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| CYTK > SEC Filings for CYTK > Form 10-Q on 6-Aug-2012 | All Recent SEC Filings |
6-Aug-2012
Quarterly Report
This discussion and analysis should be read in conjunction with our financial statements and accompanying notes included elsewhere in this report. Operating results are not necessarily indicative of results that may occur in future periods.
This report contains forward-looking statements that are based upon current expectations within the meaning of the Private Securities Litigation Reform Act of 1995. We intend that such statements be protected by the safe harbor created thereby. Forward-looking statements involve risks and uncertainties and our actual results and the timing of events may differ significantly from the results discussed in the forward-looking statements. Examples of such forward-looking statements include, but are not limited to, statements about or relating to:
• guidance concerning revenues, research and development expenses and general and administrative expenses for 2012;
• the sufficiency of existing resources to fund our operations for at least the next 12 months;
• our capital requirements and needs for additional financing;
• the initiation, design, conduct, enrollment, progress, timing and scope of clinical trials and development activities for our drug candidates and potential drug candidates conducted by ourselves or our partner, Amgen Inc., including the anticipated timing for initiation of clinical trials and anticipated dates of data becoming available or being announced from clinical trials;
• the results from the clinical trials and non-clinical and preclinical studies of our drug candidates and other compounds, and the significance and utility of such results;
• anticipated interactions with regulatory authorities regarding the clinical development of tirasemtiv (formerly CK-2017357) and the potential outcomes of such interactions;
• our anticipated filing of an investigational new drug application ("IND") for CK-2127107 with the U.S. Food and Drug Administration ("FDA");
• our and Amgen's plans or ability to conduct the continued research and development of our drug candidates and other compounds;
• our plans to seek one or more strategic partners to develop and commercialize our skeletal sarcomere activators, such as tirasemtiv and CK-2127107, and our smooth muscle myosin inhibitors;
• our expected roles in research, development or commercialization under our strategic alliances, such as with Amgen;
• the properties and potential benefits of, and the potential market opportunities for, our drug candidates and other compounds, including the potential indications for which they may be developed;
• the sufficiency of the clinical trials conducted with our drug candidates to demonstrate that they are safe and efficacious;
• our receipt of milestone payments, royalties, reimbursements and other funds from current or future partners under strategic alliances and sponsored research arrangements, such as with Amgen;
• our ability to continue to identify additional potential drug candidates that may be suitable for clinical development;
• our plans or ability to commercialize drugs with or without a partner, including our intention to develop sales and marketing capabilities;
• the focus, scope and size of our research and development activities and programs;
• the utility of our focus on the cytoskeleton and our ability to leverage our experience in muscle contractility to other muscle functions;
• our ability to protect our intellectual property and to avoid infringing the intellectual property rights of others;
• expected future sources of revenue and capital;
• losses, costs, expenses and expenditures;
• future payments under loan and lease obligations and equipment financing lines;
• retaining key personnel and recruiting additional key personnel;
• expected future amortization of employee stock-based compensation; and
• the potential impact of recent accounting pronouncements on our financial position or results of operations.
Such forward-looking statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to:
• Amgen's decisions with respect to the timing, design and conduct of research and development activities for omecamtiv mecarbil, including decisions to postpone or discontinue research or development activities relating to omecamtiv mecarbil;
• our ability to enter into partnership agreements for any of our programs on acceptable terms and conditions or in accordance with our planned timelines;
• our receipt of funds and access to other resources under our current or future strategic alliances or sponsored research arrangements;
• difficulties or delays in the development, testing, production or commercialization of our drug candidates;
• difficulties or delays in or slower than anticipated patient enrollment in our or Amgen's clinical trials;
• adverse side effects, including potential drug-drug interactions, or inadequate therapeutic efficacy of our drug candidates that could slow or prevent product approval (including the risk that current and past results of preclinical research or non-clinical or clinical development may not be indicative of future clinical trials results);
• results from non-clinical studies that may adversely impact the timing or the further development of our drug candidates and potential drug candidates;
• the possibility that the FDA or foreign regulatory agencies may delay or limit our or our partners' ability to conduct clinical trials or may delay or withhold approvals for the manufacture and sale of our products;
• activities and decisions of, and market conditions affecting, current and future strategic partners;
• the availability of funds under our grant from the National Institute of Neurological Disorders and Stroke ("NINDS") in future periods;
• our ability to issue and sell shares of our common stock under our At-The-Market Issuance Sales Agreement with McNicoll, Lewis & Vlak LLC;
• our ability to obtain additional financing on acceptable terms, if at all;
• changing standards of care and the introduction of products by competitors or alternative therapies for the treatment of indications we target that may make our drug candidates commercially unviable;
• changes in laws and regulations applicable to drug development, commercialization or reimbursement;
• the uncertainty of protection for our intellectual property, whether in the form of patents, trade secrets or otherwise; and
• potential infringement or misuse by us of the intellectual property rights of third parties.
