EmeraMed Newsletter

February 2019

The good news all of us in the US have been waiting for: The FDA recently approved and the attending physician has received the first delivery of Irminix® for compassionate use in the US in 9 years.

EmeraMed filed the necessary documents with the US FDA late in 2018 which simplifies early access in the US with our chelator/antioxidant compound named Emeramide as the INN and Irminix® as the name of the encapsulated drug.

Emeramed 2019 January Newsletter

It took a lot longer than anyone anticipated because of differences in regulatory schemes in EU vs. US but those hurdles are now behind us and we are progressing with a US FDA Investigative New Drug (IND) registered as IND#142540.

Irminix® is a new drug that rapidly captures mercury and other heavy metals. Irminix® has passed multiple safety studies in animals and human, including a Phase 1 safety and pharmacokinetic study and two small Phase 2 safety studies on mercury toxic gold mine workers and COPD patients. In all of these studies, treatment with Irminix® caused no drug related adverse events. The Phase 2a with 36 Ecuadorian gold miners found both the Irminix™ dosage groups symptoms improved, 100mg/day and the 300 mg/day, while the placebo group did not until they too received Irminix™. (see the dramatic graph below of the mercury toxic gold miner’s recovery)

As a result, over a hundred treatments have been approved in various European countries this past year for “Individual Patient Use”. The FDA has recently approved a fourth “Compassionate Use” which also requires an Institutional Review Board (IRB) to review applications and informed consents. Ultimately the physician is responsible for prescribing the treatment.

Boyd Haley, PhD. President

Boyd Haley, PhD. EmeraMed President

Since 2006 when Dr. Boyd Haley began development of this metal chelator and antioxidant it has been known by a number of different names, NBMI (scientific chemical abbreviation), approved drug name Irminix® and INN International Non-Proprietary Name Emeramide, and from 2008-2010 as the dietary supplement OSR#1®.

The many reports of health improvement from physicians, dentists and their patients who used OSR#1® have guided the Company’s development by precisely pointing toward disorders that respond rapidly to this chelator. We are now investigating with multiple Phase 2 (efficacy) trials the following conditions: Mercury Toxicity, Iron Overload Toxicity, and COPD. Most of the company’s seventy-five investors are dentists, physicians or patients who have either had personal experience with the compound or have observed improvement in their patients. They already know it works safely and effectively. Our only remaining hurdles are fulfilling the many requirements that are required for full drug marketing approval.

What does Irminix® do?

Irminix® binds a number of toxic heavy metals like mercury (Hg2+). When Irminix® captures such a metal it thermodynamically and irreversibly binds it into a chelated complex that immediately stops the metal induced toxicity. The resulting metal/Irminix® complex is a molecule that is insoluble in acid, base, water or fat. It is an almost indestructible particle that is then safely excreted over time through the bowel most likely through the well known P-450 detoxification system.

In addition, Irminix® is also a potent scavenger of hydroxyl free radicals as determined by its oxygen radical absorbancy (ORAC) scores. Irminix® will dramatically reduce oxidative stress (OS). OS is a major component of almost all diseases. Therefore, many diseases or injuries which would benefit from OS reduction are helped by Irminix®.

Some young people have reported OSR#1® even benefits hangovers. The company is not promoting the use of Irminix® for hangovers but the point is many things that make us feel bad are not necessarily a named disease and Irminix® may help many disorders too because it helps reduces OS.

Irminix® is very lipophilic (fat soluble) and has been shown in test animals to cross Blood-Brain-Barrier (BBB), cell membranes and enter mitochondria where metal toxicity and hydroxyl free radical damage typically occur.

Symptoms of Mercury Intoxication dramatically improved by Irminix®

Below is a graph prepared from the study of mercury poisoned Ecuadorian Gold Miners based on Table S3.2.1 from that trial. “Efficacy of N,N‘bis-(2-mercaptoethyl) isophthalamide on mercury intoxication: a randomized controlled trial”, Schutzmeier et al. Environmental Health (2018) 17:15

A large number of severely mercury intoxicated gold miners were screened for this trial and we accepted 36 of the worst of the worst into the study.

