Achieved initial cumulative MMR rate of 44% (7/16) by 12 weeks in response-evaluable patients, which compares favorably to precedent Phase 1 trials of approved BCR::ABL1 TKIs
Achieved initial cumulative MMR rate of 44% (4/9) by 12 weeks in response-evaluable patients who were previously treated with asciminib
ELVN-001 was well tolerated with no ≥ Grade 3 treatment-related non-hematologic toxicities reported
Company to host virtual event with Key Opinion Leaders at
ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR-ABL gene fusion, the oncogenic driver for patients with CML.
"Significant advancements have been made over the past few decades for patients with CML, and the approved TKIs provide important treatment options for patients with CML. However, there are limitations with the available therapies, including intolerance or resistance, that result in inadequate target coverage, the loss of molecular response and disease progression in many patients," said presenting investigator
“We are excited to present the first look at the safety and clinical activity of ELVN-001, which we believe supports the potential for ELVN-001 to address the limitations of the available active-site TKIs,” said
Patient Demographics
- As of the cutoff date,
March 18, 2024 , 27 patients had enrolled in the ongoing Phase 1 clinical trial across five dose levels of ELVN-001, ranging from 10mg once daily (QD) to 120mg QD. Of the enrolled patients, 16 were evaluable for molecular response by 12 weeks. - Patients enrolled were heavily pretreated:
- 70% of patients had ≥ 3 prior TKIs.
- 70% of patients had received prior ponatinib and/or prior asciminib.
- 67% of patients had discontinued their last prior TKI due to lack of efficacy.
Preliminary Efficacy
- ELVN-001 achieved a cumulative major molecular response (MMR) rate of 44% (7/16) by 12 weeks and demonstrated responses in patients with prior exposure to asciminib and/or who were TKI-resistant:
- Among post-asciminib patients, ELVN-001 achieved a cumulative MMR rate of 44% (4/9) by 12 weeks.
- Among TKI-resistant patients, ELVN-001 achieved a cumulative MMR rate of 40% (4/10) by 12 weeks.
- Among response-evaluable patients, all had improved or stable BCR::ABL1 transcript levels by 12 weeks.
- These data compare favorably to precedent Phase 1 cumulative MMR rates for approved BCR::ABL1 TKIs, particularly given the shorter time frame for response assessment and a more heavily pre-treated patient population.
Preliminary Safety
- ELVN-001 has been well tolerated, consistent with its selective kinase profile.
- A maximum tolerated dose has not been identified, and there have been no dose reductions.
- No ≥ Grade 3 non-hematologic treatment-related adverse events (TRAE) and no specific non-hematologic TRAE of any grade occurred in >11% of patients.
- Hematologic adverse events observed are consistent with the approved BCR::ABL1 TKIs.
Pharmacokinetics (PK) & Target Coverage
- ELVN-001’s PK profile supports once daily dosing with flexible administration requirements (no significant food effect and minimal risk of drug-drug interactions).
- Importantly, given the strong correlation between target coverage and 1L efficacy for the approved BCR::ABL1 TKIs,
- ELVN-001, at doses equal to or greater than 40mg QD, achieved superior target coverage compared to 2nd Generation, active-site TKIs.
- ELVN-001, at 80mg QD, achieved similar target coverage compared to asciminib.
“We are thrilled with ELVN-001’s initial Phase 1 data in heavily pre-treated patients with CML,” said
Company Event with Investigators and Key Opinion Leaders (KOLs)
Enliven is hosting a company event with KOLs today at
The event will be webcast live and can be accessed by visiting the investor relations section of the Company’s website at https://ir.enliventherapeutics.com. To participate in the live event, please register using this link. An archived webcast will be available following the event.
About the Phase 1 ELVN-001 Trial
The Phase 1 clinical trial of ELVN-001 is a dose escalation trial designed to evaluate the safety and tolerability, and determine the recommended dose for further clinical evaluation of, ELVN-001 in patients with CML with and without T315I mutations who are relapsed, refractory or intolerant to TKIs. The primary endpoint of the study is safety. Secondary endpoints include pharmacokinetics, MMR by central qPCR, duration of MMR, BCR::ABL1 transcript levels and complete hematologic response.
About ELVN-001
ELVN-001 is a potent, highly selective, small molecule kinase inhibitor designed to specifically target the BCR-ABL gene fusion, the oncogenic driver for patients with chronic myeloid leukemia. As a highly selective active site inhibitor, ELVN-001 has a mechanism of action that is complementary to allosteric BCR::ABL1 inhibitors, which may play an increasingly important role in the standard of care. ELVN-001 was also designed to have activity against the T315I mutation, the most common BCR::ABL1 mutation, which confers resistance to nearly all approved TKIs as well as activity against mutations known to confer resistance to allosteric BCR::ABL1 inhibitors.
About Enliven Therapeutics
Enliven Therapeutics is a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule inhibitors to help people with cancer not only live longer, but live better. Enliven aims to address existing and emerging unmet needs with a precision oncology approach that improves survival and enhances overall well-being. Enliven’s discovery process combines deep insights in clinically validated biological targets and differentiated chemistry to design potentially first-in-class or best-in-class therapies. Enliven is based in
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. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Enliven, as well as assumptions made by, and information currently available to, management of Enliven. 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 and expectations regarding ELVN-001; statements by Enliven’s Chief Medical Officer, Enliven’s Chief Executive Officer and
Head-to-Head Comparisons
The Company has not performed any head-to-head trials for ELVN-001. As a result, the data referenced in this press release is derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, conclusions from cross-trial comparisons cannot be made.
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