TherapeuticsMD, Inc. (TXMD) Q3 2016 Earnings Report, Transcript and Summary

Good day, ladies and gentlemen, and thank you for standing by. Thank you for joining us for the TherapeuticsMD Third Quarter 2016 Results Conference Call. Following prepared remarks from the company, we will open the call for questions. I would now like to turn the call over to TherapeuticsMD Director of Investor Relations, David DeLucia. David?

Good afternoon, everyone. Thank you for joining today to discuss our third quarter 2016 financial and business results. Following the market close, TherapeuticsMD issued a press release announcing third quarter results. The press release is available on the company’s website thepeuticsmd.com, in the Investors and Media section. On today's call from TherapeuticsMD are Chief Executive Officer, Robert Finizio; Chief Financial Officer, Daniel Cartwright; Chief Clinical Officer, Dr. Brian Bernick; Chief Medical Officer, Dr. Sebastian Mirkin; and Chief Product Officer, Julia Amadio. I would like to remind everyone that certain statements made during this conference call may be forward-looking statements. Such forward-looking statements are based upon current expectations and there can be no assurance that the results contemplated in these statements will be realized. Actual results may differ materially from such statements due to a number of factors and risks, some of which are identified in our press release and our annual, quarterly and other reports filed with the SEC. These forward-looking statements are based on information available to TherapeuticsMD today, and the company assumes no obligation to update statements as circumstances change. An audio recording and webcast replay for today's conference call will also be available online in the Investors and Media section of the company's website. For the benefit of those who may be listening to the replay or archived webcast, this call was held and recorded on November 3rd, 2016. With that, I'll turn the call over to TherapeuticsMD CEO, Rob Finizio.

Thanks Dave. Good afternoon everyone. The third quarter of 2016 represents another transformative quarter for TherapeuticsMD. The company continues to successfully execute while making significant progress advancing our two late stage pipeline assets. I'll briefly describe some of our accomplishments during the quarter and then give an outline for this afternoon's call. On July 7th, we submitted our new drug application, also known as an NDA, for TX-004HR or Yuvvexy, our approved trade name. On September 19th, our NDA was officially accepted by the FDA and we have received a PDUFA target action date of May 7th, 2017. The NDA is based upon the complete results of TX-004HR clinical program including our positive pivotal Phase III Rejoice Trial. As you look towards potential launch, our prescription prenatal vitamin business continues to provide an important footprint for commercialization. We will continue to appropriately expand our sales infrastructure to prepare for the potential launch of TX-004HR in the second half of 2017. I'll expand upon this later in the call. And now, I'd like to get onto our next product candidate, TX-001HR also known as the Combo. We currently remain on track to deliver topline results this quarter for our Phase III Replenish Trial, which is evaluating our bioidentical combination of Estradiol and progesterone for moderate-to-severe vasomotor symptoms due to menopause. We believe that TX-01HR has the potential to become the first and only FDA approved bioidentical combinations of Estradiol and progesterone for women and a valuable treatment option in the large growing and underserved market for bioidentical hormone therapy. We also announced this afternoon the addition of two key Executives to organization; Dawn Halkuff, our new Chief Commercial Officer and Yulii Bogatyrenko, our new Senior VP of Business Development. We are excited to further strengthen our company with such outstanding individuals. On today's call, we'll review these developments in our prepared remarks and then open up for Q&A. Dan will start with a review of our financial results, then I'll provide a brief review of the regulatory timelines for TX-004HR and updates around our potential launch; then Sebastian and Brian will provide a clinical and medical update. Lastly, I'll review our key Executive hires and provides and closing remarks. And at this point, I'd like turn it over to Dan.

