Ischemix, Inc.

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April 15, 2013 Issue

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Bringing through the clinic their Small Molecule Drug CMX2043 based on Chemically Modified Lipoic Acid, Ischemix, Inc. is focused on preventing PCI related Cardiac Injury and Contrast-Induced Nephropathy

About Ischemix, Inc.:

Ischemix is a privately-held, clinical-phase biotechnology company developing a portfolio of therapeutic compounds for the prevention and treatment of serious cardio-renal conditions. The Company’s lead product candidate, CMX-2043, is a chemically-modified natural compound with an excellent safety profile. In a 142-patient international Phase 2a trial in PCI patients Ischemix demonstrated the ability of CMX-2043 to prevent cardiac injury. The Company intends to initiate an additional Phase 2 trial of CMX-2043 to i) study prevention of contrast-induced acute kidney injury/nephropathy (AKI/CIN) and ii) confirm cardiac injury prevention. Ischemix is continuing pre-clinical work on its lead and pipeline compounds in other indications and is pursuing discussions with corporate partners and new investors for financial support of the Company’s clinical development plan.

David A. DeWahl, Jr.


Mr. DeWahl joined Ischemix in January 2013 as President and Chief Executive Officer. He was previously Vice President of Corporate Development for Helix Therapeutics, Inc., a private company utilizing DNA repair technology licensed from Yale University to treat patients with genetically-based diseases. Mr. DeWahl is also a co-founder of Life Science Pharmaceuticals, Inc., which is developing novel therapeutics to treat cancer, diabetes and other serious illnesses based on IP licensed from The Ludwig Institute for Cancer Research, Memorial Sloan Kettering, Dana Farber and other major academic research institutions.


Prior to his experience in the biopharmaceutical industry, Mr. DeWahl was an investment banker focused on the health care and life sciences industry for over 25 years, including positions as a Managing Director at Prudential Securities, Oppenheimer and Co., Vector Securities and Life Science Group. Mr. DeWahl has successfully raised capital and/or advised on corporate partnerships for numerous companies with biopharmaceutical and other life science products currently on the market, including Tarceva (R) (Roche/Genentech), Byetta (R) (Bristol-Myers/Amylin), Synvisc (R) (Sanofi/Genzyme), Adagen (R) (Enzon) and WinRho (R) (Cangene).


Mr. DeWahl received his BA in economics from the University of Wisconsin and his MBA in finance from Columbia University.


Cardiovascular and Renal Pharmaceuticals


Ischemix, Inc.
63 Great Road
Maynard, MA 01754



Interview conducted by: Lynn Fosse, Senior Editor, CEOCFO Magazine, Published – April 15, 2013


CEOCFO: Mr. DeWahl, would you tell us what attracted you to Ischemix?

Mr. DeWahl: I believe that Ischemix has a broadly applicable technology and family of compounds that will be effective in both preventing and treating a broad range of cardio-renal events and diseases in patients. We have pre-clinical and clinical data on our lead compound showing efficacy in preventing cardiac injury and we believe our drug will also be beneficial in preventing and treating injury to the kidney. Longer term we may be able to address heart and stroke patients as well as to improve the outcomes in organ transplants.


CEOCFO: Would you explain the technology?

Mr. DeWahl: Our lead compound is a small molecule drug called CMX-2043. It is a drug that is based on a substance that is naturally occurring in the body called lipoic acid. Lipoic acid is known to have beneficial properties. There are both nutritional supplements and a drug approved in Europe for diabetic neuropathy based on lipoid acids. What we have done, by chemically modifying and attaching certain peptides to the molecule, is to substantially enhance the effective properties of the drug in a clinical setting.  We have a recently-issued composition of matter patent on our compound.


CEOCFO: Why did you take that approach? What made you think that this would be a good idea?

