PANK2

Shares of Retrophin have plunged more than 24% in premarket trading after the San Diego-based company announced its Phase III treatment for pantothenate kinase-associated neurodegeneration did not stack up against placebo. Shares of Retrophin have plunged more than 24% in premarket trading after the San Diego-based company announced its Phase III treatment for pantothenate kinase-associated neurodegeneration (PKAN) did not stack up against placebo. This morning, Retrophin, Inc. said results from the late-stage FORT study evaluating the safety and efficacy of fosmetpantotenate compared to placebo in PKAN patients did not demonstrate a difference between the treatment groups, meaning the trial drug did not distinguish itself. In addition to failing to hit its primary endpoint, Retrophin said it also failed to hit its secondary endpoint. In its announcement, Retrophin did not provide full details of the Phase III failure. The company said it intended to analyze the data and present the information at a later medical conference. Additionally, Retrophin said it will work with study investigators to analyze the appropriate next steps for fosmetpantotenate, including the ongoing open-label extension of the study. In the FORT trial, fosmetpantotenate was observed to be generally safe and well-tolerated, the company added. As could be expected, the company noted its disappointment in the FORT study. Eric Dube said that much of that disappointment surrounded the fact that throughout the studies, the company has seen the “devastating impact of PKAN on patients and their families.” Dube said there remains a significant unmet need in this patient population, as there is no approved treatment. PKAN is a rare, genetic neurological disorder caused by a mutation in the PANK2 gene. The disruption of this metabolic pathway ultimately leads to decreased levels of coenzyme A, which is essential in biochemical reactions impacting energy metabolism, membrane integrity, signaling and other critical processes. The disease is characterized by a host of progressively debilitating symptoms that can be life-threatening. People suffering from PKAN may experience movement disorders such as dystonia, a sustained muscle contraction leading to abnormal posture, rigidity, problems swallowing, and twisting and writhing. PKAN is estimated to affect up to 5,000 people worldwide. Dube said the company will work closely with the study investigators to further analyze the results and share them with the PKAN community to “contribute to the growing knowledge of this rare disorder.” As the company determines what went wrong with FORT, the company said it remains focused on progressing its two pivotal Phase III programs evaluating sparsentan for the treatment of focal segmental glomerulosclerosis and IgA nephropathy, and continuing the advancement of its commercial portfolio. Newsletter Sign Up Sign up to get the latest life sciences news and updates delivered straight to your inbox. hbspt.forms.create({ portalId: "4413123", formId: "af9b8b3f-deb1-4d8e-936b-ad0b0447375b" });

Comet has set up shop in Kendall Square with about 10 employees. The company has plans to expand to at least double that amount over the next year as it moves from the preclinical phase to the clinical phase. With $28.5 million in financing, Cambridge, Mass.-based Comet Therapeutics is emerging from stealth mode with a focus on developing a portfolio of drug candidates that centers around efforts to re-engineer CoEnzyme-A (CoA). Comet’s CoA platform has numerous potential applications including metabolic disorders, neuro-metabolic diseases, immuno-metabolic conditions and other life-threatening diseases. In an interview with BioSpace, David de Graaf, president and chief executive officer of Comet Therapeutics, said that although the role of CoA in the body has been understood for a long time, no one had really thought to apply that knowledge in a pharmaceutical manner. CoA is known for its role in helping enzymes in the body do the job they were designed to do, including the building of and breaking down of proteins, as well as mitochondrial health and the proper functioning of the TCA cycle, which provides the energy cells need to live. CoA dysfunctions play a role in many rare, genetic disorders of metabolism. Comet will use its platform to boost the levels of CoEnzyme-A in patients as a way to kick start some of the body’s own natural defenses, such as T Cells. The compounds developed by Comet will replenish key intermediate metabolites in cellular metabolic processes. This will provide the company will a unique ability to modify and treat numerous diseases, such