It is very telling that in this double-blind placebo controlled clinical trial of mercury intoxicated gold miners the vast majority of symptoms were in the control group who had not yet received treatment. Miners receiving Irminix® at 300 mg/day clearly felt better with 7 reported adverse events (AE) vs. 24 for the controls.

The safety set found that the majority of AE occurred in the placebo controls and the fewest number of AE occurred in the gold miners who got the most (300 mg/day) Irminix®. Obviously Irminix® did a lot to relieve pain. Also evident is the fact that these were not drug related adverse events but are actually the most common symptoms of mercury intoxication. Unique among metal chelators, Irminix® has shown no drug-related adverse events either in Phase 1 and Phase 2a clinical (human) trials or when it was used by thousands of individuals as OSR#1® a dietary supplement.

Most importantly, research has again determined that use of Irminix® does not deplete any essential metals including iron, copper or zinc which are bound to their specific utilizing enzymes or transport proteins in normal healthy individuals. This was an initial concern since Irminix® binds to these metals when they are free in solution and, being redox metals induce oxidative stress and are therefore toxic.

Theory – How Irminix® Binding Toxic Metals is Relevant in a Range of Diseases

Research has found that inorganic mercury (Hg2+) displaces iron (Fe2/3+) from natural binding sites. The unbound Fe2/3+ then catalytically generates thousands of hydroxyl free radicals through Fenton type chemistry which is the predominant cause of oxidiative stress. Not only mercury and other heavy metals but other toxins have been shown to displace iron, starting the toxic reactions described above. Therefore, for a chelator to be maximally effective at treating mercury toxicity or oxidative stress, the chelator must also bind Fe2/3+ into a non-reactive complex, halting the Fenton reaction.

Irminix® has been shown experimentally in biological systems to totally inhibit the abilities of both free Fe2+ and Cu2+ redox metals to catalyze the production of hydroxyl free radicals. Based upon numerous study results the EmeraMed has theorized that irreversibly chelating Fe2/3+ and Cu2+ and reducing oxidative stress are the major factors responsible for many of the rapid and profound effects that were noted with OSR#1® in a wide range of diseases, and now in Individual Patient Treatments.

Orphan Drug Development

Both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) awarded Irminix® orphan drug designation* in 2012 for the treatment of chronic mercury toxicity. While the mechanism of Irminix® binding mercury into a strong non-reactive Irminix® -Hg complex is chemically quite simple, it has become increasingly clear that this mercury-indication is difficult to handle from a drug development and regulatory point of view. This is due to the lack of a single significant toxic clinical endpoint that is caused by mercury and mercury alone. It has been observed that about 20+ symptoms of mercury toxicity are also observed in Lyme’s disease. The challenge is to exactly determine how Irminix® works in humans, and we have developed an innovative strategy to address this obstacle.

FDA/EMA regulators have directed EmeraMed to name a specific clinical endpoint that will show the elimination of mercury’s toxic effect in chronically mercury-toxic subjects. But which endpoint? Neither the USA nor the EU considers mercury toxicity to be a significant unmet need. For indications (diseases) where the regulatory authorities feel there is a great unmet need the agencies tend to be more creative and helpful in rapidly getting a drug to market.

Iron Overload indications – Multiple Blood Transfusions – Sickle Cell Anemia, Thalassemia, Myelodysplastic Syndromes

Beta Thalassemia Major and Sickle Cell Disease are genetic disorders of hemoglobin affecting millions of people worldwide. Myelodysplastic syndromes are a group of diverse bone marrow disorders affecting several hundred thousand people globally. All three of these diseases share a common treatment protocol – blood transfusions. Since blood transfusions contain substantial amounts of free iron chronic transfusions inevitably lead to iron overload illness and hence the need for iron removal.

There are three FDA/EMA approved iron-chelators – Deferoxamine, Deferiprone and Deferasirox – all of which have toxic side effects. Exjade (Deferasirox) was recently issued a black box warning by the FDA listing acute renal impairment and failure, and death (1-10%) as common side effects. Currently, EmeraMed has ongoing in vivo animal studies that should support Phase 2a clinical studies for these three disease groups. EmeraMed has applied for a Phase 2a pilot clinical study on Beta Thalassemia Major, an iron disorder, in Albania. We are awaiting ethics approval for this project to proceed.

