GTx, Inc. (NASDAQ:GTXI) Q3 2013 Earnings Call November 12, 2013 9:00 AM ET
Mitchell Steiner – Vice Chairman and CEO
Brian Klein – Stifel Nicolaus & Co.
Good morning everyone and welcome to the GTx Incorporated Conference Call. Today’s call is being recorded.
I will turn the call over to Dr. Mitchell Steiner, CEO of GTx. Please go ahead, sir.
Thank you, operator. I will be making forward-looking comments during today’s call and I direct you to the press release of our financial results we filed this morning as well as the quarterly report we are filing on Form 10-Q with the SEC later today where we discussed the risks and uncertainties that may affect our business.
I will begin today with an update on the progress of our three late stage clinical programs. First enobosarm 3 milligrams for the prevention and treatment of muscle wasting in patients with non-small cell lung cancer. Second enobosarm 9 milligrams being developed with the treatment of Androgen receptor positive and estrogen Receptor Positive metastatic breast cancer and lastly we’ll talk about GTx-758 which is being developed for the treatment of the advanced prostate cancer.
0As for enobosarm 3 milligrams we released top line data in August from our two Phase III clinical studies POWER1 and POWER2 to support the indication for the prevention and treatment of muscle wasting in patients who have advanced non-small cell lung cancer. We have had time now to better understand the safety and efficacy of enobosarm 3 milligrams for this indication after reviewing the complete data set collected from these studies and we are in the process of preparing and submitting meeting requests and plan to meet with the regulatory agencies.
These additional POWER trial analyses may give more support for a potential regulatory path for enobosarm and we remain excited about the opportunity and our prospects for pursuing a marketing application for this indication.
First let me remind you that each clinical study enrolled approximately 325 patients who had either stage three or stage four non-small cell lung cancer in over 80 clinical sites located in the United States, Europe, Russia and South America. The objective of these studies was to determine the potential of enobosarm 3 milligrams versus placebo to prevent and treat muscle wasting in advanced non-small cell lung cancer patients when given at the same time they initiate standard first line chemotherapy consisting of a platinum doublet.
In the design of the trials FDA and European National Authorities advised focus on the need to control for chemotherapy in the Phase III program for this indication. The discussions with these agencies shared the concern that chemotherapy is frequently given to these patients throughout the course of their disease to control cancer related symptoms.
There was concern expressed that chemotherapy itself may potential influence the clinical measurements of lean body mass and stair climb power and affect trial results in patients with non-small cell lung cancer. Two possible situations could happen. Responses to chemotherapy may confound the results but over estimating the benefit of enobosarm on lean body mass and physical function in patients or conversely the potential benefits of enobosarm on lean body mass of physical function could be masked by in balances in the toxicities associated with the chemotherapy such as peripheral neuropathy or anemia.
The intention of the clinical development program was not to test enobosarm in combination with every possible type of chemotherapy used in the treatment of non-small cell lung cancer but rather to control for chemotherapy to minimize the concerns the agencies have regarding the potential for imbalances in efficacy or toxicity.
The original advice received recommended we use a single approved standard platinum doublet chemotherapy regiment as a way to control for the potential effects of chemotherapy on lean body mass and physical function. GTx chose to expand the choice of the first line platinum doublet chemotherapy regimens to better reflect current clinical practice and standard of care in the majority of academic and community oncology settings in the United States and Europe and at the same time control for chemotherapy.
Accordingly GTx conducted two Phase III clinical trials with identical inclusion and exclusion criteria, end points and durations but differing in patient populations based on their planned first line chemotherapy either a platinum plus a taxane or platinum plus a non-taxane respectively to which an add on therapy with placebo or enobosarm 3 milligrams would be used, so that any possible imbalances and benefit of toxicity related chemotherapy that may confound the results on lean body mass or physical function could be determined.
The end points for the two studies were lean body mass assessed by DXA and physical function assessed by the stair climb test although we did not have a special protocol assessment with FDA we agreed with FDA and so stated our statistical analysis plan for the studies that we would make lean body mass and physical function measurements at Day 84 the co-primary end points and that we would analyze these end points statistically by responders analyses.
