Repros: Unique opportunities in men’s and women’s health
Right now is the right moment to look closer at Repros Therapeutics.
Four companies holding confidential disclosure agreements (CDA) are currently in the Repros data room weighing the opportunity.
And CEO Joseph Podolski exudes the confidence of a 40 year veteran of drug development.
Joseph Podolski, CEO, Repros Therapeutics
“Every step he takes in 2011 is only going to drive prices higher for his lead candidates,” he says.
“We hold two highly differentiated, highly protected products that each meets a growing demand in two very large markets, one for men’s health and the other for women’s health.”
“The more astute player, one who is not afraid of a little clinical risk, has an opportunity to get involved with us now,” he suggests.
“The question is whether a pharma company plans to come into the USD 500 million testosterone market with a knock-off product, or whether they are ready to partner on a product that is clearly differentiated with patent life out to 2023.”
“We do not intend to take these drugs all the way to market ourselves,” he said, adding that “the right partner will be a company with established commercial networks looking to expand its product portfolio to spread out the cost of the marketing and sales effort.”
Building a runway to 2012
Over the past two years the tenacious Texas-based Repros has taken a beating in the stock market, run into stiff resistance from the Food & Drug Administration and for a tense moment in late 2009 seemed to be teetering on the brink of collapse.
With just enough cash to run through Q1 2011, some might think the company is again heading for collapse.
Podolski brushes aside the suggestion. In this interview with partneringNEWS he describes the company’s current status, his expectations for the near term, and the opportunities with Repros two leading drug candidates, Androxal and Proellex.
“We are working with a bank now and anticipate we will be able to raise capital to give us operating runway into 2012,” he said, “I don’t see any partner being able to move that quickly.”
“If we were ever going to go out of business, it would have been last year. We had USD 3 million in the bank and USD 11 million of creditor debt with no opportunity to raise money. So it is not by luck that we are still here. We managed to raise money, we settled all the creditor debt, and we put our programs back on track.”
“I have been with this company since 1989 and running it since 1992, with the unfortunate exception of a period during 2009 that nearly ruined the previous twenty years of work.”
“I have done a good number of deals, and I fully believe we will do a deal for Androxal before the end of 2011.”
“We will commence discussions for Proellex at about the same time, and we will likely have a deal on Proellex by the end of 2012.”
Clear clinical pathway for Androxal
Podolski said Repros is now coming out of the woods with its lead product Androxal, an oral treatment for the normalization of testosterone levels without sacrificing fertility in treatment of secondary hypogonadism.
Androxal also presents a potential for the treatment of Type II diabetes in men with low testosterone.
“The issue with Androxal has always been a clear clinical pathway, which we now have,” he said.
The current approach to treating low testosterone levels in men is to give them testosterone, typically Androgel or Testim.
“The insidious part of that approach is that once testosterone is applied to the body, the hypothalamic-pituitary system can’t tell the difference between home grown and store bought. The exogenous testosterone actually ends up suppressing the pituitary even further so that the underlying cause of this disorder is made worse by what has been approved to treat the disorder,” he said.
“What Androxal does is block estrogen at the level of the hypothalamic-pituitary axis to allow the control mechanism to sense low testosterone and begin secreting the hormone that will restore testicular production of testosterone.”
“This is completely different from anything that is in the market or in devleopment right now, and we think it is a breakthrough.”
“There are a host of advantages for Androxal over testosterone: it is not a controlled substance, you can’t abuse the drug, and you can’t pass the cream or gel to a woman or a child, which is the black box warning with testosterone gels.”
“Androxal is an oral drug that restores pituitary responsiveness that in turn drives testicular function, so that if the patient forgets to take the treatment for a day or two, unlike in the case of the topical gels that suppress the pituitary, there is no rapid fall off in the levels of circulating testosterone,” he said.
“There is even more. Because our drug puts the factory back to work, restoring testicular function, we see a host of metabolic changes, such as a reduction in triglycerides, an overall lowering of cholesterol, and most interestingly, a fairly significant impact on fasting plasma glucose.”
“This has implications for addressing a co-mordibity of secondary hypergonadism in Type II diabetic men, which has a prevalence of at least 20% in that population.”
“We are currently conducting a Phase II study in men with Type II diabetes that have low to low normal testosterone levels but who experience less than optimal glycemic control using oral agents to treat the condition. We should have interim results from that study, probably in the second quarter.”
“Back on the secondary hypogonadism front, based on the advice of the the FDA, we are beginning enrollment for an additional Phase IIb study comparing our drug this time against placebo and Testim. We have already compared ourselves successfully twice against Androgel. Now we are being compared to the second most used testosterone application.
“For this study the FDA asked that we look at men on the lower end of the hypergonadal indication with a morning testosterone level of less than 250 nanograms per deciliter. In the words of the FDA, ‘to make sure these men really need testosterone.’ ”
More proof for Proellex
According to Podolski, two companies are looking at the opportunities with the Proellex family of molecules, though neither has signed a CDA.
“Proellex is an opportunity to address a much bigger market, one measured in billions of dollars for the treatment of uterine fibroids, treatment of endometriosis, which remain major unmet needs in women’s health,” he said.
“We are now conducting a low dose escalation trial that should finish in the fourth quarter of 2011. And expect we will be able to find good agreement with the FDA for going forward.”
“Before anyone will want to license Proellex we are going to need the results of the low dose study and then an agreement with the FDA that we can go back into the clinic, hopefully at Phase III.”
“The efficacy of the drug is beyond question, the data shows this clearly. The only question remaining is delivering that benefit in a safe manner with a sufficient cushion against a known toxicity.”
Podolski said that in Phase III studies of Proellex at the highest dosage of 50 milligrams, a liver toxicity appeared, “which caused the FDA great concern, of course.”
“After review of data and a series of meetings with the FDA, the Agency lifted the hold to allow us to conduct a low dose trial. It is hard to believe that we will see even a weak signal of liver toxicity at these low doses that will be investigated.”
“Repros is among the few companies who have seen their candidate put on hold for liver toxicity and then had that hold lifted. This is a recognition of the efficacy and benefit this drug can deliver for treating uterine fibroids and endometriosis, which is huge.”
“We are pursuing multiple approaches to debug the Proellex program at this point. Oral administration remains the preferred delivery. However we have evidence from animal studies that if we apply the drug locally, for example with a vaginal suppository, we could achieve enhanced activity on fibroids and endometriotic lesions offering dramatic benefit at much lower circulating levels of the drug, perhaps one-twentieth of the oral administration and by-passing first pass liver effects.
We are also looking at second generation compounds. We probably have in our portfolio well over 100 compounds. We believe we understand what part of the original molecule generated the issues with liver toxicity. We are screening new compounds now and by the end of next year should be able to advance lead candidates into clinical programs.
“By the end of next year our low dose study will be completed. We will know which dose has a consistent effect on menstrual bleeding, a straightforward surrogate signal and the primary symptom of uterine fibroids. If the animal study continues to look promising we will open up an Investigational New Drug (IND) application for vaginal delivery. And then we will have the second generation small molecules ready for selection to move forward as well.”
“This gives us three shots on goal.”
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