We have recently worked with a Clinical Research Organization in Colombia, S. America and have produced a protocol for a pivotal Phase 2 study on an accidentally mercury intoxicated population of about 120 adolescents and adults. This protocol has been translated into Spanish and is currently under ethics committee review and will be submitted to Colombian medical regulators (INVIMA) for approval in early 2019. The intention is that this study could lead to an early approval for Irminix® in Colombia and possibly other countries. We are currently in the process of opening an IND with the FDA that will also involve this study.

COPD – Phase 2a Study was finished 2018

When Irminix® was sold as a dietary supplement under the name, OSR#1®, treatment with this compound led to a radical reduction of mucus and coughing for some patients diagnosed with COPD. Such effects do not exist with currently approved mucolytic drugs for COPD. Endpoints showing reduction of mucus and coughing within a short treatment period is what EmeraMed hoped to show in its Phase 2a COPD clinical study completion in May 2018. It was thought that COPD was produced by OS from cadmium smoking, but Cornell University has recently shown that excess iron may be involved with COPD. Furthermore, Cornell has shown that the iron chelator, Deferiprone, has an ameliorating effect. The problem with Deferiprone is that it also has a wide range of adverse side effects, and, being an inefficient iron chelator, it typically needs considerably longer treatment periods – months, not weeks.

EmeraMed conducted a small proof-of-concept Phase 2a study on 12 individuals at the Karolinska Institute and other facilities in Sweden over a short 2-week treatment period. The study found that Irminix® measurably reduced the most common symptoms of COPD in two of the 12 patients treated. That is 17% and a fantastic beginning. The data indicate that even though Irminix® does not have the ability to repair of severely damaged lung tissue it may well have the capability to prevent the oxidative stress that leads to damaged lungs and COPD if started early enough. Unsurprisingly, there were no drug related adverse reactions.

COPD – Worldwide Patent Protection Application

The patents for the treatment of COPD has been awarded to EmeraMed for the treatment of COPD has now been awarded in Japan, Russia, seven more ex-Soviet republic, and Saudi Arabia. Together with the previously awarded markets of the EU, USA, Brazil, Mexico, Peru, South Africa and Hong Kong, these provide a worldwide coverage and is valid until 2034. Patent applications processes are still ongoing in several other countries including China.

Early Access Program – Individual Patient Use Of Irminix®

There is an increasing interest in treating patients with Irminix®. A drug under development can be approved as a treatment for patients through early access government programs called Individual Patient Use or Compassionate Use provided:

  1. The drug shows promising results
  2. The drug has a favorable safety profile
  3. Adequate drugs to treat the disorder/condition are lacking.

Use of Irminix® is growing rapidly worldwide through Individual Patient Use programs. Over a hundred Individual Patient Use treatments have been sent to Germany, Switzerland, Austria, New Zealand, UK, Lebanon and US. New Zealand and Lebanon are particularly straight-forward as physicians there can prescribe without further regulatory approval. The USA is the most complicated and expensive as the FDA also requires an Institutional Review Board (IRB) to review applications and informed consents. EmeraMed does not charge for the drug, but we charge a $750/600Euro flat fee for 4.2 grams that provides a two-week treatment @ 300 mg/day. The fee pays for insurance-shipping-administrative costs. Information on our Early Access Program is found at www.emeramed.com/early-access/

The Company And The Drug Irminix®

EmeraMed Ltd is an Irish biotech company with subsidiaries in the USA and Sweden that is developing Irminix®, a metal chelator and antioxidant, as a new drug Irminix® is a drug/chelator/antioxidant that binds and, upon binding, immediately eliminates the toxicity of metals such as mercury-lead-cadmium-arsenic, as well as free or unbound iron-copper-zinc.

Thank You For Your Support

EmeraMed’s strategic and focused efforts to achieve market approval, as described in this Newsletter, are moving the company ahead rapidly. We are working diligently to insure that Irminix® will soon benefit people worldwide as an effective and safe drug for a range of diseases and conditions that lack efficient treatment, and we will keep you updated by this newsletter on EmeraMed’s progress to develop Irminix® as an approved drug globally.

Thank you for your continuing support.

Sincerely,

The Board of EmeraMed

Boyd Haley, CEO

Lexington, Kentucky, USA