Radius Recycling Inc (RDUS) 2015 Q2 法說會逐字稿

Good day, everyone, and welcome to the Radius Health second-quarter 2015 earnings conference call. Today's call is being recorded. At this time, I would like to turn the conference over to Barbara Ryan. Please go ahead.

Thank you Eugenia. Welcome and thank you to those of you joining us on the line and on the webcast this morning for a review of Radius Health's second-quarter 2015 financial and operating results. I'm Barbara Ryan, Radius Health's Investor Relations officer, and with me this morning to discuss the results and update you on our progress are Robert Ward, President and Chief Executive Officer, and Nick Harvey, our Chief Financial Officer.

Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factors section in our most recent quarterly report on Form 10-Q filed with the Securities and Exchange Commission and our other reports filed with the SEC. Any forward-looking statements represent our views as of today, August 6, 2015, only.

A replay of this call will be available on the Company's website, www.RadiusPharm.com following this call. You can find the dial-in information for the replay in today's press release as well as on the Company's website.

I will now turn the call over to Robert Ward, President and Chief Executive Officer of Radius Health.

Thank you Barbara, and thank you to everyone who has joined us on our conference call and audio webcast this morning.

The second quarter of 2015 included several key accomplishments for Radius Health. We completed our first full year as a public company, we announced the results from the ACTIVExtend trial, shared important new data on RAD1901, and recently completed a follow-on offering that provides a solid financial foundation to prepare for our evolution from a development stage to a commercial biotechnology company.

On June 5 of this year, we celebrated the one year anniversary of Radius Health's initial public offering, and we are proud to be the number one performing IPO over the 12-month period in total shareholder returns. We believe that this positive performance reflects the substantial progress we've made in our pipeline and in building our company. Our recent follow-on offering has expanded our investor base and we would like to thank our shareholders for their support that has enabled us to advance the Radius Health portfolio.

As most of you know, also in June of this year, we released additional data from our ACTIVE trial as well as the topline data from the first six months of ACTIVExtend. The ACTIVExtend trial is the 24-month open label extension in which patients from the abaloparatide and placebo-treated groups of ACTIVE trial were replaced on alendronate therapy for osteoporosis management. The ACTIVExtend six-month study results exceeded our expectations. The group previously treated with abaloparatide had no additional new vertebral fractures during the first six months of the ACTIVExtend trial.

Please remember that from the start of the ACTIVE study, the abaloparatide treated patients showed a statistically significant 87% reduction in new vertebral fractures, the highest reduction ever reported in an osteoporosis trial, and highly significant reductions in non-vertebral fractures, clinical fractures, and major osteoporotic fractures as compared to placebo. We believe that these results support our view that abaloparatide has the potential to represent a new treatment paradigm for patients at high risk of an osteoporotic fracture. With these key Phase III trials now completed, we are focused on submitting the full 25-month results for regulatory review with EMEA and FDA by year-end.

As we shared previously, our transdermal abaloparatide optimization activities have progressed throughout the quarter and we expect to initiate the clinical evaluation of optimized transdermal patch with the goal of achieving comparability to abaloparatide sub-Q later this year.

We continue to add key talent to Radius to both support our registrational submissions as well as building our commercial capabilities. Just last week, Dr. Lorraine Fitzpatrick, a globally recognized expert in the field of osteoporosis and oncology, joined Radius as our Chief Medical Officer from GlaxoSmithKline. At GSK, she led the global development group for denosumab.

During the quarter, we were very pleased to have four abstracts for abaloparatide accepted for presentation at the American Society of Bone Mineral Research this upcoming October. Dr. Felicia Cosman, a professor of clinical medicine at Columbia University in New York, will provide a plenary oral presentation of the combined Phase III results from both the ACTIVE and ACTIVExtend trials.

Also, Dr. Lorraine Fitzpatrick from Radius Health will make an oral presentation of the effects of abaloparatide on major osteoporotic fractures. Two additional posters will be presented, the results from the abaloparatide responder analysis and for those of you who are following our progress with transdermal, we will have an internal result on the transdermal development program.