In addition such statements are subject to the risks and uncertainties discussed in the "Risk Factors" section and elsewhere in this document. Operating results reported are not necessarily indicative of results that may occur in future periods.
When used in this report, unless otherwise indicated, "Cytokinetics," "the Company," "we," "our" and "us" refers to Cytokinetics, Incorporated.
CYTOKINETICS, and our logo used alone and with the mark CYTOKINETICS, are registered service marks and trademarks of Cytokinetics. Other service marks, trademarks and trade names referred to in this report are the property of their respective owners.
Overview
We were incorporated in Delaware in August 1997 as Cytokinetics, Incorporated. We are a clinical-stage biopharmaceutical company focused on the discovery and development of novel small molecule therapeutics that modulate muscle function for the potential treatment of serious diseases and medical conditions. Our research and development
activities relating to the biology of muscle function have evolved from our knowledge and expertise regarding the cytoskeleton, a complex biological infrastructure that plays a fundamental role within every human cell. Our current research and development programs relating to the biology of muscle function are directed to small molecule modulators of the contractility of cardiac, skeletal and smooth muscle.
Our drug candidates currently in clinical development include omecamtiv mecarbil for the potential treatment of heart failure and tirasemtiv for the potential treatment of diseases or medical conditions associated with skeletal muscle weakness or wasting. We are also advancing a structurally distinct, fast skeletal muscle sarcomere activator, CK-2127107, in non-clinical studies intended to enable the filing of an IND with the FDA. In addition, we are conducting preclinical research on compounds that inhibit smooth muscle contractility. These compounds may be useful as potential treatments for diseases and conditions complicated by bronchoconstriction, such as asthma and chronic obstructive pulmonary disease.
Muscle Contractility Programs
Cardiac Muscle Contractility
Our lead drug candidate from this program is omecamtiv mecarbil, a novel cardiac muscle myosin activator. In December 2006, we entered into a collaboration and option agreement with Amgen to discover, develop and commercialize novel small molecule therapeutics that activate cardiac muscle contractility for potential applications in the treatment of heart failure, including omecamtiv mecarbil. In May 2009, Amgen exercised its option under this agreement to obtain an exclusive license worldwide, except Japan, to develop and commercialize omecamtiv mecarbil and other drug candidates arising from the collaboration, and subsequently paid us an option exercise fee of $50.0 million. As a result, Amgen is now responsible for the development and commercialization of omecamtiv mecarbil and related compounds, at its expense worldwide, except Japan, subject to our development and commercialization participation rights. Under the agreement, Amgen will reimburse us for agreed research and development activities we perform. The agreement provides for potential pre-commercialization and commercialization milestone payments of up to $600.0 million in the aggregate on omecamtiv mecarbil and other potential products arising from research under the collaboration, and royalties that escalate based on increasing levels of annual net sales of products commercialized under the agreement. The agreement also provides for us to receive increased royalties by co-funding Phase III development costs of drug candidates under the collaboration. If we elect to co-fund such costs, we would be entitled to co-promote omecamtiv mecarbil in North America and participate in agreed commercialization activities in institutional care settings, at Amgen's expense.
We expect omecamtiv mecarbil to be developed as a potential treatment across the continuum of care for heart failure both as an intravenous formulation for the treatment of patients hospitalized with acutely decompensated heart failure and as an oral formulation for chronic administration.
In May 2012, the second cohort of an international, randomized, double-blind, placebo-controlled Phase IIb clinical trial designed to evaluate the safety and efficacy of an intravenous formulation of omecamtiv mecarbil in patients with left ventricular systolic dysfunction hospitalized with acutely decompensated heart failure was opened to enrollment. Following a review of the data from the first cohort in this clinical trial, in which over 200 patients were enrolled, the independent data monitoring committee concluded that the safety data supported progression to the second cohort of this trial. This trial, known as ATOMIC-AHF (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure), is sponsored by Amgen in collaboration with Cytokinetics. A decision regarding the potential progression from the second cohort to the third cohort of this clinical trial is anticipated in the fourth quarter of 2012, following a review of data from the second cohort by the independent data monitoring committee.