Thanks Rob. Our financial results for the quarter ended September 30th, 2016 are included in the press release issued today. Let me highlight a few key points about our third quarter financial results. Net revenue from the company's prescription prenatal business was approximately $5.5 million for the third quarter of 2016 compared with approximately $5.2 million for the third quarter of 2015, representing a 7% year-over-year growth. Total operating expenses for the third quarter of 2016 increased compared with the third quarter of 2015. R&D expenses during the third quarter of 2016 were approximately $14.7 million compared to approximately $16.4 million during the prior year's quarter. This change reflects a decline in clinical costs associated with our Phase III trials. SG&A expenses for the third quarter of 2016 were approximately $14.7 million compared with $7 million for the prior year's quarter. This is primarily due to an increase in personnel cost as well as sales, marketing, and regulatory expenditures to support future commercialization. We are expanding our women's health sales force and investing in pre-commercialization activities to support the potential launch of TX-004HR in the second half of 2017. We expect these factors to increase the growth rate of our SG&A expenses throughout 2017. Turning to our bottom-line, our net loss for the third quarter of 2016 was approximately $25 million or $0.13 per basic and diluted share compared with approximately $19.5 million or $0.11 per basic and diluted share for the third quarter of 2015. Finally, we finished the third quarter with approximately $147.5 million in cash compared with approximately $64.7 million at December 31st, 2015. As a reminder, our cash balance at the end of the second quarter of 2016 was $166.5 million, which equates to a cash utilization of approximately $19 million in the third quarter. We believe our strong financial position will allow us to advance our pipeline and support both our late stage products as well as achieve our goal of becoming a leader in women's health. Rob?

Thanks Dan. I'd like to provide some additional detail around the company's regulatory and launch timing for TX-004HR. Under September 19th, our NDA was accepted by the FDA and we’ve received the PDUFA target action date of May 7th, 2017. Assuming approval, we plan to launch our product in the late third quarter or early fourth quarter 2017. Currently, we have about 50 sales representatives selling our prescription prenatal vitamins in five designated regions around the country. Starting in January of 17th, we plan on expanding our sales force to over a 100 reps and adding an additional five regions creating a total of 10 regions across the U.S. The 50 reps will have -- 50 reps we have today currently call on about 4500 of the 11,000 OBGYNs that represents our target market for TX-004HR. With at least of 100 total reps we feel we can sufficiently cover all the current high prescribing doctors of VVA treatment in the women's health channel around the country. The infrastructure that we have built to our prescription prenatal vitamin business includes our long-term relationships with payers, providers, pharmacists and women. We believe this would provide us with the foundation for a strong launch of TX-004HR if approved. Sebastian will now provide a regulatory and clinical update including additional details around our Phase 3 Replenish Trial. I would like to remind everyone that we expect to announce our topline data for this trial within the next 60 days. Sebastian?

Thanks, Rob. First, I would like to congratulate our entire clinical and regulatory team for the hard work and success on the symptoms of our NDA for TX-004HR. The NDA includes all three doses that were evaluated in the rejoice trial [indiscernible]. We have also proposed a modified labeling for TX-004HR. And we are looking forward to working with FDA throughout entire review process. Now moving to TX-001HR. I’m pleased to [indiscernible] announce that all subjects have exited our Phase 3 Replenish Trial, which is evaluator our combination of identical 17β-Estradiol and progesterone for the treatment of moderate to severe vasomotor symptoms due to menopause. We are on track to release the topline results this quarter. The Replenish Trial is a randomized double-blind placebo-controlled trial that was assigned to study four active arms in approximately 1750 subjects on power to show efficacy on hot flash reduction and Endometrial Protection. We are evaluating of four different doses of TX-001HR to demonstrate for the first time the dose combination of identical hormone therapy for the treatment of hot flushes as well as endometrial protection. These doses include 1 milligram of Estradiol in combination with 100 milligrams of progesterone, 0.5 milligrams of Estradiol in combination with 100 milligrams of progesterone 0.5 milligram of estradiol in combination with 50 milligram progesterone and 0.25 milligram of Estradiol in combination with 50 milligrams of progesterone. Importantly, the highest Estradiol and progesterone doses using our trial already well-established and a standoff care for the treatment of hot flushes as well us endometrial protection. The lowest dose the combination of 0.25 milligram of Estradiol with 50 milligram of progesterone was included to help determine the lowest effective dose in the clinical trial. Now I would like to turn the call over to Dr. Bernick who will provide additional insights into the potential impacts of our products for women.

