There's an old saying, "If it isn't broke, don't fix it." Well if you are Prolor Biotech (NYSEMKT:PBTH), you might say, "If it isn't broke, make it better." And, that is exactly what PBTH is trying to do: develop better drugs. By adding an amino acid sequence known as CTP or carboxyl terminal peptide, a drug's lifespan can be extended without compromising function or increasing toxicity. Just see Merck's (NYSE:MRK) corifollitropin alfa (brand name ELONVA®).
On January 28th, 2010, Merck received marketing approval for ELONVA® in the European Union. ELONVA® is a modified follicle stimulating hormone (FSH) containing CTP (FSH-CTP) that extends the lifespan of FSH. FSH is a hormone in women (and men) that stimulates the production of eggs, which are fertilized in pregnancy. In a phase III trial in 1,509 patients, women receiving one injection of FSH-CTP achieved the same number of pregnancies as women receiving seven consecutive daily injections of FSH indicating FSH-CTP could supplant FSH as a follicle stimulant to facilitate pregnancy. However, it is interesting to note that ELONVA® does not have US marketing approval calling into question this promising technology since it is not approved by multiple drug authorities. Alternatively, Merck may be awaiting US FDA approval or compiling its New Drug Application and seeking approval later.
Regardless, other companies like PBTH are forging ahead with the CTP technology. Like Merck, PBTH has an exclusive license from Washington University to develop human therapeutics except for luteinizing hormone, thyroid stimulating hormone, human chorionic gonadotropin, and the aforementioned follicle stimulating hormone which are licensed to Merck. Currently, PBTH is developing a modified human growth hormone (hGH). In preclinical work in rats, a single dose of hGH containing three CTPs (GH-LA) exhibited increased bioactivity and prolonged half-life relative to hGH alone. More importantly, one subcutaneous injection/week of GH-LA in a two week cycle was as bioactive as hGH administered once/day indicating that weekly CTP-enhanced hGH could potentially be used as a substitute for once daily hGH injections clinically.
After completing its preclinical work, PBTH conducted a series of clinical trials beginning with a phase I study in 24 healthy males using its hGH derivative known as hGH-CTP, or MOD-4023. Note, it is not known what hGH-CTP is, whether it is the same drug as GH-LA or others used in its preclinical work; therefore, it is difficult to compare its clinical results to its preclinical work to ensure drug action consistency. Moreover, available commentary on phase I indicated safety and tolerability endpoints were met, though data is not publicly available which makes these conclusions questionable.
In a follow-up study, PBTH completed a phase II trial to measure drug activity. Growth hormone deficient adults received a once weekly dose of 30, 45, or 100% of the total seven-dose equivalent they would normally receive if given hGH daily, defined as cohort 30, 45, and 100% respectively over a total four weeks. Insulin-like growth factor 1 or IGF-1 was chosen as a marker to measure drug activity as hGH stimulates the production of IGF-1 in the liver. During the last week of treatment, all three patient cohorts achieved averaged IGF-1 levels within the therapeutic range (+/- 2 standard deviations) found in the normal population indicating weekly hGH-CTP could replace once daily injections. Further evaluation of hGH-CTP is forthcoming with the beginning of its phase II study in growth hormone deficient children.
With hGH-CTP, Prolor is attempting to enter the $3 billion growth disorders market. Its strategy is unique both clinically and financially. Clinically, weekly injections should ensure better patient compliance compared to daily injections and improve patient outcome. Financially, adding CTP to an already approved drug lowers the risk profile of developing a new drug since it is based on a drug with proven safety and efficacy thereby lowering drug development cost overall.
To protect its hGH drug candidate against competitors, PBTH has three proprietary patents. It also has a CTP platform patent that should cover another drug it is currently developing including FVII-CTP for hemophilia, a market valued at $1.3 billion. Finally, it is developing GLP1/Glucagon dual receptor agonist for type II diabetes and obesity. Combined, these markets are valued at $2 billion.
With its exclusive license, patent protection, and diverse drug portfolio, PBTH is trying to position itself firmly in the biobetter industry. However, concerns remain such as the simple fact that PBTH has yet to turn a net profit. With $28.6 million in cash and an average quarterly burn rate of $4.6 million over the last year, PBTH has enough cash to last the next year and a half. With its phase II trial using hGH-CTP in growth hormone deficient children to be completed this year, one has to wonder whether PBTH has enough capital to bring hGH-CTP to market considering it still seeks to complete a phase III trial in adults. Partnering by licensing may not only be an option but a necessity.