Turning attention now to RAD1901, this is our selective estrogen receptor degrader, or SERD, which we are evaluating in postmenopausal women with advanced estrogen receptor positive and HER2-negative metastatic breast cancer. On July 15, we announced early but very promising preclinical data showing that RAD1901 in combination with Pfizer's palbociclib, a CDK4/6 inhibitor, or with Novartis' Afinitor, an mTOR inhibitor, was effective in shrinking both resistant or wild type patient dry tumors. In the patient dry xenograft breast cancer models, the combinations with RAD1901 showed greater antitumor activity than was shown with any of the three agents alone. This combination use data will be very important to us as we evaluate the study design for continued development of RAD1901 in metastatic breast cancer.

We are continuing to screen and enroll patients in our Phase I metastatic breast cancer dose escalation study. Our objective with this study is to identify the most promising dose of RAD1901 to take forward into Phase II development. In the quarter, we submitted abstracts for the San Antonio Breast Cancer Symposium in December, and will update you on these presentations as information becomes available from the symposium organizers over the summer or early fall.

We have also expanded our capabilities in oncology. On July 20, Dr. Debasish Roychowdhury joined our Board of Directors. Previously, Debasish was Ceragon's acting Chief Medical Officer and led the development activities for their SERD program prior to the company's acquisition by Roche. Also during the quarter, we formed an oncology clinical advisory board to support us as we plan the future development of RAD1901.

As we previously reported, low dose RAD1901 demonstrated clinical future reductions in the frequency and severity of moderate and severe hot flashes in a Phase II proof concept study. By year-end of 2015, we intend to commence a Phase IIb clinical trial for basal motor symptoms. Recall this is an area of high unmet medical need with a significant interest in potential of nonhormonal therapeutic options.

Now I'd like to turn the call over to Nick Harvey, our Chief Financial Officer, who will discuss our second-quarter results and provide an update on our balance sheet.

Thank you Bob. Our cash, cash equivalents and marketable securities balance as of June 30, 2015 was $224 million. Subsequent to the end of the quarter on July 28, Radius raised approximately $323.8 million of net proceeds in the follow-on public offering of our common stock. On August 4, 2015, we repaid all amounts owed under our loan and security agreement with Solar Capital, Solar Capital and Oxford Finance. After consideration of the relevant fees required under the loan agreement, the total payment amounted to approximately $26.5 million. This prepayment results in significant savings to Radius Health over the expected cost of the full life of the loan.

We are updating our guidance on our cash burn and expect that our cash, cash equivalents and marketable securities as of June 30, 2015, together with the proceeds of the July offering, will carry us into 2018 and are sufficient to fund our development plans, US commercial scale-up and other operational activities prior to the consideration of revenue from the potential future sales of any of our investigational products.

I'll turn the call back to Bob.

Thank you Nick. Before we open the line for questions, I would like to summarize our upcoming milestones for the remainder of the year.

Having now both completed and reported the positive topline results for the Phase III ACTIVE trial and the six months of the ACTIVExtend trial, we are on track to submit an MAA in the EU and an NDA to the FDA for the investigational drug abaloparatide sub-Q by the end of this year. We are continuing our partnering discussions and are on track to have entered into a collaboration to enable global commercialization by the time of launch. We plan to initiate clinical evaluation of the optimized abaloparatide transdermal patch by year-end.

For RAD1901, we will share additional information with you later this year on our ongoing Phase I trial in metastatic breast cancer and are initiating an additional Phase I clinical trial in the European Union as we move through the third and fourth quarter. We expect to begin a Phase II trial for low-dose RAD1901 for basal motor symptoms by year-end as well.

Next week, we will be presenting at the Canaccord Genuity Growth Conference in Boston on August 12. As I said earlier, we are extremely excited to have multiple presentations of ASBMR this year, including Dr. Cosman's plenary presentation of the 25-month ACTIVE and ACTIVExtend trial design data.

So thank you for your continued interest in Radius. We felt that the quarter was a successful and exciting one.

And we are certainly happy now to entertain your questions. And operator, before we open up the call, I'd like now to ask our colleagues to join for the Q&A period. Greg Williams, our Chief Development Officer is online, Gary Hattersley, our Chief Scientific Officer, Dinesh Purandare, who leads our efforts in oncology, as well as Brent Hatzis-Schoch, our General Counsel, has joined us for the call today. So operator, I think we are now prepared to take questions.

(Operator Instructions). Ying Huang, Bank of America Merrill Lynch.

Hi, good morning. Thanks for taking my questions. First of all, I know the exploratory analysis you conducted against [Otera] showed a significant reduction in major osteoporotic fractures. I assume that's not prespecified. And do you think it's likely to be written in the label or not when the FDA approves abaloparatide?