Thank you, Sebastian. As Dr. Martin suggested the TX-001HR be approved we believe it would be the first and only FDA approved bioidentical combination of estradiol and progesterone for women wealth of medical literature supports the benefits of hormone therapy and the proposition that natural or bioidentical estrogen and progesterone are safer than the synthetic forms. We believe that this proposition is supported by the millions of annual prescriptions for on approved bioidentical combination estrogen and progesterone products that are filled through compounding pharmacies as there is no FDA approved and available bioidentical combination product. Additionally, we believe that if approved having three distinct doses of TX-001HR will allow clinicians to tailor the dose to their patient's needs as they have been a custom to with compounded therapies. Remember, before the women's health initiative results were released in 2002 hormone therapy for vasomotor symptoms due to menopause was one of the highest prescribed set of drugs across any indication in the United States. We believe that the market opportunity for these drugs continues to grow as the population of post-menopausal women has grown over 25% since 2002 and these women continue to seek therapy to alleviate their symptoms. Notably, however, since the WHI, there has been a massive change in the distribution of these therapies from non-bioidentical FDA approved hormones to the compounded hormones as women demand bioidentical hormone products. If approved TX-001HR would become the first and only FDA approved bioidentical combination hormone therapy. We believe that meeting the demands of women and their healthcare providers for bioidentical hormone products that is FDA approved based on clinically validated safety and efficacy data, creates significant opportunities for our company to convert the multibillion-dollar compounded bioidentical hormone therapy market. Next, with respect to our VVA product TX-004HR, remember the clinical development program demonstrated and onset of action as early as two weeks as well as showed negligible systemic absorption comparable to Placebo. TX-004HR lacked the messiness and inconvenience of the other products that often cause patients to discontinue or defer therapy. Therefore, we believe that TX-004HR, if approved, has the potential to be a best-in-class therapy and expand treatment options for the estimated 32 million women across the U.S. suffering from symptoms of VVA. Finally, I'd like to comment on the presence of the North American Menopause Society Annual Meeting that was held in Orlando during the first week of October as both a leading sponsor and a participant. The company continued to expand its relationships with leaders in the medical community as it pertains to the improvement of awareness and diagnosis of VVA. We had six oral presentations and posters reflecting the breadth and depth of our TX-004HR clinical program. These included key Phase III Rejoice Trial data as well as the newly presented results of our EMPOWER Survey of over 1,800 postmenopausal women and n the perceptions of VVA. The EMPOWER Survey is now available in the Investors and Media section of our corporate website. Now, I will turn the call back to Rob.

