Akebia Therapeutics Inc (AKBA) Q1 2020 Earnings Call Transcript

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Akebia Therapeutics Inc (NASDAQ:AKBA)
Q1 2020 Earnings Name
Might 5, 2020, 8:30 a.m. ET

Ready Remarks:

Operator

Good morning, girls and gents, and welcome to the Akebia Therapeutics’ INNO2VATE High-line Knowledge Readout Name and its First Quarter Monetary Outcomes and Enterprise Highlights Convention Name. As a reminder, this name is being recorded.

I might now wish to introduce your host for immediately’s convention, Kristen Sheppard.

Kristen Sheppard — Vice President, Investor Relations

Thanks, and good morning. My title is Kristen Sheppard, Senior Vice President of Investor Relations at Akebia. Thanks a lot for becoming a member of us to debate Akebia’s top-line information for INNO2VATE, our world Part Three program of our product candidate, vadadustat, for the remedy of anemia on account of persistent kidney illness in grownup dialysis-dependent sufferers.

On immediately’s name, we can even focus on Akebia’s first quarter 2020 monetary outcomes and different current enterprise highlights. We issued two press releases this morning; one containing INNO2VATE’s top-line information, adopted by one containing our monetary outcomes and different current enterprise highlights. Each of those thrilling press releases can be found on our Investor Relations web site, together with the slides for immediately’s name. In your comfort, an audio replay of immediately’s name with the slides can even be obtainable on our web site shortly after we conclude immediately’s webcast.

Becoming a member of our name immediately are John Butler, President and Chief Govt Officer; Dr. Steven Burke, Chief Medical Officer; and Jason Amello, Chief Monetary Officer.

Earlier than we start, I would wish to remind everybody that this convention name consists of forward-looking statements. Every forward-looking assertion contained on this name is topic to dangers and uncertainties that might trigger precise outcomes to vary materially from these described in these statements. Extra info concerning these elements is described within the Threat Elements and Administration’s Dialogue and Evaluation sections of our most up-to-date quarterly and annual experiences filed with the SEC, and within the cautionary observe on forward-looking statements within the slides. The forward-looking statements on this name communicate solely as of the unique date of this name and we don’t undertake any obligation to replace or revise any of those statements.

With that, I would like to show the decision over to our CEO, John Butler. John?

John Butler — President and Chief Govt Officer

Thanks, Kristen, and welcome to everybody. We’re thrilled to have the ability to announce optimistic top-line information from INNO2VATE, the primary of our two world Part Three packages learning vadadustat, our investigational oral hypoxia-inducible issue prolyl hydroxylase inhibitor, or HIF-PHI, to deal with the anemia of persistent kidney illness. This can be very rewarding to see this program yield clear, constant, and compelling optimistic outcomes.

This can be a crucial day for Akebia, nevertheless it was not completed by the Akebia group alone. I wish to sincerely thank our investigators and their employees for taking part, however most significantly, I wish to thank the almost 4,000 sufferers who participated on this program. Dialysis sufferers are among the many most in danger and hardest hit by COVID-19. Throughout these unsure occasions, we’re reminded of each the important nature of our work and the numerous must advance look after these sufferers. I would additionally wish to thank our collaboration companion, Otsuka, our companion in dialysis, Vifor Pharma, and our shareholders for supporting Akebia and our efforts so far.

The Akebia group did a unprecedented job closing the research, collaborating and analyzing the information regardless of the logistical challenges of working below the current COVID atmosphere, bringing INNO2VATE to a well timed and profitable conclusion. I am extraordinarily pleased with all of our staff. We imagine our collective efforts deliver us one step nearer to fulfilling our goal to higher the lives of every particular person impacted by kidney illness. Once more, my honest due to everybody. We would not be right here immediately with out all of you.

By way of an agenda for immediately’s name, we’ll begin with how COVID-19 is impacting our enterprise and the way we’re working to mitigate potential impacts. We issued our preliminary response to COVID on March 15th, and immediately I will present some updates. The remainder of our dialogue will probably be targeted on the optimistic top-line information that we introduced this morning, and the thrilling pathway that we have developed for vadadustat. We’ve lots of thrilling information to cowl, and so, within the curiosity of time, Jason is not going to evaluate the Q1 outcomes, however is offered for any questions you might need. As at all times, following our discussions, we’ll open the decision for Q&A.

On this difficult atmosphere, our goal to higher the lives of every particular person impacted by kidney illness is extra related and necessary than ever. Our revolutionary therapies are important to dialysis and non-dialysis CKD sufferers, who’re among the many most in danger. Persevering with to supply and assist our important therapies is a precedence, as is defending the well being and security of our sufferers, clients and staff. To that finish, we’re doing all we are able to to restrict the unfold of the virus in addition to assist kidney illness sufferers and our neighborhood.

Our group has been extremely productive below our work-from-home coverage. Whereas guaranteeing enterprise continuity, our group has continued to assist native and nationwide response efforts to the COVID-19 pandemic by donating provides and meals to front-line healthcare employees in Boston, volunteering to supply medical care at clinics treating COVID sufferers, and donating to the American Kidney Fund’s Coronavirus Emergency Fund to assist the wants of kidney sufferers.

By way of our monetary and operational efficiency, to-date, now we have not skilled any vital opposed affect from COVID-19, and our fundamentals have remained robust. As of the tip of Q1, our money runway extends nicely into 2021. With that mentioned, these are unprecedented occasions, and through COVID-19 now we have no clear visibility on what to anticipate for the upcoming weeks and months. We’re carefully monitoring demand for our marketed remedy, and we’re additionally aware of the potential macro dangers from the affect on the healthcare system and the potential affect on payer combine. Given this uncertainty, we proceed to take precautionary measures and actively monitor this evolving state of affairs.

