Algomedix Hopes New Class of Pain Drugs Will Curb Dangers of Opioids

Innovation That Matters

While the opioid epidemic in the US has become a serious public health issue, research into alternative, non-addictive pain drug research and development in the US pharmaceutical industry has not matched the urgent need. However, innovative and more nimble biotech companies may ultimately come to the rescue with unique approaches to create novel therapeutic analgesic medicines that address the real issue of chronic pain without the addictive side effects of current opioids. One such company not afraid to tackle this growing problem is Seattle-based Algomedix.    

Algomedix is a leader in the development of novel Transient Receptor Potential (TRP) therapeutics to treat serious chronic and acute pain, and has developed a novel non-opioid, non-addictive TRPA1 antagonist for the treatment of pain. This new class of pain therapeutics holds potential to overcome the significant shortcomings of opioid drugs, which have significant abuse liability and addiction concerns, and also does not have the safety limitations of non-steroidal anti-inflammatory drugs (NSAIDs). Algomedix also has a drug discovery program targeting chronic kidney disease. 

Leading Algomedix’s research for almost nine years is CEO and President Jeffrey Herz, Ph.D., who founded the company in 2010. Previously, Herz was the Scientific Founder and Director of Discovery and Pharmacology at Omeros, another Seattle-based biotech, where he led the development of Omidria, which was approved by the FDA.

WuXi AppTec Communications, as part of a new industry series, recently interviewed Herz about the clinical direction and goals of Algomedix as well as what the future holds for research in pain medicine.

WuXi: Why has the drug industry been slow in developing effective alternatives to opioid pain medicines?

Jeffrey Herz:  There are multiple reasons that have contributed to the long development process for creating alternatives to opioid pain medicines.  First, this question is really asking why superior pain medicines without the numerous serious adverse effects of opioids have not yet reached the market.  At the outset of the drug discovery process, the choice of the correct molecular target is critical to any successful approach, and due to numerous mediators and potential targets involved in pain and inflammation, the identification of key molecular targets has been a problematic issue for many years.  Building upon recent advances in human medical genetics and pain diseases has led to identification of key novel ion channels as validated targets.  Secondly, from the scientific approach, these new targets belong to the ion channel class, which typically has numerous related individual members in a given superfamily, which fulfill other functions in the human physiology. This class of ion channel targets has proved challenging for small molecule drug development, particularly for identifying small molecules which are highly specific for the desired target.  Finally, at the clinical level, placebo responses have also made it challenging to identify positive responses for some of these new drugs in development.

WuXi: Should there be more incentives for companies to develop non-addictive pain therapies? If so, what would you suggest?

Jeffrey Herz: Absolutely. Clearly, due to the magnitude of the problem in the US, a major effort supported at the Federal level, similar to the Cancer Moonshot, could be implemented with funds devoted to supporting truly novel research efforts for creating an alternative non-opioid pain medicine that spans early stage drug discovery, development and continuing through FDA approval.  This approach has not been given enough emphasis in current Federal initiatives which have focused more on opioid addiction treatment.  In addition, if private philanthropic foundations, like the Bill and Melinda Gates Foundation, and others were to make this goal one of their priorities, this could also have a major impact.  Despite historical success with pain medicines, many large pharmaceutical companies are focusing on an increasingly narrow number of therapeutic areas.  It has become clear that although a novel non-opioid pain medicine which is easy to use and addresses a large patient population can be a blockbuster drug, much like Celebrex was in the past, large pharmaceutical companies are not providing the innovation needed to create these medicines.  However, the potential for large pharmaceuticals to establish partnerships with small biotechs could greatly accelerate pain drug development and bring new solutions to the market much faster.

WuXi: What spurred your company to get into this field?

Jeffrey Herz: Algomedix saw a major unsolved problem in pain medicine with a critical unmet medical need. From a personal perspective, I knew the tragic story of a young man who was a medical student and became a victim of an opioid overdose.  As the scientific founder, with over 20 years of experience working in the field of drug discovery and development for pain and inflammation and with strong ties to my previous academic research, I realized that no major advances had been made in the field for almost two decades and so there was an urgent need for an advance in this therapeutic area.  We started with the goal of creating the next-generation analgesic medicine that could solve all of the major problems known to be associated with opioid medicines. I envisioned a critical non-opioid drug target with numerous advantages and a novel discovery approach for this specialized area of receptor-ion channels and pain that could provide the solution to this therapeutic problem.