as neurometabolic and immune-metabolic conditions. De Graaf said the company’s molecules can push the immune system into a more restive state or more active state depending on the need. While keeping targets close to his vest, de Graaf said Comet’s initial focus on diseases will be “where metabolism and neurodegenerative diseases connect,” such as Parkinson’s and Alzheimer’s. The company’s compounds have the ability to cross the blood-brain barrier, which will give Comet a tool to potentially treat neurological conditions. For instance, processes involved in myelination. Without diving too deeply into the science, de Graaf described the process as providing the body with enough Lego building blocks to enable the metabolic system to do what it needs to do. “The body will know what to do. The plans for that Lego model are inside the body,” de Graaf said in a telephone interview. Comet’s Series A financing round was funded by Canaan and Sofinnova Partners. The Series A was also supported by INKEF Capital and new investor BioInnovation Capital. The company believes the funds will be sufficient to support operations into late 2021 or early 2022. “It’s always good to raise money and start a company,” de Graaf said. Comet has set up shop in Kendall Square with about 10 employees. The company has plans to expand to at least double that amount over the next year as it moves from the preclinical phase to the clinical phase. If all goes according to plan, de Graaf said the company can move into human trials by 2021. De Graaf joined the startup Comet after serving as president and CEO of Syntimmune, a clinical-stage antibody company snapped up by Alexion Pharmaceuticals last year for $1.8 billion. In addition to that, de Graaf has also held leadership roles at AstraZeneca, Pfizer, Boehringer Ingelheim and Selventa. In addition to de Graaf, the Comet leadership team includes Chief Scientific Officer Art Taveras, a Biogen veteran who has led or contributed to more than 40 small-molecule drug discovery and development programs. Also, Comet’s chief technology officer, Enej Juscer, who has worked with multiple startups such as Acies Bio and Whey2Value, has extensive experience with CoA metabolism. The company also has a veteran board of directors, including its chairman, Peter Van Vlasselaer. Van Vlasselaer has started and overseen development and successful exits of many innovative life science companies, including immuno-oncology focused Armo BioSciences, which Eli Lilly acquired last year for $1.6 billion. Comet isn’t the only company to launch within the last year with a focus on CoA. Almost one year ago, BridgeBio Pharma launched CoA Therapeutics with a focus on developing novel small-molecules designed to increase Coenzyme-A (CoA) levels in genetic disorders where CoA deficiency is implicated. CoA had plans to enter the clinic this year with a treatment targeting pantothenate kinase-associated neurodegeneration, an autosomal recessive genetic disorder caused by mutations in the pantothenate kinase 2 gene.

Top-line data anticipated in the third quarter of 2019 Top-line data anticipated in the third quarter of 2019 SAN DIEGO, Dec. 20, 2018 (GLOBE NEWSWIRE) -- Retrophin , Inc. (NASDAQ: RTRX) today announced completion of patient enrollment in the pivotal Phase 3 FORT Study, which is evaluating the safety and efficacy of fosmetpantotenate for the treatment of pantothenate kinase-associated neurodegeneration (PKAN), a rare, progressive neurodegenerative genetic disorder. The FORT Study is designed to be registration-enabling in the U.S. and Europe, and top-line results are expected in the third quarter of 2019. “Reaching this milestone brings us closer to potentially delivering fosmetpantotenate as the first disease-modifying therapy to patients with PKAN,” said Noah Rosenberg, M.D., chief medical officer of Retrophin. “We are very grateful to the PKAN community for their support in raising awareness of this important trial, and we look forward to the readout of top-line data in the third quarter of 2019.” The Phase 3 FORT Study is an international, pivotal clinical trial designed to assess the safety and efficacy of fosmetpantotenate in approximately 82 patients with PKAN aged 6 to 65 years. The primary endpoint of the study is the change from baseline in the Pantothenate Kinase-Associated Neurodegeneration Activities of Daily Living (PKAN-ADL) scale through 24 weeks of treatment. After completing the 24-week treatment period, all patients will be eligible to receive fosmetpantotenate as part of an open-label extension. The FORT Study is being conducted under a Special Protocol Assessment (SPA) agreement, which