Merck & Co Inc (MRK) — Q1 2017 Earnings Call Transcript

Thanks, and welcome, everyone, to Acceleron's first quarter 2017 earnings conference call. The press release reporting our financial results, in addition to the presentation for today's webcast, are available on the investor's media page of the corporate website. In addition to our financial and operational results, we'll be reviewing highlights from our luspatercept Phase 2 presentation from the 14th International Symposium on MDS that took place over the weekend in Valencia, Spain. The full conference presentation is available in the science section of our website. Joining me in the room today are Habib Dable, our Chief Executive Officer; Matthew Sherman, our Chief Medical Officer; Kevin McLaughlin, our Chief Financial Officer and Chris Rovaldi, Senior Vice President, Operations and Program Management. As a reminder, we will be making forward-looking statements regarding our financial outlook in addition to regulatory and product development plans and research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent Form 10-K on file with the SEC. I would now like to return the call over to Habib Dable, our Chief Executive Officer.

Thank you, Todd. Good morning, everyone and thanks for joining us today. It's clearly an exciting time at Acceleron with recently provided program updates over the past few weeks and additional updates announced this morning. Based on faster than expected rates of patient recruitment in the MEDALIST and BELIEVE Phase 3 studies year-to-date at Celgene, our luspatercept collaboration partner recently announced that we expect full patient enrollment to be achieved this quarter versus our previous guidance of the second half of 2017. This should now put us in the position to report top line results from the Phase 3 trials by the middle of 2018. We at Celgene also announced that we plan to initiate a new Phase 3 trial with luspatercept in first-line lower risk MDS patients in early 2018. This decision is supported by results presented over the weekend at the MDS Symposium that Matt will be discussing later on this call. For the ACE-083 program, we announced plans to initiate a second Phase 2 trial in neurological disease called Charcot-Marie-Tooth disease, or CMT that causes muscle weakness in specific muscles. We expect this two-part Phase 2 study to begin in the middle of this year with the part one dose escalation results available in 2018. Our team recently hosted an educational webinar to discuss the background on CMT and our Phase 2 trial design. We were joined by a leading neuromuscular expert, Dr. David Walk, Associate Professor of Neurology and Director of the ALS and CMC Centers of Excellence at the University of Minnesota Medical Center. A reply of this event is available in the events and presentation section of the investor's media page on our corporate website. While we are working on ACE-083 trial start-up activities in CMT, enrollment and treatment are ongoing in the part one dose escalation stage of our Phase 2 trial in Facioscapulohumeral Muscular Dystrophy or FSHD. I'll now turn the call over to Matthew Sherman, our Chief Medical Officer, to review highlights from our luspatercept two presentations at the MDS from this past weekend.

