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Edited Transcript of OBSV.O earnings conference call or presentation 5-Mar-20 1:00pm GMT

Q4 2019 Obseva SA Earnings Call

PLAN-LES-OUATES Mar 31, 2020 (Thomson StreetEvents) -- Edited Transcript of Obseva SA earnings conference call or presentation Thursday, March 5, 2020 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Elizabeth Ijeoma Onyemelukwe Garner

ObsEva SA - Chief Medical Officer

* Ernest Loumaye

ObsEva SA - Co-Founder, CEO & Director

* Jean-Pierre Gotteland

ObsEva SA - Chief Scientific Officer and Head of R&D

* Mario Vincent Corso

ObsEva SA - Senior Director of IR

* Timothy M. Adams

ObsEva SA - CFO

* Wim Souverijns

ObsEva SA - Chief Commercial Officer

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Conference Call Participants

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* Ami Fadia

SVB Leerink LLC, Research Division - MD of Biopharma & Generics and Senior Analyst

* Chang Liu

Jefferies LLC, Research Division - Equity Associate

* Eric William Joseph

JP Morgan Chase & Co, Research Division - VP & Senior Analyst

* Kennen B. MacKay

RBC Capital Markets, Research Division - MD & Co-Head of US Biotechnology Research

* Mark William Connolly

Crédit Suisse AG, Research Division - Research Analyst

* Raghuram Selvaraju

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

* Vasiliana Vireen Moussatos

Wedbush Securities Inc., Research Division - MD of Equity Research

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Presentation

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Operator [1]

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Welcome to the ObsEva Year-end 2019 Financial Results and Business Update Conference Call. (Operator Instructions) As a reminder, this call is being recorded today, March 5, 2020.

I would now like to turn the conference over to Mario Corso. Please go ahead.

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Mario Vincent Corso, ObsEva SA - Senior Director of IR [2]

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Thank you, operator. This is Mario Corso, Senior Director, Investor Relations at ObsEva. Good morning or afternoon to our listeners from the U.S. and Europe, and welcome to today's call. On today's call, I'm joined by Ernest Loumaye, our Co-Founder and Chief Executive Officer; Elizabeth Garner, our Chief Medical Officer; Wim Souverijns, our Chief Commercial Officer; Tim Adams, our Chief Financial Officer; and Jean-Pierre Gotteland, our Chief Scientific Officer.

During today's call, ObsEva management will be making forward-looking statements, including, but not limited to, statements relating to financial results and trends; the process and timing of anticipated future development of ObsEva's product candidates; our oxytocin receptor antagonist, nolasiban; our gonadotropin-releasing hormone receptor antagonist, linzagolix; and our prostaglandin F2 alpha receptor antagonist, OBE022. These forward-looking statements will include comments about expected clinical trial results and regulatory pathways in the U.S., Europe and Asia as well as the therapeutic and commercial potential of ObsEva's products. These forward-looking statements are based on ObsEva's current expectations, and they inherently involve significant risks and uncertainties. ObsEva's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements.

Risks and uncertainties include, without limitation, those related to ObsEva's clinical development programs; trial time lines and results; the uncertain clinical development process, including adverse events; the success cost and timing of all development activities in clinical trials; the market potential for ObsEva's product candidates; the accuracy of ObsEva's estimates regarding expenses, capital requirements and the need for financing and other risks detailed in the risk factors and elsewhere in ObsEva's filings with the U.S. Securities and Exchange Commission, including it's 20-F report for the year ended December 31, 2019, to be filed on or around March 5, 2020 as well as other reports filed on Form 6-K and 20-F. ObsEva undertakes no obligation to update any forward-looking statements as a result of new information, future events or changes in expectations, except as required by law.

I will now turn the call over to Ernest Loumaye, our Chief Executive Officer.

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [3]

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Thank you, Mario. 2019 was a very important year for ObsEva. Most notably, the PRIMROSE 2 uterine fibroids trial for our lead compound linzagolix yielded outstanding results on the primary and important clinically relevant secondary endpoints that position linzagolix with best-in-class potential. While the IMPLANT4 trial results were disappointing. Our new partnership with YuYuan Bioscience in China enables the continued investigation of nolasiban for potential treatment in IVF.

We are now very committed and focused on achieving our objective in 2020. 2020 will bring important new clinical data for innovative R&D pipeline. The 2 ongoing Phase III trials of linzagolix for the uterine fibroids indication will read out in the second quarter, is a 6-month primary endpoint reserve for PRIMROSE 1, our U.S. trial and a 12 months treatment data for PRIMROSE 2, which is being conducted primarily in Europe. We anticipate completing enrollment of 120 women in the Phase IIa PROLONG trial of OBE022 in preterm labor in the first half of the year and plan to share results in the second half of the year when labor and delivery follow-up is completed.

