tumor DNA to a drug program.
SynLeth uses the tumor's DNA failure to choose the dependency, shape the chemistry, and design the first decisive test.
Decode the tumor DNA problem
What repair route is lost? Where is DNA copying under stress? How has treatment resistance changed the system?
Find the survival dependency
Which remaining repair enzyme or cell-division brake has become unusually important to the cancer—and why?
Build purpose-made chemistry
Design makeable, differentiated molecules around the exact biological and binding problem—not around a generic score.
Design the proof
Specify what to synthesize, which tumors to challenge, what to measure, and what result should stop the program.
Synthetic-lethality pipeline
A focused pipeline built around tumor dependencies.
PKMYT1 leads the portfolio in discovery. PARG and POLQ define future expansion into distinct survival mechanisms created by failed DNA repair and replication stress.
Discovery
PKMYT1 · current
Experimental validation
Next milestone
Hit selection
Measured activity
Hit-to-lead
Potency · selectivity
Lead optimization
Drug-like profile
Candidate selection
Preclinical candidate
Discovery · Lead program
PKMYT1
Cell-division checkpoint kinase
Releasing the CDK1 brake in replication-stressed tumors
CCNE1-high tumors race through DNA replication and can become dependent on PKMYT1 to restrain CDK1 until copying is complete. Korvionix is designing a noncanonical, conformation-locking inhibitor intended to produce a distinct CDK1 Thr14 checkpoint signature—paired with functional replication-stress biology rather than relying on CCNE1 status alone.
- CDK1 Thr14 signature
- Conformation-locking design
- Functional tumor selection
Selected primary evidenceNature 2022 ↗
Future program
PARG
Poly(ADP-ribose) glycohydrolase
Blocking the PAR repair-signal reset
DNA damage triggers PAR, a temporary repair signal that PARG clears so the system can reset. A future Korvionix program will explore differentiated PARG inhibitor chemistry in tumors where intense DNA-copying stress may make that cleanup machinery essential.
- Stalled DNA replication
- PAR signal cleanup
- New PARG inhibitor chemistry
Future program
POLQ
Backup DNA-break repair enzyme
Removing a backup DNA-repair route
When accurate DNA-break repair is lost, some tumors fall back on POLQ to patch the damage and survive. A future Korvionix program will explore small-molecule POLQ inhibitors designed to remove that backup in genetically and functionally selected tumors.
- BRCA-linked repair loss
- Backup break repair
- Small-molecule POLQ inhibition
Current stage
PKMYT1 is in computational discovery and advancing toward experimental validation. PARG and POLQ are future programs; no experimentally confirmed hit, lead, or drug candidate is claimed.
Scientific discipline
The biology can inspire the idea. Only the experiment can keep it.
Tumor genetics, protein structure, chemistry, and predicted drug behavior answer different questions. SynLeth keeps those questions separate, exposes uncertainty, and lets weak or missing evidence say “not yet” instead of hiding it inside one impressive score.
Start with causality
A tumor feature matters only when there is a testable reason it creates dependence on the target.
No score overrules the science
A strong computer result cannot cancel weak chemistry, an implausible mechanism, or an unresolved safety concern.
Biology guides testing—not ranking
Tumor markers choose where and how to test qualified molecules; they do not push weak molecules to the front.
The first result stays honest
The test and decision rules are set before data arrive. Results shape the next round only after the compound and data quality are confirmed.
Platform output
Not a score. A drug program ready for its first hard question.
SynLeth produces three linked outputs: the chemistry to make, the tumor setting in which to challenge it, and the rules that decide what advances, what stops, and what the next design round learns.
Designed around the dependency
Exact structures, why each exists, how each should engage the target, how it can be made, and what could go wrong.
Mechanism matched to context
Tumor models with the chosen DNA weakness, matched controls without it, and readouts that show whether the intended biology changed.
Know what advances—and what stops
What counts as success, what ends the idea, which data must be captured, and how the next chemistry round may change.
Company
Precision oncology built around synthetic lethality.
Korvionix builds precision oncology programs around the survival mechanisms cancer cells cannot afford to lose.
Its SynLeth platform integrates tumor biology, structural biology, medicinal chemistry, and biomarker evidence to co-design the target protein state, molecular mechanism, and patient-selection strategy rather than optimizing molecules in isolation.
Korvionix's lead program targets PKMYT1 in Cyclin E–driven tumors through a noncanonical, conformation-locking approach designed to produce a distinct CDK1–Thr14 checkpoint signature. Based in Rockville, Maryland, Korvionix is advancing the program toward experimental validation and seeking investment and strategic development partnerships.
- Platform
- SynLeth
- Programs
- PKMYT1 · PARG · POLQ
- Model
- Synthetic-lethality precision oncology
- Location
- Rockville, Maryland
- Legal entity
- Virovance Inc. · Delaware C corporation
Connect
Connect with Korvionix.
Korvionix welcomes conversations with investors, strategic partners, and organizations working across precision oncology.
Contact Korvionix