And then secondly, on RAD1901, obviously it's a bit too early, but do you guys have any plans to think which combination regimen you would rather cast in the Phase II clinical trial for that indication in metastatic breast cancer? Thank you.

Absolutely. Terrific questions. You know, as we think about the regulatory process, we have not yet submitted our NDA or MAA, and so the questions about labeling typically come up during the review cycle. So we have not yet engaged with the agency on the labeling around abaloparatide.

When we look at the European labeling for Prolia, or denosumab, you will see that the European labeling includes a detailed description of different categories of fractures, including of course major osteoporotic fractures. The US labeling traditionally has not been as detailed as the European labeling approach, so we believe that, as we go through the review process, we will be able to provide greater details for you as we learn more from our interactions with the agency.

With regards to combinations for RAD1901, we are very excited about the data which shows the preclinical models where in both tumor types that were resistant to previous drug exposure, as well as novel wild type tumors that the accommodation showed such unexpected additive or synergistic effects. Dinesh, could you share with us, as we think about the development for RAD1901, how would we think about combinations? Why do combinations matter for RAD1901?

Sure. So in the field of breast cancer, it is extremely crucial to look at tumors that have either failed on tamoxifen or are resistant to tamoxifen as well as tumors that are resistant or progressed on (technical difficulty) brand. The recently announced data shows that the synergistic combination with RAD1901 with either palbociclib or mTOR looks extremely promising. So this opens the door for us to evaluate a variety of these combinations as well as looking at other types of areas like a mutant population. So we would be looking at multiple ways to move forward, but extremely excited about the data that allows us to move in this direction very quickly.

I do want to answer one other important element about why data around major osteoporotic fractures matters. As you mentioned, we showed that, compared to teriparatide in our trial, there was a substantial reduction in major osteoporotic fractures for abaloparatide that was statistically significantly favorable as compared to the teriparatide group.

From a payor perspective in Europe, where often reference based pricing is so important, one of the considerations is whether a new agent shows equivalent therapeutic benefit, improvements in therapeutic benefits, or reduced therapeutic benefits. For those that are equivalent or reduced, realistically, reference base pricing caps the pricing opportunity. For agents that demonstrate superior activity, that's when reference-based pricing plays less of a role in the setting of the price as it comes to market. So, we believe that this difference on major osteoporotic fracture or whether it's a difference on risk fractures or difference in B&B, difference in hypercalcemia, is two different considerations. One is through the regulatory process, how that's handled in labeling. The second is for a payor as they look at the trial, which is very unusual, having the market-leading drug in the Phase III program in a trial that's larger for the market-leading drug than the original approval trial. And in that trial, a payor can see that the number needed to treat is substantially reduced with abaloparatide as compared to the teriparatide arm. And so from an economic perspective, that is for the healthcare dollar, a larger number of patients respond to abaloparatide.

So we think there's really two different conversations to be important as we go through the coming year, the regulatory conversation but also as payors look to ask the question, what's the health economic value, we think the data are very important as well.

Thanks Bob for that detailed answer. If you don't mind, just one follow-up. Can you update us where your CMC work is being done here and what's the status with CMC before the FDA (inaudible)? Thanks.

Sure. We have a global supply chain. Dr. Williams, do you want remind us how the supply chain is organized and where we are in terms of our track for both MAA and NDA submission?

Sure, thank you Bob. So as is documented in our various filings, we are working with Lonza to produce our drug substance. We are working with Vetter to produce drug product in the form of filled cartridges and also in the form of disposable pen supplier [Afixumed]. These are all well-known manufacturers who have been through numerous audits with the agency. We've completed the validation of our product manufacturer, our API manufacturing. We are in really very good shape as we move forward towards our MAA and NDA applications.

And then additionally for transdermal patch, of course our key partnership is with 3M. And I'm going to sub it.

Jeff Chen, Cowen & Co.

Hi. Good morning. Thank you for taking my questions. So the first one for Bob, maybe could you discuss in terms of are there any chances of expedited review process in the US or EU for abaloparatide injectable?

That's a very good question because when you think about the programs that exist, there's multiple paths to achieve either rolling submission or accelerated review. In our base case, we build the business model around a standard review period. As we look at programs that are suitable for abaloparatide that we believe the regulatory agency will have traction with us, we apply to be considered for those programs. So recently, we have mentioned that we had applied for the breakthrough designation.