Mr. DeWahl: The Company was started in 1999 based on the observations and interests of the founding scientist. He was conducting some experiments using lipoic acid and discovered that lipoic acid, modified with these additional peptides, had substantially improved activity in animal models, which is typically the first step that you go through in drug development. We have been fortunate to take that discovery and bring it through, most recently, a Phase 2a trial. The most important thing about our approach is that we have taken a naturally occurring compound, chemically modified it, shown that it has beneficial effects in cardiovascular settings, shown that it is a safe drug, and have demonstrated statistical significance in reducing cardiac cell damage in a one hundred and forty-two patient trial. Essentially, what the drug does is to protect cells of the body from death under certain circumstances. For example; we seek to prevent and treat ischemic injury, thus the name of our company, Ischemix. We also deal with a follow phenomenon called reperfusion. In ischemia the body’s cells are deprived of oxygen. This results in a series of events that are negative, as you can imagine, to the body’s cells. That is because without oxygen the cells cannot operate for very long. The first thing that the cells do is make internal changes to their own chemistry to try to survive with less oxygen. That sets off a series of negative events; negative sequelae, which eventually lead to apoptosis, or cell death. Interestingly, reperfusion, which is the re-administration or the availability of blood and oxygen to the cells, although it is beneficial in many respects, also has negative consequences. That is because the sudden burst of oxygen availability causes something called an oxidative burst. Therefore, even though you want to get blood and oxygen back to the cells there are negative events associated with reperfusion. We believe that our drug acts on both reducing the negative consequences of the ischemia, and also the negative consequences of the reperfusion. That is because our drug is a “cell protective” drug. It is a highly potent cytoprotective compound. We believe that, for example, we act upon what is called the Akt Pathway, which is a primary pathway for cell survival and it is well known in the academic and scientific community at this point. Our compound is an antioxidant; it reduces the oxidative damage which is a major contributor to cell death. The beneficial effects of our drug candidate are also relevant to cells and tissues in parts of the body, including the kidney. 


CEOCFO: How quickly do you need to give this? At what point would you be administering the drug?  

Mr. DeWahl: The most exciting thing about our compound is that it has, we believe, the capacity to prevent and treat cardiac and renal cell injury. Therefore, we think the application of the technology is extremely broad. We have given our compound to patients who are going in for PCI procedure (percutaneous coronary intervention) where it is known that some percentage of the patients are going to experience ischemia and reperfusion injury. In addition, we believe that our drug would potentially be helpful for patients who are undergoing organ transplant and other similar procedures. What is also very exciting is that we believe our drug could be useful “post event”. For example; if a patient has suffered a heart attack, we have reason to believe that our drug could be beneficial, even after the ischemia reperfusion imjury has already taken place, because what CMX-2043 does is to curtail and minimize the negative sequelae associated with the event. In the same way that TPA or streptokinase are frequently given to heart attack patients in the ambulance as they are being taken to the hospital, so too might our drug be administered. Therefore, there is an incredibly broad opportunity for use of the drug. The initial work that we have done in the clinic has been in the setting of PCI in which it is known that a patient is going to go in for a coronary angiogram with probably a balloon and or a stent placement. This procedure is known to cause a certain degree of ischemia and reperfusion injury. Even though the overall PCI procedure is acknowledged to be an incredibly beneficial one, there are negative events associated with some proportion of the population that receive this treatment. We have shown, in the Phase 2a trial of one hundred and forty-two patients, that we were able to achieve a statistically significant outcome in the reduction of biomarkers that are associated with the negative consequences of PCI. In particular, there are biomarkers which are enzymes that are released upon cardiac cell death. One is called troponin and the other is called CK-MB. We were very pleased in our recent one hundred and forty-two patient Phase 2a trial to show statistical significance in reduction these cardiac markers. There are substantial papers in the literature that show a very strong association between the rise in these biomarkers and the incidence of morbidity and mortality in the PCI and general surgery population. 


CEOCFO: Would you be replacing something that is administered now, or would this be a brand new addition to what is available?  

Mr. DeWahl: We believe that our drug, subject to further clinical trials and successful approval by FDA, would be useful as an addition to the existing array of drugs or procedures that are administered to a patient in this prevention setting that I have just described to you. This is one of the reasons that I found the company very attractive. We believe that we can provide the drug at a cost to the healthcare system that will result in a net savings to the health care system in a short period of time. While I am not able to comment on the price that we will use to sell the drug at this point, we have done some modeling that indicates that we believe we could save hundreds to thousands of dollars per patient by use of our drug. If we can price our drug below that on a per dose basis, we can achieve a substantial to the healthcare system, which is of paramount importance to all of us in this current environment.    


CEOCFO: Has the medical community been paying attention, or is it a bit too early?   

