The Life Sciences Report: Daniel, Sunesis Pharmaceuticals Inc. (SNSS:NASDAQ) has been around for more than 15 years. How does the Sunesis of today compare to its pioneering days?
Daniel Swisher: Sunesis was formed in 1998 with an initial focus on new discovery tools for small molecule drugs to address significant unmet needs. Since then, we've become a late-stage development and pre-commercial company focused on oncology, thus leveraging our pioneering tyrosine kinase work. In addition, we acquired worldwide rights for vosaroxin, our lead development product. What has remained constant is our strong focus on high-quality science and innovation.
TLSR: Has your program evolution been a result of changes in managerial interests over the years?
DS: I'd say our evolution has been driven primarily by shifting from a laboratory-focused, early science-based company to an integrated pre-commercial oncology company. Three of our four programs involve kinase inhibitors developed with Sunesis science, and vosaroxin is our post-Phase 3, pre-commercial asset. Our emphasis on applied innovation, late-stage development and commercialization has resulted in significant scientific progress made by our strong internal team.
TLSR: There is a great deal of focus on acute myelogenous leukemia (AML) as a cancer indication. Why is AML attractive to Sunesis, compared to other types of cancers?
DS: Our interest in AML is due to the significant unmet medical need. It's the largest acute leukemia, yet available drug therapies haven't changed in more than four decades. All preclinical and clinical indications suggest that vosaroxin will be a unique, first-in-class compound that could significantly change the standard of care in AML over time.
TLSR: Can you tell us about vosaroxin?
DS: Vosaroxin is an anticancer quinoline derivative. It came out of discovery efforts from Dainippon Sumitomo Pharma Co. Ltd. (DNPUF:OTCPK), which has been an innovator in the quinoline space for the last three decades. This molecule was attractive due to its potent activity in animal models, as well as its potential synergistic activity with leading cancer standards of care for both solid and liquid tumors. We acquired vosaroxin in 2003.
TLSR: As a topoisomerase II inhibitor, what drugs act synergistically with vosaroxin?
DS: Vosaroxin works synergistically with many therapies, from platinums to taxanes to nucleoside analogs. More impressively, in two clinical combination studies, vosaroxin has shown a very profound rate of complete response with cytarabine, the cornerstone of therapy for AML treatment, and with decitabine, a leading hypomethylating agent used to treat hematologic conditions.
TLSR: Is topoisomerase II inhibition a better strategy for AML compared to tyrosine kinase inhibition?
DS: I wouldn't necessarily say better. Hopefully, multiple new therapies will be developed that can really advance treatment of AML. These may be combinations of tyrosine kinase-targeted therapeutics, biologics, and new, broadly active cytotoxics like vosaroxin. The hope is that, since vosaroxin appears to work synergistically with cytarabine, we can layer in additional targeted therapies, including the tyrosine kinase inhibitors, over time.
TLSR: What are the AML treatment success rates for cytarabine alone, and for vosaroxin alone?
DS: With cytarabine in a relapse/refractory setting, we typically see a 15% complete remission rate. Vosaroxin alone is probably in a similar range for this population. By putting these drugs together, we've doubled the complete remission (CR) rate to about 30%.
TLSR: Would you describe the company's VALOR clinical trial?
"With vosaroxin and our kinase inhibitor pipeline, we are well positioned to become a leading oncology therapeutics business."
DS: VALOR is the largest, company-sponsored, double-blinded trial in relapse/refractory AML ever conducted. Enrolled patients had failed prior cytarabine-based induction therapy. They were randomized 1:1 in a 711-patient, multinational study across 15 countries, and received either vosaroxin + cytarabine or placebo + cytarabine over a five-day treatment cycle. The goal was to get patients into a CR, or CR with incomplete platelet recovery (CRp). Patients who improved into CR/CRp over one or two induction cycles were eligible for another two cycles of consolidation therapy. The primary endpoint was improvement in overall survival, with a key secondary endpoint being improved CR rates.
TLSR: How many months did patients typically survive with vosaroxin + cytarabine therapy, versus without?
DS: AML is a rapidly progressing disease. Among the 711 participating patients, median survival was 7.5 months for vosaroxin + cytarabine, versus 6.1 months for placebo + cytarabine. In the subpopulation of patients over age 60, a 2.1-month median survival separation was observed between the treatment groups, a clinically meaningful benefit in that older population, for which there's very little available therapy.
TLSR: In addition to AML, will the vosaroxin + cytarabine drug combination have efficacy against other types of cancers?
DS: I think that's a natural area to explore. We have a life cycle strategy for development of vosaroxin with both cytarabine and with hypomethylating agents in other settings, such as myelodysplastic syndrome (MDS). In addition, we have some earlier clinical work targeting ovarian and lung cancer. As a small company though, our primary near-term focus is to get across the regulatory finish line in AML.
TLSR: When do you expect to market the vosaroxin + cytarabine combination?
DS: We unblinded our VALOR results in October 2014, and presented the data at a late-breaking session at the American Society of Hematology in San Francisco in December 2014. We have a two-pronged approach on the regulatory side, talking to both the European health authorities and the U.S. Food and Drug Administration (FDA). We submitted a letter of intent to the European Medicines Agency in November, and expect to have a rapporteur assigned this month. Our goal is to have a marketing authorization application filed in Europe before the end of 2015, with marketing slated for late 2016 or early 2017. The U.S. could be a faster path, as we're in constructive dialogue with the FDA. If we gain clarity from the FDA and support of our data set, we would expect the rolling submission to start in H2/15. Assuming an expedited review, we could have FDA approval in 2016.