Our deal with our scientific packages and ongoing research is as necessary as ever. Our PRO2TECT research for vadadustat have superior considerably, and we proceed to anticipate top-line information mid 12 months as deliberate. Additionally, our ahead two trial for vadadustat is absolutely enrolled, and we anticipate top-line information by year-end as deliberate. COVID precautions are nevertheless inflicting a delay in enrolling new scientific trials. For ongoing trials, we’re utilizing distant monitoring and performing distant affected person visits the place potential. Our industrial and customer-facing groups are leveraging instruments and expertise to work together nearly with healthcare suppliers, together with dialysis facilities, and responding to their wants. We imagine Akebia can play an necessary function in supporting our clients and our sufferers throughout this disaster, and we’re right here to assist allow continuity of care with necessary packages like AkebiaCares.

We’re lucky that even earlier than the COVID pandemic, we had already begun implementing new enterprise continuity plans throughout our provide chain with the objective of safeguarding our potential to supply our therapies to sufferers who depend on them and driving working efficiencies throughout our enterprise. These measures look to make sure that important supplies usually are not sourced from any single provider for both AURYXIA or vadadustat. Presently, our provide chain is functioning, our producers are working, and whereas we do not at the moment anticipate a provide disruption, we imagine that now we have stock to assist mitigate the affect ought to one happen.

In sum, this unsure COVID atmosphere has offered new dangers to our enterprise. Whereas we’re working exhausting to mitigate any potential affect, we’re aware that many of those dangers and the affect to the bigger healthcare market are exterior our management. The intense spot is that our group is extra dedicated than ever to ship on our goal, and we imagine now we have great value-enhancing alternatives forward, and that is an awesome segue to our INNO2VATE information.

Once more, we’re very excited with the clear, constant and compelling efficacy and security, notably MACE information, that we introduced immediately. Vadadustat succeeded in assembly the first and key secondary efficacy endpoint in every of the 2 INNO2VATE Part Three research, confirming that once-daily oral remedy with vadadustat can enhance and preserve hemoglobin within the goal vary much like the present standard-of-care, on this case, Aranesp or darbepoetin alfa.

Vadadustat additionally achieved the first security endpoint of INNO2VATE program, outlined as non-inferiority in time to first incidence of Main Adversarial Cardiovascular Occasions or MACE, which is the composite of all-cause mortality, non-fatal myocardial infarction or non-fatal stroke. Confirming vadadustat security and demonstrated no elevated cardiovascular danger of vadadustat in contrast with the standard-of-care in grownup dialysis sufferers with anemia on account of CKD. These outcomes have been clear and remarkably constant throughout all affected person populations in dialysis with anemia on account of CKD, whether or not the affected person was new to dialysis, an incident affected person, or has been on for a few years a prevalent affected person. Importantly, all of those analyses have been based mostly on a statistical evaluation plan, and non-inferiority margins agreed to with regulators.

As we speak, there are roughly 500,000 dialysis sufferers within the US. Basically, it is a inhabitants with vital well being points. Roughly, 90% of dialysis sufferers have been handled with erythropoiesis stimulating brokers, or ESAs, to handle their anemia. The affect of this illness on sufferers with CKD is profound. Along with the well-known signs of fatigue, dizziness, and shortness of breath, anemia has been related to extra extreme opposed outcomes similar to cardiovascular problems, together with left ventricular hypertrophy and congestive coronary heart failure. A number of giant peer-reviewed research have demonstrated the elevated cardiovascular danger related to ESA use in each dialysis and non-dialysis sufferers. Physicians affiliate that danger with the EPO ranges achieved by the doses of ESA, the velocity of hemoglobin enhance, and excursions of hemoglobin above 12 grams per deciliter.

INNO2VATE information additional assist what our vadadustat improvement program has persistently demonstrated and what analysis recommend nephrologists need in a brand new remedy possibility for his or her sufferers. Vadadustat remedy was designed with the objective of sustaining physiologic EPO ranges, growing hemoglobin in a predictable method, minimizing hemoglobin excursions, and offering a handy oral dose. We imagine our information uniquely positions vadadustat as a possible new oral standard-of-care for treating all populations of dialysis sufferers, together with each incident and prevalent dialysis sufferers with anemia on account of CKD, topic to approval.

The headline for our world Part Three INNO2VATE program continues to be that we imagine it’s designed for scientific, regulatory and industrial success, and the outcomes proceed to assist that perception. INNO2VATE consists of two non-inferiority research designed to guage the efficacy and cardiovascular security throughout long-term remedy of anemia with vadadustat utilizing an energetic management, darbepoetin, an injectable ESA, which is the present customary of care. Merely put, we imagine that so as to change the usual of care, it is advisable to evaluate to the usual of care.

We thoughtfully constructed this program and our trial design after in depth dialog with the FDA and European regulators. We’ve an easy statistical evaluation plan prospectively outlined and agreed to non-inferiority margins with the FDA and EMA, and we additionally agreed with the FDA on the important thing elements of our statistical evaluation plan. Our INNO2VATE trial design has enabled an easy assortment and evaluation of MACE throughout our program and yielded a transparent and compelling information readout on each efficacy and security. We won’t wait to share these information with regulators and finally with physicians, dialysis suppliers and payers. We’re extra assured than ever that the scientific success we have demonstrated with INNO2VATE helps vadadustat’s potential for achievement on the regulatory entrance. We’re additionally assured that the INNO2VATE information will probably be extremely informative for physicians, sufferers, dialysis suppliers and payers as they make necessary choices about affected person care as soon as vadadustat is permitted.

I do know we’re all excited to get into the specifics. So let me hand the decision over to our Chief Medical Officer, Dr. Steven Burke. Steve?

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Thanks, John, and good morning, everybody. On behalf of the R&D group at Akebia, we’re very excited to share these information immediately. As John talked about, anemia on account of CKD is a severe situation characterised by decreased hemoglobin, and is related to cardiovascular occasions, hospitalization and mortality in addition to elevated danger of CKD development. The burden of CKD has a major affect on affected person high quality of life and provides vital value to our healthcare system.

