Big picture - Why invest in Motif Bio Plc
Motif Bio Plc Snapshot
Antibiotic resistance has limited the effectiveness of many existing drugs. The discovery of new antibiotics to address this resistance has not kept pace with the increasing incidence of difficult‐to‐treat bacteria. Without new antibiotics effective against resistant bacteria, the risk is that within five to ten years, routine surgeries such as hip and knee replacements, cardiac catheterization, caesarian section, and coronary artery bypass grafts would be impossible without effective antibiotics. One of the biggest threats is from methicillin‐resistant staphylococcus aureus (“MRSA”), a leading cause of hospital‐acquired infections and a growing cause of infections in healthy people. In 2013, the Centers of Disease Control (“CDC”) reported that at least 2M people became infected with bacteria that are resistant to antibiotics and at least 23,000 Americans died as a direct result of these infections – more than the annual number of deaths of people diagnosed with AIDS.
Given the urgent need to find new antibiotics to address this problem, Motif has a dedicated effort in developing new best‐in‐class antibiotics, each targeting different and unique mechanisms of action to be effective against bacteria that are resistant to most currently available antibiotics.
Motif is committed to helping resolve the looming public health crisis by developing novel antibiotics designed to be effective against multi-drug resistant bacteria. Our initial focus is on iclaprim, which may offer a rapid path to commercialization.
Iclaprim is a potential novel antibiotic, designed to be effective against bacteria that have developed resistance to other antibiotics, including trimethoprim. Iclaprim exhibits potent activity against Gram-positive clinical isolates of many genera of staphylococci, including methicillin sensitive staphylococci (MSSA) and methicillin resistant staphylococci (MRSA).
Iclaprim is a novel diaminopyrimidine antibiotic that inhibits an essential bacterial enzyme called ‘‘dihydrofolate reductase’’ (DHFR). Diaminopyrimidines are a class of chemical compounds that inhibit different enzymes in the production of tetrahydrofolate, a form of folic acid, which is required for the production of bacterial DNA and RNA.
The inhibition of DHFR represents a differentiated and underutilized mechanism of action compared with other antibiotics. We acquired iclaprim from Nuprim Inc., or Nuprim, following the completion of our merger with the company on April 1, 2015. Arpida AG, or Arpida, one of the previous owners of iclaprim, completed a comprehensive development program for iclaprim, including two successful Phase 3 trials in complicated skin and skin structure infections (cSSSI).
Iclaprim has been administered to more than 600 patients and healthy volunteers in Phase 1, 2 and 3 clinical trials and in contrast to vancomycin, a standard of care antibiotic in hospitalized patients with ‘‘Gram-positive’’ infections, no evidence of nephrotoxicity (i.e., damage to the kidneys caused by exposure to a toxic chemical, toxin or medication) has been observed with iclaprim, and, therefore, therapeutic monitoring or dosage adjustment in renally impaired patients is not required with iclaprim. ‘‘Gram-positive’’ or ‘‘Gram-negative’’ refer to how bacteria react to the Gram stain test based on the outer casing of the bacteria, and the bacteria’s cell wall structure. Each type of bacteria may be associated with different diseases. Iclaprim has also demonstrated rapid bactericidal activity and a low propensity for resistance development in vitro.
We believe that iclaprim is an attractive potential candidate for use as a first-line empiric monotherapy, the initial therapy administered prior to the identification of the pathogen, in severely ill patients who are hospitalized with ABSSSI caused by MRSA and have comorbidities, or also suffer from other health issues, such as diabetes or renal impairment. Renal impairment affects up to an estimated 936,000 of the approximately 3.6 million patients hospitalized with ABSSSI annually in the United States.
