Nymox Advances Its Mystery Prostate Weapon Into Phase III

Jul.13.12 | About: Nymox Pharmaceutical (NYMX)

Nymox Pharmaceuticals (NYMX) is a biopharmaceutical company with a market capitalisation of ~$215 million. The Nymox share price jumped to a peak of $9.29 in 2011 following the announcement of a European partnership deal with Ricordati (REC) for its lead development product NX-1207 back in December 2010. The company's current share price is $6.54. NX-1207 is unpartnered in the US. The product is currently in the midst of 3 Phase III trials. Results from the first should be announced towards the end of 2012, and results of the other 2 by mid to late 2013.

NX-1207 is a drug targeted for use in the treatment of Benign Prostatic Hyperplasia (BPH), but has potential wider applications in other conditions, including Prostate Cancer. Before I delve a little deeper into the drug itself, let me walk you through the basics of this condition. BPH is a medical term for an enlarged prostate. The prostate is an organ that is located underneath the bladder and surrounds the urethra, the tube through which urine is passed. As men get older the prostate enlarges. For some men, it enlarges to the point that it starts to cause some urinary symptoms. These include having to pass urine frequently (particularly at night), difficulty in starting to urinate, a weak stream, as well as excess dribbling or leaking of urine. Symptoms normally start in men over 45 years old, but a far more common in older men, in fact symptoms of BPH occur in as much as 80% of men over 80 years old. BPH is normally diagnosed initially by a rectal examination. Treatment options vary depending on the frequency or severity of the symptoms. Conservative options include managing fluid intake by trying to stop drinking a few hours before going to sleep, avoiding or drinking less caffeine and alcohol which make you urinate more often, and making sure the bladder is empty by voiding twice.

Medical therapy consists primarily of 2 classes of drugs, firstly the "alpha-1-adrenergic antagonists" which relax the muscle in the neck of the bladder, the prostate, and the prostatic part of the urethra (e.g. Hytrin, Cardura, Flomax, Uroxatral, Rapaflo). And secondly the "5-alpha-reductase inhibitors" which act by reducing the size of the prostate itself (e.g. Proscar, Avodart). The alpha-1-adrenergic antagonists are associated with side effects such as low blood pressure and dizziness. With the 5-alpha-reductase inhibitors, the side effects include reduced libido and ejaculatory or erectile dysfunction. These drugs also take at least 6-12 months before they reduce the size of the prostate enough to also reduce symptoms, whereas the effect of the alpha-1-adrenergic antagonists is more immediate. In some instances a combination of oral drugs are used. Patients not amenable to medical therapy can have surgery or various minimally invasive procedures. The most common surgical procedure is transurethral resection of the prostate (TURP), where a surgeon inserts a device into the urethra and removes sections of the prostate. For patients that are not good candidates for surgery or prefer not to have surgery, the other procedures are primarily thermal treatments where a device is inserted into the urethra (transurethral) and the prostate tissue is burned using radiowaves, microwaves or laser. TURP tends to have a far greater risk of ejaculatory or erectile dysfunction, as well as urinary incontinence and bleeding, however the other procedures are not always as effective. So amongst all this where does NX-1207 fit in? Well, NX-1207 has been in the making for over a decade now. In fact Nymox filed its Investigation New Drug (IND) application to the US Food & Drug Administration (FDA) in 2002. NX-1207 is a drug that is injected directly into the prostate causing it to reduce in size, and this is done by using an ultrasound-guided needle that passes through the rectum (transrectal). This is a simple procedure that can be performed in the doctor's room and dose not require analgesia or anesthesia. Although invasive, it will not cause any pain or discomfort, and can be done within 5-10 minutes. It would be done by Urologists who are all highly skilled with procedures far more complicated than this, so this method of drug administration is likely to be easily accepted by them, and would not require any special training. In terms of patient acceptance of the treatment, the reality is that symptoms of BPH can be extremely debilitating. I don't believe the route of administration would be a barrier to acceptance of this drug for those patients with moderate to severe symptoms, particularly given the advantages (outlined below) that NX-1207 can offer.

The exact mechanism by which NX-1207 works is not easily identifiable from the company documents or website, that I could see. Although after running a quick search on Nymox's patents, I believe NX-1207 has something to do with a substance called Neural Thread Protein (NYSE:NTP). As an aside, the patent's inventor is listed as Nymox's founder, CEO, and President, Dr Paul Averbach. But anyway, from what I can gather it appears that there is a link between NTP and the brain or nerve cell damage seen in Alzheimer's Disease. This discovery led to the development of Nymox's diagnostic product AlzheimAlert which detects high NTP levels in the urine of patient's with Alzheimer's Disease. Now I am not a scientist, but after reviewing the patent documents it appears that Nymox is delivering NTP to prostate cells in a conjugated form e.g. bound to an antibody that binds to an antigen or cell marker on the surface of the cells in the prostate. I could not find further details of how the NTP acts from here, but it ultimately causes cell death. In Alzheimer's Disease it seems that NTP-mediated cell death may be related to impaired insulin signalling. From subsequently digging up an archived Nymox press release from 2001, it appears that in researching into the causes of Alzheimer's Disease, Nymox unexpectedly discovered a treatment for BPH! Based on early trials (Phase I/II), the company has reported significant and rapid reduction in prostate sizes, as well as reduction in BPH symptom scores as defined by the American Urology Association (AUA) that are superior to that of oral drugs, and comparable to other surgical and invasive procedures. Moreover they report a far better side effect profile, with no sexual side effects, and several long-term outcome studies have showed sustained benefits in patients as long as 7.5 years after first treatment. Nymox has also completed studies that showed statistically significant superiority of NX-1207 over the oral drug Proscar (finestaride), a 5-alpha-reductase inhibitor which also acts to reduce the size of the prostate.

The BPH market is a crowded one and NX-1207 faces stiff competition, particularly from the other minimally invasive transurethral thermal procedures. Although many of these treatments are costly and do not have long-term follow up studies. Furthermore, they do require a short hospital admission with anesthesia. An even closer competitor for NX-1207 comes from Canadian company Sophiris Bio (SHS) which is currently developing another transrectal injectable drug for BPH, but I believe this has not reached as far in the development pathway. Other risks to Nymox and NX-1207 are the outcomes of the current trials and the FDA's interpretation of them. One of my concerns is how patients remain on placebo whilst on these long-term follow up studies. I imagine a significant amount will drop out of the study to seek treatment at some point. In addition a New Drug Application (NDA) may not take place until at least late 2013.

The economic costs from BPH to the US healthcare system is estimated to be ~$4 billion per year. I believe that a treatment that is effective and has enduring effects with minimal side effects, and that could potentially lower the burden on the healthcare system, has a much better chance of approval, reimbursement and commercial success in the long-term. NX-1207 has the potential to be such a treatment.

Note: At the end of Q1 2012, Nymox reported having enough funds for at least 12 months.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.