In February 2012, Amgen initiated a randomized, open-label, four-period cross-over Phase I study designed to assess the safety, tolerability and pharmacokinetics of multiple oral formulations of omecamtiv mecarbil in healthy volunteers. Based on the review of these data, the companies have selected oral formulations of omecamtiv mecarbil from this Phase I trial that they believe warrant further evaluation in patients with heart failure. We anticipate collaborating with Amgen in the second half of 2012 in the finalization of a protocol for a Phase II clinical trial of oral formulations of omecamtiv mecarbil in patients with heart failure. In addition, the companies anticipate making other preparations for the potential initiation of this Phase II clinical trial.
We are conducting joint research activities with Amgen under a research plan, intended to be conducted through 2012, directed to next-generation compounds in our cardiac muscle contractility program. Under our collaboration agreement, Amgen will reimburse us for the agreed research activities we perform.
The clinical trials program for omecamtiv mecarbil may proceed for several years, and we will not be in a position to generate any revenues or material net cash flows from sales of this drug candidate until the program is successfully completed, regulatory approval is achieved, and the drug is commercialized. Omecamtiv mecarbil is at too early a stage of development for us to predict if or when this may occur. We funded all research and development costs associated with this program prior to Amgen's option exercise in May 2009. We recorded research and development expenses for activities relating to our cardiac muscle contractility program of approximately $2.2 million and $1.1 million in the first half of 2012 and 2011, respectively. We recognized research and development revenue from Amgen of $2.3 million and $1.0 million in the first half of 2012 and 2011, respectively, consisting of reimbursements of full-time employee equivalent ("FTE") and other expenses.
We anticipate that our expenditures relating to the research and development of compounds in our cardiac muscle contractility program will increase if we participate in the future advancement of omecamtiv mecarbil through clinical development. Our expenditures will also increase if Amgen terminates development of omecamtiv mecarbil or related compounds and we elect to develop them independently, or if we elect to co-fund later-stage development of omecamtiv mecarbil or other compounds in our cardiac muscle contractility program under our collaboration and option agreement with Amgen.
Skeletal Muscle Contractility
Tirasemtiv, formerly known as CK-2017357, is the lead drug candidate from this program. We are also advancing a potential drug candidate from this program, CK-2127107, in non-clinical studies intended to enable the filing of an IND. Tirasemtiv and CK-2127107 are structurally distinct and selective small molecule activators of the fast skeletal muscle sarcomere. CK-2127107 arose from our optimization of a different chemical series than that which produced tirasemtiv. These compounds activate the fast skeletal muscle troponin complex by increasing its sensitivity to calcium, leading to an increase in skeletal muscle contractility. We are evaluating the potential indications for which tirasemtiv and CK-2127107 may be useful.
Each of tirasemtiv and CK-2127107 has demonstrated encouraging pharmacological activity in preclinical models. In addition, with respect to tirasemtiv, evidence of potentially clinically relevant pharmacodynamic effects has been observed in healthy volunteers, in patients with amyotrophic lateral sclerosis ("ALS"), and in patients with peripheral artery disease and claudication.
Tirasemtiv: ALS. Tirasemtiv has received an orphan drug designation from the FDA for the potential treatment of ALS. In March 2012, tirasemtiv received an orphan medicinal product designation from the European Medicines Agency for the potential treatment of ALS. In April 2012, tirasemtiv received a fast track designation from the FDA for the potential treatment of ALS.
In June 2012, we announced the publication of our Phase IIa evidence of effect clinical trial of tirasemtiv (CY 4021) in the online edition of the journal Amyotrophic Lateral Sclerosis.