Anemia is at the moment handled with injectable ESAs together with iron supplementation or purple blood cell transfusions. Whereas ESAs are efficient in elevating hemoglobin ranges, there are nicely documented security dangers related to their use. Specifically, there’s proof that sufferers administered larger doses of ESAs expertise an elevated danger of opposed cardiovascular occasions, notably stroke and likewise mortality. Contemplating the unmet medical want for secure and efficient remedy, we imagine INNO2VATE information are compelling and advance our plans for an NDA and potential approval of vadadustat.

Primarily based on Nobel prize-winning science, vadadustat was designed as a once-daily, orally administered, investigational HIF PHI to imitate the physique’s pure physiologic response to hypoxia or low oxygen. By stabilizing HIF, vadadustat up regulates transcription of endogenous erythropoietin and proteins concerned in iron absorption, transport and utilization. The rise in erythropoietin and supply of iron to the bone marrow results in elevated purple blood cell manufacturing and better hemoglobin.

The INNO2VATE program was nicely powered for efficacy and cardiovascular security and included two Part Three research, correction-conversion and conversion, which collectively enrolled 3,923 dialysis-dependent sufferers with anemia on account of CKD. This can be a very giant, rigorous, and thoughtfully designed program to check vadadustat to a present customary of care, darbepoetin alfa, an injectable ESA.

As illustrated on Slide 4, each INNOVATE research have been world, multi-center, open label however sponsor-blind, non-inferiority research. The protocols, efficacy and security endpoints in non-inferiority margin summarized on the fitting aspect of the slide have been reviewed and aligned with FDA and EMA. In each INNO2VATE research, the agreed upon main efficacy endpoint was non-inferiority of vadadustat versus darbepoetin as measured by the distinction in imply change in hemoglobin between baseline within the main analysis interval, which was between 24 and 36 weeks.

The important thing secondary efficacy endpoint additionally agreed with FDA and EMA was the non-inferiority throughout a secondary analysis interval between weeks 40 and 52. The INNO2VATE program’s main security endpoint was non-inferiority of vadadustat versus darbepoetin for time to first MACE within the mixed INNO2VATE research. MACE was outlined as all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke. The MACE occasions have been independently and blindly adjudicated by the Brigham and Girls’s Hospital’s Medical Endpoint Middle.

As proven on Slide 5, in each research, sufferers have been randomized one to 1 to obtain both vadadustat or darbepoetin. Vadadustat was initiated at a dose of 300 milligrams as soon as every day and beginning at week 4 was adjusted up or down in increments of 150 milligrams inside the vary of 150 to 600 milligrams every day. Darbepoetin was administered intravenously or subcutaneously. Sufferers already receiving darbepoetin maintained their prior dose, and people in different ESAs have been switched to darbepoetin and dosed in response to the permitted product label. Examine medicine have been titrated to realize goal hemoglobin of 10 to 11 within the US and 10 to 12 exterior the US.

Iron supplementation, ESA rescue remedy, and purple blood cell transfusions have been allowed as obligatory in response to protocol specified standards, aligning with scientific observe pointers. The correction-conversion examine evaluated 359 incident dialysis sufferers who have been on dialysis for lower than 16 weeks previous to screening. The conversion examine evaluated 3,554 prevalent dialysis sufferers receiving ESAs.

Slide 6 summarizes the affected person’s baseline traits that are related between remedy teams and consultant of the final dialysis inhabitants. As anticipated, there was a excessive proportion of sufferers with heart problems and diabetes.

Slide 7 summarizes the first and key secondary efficacy endpoint information. Within the conversion examine of prevalent dialysis sufferers, vadadustat was non-inferior to darbepoetin. The distinction in imply hemoglobin change was minus 0.17 per deciliter with a 95% confidence interval of minus 0.23 to minus 0.10. The decrease sure of the boldness interval was above the prespecified non-inferiority margin of minus 0.75. The imply hemoglobin at weeks 24 to 36 was 10.36 for vadadustat and 10.53 for darbepoetin. The hemoglobin response was maintained within the secondary analysis interval of 40 to 52 weeks.The imply hemoglobin at weeks 40 to 52 have been 10.Four for vadadustat and 10.58 for darbepoetin, with the distinction in imply hemoglobin of minus 0.18. Once more, the decrease sure of the boldness interval was above the prespecified non-inferiority margin of minus 0.75.

Within the correction-conversion examine of incident dialysis sufferers, vadadustat was non-inferior to darbepoetin. The distinction in imply hemoglobin was minus 0.31 with a 95% confidence interval of minus 0.53 and minus 0.10, with the decrease sure not crossing the pre-specified, non-inferiority margin of minus 0.75. The imply hemoglobin at weeks 24 to 36 was 10.36 for vadadustat and 10.61 for darbepoetin. The hemoglobin responses have been maintained within the secondary analysis interval of 40 to 52 weeks. The imply hemoglobin of 40 to 52 weeks was 10.51 for vadadustat and 10.55 for darbepoetin with a distinction of minus 0.07. Once more, the decrease sure of the boldness interval was above the prespecified non-inferiority margin of minus 0.75. We’re very happy with these efficacy outcomes. They’re very in step with what we noticed within the Japanese Part Three research, which have been offered at ASN final 12 months.

Now shifting to security, Slide Eight summarizes the first security endpoint time to first MACE. MACE consists of deaths, non-fatal MIs and non-fatal strokes. Evaluation of time to first MACE was based mostly on the hazard ratio from a COX mannequin evaluating vadadustat to darbepoetin. The hazard ratio for MACE was 0.96 and the 95% confidence interval was 0.83 to 1.11. The higher sure of the boldness interval was beneath the non-inferiority margin of 1.25 agreed upon with FDA and the 1.Three agreed upon with EMA.