Thanks Habib, hi, everyone. Our team just returned from the 14th International Symposium on MDS that was held in Valencia, Spain, from May 3 through May 6. There were two clinical luspatercept presentations at the conference. We had a Phase 2 PACE study update that was presented by Uwe Platzbecker from Dresden Germany, one of our principal investigators for the study. We also highlighted the poster presentation that discussed the PK/PD response relationship of luspatercept in MDS patients. The Phase 2 trial presentation focused on the lower risk MDS expansion cohort patients not eligible for our ongoing MEDALIST Phase 3 study. The new expansion cohort patients include erythropoiesis stimulating agent or ESA naïve patients where ring sideroblast positive with baseline erythropoietin levels below 200 and ring sideroblast negative patients with any baseline EPO level regardless of ESA experience. We refer to patients with these baseline features as first-line lower risk MDS patients. Before going into our data, I would like to provide some context by outlining results from two ESA Phase 3 studies presented in 2016. On the left side of the slide, we are showing the darbepoetin alpha Phase 3 study, primary outcome measure, the International Working Group's Hematologic Improvement in the response or IWG HI-E which is at least a 1.5 gram per deciliter increase in hemoglobin sustained for eight weeks. In this 147 patient Phase 3 trial, 14.7% or 11 out of 75 patients in the active arm met the primary endpoint. All 11 responders had baseline EPO levels below 100 and there were zero responders above 100 EPO levels at baseline. Only one of the 11 responders had a baseline transfusion burden. 27 out of 28 patients entered the study with a baseline transfusion burden did not meet the primary endpoint response. On the right side of the slide, we are viewing the Epoetin Alpha Phase 3 primary endpoint analysis. This study also used the IWG HI-E response criteria as the primary endpoint. In this 130 patient Phase 3 trial, 31.8% or 27 out of 85 patients in the active arm met the primary endpoint. This study stratified responders by baseline EPO levels above or below 200 with all 27 responders having baseline EPO levels below 200 and zero responders above 200. These results led to Epoetin Alpha's recent approval in France for the subset of lower risk patients with baseline EPO levels under 200. It is also important to note the low placebo response rates in each of these studies. On this slide we've broken down response rates in our luspatercept Phase 2 by ESA exposure with patients either having received prior ESA treatment or never received an ESA and are ESA naïve. When looking at the IWG HI-E response criteria, 51% of ESA naïve patients treated with luspatercept achieved this clinically meaningful response criteria; this is a similar response rate to patients who have had prior ESA treatment. On the right side of the slide, we are evaluating red blood cell or RBC transfusion dependence response which is derived as a period greater than or equal to eight weeks without receiving transfusions. 48% of ESA naïve patients treated with luspatercept achieved transfusion independence while 33% of prior ESA treated patients also achieved transfusion independence. The swimming chart on this slide shows patient response by duration of RBC transfusion independence for ESA naïve patients receiving luspatercept treatment. Each line represents a patient's treatment period. A solid blue section of the line identifies the transfusion-free period of at least eight weeks. RBC transfusion events are shown with red dots for each patient. The right-facing arrows at the end of some of the lines mean that treatment is still ongoing. The median duration of transfusion independence is 8.7 months with a range of two to 27 months. On this slide we are looking at luspatercept response rates in RS negative patients regardless of ESA experience stratified by baseline EPO levels. In the RS negative patients, 6 of the 14, or 43% of patients achieved the HI-E response; and 4 out of 7, or 57% achieved RBC transfusion independence. At baseline EPO levels above 500, RS negative patient response rates dropped significantly. Let me summarize the key takeaways from our Phase 2 update. We achieved high response rates in the lower risk EPO level bands where physicians currently use ESAs off-label, including both RS positive and negative patients. These results compare favorably to historical rates of response with ESA treatment. More specifically, in RS negative patients, response rates are high in patients with baseline EPO levels below 500. Luspatercept was generally well tolerated for patients on treatment up to and now exceeding 24 months of drug exposure. These updated Phase 2 results support the decision to expand luspatercept's clinical development into a first-line lower risk MDS Phase 3 trial in early 2018. I will now turn the call over to Kevin McLaughlin, our Chief Financial Officer, to run through the financials for the quarter.

Thanks, Matt. Our cash, cash equivalents and investments as of March 31, 2017, were $213.2 million. This compares to December 31, 2016 cash, cash equivalents and investments of $234.4 million. As a reminder, we believe that our existing cash, cash equivalents and investments will be sufficient to fund our projected operating requirements into the second half of 2019. Collaboration revenue for the first quarter was $3.7 million; the revenue is all from our Celgene partnership and is primarily due to cost-sharing revenue of $3.6 million related to expenses incurred by the company in support of our partnered programs. Total costs and expenses for the first quarter were $29.5 million; this includes R&D expenses of $21.7 million and G&A expenses of $7.8 million. Other income net for the first quarter was $500,000, primarily due to interest income. The company posted a net loss for the first quarter ended March 31, 2017 of $25.4 million. I will now turn the presentation back over to Habib for final remarks.

