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Expert Financial Analysis and Reporting

Effective Treatment of Hyperkalemia Promises to be a Multi-billion Opportunity

Key Points

  • There are no effective treatment options for long term treatment of hyperkalemia (high potassium levels).
  • My research suggests that the annual addressable market could be in the tens of billions of dollars in the US.
  • Two emerging biotechnology companies have almost simultaneously developed effective drugs for hyperkalemia.
  • Relypsa’s patiromer could be introduced in the US in late 2015 and ZS Pharma’s ZS-9 is about six months behind.
  • This note is a primer intended to help investors evaluate what I believe is a huge opportunity for these drugs. Reports on each company are close to being finished.

Investment Significance of this Report

A little over six months ago I heard a presentation for the first time by Relypsa (RYYP) at a biotechnology company conference. I attend a number of conferences each year and also listen to webcasts from others. In this way, I screen a lot of companies each year as well as keep up to date on companies I am already involved with and their competitors.

I have learned from hard experience that it is dangerous to listen to a presentation for the first time and think that you understand a company. The presentations tend to over-emphasize the positives and underestimate or dismiss the negatives. Both large companies and small companies do this and there is nothing overly sinister about this. It is just that managements have their lives tied up in their companies and this introduces biases. This would be true for me and you if we were in their situation. Anyway, I always question my initial impressions of companies.

That said I walked away from the Relypsa presentation with very positive impressions. I was persuaded that hyperkalemia can be life threatening in some situations and should be promptly addressed when it occurs. However, there is no effective therapy. The addressable market appears to be huge as hyperkalemia is a frequent complication of late stage hypertension, heart failure and diabetes which are diseases with large incidences of occurrence. Relypsa’s patiromer looked to me to be a very effective drug with good clinical data that should be approved at its October 21, 2015 PDUFA date. What is there not to like in this scenario?

As I was working on my analysis of Relypsa, I found that ZS Pharma (ZSPH) was following closely behind patiromer with a drug called ZS-9 that has a different mechanism of action. It also looks to be a very good drug with good clinical data that could be approved six to nine months after patiromer. It is not responsible to analyze one company without analyzing the other so I have done my analysis of each in parallel.

Both Relypsa and ZS Pharma came public in 2014 with very successful initial public offerings and both recently did a follow-on that was well received. They are both awash with cash. There is a battle going on between analysts who cover each company, the most influential of whom are those who work for the investment banks who help raise capital for them. They are going back and forth about the relative merits of each drug; there seems to be some bias toward the company that is a banking client.

An investor can listen to one group of analyst’s arguments and come away positive on one company and negative on the other. Then you can listen to the other group and reverse your opinion. I am in the late stages of finishing reports on both companies and will be publishing soon. My research does show that there are meaningful differentiations between patiromer and ZS-9 that will affect market share. However, this is not a zero sums game and the market opportunity appears to be in the billions of dollars. One company may do better than the other, but both are likely to be successes.

This report is intended to provide background that can help you to understand hyperkalemia and the market opportunity. Hopefully you will find this useful in understanding and informing your opinion on Relypsa and ZS Pharma. I will be issuing my investment theses when I publish reports on these companies. I think that these stocks have the potential to be excellent long term performers, but I would caution that they are not undiscovered as Relypsa has a market capitalization of $1.4 billion and ZS Pharma is at $1.1 billion.

The Role of Potassium in the Body

Potassium is the major positive ion (cation) that is found in cells. Other important ions are sodium, chloride, calcium, and magnesium. The balance of these ions in the body is essential for normal functioning of cells and organs. Potassium is the eighth most common element by mass (0.2%) in the human body, so that a 160 pound adult contains a total of about 0.3 pounds of potassium.

Potassium is essential for many bodily functions such as the regulation of the heartbeat, contraction of skeletal and smooth muscles, the amount of water retained in the body and a healthy blood pH level. Potassium plays a role in every heartbeat so that a hundred thousand times a day, it helps trigger the electrical energy that causes the heart to contract and pump blood through the body. A seriously abnormal increase in potassium (hyperkalemia) or decrease in potassium (hypokalemia) can profoundly affect the chance of irregular heartbeats (arrhythmias), which can be potentially fatal.

