Enliven Therapeutics Announces FDA Alignment on ENABLE-2 Phase 3 Trial Design for Relcobatinib (ELVN-001) in Previously Treated Chronic Myeloid Leukemia

ENABLE-2 is expected to enroll approximately 450 previously treated adults in a direct comparison with second-generation therapies.

Rhea-AI Summary

Enliven Therapeutics (ELVN) has reached FDA alignment on the final design of ENABLE-2, its Phase 3 trial of relcobatinib.

The planned randomized trial is expected to enroll approximately 450 adults with chronic myeloid leukemia previously treated with one or more tyrosine kinase inhibitors. Participants will receive relcobatinib or an investigator-selected second-generation inhibitor. The primary endpoint is major molecular response at Week 24, a measure of treatment response; the key secondary endpoint assesses the same response at Week 96. The design makes an improvement of at least 10 percentage points over the control arm sufficient to demonstrate statistical superiority. Enliven remains on track to initiate ENABLE-2 before year-end 2026.

2 points · 0 major

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Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.

It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.

Rhea-AI Sentiment measures something else, the tone of the wording.

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Hollow bars mark forward-looking points. How the balance works

Positive

• Moderate pointFDA alignment reached on the final design of the ENABLE-2 pivotal Phase 3 trial.
• Minor point. Forward-looking: it has not happened yet and may not happen.ENABLE-2 initiation remains on track before year-end 2026, Enliven said.

Negative

• None.

Key Figures

Planned enrollment: Approximately 450 adults Randomization: 1:1 Relcobatinib dose: 80 mg once daily +4 more

Planned enrollment

Approximately 450 adults

ENABLE-2

Randomization

1:1

Relcobatinib versus investigator-selected second-generation TKI

Relcobatinib dose

80 mg once daily

ENABLE-2 treatment arm

Primary endpoint

MMR at Week 24

ENABLE-2

Key secondary endpoint

MMR at Week 96

ENABLE-2

Superiority threshold

At least 10 percentage points

Improvement in MMR rate over control arm sufficient to demonstrate statistical superiority

Planned trial initiation

Before year-end 2026

ENABLE-2

Previous Clinical trial Reports

1 past event · Latest: Jun 11

Same Type 1 event

1. Jun 11

   Phase 1 data

   24h Move

   +9.1%

   Earlier FDA alignment and Phase 1 response data preceded today's finalized ENABLE-2 design details.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

major molecular response, tyrosine kinase inhibitors, bcr::abl1 gene fusion, atp-competitive inhibitor

4 terms

major molecular response medical

"major molecular response (MMR) at Week 24"

Major molecular response is a clinical milestone in treating certain blood cancers that means the amount of disease-specific genetic material in a patient’s blood has dropped by about 99.9% from a standardized baseline. Investors care because MMR is a clear, measurable sign that a therapy is working; it influences regulatory decisions, physician adoption and sales prospects, so it functions like a performance score that can change a drug’s commercial value.

tyrosine kinase inhibitors medical

"previously treated with one or more tyrosine kinase inhibitors (TKIs)"

Drugs that block specific enzymes called tyrosine kinases, which act like on/off switches in cells and help control growth and division; by turning those switches off, these medicines can slow or stop the growth of cancers and some non-cancer conditions. They matter to investors because clinical trial outcomes, regulatory approvals, patent protection and competition determine sales potential and risk—think of them as targeted tools whose success can sharply change a drugmaker’s future revenue.

bcr::abl1 gene fusion medical

"specifically target the BCR::ABL1 gene fusion"

A BCR::ABL1 gene fusion is a specific abnormal gene formed when parts of the BCR gene on chromosome 22 and the ABL1 gene on chromosome 9 join together because of a chromosomal translocation (commonly called the Philadelphia chromosome). The fused gene makes an always‑on (constitutively active) ABL tyrosine kinase that drives uncontrolled growth of certain white blood cells; the fusion is a diagnostic and disease‑monitoring marker in certain leukemias and is detectable by tests such as PCR and FISH. There are different fusion transcript variants (for example e13a2, e14a2) that affect molecular test results and naming but all represent the same underlying BCR::ABL1 fusion event producing abnormal kinase activity.