As I mentioned, we are particularly pleased with the recently announced partnership with YuYuan Bioscience in China, which will allow for further exploration of the potential utility of nolasiban in IVF, result of financial outlay from ObsEva. I continue to believe that oxytocin antagonists have the potential to improve live birth rates following IVF. In summary, we continue to advance the development of potential first-in-class and/or best-in-class NCs in our pipeline and look forward to important clinical data readouts over the course of this year.

With that overview, I will now turn the call over to our Chief Medical Officer; Elizabeth Garner to provide a more detailed update on our pipeline programs.

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [4]

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Thank you, Ernest. I will now provide an update on each of our clinical development programs, starting with linzagolix. Without a doubt, ObsEva's most exciting highlight of 2019 was our first Phase III trial results for the oral GnRH receptor antagonist linzagolix for the treatment of heavy menstrual bleeding due to uterine fibroids.

In December 2019, we announced 6 months primary endpoint results for the PRIMROSE 2 trial that exceeded our expectations for both the high and the low dose arms. In women receiving the high dose of linzagolix, 200 milligrams plus hormonal add-back therapy, a response rate of 94% was achieved, which we believe positions linzagolix for best-in-class potential.

In addition, as the only company developing low dose option without add-back therapy. The response rate of 57% indicates that a significant proportion of women may achieve symptom release with the 100-milligram dose, without exposure to hormonal add-back therapy.

We believe our unique approach provides the potential for a more personalized approach to the treatment of uterine fibroids, especially for women who may not need, can't take or do not wish to use add-back therapy.

The secondary endpoints from PRIMROSE 2 were equally impressive, with 81% of women achieving cessation of bleeding or amenorrhea, which has only been demonstrated in approximately 50% of women and other GnRH antagonist clinical trials.

In addition, linzagolix showed statistically significant improvement in pain and uterine volume and is the only GnRH antagonist who have shown statistically significant reductions in fibroid volume, which clinicians point to as an important differentiator in the class.

Wim will be sharing some new market research on the importance of all these metrics to women suffering from uterine fibroids. I also note the baseline characteristics of the PRIMROSE 2 study population. In particular, menstrual bleeding volume and anemia rates indicate that like other companies developing oral generation agonist, we're studying women with severe disease.

As Ernest mentioned, we look forward to the 12-month treatment results from PRIMROSE 2 in the second quarter of this year. We also anticipate the 6-month primary endpoint results from our second pivotal trial for the uterine fibroids indication, PRIMROSE 1, the U.S.-only trial.

Given the substantially larger proportion of African-American women in PRIMROSE 1 and the corresponding higher baseline weight and BMI, all leading to a more similar population to those studied in the ELARIS and LIBERTY trials. We expect the BMD change in PRIMROSE 1 will be even less relevant than that seen in PRIMROSE 2.

Based on the results of the post trials and feedback from regulatory bodies on our submission strategy, we anticipate MAA submission for the fibroids indication by the end of 2020 and NDA submission in the first quarter of 2021.

In 2019, we began enrolling into our 2 Phase III clinical trials of linzagolix for the treatment of endometriosis associated pelvic pain, EDELWEISS 2 and EDELWEISS 3.

We expect both of these trials to continue enrolling women over the course of 2020 and '21. Based on our prior Phase IIb results, we believe that linzagolix also has best-in-class potential in the endometriosis indication, in particular, based on the similar efficacy observed in women receiving the low dose of 75 milligrams without add-back therapy to that observed in women receiving the high dose of 200 milligram with add-back therapy.

As with uterine fibroids having 2 highly effective doses of linzagolix potentially provides endometriosis patients with better options for treatment.

Now turning to OBE022, our oral prostaglandin F2 alpha antagonist in development for delaying child birth and pregnant women experiencing preterm labor.

The Phase IIa prolonged trial is designed to assess whether the addition of OBE022 to atosiban, the standard of care in Europe, increases the proportion of women who do not deliver within a 7-day treatment period.

Part B of the trial has proceeded very well, and the IDMC has provided us with a recommendation to continue enrolling patients without protocol changes based upon their interim review of safety data at the 60-patient time point. We expect to receive another IDMC update at the 90 patient time point, and we anticipate reaching the target of 120 patients enrolled in the second quarter of this year.

We look forward to results from the trial in the second half of this year, at which time, we will determine the next steps in the development of OBE022.

This concludes the R&D update, and I will now turn the call over to our Chief Commercial Officer, Wim Souverijns, who will discuss recent market research that has added to our enthusiasm about the prospects for linzagolix, as potentially best-in-class for the treatment of heavy menstrual bleeding due to uterine fibroids.

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Wim Souverijns, ObsEva SA - Chief Commercial Officer [5]

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Thank you, Beth, and hello to everyone joining us for today's call. Before sharing some of our new market research, we'd like to remind everyone on the importance of what we're doing. Aiming to bring a new therapeutic to women suffering from the serious life altering condition of uterine fibroids. Approximately 4 million women are diagnosed and treated with the condition in the U.S., and we have no new drug therapy approved in the U.S. outside of Lupron for short-term management brand surgery, patients often opt for NSAIDs oral contraceptives to reduce bleeding and pain, neither of which are very effective.

