Rockwell Medical, Inc. (RMTI) Earnings Call Transcript & Summary

Good afternoon, and welcome to the Rockwell Medical 2020 Management and KOL Conference Call. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Russell Ellison, President and CEO. Dr. Ellison, please go ahead.

Good afternoon. It is a pleasure to speak with you all. On behalf of myself and the management team at Rockwell Medical, I'd like to thank you for joining us for this important update. The purpose of today's call is to make you aware of plans we have to pursue new indication opportunities for our innovative platform technology, ferric pyrophosphate citrate, or FPC. FPC is a true second-generation parenteral iron. It was developed to replace iron loss in patients with anemia in an entirely different way. This unique and differentiated molecule provides a novel mechanism of action with a physiologic approach. FPC donates iron directly to circulating transferrin, making it immediately bioavailable for critical body processes, which allows the body to use the iron in a physiologic manner. It is the unique properties of FPC that we believe makes the proposed new indications for FPC feasible and attractive. We believe there is a great opportunity for value creation at Rockwell and for our stockholders through the development of our FPC platform in new indications above and beyond the hemodialysis application where there are significant needs to transform the way iron deficiency is managed. This belief is driving our company vision to transform the way iron deficiency and iron deficiency anemia are managed and to establish a new standard of care to address the unmet needs of millions of people affected by this problem. FPC is currently marketed under the brand name Triferic for the replacement of iron and maintenance of hemoglobin in dialysis patients. And today, we will explain potential new therapeutic indications for FPC. Our first priority is for the treatment of iron deficiency anemia in the home parenteral infusion setting. And under consideration is the potential for FPC to treat iron deficiency in hospitalized patients with acute heart failure. Joining me on the call today from Rockwell are Dr. Marc Hoffman, our Chief Medical Officer; and Tim Chole, our Vice President of Marketing and Commercial Strategy. Also on the call are 2 key external experts who have generously agreed to share their perspectives with you on the new FPC opportunities. They are Connie Sullivan, President and CEO of the National Home Infusion Association; and Dr. Inder Anand, Cardiologist and Professor Emeritus from the University of Minnesota. Ms. Sullivan and Dr. Anand, many thanks for being with us. Before we begin the presentation, I would like to remind you that today's call will include forward-looking statements within the meaning of the federal securities laws, which are subject to significant risks and uncertainties that could cause the company's actual results to differ materially from the forward-looking statements. Please review the forward-looking statements disclosure contained herein and on Form 8-K, which was filed with the SEC immediately prior to this call as well as the Risk Factors section of our quarterly report on Form 10-Q for the quarter ended June 30, 2020, filed with the SEC. This conference can be accessed on the Rockwell Medical Investor Relations page. This call is being recorded for audio rebroadcast and can be also accessed on the same webpage. This is an exciting time for Rockwell Medical as we have established a foundational business and we have repositioned the company for growth. Rockwell is a commercial stage company with an innovative platform technology and a solid development pipeline. Our base business is in dialysis concentrates, where we are the #2 supplier in the U.S. with over $60 million in annual revenue. We also currently market the branded pharmaceutical product Triferic, an application of FPC for iron replacement and maintenance of hemoglobin in hemodialysis patients with 2 FDA-approved formulations. FPC, however, is a true platform technology, and we have established a development pipeline for FPC to realize growth for the company from new indications. We estimate the market potential for FPC across multiple indications to be in excess of $1 billion worldwide. Finally, we have assembled an experienced group of leaders in whom I have tremendous confidence and who I believe are uniquely suited to help us accelerate our growth and reach our goals. The following presentation is the culmination of a comprehensive strategic opportunities analysis project which began months ago. Our overall objective for the project has been to expand the use of the FPC molecule for patients through the development of FPC to treat additional medical conditions with unmet clinical needs. We began by consolidating insights from our internal experts, those who have had a deep understanding of the FPC molecule and its potential as a unique therapeutic. Next, we initiated a formal indication prioritization project and engaged a third-party strategic analytics firm to help us perform the initial task of identifying the opportunities with the best clinical and commercial potential. Extensive market research, Medical Advisory Board interactions and expert consultant interviews were then leveraged to support our assumptions as we built initial market opportunity assessments and clinical development plans for each of the top opportunities identified. Now our agenda for the call is as follows: We'll begin by reviewing the FPC molecule to set the stage for how it can uniquely deliver 100% immediately bioavailable iron for use in critical physiologic processes. Next, we'll explain our plans to pursue an indication for FPC for the treatment of iron deficiency anemia in patients requiring home infusion therapy. This is an exciting opportunity where we believe FPC can uniquely meet a significant clinical need in an area of modern medicine which is experiencing tremendous growth. Finally, we will highlight another potential groundbreaking novel application for FPC that is under consideration: treatment of acute decompensated heart failure in hospitalized patients. Before the end of the call, we will have time for a Q&A session, where today's call participants will be available to answer your questions. To begin, I'd like to provide you with an overview of our novel iron replacement therapeutic, ferric pyrophosphate citrate. Today, FPC is available on the market under the brand name Triferic as the first and only treatment indicated for the replacement of iron as a maintenance therapy in adult patients with hemodialysis-dependent chronic kidney disease. FPC is a novel iron therapeutic that donates iron directly and completely to transferrin, bypassing sequestration in the liver. In clinical trials in the dialysis population, FPC maintained hemoglobin without unnecessarily increasing the in the body's iron stores. And it was extremely well tolerated with a safety profile similar to placebo. Importantly, there was no inflammatory response to FPC observed, and there was no increase in the iron-regulating protein hepcidin associated with the administration of FPC. These are all properties that make FPC uniquely suited for further