Howard Robin
Analyst · Brean, Murray
Thank you Jennifer, and thanks to everyone for joining us this afternoon. Nektar continues to make significant progress this year advancing our clinical and preclinical programs and greatly strengthening our financial position. I would like to give you a business update and then hand the call over to John for a review of the financials. Last month, we completed a $125 million private placement of Senior Secured Notes that strengthens our balance sheet without any dilution to our shareholders.
These Notes, which have no equity or warrants associated with them, are due in July of 2017 and callable by Nektar beginning in July of 2015. Importantly, the notes have no financial performance targets and we retain the freedom to operate our business as we have in the past, including, for example, our ability to enter into collaborative transactions or monetize royalties.
We are very pleased with this transaction which we believe reflects the strength of Nektar’s proven technology and our late-stage pipeline. The placement of these secured notes builds on the $124 million sale of nonstrategic royalties that we completed in the first quarter of this year. Funds from these 2 transactions will be used to repay the remaining balance on our convertible debt which is due in September of this year. This will eliminate the significant dilution associated with convertible debt for Nektar.
After repayment of the convertible debt, we now expect to end 2012 with approximately $300 million in cash and investments which should give us multiple years of working capital and bring us through many important potential product milestones. Now I’d like to review the significant progress we’ve made with our clinical pipeline in the past quarter. Let me start first with an update on naloxegol, a peripherally-acting mu-opioid receptor antagonist being developed by AstraZeneca as a once-daily oral tablet for the chronic treatment of opioid induced constipation or OIC. In 2011, AstraZeneca initiated a global and comprehensive Phase 3 clinical program for naloxegol. The planned registration package will include 2 pivotal studies to evaluate the efficacy and safety of naloxegol in patients with chronic non-cancer pain, a 6-month extension study, and a long-term safety study. The 2 pivotal placebo-controlled studies each include an estimated 650 patients with OIC with a primary endpoint based on a 12-week treatment period.
In addition, one of the pivotal studies has a 6-month double-blind extension. Finally, the 52-week long-term safety study is a randomized, open label study design. This comprehensive Phase 3 program is the only one of its scope and size for the treatment of opioid induced constipation. We are very pleased to report today that AstraZeneca and Nektar anticipate announcing high-level results from the 2 pivotal studies and the extension study in the fourth quarter of this year. AstraZeneca is also planning a full presentation of the efficacy results at a scientific meeting in 2013. Results from the 1,135 patient long-term open label safety study are anticipated in the first quarter of 2013.
Importantly, AstraZeneca remains on track for mid-2013 global regulatory filings for naloxegol. There are an estimated 100 million chronic pain patients worldwide that are treated with opioids and up to 50% of these long-term pain patients develop constipation. AstraZeneca estimates that there are 5 key markets that account for over 90% of patients taking opioids for chronic pain. These are the U.S., Canada, France, Germany and the UK. Primary care practitioners and pain management specialists make up the majority of prescribers in these key markets. AstraZeneca, with its global presence, is an ideal development and commercial partner for naloxegol.
Under our agreement with AstraZeneca, Nektar is entitled to receive $95 million upon acceptance of regulatory filings in the US and EU. We will receive an additional $140 million in regulatory and launch milestone payments when naloxegol is approved and launched in the US and EU. Nektar is also entitled to significant escalating double-digit royalties on product sales of naloxegol and up to $375 million in additional sales milestones at certain commercial sales levels. As a reminder, AstraZeneca is responsible for all costs of development and commercialization of naloxegol. We are very excited about the advancement of this program and look forward to the studies completing this year.
I’d now like to update you on the significant progress we’ve made with NKTR-181, our novel mu-opioid agonist molecule, the first opioid analgesic of its kind. As a new molecule, NKTR-181 has been specifically engineered with a number of important properties inherent to the molecule. First, NKTR-181 has been designed to enter the CNS slowly, thereby avoiding the dopamine rush of traditional opioids that is associated with euphoria and can lead to abuse and addiction. This slower rate of entry should also reduce other serious CNSmediated side effects seen with traditional opioids, such as sedation and respiratory depression.