After years of suffering, as a last resort, many women opt for surgery to approximately 300,000 hysterectomies performed each year in the U.S. for fibroids. With the arrival of the GnRH antagonist, a new long anticipated option will soon be available that has the potential to replace surgery with effective medical therapy. We aim to contribute to the success of this class with a potentially best-in-class compound that can address the needs, most women diagnosed with uterine fibroids.

In this context, we were very excited with the results of PRIMROSE 2. Our assumption had been, that linzagolix will primarily be differentiated from the other drugs, and they caused by being the only option offering an effective partial suppression regimen, without the need for add-back therapy for the fibroid indication.

Based on our data, linzagolix indeed delivering that promise. But importantly, its full suppression regimen with incumbent add-back therapy show the potential to be really best-in-class. If these data are confirmed in PRIMROSE 1, linzagolix could offer not only the choice patients are looking for, but also the efficacy and safety both patient and clinicians needs.

In order to validate our assumptions, we commissioned a patient based market research study to assess how women view the importance of individual attributes of a potential uterine fibroids therapy as well as the overall profile of potential new treatments.

Using a choice-based method, we were able to drive the incremental importance of key attributes of a potential therapy in over 100 American women suffering from heavy menstrual bleeding due to uterine fibroids. And it included, reduction in pain and bleeding, the need for add-back therapy and side effects such as hot flashes.

The results provide important insights into patient preferences, and outline how the profile of linzagolix can meet the varying needs of women suffering from this condition. The first takeaway is that women are looking for a drug that has the full package. Not enough to score well only 1 attribute, but the new therapy has to perform well on all aspects, including efficacy, tolerability, safety, leaving convenience, which we know is important for compliance.

Secondly, from the efficacy perspective, it's interesting but probably not surprising that pain relief is more highly designed by patients than reduction in bleeding, although the latter is also very important. This shows the importance of pain relief as a secondary endpoint in our ongoing Phase III program.

Finally, one of the question we hear most often is, whether women care about add-back therapy? Well, our research tells us they do. Women indicated they're sensitive to the court administration of add-back therapy, expressing a preference for non-add-back regimens.

So bottom line, our big picture takeaway is that a new therapeutic addressing the needs of women suffering from heavy menstrual bleeding to treat uterine fibroids should score well on a broad range of clinically relevant attributes and provides choice, as not all women seek the same things from their treatments. This market research study confirms our development strategy and strengthens our conviction that linzagolix has the potential to be best-in-class. Together with the many women suffering from uterine fibroids were easily awaiting the near-term second Phase III readouts.

With that, I will now turn the call over to our CFO, Tim Adams, for a brief financial review.

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Timothy M. Adams, ObsEva SA - CFO [6]

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Thank you, Wim, and good morning or good afternoon, everyone. I would like to spend a few minutes outlining year-end 2019 financial results and our financial outlook. Our net loss for the year ending December 31, 2019, was $108.8 million or $2.49 per share, this compares with a net loss of $76.7 million or $1.91 per share for the year ended December 31, 2018.

The year-over-year increase in net loss was largely attributed to the increased spending on the clinical development for linzagolix and nolasiban. Research and development expenses were $88.1 million for 2019 versus $62.9 million for 2018. This increase resulted from the expansion of clinical trial development for linzagolix and nolasiban.

G&A expense in 2019 was $19.1 million as compared to $14.3 million in 2018. This increase was primarily attributed to higher staff costs for pre-commercial activities for nolasiban.

Our cash balance as of December 31, 2019, was $69.4 million as compared to $138.6 million at year-end 2018. Cash used in operations during 2019 was $90.6 million, reflecting continued spending in support of our pipeline. Based upon our budget assumptions for 2020, including cost savings from the stoppage of nolasiban clinical development in the U.S. and Europe, we expect 2020 use of cash to be below the 2019 level.

Therefore, we anticipate current cash on hand as well as the availability of the second $25 million tranche from Oxford Finance upon the successful results of PRIMROSE 1 will fund our operations into the first quarter of 2021.

Importantly, this outlook does not include potential cash received from a linzagolix' U.S. partnership, which we have stated to be one of our 2020 corporate objectives. Thank you.

And operator, we are ready for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from Kennen MacKay with RBC Capital Markets.

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Kennen B. MacKay, RBC Capital Markets, Research Division - MD & Co-Head of US Biotechnology Research [2]

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I was wondering on the questionnaire, the commercial questionnaire for potential patients. If you could just elaborate on how these patients were thinking about bone loss and sort of the severity of bone loss? And how that compared to some of the data that we've seen so far, if that was primarily just focused on efficacy?

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Wim Souverijns, ObsEva SA - Chief Commercial Officer [3]

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Kennen, it's Wim here. Do you hear me?

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Kennen B. MacKay, RBC Capital Markets, Research Division - MD & Co-Head of US Biotechnology Research [4]

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Yes.