Thanks Brian. I'd like to comment on today's announcement of our two key Executive hires. It brings me great pleasure to announce the hiring of Dawn Halkuff, our new Chief Commercial Officer; Yulii Bogatyrenko, our new Senior VP of Biz Dev. We believe both individuals will help us achieve our goals of becoming a leader in women's health. Dawn has held Senior Executive positions for over 20 years, specific to commercialization and marketing of numerous products. She joins from Pfizer where she held senior leadership roles in women's health since 2010. Most recently, she was Senior Vice President of the Global Wellness Organization within Pfizer Consumer Healthcare and a member of the Consumer Global leadership there. Prior to that she was commercial lead for sales and marketing of the Women's Health division of Pfizer, focusing on the company's reinvestment in postmenopausal hormone therapy treatment including PREMARIN Vaginal Cream and Oral hot flash treatments. Lastly, she was the Head of Global Innovation for Weight Watchers International, in charge of creating new weight loss products, services, and solutions for women across the globe. Dawn's experience commercializing new drugs and products precisely targeted at women makes her a perfect fit for our company. She is a proven consumer expert, motivating women to initiate the necessary steps to confront personal issues that can be medically treated as well as connecting all professional stakeholders. This experience is needed for a successful launch of both of our products. Specifically, the TX-004HR only 7% of the 32 million women suffering from VVA received prescription hormone therapy. Will due to lack of prescription treatment in this market, we believe Dawn's experience combined with the differentiated product profile will help us bridge this treatment gap for the postmenopausal women suffering from VVA, if approved. Yulii Bogatyrenko has over 20 years of experience in the biopharmaceutical industry. Mostly recently he was Senior Vice President of Business Development at Paratek Pharmaceuticals where he developed global and regional partnerships for the company's anti-infective products and led the U.S. alliance with Allegan for the company's dermatology products. Specific to women's healthcare, prior to Paratek, he was a Vice President and General Manager at Teva Pharmaceuticals, where he led an ex-U.S. Specialty Women's Health business in Latin America, Asian -- Asia, Middle East, India, and Africa. Prior to Teva, he had global responsibility for Bayer's Women's Health franchise. We believe Yulii's business development experience specific to women's health as well as his long-term relationship with major players in the pharmaceutical industry, will help us pursue opportunistic commercialization strategies and evaluate ex-U.S. licensing opportunities around the world. In summary, TherapeuticsMD is positioned in the right place at the right time and we continue to execute on all of our goals. Each of our two late stage assets represents significant near-term revenue opportunities for our company. We have numerous tailwinds supporting our late stage product pipeline, including positive demographic changes, favorable regulatory dynamics, and a lack of innovation and promotion by large pharma in the treatment of postmenopausal health. We believe both of our potential next-generation products targeted at large growing in underpenetrated markets represents a multibillion-dollar opportunity. Pricing and formulary access are key issues facing the pharmaceutical industry today. I'd like to remind everyone we currently have limited or no applicability with both TX-004 and TX-001 in this arena, if approved. We expect to price our product superiority with existing therapies and believe both classes of drugs will continue to be managed by payers. In addition, we continue to attract the top talent in the women's health industry to ensure a smooth transition to commercialization. In closing, I'd like to just remind everyone we have two major upcoming catalysts. First PDUFA target action date that's about six months away for TX-004HR or Yuvvexy; and second, we expect to report topline data from the Replenish Trial within the next 60 days. We're as confident, healthy, and well-positioned as we've ever been. And with that being said, I'll turn it over to the operator for questions.

[Operator Instructions] Our first question or comment comes from the line of Annabel Samimy from Stifel. Your line is open.

All right. So, a few quarters ago, you had provided update on the cases of hyperplasia that you had seen with [Indiscernible], which generates simply very low and in line with currently available treatments you have. Any other updates on that hyperplasia to-date?

Hey Annabel. This is Sebastian. Thank you for being in the call. So, let me make very clear. The data is fully, fully blinded for us, for the patients, for the physicians, right. So, don't have any [Indiscernible] of information. But to make sure that you understand what we said back then and what we're going to say now is so far there is not different information of the one that we reported back then. There's not a single case of consensus of blood pressure throughout the clinical trial.

Okay, great. And then just wanted to about the doses for a minute, you had mentioned, the top two doses were already well-established, the bottom was to establish lowest effective dose. You don’t really talk about the 0.5 and 50 progesterone, would that be I guess the lowest dose you might be going with? How does that dose fit into the marketplace? And I guess I caught little bit later in the comments you had three distinct doses that you're going for, does that mean that you are just establishing the last dose as lowest effective dose just to have that for the FDA. I guess can you just explain your comments little bit. Thanks.

Thanks, Annabel. This is Brian Bernick. You are correct. We have four active doses the fourth dose been 0.25-50 milligram dose that was included to help determine the lowest effective dose in the clinical trial based on the FDA guidance so that was put in as an ineffective dose. The highest doses of estradiol and progesterone included in this trial already approved separately for hot flashes as well as the standard of care for endometrial protection. When no one has proven before if the right ratio of progesterone and a continuous combined fashion with estradiol on that is what this trial was set to do and we expect positive results. I hope that answers your question.

So the 0.5 to 50 is lowest effective dose that you’re actually going for? And 0.5 to 50 is put in there as an ineffective dose?