The responder analysis required at day 84 more patients in the study had maintained or showed an improvement in lean body mass and that they were more patients who had at least a 10% improvement in physical function in the treated group compared to the placebo. Based on input from the EMEA representatives however rather than having co-primary end points we specified physical function as the primary end point and lean body mass as the most important secondary end point.
We pre-specified in our statistical analysis plan that the same end points would be assessed using the longitudinal continuous variable statistical analyses. This would allow us to compare to changes over time in physical functions of lean body mass in the treated versus placebo groups in each study, especially if they had a decline in the lean body mass and/or physical function from baseline.
The EMEA representatives we met with stated that they wanted to see the effects of physical function as the primary end point and the effects on lean body mass as a key secondary end point for the studies and also indicated they would look at the totality of the data to determine clinical benefit.
As we stated in our August 19th press release and during our conference call that morning we failed to meet the co-primary end points of lean body mass and physical function assessed statically using the responder analysis as agreed upon with FDA. It remains clear though that enobosarm had a consistent positive effect on maintaining or improving lean body mass compared to placebo in both studies. By the responder analysis a larger proportion of patients receiving enobosarm maintained or increased lean body mass at both Day 84 and Day 147 in both clinical trials compared to placebo.
In the POWER1 trial with taxanes this equated to a P value of 0.036 at Day 84 and a P value of 0.026 at Day 147. And in the POWER2 trial with non-taxanes the P values were 0.113 and 0.013 respectively.
Using the longitudinal continuous variable statistical analyses declines in lean body mass and stair climb power were observed in the placebo groups in both studies. The POWER1 taxane clinical study met the pre-specified primary end point for physical function of change in stair climb power through Day 84 with a P value equaling 0.0147 and the secondary end point of change in lean body mass through Day 84 0.002 and change in stair climb power through Day 147 p equal 0.0492 and change in lean body mass at Day 147, which is less than 0.0001.
In contrast POWER2 the study using non-taxanes did not meet the primary end point change in physical function but had consistent effects on improving lean body mass through Day 84 and Day 147 with a P equaled 0.0227 and 0.0036 respectively.
Enobosarm was well tolerated in both clinical studies and although only minor differences in averse events were observed between the enobosarm 3 milligram and placebo groups in each of the POWER1 and POWER2 trials there were notable differences in the adverse event profile between studies. With anemia and other hematologic toxicities and nausea and vomiting being more prevalent in the POWER2 non-taxane clinical trial.
By controlling for chemotherapy GTx is able to better understand the impact of chemotherapy side effects as possible confounders that could explain the physical function end point in POWER2 non-taxane study.
We are still evaluating these results. Survival is being assessed as another safety end point as specified in our statistical analysis plan pooled overall survival data will be assessed after 450 of the approximately 650 patients in the two studies have died which we currently expect will have occurred by March or April of next year. We have seen no adverse effects on overall survival from enobosarm treatment from the survival data received to-date. And we expect this to remain the case.
Interestingly however, we have seen in a post half landmark survival analysis of patients who have had their Day 84 clinical co-assessment a potential survival benefit among patients who maintained or increasing lean body mass regardless of treatment. This continues to be the case following the survival assessment after 450 deaths we believe there’s even a stronger case to be made focusing on maintaining or improving lean body mass in this critically ill patient population with Enobosarm 3 milligram treatment.
While we’re disappointed that both POWER studies did not meet the pre-specified responder analysis criteria at Day 84, we believe the overall results are compelling, including the consistent positive effects on physical function and muscle in the POWER1 taxane study and on muscle in the POWER2 non-taxane study that fact that Enobosarm was well tolerated by patients in both studies and the association of maintaining and improving lean body mass as a potential survival signal.
Accordingly we are in the process of preparing and submitting meeting requests to both FDA and European authorities to discussed a feasible regulatory path forward and we’ll report back once we have better regulatory clarity.