Slide 9 shows the Kaplan-Meier curves for time to first MACE occasion within the two teams. The purple line is the darbepoetin group and the blue line is the vadadustat group.

Slide 10 summarizes remedy rising opposed occasions and the most typical remedy rising opposed occasions occurring in higher than or equal to 10% of sufferers in both group within the two research. The frequent occasions included diarrhea, pneumonia, hypertension, hyperkalemia. These occasions have been related between remedy teams in each INNO2VATE research. It’s nice to acquire such clear, simple optimistic efficacy and security outcomes immediately to show the potential of vadadustat to deal with anemia of CKD and grownup sufferers on dialysis, topic to regulatory approval. We’re happy with the findings, and excited to current the complete information from INNO2VATE along with our information from our PRO2TECT program later this 12 months at a medical convention, and publish the leads to peer-reviewed journals. The R&D group is already engaged on the NDA, which we’ll file as shortly as potential following the PRO2TECT information readout.

I’ll now flip the decision again over to John. Thanks.

John Butler — President and Chief Govt Officer

Thanks, Steve. We imagine now we have a powerful, compelling and really simple dataset for vadadustat. By way of what’s subsequent, I’ll remind you that INNO2VATE is the primary of many doubtlessly transformational near-term milestones. We imagine we have developed an thrilling path ahead for vadadustat and Akebia, and though the COVID-19 atmosphere stays unsure, we proceed to make stable progress advancing these actions.

In collaboration with our companion, Mitsubishi Tanabe, we’re advancing key pre-commercial actions in assist of the primary regulatory approval of vadadustat anticipated in Japan this 12 months. Upon approval, vadadustat is predicted to be the primary HIF-PHI that will be obtainable to deal with anemia on account of CKD in each dialysis and non-dialysis dependent grownup sufferers in a serious market.

As I discussed earlier, now we have considerably superior PRO2TECT, our world Part Three examine evaluating the security and efficacy of vadadustat in non-dialysis dependent grownup sufferers with anemia on account of CKD. We have achieved the goal variety of MACE occasions for the examine and anticipate top-line information mid-year as deliberate. As well as, we bolstered our mental property place for vadadustat confirming for each Akebia and our collaboration companion Otsuka are positioned to execute on plans to launch vadadustat within the UK, and doubtlessly the remainder of Europe upon approval.

We won’t wait to get these information in entrance of the FDA and different regulatory businesses as quickly as potential. Upon profitable completion of our Part Three program, and with PRO2TECT information in hand, we plan to submit the regulatory filings for advertising approval of vadadustat for each dialysis dependent and non-dialysis grownup sufferers within the US as shortly as potential, after which in different areas in collaboration with Otsuka. And that is not all. We’ve an settlement with Vifor Pharma to doubtlessly entry the Precedence Assessment Voucher or PRV for the vadadustat NDA with the FDA to expedite evaluate. Whereas there’s extra work to be carried out, we imagine this path would meaningfully improve the potential of bringing vadadustat to sufferers as shortly as potential, topic to regulatory approval.

We’ve an incredible quantity of confidence in these information. So we’re additionally working very exhausting on pre-commercialization exercise. So, once more, we imagine the settlement now we have with Vifor distribute vadadustat as their unique HIF within the US to Fresenius clinics and sure different dialysis facilities has the potential to construct momentum and assist fast adoption of vadadustat upon approval, and as much as 60% of dialysis sufferers within the US. We imagine these information assist vadadustat’s potential to be the brand new oral customary of look after anemia on account of CKD in dialysis sufferers upon approval.

Wrapping up, we’re extraordinarily excited in regards to the prime line information. The group is working as shortly as potential to organize the complete information for presentation and publication at an upcoming medical convention. We’re proper the place we wish to be, nicely positioned to proceed advancing our goal to higher the lives of every particular person impacted by kidney illness.

With that, I will open up the decision to questions. Please observe that we’ll reply questions based mostly on the highest line outcomes disclosed within the press launch. Jason can also be obtainable to reply any questions pertaining to our first quarter monetary outcomes.

Operator, we’re prepared for the primary query.

Questions and Solutions:

Operator

Thanks. [Operator Instructions] Our first query comes from Chris Raymond with Piper Sandler. Your line is now open.

Allison Bratzel — Piper Sandler — Analyst

Hello. That is Ally Bratzel on for Chris. Congrats on the information. So, first, simply on PRO2TECT, I do know you’ve got talked about this a bit within the ready remarks, however are you able to simply discuss your confidence in having the ability to disclose the pre-dialysis information midyear, and the power to file an NDA later this 12 months, And the way possibly we must always alter our timing expectations if COVID continues to be in full swing at that time? After which, simply usually on the precise pre-dialysis readout, how does INNO2VATE change your confidence in reaching the primary endpoint in PRO2TECT?

John Butler — President and Chief Govt Officer

Thanks, Ally. Thanks for the questions. So, as I discussed, PRO2TECT is on time for mid-2020. I imply, we’re clearly persevering with to watch the COVID state of affairs, however as of immediately, we really feel very assured that we’ll have the ability to ship that information in mid-2020. After which we’ll transfer as shortly as potential to a submitting, and clearly the timing will probably be dependant on after we get the PRO2TECT information, nevertheless it’s an extremely thrilling second for us.

And to your second query round how does INNO2VATE affect, how we really feel about PRO2TECT, look, I believe it is necessary that the design is similar, mainly that we’re PRO2TECT with the identical energetic management, the identical information assortment, and many others. On the identical time, it is a totally different program. So, we’ll see this information very, very quickly, and we won’t wait to see it, and we could not be extra excited in regards to the path now we have going ahead.