Thanks Kevin. So looking ahead we expect several key milestones over the next 12 to 18 months. For the luspatercept program, we expect to complete enrollment in both the MEDALIST Phase 3 trial in MDS and the BELIEVE Phase 3 trial in beta-thalassemia in the second quarter of 2017. In addition to our ongoing Phase 3 studies, we plan on initiating three clinical trials with luspatercept. In early 2018, we expect to initiate a Phase 3 trial in first-line lower risk MDS patients. Phase 3 trials in myelofibrosis and in non-transfusion dependent beta-thalassemia are planned to begin by year-end, and we're also expecting to report additional Phase 2 study results at medical conferences throughout the year. I would like to note that given the Phase 2 MDS update this last weekend at the MDS Symposium, our MDS presentation at E-HI next month will be about a two month update. We look forward to providing a larger update at ASH in December. Turning to ACE-083, we anticipate having initial data from the Part 1 dose escalation arm of the Phase 2 FSHD trial by late 2017. This update will include results from dose cohort 1. Our trial and CMC will start mid-year with Part 1 results expected in 2018. Moving to dalantercept in RCC, based on recently reaching this 82nd PFS event, which is the prespecified number event determining results for the primary endpoint, we now expect to report topline results on the primary outcome measure of progression-free survival this quarter. We also continue working towards initiating a Phase 1 healthy volunteer study of ACE-2494. Finally, given all of our recent progress in the clinic, we now plan to host a research and development day later this year to discuss our ongoing preclinical research and provide additional details for some of our planned clinical trials. Stay tuned for further event details over the next few months. And with that, I will open the call to questions. Operator?

Thank you very much and congratulations on the results in ESA naïve and low-risk MDS, very interesting. First, I don't know if you could give us a sense of what proportion of low-risk MDS patients have baseline EPO less than 500; just to help us in sort of mentioning this opportunity. And secondly, the summer plots that you presented for the patients who are transfusion independent for eight weeks have a concentration of transfusions when patients fail; they seem to be repeated transfusions; so wondering is that to be expected and do you believe that there is any loss of activity of the drug with prolonged exposure or are you seeing any neutralizing antibodies to the drug? I mean my last question is a dose question, which is, you appear to be using wide-based dosing but would you envisage ultimately having standardized dosing and would dosing differ between the low-risk and ESA naïve and the ESA experienced populations? Thanks. Apologies for all the questions.

Thanks, Geoff. So with the details of the study, I will hand it over to Matt, and then I'll follow up with that in terms of the population in terms of the percentages.

Hi Geoffrey, this is Matt. So let me take the second question you're asking, which related to win-win class and the transfusion seen sometimes in patients after they'd have a prolonged period of transfusion dependence. As you know, the average age of onset of MDS patients is at 70 years; in our study, the median age was 72 years and patients are often elderly in the Phase 2 trial. So the disease in the elderly many patients have co-morbidities. So if you look out over several years in these patients' history, they often have other medical illnesses of problems that arise. It might be related to a period of infection for example, when a patient might have a bacterial oral infection; they're sick and they need a boost in transfusions for a period of time. More specifically, for one of our patients, there was a period of GI bleeding that was unrelated to the drug that occurred due to another issue and that requires some transfusions as well. So it is those kinds of events that account for these small bursts of transfusion; we've not seen any drop off of the efficacy of the drug though over time.

Great, thanks.

And then in terms of weight-based dosing question, I think we’re very comfortable with the PK/PD modeling that we've done for this protein to show that the efficacy that we're seeing does require weight-based dosing, so there's no plan to do flat dosing in the near future.

And then, Geoff, regarding your question regarding the percentage of patients below EPO 500, we estimated the majority of those patients that will be from zero to 500, probably somewhere around 70% to 80%.

Right, thanks very much for all the answers, appreciate it.

Good morning guys, thanks for taking my questions. I guess the first one on the frontline MDS study, the language being used there fairly broad in first-line treatment, somewhat delicate given the partnership with Celgene but can you definitively answer will there be RS negative patients enrolled in that study? And should we expect any sort of cut off based on EPO levels and in terms of inclusion criteria? And then secondly, just any comment on the duration you've seen so far in the RS negative segment relative to what we see in the RS-positive segment. Thank you.

Hi Carter, this is Matt. So yes, right now we're describing the frontline study because I think really it builds on the excitement that we've seen in this, yes they may be of population; there is tremendous enthusiasm that came out of the Symposium meeting in Valencia just over last week and this weekend. Highlighting which covers up as one of the leading drugs now in phase three development, moving into the frontline setting sets us up for going head-to-head to the ESA therapy. The data that we generated ratios with very robust rates we are seeing with patients in baseline EPO levels within 500, which is the majority of patients. The ESA-naive population both importantly includes both RS positive and our RS negative patients. The duration of responses, although it's still early days, does not show any significant difference between those two populations. So if you move forward with this program, there will be more details forthcoming, and we will be able to update folks on the specifics of the study status and collaboration with Celgene now towards later this year as we have the details to discuss.

Thank you.

