ITEM 2. | MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS |
The following discussion contains management’s discussion and analysis of our financial condition and results of operations and should be read together with the unaudited condensed consolidated financial statements and the notes thereto included in Part I, Item 1 of this quarterly report and with our audited consolidated financial statements and related notes thereto for the year ended December 31, 2018, included in our Annual Report on Form10-K. This discussion and other parts of this quarterly report contain forward-looking statements that involve risks and uncertainties, such as our plans, objectives, expectations, intentions and beliefs. Our actual results could differ materially from those discussed in these forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those identified below and those discussed in the section entitled “Risk Factors” included in our Annual Report on Form10-K for the year ended December 31, 2018.
Overview
We are a clinical stage drug development company advancing targeted therapeutics for the treatment of patients with unmet medical needs in hematology and oncology. We have a highly experienced management team with a proven track record of success in hematology and oncology drug development. We are an ambitious company, oriented towards achieving the successful registration and commercialization of our product candidates.
During the third quarter of 2018, we acquired from Gilead Sciences, Inc. (Gilead) our lead product candidate momelotinib, a potent, selective and orally-bioavailable JAK1, JAK2 and ACVR1 inhibitor. Momelotinib has been investigated in two completed Phase 3 trials for the treatment of myelofibrosis and has demonstrated a potentially differentiated therapeutic profile encompassing anemia-related clinical benefits, as well as achieving substantive splenic volume reduction and constitutional symptom control.
In December 2018, we reported new clinical data for momelotinib collated from the two completed SIMPLIFY Phase 3 clinical trials and a translational biology study in transfusion dependent patients with myelofibrosis. Data from the latter study were also concurrently presented in a poster at the 60th American Society of Hematology Annual Meeting & Exposition in San Diego, California. We reported aggregated transfusion independence responses from more than 150 intermediate and high-risk transfusion dependent myelofibrosis patients demonstrating robust and consistent response rates within and across the clinical studies. More than 44% of these patients became transfusion free for at least 12 weeks and nearly 50% were transfusion independent for at least 8 weeks.
We are currently advancing discussions with regulators to determine the registration path for momelotinib and anticipate reporting next steps in the second quarter of 2019. Our anticipated registration strategy envisions conducting one additional Phase 3 trial in second line myelofibrosis patients, in order to recapitulate the meaningful clinical benefits observed in the two previously completed Phase 3 trials, and we have started undertaking preparatory activities for this planned study.
We are also advancing SRA737, our potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1). Chk1 is a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In cancer cells, intrinsic replication stress is induced by factors such as oncogenes (e.g.,CCNE1 orMYC), genetic mutations in DNA repair machinery (e.g.,BRCA1 orFANCA), genetic mutations leading to a dysregulated cell cycle (e.g.,TP53 orRAD50) or other genomic alterations. Replication stress can also be induced by certain exogeneous factors, such as the use ofnon-cytotoxiclow-dose gemcitabine (LDG). This replication stress results in persistent DNA damage and genomic instability leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic replication stress, either alone or in combination with LDG, in a range of tumor indications. The combination of SRA737 with other modalities, such as other agents that target the DDR network and certain chemotherapeutics, may also provide synergistic anti-tumor activity via a variety of potential biological mechanisms. Importantly, the oral bioavailability of SRA737 may afford greater dosing flexibility for both monotherapy and combination therapy settings than is possible with intravenously administered agents.
We are pursuing an innovative development plan for SRA737, which is currently being evaluated in two Phase 1/2 clinical trials in patients with advanced cancer. OurSRA737-01 trial is intended to evaluate SRA737’s potential to induce synthetic lethality as monotherapy, while theSRA737-02 trial is intended to evaluate the combination of SRA737 potentiated bynon-cytotoxic LDG. We expect to report preliminary data from both trials at the 2019 ASCO Annual Meeting being held in early June 2019.
In addition, we have designed clinical trials and have conducted preclinical research evaluating SRA737 in combination with otherDDR-targeted agents, including polyADP-ribose polymerase (PARP) inhibitors, as well as with immuno-oncology therapeutics, that could guide the next planned wave of clinical development for our asset, potentially further broadening its therapeutic utility.
| • | | In the first quarter of 2018, we announced an agreement with Janssen Research & Development, LLC (Janssen), under which they have agreed to supply us with the PARP inhibitor niraparib, facilitating the potential initiation of a PARP inhibitor combination trial with SRA737 for the treatment of prostate cancer. We are currently evaluating the optimal timing to commence this trial within the context of our recently expanded portfolio. |
15