In April 2012, at the American Academy of Neurology (AAN) 64th Annual Meeting, data was presented from both Parts A and B of CY 4024, a Phase II, two-part, randomized, double-blind, placebo-controlled, multiple-dose, safety, tolerability, pharmacokinetic and pharmacodynamic clinical trial of tirasemtiv in patients with ALS. Patients in Part A of this trial were not taking riluzole; patients in Part B received riluzole at the reduced dose of 50 mg daily. In this trial, tirasemtiv appeared to be generally safe and well-tolerated when dosed daily at 125 mg, 250 mg, and 375 mg once daily for two weeks. Encouraging dose-related trends were observed in ALS Functional Rating Scale in its revised form, or ALSFRS-R (a clinically validated instrument designed to measure disease progression and changes in functional status) and maximum voluntary ventilation, or MVV (a clinical assessment of pulmonary function and endurance). As expected, plasma concentrations of tirasemtiv were unaffected by co-administration with riluzole, while riluzole levels increased during co-administration with tirasemtiv. Adverse events and clinical assessments during treatment with tirasemtiv appeared similar, with or without co-administration of riluzole. Dizziness, the most commonly reported adverse event, was mostly mild and generally began and resolved early after initiating treatment.
Also in April 2012 at the AAN Annual Meeting, data was presented from CY 4025, a Phase II, randomized, double-blind, placebo-controlled, multiple-dose, clinical trial of tirasemtiv in patients with ALS receiving riluzole at the reduced dose of 50 mg daily. In this trial, the twice-daily dose-titration regimen of tirasemtiv appeared to be generally safe and well-tolerated; the majority of patients were titrated successfully to a tirasemtiv dose level of 250 mg twice daily. Encouraging trends toward functional improvements were observed in patients receiving tirasemtiv versus those receiving placebo. In this trial, tirasemtiv treatment was associated with increases in the ALSFRS-R that were similar in direction, and in MVV that were similar in both direction and magnitude, to those observed in CY 4024.
During the second quarter of 2012, we submitted a proposed clinical trial protocol to the FDA for a Phase IIb trial designed to evaluate the longer-term safety, tolerability and efficacy of tirasemtiv in patients with ALS. The trial, called CY 4026, is intended to be an international, randomized, double-blind, placebo-controlled, dose-titration, clinical trial of tirasemtiv dosed twice-daily in patients with ALS. The trial is designed to enroll approximately 400 patients who are expected to receive tirasemtiv or placebo for three months. The proposed primary endpoint is the ALSFRS-R. Proposed secondary endpoints include MVV. Also during the second quarter, we met with the European Medicines' Agency Scientific Advice Working Party to seek advice and protocol assistance in connection with our interest in further expanding the clinical development program for tirasemtiv to include countries in Europe.
Tirasemtiv: Myasthenia Gravis. We continue to enroll and dose patients in our Phase IIa evidence of effect clinical trial of tirasemtiv in patients with generalized myasthenia gravis (CY 4023). This clinical trial, initiated in January 2011, is being funded by a $2.8 million grant from the National Institute of Neurological Disorders and Stroke ("NINDS"). Patients will receive single oral double-blind doses of placebo and tirasemtiv at 250 mg and 500 mg, each administered in random order approximately one week apart. The primary objective of this trial is to assess the effects of tirasemtiv on measures of muscle strength, muscle fatigue and pulmonary function in these patients. The secondary objectives of this clinical trial are to evaluate and characterize the relationship, if any, between the doses and plasma concentrations of tirasemtiv and its pharmacodynamic effects; to evaluate the safety and tolerability of tirasemtiv administered as single doses to patients with myasthenia gravis; and to evaluate the effect of tirasemtiv on investigator- and patient-determined global functional assessment and the Modified MG Symptom Score, an assessment combining patient reports and physician evaluations to assess the severity of symptoms due to myasthenia gravis. We anticipate that data from this clinical trial will be available in the second half of 2012.
The NINDS grant was awarded to us in 2010 under the American Recovery and Reinvestment Act of 2009, and was intended to support for three years our research and development of tirasemtiv for the potential treatment of myasthenia gravis. We recognized revenue under this grant arrangement of $0.6 million and $0.8 million in the first half of 2012 and 2011, respectively, which we recorded as research and development, grant and other revenues.
CK-2127107. We continue to conduct non-clinical studies of CK-2127107 intended to support an IND or foreign equivalent. We anticipate filing an IND or foreign equivalent for CK-2127107 by the end of 2012.