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Wim Souverijns, ObsEva SA - Chief Commercial Officer [5]

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So in the questionnaire, we brought the bone loss -- there to my -- at least, there were not a big -- there's no prospect on bone loss. We conducted a study before we got the results for PRIMROSE. So we didn't have numbers at that stage. But we brought it in as a part of the profile of the drug, but it was not picked up as issue by patients.

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Kennen B. MacKay, RBC Capital Markets, Research Division - MD & Co-Head of US Biotechnology Research [6]

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Got you. And has there been any evolution in terms of discussion with regulatory authorities around that? Or is that something that we're still waiting on the next data set for?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [7]

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Yes, it’s Ernest speaking. No, we have not engaged with regulatory authorities concerning the overall efficacy and safety profile yet. We are in a process to talk to the FDA and National European Agency, in order to share with them the proposed data set which will be submitted and this consultation process is ongoing.

By contrast, we had some KOL advisory board in the United States. And Wim, maybe you can and maybe Elizabeth you can at least a little bit elaborate on the feedback from this U.S. KOL about efficacy, but also BMD.

Elizabeth, you want to start?

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [8]

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Yes, certainly. The advisory board consisted of a number of top experts in the U.S. in uterine fibroids and we presented the data from PRIMROSE 2, all of the safety and the efficacy data that we have so far. The reaction was overall extremely positive about the prospects for linzagolix and its efficacy. In terms of BMD, we certainly did not hear any concerns whatsoever from the clinicians, what they felt was, just as we've been saying, the study population was extremely important, and that we expect, as we've said, that the results from PRIMROSE 1 will more closely reflect the -- given the population, looking more similar to the populations in the elagolix and the relugolix trials, we anticipate that it will have similar results ultimately. And that the overall package in terms of BMD is really not of any concern. We know also, of course, that the FDA will be looking for the 52-week data as well as recovery, and that was another thing that the experts talked about, the recovery is very important. And what they've seen so far, we also presented some data from the EDELWEISS endometriosis trials, and they were very encouraged around the amount of bone recovery that we've seen in that population.

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Operator [9]

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Our next question comes from Ami Fadia with SVB Leerink.

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Ami Fadia, SVB Leerink LLC, Research Division - MD of Biopharma & Generics and Senior Analyst [10]

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I had a couple of questions. Just as a follow-up to the market research, takeaways that you shared with us. Can you talk about some specifics around -- you mentioned that patients do not care about -- do not had a preference for non-add-back regimen. Can you give us some statistics of how many women preferred that? And with regards to kind of the KOL feedback that you've got, how do they think about the BMD loss in the context of the duration for which they would treat patients with. And then I have 1 or 2 other questions.

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [11]

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Wim, do you want to address the add-back perception by divisions?

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Wim Souverijns, ObsEva SA - Chief Commercial Officer [12]

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Yes, I will. So Ami, so we didn't do an epidemiology study as such. But in the patients that we tested, there were about 100 patients. And we find that about 1/3 of the women have a preference not to use add-back therapy, okay? And we see a tendency for women that are slightly older to have more reluctance. So now extrapolating that to 30% of the population is bit of like a leap here. But it's clear that there is a significant proportion of women that do care about the -- that are aware of bone location therapy and some of the challenges it has, but to about 1/3 of the patients.

And to complement that, maybe on the physician's side, we ask a similar question because we did a physician research as well, including some patient records. Physicians have less of a concern with add-back, particularly in the U.S., okay? So -- and the reason for that is that they use add-back at the moment, only very short-term with Lupron. So they haven't kind of abort the idea of using long-term add-back and the potential impact of that. So their perception is add-back is probably not that -- not big a deal, but the patients do express that.

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [13]

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And Elizabeth, maybe you can confirm that was also the feedback from KOL?

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [14]

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Yes, indeed, that was. Definitely, there was a -- we also had a patient's advocate there, who reflected and confirmed a lot of the information we got from market research, and that was one of the items as well.

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Ami Fadia, SVB Leerink LLC, Research Division - MD of Biopharma & Generics and Senior Analyst [15]

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Okay. With regards to -- sorry, go ahead.

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [16]

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I was just going to say, do you want me to speak to the BMD question that you want -- asked up as well, Ami?

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Ami Fadia, SVB Leerink LLC, Research Division - MD of Biopharma & Generics and Senior Analyst [17]

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Sure.

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [18]

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Unless you had a follow-up to the first question?

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Ami Fadia, SVB Leerink LLC, Research Division - MD of Biopharma & Generics and Senior Analyst [19]

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No, no, please go ahead on the BMD.