The abuse and diversion of opioids is a serious public health issue and solutions to this problem are desperately needed. In May, we received Fast Track designation from the FDA for the NKTR-181 development program for the treatment of moderate to severe chronic pain. This designation underscores the unique potential that NKTR-181 has to address the urgent medical need for pain therapies with less abuse potential and fewer side effects.
As an NCE, NKTR-181’s potentially differentiating properties are inherent to its new molecular structure and are not a result of a physical barrier or formulation. The Phase 2 trial of NKTR-181 for the treatment of chronic pain is now underway. The study utilizes a placebo-controlled design to assess the efficacy, safety and tolerability of NKTR-181 in 200 opioid-naïve patients with moderate to severe chronic pain from osteoarthritis of the knee. This Phase 2 study utilizes an enriched enrollment study design that is a standard design used in the development of opioid compounds.
We will also be conducting a human abuse liability study, which will compare the likeability of NKTR-181 to commonly abused opioids in approximately 20 recreational drug users. We expect to complete the Phase 2 development program for NKTR-181 by the middle of next year.
Our next novel opioid molecule, NKTR-192, has a distinct profile from NKTR-181. It is also designed to have reduced abuse liability and fewer CNSmediated side effects but is short-acting and designed for the treatment of acute pain. We have successfully completed our first Phase 1 single ascending dose pharmacokinetic study for NKTR-192, which confirmed that the PK profile of NKTR-192 is well-suited for the treatment of acute pain.
Next month, we will start a second Phase 1 study to evaluate single ascending doses of NKTR-192 on both PK and pharmacodynamic endpoints. The second study should be complete by the end of the year. With NKTR-181 and NKTR-192 in our pipeline, Nektar can address both the chronic and acute pain markets. In the US alone, there are over 148 million opioid prescriptions written annually for patients with chronic pain, and over 100 million prescriptions written annually for acute pain conditions. We are extremely excited about the advancement of these important new pain candidates and we look forward to sharing more on NKTR-181 and NKTR-192 as they move through clinical development.
Now let’s talk about etirinotecan pegol, or NKTR-102, our targeted topoisomerase inhibitor being developed as a single agent in several tumor settings. Recruiting is going very well in Nektar’s ongoing Phase 3 BEACON study of etirinotecan pegol in patients with metastatic breast cancer. BEACON is an open label, randomized head-to-head trial, which will enroll approximately 840 patients comparing single-agent NKTR-102 to an agent of physician’s choice with a primary endpoint of overall survival. To date, we have initiated over 80 clinical sites in the U.S., Canada, and Europe. We are planning approximately 160 sites worldwide.
Enrollment in the BEACON study is expected to be completed in 2013 with data expected in 2014. We believe etirinotecan pegol could provide physicians and patients with an important and much needed new therapeutic weapon in fighting breast cancer. Cross-resistance is a key problem with existing therapies. As the only targeted topo I inhibitor being developed in breast cancer, etirinotecan pegol offers a different mechanism of action from microtubule inhibitors, which are the most commonly used drugs to treat these patients. If the BEACON study is successful, NKTR-102 will have the opportunity to become a worldwide standard of care in advanced breast cancer. In platinum-resistant ovarian cancer, our Phase 2 expansion study is ongoing. We expect that the study will conclude towards the end of 2012. Following its conclusion, we will analyze the final data and meet with the FDA and the EMA to discuss our regulatory options and possible next steps for the development of NKTR-102 in ovarian cancer.
This week, we announced our first investigator-sponsored study with NKTR-102 in patients with avastin-resistant high-grade glioma. The Phase 2 single-arm study is being conducted by Dr. Lawrence Recht at Stanford Cancer Institute and will enroll up to 20 patients with glioma. Dr. Recht is Professor of Neurology and Neuroscience at Stanford and is a world-renowned specialist in cancers of the brain. We are excited about Dr. Recht’s interest in our technology, and NKTR-102’s potential to help a patient population that currently has little to no treatment options.