Preclinical Research. At the April 2012 AAN Annual Meeting, we presented results from a preclinical study designed to examine the effects of tirasemtiv in SOD1 mutant transgenic mice, a model of ALS in humans. Company scientists concluded that mice treated with tirasemtiv maintained hind limb grip strength during disease progression and that tirasemtiv increased muscle strength of a nerve-muscle pair in situ. There appeared to be a delay in the time to a pre-specified humane endpoint in the tirasemtiv-treated mice compared to the age-matched control SOD1 mice. The authors concluded that the preclinical findings support the hypothesis that tirasemtiv may benefit patients with ALS by increasing force generation in fast skeletal muscle fibers.
Tirasemtiv and CK-2127107 are at too early a stage of development for us to predict if or when we will be in a position to generate any revenues or material net cash flows from the potential commercialization of these compounds. We currently fund all research and development costs associated with our skeletal muscle contractility program. We recorded research and development expenses for activities relating to our skeletal muscle contractility program of approximately $11.4 million and $12.9 million in the first half of 2012 and 2011, respectively. We anticipate that our expenditures relating to the research and development of compounds in our skeletal muscle contractility program will increase significantly if and as we advance tirasemtiv, CK-2127107 or other compounds from this program into and through development.
Smooth Muscle Contractility
Our smooth muscle contractility program is focused on the discovery and development of small molecule smooth muscle myosin inhibitors, which may be useful as potential treatments for diseases and conditions associated with excessive smooth muscle contraction, and leverages our expertise in muscle function and its application to drug discovery. Our inhaled smooth muscle myosin inhibitors have demonstrated pharmacological activity in preclinical models of bronchoconstrictive diseases and may have applications for indications such as asthma or chronic obstructive pulmonary disease. Our smooth muscle myosin inhibitors, administered orally or intravenously, have also demonstrated pharmacological activity in preclinical models of vascular constriction. We continue to conduct preclinical research on compounds from this program.
Our smooth muscle myosin inhibitors are at too early a stage of development for us to predict if or when we will be in a position to generate any revenues or material net cash flows from their commercialization. We currently fund all research and development costs associated with this program. We recorded research and development expenses for activities relating to our smooth muscle contractility program of approximately $1.5 million and $2.8 million in the first half of 2012 and 2011, respectively. We anticipate that our expenditures relating to the research and development of compounds in our smooth muscle contractility program will increase significantly if and as we advance compounds from this program into and through development.
Development Risks
The successful development of any of our drug candidates is highly uncertain. We cannot estimate with certainty or know the exact nature, timing and costs of the activities necessary to complete the development of any of our drug candidates or the date of completion of these development activities due to numerous risks and uncertainties, including, but not limited to:
• decisions made by Amgen with respect to the development of omecamtiv mecarbil;
• our potential inability to obtain the additional funding necessary for us to conduct a registration program for tirasemtiv for the potential treatment of ALS;
• the uncertainty of the timing of the initiation and completion of patient enrollment and treatment in our clinical trials;
• the possibility of delays in the collection of clinical trial data and the uncertainty of the timing of the analyses of our clinical trial data after these trials have been initiated and completed;
• delays or additional costs in manufacturing of our drug candidates for clinical trial use, including developing appropriate formulations of our drug candidates;
• the uncertainty of clinical trial results, including variability in patient response;
• the uncertainty of obtaining FDA or other foreign regulatory agency approval required for the clinical investigation of our drug candidates;
• our potential inability to obtain additional funding and resources for our development activities on acceptable terms, if at all, including, but not limited to, our potential inability to obtain or retain partners to assist in the design, management, conduct and funding of clinical trials;
• the uncertainty related to the development of commercial scale manufacturing processes and qualification of a commercial scale manufacturing facility; and
• possible delays in the characterization, formulation and manufacture of potential drug candidates.
If we fail to complete the development of any of our drug candidates in a timely manner, it could have a material adverse effect on our operations, financial position and liquidity. In addition, any failure by us or our partners to obtain, or any delay in obtaining, regulatory approvals for our drug candidates could have a material adverse effect on our results of operations. A further discussion of the risks and uncertainties associated with completing our programs as planned, or at all, and certain consequences of failing to do so are discussed further in the risk factors entitled "We will need substantial additional capital in the future to sufficiently fund our operations," "We have never generated, and may never generate, revenues from commercial sales of our drugs and we may not have drugs to market for at least several years, if ever," "Clinical trials may fail to demonstrate the desired safety and efficacy of our drug candidates, which could prevent or significantly delay completion of clinical development and regulatory approval" and "Clinical trials are . . .
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