Allison Bratzel — Piper Sandler — Analyst

Nice. After which, possibly one other query on the non-inferiority margin, so that you indicated you’d agreed to — prospectively agreed with FDA to MACE non-inferiority margin of 1.25, however 1.Three for EMA. Might you discuss why the businesses differ, or possibly the way you and FDA got here to the settlement on that 1.25 quantity once I assume previously for renal drug [Phonetic], they solely requested for 1.3, after which possibly when you can handle if there’s any cause to assume FDA would search for a distinct non-inferiority margin for PRO2TECT for the pre-dialysis program.

John Butler — President and Chief Govt Officer

So, it was in depth dialogue with each regulatory businesses, and we’re very snug with the place we landed with each, and most significantly, while you take a look at the information, with an higher sure of 1.11, we’re comfortably inside the non-inferiority vary for both regulatory authority. So, we’re very, very happy with what we have proven you immediately, and once more, we’re hoping to point out the identical from PRO2TECT.

Allison Bratzel — Piper Sandler — Analyst

Nice. After which, possibly simply final query for me, may you discuss your present expectations for a possible end result for vadadustat?

John Butler — President and Chief Govt Officer

Nicely, that is — and comes as much as the FDA. So we’ll wait and see. We’ll have each units of knowledge to place in entrance of them as shortly as we are able to, and we won’t wait to place this information in entrance of the regulators. So in the event that they wish to have an end result, we will probably be very prepared for it.

Allison Bratzel — Piper Sandler — Analyst

Okay, nice. Thanks a lot, and congrats once more.

John Butler — President and Chief Govt Officer

Thanks, Ally.

Operator

Thanks. Our subsequent query comes from Eric Joseph with JPMorgan. Your line is now open.

Eric Joseph — JPMorgan — Analyst

Hey, guys. Thanks for taking the questions, and congrats on the Part Three readout right here. John, I needed to choose up in your feedback about how these research have been designed, and also you intentionally selected to go in opposition to the design to check the research in opposition to customary of care. Are you able to simply communicate to how nephrologists view the relative danger good thing about Aranesp versus Epogen, or darbepoetin alfa versus — darbepoetin alfa, and whether or not there’s any significant distinction right here, and that type of may assist in our potential to make type of crosstalk comparisons from INNO2VATE to the dialysis-dependent research with vadadustat?

John Butler — President and Chief Govt Officer

Eric, I did not perceive the final a part of that query. I did not hear you clearly.

Eric Joseph — JPMorgan — Analyst

Certain. There’s going to be some motivation to try to make crosstalk comparability between vadadustat and roxadustat. You may have totally different comparators between the 2 end result research. You are utilizing darbepoetin and versus their Epogen, I am simply questioning when you may communicate to how physicians view the relative danger profit profile of the 2 opponents — of the totally different ESAs?

John Butler — President and Chief Govt Officer

So, what physicians are searching for, Eric, is obvious, simple, and constant information, and that is what we have delivered them immediately. And importantly, when you concentrate on vadadustat, the truth that now we have identical comparator in INNO2VATE and PRO2TECT, that is all a part of how we design this system for scientific, regulatory, and industrial success. We have step one with scientific success with INNO2VATE, and imagine the readability of this information and the way simple it’s will result in regulatory and industrial success for us as nicely.

Eric Joseph — JPMorgan — Analyst

Obtained it. And simply coming again to potential — and simply questioning to — going again to this potential affect from the COVID pandemic, is there any — was there any impacts within the INNO2VATE readout right here the place sufferers have been unable to come back in for his or her, I suppose, secondary efficacy follow-up assessments, and I suppose whether or not you anticipate any affect on whether or not — yeah, sorry, whether or not there’s any affect from COVID within the full assortment of the information in INNO2VATE and the way you may anticipate any affect it impacts from the pandemic as nicely?

John Butler — President and Chief Govt Officer

Certain, Eric. I will ask Steve to handle that.

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Yeah, hello, Eric. No, there wasn’t any problem as a result of we introduced completion of this — we met our MACE on the finish of final 12 months, and so we instructed the websites to deliver their sufferers again as quickly as potential. And so, they made their end-of-treatment visits and the end-of-study visits have been allowed to be carried out by telephone, in any case by the protocol. So it had actually no affect on our potential to gather the information. And with PRO2TECT, clearly there’s nonetheless a while to come back, however given the expertise we had with INNO2VATE we really feel like we’re assured within the mid-2020 timeline. However we’ll replace that if we have to on COVID, however clearly we have been trying actually carefully at it, and really feel very assured within the timing.

Eric Joseph — JPMorgan — Analyst

Obtained it. Thanks for taking the questions.

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Thanks, Eric.

Operator

Thanks. Our subsequent query comes from Difei Yang with Mizuho Securities. Your line is now open.

Difei Yang — Mizuho Securities — Analyst

Hello. Good morning. To begin with, congratulations on the Part Three readout, and only a couple questions. How ought to we take into consideration non-inferiority margins for the NDD inhabitants, is it an inexpensive assumption what you have got reached settlement with the regulatory company in DD could be carried over to NDD? Then the second query is that, would you give us an replace on whether or not the ultimate settlement with Vifor was signed and what is the standing on that, after which lastly, possibly if Jason may touch upon money runway?

John Butler — President and Chief Govt Officer

Nice. So, thanks, Difei. So the 1.25 non-inferiority margins that we had for INNO2VATE is similar non-inferiority margin we’re utilizing for PRO2TECT. In order that’s very clear, and equally with EMA at 1.3. That was the primary query. The second query was?

Kristen Sheppard — Vice President, Investor Relations

On Vifor.

John Butler — President and Chief Govt Officer

Vifor, sure, thanks. In order that’s nonetheless — we’re nonetheless working by means of that. There was no urgency to get that finalized. Really feel very assured in having the ability to make that occur and clearly with this information in hand we’re all very excited to place that in place, after which on the money runway aspect, Jason, you wish to take that?

