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5		-= Overview =
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	7	+==== Overview ====
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7	7	Titan Pharmaceuticals is a pharmaceutical company developing proprietary therapeutics for the treatment of serious medical disorders. The company's product development programs utilize its proprietary long-term drug delivery platform, ProNeura™, and focus primarily on innovative treatments for select chronic diseases for which steady state delivery of a drug provides an efficacy and/or safety benefit.
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9	9	Probuphine®, its first product candidate based on the ProNeura platform, was approved by the FDA in May 2016 for the maintenance treatment of opioid dependence in patients who are stable on low to moderate doses of daily sublingual buprenorphine treatment. The company licensed development and commercialization rights of Probuphine for the U.S. and Canadian markets to Braeburn Pharmaceuticals, Inc., or Braeburn.
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27	27	The ProNeura platform was developed to address the need for a simple, practical method to achieve continuous long-term drug delivery, and, depending on the characteristics of the compound to be delivered, potentially can provide treatment on an outpatient basis over extended periods of up to 12 months. The company believe that the benefits of this technology have been demonstrated by the clinical results to date with Probuphine, and the development and regulatory process have been affirmed by the FDA approval of this product. Titan Pharmaceuticals has been evaluating opportunities to develop this drug delivery platform for other potential treatment applications in which conventional treatment is limited by variability in blood drug levels and poor patient compliance and where existing therapeutic compounds have sufficient potency to be effective at low doses.
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29		-= Product Pipeline =
	31	+==== Product Pipeline ====
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31		-== Probuphine ==
	33	+**Probuphine**
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33	33	The company developed Probuphine for the maintenance treatment of opioid dependence. Upon subdermal insertion in a patient, Probuphine is designed to release medication continuously and maintain a stable, around the clock blood level of the drug buprenorphine, an approved agent for the treatment of opioid dependence. Probuphine has been shown to provide six months of medication following a single treatment and was approved by the FDA in May 2016 for the maintenance treatment of opioid dependence in clinically stable patients who are receiving treatment with an oral formulation of buprenorphine at a dose of 8mg/day or less.
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41	41	In late November 2017, the company announced that the company had entered into a binding term sheet with Molteni for commercialization of Probuphine in Europe and certain other territories. On March 21, 2018, the company announced that the company had entered into the Purchase Agreement pursuant to which Molteni acquired the European intellectual property related to Probuphine, including the MAA, and will have the exclusive right to commercialize the Titan supplied Probuphine product in Europe, as well as certain countries of the Commonwealth of Independent States, the Middle East and North Africa, or the Molteni Territory. The Purchase Agreement superseded the license arrangement contemplated by the term sheet. The company received an initial payment of €2.0 million (approximately $2.4 million) upon execution of the Purchase Agreement and Titan Pharmaceuticals is entitled to receive milestone payments totaling €4.5 million (approximately $5.5 million) upon the achievement of specified regulatory and product label milestones. Additionally, Titan Pharmaceuticals is entitled to receive earn-out payments for up to 15 years on net sales of Probuphine in the Molteni Territory ranging in percentage from the low-teens to the mid-twenties. Titan Pharmaceuticals is working with Molteni in connection with the European regulatory approval process, including addressing questions that have been posed by the EMA.
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43		-== ProNeura-Ropinirole for Parkinson’s Disease ==
	45	+**ProNeura-Ropinirole for Parkinson’s Disease**
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45	45	Parkinson’s disease, or PD, is a disease of the central nervous system characterized by the loss of dopaminergic neurons, which leads to increasing activity in the brain region that influences movement and motor function. According to the Parkinson’s Disease Foundation, more than one million people in the U.S. suffer from PD, and this number is projected to double by 2030. Early stage PD patients are treated with daily doses of drugs designed to replace dopamine in the brain. However, these therapeutics typically lose their benefits after several years of chronic treatment, and trigger serious side effect. About one-third of the treated patients develop motor response fluctuations and/or drug-induced dyskinesias within only three to five years of treatment, and these symptoms are present in almost all patients after 10 to 12 years. Clinical and nonclinical research indicates that these motor side effects arise from the pulsatile dopaminergic stimulation resulting from current oral treatment. Continuous dopaminergic stimulation, or CDS, by subcutaneous infusion has been shown to palliate these motor complications, as well as to delay or prevent the onset of dyskinesias. The company believe its ProNeura drug delivery technology provides a clinically-validated platform to safely and conveniently provide CDS for several months from a single treatment. Further, the subdermal placement of these implants eliminates many of the device-related complications associated with existing treatment modalities.