Right, so the 0.25-50 was put in as an ineffective dose to assess what the lowest effective dose would be and while it is the possibility it could be effective. The reason that was put in is put in at the FDA's guidance to help determine the lowest effective dose.

[indiscernible] to answer your question directly we do expect the 0.5-50 to be effective in given signs that should be the lowest effective dose but we thought that in a VVA trials as well.

Okay. All right, great. And there is no chance that you believe that 0.25 to 50 could be effective?

We don’t want to say no chance. It could be.

Okay.

But we’ll see, right?

Okay. And then if I could ask one last question I mean you’ve been to number of medical meetings at this point I'm hoping to get a sense for me as to how you start changing physician perception around bioidentical because it seems to me anecdotally we still have this idea that there is nothing better from a safety perspective about bioidenticals and you’re not really necessary testing on for safety parameters that’s different from what's been tested before for the synthetic. So how do you sort of start changing the mentality about bioidenticals and how they are possibly more differentiated than the synthetics?

So Annabelle, this is Rob. So I’ll talk about the business case and then I’ll turn it over to Brian on the physician standpoint maybe Sebastian as well. So I just want to be clear why we’re developing this drug. So there is an overwhelming market overwhelming market that is compounded today. The compounding drops have never been proven safe or effective; it’s filling a necessary gap in the market probably about 30 million prescriptions a year. Given the regulatory environment in the complete loss of reimbursement for those drugs forcing the compounders to eliminate or have very low margins that we are trying to meet that need. We are not trying to come out and say compared to the very small synthetic FDA approved market that was 110 million scripts is now down to about 6 million. We’re not trying to say or just safer or better given the class labeling in this class. We’re trying to say women want bioidenticals pharmacies are compounding them there is a lot of risk associated with compounding, the laws of change their and assuming we got FDA approval those would considered essential copies as well as the economic environment in the pharmacy where they used to make a good $90-$100 a script has gone down to odd numbers $3 to $5 net profit for pharmacy whereas we can hopefully improve their margins even pricing at parody with the existing FDA approved solution on the market today. With that being said, bioidentical science progesterone itself when compared head to head in studies like Pappy and some of the other ones a recent NIH study of Finnish study replenish if you look at our slides we have a whole slide articulating this seems to have less off target effects then progestins since it's neutral to the [indiscernible] sites, glucocorticoid sites in androgen sites given there is a black box label and class labeling year. I know we will have to reference progesterone since it’s a 505(b)(2) and estradiol so some of that data will make it in there, but we are not going to have a highly differentiated safety profile when compared to the synthetics. Brian, do you want to anything?

No I would just add that I think that we have here is that the standard of care in the treatment with these drugs has become the compounded drugs by them FDA approved drugs and so I think that we don't have the challenge of working with physicians to get them to feel comfortable with it.

Okay. Great. Thank you.

Annabelle?

Yes.

So, I just want to clarify Sebastian's answer. I’m not sure I understood the question so they updated hyperplasia numbers. Look we’ve been monitoring the safety data throughout the duration of the trial and we haven't seen any safety signals, period including endometrial hyperplasia and the data is I just want to be very clear still winding. Okay.

Okay. Great. Thank you.

Thank you.

Thank you. Our next question or comment comes from the line of Jami Rubin from Goldman Sachs. Your line is open.

Hi. This is Jonathan on the call for Jami. In your Investor deck you provided additional color on how you segment the market based on past and current use of the patient? Now can you talk about how you intend to target these individual segments and what you see as low hanging fruit in the early days of Yuvvexy launch? You’ve assume that 18% of the market has previously used hormone therapies before and sent to discontinue treatment that Mary of the market that you expect will be easy to target and what’s your strategy there and how do you expect to penetrate the 50% of the market that’s never sought hormone replacing therapy treatment. And what’s your expected penetration in the long-term this year? And if you will, I have a second question afterwards if you have time.