On March 2, 2016 we announced the dosing of the first patient in our two REVIVE (Randomized Evaluation intraVenous Iclaprim Vancomycin trEatment) Phase 3 clinical trials in ABSSSI. Data from the first REVIVE trial (REVIVE-1) is expected in the second quarter of 2017. Data from the second REVIVE trial (REVIVE-2) is expected in the second half of 2017. If successful, we believe the data from the two REVIVE trials will satisfy the requirements to submit a New Drug Application (NDA) in the United States and a Marketing Authorization Application (MAA) in Europe to obtain marketing approval for an IV formulation of iclaprim in the treatment of ABSSSI caused by Gram-positive pathogens, including resistant strains such as MRSA. If approved, we believe that iclaprim can become a valuable addition to the formulary of life-saving antibiotics used by hospital physicians.
We plan to complete preparations for our INSPIRE (Iclaprim for NoSocomial PneumonIa gRam- positive pathogEns) Phase 3 clinical trial with iclaprim in patients with HABP, including patients with VABP, by the end of 2016. Subject to the availability of funding, we would look to start dosing patients thereafter. There are approximately 1.4 million patients hospitalized annually in the United States with HABP, including patients with VABP. We believe that iclaprim is well suited for use as a first-line empiric therapy for patients with HABP, including patients with VABP, based on data from a Phase 2 clinical trial, which demonstrated iclaprim’s efficacy in this patient population. Additionally, in a Phase 1 healthy volunteer trial, concentrations of iclaprim at the site of infection in the lungs were considerably higher than concentrations in plasma.
In July 2015, the U.S. Food and Drug Administration, or FDA, designated the IV formulation of iclaprim as a Qualified Infectious Disease Product (QIDP) for ABSSSI and HABP. QIDP status grants iclaprim regulatory Fast Track designation, Priority Review and, if approved, a five-year extension to the statutory market exclusivity period in the United States, resulting in 10 years of market exclusivity from the date of approval. If approved by the European Medicines Agency, or EMA, we expect that iclaprim will qualify for eight years of data exclusivity and an additional two years of market exclusivity in the EU. If approved by the Pharmaceuticals and Medical Devices Agency (PDMA) in Japan, we expect that iclaprim will qualify for eight years of data exclusivity (which may be extended to 10 years for orphan or pediatric indications) and an additional two years of market exclusivity in Japan.
We believe that iclaprim is well suited for use as a first-line empiric monotherapy in patients with ABSSSI who are comorbid with renal impairment for the following reasons:
iclaprim achieved high cure rates against the common Gram-positive causal organisms, including MRSA, in patients with cSSSI in completed Phase 2 and 3 trials;
although the FDA has not yet made any determination regarding the safety and efficacy of iclaprim, in clinical trials involving over 600 patients and healthy volunteers, iclaprim exhibited a safety and tolerability profile comparable to that demonstrated by vancomycin and linezolid;
iclaprim has demonstrated no nephrotoxicity, eliminating the requirement for therapeutic monitoring or dosage adjustment in renally impaired patients;
no cases of symptomatic hypoglycemia have been reported in iclaprim-treated patients with diabetes mellitus receiving insulin or oral hypoglycemic agents;
iclaprim has demonstrated no clinically significant drug-drug interactions (DDIs) with selective serotonin reuptake inhibitors (SSRIs), or vasopressors; and
no cases of myopathy or rhabdomyolysis have been reported in iclaprim-treated patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment.
We also believe that iclaprim is well positioned as a first-line empiric therapy for patients with HABP, including patients with VABP, for the following reasons:
iclaprim achieved high cure rates against the common Gram-positive causal organisms, including MRSA, in patients with HABP, including patients with VABP, in a completed Phase 2 trial;
iclaprim has demonstrated high and sustained concentrations in epithelial lining fluid (ELF) and alveolar macrophages which were 20-30 times the plasma concentration, respectively, throughout an entire 7-hour sampling period; and
iclaprim has demonstrated no clinically significant DDIs with commonly used antibiotics in patients with combined Gram-positive and Gram-negative infections.
Motif intends to build a portfolio of novel antibiotics by licensing drug candidates from organizations specializing in antibacterial research. Motif is pursuing several programs in various stages of development.