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [20]

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Okay. So in terms of BMD, the KOLs, as I said, they felt that the data that we've seen so far, were encouraging. They really did not express any concerns at all about what they've seen in certainly 100-milligram dose. If anything, they felt that they were more interested sort of in the efficacy, right, around 100-milligram, and sort of how that's going to look over time. But from a BMD perspective, that was really not a real issue for them. They understand, as I mentioned, that this is only the 24-week data so far. We need to see 52-weeks, but that they expect, given what they've seen so far, that the pattern will likely be typical, right, meaning that usually BMD loss with estrogen depletion happens pretty quickly, but then tends to plateau over time. So their expectation on our results in the 100-milligram is that, we may see a slight increase, but they don't anticipate a substantial increase in the amount of BMD loss by week 52. And then, of course, the recovery rate is also a big piece.

And again, what results we've seen so far in -- from linzagolix, in the EDELWEISS trials suggest that recovery will occur pretty quickly as well. And of course, the last thing is the population, right? They're very interested in seeing what we -- how we envision the PRIMROSE 1 in a population that reflects more closely the U.S. population and the population studied in elagolix and relugolix. Another piece that came up, I would add, is the vitamin D and calcium. I think it's very important to remember that, we did not used vitamin D and calcium in these fibroids trials at the specific request of the FDA. And what we have gleaned as best we can without breaking confidentiality with these folks is that, it is likely that in the other fibroids studies, there has been at least some use of vitamin D and calcium. And we know from even the elagolix trials and the NDA review that vitamin D and calcium had a pretty important impact on BMD loss. And so indeed, if those are differences between our trial and the other studies. That's an important factor that certainly the FDA would consider.

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Ami Fadia, SVB Leerink LLC, Research Division - MD of Biopharma & Generics and Senior Analyst [21]

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Got it. Just 2 other quick questions. Just with regards to OBE022. At the 90-patient time point, what specifically is the IDMC is going to look for? And just with regards to the readouts coming up, can you give us a narrower time frame of when we could get PRIMROSE 1 and the 12-month data on PRIMROSE 2?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [22]

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So for the 90th patient in OBE022, IDMC is primary focused on safety. Are we harmful or not with the drug. And clearly, so far, it has been -- really support by the IDMC continue without changing the protocol. So that's the message we are waiting for from the IDMC. And then we will certainly announce when we complete the enrollment of the patients, the last patient, 120, so which will then lead to the time lines for the readout open -- full readout of the trial, which is expected indeed before year end. In terms of the readout of the 2 fibroids study, we confirmed that we would readout in Q2 this year.

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Operator [23]

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Our next question comes from Eric Joseph with JPMorgan.

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Eric William Joseph, JP Morgan Chase & Co, Research Division - VP & Senior Analyst [24]

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Just one on PRIMROSE here. You've been pretty clear about the expectation of seeing less of a bone impact for the 100-milligram mono dose, given the higher BMI in the trial. Can you talk a little bit about your -- the relative efficacy expectation at that dose regimen, whether there's any correlation between BMI and NBL response rate?

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [25]

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Not that we've seen thus far. Obviously, in PRIMROSE 1 with a larger population of women of higher BMI and weight. And of course, more African-American women will be able to get a better sense of that. But there's no indication and no reason necessarily from a, sort of, clinical perspective to expect that efficacy would be different from a blood loss perspective. I think, one thing that will be interesting to see is, we expect that -- we do know that African-Americans tend to have much bulkier fibroids. The amount of bleeding is similar, generally. And we know, as I mentioned in the talks, that the amount of bleeding in the PRIMROSE 2 population is very significant, right, over 200ml.

But fibroids do tend to be bulkier in the African-American population. So we'll be very interested to see what the effects of linzagolix are on shrinking those larger fibroids, but we're certainly very optimistic about what we'll see. So there's nothing that, to me, at least suggests that we should see reduced efficacy. That said, it'll be a challenge to beat 93% or 94%, right? So that will be interesting to see.

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Eric William Joseph, JP Morgan Chase & Co, Research Division - VP & Senior Analyst [26]

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Got it. And assuming positive data here, just how to think about the gating steps to additional interactions with regulatory bodies before an NDA submission? Do you need to wait for a similar 52-week data or 52-week follow-up from PRIMROSE 1 to have those discussions, or to set meetings?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [27]

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No, no. It's Ernest speaking. No, we'll -- we have ongoing interaction with the U.S. FDA and with European National Authority in order to get their feedback on the package. We are planning to submit for DMA and NDA, respectively. And this is ongoing now, and we don't need to wait for the results of PRIMROSE 1 for interacting at that level. The question is really, this acquired the data we're going to present. These are the protocols. These are the number of patients. These are the follow-up duration and so forth. That we are going to have in our submission. So that's ongoing, and we will hear about that in the second quarter.

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Operator [28]

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Our next question comes from Martin Auster with Crédit Suisse.

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Mark William Connolly, Crédit Suisse AG, Research Division - Research Analyst [29]

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This is Mark on for Marty. I guess, first, could you provide some more details on how partnership discussions have been going? And how soon you think an agreement may be closed? And then second, I was wondering, can you provide more qualitative details regarding how enrollment is going for the EDELWEISS trials. For instance, how many sites do you have up and running? And should we expect these 2 EDELWEISS trials -- should we expect enrollment of the 2 to be completed at the same time?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [30]

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So for the first question, in terms of partnership, we are certainly very active and interacting with our companies. There is nothing final or definitive at this stage, and we cannot comment on timing of conclusion of other potential partnership. In terms of enrollment and number of sites for the EDELWEISS, Jean-Pierre, can you step in? On order of magnitude because I don't know if -- yes go ahead.