Jason Amello — Senior Vice President and Chief Monetary Officer

Certain. Hello. It is Jason. So our money runway stays on steerage as we beforehand communicated with our year-end earnings launch and with this launch as nicely, staying nicely into Q 2021, we really feel very assured with our money place with that type of a runway. And in order that hasn’t modified. And we have additionally, to get to that stage of runway, beforehand we have recognized value financial savings and efficiencies to allow us to try this, which additionally positions us nicely given the present pandemic state of affairs. So we really feel very assured with our money place.

Difei Yang — Mizuho Securities — Analyst

Thanks, Jason. And only one fast follow-up close to the FDA submitting timeframe. So, is it an inexpensive assumption usually for, if PRO2TECT is optimistic, the standard lag time and the readout is a few quarters?

John Butler — President and Chief Govt Officer

I am sorry, about…

Kristen Sheppard — Vice President, Investor Relations

Timing.

John Butler — President and Chief Govt Officer

So, Difei, we’re not guiding on actual timing for submitting. When now we have PRO2TECT in palms, then I believe we’ll be higher ready to try this, and the message I need you to listen to is that after we get PRO2TECT, we’ll work really, not after we get PRO2TECT, we’re working already to be — to speculate shortly as potential by means of an NDA submitting, however with PRO2TECT in hand that would be the gating merchandise. So, we will probably be shifting. Like I mentioned earlier than, we’re so enthusiastic about this. We wish to get this entrance of regulators as shortly as potential. And I imply, type of coming again to your final query, it is so excited to be in a spot the place now we have a powerful money place, one set of Part Three information in hand, after which a number of different thrilling milestones which can be proper in entrance of us, the Japan approval and PRO2TECT information. So, the corporate is in unimaginable robust place proper now.

Difei Yang — Mizuho Securities — Analyst

Thanks a lot for taking my questions, and congrats once more.

John Butler — President and Chief Govt Officer

Thanks, Difei.

Jason Amello — Senior Vice President and Chief Monetary Officer

Thanks a lot, Difei.

Operator

Thanks. Our subsequent query comes from Bert Hazlett with BTIG. Your line is now open.

Bert Hazlett — BTIG — Analyst

Thanks, and let me provide my congratulations as nicely, fairly an effort and terrific consequence. By way of the MACE endpoint that readout, have been there any elements of the MACE all-cause mortality, MI, or stroke that have been stronger than others? I do know you’re releasing prime line information immediately, however when you may information just a little bit that may be useful?

John Butler — President and Chief Govt Officer

Yeah, Bert, you mentioned we’re releasing prime line information immediately. However, I imply, I believe the headline for you is constant. This information was extremely constant throughout efficacy, security, and MACE as crucial security and that features all of the elements as nicely.

Bert Hazlett — BTIG — Analyst

Okay, thanks. After which, let me attempt to come on the identical query with regard to remedy — severe TEAEs. It regarded like there was just a little bit decrease severe treatment-emergent opposed occasions on the vadadustat — with using vadadustat. Are you able to make any common feedback about what you’re seeing there on the security aspect?

John Butler — President and Chief Govt Officer

Once more, we’re extremely happy with the security that I will ask Steve to make some feedback.

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Yeah, I believe the general security profile was very optimistic, and together with — there was no circumstances of excessive prevalent incidents. As you keep in mind, we had a single case a very long time in the past. And after we checked out hepatotoxicity, no distinction between the remedy teams, so, very, very happy with the entire security information that I’ve seen immediately.

Bert Hazlett — BTIG — Analyst

Okay, thanks. After which, only one extra query concerning Vifor Pharma and using the precedence evaluate voucher, may you simply undergo the choice tree that you will use as to whether or not you impact that transition? Just a bit bit extra shade can be useful.

John Butler — President and Chief Govt Officer

Yeah, certain, Bert. So, clearly step one will probably be to come back to settlement on the ultimate economics across the PRV, and that is — like I mentioned, that is an energetic course of and I haven’t got any considerations that we’ll get that carried out. The info that now we have generated right here with INNO2VATE would assist — completely assist utilizing a PRV. Like I preserve saying, I can not wait to get this information in entrance of regulators. It is that clear, clear, and constant. So, however clearly we’ll have that dialog with Vifor and, once more, I believe they will agree. I believe they will be as enthusiastic about this information as we’re.

Bert Hazlett — BTIG — Analyst

Terrific. Let me slide in yet another if I may. The WuXi provide deal, may you simply touch upon why you felt the necessity to have a 3rd industrial provide settlement in place for vadadustat?

John Butler — President and Chief Govt Officer

So we even have two API suppliers and that’s clearly simply minimizing any type of provide danger. So, on the API aspect, now we have Esteve and WuXi, after which we even have the third provider is for drug product, API.

Bert Hazlett — BTIG — Analyst

Okay. Thanks. Congratulations once more.

John Butler — President and Chief Govt Officer

Thanks, Bert.

Operator

Thanks. Our subsequent query comes from Chad Messer with Needham. Your line is now open.

Chad Messer — Needham — Analyst

Nice. Thanks. Good morning. And let me add my congratulations on the information. We have clearly been working exhausting to get up to now. Is there any remark you may make on tour information and the way that look, I do know in your opening remarks, you commented on HIFs and the way one of many nice guarantees of this class is giving very physiological and constant hemoglobin response.

John Butler — President and Chief Govt Officer

Yeah. Once more, Chad, what it’s best to hear from me is the extent of pleasure. We’re not going to enter specifics of that information, will probably be offered with the information, hopefully at ASN, that is our expectation. However once more, I imply, as we talked earlier than in regards to the Spherix information that was carried out, this impartial analysis, and we talked about it from Q1. What our physicians searching for so as to undertake a brand new remedy for anemia, and that is among the key areas. Firstly, it’s a physiologic EPO stage, a gradual enhance in hemoglobin, avoiding excursions, and a handy oral dose. We’ve confirmed throughout our improvement program that we are able to do this and INNO2VATE information completely helps that as nicely. So, we really feel like we’re positioned extremely nicely from a industrial perspective in addition to from a regulatory perspective.

