SRRA: Sierra Oncology Analysis and Research Report
2018-09-14 - by Asif , Contributing Analyst - 58 views
Sierra Oncology is a clinical stage drug development company advancing targeted therapeutics for the treatment of patients with cancer. Sierra Oncology is focused on developing an emerging pipeline of next generation therapies that target the DNA Damage Response (DDR) network. Sierra Oncology has a highly experienced management team with a proven track record of success in oncology drug development. Sierra Oncology is an ambitious company, oriented towards achieving the successful registration and commercialization of its product candidates.
The company's lead product candidate, SRA737, is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1). Chk1 is a key regulator of cell cycle progression and the DDR replication stress response. In cancer cells, intrinsic replication stress is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g., BRCA1 or FANCA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. 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 and have utility as a monotherapy 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.
Sierra Oncology is pursuing an innovative development plan for SRA737, which is currently being evaluated in two Phase 1/2 clinical trials in patients with advanced cancer. The company's SRA737-01 trial is intended to evaluate SRA737’s potential to induce synthetic lethality as monotherapy, while the SRA737-02 trial is intended to evaluate the combination of SRA737 potentiated by subtherapeutic, low dose gemcitabine.
In January 2017, the company successfully transferred sponsorship of these two trials from the prior sponsor to the company and in May 2017, the company received clearance to enhance these studies by incorporating the prospective enrollment of patients with genetically-defined tumors that harbor genomic alterations hypothesized to confer sensitivity to Chk1 inhibition via synthetic lethality. In June 2017, the company presented these innovative clinical designs in two Trials in Progress posters at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.
On February 27, 2018, the company provided an update on its SRA737 and SRA141 development programs. For the SRA737-01 Phase 1/2 Monotherapy trial, the company reported that the Dose Escalation Phase 1 portion of the study was in the final stages of optimizing the SRA737 dose regimen and the Cohort Expansion Phase 2 portion was ongoing. The company reported that the Phase 2 portion of the study was being expanded to include a sixth indication (CCNE1-driven ovarian cancer) and that target enrollment for the Phase 2 portion would total 120 patients across six genetically-defined cohorts.
During the second quarter, the company further refined its monotherapy study to focus on high grade serous ovarian cancer (HGSOC), supported by emerging data in the field that provides clinical validation for Chk1 inhibition in this indication. Accordingly, Sierra Oncology is prioritizing the enrollment of approximately 65 genetically defined HGSOC patients into this trial, while continuing to enroll patients into the trial’s other indications, although with lower priority.
For the SRA737-02 Phase 1/2 Low Dose Gemcitabine Combination trial, during the second quarter, the company commenced the Cohort Expansion Phase 2 portion of this trial, which is targeting enrollment of 80 patients across four indications. The company plan to modify this study to add and prioritize enrollment for a cohort of 20 genetically defined HGSOC patients, replacing an originally proposed cohort of urothelial cancer patients. The company expect to report preliminary data from both trials in the first half of 2019.
Concurrently, Sierra Oncology is designing clinical trials and conducting preclinical research evaluating SRA737 in combination with other DDR-targeted agents, including poly ADP-ribose polymerase (PARP) inhibitors, as well as with immuno-oncology therapeutics, that will guide the next planned wave of clinical development for its asset, potentially further broadening its therapeutic utility. In the first quarter of 2018, the company announced an agreement with Janssen Research & Development, LLC (Janssen), under which they have agreed to supply it with TESARO’s ZEJULA® (niraparib), facilitating the planned initiation of a PARP inhibitor combination trial with SRA737 for the treatment of prostate cancer in the fourth quarter of 2018. Sierra Oncology is also evaluating the opportunity for SRA737 to be combined with immuno-oncology agents and are evaluating a potential clinical study for this combination.
Sierra Oncology is also advancing SRA141, a potent, selective, orally bioavailable small molecule inhibitor of cell division cycle 7 kinase (Cdc7). Cdc7 is a key regulator of DNA replication and is involved in the DDR network, making it a compelling emerging target for the potential treatment of a broad range of tumor types. Sierra Oncology has completed all gating preclinical research for SRA141 and plan to submit an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) in the second half of 2018 in order to commence clinical trials with this drug candidate. Upon dosing of the first patient in the first Phase 1 clinical trial of SRA141, a milestone payment of $4.0 million will be due to Carna Biosciences, Inc. (Carna), the licensor of this asset.