Now, in the field of osteoporosis, there's never been a drug that's been given a breakthrough designation but we thought it was because of the emerging clinical profile that abaloparatide would be a drug that be a drug that would be likely to meet those standards. So originally, at the end of Phase II with only DMD data we applied, and the HC indicated that it's fracture data that's the basis of an evaluation. And so we shared data around the primary and secondary endpoint from the ACTIVE trial. The agency said that on their review of the primary endpoint, they were looking for drugs with non-overlapping confidence intervals as a part of their calculations. Based on the primary endpoint, they rolled back that they were not willing to grant a breakthrough designation.

Now there are other agency programs that we believe we are eligible for, and as we go through the regulatory process, we will engage with the regulators to apply for each of the possibilities for that. Now if we do achieve a successful either rolling submission or early or priority review, of course we will let everyone know.

Thank you. That's very helpful. And maybe if you can, just give us some insight on the patch development pathway. So you will start a clinical evaluation. What would come after that trial?

That's a terrific question. We think patch technology allows physicians who have not previously used anabolic therapies because they're injectable drugs to consider how to add anabolic therapy into their practice. For other physicians who today use injectable anabolics, we believe it's the clinical data that really is the basis of decision-making.

Remember, in our Phase III trial, we have shown that the physiologic response to abaloparatide is different than the response to other peptides. So as we think about competition in the space, it's about both the peptide as well as the technology platform. But Dr. Hattersley, could you remind us of what's been accomplished to date, where we are today and what's next with the Radius transdermal program?

Of course. So back in 2014, we previously reported the results from a six-month Phase IIb/d study in which approximately 250 women, postmenopausal women, with osteoporosis received administration of our transdermal patch. We were very encouraged to see dose-dependent increases in BMD in both the spine, the hip and the femoral neck. Our current plan is to build on that extensive clinical experience with the current -- optimization of our current patch.

So Dr. Hattersley, we decided, based on those very promising results, to optimize the patch. We didn't take the patch forward because there were differences in BMD, differences in PK and differences of biomarkers. Why -- and we've gone down optimization path. What are the regulatory implications of how to get a patch that doesn't match sub-Q?

Great question. So based upon those parameters not matching, it would raise questions about bone quality, and therefore could potentially require a fracture study to be conducted. Our current strategy is to optimize the transdermal patch so that we can achieve pharmacokinetic equivalence to the sub-Q injection, and therefore allow a more simple glitching strategy to sub-Q. So our current efforts are all focused on optimizing the transdermal patch so we can achieve bioequivalence to sub-Q.

Our goal is that for a physician who would select injectable abaloparatide or for a physician who might select transdermal abaloparatide, we would like to be in a position where they'd have confidence that the clinical response is the same regardless of route of administration. We believe there are some patients for whom injectable therapies are actually quite acceptable. If you look at the market today, the market-leading products in osteoporosis, as we speak, are injectables. If we look at the management of rheumatoid arthritis, the market-leading products are injectables. We do think the patch will extend the market, but we think it's a complementary product to an injectable. Does that answer your question?

Yes. And obviously the option between the patch and the injectable is definitely a nice advantage. Just in terms of -- I know the competitors have to carry out a Phase III trial to compare their products. Is that also the pathway for the patch here?

Well, remember, when we conducted our FRACTURE trial, that was a major undertaking. Took us about three years, 30 sites across 10 countries, allowing comparisons of our subcutaneous product to both placebo and the active comparator arm of teriparatide. If we were taking forward a patch that required a FRACTURE trial, it would be a task to repeat that size of undertaking with the patch. With a patch that is comparable to the sub-Q, we believe that there's other regulatory paths that would be much more applicable and well trod that may not require a fracture drop. Dr. Williams, could you just remind us, why does bioequivalence open a different regulatory path?

Sure Bob. So from the perspective of bioequivalence, if we have clinical pharmacokinetics, it would be expected that we would have comparable biomarkers, we would have comparable effects on bone, and we would be in essence validating the fracture reduction associated with the transdermal product relative to the sub-Q for which we've already run an extensive fracture program. So the work that we are doing in optimizing the transdermal really fits very well with this alternative pathway.