Chad Messer — Needham — Analyst

Okay, thanks. That is useful. However after all, we look ahead to seeing the remainder of the information when it is obtainable. And possibly simply additionally an replace on the regulatory course of in Japan. I do know your companion filed final July, is the expectation nonetheless for potential approval this summer time and any updates on regulatory interactions there? And possibly, are you able to touch upon how lengthy it takes to type of launch and get reimbursement in Japan typically?

John Butler — President and Chief Govt Officer

So, thanks for the query. We’re working carefully with Mitsubishi on pre-commercialization actions. All the pieces appears to be on observe there. And as we have talked about earlier than, if PMDA takes the conventional 12-month cycle, it will likely be a July approval. And as I mentioned, we’re engaged on pre-commercialization. It is going to be — we’ll transfer — our companion Mitsubishi will transfer as shortly as potential to launch the product. We actually anticipate it to be launched this 12 months.

Chad Messer — Needham — Analyst

Okay, nice. Thanks and congrats once more.

John Butler — President and Chief Govt Officer

Thanks, Chad.

Operator

Thanks. Our subsequent query comes from Ed Arce with H.C. Wainwright. Your line is now open.

Ed Arce — H.C. Wainwright — Analyst

Hello, everybody. Thanks for taking my questions and congrats on this very optimistic information set to your Part Three and look ahead to the following one quickly. Few questions for me. Principally for Dr. Burke, first is, have been there any deaths in both of the examine or both examine? Second is, when you may focus on a bit extra on how the titration of the drug both up or down compares to the extent of titration, in different phrases how energetic that was relative to Aranesp within the examine? After which, thirdly, now we have the treatment-emergent occasions. I see right here that the numbers have been very constant and related. However when you take a look at, particularly, hypertension and diarrhea, the 2 research seem like numerically one was larger and one was decrease. Maybe you might focus on something you might need seen there with these two, after which I’ve a follow-up. Thanks.

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Certain. We had a technical issue right here, so I heard the primary query and the third, however not the second. So let me reply the primary two that I keep in mind. Beginning with the third query. So, the conversion examine was a lot, bigger virtually 10 occasions as giant because the correction-conversion examine. So, I might put extra inventory within the AD desk for that examine. And the smaller the examine, the much less dependable are the outcomes.

So — and the primary query was deaths, sure. Nicely, as , the first security measure was MACE, which incorporates demise, all-cause demise and the non-fatal stroke and non-fatal MI. Nearly all of the occasions within the MACE evaluation have been deaths. And while you look throughout your entire examine, there have been fewer deaths within the vadadustat handled sufferers than they have been within the darbepoetin handled sufferers. So once more, as John alluded to earlier, very constant security outcomes across the MACE endpoint. And I missed the center query, I am sorry.

Ed Arce — H.C. Wainwright — Analyst

Okay, truthful sufficient. So, the second query was across the titration schedule, you began with 300 after which went both up or extra probably — down or extra probably up after week 4. I used to be simply questioning how energetic all through the examine that titration was on drug relative to the comparator Aranesp and its personal schedule.

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Yeah. The medicine may very well be titrated beginning at week 4, they usually have been titrated up or down as you indicated. I’m nonetheless analyzing that information, so I do not understand how continuously the doses have been adjusted in a really granular sense, however now we have that information and that will probably be offered. And the important thing was, you have been titrating to get into the goal vary for each, and we have been efficiently ready to try this, unsurprisingly with each medicine. So, it was very, very clear.

Ed Arce — H.C. Wainwright — Analyst

Nice. After which, only one final query for me. On the slide deck that you simply offered this morning, Slide 9 right here on the Kaplan-Meier curve, it does seem like there’s a sudden enhance on the darbepoetin occasions at about 168 weeks. Any remark you want to make there?

John Butler — President and Chief Govt Officer

Nicely, that is simply the character of the Kaplan-Meier curves. For those who take a look at the underside of the slide, the variety of folks in danger for having a MACE occasion decreases over time. And while you get to the very finish of the examine, one occasion can have a major affect on the looks of the Kaplan-Meier curve, however I might discourage you from trying on the finish of Kaplan-Meier curves and look towards extra the start within the center. When you see huge jumps or lengthy flat stretches, it means there’s only a few sufferers in danger.

Ed Arce — H.C. Wainwright — Analyst

Understood. Thanks once more.

John Butler — President and Chief Govt Officer

Thanks, Ed.

Operator

Thanks. Our subsequent query comes from David Lebowitz with Morgan Stanley. Your line is now open.

David Lebowitz — Morgan Stanley — Analyst

Good day. Thanks for taking my query. Once you take a look at this information as of so far and also you see doubtlessly bringing this to market within the dialysis inhabitants, how do you see your self differentiating this versus EPO versus darbepoetin. Then your drug is an oral, however they’re already entering into for dialysis anyway. So, they’re used to getting infusions and whatnot? And what is the message with this information for dialysis?

John Butler — President and Chief Govt Officer

Yeah. We expect this information completely helps our industrial alternative in dialysis, David. It is — once more I am going again to the reply I gave earlier. Once you take a look at what physicians are searching for, physicians, they take a look at that distinction in EPO ranges in excursions and in a gradual enhance in hemoglobin.These are all associated to security for them. After which, after all the handy oral dose issues quite a bit within the non-dialysis affected person and residential dialysis sufferers, which after all we’re shifting to, however will probably be crucial in dialysis as nicely. So, vadadustat positions terribly nicely in each dialysis and non-dialysis versus darbepoetin alfa or another ESA.