Turning to our ongoing Phase II clinical study evaluating enobosarm 9 milligrams for the treatment of Androgen Receptor Positive and Estrogen Receptor Positive metastatic breast cancer in women who previously responded to hormonal therapy we plan to be fully enrolled in this 20 patient clinical study this quarter and expect that the last patient in the study will have reached the six months assessment end point late in the second quarter of next year.
Literature suggests that up to 80% of women with metastatic breast cancer will be positive for both Estrogen Receptor and Androgen Receptor. And our current study is certainly confirming this observation. Prior clinical studies have shown that women with metastatic breast cancer who have been previously treated with tamoxifen and whose cancer has progressed have responded to non-selective non [aromitizable] androgens which are androgens that cannot be converted to estrogen and with overall response rates ranging from 20% to 60%.
Although these non-selective non aromitizable androgens have been used and are recommended in the NCCN guidelines as treatment for metastatic breast cancer the unwanted side effects including an increase in facial and body hair, enlargement of the voice box, acne and edema have limited their wide spread clinical use.
GTx believes that in selective androgen receptor modulator like Enobosarm by targeting the androgen receptor in metastatic breast cancer has the potential to provide clinical benefit to women with advanced breast cancer by treating their disease while minimizing the unwanted masculanizing side-effects associated with androgen unlike steroidal androgens Enobosarm cannot be converted to an estrogen that could be detrimental in breast cancer.
The women in our Phase II clinical trial are receiving an oral 9 milligram dose of Enobosarm once a day until they show evidence of clinical progression will have completed 336 days of treatment with Enobosarm. The primary end point of the study is clinical benefit response which will be assessed at six months and is defined as either those women receiving treatment who have demonstrated a complete response disappearance of the all targeted regions, partial response at least a 30% decrease in the some of the diameters of the targeted legions or stable disease, no disease progression from baseline.
Assuming we see evidence after six months of treatment of Enobosarm 9 milligrams has sufficient clinical benefit responses we will either expand the study to include additional women with metastatic breast cancer to confirm the dose, where safety remains satisfactory we may increase the dose to further define efficacy and safety.
To-date Enobosarm treatment has been well tolerated at the 9 milligram oral daily dose. With regard to the GTx 758 Capesaris program GTx is enrolling an open label Phase II clinical study of GTx 758 treatment with metastatic castration-resistant prostate cancer. The Phase II study was originally designed to evaluate the safety and effectiveness of three doses of GTx 758, 125 milligrams, 250 milligrams and 500 milligrams oral daily dose.
The primary end point of the study is to proportionate patients with the greater than 50% reduction from baseline and serum PSA by Day 90. Other key end points include free testosterone levels, sex hormone binding globulin levels and the total testosterone levels in the study subjects.
Prostate cancer progression is also being monitored. In addition to clinical studies evaluating the ability of GTx 758 to treat certain estrogen deficiency side effects associated with androgen depravation therapy such as hot flashes, bone loss and insulin resistance. After reviewing data collected today from the GTx 758, 125 milligram dosing arm showing the ability of the drug to substantially increase sex hormone binding globulin and lower free testosterone the clinical protocol was recently amended to eliminate the third dosing arm of 500 milligrams originally designed for the study and to increase the number of subjects to be enrolled in the 125 milligram and 250 milligram dosing arms to 38 subjects per arm.
The number of subjects per arm was increased to provide greater confidence in the safety of GTx 758 and to-date we have seen no evidence of venous thromboembolic events or SAEs. Enrollment in 125 milligram cohort is ongoing and assuming there continues to be no unacceptable incidents of venous thromboembolic events observed in patients in this cohort GTx will then make the decision whether to proceed with dosing of the 250 milligram cohort.
Treatment of prostate cancer with primary androgen depravation therapy improves prostate cancer symptoms but patients eventually develops castration resistance prostate cancer as their cancer adapts and uses the available free testosterone in the blood stream to grow.
When primary androgen depravation therapy fails the majority of patients develop non-metastatic castration resistance prostate cancer for which they are no approved secondary hormone therapies. We believe GTx can offer a unique secondary hormonal model treatment option for men with non-metastatic castration resistant prostate cancer.