Just to remind you of where we are today, there's been substantial progress in the optimization work. We will be back into humans to replicate the data we generated in the primate model, and then we'd move forward with a more formal trial. At the end of that program, we will be engaging with the agency to discuss with them directly all of the questions that you've asked here on the phone today. So as is always the case, until we've had that regulatory action, we will seek additional feedback from the FDA, but we shared with you today what is our understanding of what the landscape should look like.

That super helpful. Thanks very much. If I may, just one more on RAD1901. In terms of the update at San Antonio, can you just give us a little additional color on how many patients might we see data from as well as what type of data might we be able to get a first look at about the drug? Thanks.

Remember, right after ASCO, the San Antonio abstracts were submitted, and the symposia has not yet made the determinations on what's been accepted. So as soon as we know what's accepted, we will be back with greater information. Dinesh, when you think about progress in the Phase I, our objective is to identify a dose to take into Phase II.

Yes.

If the drug is tolerable, so you move through all of the cohorts, then it takes longer to finish the Phase I than if the drug has toxicity and you immediately hit the ceiling. Could you just remind us in the Phase I study design how does the three by three design work? I know you start at 200 (multiple speakers) the trial potentially.

Thank you Bob. So the three by three design that we have for RAD1901 in oncology starts at a dose of 200, goes to 400, 600, 800, and 1,000, and then grows seven cohort of patients, three patients in each cohort, and they have to stay on treatment for approximately 28 days to a month. And that's how we will be making progress in enrolling -- continuing to enroll patients in a variety of cohorts. So as per Bob's point earlier, depending on what cohorts we enroll, and that trial is enrolling well, we should be coming out with the data pretty soon.

So we have completed a 52 healthy volunteer maximum tolerated dose study that went from 200 milligrams to 1,000 milligrams. We anticipate that, since that study is completed, that we will have the data in September and at that time will make the tolerability profile available.

Remember, our goal to identifying the Phase I dose, anticipating that the drug is fully tolerated and we run through all of the cohorts, that's likely to be an early 2016 event. If there were toxicity that limited it, then there would be an earlier identification. Based on the healthy volunteer study, between 200 milligrams and 1,000 milligrams, we did not hit a formal dose limiting toxicity.

Thanks again for taking my questions.

Eun Yang, Jefferies.

This is Carmen on for Eun. Thanks for taking the question. So, following the ACTIVExtend 25-month data and exploratory analysis of ACTIVE for abaloparatide, do you think you will likely be able to price (technical difficulty) at some premium to (technical difficulty)

When you think about the unmet medical need in osteoporosis, in the US alone, it is estimated that each year there are 2 million patients that have an osteoporotic fracture at any site. We estimate that, in the current year, 50,000 US-based individuals will be treated with Forteo or less. So if you said in the current market, the unmet medical need is substantially greater than the number of patients that are using anabolic therapy today.

So when picking a price, one of the questions that we want to make sure we think very thoughtfully about is the health economic value for abaloparatide. If we are payors and we are making a decision on how to invest our healthcare dollar, picking a product that offers the greatest benefit for the highest unmet medical need patients is really what the payors are being asked to do. So when we pick a price that allows a payor to say we understand the health economic value of abaloparatide, we think of abaloparatide as health economically justified to treat this much larger number of patients with high unmet medical need. That would be an important consideration in our pricing.

We do think that based on traditional models as we look at comparisons, there's reasons we believe that the improvements in clinical efficacy would suggest that premium pricing could be a path to go down on, but remember there are such a large number of patients today who are not receiving therapy, we will want to make sure that access is kept in mind so that patients who are in need of therapy have the ability to access what we hope to be an important contribution to the field.

Great. Thank you so much. And then one more on abaloparatide. (technical difficulty) do you think a majority of sales will likely come from anabolic market expansion or market share gain from Forteo?

That's a terrific question. When you think of the market, since it's a two-year treatment period, typically the patients turn over, so to speak, over a short period of time. Forteo launched over a decade ago, so if you said the physicians who today routinely use Forteo made their decision to adopt Forteo some time ago, and so that market is relatively stable, but currently represents a collection of physicians who understand anabolic therapy, we would anticipate would be the early adopters.