Hyperkalemia (Too Much Potassium)

The body needs to regulate levels of potassium in the blood within a range of 3.5 to 5.0 mEq/L. Hyperkalemia is generally defined as blood potassium levels above 5.0 mEq/L. Here is a way to think about the significance and the need to treat of different levels of hyperkalemia:

  • Mild to moderate hyperkalemias of >5.0 to 6.0 mEq/L usually requires treatment intervention. Some physicians may begin to treat at 5.0 mEq/L and at 6.0 probably every patient will be treated to lower potassium levels.
  • Potassium levels of >6.0 to 7.0 mEq/L are considered to be high and dangerous and require prompt action.
  • Having a blood potassium level at the upper end of the >6.0 to 7.0 mEq/L range or higher could cause a life threatening cardiac arrhythmia at any moment; it requires immediate treatment, usually dialysis.

Relypsa surveyed physicians to determine when they would intervene to treat hyperkalemia. Approximately 40% of physicians indicated that they would likely intervene with a treatment for hyperkalemia at a serum potassium level between 5.0 to 5.5 mEq/L, which Relypsa defines as mild hyperkalemia. Treatment would be much more aggressive at potassium levels above 5.5 mEq/L.

Causes of Hyperkalemia

The vast majority of potassium is bound up in cells, but it also is found in the extracellular space. The normal physiological process for removing excess potassium is through excretion in the urine. In normal humans about 90% of excess potassium is excreted through the urine and 10% is excreted through the feces. In patients with compromised kidney function, the relative amount of potassium in the colon goes up because less urine is excreted.

The kidney is the primary organ involved in potassium removal. Hence chronic kidney disease, hypertension and heart failure which diminish kidney function and urine output often cause hyperkalemia. Type 2 diabetics can suffer from imbalances of potassium between the extracellular and intracellular fluid compartments because insulin plays an essential role in shifting potassium into the intracellular compartments. There are also a number of commonly used drugs that cause elevated potassium levels, including RAAS inhibitors, transplant medicines and nonsteroidal anti-inflammatory drugs.

Consequences of Hyperkalemia

Potassium plays a key role in regulating electrochemical signals in nerve and muscle cells and importantly in the beating of the heart. Cardiac arrhythmias are the leading cause of mortality in hyperkalemia patients, and can develop with few symptoms; cardiac arrhythmias can occur suddenly and require immediate hospitalization. They also can result in sudden death.

The morbidity and mortality impact of hyperkalemia is significant. Hyperkalemia is detected in between 1% and 10% of all hospitalized patients although this is not usually the reason they were admitted. One study suggested that although hyperkalemia patients represented only 3.2% of the total patient population in the hospital, it accounted for 16% of the total hospital deaths due to ventricular fibrillation or cardiac arrest.

Risk increases sharply as serum potassium levels increase. According to a 2009 study published in the Archives of Internal Medicine, the one-day mortality rate was roughly 17 times higher for admitted patients with serum potassium above 6.0 mEq/L versus those with serum potassium less than 5.5 mEq/L. Patients with serum potassium levels between 5.5 and 6.0 mEq/L had a one-day mortality rate six times higher than those with less than 5.5 mEq/L.

Quick reduction of high potassium levels essential and life-saving in many situations. Another study, in hospitalized patients receiving critical care, showed that the reduction of serum potassium by more than 1 mEq/L in the 48 hour period after hospitalization decreased the risk of patient mortality. These studies suggest that treating hyperkalemia in the acute and chronic settings can have a significant impact on patient outcomes by reducing the risk of death.

A JAMA article in 2012 studied the rate of in-hospital mortality and morbidity. The death rate increases gradually as the potassium level goes up to 4.0 to 4.5 and increases dramatically above 5.0. At levels of 6.0, the mortality rate is about 4%; this is roughly comparable to the mortality rate from heart attacks! This is shown below:


Risk of hyperkalemia March 31, 2015

Unmet Need for Drugs to Treat Hyperkalemia

There is a great unmet need for drugs that can effectively treat excess levels of potassium (hyperkalemia) as there are no good treatment options. The only approved drug for hyperkalemia is Kayexalate which was introduced 50 years ago. However, it has side effect issues that limit most of its use to short term and its efficacy is questionable.

Kayexalate has never been studied in a controlled clinical trial and there are mixed opinions on its effectiveness. It is a cumbersome drug to take as it is given as an oral dosage form two to four times a day or as an enema. The mechanism of action causes Kayexalate to swell in the intestines to around three times its size at ingestion and results in constipation so that it is often given with a laxative. This in turn can cause severe diarrhea to the extent that patients often refuse to stay on the drug. It is associated with a host of gastrointestinal side effects, some of which are quite dangerous.