WuXi: How does your approach and technology differ from other companies in this field?  What are your advantages?

Jeffrey Herz: A unique advantage of the Algomedix approach is that the molecular target for our drug is a validated non-opioid target which is critical for both sensing and integrating pain signals at the first stage of neural processing. This target is located in the peripheral nervous system on the endings of specialized nociceptor (pain sensing) nerve fibers. This means that we can specifically block pain signals without having any other effect on sensory modalities.  In addition, the molecular mechanism of action of our drug is very well-defined.  Furthermore, the peripheral site of action means that our drug does not need to enter the brain to be effective.  This peripheral mechanism of action combined with high specificity provides numerous advantages to eliminate the possibility of adverse effects that are common to many other pain drugs which act in the CNS, such as sedation, sleepiness, ataxia and other CNS effects.

In contrast to the typical high-throughput screening approach used by large pharmaceutical companies to initially identify active compounds, Algomedix employs a rational pharmacology approach to identify new drug leads with superior drug-like properties which include properties predicted to lead to oral bioavailability, adequate chemical and metabolic stability and the absence of toxic effects.  In addition, our approach was designed to create an allosteric inhibitor of the TRP function, which has additional advantages.  This has proved to be highly successful approach.  It allows Algomedix to start with small molecules that have the greatest potential for optimization to achieve the complex requirements of a small molecule drug. This has enabled Algomedix to achieve drugs with right combination of potency, oral bioavailability, and desired metabolic stability that create an effective new drug. Thus, Algomedix has succeeded in creating a new pain drug for the TRPA1 target with a novel mechanism of action and superior properties while many other large pharmaceutical companies and biotechs have failed. The above, combined with the mode of action in the peripheral nervous system, has created a pathway to a safe and effective novel pain medicine.

WuXi: What are the risks and side effects associated with your medicines?

Jeffrey Herz: To date, our pain medicine does not have any known risks or obvious side effects.  Animals dosed with these medicines appear completely normal, and don’t show any adverse effects.  Because our medicine is known to act in the periphery and only very low levels are present in the brain while providing effective pain inhibition, the medicine does not appear to have any of the side effects often seen with medicines acting in the central nervous system.

WuXi: How would you compare the effectiveness of your pain medications to opioid pain drugs?

Jeffrey Herz: The pain medication we are developing appears to be at least as effective, or more so, than some of the moderate to severe pain drugs, such as Vicodin or OxyContin.  This is based on direct comparison in the same animal model of chronic neuropathic pain using a mg/kg basis to compare known drugs in reversing established chronic pain.

WuXi: Will there be an increase in companies entering the field over the next 5-to-10 years?

Jeffrey Herz: It does not appear at this time that there will be many new companies entering this highly specialized area.

WuXi: Should addictive opioid drugs be eliminated, or is there still a place for them in treatment of chronic pain?

Jeffrey Herz: There is still an important and legitimate need for a certain group of opioid pain medicines for many patients.  I don’t believe we can simply eliminate this class of drugs for patients suffering from severe chronic pain who require these medicines.  When there is a highly effective, approved alternative pain medicine on the market, it is likely we will see a rapid and significant decrease in the use of certain types of opioid medications.

WuXi: Are you looking for partnerships to help advance your technology?

Jeffrey Herz: Yes, we are seeking partnerships with large pharmaceutical companies to advance the development of novel pain drug.

WuXi: What impact will your new drug have on the health care system?  Will there be substantial cost savings?

Jeffrey Herz: It is anticipated that the new Algomedix pain drug could have a major impact on the health care system since there is an extremely large market for moderate-to severe pain drugs, and the detrimental societal effects linked to the abuse of opioids have a major impact throughout the health care industry.  Yes, without doubt, this new non-opioid pain medicine which will have no addiction potential and abuse liability will yield major cost savings for the health care system as a consequence of a direct beneficial effect on the opioid drug epidemic, reducing abuse and addiction, and saving at least 20,000 lives each year in the US.

WuXi: How soon will effective, non-addictive chronic pain medicines be available?

Jeffrey Herz: This is difficult to answer, but it appears possible that in another two to three years we could see new first-in-class non-opioid pain medicines being approved.  This depends highly on the resources that are made available to advance the drugs that are currently in development.

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