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47	47	Based on these principles the company designed an implant to deliver the drug ropinirole and conducted appropriate non-clinical studies, including a non-clinical study in an MPTP Parkinsonian primate model and demonstrated that a sustained non-fluctuating plasma level of ropinirole could be delivered safely for several months following implantation and could control PD symptoms without triggering dyskinesias in severely lesioned primates. Following further optimization of the implant and completion of the IND enabling non-clinical studies, the company submitted the IND application to the FDA in early 2017 and it was cleared in August 2017 for commencement of the proposed Phase 1/2 clinical study. The trial is an open-label, sequential, dose escalation study that will enroll approximately 20 subjects with idiopathic Parkinson's disease. The primary objectives are to characterize the pharmacokinetic profile of the ropinirole implants, to evaluate their safety and tolerability, and to explore potential signals of efficacy using established disease-specific assessment scales. Patients on a stable dose of L-dopa plus oral ropinirole will have their oral ropinirole switched to ropinirole implants for three months of treatment. This study is being conducted at three clinical research sites in the U.S. that specialize in the treatment of Parkinson’s disease. The first patient was treated in October 2017 and initial data from the early patients in the study is expected in the first half of 2018. The company will evaluate this data for appropriateness of the dose and the blood level of the drug, and further progress in the study will be determined based on these findings, as well as the availability of funds.
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49		-== Other ProNeura Product Feasibility Programs ==
	51	+**Other ProNeura Product Feasibility Programs**
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51	51	The company's goal is to expand its product pipeline using the ProNeura implant platform, and Titan Pharmaceuticals has been opportunistically evaluating other drugs and disease settings for use with the ProNeura platform in potential treatment applications where conventional treatment is limited by variability in blood drug levels and poor patient compliance. Together with Opiant Pharmaceuticals, Inc., or Opiant, the company began conducting a feasibility assessment of a subcutaneous implant using its proprietary ProNeura™ sustained release technology to administer an opioid antagonist. A product that may deliver non-fluctuating, therapeutic levels of an opioid antagonist continuously for up to six months may be ideally suited for the prevention of opioid relapse and overdose. Titan Pharmaceuticals is targeting to complete this assessment in the first half of 2018 and, if appropriate, seek support from agencies such as the National Institutes of Health for advancing a product candidate. Titan Pharmaceuticals is collaborating with the Walter Reed Army Institute of Research, or WRAIR, and the Southwest Research Institute in the early non-clinical evaluation of the ProNeura platform in malaria prophylaxis. The early data from this collaboration is encouraging and has been presented by the WRAIR staff at several conferences, and WRAIR is now seeking additional funding from the Department of Defense to continue the program with additional non-clinical testing of the implant formulations in large animal studies. Early non-clinical testing is being conducted for the development of a kappa opioid receptor agonist implant for the treatment of chronic pain. If successfully developed and approved, this would offer a potential non-addictive opioid analgesic for the treatment of chronic pain. Formulation studies and early in vitro testing is being conducted for the potential development of an implant with a currently approved peptide for the treatment of adult type 2 diabetes mellitus. Also, in 2017 the company completed early non-clinical development focused on formulation optimization of an implantable triiodothyronine (T3) product for the treatment of hypothyroidism. Any further development will depend on availability of resources and interest from partners.
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53		-== License Agreements ==
	55	+**License Agreements**
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55	55	In December 2012, the company entered into a license agreement, or the Braeburn Agreement with Braeburn pursuant to which the company granted Braeburn an exclusive right and license to commercialize Probuphine in the United States of America and its territories, including Puerto Rico, and Canada, or the Braeburn Territory. Under the Braeburn Agreement, as amended to date, Braeburn made a non-refundable up-front license fee payment of $15.75 million in 2012 and a milestone payment of $15 million upon FDA approval of the NDA in May 2016. Under the Braeburn Agreement, Titan Pharmaceuticals is entitled to receive royalties on net sales of Probuphine ranging in percentage from the mid-teens to the low twenties. The Braeburn Agreement also provides for up to $165 million in sales milestones and $35 in regulatory milestones, as well as royalties, up to an aggregate of $50 million, on a percentage of sales in the low single digit by Braeburn, if any, of other continuous delivery treatments for opioid dependence and can elect to receive low single digit royalties on sales, if any, by Braeburn of other products in the addiction market in exchange for a similar reduction in its royalties on Probuphine.