Hi guys, thanks a lot for taking the question. My question on efficacy of the RS-negative population have been answered, but I have a couple questions on the safety. You mentioned in the press release that there were several occasions of anxiety that were classified grade three and drug related. Can you give us some color on that, and is there any mechanism that could suggest this is related to something the drug is doing? Thanks.

Hi Andrew, again this is Matt. So the safety profile of this drug has actually been very, very well tolerated over the multiple years now that it's been in our many years now been in development. The small numbers of related grade three adverse events that we admitted have not been anything that we can specifically say relates to the mechanism of the drug. And again the occurrences of those have generally been at very low frequency.

Okay, but was there a reason that the investigators determined it was drug-related?

Yes, this is ultimately based on the investigator's interpretation of the patient's experience, particularly the timing of the event in relation to the drug administration. It's more subjective than objective, and a randomized control trial is needed to determine if any of these events occur more frequently in the treatment group compared to the control group. These events should not reach the level of serious adverse events, so they were generally better tolerated by patients.

Okay. Is that something that is coded pro-fusion cited beyond this patient population?

Yes, given the elderly population, they often have several co-morbidities. With cardiovascular disease being a major concern among these patients, they may have active cardiovascular issues, such as those indicated by a recent MRI, but many have also had a long history of hypertension and atherosclerotic heart disease. It is not surprising that there would be occurrences of other adverse events during patient participation in a multi-year clinical trial.

Hey guys, thanks for taking our questions. Maybe just one if you had any kind of hypothesis on why the RS negative and high baseline didn't exhibit response, just anything kind of that you're hypothesizing in there? And then I just wondered, as relating to the two luspatercept which can roll faster than expectation, was it consist of dynamic that kind of the traffic and minimum awareness of physicians? Or kind of what drove your faster timeline enrollment? Thanks.

Hi Alethia, this is Matt. For your first question about the lack of response in patients with high baseline EPO levels, this really indicates the stage of their disease; those patients have severely affected bone marrow. Their own EPO levels have been significantly elevated, and they have struggled with ineffective red blood cell production to the point of exhausting their marrow. In this situation, luspatercept has shown limited effectiveness, as have other therapies aimed at increasing red blood cells, which isn't surprising and highlights the advanced state of these patients' conditions. Regarding the accelerated enrollment in the Phase 3 trial, this clearly reflects the growing enthusiasm and momentum surrounding treatment opportunities for luspatercept. It also underlines the very few options available for these patients. This combination really fueled a quicker rate of participation, even considering that randomized placebo-controlled trials can sometimes face enrollment challenges. Many patients recognize that they may not want to be in the placebo group, but given the limited options and the excitement for luspatercept, we were very pleased with the enrollment numbers.

Thank you.

Good morning, and thank you for taking my question. Congratulations on the data you presented over the weekend. I noticed you've begun to draw down on the RS-negative population. I'm curious about your explanation regarding why some may not be responding to luspatercept in this context. Is there any correlation to myelofibrosis? While the scenarios are not identical, you have an exhausted marrow in NMS, yet you've still observed some intriguing responses there. I'm just trying to understand how these two findings can be reconciled.

Hi Mike. So yes, first in regard to your question what I think you're referring to is not an RS-negative patient, but RS-negative patients with high EPO levels. In that context, thinking about the marrow, I think it is a very different situation though in the myelofibrosis patients; their marrows aren't actually highly reactive. Marrows in myelofibrosis accounts for the fibrotic nature in their marrow. So, as we showed last year, you're quite familiar with the data that we presented with high degree of erythropoietin response in patients who had really advanced and that was the investigator-initiated trial that was done by surgical for cellstack at MD Anderson. And on that basis, we certainly moved ahead to initiate the Phase 2 trial of luspatercept in patients with myelofibrosis, so there's still a high degree of enthusiasm and optimism right now to be working with those patients; it's a very distinct disease from MDS.

Thank you for taking the question. All the others I pondered were answered, so thank you.

Hi, good morning, thanks for taking my question. Maybe we'll take it over to the ACE-083; I am just wondering if we could further elaborate perhaps on the addition of CMT muscle weakness is really an issue for some of these patients, and do you expect that the volume enhancement that you are going to see with muscle weakness? And perhaps you can point to data that might suggest your approach is differentiated in that respect to other myelofibrosis? Thank you.