Please click here to see the pipeline overview
BOARD OF DIRECTORS
Richard C.E. Morgan, Chairman
Richard C.E. Morgan is Chief Executive Officer of Amphion Innovations plc. Over the course of his career, Mr. Morgan has been directly involved in the start-up and development of more than 35 companies in the information technology, healthcare, and biotechnology industries. Mr. Morgan was a founder and Chief Executive Officer of Amphion Capital Partners LLC (the predecessor company). He was also the Managing General Partner of Amphion Partners LLC (formerly known as Wolfensohn Partners, LP) a position which he retains, although the partnership is no longer active. Before joining Wolfensohn, Mr. Morgan spent 15 years with Schroders plc, a British merchant bank, where he was a member of the Board of the merchant bank and head of the Schroder Strategy Group, which he founded. Mr. Morgan, a British citizen, was raised in Kenya and educated in England. He graduated with a B. Engineering First Class Honors from the University of Auckland, New Zealand. In 1982 he completed the Advanced Management Program at the Harvard Business School. He is currently also Chairman of Axcess International, Inc., FireStar Software Inc., PrivateMarkets, Inc., and WellGen, Inc.
Graham Lumsden, Chief Executive Officer, Director
Graham Lumsden, Chief Executive Officer of Motif, is responsible for all aspects of the strategy, management, and operations of the Company. Prior to joining Motif, Mr. Lumsden was Worldwide Business Leader, Contraceptives and Osteoporosis at Merck & Co., Inc. where he previously held other international senior leadership roles as well as senior marketing positions. Mr. Lumsden has a proven record of success leading change and delivering results at Worldwide Vice President level including cross-functional team leadership, new product launches, pre-clinical / clinical development, regulatory strategy, IP strategy / litigation, and domestic / international sales and marketing. Mr. Lumsden is a member of the Royal College of Veterinary Surgeons (MRCVS), holds a masters from the Chartered Institute of Marketing (MCIM), and is a dual citizen of the U.S. and UK.
Robert Dickey, IV, Chief Financial Officer
Robert Dickey IV, Chief Financial Officer, has broad senior leadership experience at public and private life sciences companies. Prior to Motif, he was CFO at Tyme Technologies, a publicly-traded oncology company. Prior to Tyme, he was CFO at NeoStem, Inc. (now Caladrius Biosciences), a public, regenerative medicines company. He previously served as SVP at Hemispherx Biopharma, SVP, CFO and Business Unit Manager at StemCyte, Inc., CFO at Locus Pharmaceuticals and COO and CEO at Protarga, Inc. Before that, he spent 18 years as an investment banker, mostly at Lehman Brothers, with a background split between M&A and capital markets transactions. Mr. Dickey holds an MBA from The Wharton School, University of Pennsylvania, and an AB from Princeton University.
David Huang, M.D., Ph.D, Chief Medical Officer
Dr. Huang is a senior pharmaceutical research executive, and the former Chief Medical Officer at ContraFect Corporation. Dr. Huang also led a drug development group in anti-infectives at Pfizer. Dr. Huang has over 15 years of clinical, academic and research experience in infectious diseases. He has served as a faculty member at Baylor College of Medicine and currently as an adjunct Assistant Professor at Rutgers New Jersey Medical School. He continues to see patients at the Veterans Affairs Medical Center in Houston. His research interests include bacteriology and virology, especially the epidemiology, pathogenesis, and treatment of multi-drug resistant organisms. He is experienced in designing, executing and closing out Phase I – III clinical trials for both antibacterials and antiviral agents. Dr. Huang completed his medical school at the University of Texas at Houston Medical School, and completed his internship and residency in internal medicine at the University of Texas at Southwestern and fellowship in infectious diseases at Baylor College of Medicine. He is board-certified in both internal medicine and infectious diseases.