We talked a month ago about incident fractures, many of these patients are presenting at hospitals who are managed by orthopedic surgeons or managed by fracture liaison services. Today, we estimate that represents about 4% of the use of teriparatide. We think that there is a substantial unmet medical need in that area. And so as we would go forward, we think that success with abaloparatide is based on two things: for physicians who use anabolic therapy today, ensuring that they understand the reasons why abaloparatide may be an effective choice for their patients; and for physicians who are managing osteoporotic fracture patients but have not adopted anabolic therapy. We think, for those physicians, it's a different decision path. So we really see it as two markets that will evolve, the market that represents the "as is" use of anabolic therapy, and the much larger opportunity for addressing the needs of patients who today are not receiving therapy.

Okay, great. And just one more on RAD1901 if I could. It looks like, on tolerability, RAD1901 could potentially be better than Roche's ARN-810 in terms of diarrhea. Do you expect there will also be some differentiation on efficacy?

That's a terrific question. When we think of the preclinical data such as the data we just showed, we believe there is an emerging profile that suggests RAD1901 looks quite different than other agents that individuals have been studying previously. And you are right. Tolerability is a very important part, particularly as we think about combinations. But this question of tumor regression versus tumor stasis, what is the profile that would emerge from RAD1901?

Now, preclinically, Dinesh, we've done a number of preclinical studies comparing RAD1901 to tamoxifen and fulvestrant. Could you walk us through how do the two agents compare as we look at --

Sure. In a variety of preclinical settings that we have done, RAD1901 compares extremely well versus tamoxifen and for this time in regressing the tumors. In particular, I think that there is an emerging area of the resistant tumors from this trend as well. And as you would expect, while this trend doesn't do well over there and whereas RAD1901 shows marked tumor inhibition.

So as we think about tumor resistance, these are the estrogen sensitive receptor mutants, or ESR-1 mutations.

Mutations.

The receptor itself actually changes the amino acids so that tamoxifen [Vasex] can no longer bond or block. Gary, I know that we've done some additional modeling. Do you have reasons or data that suggests that those emerging resistant receptors will or will not interact with RAD1901?

Yes, absolutely. I think the preclinical data that is emerging around estrogen receptor mutations so far as is very encouraging, particularly in breast cancer models that are resistant to

fulvestrant and tamoxifen. We're seeing very good efficacy with 1901. So I think that it's very, very encouraging.

Thank you.

Mara Goldstein, Cantor Fitzgerald.

Thanks very much for taking the question. Just to go back to the expectation around possible data at San Antonio Breast Cancer Symposium, maybe you can just remind us, at ASCO, the number of patients and what we saw knowing and understanding that the San Antonio abstracts review and what might have been submitted at that time relative to when should you present data at San Antonio five months later, what we could expect in terms of number of cohorts and things like that?

Mara, remember, at ASCO, we had submitted a poster that was in the clinical design section. It really talked about the design of the Phase I study. We have not been in a practice of updating enrollment. As you know, there's a high degree of competition in this space. We've expanded exponentially the number of sites enrolling patients in the trial, and we are quite comfortable that we are on track for our key objective, which is to identify the dose going forward. We will find out from San Antonio the abstracts that have been accepted as we move through August and September, and as soon as we know, we will be back to share that information with the field.

Okay. And then just with respect to the optimization of the transdermal, what exactly would you be looking for in an interim result there?

Sure. Dr. Hattersley, do you want to talk about what is optimization? What are the types of studies we do in primates?

Absolutely. As Bob described a little bit earlier, our strategy is to reach the patch to sub-Q based upon a bioequivalence. So we've recently reported results from primate clinic pharmacokinetic studies where we've optimized the patch that can achieve a profile that's comparable to the sub-Q injection. And so our next clinical study will be focused really on replicating those primate study results in which we take the optimized patch into -- back into the clinic and compare it to the sub-Q to assess whether comparability to sub-Q is able to be achieved.

And at ASBMR this year, we do have a poster that's been accepted with the transdermal program that we will focus on.

Okay. And just in terms of the scope of that in terms of what numbers we should be looking for, just so --

Are you thinking in terms of when we do the replicative study in humans, how many does it take to (multiple speakers)?

Yes, exactly. Thanks Bob.

We will start that activity this year. Remember, once we identify the patch, they have to be manufactured. So we are in the process now of preparing those patches. An important part is to make sure that we make enough patches so that when replicative study results are available, we're prepared to move forward with additional clinical studies. So the real time related event for us is very basic making the clinical supplies. The replicative study itself is relatively quick once started, and then after that, we will do a more formal study where one element will be to do a formal bioequivalence arm, but we anticipate at this time that we would also do a BMD and/or patient reported outcome studies along with that. So at the time we submit transdermal patch, physicians and patients would have an opportunity to share their experiences with the product prior to its submission for regulatory review.

