SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS AND INDUSTRY DATA
This Annual Report on Form 10-K contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Annual Report on Form 10-K, including statements regarding our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans and objectives of management and expected market growth are forward-looking statements. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
These forward-looking statements include, among other things, statements about:
We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We have included important factors in the cautionary statements included in this Annual Report on Form 10-K particularly in the "Risk Factors" section, that could cause actual results or events to differ materially from the forward-looking statements that we make. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, collaborations, joint ventures or investments that we may make or enter into.
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You should read this Annual Report on Form 10-K with the understanding that our actual future results may be materially different from what we expect. We do not assume any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.
REFERENCES TO CATABASIS
Except as otherwise indicated herein or as the context otherwise requires, references in this Annual Report on Form 10-K to "Catabasis," "the company," "we," "us," and "our" refer to Catabasis Pharmaceuticals, Inc.
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PART I
Item 1. Business
Overview
We are a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics based on our proprietary Safely Metabolized And Rationally Targeted, or SMART, linker drug discovery platform. Our SMART linker drug discovery platform enables us to engineer product candidates that can simultaneously modulate multiple targets in a disease. Our proprietary product candidates impact pathways that are central to diseases where efficacy may be optimized by a multiple target approach. Our primary focus is on treatments for rare diseases. We are also developing other product candidates for the treatment of serious lipid disorders. We have applied our SMART linker drug discovery platform to build an internal pipeline of product candidates for rare diseases and plan to pursue partnerships to develop additional product candidates.
CAT-1004 is an oral small molecule that we believe has the potential to be a disease-modifying therapy for all patients affected by Duchenne muscular dystrophy, or DMD, regardless of the underlying dystrophin mutation. DMD is an ultimately fatal genetic disorder involving progressive muscle degeneration. CAT-1004 is a SMART linker conjugate of salicylate, a non-steroidal anti-inflammatory drug, and the omega-3 fatty acid docosahexaenoic acid, or DHA, a naturally occurring unsaturated fatty acid with anti-inflammatory properties. We designed CAT-1004 to inhibit NF-kB, or nuclear factor kappa-light-chain-enhancer of activated B cells, a protein that is activated in DMD and drives inflammation, fibrosis and muscle degeneration, and suppresses muscle regeneration. In animal models of DMD, CAT-1004 inhibited NF-kB activity, reduced muscle degeneration and improved muscle regeneration and function. Beneficial effects were observed in skeletal, diaphragm and cardiac muscle. In Phase 1 clinical trials in adults, CAT-1004 inhibited NF-kB and was well tolerated with no observed safety concerns. The United States Food and Drug Administration, or FDA, has granted orphan drug, fast track and rare pediatric disease designations to CAT-1004 for the treatment of DMD. The European Commission, or EC, also has granted orphan medicinal product designation to CAT-1004 for the treatment of DMD.
We are currently conducting the MoveDMD Phase 1/2 trial of CAT-1004 in boys with DMD between ages four and seven. We reported positive top-line results from Part A of the MoveDMD trial in January 2016. Top-line results indicated that all three doses of CAT-1004 studied were generally well tolerated with no safety signals observed. Top-line pharmacokinetic results demonstrated CAT-1004 average plasma exposure levels consistent with those previously observed in adults at which inhibition of NF-kB was observed. Subject to regulatory approval of our proposed protocol, we expect to initiate Part B of the MoveDMD trial in the first half of 2016 and to report top-line Part B data in late 2016, contingent on patient enrollment. If the results from our MoveDMD clinical trial and discussions with regulatory authorities regarding a pivotal trial are positive, we intend to initiate a six-month Phase 3 pivotal clinical trial of CAT-1004 in 2017. If the results from the Phase 3 clinical trial are positive, we intend to seek marketing approval for CAT-1004. We hold rights to CAT-1004 throughout the world.
Our CAT-2000 series is our other clinical-stage program. We applied our SMART linker drug discovery platform to engineer the CAT-2000 series product candidates to inhibit the Sterol Regulatory Element Binding Protein, or SREBP, pathway. We used different SMART linkers to produce two CAT-2000 series product candidates, CAT-2054 and CAT-2003. These product candidates possess different pharmacokinetic and biodistribution characteristics. CAT-2003, our first generation product candidate, is an orally administered molecule that inhibits the SREBP pathway predominately in the intestine. CAT-2054, our second generation product candidate, is an orally administered molecule that inhibits the SREBP pathway predominately in the liver. We are developing CAT-2054 for serious lipid disorders such as hypercholesterolemia.
Hypercholesterolemia is a disease that increases the risk of cardiovascular events. By modulating the SREBP pathway, CAT-2054 may inhibit production of important cholesterol metabolism proteins, such as proprotein convertase subtilisin kexin 9, or PCSK9; 3-hydroxy-3-methyl-glutaryl-CoA reductase, or HMG-CoA reductase; adenosine triphosphate citrate lyase, or ATP citrate lyase; and Niemann-Pick C1-like 1, or NPC1L1. In a clinical trial of CAT-2003, we observed statistically significant reductions in triglycerides and low-density lipoprotein cholesterol, or LDL-C, suggesting an impact of SREBP modulation on cholesterol metabolism. Because the liver is the primary regulator of cholesterol metabolism, we specifically designed the SMART linker in CAT-2054 to deliver more of the intact conjugate to the liver than CAT-2003. We believe that CAT-2054, if approved, has the potential to be the first therapy to simultaneously modulate cholesterol synthesis, clearance and absorption. By inhibiting SREBP, a master regulator of lipid metabolism in the body, CAT-2054 has the potential to significantly reduce LDL-C; it may also have beneficial effects on other metabolic parameters such as triglycerides, glucose and liver fat. This profile may differentiate CAT-2054 from currently approved therapies for hypercholesterolemia and others in development. We are developing CAT-2054 to be used in addition to statins in patients who cannot achieve their LDL-C goals with statins alone. In August 2015, we announced positive top-line Phase 1 clinical trial data for CAT-2054. Based on these data, we initiated a Phase 2a trial in patients with hypercholesterolemia in December 2015, which is ongoing. We anticipate that we will report top-line data from the Phase 2a trial in the third quarter of 2016. Additionally, we are currently conducting studies and have generated positive data in preclinical models that support the therapeutic potential of the CAT-2000 series in Nonalcoholic Steatohepatitis, or NASH. We hold rights to CAT-2054 throughout the world, and we intend to seek a partner for the program prior to initiating Phase 3 clinical trials.
CAT-4001 is a SMART linker conjugate of monomethyl fumarate and DHA. CAT-4001 is a small molecule that activates Nrf2 and inhibits NF-kB that we are developing as a potential treatment for neurodegenerative diseases such as Friedreich's ataxia and amyotrophic lateral sclerosis, or ALS. Nrf2, or Nuclear factor (erythroid-derived 2)-like 2, is a gene transcription factor, a protein that works inside of cells to control the expression of genes, that controls the body's response to cellular stress and oxidative damage. We believe that CAT-4001 modulates the disease pathway by enhancing the movement of Nrf2 to the nucleus of the cells and inhibits NF-kB by reducing the movement of activated NF-kB to the nucleus of the cells. The Nrf2 and NF-kB pathways have been implicated in Friedreich's ataxia and ALS. We plan to conduct investigational new drug application, or IND, enabling studies in 2016 for CAT-4001. We hold rights to CAT-4001 throughout the world.