Trethera Lands Second Fast Track for TRE-515 in Lung Cancer

Trethera Corporation has won its second FDA Fast Track Designation for TRE-515, the Sherman Oaks, California biopharmaceutical company announced 1 October 2026. The new designation covers TRE-515, a first-in-class oral deoxycytidine kinase (dCK) inhibitor, used alongside a KRAS G12C inhibitor in patients whose KRAS G12C-mutant non-small cell lung cancer has progressed after anti-PD-(L)1 therapy and platinum-based chemotherapy. It follows a Fast Track Designation the same drug won in July 2025 for a very different disease, metastatic castration-resistant prostate cancer — evidence, Trethera says, that blocking the same metabolic pathway can matter across unrelated tumor types.

From a UCLA bench to Sherman Oaks

Trethera Corporation is a privately held, clinical-stage biopharmaceutical company based in Sherman Oaks, California. It was incorporated in 2013 as Triangle Therapeutics — a different company from the 1990s HIV-drug maker Triangle Pharmaceuticals of Durham, North Carolina, which Gilead Sciences acquired in 2003, and which, despite the similar name, shares no corporate lineage with Trethera. Trethera's science traces instead to UCLA, where researchers Caius Radu, Johannes Czernin, Mike Jung and Owen Witte — whose prior work helped produce the approved prostate-cancer drugs Xtandi and Erleada — studied deoxycytidine kinase, or dCK, an enzyme now central to the company's entire pipeline.

TRE-515's path to a second Fast Track

1. 2013

   Trethera incorporated

   Registered in Sherman Oaks, California, as Triangle Therapeutics, later renamed Trethera Corporation.

2. 2015

   UCLA science becomes a pipeline

   UCLA researchers Caius Radu, Johannes Czernin, Mike Jung and Owen Witte license deoxycytidine kinase research into what becomes the company's lead drug program.

3. 23 September 2021

   Phase 1 trial begins

   The first-in-human, open-label dose-escalation study of oral TRE-515 in advanced solid tumors (NCT05055609) begins enrolling.

4. June 2025

   UCLA license widens

   A new exclusive license with UCLA extends TRE-515's intellectual-property estate into autoimmune and inflammatory-disease uses, with potential exclusivity to February 2045.

5. 9 July 2025

   First Fast Track Designation

   FDA grants Fast Track status to TRE-515 combined with radioligand therapy (lutetium Lu 177 vipivotide tetraxetan, Pluvicto) for PSMA-positive mCRPC.

6. 10 September 2025

   Phase 1 enrollment completes

   The final patient enrolls in the solid-tumor dose-escalation trial; patients tolerated 40 mg to 1,440 mg daily doses, a 36-fold range, without dose-limiting toxicities.

7. 16 December 2025

   $2.7 million NIH grant

   NIH awards a Small Business Innovation Research grant to test TRE-515 with KRAS inhibitors in NSCLC mouse models, ahead of the clinical Fast Track filing.

8. 1 October 2026

   Second Fast Track Designation

   FDA grants Fast Track status to TRE-515 combined with KRAS G12C inhibitors for pretreated, KRAS G12C-mutant NSCLC.

9. Ahead

   A combination trial still to register

   Trethera has not disclosed a start date for a dedicated TRE-515-plus-KRAS-G12C-inhibitor trial; NCT05055609's solid-tumor data remains the designation's clinical support.

