Robert Linke, president and CEO of Embera Neurotherapeutics, a specialized biopharmaceutical firm based in Shreveport, Louisiana spoke with Drug Discovery & Development via email about his company’s progress on the development of drugs that battle addiction.
Please discuss your background. Where are you from? Where did you go to school?
I grew up in rural southwestern Michigan. I went to Albion College, a small private school in Michigan, where I received B.A. degrees in economics and mathematics. After spending two years in consulting with Accenture (Andersen Consulting in those days) I attended Harvard Business School (HBS), earning an MBA.
How did your career get started?
I was bitten by the healthcare bug working for Baxter International during the summer between my two years at HBS. I joined Baxter after business school as a product manager and have been in the industry ever since, spending 12 years at Baxter and a spinout of Baxter, Caremark, in marketing, sales and general management positions, always being closely involved in the development and commercialization of new products. For the last 18 years I have been an entrepreneur, having built a biotech company, diagnostic company, and most recently assembling a team of drug developers with over 100 years of experience and leading partners to advance EMB-001 through clinical development at Embera.
Explain Embera’s pipeline.
Embera is developing EMB-001 for smoking cessation, cocaine use disorder and other addictions. The candidate is a patented combination product comprising two FDA-approved medications, the cortisol synthesis inhibitor metyrapone and the benzodiazepine oxazepam. The innovation is based on insights into the physiologic responses to stress in addiction. EMB-001 is thought to act by mechanisms distinct from those of existing addiction treatments and is hypothesized to reduce the increased activity in the stress response system induced by cues that contribute to the acquisition and maintenance of addiction. With additional capital we plan to expand our development pipeline, with EMB-001 indications for methamphetamine, alcohol, and cannabis dependence.
Why is the company developing drugs to battle addiction?
There is a tremendous need for new addiction treatments today given the limited options available to patients. EMB-001 has the potential to treat a range of addictions given its mechanism is not specific to a particular addictive substance. By modulating the stress response system that drives the underlying craving associated with all addictions, we feel that EMB-001 has the potential to address a range of addictions. Our lead products are for cocaine dependence (clinically referred to as cocaine use disorder (CUD)), one of the most significant unmet needs in addiction today given that there are no approved treatments, and for smoking cessation (clinically referred to as tobacco use disorder), the biggest addiction in the world today that numbers over 1 billion smokers. Embera is developing EMB-001 for smoking cessation based on results of a preclinical nicotine dependence model where we compared EMB-001 to the leading prescription product on the market, Chantix®, and found that EMB-001 demonstrated a more significant effect on the reduction of nicotine dependence parameters.
Elaborate on the development process for your lead candidate EMB-001. How did you acquire the compound and please talk about the study results so far.
Embera licensed the EMB-001 technology from Louisiana State University’s medical school in Shreveport, Louisiana. Dr. Nicholas Goeders, a professor at the medical school, discovered the EMB-001 combination based on his 30 years of NIH-funded research.
In terms of results to date demonstrating EMB-001’s effect, a pilot clinical study in cocaine-dependent human subjects has been completed, showing the potential for EMB-001 to be effective in this disorder. In addition, positive effects have been published in preclinical models of nicotine, cocaine, and methamphetamine addiction.
At the end of 2015, we completed a Phase 1 safety and pharmacokinetic study in smokers that met the primary endpoints of safety and tolerability. In addition, exploratory smoking measures from the study support a planned Phase 1b study in tobacco use disorder, which is scheduled to begin in late 2016.
What opportunities or challenges do you feel this candidate could have when it comes to regulatory approval?
The regulatory path for approval of EMB-001 is clearly defined by the FDA. There are several advantages that EMB-001 has over new chemical entities (NCE’s) entering Phase 2 clinical trials that have de-risked product development compared to NCE’s at this stage of development. Given that EMB-001 is a combination of two FDA-approved products, there is a long history of safe use for the individual components of EMB-001 that NCE’s do not have entering Phase 2. In addition, unlike most NCE’s entering Phase 2, there is data demonstrating the effect of EMB-001 in a pilot study in cocaine dependent subjects. That said, our most significant challenge as we pursue regulatory approval is demonstrating efficacy in a larger Phase 2 study, the development phase with the greatest risk for all drugs in the development process.
How will it have an advantage against other therapies?
Current approved medications for treating addictions either (i) block the addictive substance’s effect, but not its use (Vivitrol® by Alkermes) or (ii) mimic its effect with a safer substance (Suboxone®, methadone, nicotine replacement therapy). In contrast, EMB-001’s approach, modulating stress response, has potential to substantially reduce cravings and loss of control, potentially preventing relapse and resulting in long-term abstinence from drug use.
Can you discuss any other issues when it comes to developing these addiction treatments?
Addiction has not been a focus of large pharmaceutical companies. As a result, there are fewer products in development and far fewer resources being devoted to addiction compared to other diseases like cancer, diabetes, and neurodegenerative diseases. Consequently, there are significant unmet needs in addiction. For example, there are no approved pharmaceutical treatments for cocaine and methamphetamine addiction today, the two most significant stimulant addictions. In fact, EMB-001 is the leading product in clinical development for cocaine use disorder, having successfully advanced through Phase 1. The opioid addiction crisis and its broad impact on the US population has brought new attention to addiction as a disease that needs to be treated with medical interventions, not just counseling.
What are the company’s plans for the rest of the year?
With the Phase 1 study completed we plan to advance two indications of EMB-001 in development. The first is a Phase 1b clinical study in cocaine use disorder (CUD). In addition, we plan to initiate a Phase 1b smoking cessation study that could provide initial efficacy measures for EMB-001 in a smoking population. To support this work, we are looking at potential grants and we are raising a round of financing to fund both indications through the next stage of clinical development.