A low potassium diet presents significant compliance issues. Potassium is ingested from a broad range of foods-fruits vegetables, meats- which makes compliance very difficult. Diuretics are used off-label in some patients to increase the excretion of urine and potassium with it. However, the increased urine flow can create problems in patients with damaged kidneys and this is a large part of the hyperkalemia population. In the emergency room, there are a number of drugs that are effective in the short term treatment of hyperkalemia, but lose effectiveness in a matter of hours. Dialysis is very effective for severe cases, but obviously is not appropriate for the overwhelming majority of patients. On an overall basis there are no effective drugs for long term control of hyperkalemia.

The Addressable Market is Huge

When I first started doing research on patiromer and ZS-9 and their role in hyperkalemia, I did not understand how large the addressable market might be. A major cause of hyperkalemia is impaired kidney function which often is an end stage complication from such highly prevalent diseases as hypertension, heart failure and diabetes.

There is also a paradoxical cause of hyperkalemia. Drugs like angiotensin converting enzyme inhibitors (ACEs), angiotensin II receptor blockers (ARBs) and aldosterone antagonists (AAs) are used ubiquitously in treating hypertension and heart failure. They are extremely effective therapies but their mode of action also can cause hyperkalemia as a side effect so that when this occurs their dosages have to be reduced to less effective levels or sometimes the drug must be halted entirely. These drugs generate tens of millions of prescriptions each year.

There are two important treatment settings for ZS-9 and patiromer: the emergency room and the outpatient setting in the doctor’s office. Because of the lack of effective therapy, physicians in the outpatient setting when they see alarmingly high levels of potassium, somewhere ≥6.0 mEq/L, immediately send their patients to the emergency room. Treatment in the ER involves some short acting therapies to maintain the patient for a few hours but the only effective therapy is dialysis. About half of the diagnosed cases of hyperkalemia are first treated in the emergency room. Currently, there is no effective therapy when these patients are sent home even though chronic therapy is needed.

There are estimated to be about 500,000 emergency room visits per year for hyperkalemia. Most of Kayexalate is used in this acute setting. Remember that Kayexalate is a difficult drug to take so that it is not used widely in the outpatient setting. Later in this report I give my reasoning that shows that if ZS-9 and patiromir replace all Kayexalate usage in the US, which should be relatively easy, that it would result in $400 million of sales. I would caution that my estimate may be high as ZS Pharma and Relypsa are more comfortable with a $200 million number.

This does not mean that the hospital setting is not an important market opportunity. It seems highly probable that patients will be sent home from the emergency room with a prescription for ZS-9 or patiromer. These drugs will be used as chronic therapy for the rest of the patients’ lives and I am estimating that these drugs will be priced at $7,000 per year. The size of the annual addressable market resulting from initial treatment in the hospital setting that leads to chronic use could be $1.7 to $3.5 billion. To the extent that some of these may be repeat visits, this estimate would be high but in any event this is a huge patient audience.

The outpatient market or patients who are first treated in the physician’s office promises to be much larger. Relypsa has estimated that there are 15.4 million patients with chronic kidney disease due primarily to hypertension and diabetes and 4.9 million have advanced to stage 3 and 4 disease (the two most advanced stages) of which 2.5 million have hyperkalemia. There are 2.3 million heart failure patients and of these 0.5 million have hyperkalemia. This suggests that the potential addressable market is about 3.0 million patients.

Many of these chronic kidney disease and heart failure patients are being treated by the renin angiotensin aldosterone inhibitor (RAASi) drugs. However, because of the hyperkalemia caused by these drugs they often must be dosed at sub-optimal levels or may have to be taken off the drugs. This is the patient group that could immediately benefit from ZS-9 and patiromer. I don’t have a precise estimate on what the size of this outpatient market opportunity can be as there is currently no therapy that can be looked at to gauge the size of the market. However, intuitively it would seem to be huge as judged by the tens of millions of prescriptions written each year for RAASi drugs.

Relypsa and ZS Pharma have not given guidance, but a price of $7,000 per year is a reasonable guess. The price of Sensipar is $600 per month and staying at this range may be acceptable to payors. This results in a staggering addressable market of $21 billion (3 million patients multiplied by $7,000 per year).This results in a staggering addressable market of $21 billion (3 million patients multiplied by $7,000 per year).