David Lebowitz — Morgan Stanley — Analyst

Thanks for taking my questions.

Kristen Sheppard — Vice President, Investor Relations

Thanks.

John Butler — President and Chief Govt Officer

Thanks, David.

Operator

Thanks. Our subsequent query comes from Kennen MacKay with RBC Capital Markets. Your line is now open.

Kennen MacKay — RBC Capital Markets — Analyst

Hello. Thanks for taking the query and congrats to the entire group, and large congrats to you John for getting vadadustat from the beginning, all the way in which to the end line right here. This can be a actually spectacular information.

John Butler — President and Chief Govt Officer

Thanks, Kennen.

Kennen MacKay — RBC Capital Markets — Analyst

So, these information together with these from roxadustat, I believe actually do validate the category, particularly versus Aranesp in dialysis-dependent CKD really, actually yearly related information with the very same MACE hazard ratio. So, possibly with that in thoughts, I would actually love your perspective and the group’s perspective on how this adjustments your considering in pre-dialysis CKD across the PROT2ECT trial and type of particularly concerning how the management arm, when you’re utilizing right here energetic Aranesp management may affect outcomes popping out of that management — I imply, out of that trial versus what we have seen from roxadustat which have utilized their placebo.

After which, individually, two fast housekeeping questions, one monetary, one scientific. Monetary first, now that the dialysis information is matured and there is going to be a a lot larger focus right here, are you able to assist us with type of a ballpark for the way we must always mannequin the royalty and income cut up in dialysis-dependent CKD with the Vifor and for senior gross sales settlement?

After which on the scientific aspect, you had talked about no circumstances of Hy’s Legislation, which is an enormous aid, are you able to possibly simply elaborate have been there another liver alerts, liver operate take a look at elevations that we’re seeing to only assist put that to mattress? Thanks a lot and congrats once more.

John Butler — President and Chief Govt Officer

Thanks a lot, Kennen. So, going again to [Speech Overlap] lots of totally different instructions and that is nice. So, once more, your query about non-dialysis and PRO2TECT. Look, I imply, from our perspective, and you’ve got heard me say this for 4 years now. That is all in regards to the design. We designed our program in collaboration or actually session with the FDA and EMA. And having the energetic management, keep in mind, that is about regulatory success, scientific success, industrial success. And having an energetic management in non-dialysis is what the regulators requested for and we’ll ship that to them.

And we needed a design that was as constant as potential throughout your entire program INNO2VATE and PRO2TECT, and that is how we have designed it. Now with INNO2VATE information in hand, and as I mentioned earlier, it is the identical evaluation, identical design, identical construction, and many others, for PRO2TECT. Now it is a totally different affected person inhabitants separate examine, all of us need to see the information. However I believe that that related design is a vital side of pacing about PRO2TECT.

On the Vifor settlement, we have not disclosed what the revenue share with Vifor is. We mentioned that it’s — that we preserve the overwhelming majority of the earnings. And naturally, we cut up these with Otsuka. So, Vifor takes their piece after which the stability is cut up between Otsuka and Akebia.

Kennen MacKay — RBC Capital Markets — Analyst

After which, the third — Steven, you haven’t talked in regards to the LFTs.

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Yeah. The LFTs, you are proper, there was no circumstances of Hy’s Legislation within the examine and we had hepatotoxicity as an opposed occasion particular curiosity, there was no distinction between the remedy teams, we additionally analyzed take a look at the proportion of sufferers who had ALT, AST potential, and many others, above a sure threshold. And there was no enhance in that with that vadadustat. So it regarded excellent from a hepatic security perspective. Yet another space — we’re very, very happy with the information.

John Butler — President and Chief Govt Officer

Go forward, Kennen.

Kennen MacKay — RBC Capital Markets — Analyst

No, congrats once more on the clear security profile. Possibly simply going again to that first query of mine. In your thoughts, enthusiastic about the pre-dialysis setting, CKD, would you anticipate an Aranesp arm to check possibly higher or worse on MACE versus placebo. Once more, simply enthusiastic about the very related information in dialysis dependent with the energetic management and enthusiastic about possibly what the hazard ratio may seem like in pre-dialysis, particularly on MACE, it looks like when you have been numerically below one, with that hazard ratio, may provide you with an actual industrial benefit in that setting computing versus among the different gamers on the market. Thanks and congrats once more.

Steven Okay. Burke — Senior Vice President, Analysis and Improvement and Chief Medical Officer

Yeah, thanks. Thanks, Kennen. Yeah, we’re clearly just some months from seeing that information. So we’re excited to see it, and we do assume that the similarity of design between INNO2VATE and PRO2TECT issues quite a bit, and we simply cannot wait to share the information after we get it. I imply, similar to we truthfully could not be extra pleased with the information that we’re sharing with you immediately. I want ASN was subsequent week in order that we are able to share the complete information bundle. And I am certain I will really feel equally round — round PRO2TECT, however all of us have to attend and see that information. The subsequent query please?

John Butler — President and Chief Govt Officer

That is it.

Operator

Thanks, this concludes our question-and-answer session. I might now like to show the decision again over to John Butler for closing remarks.

John Butler — President and Chief Govt Officer

Thanks, Joella, and due to all of you for becoming a member of us immediately. I began — dialysis sufferers are among the many most in danger throughout this pandemic. And we’re doing all we are able to as an organization to assist them that’s clearly our mission. It actually feels great immediately to announce information, that may be a true innovation that we imagine has the chance to considerably assist these sufferers. Once more I wish to thank the investigators and their employees. I wish to thank the sufferers who participated within the trial, and I wish to thank the Akebia group for all they did to ship this excellent consequence to us immediately. Thanks a lot for becoming a member of us. We look ahead to updating you sooner or later.

Operator

[Operator Closing Remarks]

Period: 58 minutes