The company retain the global commercialization rights to both SRA737 and SRA141.
Since inception, Sierra Oncology has devoted substantially all of its resources to research and development activities, including the clinical development of its current product candidates SRA737 and SRA141 and its former product candidate PNT2258, and providing general and administrative support for these operations. Sierra Oncology has never generated revenue and have incurred significant net losses since inception. The company's net losses were $12.0 million and $23.5 million for the three and six months ended June 30, 2018 and $10.3 million and $21.4 million for the three and six months ended June 30, 2017. As of June 30, 2018, the company had an accumulated deficit of $647.6 million. The company expect to incur significant expenses and increasing operating losses for the foreseeable future. The company anticipate that its expenses will increase substantially as we:
- invest to further develop its product candidates, SRA737, a small molecule inhibitor targeting Chk1 and SRA141, a small molecule inhibitor targeting Cdc7;
- achieve development milestones that trigger payments due to its licensors, including a milestone payment of $4.0 million that would be due to Carna upon dosing of the first patient in the first Phase 1 clinical trial for SRA141;
- acquire or in-license additional product candidates and technologies;
- develop additional product candidates;
- hire additional clinical, scientific, drug development and management personnel, as well as personnel to support any future commercialization efforts;
- invest in scaling its manufacturing capacity to support development and its global commercialization strategy;
- seek regulatory and marketing approvals for any product candidates that the company may develop;
- ultimately establish a sales, marketing and distribution infrastructure to commercialize any drugs for which the company may obtain marketing approval;
- defend against and resolve lawsuits or other legal issues;
- maintain, expand and protect its intellectual property portfolio; and
- add operational, financial and management information systems and personnel to continue to operate as a public company.
Sierra Oncology has funded its operations to date primarily from the issuance and sale of its common stock through public offerings, and its convertible and redeemable convertible preferred stock in private financings and, to a lesser extent, through debt financings and exercises of its preferred stock warrants. As of June 30, 2018, the company had cash and cash equivalents of $125.4 million.
Liquidity and Capital Resources
Since its inception, Sierra Oncology has never generated revenue and have incurred significant net losses. The company's net losses for the three and six months ended June 30, 2018 were $12.0 million and $23.5 million and for the three and six months ended June 30, 2017 were $10.3 million and $21.4 million. As of June 30, 2018, the company had an accumulated deficit of $647.6 million. The company's principal sources of liquidity as of June 30, 2018 were cash and cash equivalents of $125.4 million.
On March 6, 2018, the company completed an underwritten public offering of an aggregate of 21,850,000 shares of common stock at a price to the public of $2.25 per share. The aggregate net proceeds received by it from the offering were $46.0 million, net of underwriting discounts and commissions and offering expenses of $3.2 million.
As of June 30, 2018, the company did not have any outstanding borrowings or any debt arrangements.
The company expect to incur significant expenses and increasing operating losses for the foreseeable future. The company anticipate that its expenses will increase substantially as we.
To fund its current operating plans, the company will need to raise additional capital. The company's existing cash and cash equivalents will not be sufficient for it to complete development of its product candidates and, if applicable, to prepare for commercializing any product candidate that may receive approval. Accordingly, the company will continue to require substantial additional capital to continue its clinical development and potential commercialization activities; however, the company believe that its existing cash and cash equivalents will be sufficient to fund its current operating plans through approximately mid-2020. The company cannot assure you that the company will ever be profitable or generate positive cash flow from operating activities. However, its forecast for the period of time through which its financial resources will be adequate to support its operations is a forward-looking statement that involves risks and uncertainties, and actual results could vary materially. The amount and timing of its future funding requirements will depend on many factors, including the pace and results of its preclinical and clinical development efforts.
The company plan to continue to fund its current operating plans’ needs through equity financings or other arrangements. To the extent that the company raise additional capital through future equity financings, the ownership interest of its stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of its existing common stockholders. If the company raise additional funds through the issuance of debt securities, these securities could contain covenants that would restrict its operations. There can be no assurance that such additional financing, if available, can be obtained on terms acceptable to it. If Sierra Oncology is unable to obtain such additional financing, the company would need to reevaluate its future operating plans.