Potential in Replacing Kayexalate Usage

There are about 500,000 patients who are treated at some point each year with Kayexalate which equates to a penetration of about 17% of patients. About half of Kayexalate is used in the hospital and half in the out-patient setting but it is seldom used for more than two days because of side effects.

ZS Pharma estimates that there are 200 million grams of Kayexalate used each year primarily in the hospital setting. At a dose of 100 grams per day, this represents 2 million patient days of therapy. I am estimating that ZS-9 and patiromer will be priced at $7,000 per year or roughly $20 per day. Hence the size of the market represented by patient days of Kayexalate therapy would be of Kayexalate priced at ZS-9 prices could be $400 million. ZS Pharma and Relypsa are more cautious on the size of the market. They are probably more comfortable with a $200 million estimate.

I want to emphasize that Kayexalate is used principally on an acute basis while ZS-9 and patiromer will be used chronically. Currently, Kayexalate is used for a day or few days and discontinued. If ZS-9 and patiromer replace Kayexalate, they would likely be continued on a chronic basis. This might mean that replacing all Kayexalate use could result in billions of sales.

Use of Renin Angiotensin Aldosterone Inhibitors (RAASI) Is an Important Cause of Hyperkalemia

One of the most significant causes of hyperkalemia results from the widespread use of renin angiotensin aldosterone inhibitor (RAASi) therapies such as:

  • Angiotensin receptor blockers (ARBs) such as Losartan, Cozaar, Avapro and Diovan,
  • Angiotensin converting enzyme inhibitors (ACEs) such as Vasotec Capoten, Vasotec, Zestril and Accupril and
  • Aldosterone antagonists (AAs) such as spironolactone and eplerenone.

These drugs are used ubiquitously in the treatment of hypertension and heart failure. Clinical studies have shown that through controlling hypertension they reduce proteinuria and in doing so preserve kidney function and delay progression to end stage kidney disease and the need for dialysis. They are also used to treat chronic heart failure and have been shown in clinical studies to decrease hospitalization, worsening of heart failure and reduce all-cause mortality. They are extremely important drugs.

These drugs all lower blood pressure through reducing the levels of the hormone aldosterone. However, aldosterone has the effect of lowering potassium so that as it is lowered potassium is increased leading to hyperkalemia which brings a new risk. This is a conundrum for doctors because they want to maintain patients on RAAS inhibitors. Hence, there is a great need for drugs which can treat hyperkalemia and allow patients to remain on RAASi therapy.

The Kidney Disease Outcomes Quality Initiative (KDOQI) provided guidelines on the use ACEs, ARBs and AAs in chronic kidney disease. In general, the highest tolerated dose is recommended. If hyperkalemia occurs, the dose should be reduced to the level that potassium falls in the normal range and if that is not possible, the drugs should be discontinued. Relypsa’s market research suggests that only 25% of patients can be treated with the optimal dose of RAASi, 42% can be treated at a sub-optimal dose and 33% cannot tolerate the therapy. Hyperkalemia is almost always the cause because otherwise these drugs are pretty well tolerated.

Importance of Treatment of Chronic Kidney Disease and Heart Failure Patients with RAAS Inhibitors

RAAS inhibitors are a first line treatment for hypertension and have been shown to delay progression to chronic kidney disease. This is made clear by widely accepted treatment guidelines which importantly include the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative, or KDOQI, and the American College of Cardiology and the American Heart Association, or ACC/AHA.

These guidelines recommend use in majority of patients with chronic kidney disease and/or heart failure. RAAS inhibitors have been shown through outcomes studies to preserve kidney function and delay the time to end stage renal disease in chronic kidney disease patients and decrease all-cause mortality in heart failure patients.

The Problems with Kayexalate

Kayexalate is an ion exchange resin that uses sodium as the exchange ion. Sodium ions are released from the resin and replaced by potassium, magnesium, calcium and hydrogen ions. The potassium exchange occurs primarily in the large intestine and the polymer now containing potassium ions is excreted in the feces. The efficiency of this process can be unpredictable.

Kayexalate was introduced as a treatment for hyperkalemia in 1958 before there were FDA administered requirements to prove safety and efficacy for new drugs. There have been no controlled trials that define its efficacy and safety profile and it has never undergone an FDA review. In September 2009, the label was changed to warn of cases of intestinal necrosis, which might be fatal, and other serious gastrointestinal adverse events (bleeding, ischemic colitis, perforation) that have been reported in association with Kayexalate use. The label warns against use in patients who do not have normal bowel function.