Other agents under development basically have the same mechanism of action as androgen receptor antagonists and only have activity against the androgen receptor signaling pathway and prostate cancer cells as a means to prevent metastatic progression.
As an oral estrogen receptor agonist GTx 758 is a new chemical entity with a unique drug mechanism. GTx 758 not only effects the androgen receptor signaling pathway in prostate cancer cells by maximally suppressing circulating free testosterone but also through its estrogenic effects provides the potential to improve bone quality by decreasing bone turnover. Bone only agents such as [Vismodegib] and denosumab have been shown to prevent bone metastatic disease and treat skeletal related events in patients – in prostate and other cancers with a dual mechanism to prevent metastatic disease that is directly by reducing available free testosterone to prostate cancer cells and indirectly by improving bone quality to make the bone environment more resistant to metastases. GTx 758 could become a preferred secondary hormone therapy for men with non-metastatic castration resistance prostate cancer.
Moreover by replacing estrogen GTx 758 may also provide the pro-estrogenic benefits to improve other estrogen efficiencies side effects commonly associated with primary androgen depravation therapy such as hot flashes, bone loss and fractures and metabolic syndrome insulin resistance. We plan to meet with FDA to discuss data from our ongoing Phase II clinical study and our proposal to use GTx 758 treatment with advanced prostate cancer.
Our goal is to develop GTx 758 as the first secondary hormonal therapy in men who have non-metastatic castration resistant prostate cancer. The short-term objective is to complete our current Phase II safety and dose finding clinical study of GTx 758 in metastatic castration resistant prostate cancer patients. Our regulatory objective is to find a way forward with the regulatory agency that will allow us to use an earlier end point like progression free survival rather than overall survival as the clinical benefit end point required for approval in men with non-metastatic castration resistant prostate cancer.
This morning we also released our financial results for the third quarter ended September 30, 2013. Well I will not review the financial results in detail let me point out that we reported $21 million in cash, short term investments as of September 30, 2013 and we have no debt or warrants outstanding.
Marc Hanover and I will be happy to answer questions you may have about our financial results during the Q&A. Operator we’re now ready for the first question.
(Operator Instructions) And your first question is from the line of Brian Klein from Stifel. Please go ahead.
Brian Klein – Stifel Nicolaus & Co.
Hi guys, thanks for taking my questions. So first on Enobosarm, as you think about the path forward and as you head for, move forward with the FDA would you consider conducting another study in the U.S. to confirm where are positive trends in benefit?
Right, so good question. So the way we’re looking at it right now is we need to really – let’s take a step back. So the first step is that we, the drug has continued to perform in the manner that the drug was developed. It’s a muscle drug and in every single clinical study we have done it improves muscle. And we also learned in the two Phase IIIs that we performed, again unambiguously this drug builds muscle and we also learned in these two Phase IIIs and also the additional other eight clinical studies that we have done that it’s a safe drug.
And so now with safety and the ability to build muscle and many of these trials are also showing an improvement in physical function first thing we have to say to ourselves is you know the drug works. So now the question is, what do we need to do to get this to work with the regulators and get and find a path forward and so the way to handle that is that we provide the information both to EMA and to U.S. and the goal here is to let the regulators tell us what the next steps will be with this drug.
Because the drug has efficacy in muscle and is safe, from the studies that we have done so far, including two large Phase IIIs we believe there is a path forward but it will be up to the regulators to tell us what that path forward could be.
Brian Klein – Stifel Nicolaus & Co.
Great, thanks. And then on Capesaris, following the data from a competitor product Enzalutamide, with the PREVAIL data where they show the survival advantage, just wondering, I know your comments you suggested you might be able to move forward with PFS endpoint, do you find that the patient population will be changing at the point where you are going to be starting your final registrational program and do you think that the commercial opportunity begins to diminish as additional agents come into the approval?
