South San Francisco based Cytokinetics, Incorporated and Astellas Pharma Inc. of Tokyo, Japan, have announced amendments expanding their research collaboration alliance for development and commercialization of skeletal muscle activators.
The two companies have been cooperating on research and development efforts, the objective being to advance novel treatment therapies targeted on the skeletal sarcomere — the basic fundamental unit of skeletal muscle contraction consisting of a myofibril in striated muscle tissue and several key proteins — for muscle weakness disorders associated with muscular atrophy and certain non-neuromuscular indications.
The companies’ pooling of effort and resources has now been expanded to accelerate development of the fast skeletal troponin activator CK-2127107 for treating Spinal Muscular Atrophy (SMA) and possibly other neuromuscular diseases and conditions. Troponins are a complex of three regulatory proteins (troponin C, troponin I, and troponin T) integral to contraction of skeletal and cardiac muscle, but not smooth muscle. Under the revised collaboration agreement, Cytokinetics will launch a Phase II clinical trial projected to commence in 2015 for CK-2127107 in SMA patients, and Cytokinetics and Astellas will cooperate on joint development toward possible joint commercialization of CK-2127107 and potentially other fast skeletal troponin activators for treating neuromuscular disease.
SMA, a severe and devastating neuromuscular disease, is one of the most common fatal genetic disorders, occurring in 1 in every 6,000 to 10,000 live births. The disease presents with variable degrees of severity as progressive muscle weakness that results in respiratory and mobility impairment. The four SMA categories are named for the age of the victim at initial onset of muscle weakness and related symptoms: Type I (Infantile), Type II (Intermediate), Type III (Juvenile) and Type IV (Adult onset).
Life expectancy and severity vary by SMA type. Type I has the grimmest prognosis, with a life expectancy ranging no greater than 2 years from birth, while Type IV sufferers can have up to normal lifespans but with increasing weakness of proximal muscles of the extremities, that will eventually result in mobility inhibitions. Currently, treatment options for SMA patients are limited, and there is a high unmet need for new therapeutic options, both to address symptoms directly and to slow disease progression.
Cytokinetics is an emerging growth biotechnology company dedicated to discovery, development and commercialization of therapeutic agents and leverage of its expertise in cytoskeleton and muscle function biology in pursuit of new treatments for multiple disease categories. The company considers its most important distinguishing attribute to be a commitment that translates its particular focus on the cytoskeleton into a Research and Development pipeline for multiple, first-in-class therapeutic agents. All programs Cyberkinetics is currently pursuing are concentrated on novel therapeutic approaches to critical unmet clinical needs hoped to provide substantial benefits to patients.
All of Cyberkinetics’ drug candidates and potential drug candidates derive from the company’s cytoskeletal research activities with specialization in the field of cytoskeleton the biology that potentially positions the company to discover and develop novel therapeutics. This focus and resulting knowledge and expertise that Cyberkinetics has developed, especially with proprietary technologies that permit them to evaluate cytoskeletal protein function in high information content biological assays, has allowed the company to increase the efficiency of their drug discovery programs. Each potential drug candidate in clinical and preclinical research has a novel mechanism of action compared to currently-marketed pharmaceuticals, particularly research and development programs relating to muscle function biology directed to small molecule modulators of muscle contraction.
Cyberkinetics says it intends to leverage its experience in muscle contractility to expand its current product pipeline, and they expect to continue identifying new potential candidates potential suitable for clinical development, such as the extended their joint research program with Astellas that is focused on discovering additional skeletal sarcomere activators through 2016.
Under the amended agreement, Astellas will pay Cytokinetics will $55 million, including $30 million as an upfront license fee, a $10 million Astellas purchase of Cytokinetics common stock, and a $15 million milestone payment associated with Astellas’ decision to move CK-2127107 forward into Phase II clinical development. Cytokinetics also expects to receive potentially in excess of $20 million from Astellas to reimburse the company for planned research and development expenses over 2015-2016. Under terms of the revised agreement, Cytokinetics could receive more than $600 million in pre-commercialization and commercialization milestone payments, including over $100 million payable for CK-2127107 in each of SMA and other neuromuscular indications. Agreed terms also include escalating royalties that will be paid to Cytokinetics as sales of the product ramp up. Cytokinetics also retains an option to co-fund development of CK-2127107 in SMA and other neuromuscular applications in exchange for higher milestone payments and royalties, and should Cytokinetics exercise its co-promotion option, certain expenses associated with promotional activities will be reimbursed by Astellas.