atp-competitive inhibitor technical

"best-in-class ATP-competitive inhibitor for patients with CML"

An ATP-competitive inhibitor is a drug that blocks an enzyme by occupying the same spot where the cell’s energy molecule, ATP, normally binds, preventing the enzyme from working. For investors, this mechanism matters because it influences how potent and selective the drug is, how easily resistance or side effects might arise, and how the therapy will be dosed and positioned commercially—similar to putting the right-shaped key in a lock to stop it from turning.

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Enliven remains on track to initiate ENABLE-2 before year-end 2026

BURLINGAME, Calif., Oct. 6, 2026 /PRNewswire/ -- Enliven Therapeutics, Inc. (Enliven or the Company) (Nasdaq: ELVN), a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics, today announced that it has reached alignment with the U.S. Food and Drug Administration (FDA) on the final design of the ENABLE-2 pivotal trial, a Phase 3 trial of relcobatinib (ELVN-001) in patients with previously treated chronic myeloid leukemia (CML).

United States Adopted Names (USAN) Council has adopted relcobatinib as the nonproprietary name for ELVN-001. Relcobatinib is an investigational, potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR::ABL1 gene fusion, the oncogenic driver of CML.

"We are pleased to have reached alignment with the FDA on the design of the ENABLE-2 pivotal Phase 3 trial, providing a clear path to initiate the trial before year-end," said Helen Collins, M.D., Chief Medical Officer of Enliven. "ENABLE-2 is designed to directly compare relcobatinib to the second-generation TKIs and evaluate its potential to be the best-in-class ATP-competitive inhibitor for patients with CML. We are encouraged by the enthusiasm from physicians and the broader CML community as we prepare to initiate the trial."

ENABLE-2 Phase 3 Trial Design: A 2L+ Pivotal Trial for Patients with CML
ENABLE-2 is a planned randomized 2L+ phase 3 trial expected to enroll approximately 450 adults with CML previously treated with one or more tyrosine kinase inhibitors (TKIs). Participants will be randomized 1:1 to receive either relcobatinib 80 mg once daily or an investigator-selected second-generation TKI (dasatinib, nilotinib, or bosutinib). The primary endpoint is major molecular response (MMR) at Week 24, with the key secondary endpoint of MMR at Week 96.

With approximately 450 patients, the trial is designed such that an improvement in MMR rate of at least 10 percentage points over the control arm would be sufficient to demonstrate statistical superiority. We believe this difference would represent a clinically meaningful improvement over currently available second-generation TKIs.

The Company remains on track to initiate ENABLE-2 before year-end 2026.

About Enliven Therapeutics
Enliven is a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics to help people not only live longer, but live better. Enliven aims to address existing and emerging unmet needs with a precision medicine approach that improves survival and enhances overall well-being. Enliven's discovery process combines deep insights into clinically validated biological targets and differentiated chemistry to design potentially first-in-class or best-in-class therapies. Enliven is based in Burlingame, California. To learn more, visit www.enliventherapeutics.com and connect with us on LinkedIn and X. 