It can be given by mouth 1 to 4 times a day as a liquid suspension in which a powder is mixed with water or flavored syrup. The patient must remain upright and not lay down for at least an hour after dosing. It takes Kayexalate about 7 to 10 hours to enter the colon where much of the potassium exchange occurs. This produces a slow onset of action. Given rectally, the onset of action is quicker.

Kayexalate is a difficult drug because it absorbs water and swells (to perhaps three times the size at ingestion) causing constipation. Because of this, sorbitol is often co-administered as a laxative. This can lead to severe diarrhea so that patients need to be near a commode when taking the drug. As one emergency room physician said, patients hate it and nurses who may have to clean up after a patient mishap also hate it.

How Hyperkalemia is Treated in the Hospital

The hospital and especially the emergency room is the smaller of two market settings for ZS-9 and patiromer. Taking care of hyperkalemia is one of the first things that emergency room doctors learn. The incidence of hyperkalemia is 1% to 10% of hospitalized patients and a 2006 survey estimated that there were over 500,000 hospital admissions due to hyperkalemia in that year. There is no efficacious, well tolerated commercial drug for the treatment of hyperkalemia in the emergency room for a period of longer than a few hours other than Kayexalate.

The mortality rate within one day of a hyperkalemic event for a patient with mEq/L < 5.5 is 0.2%. Between 5.5 and 6.0 it is 1.4% and >6.0 it is 3.7%. For comparison, the death rate from a heart attack is about 4%. Hence mEq/L > 6.0 is equivalent to a heart attack. Patients with very high hyperkalemia of 7.0 or lower can literally go from appearing normal to having a cardiac arrhythmia and sudden death in a matter of minutes. Needless to say, when patients show up with serum potassium levels >5.5 mEq/L, the emergency room physician is concerned that he is treating a patient at risk of death.

The very best acute treatment of hyperkalemia is dialysis and this is the appropriate treatment for potassium levels greater than 6.0. However, this is invasive, complicated, expensive and not always immediately available. Imagine if a patient shows up in the middle of the night and there is no nephrologist on duty and one has to be summoned out of bed to come to the hospital to do an emergency dialysis.

In the interim prior to dialysis, the emergency room doctor has several short term actions that he can take. These are temporizing treatments that buy the physician some time until dialysis can be performed. The common thread of each of these treatments is that they cause potassium to shift from fluids into cells thereby lowering serum potassium. However, they only act for a short period of time and doing all the following options in sequence only can buy the physician a few hours. These options are:

  • Calcium given intravenously moves potassium out of fluids and into the cell and can normalize EKG and remove the risk of a cardiac arrhythmia in less than a minute. This is a spectacular result, but it only works for 30 to 60 minutes and re-administration does not produce the same results.
  • Sodium bicarbonate causes hydrogen to come out of cells and potassium to go in but again this only lasts for one half hour or so and too much can kill the patient.
  • Insulin given IV with glucose increases glucose intake into cells and brings potassium with it. This temporarily shifts potassium into the cell. However, insulin causes severe hypoglycemia and to offset this patient has to be given glucose in a big bag of water. However, this significant increase in fluid intake is a big problem in patients who have impaired kidney function which limits their ability to urinate. Still, this can work for a short term
  • Another possible action is to give the asthma drug albuterol. However, albuterol increases the heart rate and in patients already at risk of cardiac arrhythmias, this increases the risk.
  • Loop diuretics in patients which increase the secretion of urine and with it potassium are another possibility, but this doesn’t work well in patients with renal impairment; it can lead to fluid retention.

Treatment of Hyperkalemia in the Doctor’s Office

The second and larger market setting for ZS-9 and patiromer is the doctor’s office. A physician encountering a patient with potassium levels of > 6.0 mEq/L will probably send the patient immediately to an emergency room for treatment. For patients below that threshold, the options are limited.

A low potassium diet is not a good option as many of the fruits, vegetables and meats that are staples of our diets are high in potassium. Loop diuretics can be used to increase urine flow, but in patients with impaired kidney function can lead to a dangerous fluid retention. If the patients are on RAASi drug therapy, the dose can be lowered, but physicians are reluctant to do this because of the clinical benefit of these drugs. Kayexalate is an unappealing option as it is very difficult to keep patents on this drug long term. There is a tremendous unmet medical need for a safe drug to treat hyperkalemia.