Sure. That's a pretty broad question and I'll try to sum it up his best I can for call here and we will get into much, much more segmentation in detail here in Q1 of 2017 of exactly how and why we're going after each portion of the VVA market. But to answer your question directly the people on the phone understand other 32 million women only 7% that suffer from moderate to severe vulvovaginal atrophy are seeking treatment that 18% of the women that are aware that have this issue have gone over the estrogen hurdle and stopped treatment because of our data suggests and other large studies that they are not comfortable with the current drugs that are in the market. So that’s varying reasons. We believe our data with a fast onset of action with a clear effect of dyspareunia with multiple dosing options with hopefully if approved new lower effective doses and very easy to use easy to prescribe time efficient manner for both women and being able to use it for the first time in ambulatory nature as adopted before bed they can use it with less than 2 to 3% of the act of preventing any vaginal discharge overcomes about every one of the documented complaints in that 18% the market. So we think that's very right for us to attract them back into the uses population. We think our product given the user satisfaction is somewhere between 76 and 95% found it easy to use or use it again given the ratings of the legacy products between 39 and 41% is very, very ripe as far as the 25% of the population that uses over-the-counter lubricant and is not comfortable using estrogen we believe they are very sensitive to systemic estrogen exposure given that are 4 µg and 10 have a negative area under the curve compared to placebo that means the estrogen our data suggest the estrogen is not all elevated is not elevated in the body when using our product compared when just using placebo we think that is a very good tool as well as the other things I mentioned to attack that 25%. And lastly the 50% of women that are not seeking treatment today almost that is an awareness problem industry is completely struggled with. And those women are not seeking treatment and not aware this can easily be with the legacy products be safely and adequately treated. That’s one of the reason we brought on someone like Dawn Halkuff. She is an absolute consumer expert. She has been doing this for whole career she know this product space and she if you think of what women go through when they're not comfortable having sex and they’re having all these vaginal issues as they get older in postmenopausal. Well, it’s associated with shame and women are not comfortable talking about that. And if you look at back where Dawn started at weight watchers very, very similar parallel going on all the way to where she was in the consumer health side for Pfizer and we certainly are coming up with strategies to go after the market. I'm just not that I want to articulate that and if it's okay we’ll save that for another day.

Sure and my question -- my second question is on pricing. As a more convenient and superior product form our assumption with that the price would be a little bit higher and present a premium to the existing therapies. We’re just hoping that you could comment on what your assumption is and why you're pricing up the price point that you are?

Because the market -- couple of reasons, first of all these are what we call unmanaged classes so you do not have to go through for the most part with major payers, P&T review to get any formula or inclusion at Tier 3. That is a huge obstacle and a huge headwind facing our industry today and seems to be clearly affecting the stock prices and earnings. With that said we also believe in price imparity given the size of the market by market and the cost of goods sold. We are in a situation to really take market share and do not have any issues with payer inclusion and to cover a lot of ground much faster and we believe it’s the right thing to do for women and we believe it's still of very massive market that we can undertake and this is one of the key strategies.

Sure. Thank you.

Thank you. Good question.

Thank you. Our next question or comment comes from the line of Kumar Raja from Noble Financials. Your line is open.

Hi. Thank you for taking my questions. So out of these patients who are like 7% who are being prescribed right now. What percentage are treated by other specialties other than OBGYN and what is the strategy to target these patients, obviously, like last time you said about collaboration, so you can explain on that?

Yes, obviously, so this is Rob again. So, the 7% being treated for mostly OBGYNs and its select set of PCPs. We believe that the PCPs today that do prescribe which would extend to a much bigger population of women are not as aware of the issue and when they are aware of the issue, the current products take a lot of time to educate women and prescribe as well as just the whole fear of estrogen. Given [RP] case, if approved, and included in the label, which we're pulling for, we believe the compared to Placebo, the lack of estrogen increasing on the lower doses in the blood serum certainly would be a very good tool at disarming this issue with both women and prescribers that are not prescribing today. In addition to that, the simplicity of the packaging, the inner, outer insertion in the vagina of the gel tab and the quick dissolution -- it's about an hour and 20 minutes for very patient, would allow PCP to not have to put a woman in stir-ups, teach her how to use it and change the dosing. There's a lot of analogies here to something like of a Z-pack, a Medrol Dosepak, or even an EpiPen where it can prescribed over the phone or a sample could be simply handed to a woman and it's intuitive. It's very comfortable use, which is the last piece and has very little vaginal discharge. And the onset of action, the data suggest that we do, so unlike the existing products, which are week five to week 12, I believe, they are refilling a prescription before they see efficacy. So put all that together, we believe that we should have a good shot, if done correctly, at expanding the market and we have the right clinical data if it's approved and included to go out there and get that done.