“We are pleased to expand our collaboration with Astellas to enable the joint pursuit of CK-2127107 in SMA and other potential neuromuscular indications as well as the indications which were the initial focus of our collaboration,” says Cytokinetics President and Chief Executive Officer Robert I. Blum in a release. “We are impressed with Astellas’ strategic vision for skeletal muscle activators and look forward to increasing the scope of our activities to prioritize the treatment of neuromuscular diseases that may benefit from our novel mechanism approach to increased muscle function and time to muscle fatigue.”
“We are excited to expand our collaboration with Cytokinetics and to advance this drug candidate into Phase II,” comments Astellas President and Chief Executive Officer Yoshihiko Hatanaka. “We are encouraged by the result of the completed Phase I studies for CK-2127107 and are hopeful for the future of this new frontier of muscle biology. The expansion of our alliance is a testament to our productive collaboration together and illustrates the broad potential that we envision for this program.”
Collaboration Scope Expanded
Cytokinetics and Astellas originally established their collaboration in 2013 when Cytokinetics exclusively licensed rights to Astellas for co-development and commercialization of the CK-2127107 fast skeletal troponin activator drug candidate for potential use in non-neuromuscular indications. Under the collaboration’s initial scope, Cytokinetics completed clinical development activities for CK-2127107 Phase I and additional Phase II readiness activities. With their expanded collaboration, the companies have now agreed to move CK-2127107 forward into Phase II clinical development initially focused on SMA.
Skeletal muscle contraction dynamics are driven by the sarcomere, with the skeletal muscle myosin being the particular cytoskeletal motor protein that converts chemical energy into mechanical force through an interaction with actin — another protein that forms the muscle cells’ contractile filaments, and is also involved in the dynamics of motion in other types of cells. Actin-myosin interaction is dependent on a set of regulatory proteins, including tropomyosin and several types of troponin, and on intracellular calcium level changes. Cytokinetics’ CK-2127107 drug candidate, a novel skeletal muscle activator developed under the company’s skeletal muscle contractility program, acts by slowing the regulatory troponin complex of fast skeletal muscle fibers on the rate of calcium release that sensitizes the sarcomere to calcium, resulting in increased contractility of skeletal muscles.
The companies say demonstrated pharmacological activity of CK-2127107 may lead the way toward new therapeutic options for diseases associated with muscle weakness and/or muscle fatigue. A skeletal muscle activator has been shown in non-clinical Spinal Muscular Atrophy models demonstrated increases in skeletal submaximal muscle force responding to neuronal input as well as delayed onset and reduction in muscle fatigue severity. Five completed Phase I clinical trials in healthy volunteers have evaluated safety, tolerability, bioavailability, pharmacokinetics and pharmacodynamic characteristics of CK-2127107.
Looking ahead, joint development programs may include other neuromuscular applications such as the partners may agree on in future, and with the expanded collaboration, Cytokinetics and Astellas have agreed to continue with joint research activities through 2016. Under the amended agreement, Astellas is granted exclusive rights to co-develop and commercialize CK-2127107 along with other fast skeletal troponin activators for both non-neuromuscular indications and certain neuromuscular indications (including SMA), plus potentially other novel mechanism skeletal muscle activators for which Cytokinetics holds development and commercialization rights; Under mutually agreed conditions, Cytokinetics will be able to co-promote and conduct specified commercial activities in North America and Europe. Cytokinetics may also continue to independent development outside the collaboration of tirasemtiv, another fast skeletal troponin activator which has recently completed Phase II clinical trials for potential treatment of amyotrophic lateral sclerosis (ALS) and possibly other neuromuscular disorders subject to certain agreed limitations.
Cytokinetics Conference Call / Webcast
Cytokinetics will be hosting a conference call scheduled for January 5, 2015 at 8:30 a.m. Eastern Time, which will also will be simultaneously webcast and accessible in the Cytokinetics Web site’s Investor Relations section.
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Conference call live audio will also be accessible via telephone to investors, news media and the general public by dialing either (866) 999-2985 (CYTK) (United States and Canada) or (706) 679-3078 (International) and typing in the passcode 52398702.
The webcast will be available in an archived replay of via the Cytokinetics website until February 5, 2015, and will also be available via telephone beginning January 5, 2015 at 11:30 a.m. Eastern Time until February 5, 2015 by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (International) and typing in the passcode 52398702.
Astellas Pharma Inc.
Astellas Pharma Inc.