“Fast Track designation in lung cancer represents an important milestone for TRE-515 and further validates our strategy of combining dCK inhibition with targeted cancer therapies.” Dr. Ken Schultz, Chairman and Chief Executive Officer, Trethera Corporation — 1 October 2026 announcement

TRE-515's second designation, in four figures

2ndFDA Fast Track Designation for TRE-515, after mCRPC in July 2025

Oct 1, 2026date FDA granted the new Fast Track Designation, for NSCLC

2013year Trethera was founded in Sherman Oaks, California, as Triangle Therapeutics

40–1,440 mgdaily TRE-515 doses tolerated with no dose-limiting toxicities in Trethera's Phase 1 trial

Figures from Trethera's own announcements (GlobeNewswire, 1 October 2026 and 16 December 2025) and its Phase 1 trial disclosures (NCT05055609).

dCK and the nucleoside salvage pathway

Cells can build the DNA building blocks called deoxyribonucleotides two ways: synthesizing them from scratch, or recycling deoxynucleosides already circulating in the body through what's called the salvage pathway. Deoxycytidine kinase, or dCK, is the rate-limiting enzyme of that salvage route. TRE-515 is a first-in-class oral small-molecule inhibitor designed to cut off that resupply line specifically in cells under replication stress, a condition common in tumors and one Trethera says intensifies once a KRAS G12C inhibitor is already pressuring a cancer cell's growth machinery. In preclinical studies using specialized PET imaging, Trethera reported that KRAS-inhibitor-treated tumors kept using dCK activity to survive the pressure, and that adding TRE-515 shut that activity down entirely.

Three claims the data still has to carry

01

A shared vulnerability

Trethera's rationale rests on tumors leaning harder on the salvage pathway once a KRAS G12C inhibitor is already stressing them — a combination hypothesis built on preclinical and PET-imaging work, not yet proven in a human combination trial.

02

One drug, two cancers

The same oral dCK inhibitor now carries Fast Track status in two unrelated diseases — prostate cancer paired with radioligand therapy, and lung cancer paired with KRAS inhibitors — which Trethera frames as evidence of a broadly applicable mechanism rather than one tuned to a single tumor type.

03

Still Phase 1

Every figure behind this designation — the safety data, the PET imaging, the dose range — comes from a solid-tumor monotherapy trial. No dedicated TRE-515-plus-KRAS-inhibitor combination study has yet been publicly registered.

A second Fast Track, a harder tumor

Fast Track Designation speeds up FDA's review process and allows more frequent interaction with the agency; it does not itself authorize marketing, and TRE-515 remains years, at best, from a combination-specific trial readout. What makes the NSCLC designation notable is the population it targets: patients whose KRAS G12C-mutant lung cancer has already progressed through an anti-PD-(L)1 checkpoint inhibitor, platinum-based chemotherapy, and a KRAS G12C inhibitor itself. Trethera's own NIH grant application, funded in December 2025, put a number on the specific subset of patients it is chasing: the roughly 60 percent of KRAS G12C-mutant NSCLC patients who either never respond to a KRAS G12C inhibitor alone or relapse after an initial response.

A market built on two approved drugs

Sotorasib (Amgen's Lumakras) and adagrasib (Mirati Therapeutics/Bristol Myers Squibb's Krazati) were the first two KRAS G12C inhibitors FDA approved, in 2021 and 2022 respectively, and together they created the category TRE-515 is now trying to extend rather than enter head-on. Newer, better-tolerated KRAS G12C inhibitors are already in late-stage testing, and so are entirely different combination strategies built around next-generation RAS inhibitors — meaning any eventual approval for TRE-515 would land into a field already being reshaped by several rivals well before Trethera finishes even a combination-specific Phase 1 trial.

KRAS inhibitors' climb to $3.65 billion

$720.0M → $3.65B

Global KRAS inhibitors market, 2025 actual to 2034 forecast, per Fortune Business Insights.

2025$602.0M

2026$720.0M

2034$3.65B

Sources: Fortune Business Insights, KRAS Inhibitors Market report

Regulatory News outlook

TRE-515 is not competing for first-line share of that market; its targeted population is the subset of KRAS G12C patients who have already progressed on a KRAS G12C inhibitor, a slice Fortune Business Insights does not break out on its own.