Rajesh B. Shukla, Ph.D., Vice President, Clinical Operations
Dr. Shukla brings drug discovery, clinical development, and clinical operations experience from entrepreneurial and established pharmaceutical companies as well as with HHS and DoD/MoD agencies. Prior to joining Motif, Dr. Shukla headed early through NDA stage clinical development programs in Infectious Diseases, Epilepsy, Oncology, Endocrinology, Asthma, and Anaphylaxis clinical programs at Pfizer, Bristol-Myers Squibb, Bracco Diagnostics, Teva and, most recently, Acorda Therapeutics. He began his pharmaceutical career at Bristol Myers-Squibb with a discovery focus in Oncology, CNS, and late clinical stage experience in Anti-infectives programs. Dr. Shukla completed his bachelor’s degree in Biochemistry from Lehigh University and his Ph.D. from Carnegie-Mellon University followed by a postdoctoral fellowship at Yale University.
Robert Bertoldi, Director
Robert Bertoldi is President and CFO of Amphion Innovations. Mr. Bertoldi was a founder President and CFO of Amphion Capital Partners LLC (the predecessor company) and VennWorks LLC. Mr. Bertoldi is also a general partner of Amphion Partners LLC (formerly known as Wolfensohn Partners, LP). Prior to that, he served as Chief Financial Officer for James D. Wolfensohn, Inc. and Hambro America Inc. He began his career at KPMG and left as a manager in the investment services department. Mr. Bertoldi received a B.A. in Accounting and Economics from Queens College, New York in 1976 and became a Certified Public Accountant in 1978. He is a member of the AICPA and NYSCPA.
Craig T. Albanese, M.D., M.B.A., Non-Executive Director
Craig T. Albanese, M.D., M.B.A., is the Senior Vice President and Chief Operating Officer, New York-Presbyterian/Morgan Stanley Children’s Hospital and Sloane Hospital for Women.
Dr. Albanese is responsible for overseeing all operations and managing the strategic direction of the children’s and women’s hospital. He has spent the last 15 years in various leadership positions in healthcare. Prior to his position at New York Presbyterian (NYP), he spent 14 years at Stanford Children’s Health, most recently serving as the Vice President of Quality and Performance Improvement. He also served as the John A. and Cynthia Fry Gunn Director of Pediatric Surgical Services at Lucile Packard Children’s Hospital, and was a Professor of Surgery, Pediatrics, and Obstetrics and Gynecology at Stanford University Medical Center.
Prior to this, Dr. Albanese held faculty appointments and leadership roles at the Children’s Hospital of Pittsburgh and the University of California, San Francisco. After receiving his medical degree from SUNY Health Science Center in Brooklyn, Dr. Albanese was a resident and chief resident in general surgery at Mount Sinai Medical Center. He then completed pediatric general surgery and critical care research fellowships at Children’s Hospital of Pittsburgh.
Dr. Albanese also holds a Master’s in Business Administration from the Leavey School of Business at Santa Clara University. He has published more than 160 peer reviewed articles, was an NIH-funded investigator, and the program director for Stanford’s pediatric general surgery fellowship. An expert in management and improvement science and operations, he published a best-selling book on improvement science in health care entitled, “Advanced Lean in Healthcare. His recent work at NYP has been aimed at implementing a daily management system across NYP’s 6 hospitals. Dr. Albanese is also the executive sponsor for Graduate Medical Education at NYP, the nation’s largest single site training program.
Bruce Williams, Non-Executive Director
Bruce Williams has significant operational experience in the Pharmaceutical and Biotech industries. Mr Williams was an executive director of Ortho Biotech where he led the marketing of this Johnson & Johnson subsidiary’s lead product Procrit (epoetin alfa) from pre-launch through to its first year on the market, realizing $1 billion of revenue. Mr Williams was previously senior vice president of sales and marketing at Celgene Corporation where he built the company’s commercial and distribution infrastructure to support the launch of its first product Thalomid (thalidomide). Mr Williams was previously senior vice president, Sales and Marketing at Genta Incorporated where he lead the negotiaton of a licensing and co-development/co-marketing agreement with Aventis for the company’s lead product. The company realized over $300 million in proceeds from this agreement. Mr Williams currently serves on the boards of Motif and Afaxys Incorporated. He also Chairs the Board of Trustees of Rutgers Preparatory School, New Jersey’s first independent school.