Hi Chris, let me answer the question about the role of ACE-083 and CMT and make a comparison to FSHD as well. So these are two neuromuscular diseases that we targeted now for Phase 2 trials to investigate the role of ACE-083. ACE-083 first is a broader acting agent than just a myostatin inhibitor; so as we discussed, it inhibits multiple negative ligands that can regulate muscle growth and function. But these two diseases are distinct, and I think there are two-pronged approaches. It's important to recognize that in FSH dystrophy, there is an impairment in the muscle itself; it is a muscle dystrophy. So our expectations to increase muscle strength in that setting. In CMT, the muscles impact is due solely to the innervation for the nerve to the muscle that isn't here. So the muscle itself is relatively healthy and undergoes atrophy after a prolonged period of this innervation. So in that setting again, increasing the volume, the strength, the function of the existing muscle to help those patients overcome their impairment. We had a webinar a month and a half ago about the study, I think it's really informative for folks to actually try to listen to some of the details that were presented by Dr. David Walk; but these are patients who are pretty troubled by their illness, presenting with a high-step gait leading to trips and falls in these patients, without any therapeutics available for these patients other than just orthopedic bracing of their ankle. They're quite incoherent in their mobility. So the ability of FSHD to increase strength I expect will be a very significant benefit for these patients. I guess I should also mention the ongoing preclinical work that we've done as well have supported the role of the ACE-083 to increase muscle function across a wide number of preclinical models in different neurological diseases, so again that adds to the evidence for the potential benefit for the agent in these Phase 2 trials.

So just to be clear, you expect not only you'll see the volume enhancement with your myostatin inhibition but also an increase in strength?

The trials are structured as two-part studies. The first part is an open-label trial that includes a small dose escalation component, focusing mainly on muscle volume as the primary outcome, which we have already demonstrated in healthy volunteers. The second part involves a randomized, placebo-controlled trial where we will evaluate not only muscle volume but also muscle strength through fixed stress testing and hands-on performance assessments along with various functional outcome measures. As the trials progress, we will emphasize the significance of these outcome measures. They include assessments like the six-minute walk test, the 10-meter walk run activity to evaluate upper extremity performance known as the pull test, and a test called the burden balance test in the CMT population. This latter test consists of 14 components that assess patients' abilities to maintain balance while standing or sitting on one foot and turning in a full circle. These tests provide a comprehensive evaluation of muscle function. Additionally, both studies will analyze patient gait using advanced gait analysis techniques to assess improvements in ambulation. I am looking forward to seeing the results as the trials develop over the next year.

Okay, thank you.

Hi guys, thank you so much for taking my question, and then congratulations on the data presented over the weekend. So for the ESA-naive, I know you said you're going to talk about details later. I was just curious since you've presented both HIV and transfusion dependent data could you talk about what the potential primary point could be? And also for myelofibrosis, just wondering when we can hear more about the trial design mainly, but what patient population you wish to target, thank you so much.

Again, this is Matt answering the question. So good questions but I don't think I have a lot of information right now to share with you. As we get further along with the specifics of the design for the command study in the first-line MDS patient population to be able to talk specifically, my end points would be and the specifics of the patient population, I know people would want to look forward to the specific eligibility criteria that we certainly have shown the range of activity we've seen in the lower Phase level of patients and the ESA-naive population as well too, but I think that that's as far as we can talk about the specifics today; but stay tuned later in this year. In terms of myelofibrosis, I think it's really similar as we get a little closer, get a little more keyed up to be giving a Phase 3 trial. I think together with our partners at Celgene we'll be able to align the eligibility criteria in the specific end points and the study population for the MF study as well.

Okay, great thank you. Can I sneak in just one more question about the launch itself? Just wondering how we will receive the data, is there any likelihood of the data at ASCO or do you expect press release the data now that it's been advanced from second half to the second quarter?

Yes. So I can start to let people know where we are with that study if I can jump in about how the data will be released too, but we did talk about we reached our 82nd PSFGN as that was prospectively prescribed in the study designed to do the analysis for the top-line results, to show the effect of luspatercept combination with exutinib versus single-agent exutinib plus placebo. We've met a second event and we also completed the enrollment of 130 patients, so just now doing the analysis. And we can talk about that when we have the data presented.

Sure.