Forward-Looking Statements
This press release contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended) concerning Enliven and other matters that involve substantial risks and uncertainties. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations and financial condition, or otherwise, based on current beliefs of Enliven's management, as well as assumptions made by, and information currently available to, Enliven's management. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "anticipate," "plan," "likely," "believe," "estimate," "project," "intend," and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Statements that are not historical facts are forward-looking statements. Forward-looking statements in this press release include, but are not limited to: statements regarding the potential of, and plans regarding, market opportunities, and expectations regarding relcobatinib (ELVN-001); statements regarding the potential profile, activity, selectivity, safety, tolerability, efficacy, differentiated attributes, therapeutic benefit and potential best-in-class or complementary profile of relcobatinib to allosteric inhibitors; the interpretation of data from the ongoing ENABLE trial, including MMR rate, safety and tolerability data; comparisons to historical or precedent clinical trial results; the timing, content and availability of additional clinical data and presentation materials; the continued conduct, design, objectives, endpoints, dose selection and future clinical evaluation of relcobatinib, including the planned ENABLE-2 Phase 3 trial, the statistical power, sample size assumptions and expected treatment effect sizes for ENABLE-2 and the belief that such treatment benefit would be clinically meaningful, the potential timing of initiation of ENABLE-2, the potential timing and outcome of further FDA discussions and the finalization of additional Phase 3 trial design details; and statements by Enliven's Chief Medical Officer. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various risks and uncertainties, including, without limitation the limited operating history of Enliven; the potential for interim, topline and preliminary results from Enliven's clinical trials to materially change as additional patient data become available or following more comprehensive review; the potential for results from the ongoing or any future clinical trial of relcobatinib to differ from the results of earlier trials of relcobatinib; relcobatinib failing to demonstrate sufficient safety, efficacy, tolerability, durability, differentiated attributes or therapeutic benefit in current or future clinical trials; risks associated with unexpected events during the remainder of the ENABLE trial including serious adverse events, toxicities, dose reductions, discontinuations or other undesirable side effects; delays or difficulties in recruiting, enrolling or maintaining patients in relcobatinib clinical trials; the risks of delays in completing the ongoing ENABLE trial or initiating ENABLE-2; Enliven failing to complete the ongoing ENABLE trial, to present additional data, to initiate ENABLE-2 or to advance relcobatinib through clinical development; regulatory authorities disagreeing with Enliven's clinical trial design, dose selection, endpoints or interpretation of data, or requiring additional studies or diagnostics; the risk that statistical assumptions underlying the ENABLE-2 trial design may not hold, including assumptions regarding treatment effect sizes, comparator arm performance and statistical power; lack of reliability of cross-trial comparisons because the referenced data are derived from different clinical trials at different points in time, with differences in trial design and patient populations, and results may differ in head-to-head studies; developments relating to Enliven's competitors and industry which may affect the development or potential market opportunity for relcobatinib; and the potential inability of Enliven to obtain regulatory approval for, or ultimately commercialize or license, relcobatinib or other product candidates; Enliven's limited resources; Enliven's limited experience as a company in designing and conducting clinical trials; the ability to attract, hire, and retain highly skilled executive officers and employees; the ability of Enliven to protect its intellectual property and proprietary technologies; the scope of any patent protection Enliven obtains or the loss of any of Enliven's patent protection; reliance on third parties, including medical institutions, contract manufacturing organizations, contract research organizations and strategic partners; geopolitical developments, general market or macroeconomic conditions; Enliven's ability to obtain additional capital to fund Enliven's general corporate activities and to fund Enliven's research and development; and other risks and uncertainties more fully described in Enliven's filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in Enliven's Annual and Quarterly Reports on Form 10-K and Form 10-Q filed with the SEC and in Enliven's future SEC filings. Except as required by applicable law, Enliven undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

This press release contains hyperlinks to information that is not deemed to be incorporated by reference into this press release.

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SOURCE Enliven Therapeutics, Inc.

FAQ

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When does Enliven expect to start the ENABLE-2 trial?

Enliven remains on track to initiate ENABLE-2 before year-end 2026. It has reached FDA alignment on the trial's final design.

What will Enliven's ENABLE-2 trial measure?

The primary endpoint is major molecular response at Week 24, with the key secondary endpoint measuring that response at Week 96. With approximately 450 patients, the trial is designed so an improvement of at least 10 percentage points over the control arm would be sufficient to demonstrate statistical superiority.

What treatments and doses will patients receive in Enliven's ENABLE-2 trial?

Participants will be randomized 1:1 to relcobatinib 80 mg once daily or an investigator-selected second-generation tyrosine kinase inhibitor. The control treatment options are dasatinib, nilotinib, or bosutinib.