TLSR: Can you describe your collaboration with Takeda Pharmaceutical Co. Ltd. (TKPYY:OTCMKTS)?
DS: We have an ongoing collaboration with Takeda Pharmaceutical around MLN2480, which is an oral, small molecule pan-Raf inhibitor. This compound came out of Sunesis discovery laboratories in a prior collaboration with Biogen Inc. (BIIB:NASDAQ) focused on kinase inhibitors. When Biogen decided to redirect its efforts outside of oncology, we agreed to an assignment of that collaboration to Takeda, where there was strong interest in building out a pipeline of small molecule cancer therapeutics. Takeda has since taken MLN2480 into the clinic, and recently presented single-agent activity in a range of metastatic melanoma patients. Takeda is now looking at combination studies with three different agents to explore their utility both in melanoma and in other cancer settings. This is a fully funded collaboration, with Sunesis retaining milestone and royalty rights. We also have an option for future co-development and co-promotion.
TLSR: Is there a history of pan-Raf inhibitors for the treatment of melanoma?
DS: Roche Holding AG (RHHBY:OTCQX) and others have brought B-Raf inhibitors to market. The challenge with B-Rafs is that resistance emerges typically within a year of treatment. The hope is that pan-Raf inhibitors with novel drug combinations could have better long-term clinical activity profiles in melanoma and other tumor types.
TLSR: I noticed that your kinase inhibitor programs are now receiving increased support. What's new in this space?
"Our emphasis on applied innovation, late-stage development and commercialization has resulted in significant scientific progress."
DS: About a year ago, Sunesis reacquired full rights to two preclinical kinase inhibitor programs. SNS-062, a Bruton's tyrosine kinase (BTK) inhibitor, is the most advanced, and binds differently than ibrutinib (Imbruvica; Pharmacyclics Inc. (PCYC:NASDAQ))—an FDA-approved BTK inhibitor for treatment of mantle cell lymphoma and chronic lymphocytic leukemia. Last year we successfully completed toxicology, and we are now preparing an investigational new drug (IND) application targeting B-cell malignancies.
TLSR: What was the pathway leading to reacquisition of SNS-062?
DS: Like the Raf program, SNS-062 was originally part of a multikinase collaboration with Biogen Idec, and was a part of the original Sunesis portfolio. In fact, it is still a part of this collaboration in the context of immunology. Because this compound has a promising profile for cancer, we negotiated full rights to direct the development and, hopefully, commercialization efforts of SNS-062 for oncology indications.
TLSR: What about the PDK1 inhibitor program?
DS: PDK1 serves as a master switch in the Akt/PI3K pathway. Inhibitors of this class of kinases have not previously gone into clinical development. This program originated with the Sunesis/Biogen collaboration from 2004, and was transferred to Takeda/Millennium in 2012. Because Takeda was more focused on Raf, we were able to reacquire the PDK1 rights early last year.
We currently have two promising, late-stage, lead compounds, and we intend to select one as an IND-track development candidate later this year. We see potential for PDK1 inhibitors in both solid and liquid tumors, and will evaluate the best path forward over the next 12 months.
TLSR: What should investors look for from Sunesis over the next 12–18 months?
DS: Transformational milestones from late-stage development to commercial will be key. Vosaroxin will be leading the charge, hopefully gaining regulatory traction both in the U.S. and the European Union. If approved, commercial launches will involve some combination of Sunesis and partnered resources. The expected revenue stream will provide the means necessary to more broadly explore vosaroxin in other indications, while building a pipeline of promising kinase inhibitors as next-generation targeted therapeutics.
This expanded pipeline will build on the Millennium partnership with the pan-Raf program, generating Phase 2 combination data, with Sunesis moving the BTK and PDK1 programs into the clinic. In terms of planning for long-term success, we've been very diligent in securing intellectual property patent protection on vosaroxin, and we now have families of issued patents that extend our product exclusively out to 2030 in the U.S. With vosaroxin and our kinase inhibitor pipeline, we are well positioned to become a leading oncology therapeutics business.
TLSR: Thanks for much for your time, Daniel.
Daniel N. Swisher Jr., president and CEO of Sunesis Pharmaceuticals, Inc., joined Sunesis as the chief business officer in 2001. In 2003, he became chief financial officer and, in 2005, he was promoted to his current position. Prior to joining Sunesis, Mr. Swisher served in various management roles, including senior vice president of sales and marketing for ALZA Corp. from 1992 to 2001. He also serves as chairman of the board of Cerus Corp., a biopharmaceutical company. Mr. Swisher holds a bachelor's degree from Yale University, and a master's degree in business administration from the Stanford Graduate School of Business.
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1) Daniel E. Levy conducted this interview for Streetwise Reports LLC, publisher of The Gold Report, The Energy Report, The Life Sciences Report and The Mining Report, and provides services to Streetwise Reports as an independent contractor. He or his family owns shares of the company mentioned in this interview: None.
2) Sunesis Pharmaceuticals, Inc. paid Streetwise Reports to conduct, produce and distribute the interview.
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