In addition to the small molecules we just discussed, a key element of Nektar’s success in building our pipeline is our ability to enable protein and peptide therapeutics, such as BAX 855 and OMONTYS. BAX 855 is a PEGylated long-acting form of ADVATE that is partnered globally with Baxter for the treatment of hemophilia A. BAX 855 is currently in a Phase 1/2 clinical study which is expected to complete this year. Baxter is targeting the start of Phase 3 by the end of 2012. We are very excited about this program. Baxter is a world leader in the treatment of hemophilia, and ADVATE, their Factor VIII molecule is approved in 53 countries with sales in excess of $2 billion annually. In preclinical studies, BAX-855 achieved a profile that supports its potential to be dosed less frequently than ADVATE.
Analysts estimate an annual market potential of $3-4 billion for long-acting Factor VIII products. Under our agreement with Baxter, Nektar will receive significant royalties on net sales of BAX 855. We are very pleased to be partnered with Baxter on this important development program for their ADVATE franchise. OMONTYS, marketed by Affymax and Takeda, is another successful example of the application of Nektar’s technology platform. In fact, OMONTYS is the 8th product approved that was enabled by Nektar polymer conjugate technology. Affymax and Takeda launched Omontys in April and they recently announced 2 supply agreements. One with Fresenius, one of the world's leading dialysis providers and another with U.S. Renal Care, representing one of the top 10 providers in the U.S.. Analyst estimates for OMONTYS range as high as $700 million in the US dialysis market alone. Our agreement with Affymax includes mid-single digit royalties on global sales of OMONTYS, as well as manufacturing revenues.
Now moving on to another important partnered program, Amikacin Inhale, which is being developed to treat gram negative pneumonias in patients on ventilators in the ICU. Devices for the Phase 3 study of Amikacin Inhale have been manufactured and are undergoing final stability studies. Bayer has selected its CRO and has started Phase 3 activities. They expect to initiate dosing in early 2013. The Phase 3 program for Amikacin inhale will be conducted under an SPA, which will enroll approximately 1,200 patients with a primary endpoint of clinical test of cure. Amikacin inhale represents considerable potential economic value for Nektar. Gram negative bacteria make up 70% of all ICU pneumonias and are associated with very high rates of morbidity and mortality.
Current IV standard of care therapies are limited by their inability to reach effective concentrations in infected lungs. By targeting the lungs directly with antibiotic, Amikacin Inhale could emerge as a very important treatment for these deadly pneumonias. Upon commercialization, Nektar will receive a flat 30% royalty in the US and an average ex-US royalty of approximately 20% on all product sales.
Finally, before I hand the call to John, let me remind you that in addition to our clinical programs, we have several preclinical candidates in late-stage research, including NKTR-171 for neuropathic pain and NKTR-214 for cancer immunotherapy. We plan to announce our next IND candidate by the end of this year.
Nektar is in an enviable position scientifically, clinically, and financially. We have built an incredibly diverse pipeline over the last 5 years. We have 2 programs in Phase 3, naloxegol and NKTR-102. 2 programs preparing for Phase 3, BAX 855 and amikacin inhale, and 2 pain programs, NKTR-181 and NKTR-192 in Phase 2 and Phase 1, respectively.
These programs capitalize on different aspects of our technology platform across multiple therapeutic areas, spreading development risk and clearly demonstrating the breadth and depth of opportunities available to us with both large and small molecules. Further, our scientific strategy, to address proven human disease targets with well-understood mechanisms of action, should increase probability of success while still allowing us to address significant unmet needs.
There are very few technologies in the pharmaceutical industry that are capable of generating such a diverse, innovative, and valuable pipeline. I am exceptionally proud of the team at Nektar and I’m exceptionally proud of the company we are building.
With that, I will now turn the call over to John. John?