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Jean-Pierre Gotteland, ObsEva SA - Chief Scientific Officer and Head of R&D [31]

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Yes. So for entrants, you're right, for the EDELWEISS 2 study, where -- which is exclusively in the U.S. We have about 125 sites. And for EDELWEISS 3, which is in Europe and in the U.S., we have about 90 sites, 75 sites in Europe and about 25 in the U.S., big list. And so that the enrollment is the -- is ongoing and according to schedule.

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Mark William Connolly, Crédit Suisse AG, Research Division - Research Analyst [32]

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Got it. And so do you think -- I guess, maybe if you could comment just kind of on expectations of when you think enrollment will be completed for that trial?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [33]

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This maybe a little bit early, too. Jean-Pierre?

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Jean-Pierre Gotteland, ObsEva SA - Chief Scientific Officer and Head of R&D [34]

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Yes, yes. So we're expecting enrollment -- we're expecting enrollment will be completed during the due course of 2021 to report results early 2022.

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Operator [35]

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Our next question comes from Liana Moussatos with Wedbush.

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Vasiliana Vireen Moussatos, Wedbush Securities Inc., Research Division - MD of Equity Research [36]

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Are there any slowdowns for nolasiban development in China for coronavirus? And how should we think about R&D in 2020 versus 2019? And can you talk a little bit about what is the minimum result for OBE022 for clinical meaningfulness in the prolonged study, and we see the data in the second half?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [37]

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So Ernest speaking for the Yuyuan partnership. No, we are in the organization phase. So it's a telecommunication between the 2 companies, setting the staffing committee and exchanging the information. We -- remember, well, 30 days to transfer the information for recurring R&D. So no adverse impact for the moment. The -- on the administrative part, I would say, and the organizational part of study. Your second question, was it about finance comparing '19 versus '20?

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Vasiliana Vireen Moussatos, Wedbush Securities Inc., Research Division - MD of Equity Research [38]

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For R&D?

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Timothy M. Adams, ObsEva SA - CFO [39]

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Liana, it's Tim. So on R&D, overall, in 2020, you'll see R&D spend go down, of course, because of nolasiban. When you see the financial statements filed later today, you'll see the breakout of the third-party spend with our partners for the trials. Nolasiban in 2019 was approximately $17 million, and that will be a very small number in 2020, as we continue to follow the patients from the previous trials.

For linzagolix in 022, those numbers in 2020 will be approximately the same as what you saw in 2019. But again, the overall savings in R&D is coming out of nolasiban, which will be down substantially year-over-year.

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [40]

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And your last question regarding OBE022. So this is obviously a proof of concept. So anything regarding slowing down labor, dealing birth is relevant. We have defined one endpoint, which is the -- a proportion of patient would not deliver, 7 days after treatment initiation. You remember that OBE022 is given for 7 days. And the study has been based on some power to detect a difference of 15% between a placebo plus atosiban versus atosiban plus OBE022 in the proportion of patients not delivering on day 7 after treatment initiation.

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Operator [41]

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Our next question comes from Ram Selvaraju with H.C. Wainwright.

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Raghuram Selvaraju, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [42]

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Can you hear me?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [43]

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Yes.

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Raghuram Selvaraju, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [44]

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So I wanted to start with some questions, regarding the strategic discussions around a potential partnership. Firstly, could you give us a sense of what you are prioritizing as you sift through potential deal structures, and whether that's on the level of upfront payment, size of commercial organization, familiarity with women's health. What's most important to you, as you look for the best possible partner on linzagolix?

Secondly, I want to ask whether you expect to have any kind of active role in the U.S. commercialization efforts, assuming you obtain a partner and that partner would be taking primary responsibility. And lastly, if there are any territories specifically, which are particularly important for you to maintain commercial control of the product? And if so, why?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [45]

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Okay. Thank you, Ram. So clearly, I think a criteria, which is going to be important for us is to have a company, which is having a sales force on -- in the women's health and the track record on that, that's for sure. Remember, we say publicly that our primary objective is to have a partner for the United States, which is the largest market, but also a market which is demanding in terms of investment to compete and optimize the commercial opportunity. I don't think we can comment on the future, on the potential partnership. We do not intend up yearly to keep commercial rights or contribution in the United States. But everything, obviously, can be discussed in the terms of a specific structure, but that's not our initial intention. And for your last question, I think we have to be opportunistic here. And I don't see there is a specific region where we want to keep the right for, at any price. Clearly, we are a European company. And so basically staying in Europe, and that's our closest market. But again, I think, we need to be opportunistic with -- I repeat, priority is to have a partnership for U.S. commercialization.

