Pipeline

BCR-ABL Program: ELVN-001

ELVN-001, is a potent, highly selective, small molecule kinase inhibitor designed to specifically target the BCR-ABL fusion gene product, the oncogenic driver for patients with chronic myeloid leukemia (CML). ELVN-001 targets the ATP-binding site of the ABL1 kinase domain and binds to a unique P-loop “folded-in” active conformation of ABL1, creating a narrow selectivity tunnel against the broader kinome.

ELVN-001 was also designed to have activity against the T315I mutation, the most common BCR-ABL mutation, which confers resistance to nearly all approved tyrosine kinase inhibitors (TKIs), as well as activity against mutations known to confer resistance to allosteric BCR-ABL inhibitors. 

Although the approval of BCR-ABL TKIs has significantly improved the life expectancy of patients with CML, tolerability, safety, resistance and patient convenience concerns have become more prominent as patients can now expect to live on therapy for decades. These issues can result in the loss of molecular response and disease progression for many patients and drive approximately 20% of patients to switch therapy within the first year of therapy and approximately 40% to switch in the first five years of therapy. 

As a highly selective active site inhibitor, ELVN-001 has a unique mechanism of action, and therefore potentially represents a complementary option to allosteric BCR-ABL inhibitors, which may play an increasingly important role in the standard of care.

We believe that, given its marked kinome selectivity, attractive drug-like properties, and activity against T315I, ELVN-001 has the potential to represent an improved option for patients with CML across all lines of therapy in the future. Importantly, ELVN-001 was designed to be a more attractive option for patients with comorbidities, on concomitant medications or desiring more freedom from stringent administration requirements.

ELVN-001 is currently being evaluated in the ENABLE study, a Phase 1 clinical trial, in adults with CML. Positive proof of concept data from the study were recently announced and can be found on the Program Presentations & Publications section of the website. To learn more about the ongoing ENABLE study, visit clinicaltrials.gov. (NCT05304377).

HER2 Program: ELVN-002

ELVN-002, is a potent, highly selective, central nervous system (CNS) penetrant and irreversible HER2 inhibitor with activity against wild type HER2 and various HER2 mutations. The overexpression, amplification or mutation of HER2 is closely associated with aggressive forms of solid cancers, including breast cancer (BRC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and several others.

ELVN-002 is designed to inhibit wild-type HER2 and key mutations of HER2, while sparing wild-type EGFR and avoiding EGFR-related toxicities. We believe that if ELVN-002 achieves this profile, it will be able to achieve an improved therapeutic index compared to current approved and investigational TKIs as well as provide a meaningful therapeutic option to patients with brain metastases, a key mechanism of resistance to current therapies in patients with NSCLC, BRC and other HER2 driven cancers. Additionally, ELVN-002 was specifically designed to enable rational combination therapies, which we believe will be important for the treatment of patients with metastatic HER2 overexpressing and amplified cancers. 

Due to the recent approvals and success of antibody drug conjugates (ADC) targeting HER2 expressing cancers, the HER2-altered cancer treatment paradigm is shifting. Because of this dynamic and the fact that a standard of care regimen has not been established for patients that progress or are intolerant to this new treatment modality, we believe there is a significant patient need and market opportunity in the post-ADC setting. Based on precedent established by tucatinib in HER2+ BRC and CRC, we believe dual HER2-targeting may represent an important treatment option for patients with HER2+ cancers, especially for those who progress or are intolerant to previously approved treatments.

Our focus for this program is NSCLC, BRC and CRC as a single agent and/or in combination with standard of care.

ELVN-002 is being evaluated in a Phase 1 trial as a monotherapy agent in people with HER2+ and HER2 mutant tumors. As part of that trial, we are also enrolling patients with HER2+ metastatic breast cancer (MBC) in an exploratory cohort in combination with ado-trastuzumab emtansine and patients with HER2+ NSCLC in an exploratory cohort in combination with trastuzumab deruxtecan. To learn more, please visit www.clinicaltrials.gov (NCT05650879).

ELVN-002 is also being evaluated in combination with trastuzumab with or without chemotherapeutic agents in people with HER2+ solid tumors. To learn more about the Phase 1 study, please visit www.clinicaltrials.gov (NCT06328738).

Additional Programs

We believe that our development approach, which is rooted in validated biology and differentiated chemistry, represents a unique opportunity to provide patients with medicines offering improved therapeutic profiles. To capitalize on this opportunity, we continue to support and advance our research pipeline in areas in which we believe we can solve complex medicinal chemistry problems in a target- and indication-agnostic approach.