indicates concurrence by the U.S. Food and Drug Administration (FDA) that the design of the trial can adequately support the filing of a New Drug Application (NDA). About PKAN PKAN is a rare, genetic and life-threatening neurological disorder characterized by a host of progressively debilitating symptoms that typically begin in early childhood. People suffering from PKAN may experience movement disorders such as dystonia (sustained muscle contraction leading to abnormal posture), rigidity, dysphagia (problems swallowing), and twisting and writhing, as well as visual impairment. PKAN is estimated to affect up to 5,000 people worldwide. PKAN is caused by a mutation in the PANK2 gene, which encodes a critical protein that phosphorylates vitamin B5 (pantothenate), generating phosphopantothenate. The disruption of this metabolic pathway ultimately leads to decreased levels of coenzyme A (CoA), which is essential in biochemical reactions impacting energy metabolism, membrane integrity, signaling and other critical processes. About Fosmetpantotenate Fosmetpantotenate is a novel investigational small molecule replacement therapy designed to pass the blood-brain barrier and be converted to phosphopantothenic acid (PPA). PPA synthesis is a key step in the biosynthesis of CoA. Preclinical findings suggest fosmetpantotenate has the ability to pass the blood-brain barrier and restore CoA levels. Fosmetpantotenate, which has the potential to be the first approved treatment targeting the underlying cause of PKAN, has been granted orphan drug designation for the treatment of PKAN by the FDA and European Commission, as well as Fast Track status in the U.S. by the FDA. In a Phase 1 study, fosmetpantotenate was found to be generally well-tolerated in healthy volunteers and it is currently being evaluated in the pivotal Phase 3 FORT Study conducted under a SPA agreement with the FDA. About Retrophin Retrophin is a biopharmaceutical company specializing in identifying, developing and delivering life-changing therapies to people living with rare disease. The Company’s approach centers on its pipeline featuring late-stage assets targeting rare diseases with significant unmet medical needs, including fosmetpantotenate for pantothenate kinase-associated neurodegeneration (PKAN), a life-threatening neurological disorder that typically begins in early childhood, and sparsentan for focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN), disorders characterized by progressive scarring of the kidney often leading to end-stage renal disease. Research in additional rare diseases is also underway, including a joint development arrangement evaluating the potential of CNSA-001 in phenylketonuria (PKU), a rare genetic metabolic condition that can lead to neurological and behavioral impairment. Retrophin’s R&D efforts are supported by revenues from the Company’s commercial products Chenodal ® , Cholbam ® and Thiola ® . Retrophin.com Forward Looking Statements This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “may”, “might”, “believes”, “thinks”, “anticipates”, “plans”, “expects”, “intends” or similar expressions. In addition, expressions of our strategies, intentions or plans are also forward-looking statements. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and uncertainties associated with the Company’s business and finances in general, success of its commercial products as well as risks and uncertainties associated with the Company’s preclinical and clinical stage pipeline. Specifically, with respect to fosmetpantotenate, the Company faces risk that the Phase 3 clinical trial of fosmetpantotenate will not demonstrate that fosmetpantotenate is safe or effective or serve as the basis for an NDA filing as planned; risk that fosmetpantotenate will not be approved for efficacy, safety, regulatory or other reasons, risk associated with enrollment of clinical trials for rare diseases and risk the clinical trial may not succeed or may be delayed for safety, regulatory or other reasons. The Company faces risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates; risk relating to the Company’s dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and intellectual property rights of third parties; and risks and uncertainties relating to competitive products and technological changes that may limit demand for the Company’s products. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Investors are referred to the full discussion of risks and uncertainties as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission. Contact: Chris Cline, CFA Vice President, Investor Relations & Corporate Communications 760-260-8600 IR@retrophin.com