Role of Ions in Creating Electricity in the Body

For those of you would like a little more background on the role of potassium ions in the body, I have included this section.

Daily life processes are the result of energy production from electrical, chemical, mechanical and electromagnetic sources. Substances obtained in human diets are responsible for generating electrical energy that is central to nerve conduction and muscle contraction. Electricity results from the attraction and repulsion of negative and positive charged particles that cause them to move. In the human body, ions are the key structures which create electrical energy. An ion is an atom or group of atoms that has an electrical charge by virtue of having lost or gained one or more electrons.

Body fluids both inside and outside of cells are electrolyte solutions or water suspensions of ions. These electrolyte solutions both inside and outside the cells contain equal amounts of positive (cations) and negative (anions) ions making the body as a whole electrically neutral. The cell membrane separates these ionic solutions.

Generation of electrical energy results from a small amount of anions accumulating on the inside of the cell membrane and an equal number of cations accumulating outside the membrane in the resting state of a cell. This difference in ion concentrations on opposite sides of the cell membrane creates an electrochemical gradient which can be compared to a battery where one end has a larger concentration of positively charged particles and the other end a greater concentration of negatively charged particles. Completing the circuit by connecting the ends of the battery allows charged particles to move between the two ends creating energy as an electrical current. A similar energy source arises in the body as charged ions move across the cell membrane.

The nervous and muscular systems of humans use the electrolyte properties of ionic sodium and potassium, assisted by lesser trace elements to generate currents across the membranes of their cells. The opposite charges of ions cause two types of gradients. Electricity or movement of charged particles results from the electrochemical gradient across the cell membrane results from a chemical gradient that moves ions from an area of high concentration to an area of low concentration. The electrical gradient moves ions of one charge to an area of ions of the opposite charge. The result of this current is the transmission of nerve impulses which causes contraction of muscle tissue. This process is aided by factors which cause a change in the permeability of the cell membrane.

This movement of ions results in a flow of charged particles into and out of the cell, creating an electrical current.  Calcium, potassium, sodium, chloride, and copper ions are some key ions that participate in the body's electrical events. Potassium is the major positive ion inside the cell. Sodium is the major positive ion found in the fluid outside the cell. Ionic chlorine is the most abundant negative ion. Imbalances of any of these ions or certain trace ions in the body or inhibition of sodium ion transport across the cell membranes can lead to dysfunction in the conduction of electrical messages.

Dietary minerals are mainly inorganic ions. They are essential nutrients that must be obtained from the diet. Remember that cations carry a positive charge and anions a negative charge. The most important cations are sodium, potassium, magnesium and calcium. The most prominent anions are chloride, phosphate and bicarbonate.

The following is a brief description of the roles on these ions in the body:

  • Sodium ions are the principal cations found outside cells in the body. They help regulate and control the level of body fluids. Too little leads to diarrhea, anxiety, a decrease in body fluids, and circulatory failure. Too much increases water retention, leading to high blood pressure (hypertension).
  • Potassium ions are the principal cations found inside cells in the body. Potassium ions help regulates cellular functions, including nerve impulses and heartbeats, and the level of body fluids.
  • Chloride ions are the principal anions found outside cells in the body. They serve as counter ions (ions necessary to balance electrical charge) in the extracellular fluid.
  • Calcium ions occur mainly in the skeleton and account for 1.5–2% of body mass.  Calcium is essential for building and maintaining bones and teeth. It also plays a crucial role in blood clotting, muscle contraction, and the transmission of nerve signals to cells.
  • Magnesium ions are found mainly in the bones, but they are also vital components of many enzymes used in cellular processes.
  • Phosphate ions exist mainly in body fluids. About 85% of the phosphorus-containing ions in the body are in the bones. They also play an important role in producing energy.
  • In addition to the above ions, the body needs smaller amounts of ions found in trace minerals. These include the iron, chromium, copper zinc, fluoride, iodide, and bicarbonate, as well as the hydrogen ion. Also required are compounds of manganese, molybdenum, and selenium, although these are not necessarily in the form of simple ions.






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  1. Wow, just wow. I’ve picked out what I’m going to sell when the reports come out. Sitting on “G,” waiting for “O.”

  2. The story keeps getting better for RLYP, with excellent DDI data reported today. My only question is how soon can we expect another report on this company, that now has an approved and launched drug?

    Thank you


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