Curis, a biotechnology company focused on the development of emavusertib, an orally available small molecule inhibitor of Interleukin-1 receptor associated kinase (IRAK4), has reported encouraging progress in its clinical programs. The company's lead candidate, emavusertib, is being evaluated in three key areas: as a monotherapy in relapsed/refractory acute myeloid leukemia (AML) with FLT3 or splicing factor mutations, as a doublet therapy with ibrutinib in relapsed/refractory primary central nervous system lymphoma (PCNSL), and as a triplet therapy in frontline AML in combination with azacitidine and venetoclax.

Business Overview

Curis is a clinical-stage biotechnology company dedicated to the development of innovative drug candidates for the treatment of human cancers. The company's lead program, emavusertib, is a potent and selective small molecule inhibitor of IRAK4, a key regulator of the Toll-like receptor (TLR) and Interleukin-1 receptor (IL-1R) signaling pathways. These pathways are frequently dysregulated in various hematological malignancies, making IRAK4 an attractive therapeutic target.

Emavusertib's Potential in Relapsed/Refractory AML

Curis is evaluating emavusertib as a monotherapy in the TakeAim Leukemia Phase 1/2 study, which is enrolling patients with relapsed/refractory AML and high-risk myelodysplastic syndromes (hrMDS). The company recently announced that it will be presenting updated data from this study at the upcoming European Hematology Association (EHA) conference, including results from 25 new patients. This will bring the total number of patients evaluated to 30.

The data will include 12 patients with FLT3 mutations and 20 patients with splicing factor mutations, with 2 patients having both mutations. In the FLT3-mutant population, the company aims to outperform the benchmark set by the FLT3 inhibitor gilteritinib, which has demonstrated a 21% complete response (CR) or complete response with partial hematologic recovery (CRh) rate in relapsed/refractory AML patients. Curis believes emavusertib's ability to target both FLT3 and IRAK4 can help overcome the adaptive resistance seen with FLT3 inhibition alone.

In the splicing factor-mutant population, the company faces an even greater unmet need, as there are currently no approved therapies, and the expected survival for these patients is only a few months. The only published study on the use of the azacitidine-venetoclax (aza-ven) doublet in this setting reported a 0% response rate in a small cohort of 5 patients. Curis is hopeful that emavusertib's novel mechanism of action can demonstrate clear single-agent activity in this challenging population.

Emavusertib in Relapsed/Refractory PCNSL

Curis is also evaluating emavusertib in combination with ibrutinib in the TakeAim Lymphoma Phase 1/2 study, which is focused on patients with relapsed/refractory PCNSL who have failed prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor. The company previously reported data for 5 such patients and now expects to present data for approximately 15 patients at a future medical conference, likely the American Society of Hematology (ASH) meeting in December 2024.

The rationale for this combination is that emavusertib can target the TLR/IL-1R pathway, which is a key driver of NF-κB activation in lymphoma, while ibrutinib targets the B-cell receptor pathway. By blocking both pathways, the company believes it can more effectively overcome the adaptive resistance seen in patients who have failed prior BTK inhibitor therapy.

Emavusertib in Frontline AML

In addition to the relapsed/refractory settings, Curis has also initiated a Phase 1 study evaluating emavusertib in combination with azacitidine and venetoclax (the "AML Triplet" study) in frontline AML, regardless of mutation status. This study aims to assess the safety of adding emavusertib to the current standard of care aza-ven doublet, with the goal of potentially establishing a new benchmark for frontline therapy in AML.

The company believes that by targeting IRAK4, which is not addressed by either azacitidine or venetoclax, emavusertib can enhance the efficacy of the aza-ven combination. Curis expects to have preliminary safety data from this study by the end of 2024, likely at the ASH conference.

Financials

For the full year 2023, Curis reported a net loss of $47.4 million and revenues of $10.0 million. The company's annual operating cash flow and free cash flow were both -$38.4 million.

In the first quarter of 2024, Curis reported a net loss of $11.9 million, or $2.05 per share, compared to a net loss of $11.6 million, or $2.39 per share, in the same period of 2023. Research and development expenses increased to $9.6 million from $9.1 million, primarily due to higher employee-related costs. General and administrative expenses were $4.9 million, compared to $4.8 million in the prior-year period.

As of March 31, 2024, Curis had $40.7 million in cash, cash equivalents, and investments, which the company believes should enable it to maintain its planned operations into 2025. The company continues to be in a solid cash position and is focused on advancing its clinical programs for emavusertib.

Risks and Challenges

Curis faces several risks in its development of emavusertib, including the ability to successfully enroll and complete its ongoing clinical trials, obtain regulatory approvals, and ultimately commercialize the drug. The company also faces the risk of potential delays or setbacks in its clinical programs, as well as the challenge of securing additional funding to support its operations.

Despite these risks, Curis remains optimistic about the potential of emavusertib. The company expects to provide additional updates on its clinical programs in the coming months, including the top-line data from the TakeAim Leukemia study at the upcoming EHA conference and further data from the AML Triplet study later this year.

Conclusion

Curis has made significant progress in advancing emavusertib across multiple hematological malignancies, including relapsed/refractory AML and PCNSL, as well as frontline AML. The company's focus on targeting the IRAK4 pathway, which is not addressed by existing therapies, has the potential to establish new benchmarks for treatment in these difficult-to-treat patient populations. With upcoming data readouts and the initiation of the AML Triplet study, Curis is well-positioned to continue its momentum and drive further advancements in the treatment of these devastating diseases.