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57	57	In February 2016, Braeburn informed it that it has entered in a sublicense agreement with Knight Therapeutics, Inc., or Knight, a specialty pharmaceutical company, whereby Braeburn has granted to Knight the rights to commercialize Probuphine in Canada.
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59		-= Intellectual Property =
	61	+==== Intellectual Property ====
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61	61	The company's goal is to obtain, maintain and enforce patent protection for its product candidates, formulations, processes, methods and any other proprietary technologies, preserve its trade secrets, and operate without infringing on the proprietary rights of other parties, both in the United States and in other countries. The company's policy is to actively seek to obtain, where appropriate, the broadest intellectual property protection possible for its current product candidates and any future product candidates, proprietary information and proprietary technology through a combination of contractual arrangements and patents, both in the United States and abroad. However, patent protection may not afford it with complete protection against competitors who seek to circumvent its patents.
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69	69	Future court decisions or changes in patent law might materially affect the patents or patent applications, including, but not limited to, their expiration dates.
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71		-= Competition =
	73	+==== Competition ====
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73	73	The pharmaceutical and biotechnology industries are characterized by rapidly evolving technology and intense competition. Many companies of all sizes, including major pharmaceutical companies and specialized biotechnology companies, are engaged in the development and commercialization of therapeutic agents designed for the treatment of the same diseases and disorders that the company target. Many of its competitors have substantially greater financial and other resources, larger research and development staff and more experience in the regulatory approval process. Moreover, potential competitors have or may have patents or other rights that conflict with patents covering its technologies.
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77	77	If successfully developed and approved for commercialization, its ProNeura ropinirole product for PD will face competition primarily from numerous daily dose dopamine agonist treatments currently in use that provide symptom relief from disease related immobility, as well as the complications associated with long-term levodopa therapy (e.g. dyskinesias, tolerance). Approved products in the U.S. in addition to Requip XL®, which is marketed by GlaxoSmithKline, include Apokyn® (US WorldMeds LLC), Parlodel® (Novartis Pharmaceuticals Inc.), Mirapex ER® (Boehringer Ingelheim Pharmaceuticals Inc.) and Neupro® (UCB Inc.). There is a strong need for products providing continuous, stable, long term delivery of dopamine and dopamine agonists and the FDA recently approved a product called Duodopa®, the first and only treatment delivered via catheters directly into the duodenum that is capable of providing 16 continuous hours of carbidopa and levodopa for treatment of motor fluctuations in advanced PD. Duodopa is marketed globally by Abbvie. Also, Titan Pharmaceuticals is aware of products in mid-stage clinical development that are capable of short to medium-term subcutaneous and subdermal delivery of levodopa/carbidopa using pumps.
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79		-= Manufacturing =
	81	+==== Manufacturing ====
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81	81	The manufacturing of Probuphine has primarily been conducted at DPT Laboratories, Inc., or DPT, and Titan Pharmaceuticals has expanded the manufacturing facility at this contract manufacturer to establish commercial scale capability to support the market launch of Probuphine and ongoing demand. Titan Pharmaceuticals has entered into a commercial manufacturing agreement with DPT that governs the terms of the production and supply of Probuphine. During a part of 2017, the company continued to supply and support Braeburn while an agreement between Braeburn and DPT for the supply of Probuphine was being finalized. Pursuant to the Purchase Agreement, Titan Pharmaceuticals is responsible for the manufacture and supply of Probuphine as needed for the Molteni Territory.
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83	83	To date, Titan Pharmaceuticals has obtained the supply of bupenorphine from Teva Pharmaceuticals, Inc. under a commercial supply agreement similar to the one with DPT.
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85		-= Sales and Marketing =
	87	+==== Sales and Marketing ====
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87	87	The company do not currently have any sales and marketing capability. As its licensee, Braeburn has sole responsibility for sales and marketing of Probuphine within the United States and, through its sublicensee, Knight Pharmaceuticals, Inc., in Canada. Molteni has sole responsibility for the commercialization of Probuphine in the Molteni Territory. The company's current plans are to make similar arrangements for the commercialization of any additional products the company may successfully develop based on its ProNeura technology.
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89		-= References =
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