How we got here: Fortune Business Insights values the global KRAS inhibitors market at $720.0 million in 2026, growing at a 13.01% compound annual rate to $3.65 billion by 2034. If post-progression patients represent roughly a third of the treated population — an illustrative share, not a published figure — that implies a combination-therapy opportunity on the order of $1.2 billion of the 2034 forecast, not a company-specific projection.

TRE-515 against an already-approved field

Product	Mechanism	Role in NSCLC	FDA status
TRE-515 + KRAS G12C inhibitor (Trethera)	Oral dCK / nucleoside-salvage inhibitor, added to an approved KRASi	For patients progressing after a KRAS G12C inhibitor, anti-PD-(L)1 therapy and platinum chemotherapy	FDA Fast Track Designation, Oct 2026
Sotorasib (Lumakras, Amgen)	Direct KRAS G12C inhibitor	First-approved KRAS G12C monotherapy	FDA approved, May 2021
Adagrasib (Krazati, Mirati Therapeutics/Bristol Myers Squibb)	Direct KRAS G12C inhibitor	Second-approved KRAS G12C monotherapy	FDA approved, Dec 2022
Divarasib (Roche/Genentech)	Next-generation KRAS G12C inhibitor	Outperformed first-generation KRASi head-to-head in Phase III KRAScendo-1	Phase III, not yet FDA approved
Daraxonrasib (Revolution Medicines)	RAS(ON) multi-selective inhibitor	Combination doublets for KRASi-naive and -experienced NSCLC	Phase III ongoing

From each company's own labelling and FDA/trial records; not a clinical comparison. TRE-515 is designed to pair with an approved KRAS G12C inhibitor rather than replace one.

What Phase 2 still has to show

Trethera has not stated a timeline for starting a dedicated TRE-515-plus-KRAS-G12C-inhibitor combination trial, and the company has not disclosed response-rate or survival data for that specific combination in humans. The Fast Track designation rests on the existing solid-tumor monotherapy trial and on preclinical mouse and PET-imaging work, part of it funded by the December 2025 NIH grant. Trethera is privately held and does not publicly disclose its revenue, headcount or full funding history; outside trackers list cumulative funding in the tens of millions of dollars, without a single figure the company itself has confirmed.

• Designation, not approval: Fast Track speeds FDA's review queue; TRE-515 is not cleared, approved or on the market in any indication.
• No combination trial registered yet: the designation's clinical support is NCT05055609, a solid-tumor monotherapy study, not a KRAS-inhibitor combination trial.
• Timeline undisclosed: Trethera has not said when a dedicated lung-cancer combination study will begin enrolling patients.

Frequently asked questions

What did FDA grant Trethera?

A Fast Track Designation, announced 1 October 2026, for TRE-515 in combination with KRAS G12C inhibitors, for patients with KRAS G12C-mutant non-small cell lung cancer (NSCLC) who have progressed after anti-PD-(L)1 therapy and platinum-based chemotherapy. Fast Track speeds FDA's review process; it is not a clearance or approval, and the combination has not yet been tested in a dedicated clinical trial.

Why is this Trethera's second Fast Track designation?

It follows an FDA Fast Track Designation on 9 July 2025 for TRE-515 combined with radioligand therapy (lutetium Lu 177 vipivotide tetraxetan, marketed as Pluvicto) in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) — a different cancer type and a different combination partner, both built on the same oral dCK inhibitor.

What does TRE-515 actually do?

TRE-515 is a first-in-class oral inhibitor of deoxycytidine kinase (dCK), the rate-limiting enzyme of the nucleoside salvage pathway cells use to recycle DNA building blocks. Trethera's hypothesis is that tumors already under stress from a KRAS G12C inhibitor lean harder on that salvage route, and that blocking it with TRE-515 closes off a resistance escape hatch.

Is Trethera a public company?

No. Trethera Corporation is privately held, headquartered in Sherman Oaks, California, and incorporated in 2013 as Triangle Therapeutics, built on deoxycytidine kinase research from UCLA. It has not disclosed a single reconciled public figure for its total funding or revenue.