Mary Lake Polan, M.D, Ph.D, MPH, Non-Executive Director
Mary Lake Polan, M.D., Ph.D., M.P.H., is a Clinical Professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at Yale University School of Medicine. Dr. Polan specializes in reproductive endocrinology and infertility and hormonal issues related to gynecology patients and menopause. She received her bachelor’s degree from Connecticut College and her Ph.D. in Molecular Biophysics and Biochemistry and M.D. from Yale University and completed her residency and Reproductive Endocrine Fellowship in the Department of Obstetrics and Gynecology at the Yale University School of Medicine. Dr. Polan received her M.P.H. (Maternal and Child Health Programme) from the University of California, Berkeley.
Dr. Polan served on the board of Wyeth Pharmaceuticals prior to its acquisition by Pfizer and currently serves on the board of Quidel Corp, San Diego, CA and on the boards of several privately held life sciences companies. She chairs an SAB in Women’s Health for the Proctor and Gamble Company and several other advisory boards of private life sciences companies. She is also a Managing Director of Golden Seeds, an angel investing group which invests in women led companies.
Zaki Hosny, Non-Executive Director
Zaki Hosny is an independent consultant to life sciences companies. Mr. Hosny spent most of his career at Merck & Co in marketing and general management positions around the globe, including management responsibility for the company’s business in major markets in Europe. Mr. Hosny also held senior marketing roles with worldwide responsibility for cardiovascular and other franchises, and was closely involved in the clinical development of some of the company’s major products.
Mr. Hosny was Chief Executive Officer of Motif from 2006-13, and Deputy Chairman of its Board of Directors. Mr. Hosny is currently a Senior Advisor to the Albright Stonebridge Group, a strategic consultancy firm based in Washington, DC; Business Development Advisor to ClinTec International, a contract research organisation based in Glasgow, Scotland; and a consultant to Harel Consulting of New Jersey, and Mettle Consulting of the UK. Mr. Hosny is based in Princeton, NJ and is a graduate of Cambridge University with an MA in history and law.
Charlotta Ginman, Non-Executive Director
Charlotta Ginman has substantial experience in financial and operational management gained during her career in investment banking and global telecommunications. Joining Ernst & Young and later appointed to senior roles with JP Morgan, Deutsche Bank and UBS, Ms. Ginman progressed to director of finance at Nokia Corporation, overseeing a number of acquisitions and led the successful sale of Nokia’s luxury mobile phone division, Vertu Corporation, to a private equity group. During the last two years she has been appointed as a non-executive director onto the boards of Wolfson Microelectronics plc (until its sale to Cirrus Logic in Aug 2014), Kromek Group plc where she also acts as chair of the audit committee as well as onto the board of Pacific Assets Trust plc, all UK based listed companies. A qualified chartered accountant in England and Wales, Ms. Ginman also holds an MSc in Economics from the Swedish School of Economics and Business Administration in Helsinki.
Jonathan E. Gold, Non-Executive Director
Jonathan Gold is a Managing Director of JEG Capital LLC, a family office and asset manager. Previously he was a Portfolio Manager for the Federated Kaufmann Funds from 2004 until 2012. The Federated Kaufmann Funds are aggressive growth mutual funds which currently have approximately $10B billion in assets under management. Prior to that Mr. Gold was a partner in Amphion Capital and Wolfensohn Partners (originally affiliates of James D. Wolfensohn Inc) where he was active in financing and growing early stage life sciences and information technology companies from 1995 to 2004. Early in his career, Mr. Gold was a financial analyst for Prudential’s Realty Group, which managed over $10 billion in equity real estate and over a $20 billion dollar portfolio of mortgages. Mr. Gold received his B.S. and MBA in Finance from New York University’s Stern School of Business.
Nominated Advisor and Joint Broker
Zeus Capital Ltd.
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Northland Capital Partners Limited
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Plumtree Capital Limited
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Reporting Accountants and Auditors to the Company
Crowe Clark Whitehill LLP
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Media and Investor Relations
Walbrook PR Ltd
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Tel: 020 7933 8780
Email: [email protected]
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Reed Smith LLP
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United States of America
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