Great question. So the first thing is the way I see it is that when prostate cancer drugs started coming out in patients with metastatic castrate resistant prostate cancer overall survival is what you needed to hit in order to get the drug approved. And then as they moved into the pre chemo space it wasn’t just overall survival but it was sort of a combination of progression free survival and overall survival.
And now with Enzalutamide and abiraterone has become clear that there is a correlation between PFS and overall survival to a point that we hope that the agency would agree that going for an earlier time point using just a PFS endpoint will be acceptable. We have watched the same evolution occur in other cancer types and we also are watching other cancer types how multiple agents are being used in other cancer. In fact in lung cancer you know how many different flavors of EGR receptor molecules are out there between antibodies and small molecules all going for the same target.
So I think in prostate cancer we’re just beginning, we are not ending. I think that if we have an agent that had a different mechanism of action then I think there is going to be some advantages. I think if you have a drug that has the same exact mechanism of action then the question could become what are the features of your drug, whether it’s efficacy or safety that will allow us to make a decision as a physician, why we want to use one androgen receptor antagonist versus another. But coming in with a new drug like this one in which in addition to having potential efficacy in treating the cancer itself and making bone stronger, so that you can prevent mix and then on top of that treating the side effects of androgen deprivation therapy we think we have a place.
One is a biggest concerns of primary ADT, primary androgen deprivation therapy is it does lower testosterone and any agent that continues to work by lowering testosterone will continue to increase the side effects, the estrogen deficiency side effects which can be quite serious, including fractures, hot flashes and metabolic syndrome and insulin resistance. So any of these other drugs that are coming out, whether it’s abiraterone, prednisone, enzalutamide, [oregon’s] drug I mean these drugs are very effective in dealing with testosterone, testosterone pathways by the end of the day they are going to continue to make the estrogen deficiency side effects worse or they are going to have to be given an addition with potentially expensive drugs like Xgeva to treat the prolia to treat the bone loss or to treat patients to prevent skeletal related events.
GTx-758 is uniquely positioned because we could be a bone drug and a prostate cancer drug and could be given and recently I made the comment, the first secondary hormonal therapy the concept there is as soon as the patient breaks through primary androgen deprivation therapy and has a rising PSA and has non-metastatic castrate resistant prostate cancer, where are you going to go to? Do you want to try to find something that will treat the side effects of ADT and treat the cancer itself and use an endpoint that is clinically meaningful such as progression free survival? Or do you want to go for something that’s going to shutdown testosterone and potentially aggravate or make the estrogen deficiency side effects worse?
So I think that commercial opportunity for GTx-758, given this kind of potential therapeutic profile is attractive and is very different. And if I came back and said I have the third androgen receptor antagonist, or I have the third Liase inhibitor. I mean you have already seen one company bow out that had a Liase inhibitor recognizing that space is taken.
With that said I think that running these trials, there are 100,000 patients a year with non-metastatic castration resistant prostate cancer is a large market opportunity and patients will continuously look for therapies that will improve their symptoms and more importantly treat their cancer.
So I think we will have a place and I do think that the goal would be to be able to do the studies against placebo and these other drugs will always be available if the patients fail and I am hoping will do is will convert prostate cancer into more of a chronic disease which means that it’s not you use one and the patient dies, you use one hormonal therapy and then you follow it by a second, you follow it by third and the goal is like in breast cancer to continue to treat these patients that are hormonally sensitive.
Unfortunately there is still a large subset of patients, probably over 50% of the patients that have disease that are not hormonally sensitive and they will march right to all kinds of hormone therapy very much like triple negative disease and breast cancer and those patients will need other therapies. So I think this is really just a beginning in prostate cancer and it’s not a mop up operation at this point.
Brian Klein – Stifel Nicolaus & Co.
Great, thank you.
(Operator Instructions) There are no further questions and I would now like to turn the call back over to Dr. Steiner for closing remarks.
Thank you very much operator. I would like to thank you all for your interest in GTx and we look forward to updating you in near future. Thank you for being on our call.
Thank you for your participation in today’s conference. This concludes the presentation. You may now disconnect. Good day.
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