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Raghuram Selvaraju, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [46]

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Okay. And then just a couple of other quick items. I think this next one is probably for Wim. I was wondering if you could comment on the commercial experience so far with GnRH receptor antagonist, notably of course, Orilissa. And what kind of learnings you have managed to extract from that experience, such as it is, and to extent you can potentially incorporate this into the pre-commercial planning, as it were for linzagolix. In particular, I was interested in your views on challenges and opportunities with regard to keeping patients on GnRH receptor antagonist for prolonged periods of time? And what are some of the barriers that are typically encountered with respect to this? And how the picture is evolving for a drug like Orilissa? And to What extent that could potentially be applicable to linzagolix as well?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [47]

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Wim?

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Wim Souverijns, ObsEva SA - Chief Commercial Officer [48]

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Yes, Ram. Very good question. I think, the first answer, which we already kind of provided in previous calls, that there are a few things that have kind of led to the less than fabulous uptake of Orilissa in the market. I think, the pricing is a very important one. I mean there was a very high price set for Orilissa, which is unexpected, unexpected by us, competitors in the market as well. And it has created significant backlash, particularly with OB/GYN and who are not used and don't have time to get coverage for their patients. So if you have had 3 patients coming into the office, when you think they should get the drug. And then you can't get coverage for them, we kind of give up on them. So that, I think, is a really key strategic decision they made upfront that has hindered or has challenge their uptake. The interesting thing, what we learned from our ad board last week is, though, from a physician's perspective. And I think that answers your question on the long-term use of the GnRH antagonist. If you remember, we have a slide that outlines the PK profile of the different GnRH antagonist. And as you probably remember, for elagolix, there's a very short half-life.

Now elagolix launched recent studies without having add-back in the label. So they had a monotherapy, a lower dose or a higher dose, BID, for different patients. And the issue they have is, that because the short half-life, patient see fluctuation in the course of the day. And there's a lot of -- there -- the physicians were quite as -- and Beth can speak better about this in a second, but physicians didn't feel that the particular PK profile, the elagolix, lend itself to get a good experience for patients and a long-term use of the drug. And so in that -- my perspective, we have a very different profile. We are having a drug with the ideal PK half-life of 12, 13 hours, which allows it to have a very comfortable once-a-day dosing without -- with consistent exposure of the drug situation. So symptoms are not coming back. We heard from the subdivision saying, if a patient misses a pill on Orilissa, they see the symptoms right away, okay? So it's -- this -- that profile is not ideal for a long-term use of the drug. But Beth, maybe if you can add to it?

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [49]

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I think you've covered it pretty well, Wim. And so that's I agree with that, that was the feedback.

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Raghuram Selvaraju, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [50]

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Okay. And then that's very helpful. And then, Liz, I had two quick questions for you. One is with respect...

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [51]

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Can I just one -- I'm sorry, I just wanted to add a little bit to what Wim has said also. The other thing that we heard loud and clear from the advisers is certainly the things that Wim covered already. And in terms of the issues with prior off and all that, but as an OB/GYN and myself, I can tell you is it's just not going to happen in that tough physician community. The other thing that we heard that was really clear was there's a lot of confusion out there by doctors. In fact, a couple of the advisers said, I get calls every single day from general GYNs out there in the field. They just -- they're just uncertain and they just don't quite know how they're -- what they're supposed to do with elagolix low, high, what are we supposed to do? What that tells us and women's already been thinking about this, and he's already said this himself, messages have to be crystal clear, right? We got to really direct these doctors so that they understand. I think that's definitely been an issue on what we heard from the advisers.

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Raghuram Selvaraju, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [52]

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Okay. That's also very helpful color as well. The medical questions that I wanted to address to you is are the following. Firstly, you've mentioned a couple of times. The notable differences in baseline characteristics of the population enrolled into PRIMROSE 1 versus PRIMROSE 2. I was wondering if this would lead us to have differential expectations regarding specifically placebo responder rate. Or if -- as you previously had indicated for PRIMROSE 2, you anticipate a placebo responder rate in PRIMROSE 1 that is similar to that of PRIMROSE 2?

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [53]

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So yes. And the populations are indeed different, as you've said, and we've described that. That said, I don't see a direct relationship necessarily between the population and what we might expect around the placebo rate. And this was actually a topic that was discussed with the advisory board as well, that I think is really important. So I'm glad you brought it up. What the advisers found interestingly enough is, they felt pretty much uniformly that the placebo rate that we observed in our trial of 29.4 is more expected than less expected in a population such as this, anything where you're dealing with some subjective symptoms, including pain and things like that. And so they were not in any way surprised by our results. As well, they also confirmed, as we already knew that the elagolix trials and others were actually -- we've said this, that they were actually powered on expectation for a placebo response of 30. That was the expectation going into the -- certainly, the elagolix fibroids trials. So if anything, they were more surprised by the placebo rates in those trials as compared to ours. And then lastly, from a clinical perspective, they agreed with us, in terms of -- clinicians do not look at this. It's completely irrelevant for a clinician who's thinking about a drug and its response rate. So they pointed to our efficacy and said, that's what we really -- should be focusing on.