Okay. And if I could just ask sort of a broader corporate question as it relates to the oncology effort. Clearly you've put a lot of increased manpower into that effort, and creating almost an organization within your organization around that. And I'm just wondering if maybe you can speak to or perhaps you can speak to the changes within the organization, what you're putting in place and what are the sort of major focal points of how to -- of what we can be looking at within oncology as a group within Radius.

Yes. So, if you think of what has happened with Radius, particularly now that we've completed our most recent offering, is it enables us to focus on developing an oncology pipeline. So RAD1901 is a very interesting molecule, and I think, as Dinesh had shared earlier, as we think about Phase II, there's a number of development options. So first, landing on the right dose, and then second, going to Phase II study that may be combinations, reasons to believe we could consider doing the adjuvant, it could be the potential to explore adjuvants. There's a number of branch points once you have that Phase II dose in hand.

Remember, in our pipeline, RAD140 is an IND-ready asset. It's a selective androgen receptor modulator. Right now, scientific literature suggests that there is a significant need in triple negative breast cancer and that selective androgen receptor modulators have the potential to be therapeutically useful. That's an area we would like to explore more continuously so that, as we digest our current clinical portfolio, that RAD140 then is able to march forward and move into the clinic. The timing of that really relates on the progress we make on the programs that we have on our plate today. So we want to make sure we have continuous product innovation, that we are able to scale the organization to ensure that the programs are fully supported, that teams are able to focus on these different therapeutic or product related applications, and then also to ensure that we have pipeline progress so that as we look at the company over time, we have early-stage programs, we have mid-stage programs and programs that advance into the final stage of review.

So if we looked across the portfolio today, we would look at abaloparatide sub-Q, having completed the major Phase III trials, now tracking towards MAA and NDA submission, and we think the line extension of transdermal patch as a follow-on in that same women's health footprint. A vasomotor would be another product that would launch into that same commercial footprint, so it gives us the ability to continue to innovate in a therapeutic area.

In oncology, 1901, as we explore its potential across breast cancer, we have the potential to come back and evaluate whether ovarian cancer or endometrial cancer are suitable for further expansion, as well as thinking about bringing RAD140 into clinical element as either a complement to 1901 or to explore a triple negative. So as we think about the Company, our goal is to stable innovation, building out a portfolio that matures in different timescales, so that the organization is able to leave both through the development phase but then also is now growing capability so that, as the Company comes closer to commercialization, we are prepared to launch commercialized products as well.

Okay, thank you. I'll step back into queue.

(Operator Instructions). John Newman, Canaccord.

Thanks for taking the question. The question is when would you make the decision as to whether or not you want to advance RAD1901 as a single agent or in combination? It seems like you are -- generated some interesting preclinical data for the combinations, but you also obviously have a Phase I study ongoing. I'm just wondering. When would you make the decision as to whether or not to take it forward in combination or take it forward as a single agent? Thanks.

Thanks John. 140 is a very exciting molecule. We saw in the press that Astellas had recently recognized the value of selective androgen receptor modulators. So remember they announced a commitment to this space. So as we think about the evolution of selective androgen receptor modulators, we think it's going to be a field that "starts to get hot" as we move through the next year or two.

So, Dr. Hattersley, I know it's early in our thinking. We haven't really talked much about 140 previously. As you think about combos or single agents, does it make sense to start with one of them as a first step?

Yes. I think the emerging information really reinforces the role of the androgen receptor in metastatic breast cancer not just in ER negative but also in ER positive metastatic breast cancer. So as Bob just described, there are some very interesting exciting opportunities as a monotherapy, but also the potential of combining RAD140 with another agent as a combo therapy is something that of course we are very interested in.

Remember John, as we talk about the literature suggesting that there's potential applications, we are in the process internally of now generating data that would be "our own data". As we share with you our thinking today, it is really based on what we see in the field and what's happening in the literature in general. As we make progress internally, of course we'll come back and share that information with you.

Great, thank you.

There are no more questions registered at this time.

Thank you very much Eugenia. We appreciate everyone's involvement in the call here today and will look forward to sharing with you next quarter the activities and events as they occur going forward. Thank you.

This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.