And you have touched on pricing, so have you had any negotiating with effect [ph] all what kind of feedback are you getting so far?

Absolutely. So, obviously, we can't discuss it with payers till its approved, but we certainly have some ad comps and some feedback on it. From every payer, we get the same -- everyone large or small, this is page four, five to us, this is the class that we haven't seen growth in a long time. Unless you go and price it at a significant premium, we don't expect you to have any P&T review. So, in essence, just don't be greedy.

Okay, great. Thank you for taking my questions.

Thank you.

Thank you. We have time for one last question. Our final question or comment comes from the line of Tyler Van Buren from Cowen and Company. Your line is open.

Hi there and congratulations on looks like two great commercial hires.

Thanks Tyler.

Yes. And given the combo 001 readout at the end of this quarter, so want to discuss a little bit further the -- with respect to the endpoints, the incidents of endometrial hyperplasia being less than 1% seems pretty darn straightforward, but wanted discuss the vasomotor symptoms endpoints. You're looking obviously both at four weeks and 12 weeks, and then you're also looking at number and severity of hot flashes. So, a few moving parts there. I want to get a better understanding of what exactly is required for approval for each dose? And hopefully you can just remind us of that. And then with respect to clinical utility and what physicians will view as meaningful, especially with a number of hot flashes or severity as well, what magnitude of reduction is the threshold, what important whether that's absolute magnitude or relative to Placebo? Thank you.

Hey Tyler. So, the FDA has a clear guidelines right on want to measure in this clinical trial. So, you're absolutely right. The four primary endpoints are the journey from baseline in the number and severity of hot flashes and withdrawal, right. I want to show plain success in the clinical trial is statistical difference versus placebo, right. That's number one. What is clinically meaningful? Each of this compounds has a different efficacy as you're aware, right. So, we have required tools embedded in the clinical trial to determine what would be clinically meaningful for a given women, right. So, that also is going to be determining in our clinical trial.

If I could add one thing there. Tyler, so this is Rob and this is more of a business thing. So, obviously, we're shooting for a clear delta here. There has been a lot of approvals, so it was a very clear history, precedent, and guidance from the FDA on their website under estrogen and progesterone guidance -- progesterone guidance. But I do want to stay and it goes back to Annabel's question as well that you're bringing up, if you look at Activella, Enjuvia and even Paroxetine at the lowest dose, none of them had the two -- the standard two separations at week four and week 12. They all had either one or two hot flash separations somewhere later, but didn't hit the two co-primaries. So, kind of more effectively answer Annabel's question, those three drugs -- Paroxetine had, I believe, one hot flash separation, not two, I believe it was week eight or 12 and I know you Activella's lowest dose had, I believe, one or two at week 10 and they were both approved as well as Enjuvia [Indiscernible] drugs. So, look, finger's crossed on that one. It's obviously in there to be an ineffective dose. We do believe the .550 will work and we'll see here topline data, but don't give up hope on the .2550, you never know, if we can get one separation hot flash before week 12 that would be best to both worlds because it would have a chance of being approved, if the FDA wants to approve it, but it also show that it's an ineffective dose at the lower threshold.

Okay, that's helpful. Thank you.

Thank you.

All right. So, with that being said, this is Rob Finizio, I'd just like to wrap-up the call and remind everybody that we will be on time or we absolutely intend to be on time with date of this quarter in less than 60 days and we look forward to speaking with all of you on that call after we present the topline data. Thank you very much and look forward to keeping in touch.