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Raghuram Selvaraju, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [54]

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And to that point, I had what maybe a naive question here. But given the results seen so far for linzagolix, specifically on amenorrhea. I was wondering, if there is the possibility of applying linzagolix in the distinct patient population of those suffering from menorrhagia? And if you could maybe walk us through some of the reasons why menorrhagia develops? And if there are subpopulations, sub buckets as it were, of patients who suffer from this condition, heavy menstrual bleeding, which may not necessarily be to uterine fibroids per se, where linzagolix might potentially be helpful? Or if this is just not an area where the drug would be applicable at all?

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [55]

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Yes, that's very interesting. We're hitting on a lot of topics that came up at the advisory board. One of the things we did at the latter part of the meeting was we opened the floor really to the advisers. We said, look, what else do you -- what else are you interested in from a clinical perspective? What other things could we be looking at? And that was definitely one of the items that, heavy menstrual bleeding in women who don't necessarily have a structural problem in the uterus, such as uterine fibroids.

So yes, it is of interest to us. We certainly have no plans to explore anything from a clinical trial perspective immediately, but it is absolutely something that we're interested in. There is definitely a population of patients out there who have "unexplained" heavy menstrual periods. So it is something we certainly would consider exploring, and no reason to believe that linzagolix would not be effective in that diagnosis.

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [56]

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Yes. And Ernest, I would like to add, Ram, that clearly control of bleeding by GnRH antagonist is mediated to modulation of estrogen and progesterone. And therefore, there is nothing which is strictly related to the change of fibroids volume, for example. So your comment is absolutely pertinent. And as Elizabeth just mentioned, that certainly a point of interest for the practicing gynecologist and the potential additional indication.

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Operator [57]

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And we have a question from Chang Liu with Jefferies.

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Chang Liu, Jefferies LLC, Research Division - Equity Associate [58]

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This is Chang for Biren. I have 2 questions. First one is about linzagolix. So you've mentioned before that, for the trial, vitamin D and calcium are specifically not allowed by FDA, but have been used in other trials. So do you have a sense like what is the impact of those usage in other drugs? And what are your expectation, like moving forward in the real world, when patients are actually using linzagolix with those supplements, in your patient? And the second question is about OBE022. So for that one, have you talked with FDA, in terms of the regulatory path forward? Do they require other like a Phase III trial? Or what kind of discussion you had so far?

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [59]

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So let me answer the second question. And then Elizabeth will comment on the first question. No, we have not yet talked to the FDA. This is really a proof of concept. It's a new mechanism of action in a combination with atosiban in Europe. And based on the data, then we'd enter discussion with the authorities. Elizabeth, I think there was about 2/3 of patients in the EDELWEISS endometriosis trial, which we see in vitamin D and calcium and there is some indication and impact on the FDA documents?

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Elizabeth Ijeoma Onyemelukwe Garner, ObsEva SA - Chief Medical Officer [60]

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Yes. And those at even -- an even higher proportion that use calcium and/or vitamin D. So either one or both. I think it was more in the closer to the 80%, 83%, 86% or so. And indeed, there was an analysis done. Keep in mind, it was not prespecified, right? So it was the post-hoc analysis. And also keep in mind, patients are not randomized, right, to take vitamin D or not. They -- generally, the vast majority of patients did use it. But there was a clear evidence of an improvement in BMD loss in the lumbar spine is what FDA specifically looked at. They saw probably around 0.5%, 0.6% difference. So if you think about our trials and things about the 100-milligram arm, we're looking at, at most, right now, about a 2% BMD loss. Subtract half of that 0.5%, you start to get into ranges that are well within -- especially given the population, well within what one would expect. What FDA said to that is that they certainly seem to believe that there was an effect. But obviously, it was limited because it was a post-hoc analysis. But I would say the FDA regulators certainly know that vitamin D and calcium have an effect, which is, I think why they ask us specifically not to use it in our fibroids studies, right? They wanted to see sort of worst-case scenario, what happens with linzagolix, when those supplements are not added.

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Operator [61]

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And I'm showing no further questions at this time. I'd like to turn the call back to Ernest for closing comments.

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Ernest Loumaye, ObsEva SA - Co-Founder, CEO & Director [62]

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Thank you. So clearly, 2019 was an important year for us at ObsEva and 2020 will bring some very important Phase III clinical data that will mark further progression towards commercializing therapies that address this significant unmet needs that millions of women face every day. And I would like to stress that at the time where most of the pharma companies have walked away of human trials, we are really committed to continue developing new drug for those patients. We, therefore, look forward to providing our next update in May with Q1 '20 financial results, and I would like now to thank you, and this ends our call. Thank you very much.

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Operator [63]

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Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.

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Timothy M. Adams, ObsEva SA - CFO [64]

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All right.