Mr. DeWahl: We have had a number of articles that have been published around the area of understanding the relationship of cardiac biomarkers and morbidity/ mortality consequences. There was an article in the Journal of the American Medical Association in 2012 which underscored the strong association in the general surgery population between a post-procedural rise in the aforementioned cardiac injury biomarkers and increased incidence of morbidity and mortality. There have also been other papers published specifically with respect to the negative consequences of cardiac biomarker rise in patients that have undergone PCI. As a small private company we have not published a lot of papers of our own pre-clinical and clinical data. We expect to be in a position to do that in the future. We are very fortunate to have accrued a couple key opinion leaders in the cardiac space who feel very excited about the potential use of our drug and have told us that they would like to use this drug on their patients once it becomes available on the market.


CEOCFO: Will you be looking to do joint ventures or partnerships as you go forward? How far will you be going it alone?       

Mr. DeWahl: That is a very good question. As you know, the costs of entering into pivotal Phase III trials in the cardiovascular area are typically fairly significant. However, another thing that I find interesting about the opportunity we have at Ischemix is that, due the very safe nature of the drug that we have already demonstrated, and the fact that the drug is only administered once in the case of preventing the negative consequences of PCI, we believe that we are in a position unlike many other cardiovascular drugs to seek FDA approval based on trials that are of significantly smaller size. A typical cardiovascular drug for a chronic, daily therapy such as an anti-hypertensive, may be required to study their compound in as many as ten, twenty or thirty thousand patients. We believe, based on what we know now, that we could run pivotal trials in patient populations perhaps as low as one thousand patients in each of two pivotal trials. Therefore, we believe our costs to get an approved product may be substantially lower than the typical cardiovascular product. However, that being said, we are still a privately financed company and we do expect to be looking for capital from both institutional investors as a private company, and also exploring aggressively partnering with larger pharmaceutical companies.      


CEOCFO: Is cardiovascular in favor with investors these days?

Mr. DeWahl: I think what is in favor with investors are drugs where you have very good data. While it may be true that cardiovascular drugs go in and out of favor, I think that it is also true that recently there have been very few innovations in the cardio-renal space. Most of what you see are additional hypertensives for chronic therapy. There is not really any preventative measures that could be taken from a pharmacologic nature, that I am aware of, to reduce the incidence of the issues associated with a PCI procedure, not are there any therapies available to prevent AKI/CIN. Therefore, I think we will find sophisticated investors and companies who will appreciate the value of our data that we have generated so far and that which we tend to produce going forward. I should also mention that we have another potential major indication for our drug candidate, and that is in the area the kidney. It is well understood that in the process of doing a coronary angiography or any other procedure involving the use of contrast media, a certain portion of the population will suffer something called “contrast-induced nephropathy”, which results in acute kidney injury and could lead to more significant injury over time, including the requirement to go on kidney dialysis, or even death. Therefore, in addition to pursuing the cardiovascular indication in PCI patients and then more broadly, as I mentioned, treatment of various cardiovascular diseases, we also believe that we have a significant opportunity in the renal space. I think that you will find that if you talk to people involved in this area that there is a tremendous concern over the number of patients that do suffer from contrast-induced nephropathy. I would point out that there are, in general, over the entire population of the United States, somewhere between seven and ten million instances a year where patients are receiving a contrast media. Therefore, it is a fairly large market opportunity. By way of comparison, there are about one million PCIs done in this country per year; just to give you a comparative look. Both of those populations are very significant.   


CEOCFO: Why should Ischemix Inc stand out for investors and people in the business community?

Mr. DeWahl: Just to sum up; we have got a compound that has been shown to be safe. That is not surprising, given that it is a naturally occurring compound in the body. Therefore, we have got a safe product. We have completed a successful one hundred and forty-two patient Phase 2a trial showing statistical significance in patients who are undergoing PCI. We also have, what we believe, is a multi-modal mechanism of action, operating on different pathways, including Akt, so we believe that sets us up to be able to be extremely effective and to become a first in class cytoprotective agent. We are addressing markets where there is not pharmaceutical alternative at this time for the prevention of PCI related cardiac injury, as well as what I referred to earlier as contrast-induced nephropathy. We also have a pipeline of candidates in various stages of preclinical development, which we think could be used in multiple cardiovascular indications and renal indications. We also have, as a small company, quite a talented multi disciplinary management team.


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“I believe that Ischemix has a broadly applicable technology and family of compounds that will be effective in both preventing and treating a broad range of cardio-renal events and diseases in patients. We have pre-clinical and clinical data on our lead compound showing efficacy in preventing cardiac injury and we believe our drug will also be beneficial in preventing and treating injury to the kidney. Longer term we may be able to address heart and stroke patients as well as to improve the outcomes in organ transplants.”- David A. DeWahl, Jr.


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