So we are at database analysis now, we've already passed through the late breaker time period for the presentation; so you could expect that would just be a press release from us outlining the top-line results.

Okay, thank you so much.

Thank you for taking the question. I guess one quick one for me and just on ACE-083 and FSHD data later this year; how do you intend to communicate that? And last question, should we expect that press release or medical conference or that in an investor event? How should we be thinking about that?

Hey Whitney, it is Todd. Yes, there are multiple muscle conferences in the second half of the year, but most likely we will just end up giving out a top-line press release on dose cohort 1 late in the year. Then you could expect further details from that potentially at the muscular dystrophy association conference in March or one of the muscle conferences early in 2018 for dose cohort 1.

Hi guys, thanks for taking my question. I think there most my questions have been asked, so I'll just ask on the luspatercept Phase 2 data in the first-line lower risk MDS patients, are you going to continue following patients and provide an update on expansion studies every six months like you're doing with the earlier Phase 2 study?

Hi Ed, thanks for the question. So yes, that was actually exactly the plan. Just to put into context, when we did the first part of the Phase 2 study we had a total of 58 patients from the first part through the first extension cohort. The second extension cohort including RS-negative patients was probably about 50 additional patients, and 31 of those patients were available for this update at the Symposium meeting. So we anticipate approximately 24 patients that we will have data for the next update in 2017 to include the remaining patients who are enrolled, as well as showing the extension; you know, the durability of activity in these patients as we have done over several years for the first cohort of patients.

Hi everyone, I appreciate the opportunity to ask a question. This is Jason filling in for Paul. I also want to congratulate you on the data. I have a couple of quick questions; although we've discussed the EPO issue before, I want to clarify whether patients with higher baseline EPO levels experience less effect, or if it functions more like a step-wise process where efficacy diminishes around levels of 400/500. Additionally, I'm curious about your product, as I've noticed a few patients continue therapy despite having a strong response. Could you explain why a patient might choose to discontinue? Thank you.

Hi Jason, regarding your first question about EPO levels, there tends to be a drop-off. When we analyzed data with different baseline EPO levels, we found minimal difference in response rates for high EPO responses, with over 63% response for levels below 200 compared to 53% for the 200 to 500 range. However, for levels above 500, the response dropped to 27%, indicating that the cutoff of 500 represents reduced efficacy, and we have observed this decline in activity. Nevertheless, Phase 3 trials are more active, particularly in a lower range. We noted that the Phase 3 trials for Darbepoetin and Epoetin show activity primarily for baseline EPO levels below 100 or perhaps up to 200, but not significantly for patients between 200 and 500 grams. Therefore, we see a clear benefit in that patient group. As for discontinuation, some patients drop out for various reasons, often related to social factors such as the logistics of participating in clinical trials. Many of these patients are older and must manage frequent visits to clinics, sometimes traveling 50, 60, or even 100 kilometers for treatment, which affects their continued involvement in the trial over time.

Awesome. Thank you so much for taking the questions.

Sorry about that, can you hear me now?

My apologies. I just wanted to ask about the reasons for patients withdrawing from the trial. Specifically, for those who stop responding, is there a biological reason behind it? Do they stop producing colony-forming units, or is it more about the patients' decision to move on after feeling good about their response? I'm curious if we can identify different reasons for why some patients do not continue in the trial.

Hi Mike. They mentioned that several patients withdrew for social reasons related to their willingness to participate in the trials, particularly considering their age. Sometimes, it was due to disease progression; these patients may experience progression unrelated to their anemia but can maintain their response to luspatercept. There are various reasons for these patients discontinuing the study, but this did not appear unusual compared to other studies we've examined regarding patient dropouts.

Alright, okay.

I mean as a physician who has treated MDS in the past too, I think this kind of activity is fairly impressive activity and I think that was reflected by the enthusiasm that both the investigators from the trial, as well as from the general MDS community appreciated at the MDS Symposium Conference, given the very limited options that these patients have. It was clearly very enthusiastic reception for the data at the meeting in Valencia.

Alright, thank you.

Yes, thank you, operator. So obviously an awful lot of interest and excitement over the recent data announcement. So I thank you all for your questions and I do look forward to meeting with you at some future investor conferences and medical meetings as we head into the December month and wishing you all a great day. Thanks everybody.