exploration in the 2 areas that will be presented today. We consider FPC to be a true second-generation parenteral iron. Unlike other IV iron compounds, which are classified as iron oxide nanoparticles, or IONPs, FPC is a water-soluble iron salt with a low molecular weight. There is no carbohydrate shell required to shield the iron in FPC because it is tightly bound to the pyrophosphate and citrate. However, the iron-binding affinity of transferrin, the body's circulating iron transport protein, is slightly higher, which enables FPC to donate 100% bioavailable iron to transferrin immediately once in the blood. This means that FPC utilizes the body's natural iron transport process. The amount of free or unbound iron released from FPC is negligible. And no FPC-associated increase in oxidative stress or inflammation has been observed. In this clinical pharmacokinetic study of FPC administered to healthy volunteers, you can see how the amount of total serum iron is nearly equal to the amount of FPC-bound iron at every time point, indicating that iron from FPC is quickly donated to transferrin and is not released as free iron. IV iron is commonly administered for the treatment of iron deficiency with or without anemia to compensate for blood losses and to overcome inflammatory sequestration of iron. However, IV iron products are made up of iron cores with a carbohydrate shell and require uptake and processing by macrophages within the reticuloendothelial system. With concurrent inflammation, a considerable proportion of iron derived from these iron carbohydrate complexes is sequestered within macrophages and in the liver because of the hepcidin-blocked iron release. Hepcidin expression is stimulated by iron overload and inflammation. Inflammation causes a marked increase in hepcidin concentrations, resulting in a block, impeding recycling of iron for macrophages, mobilization of iron from stores in hepatocytes and absorption of iron from the diet. Iron supply is reduced, and plasma iron and transferrin saturation fall, restricting iron delivery for erythropoiesis. In contrast, FPC enters the circulation and rapidly donates iron to transferrin for transport to the erythroid marrow for red blood cell production to maintain circulating hemoglobin concentration. FPC does not require uptake and processing by macrophages for iron utilization, therefore, bypassing liver sequestration by hepcidin. The excellent safety profile of FPC has been established through both the clinical development program and post-marketing surveillance. During the clinical development of Triferic, FPC demonstrated a safety profile similar to placebo in more than 100,000 doses. Most importantly, FPC had no events of special interest for use with IV iron: no iron overload, serum ferritin did not increase and no anaphylaxis. These trends have continued through the post-launch experience with Triferic and more than 1.2 million exposures to the product. It should be noted that all parenteral iron products, including Triferic, regardless of this clinical and safety data, will carry what is referred to as a class effect label warning for hypersensitivity. At the extreme, hypersensitivity may result in full-blown anaphylaxis. However, several of the other iron products have additional warnings and precautions for use that Triferic does not. Specifically, 2 of these products carry a black box morning. Additionally, all other IV iron products have observation requirements for up to 30 minutes after dosing within their label, while Triferic does not. Not only does Triferic not have this added burden for administration, but in its dialysate application, it is put in the central liquid bicarbonate loop at dialysis clinics and administered to 30 to 40 patients simultaneously. FPC is currently only marketed for use in dialysis-dependent end-stage kidney disease patients under the brand names Triferic and Triferic AVNU. We have 3 FDA-approved formulations for this application to then enable FPC to be mixed and delivered via liquid dialysate and the new intravenous formulation, Triferic AVNU, that can be administered to any hemodialysis patient regardless of the biocarbonate technology utilized. Triferic dialysate was commercially launched in the second quarter of 2019, and commercial launch of Triferic AVNU is expected in the fourth quarter of this year. Because FPC has already been studied and approved for clinical use, the safety and efficacy of the product as an iron replacement therapy has been well established. This means that FPC is Phase II ready for new indication opportunities, which we will discuss in detail today. Our top priority will be to pursue an indication for FPC for the treatment of iron deficiency anemia in patients undergoing home infusion therapy. FPC has the potential to address significant unmet need for home infusion patients. The market opportunity is large, and the clinical risk of pursuing the indication is low. In fact, Rockwell engaged in a Type C meeting with FDA in 2017 to discuss this application. And therefore, much is known already what would be required for approval. We are also considering the potential for FPC as a treatment for iron deficiency in acute heart failure. Though we have not yet discussed it with the FDA, it will be necessary for us to develop a full clinical plan and review it with the FDA in the context of a Type C consultation, including a discussion of Phase III study endpoint. The clinical risk of pursuing this indication is currently unknown and cannot be quantified until the Type C meeting is held. We do know that current FDA guidance states that if the planned treatment is for short-term use, typically less than 10 days, for example, a 5-day treatment in hospitalized patients, there is generally no requirement for long-term mortality data. However, we will need to confirm this and other outstanding issues in our Type C meeting with the FDA. With each of these new indications for FPC, there will be a separate NDA developed, distinct and differentiated product presentations and unique J-codes for each. As such, Rockwell could consider the possibility of partnership following completion of Phase II studies for one or both opportunities, either together or independently. To begin, we will now introduce you to the opportunity of an indication of FPC for the treatment of iron deficiency anemia and the maintenance of hemoglobin in home infusion therapy, and it is my pleasure to introduce you to Connie Sullivan. Ms. Sullivan is the current President and Chief Executive Officer of the National Home Infusion Association. She has over 25 years of experience in home infusion clinical practice, operations and executive leadership. Ms. Sullivan is also a member and an expert consultant for the U.S. Pharmacopeia and serves on the expert committee for sterile compounding. She is a home infusion industry leader and a patient advocate. We are pleased to have Connie as our guest to introduce us to the rapidly expanding and increasingly important home infusion therapy market and to help us understand the unmet clinical needs of home infusion patients suffering from iron deficiency anemia. Connie?

Thank you, Russell. It's a pleasure to be on the call today to provide an overview of the home infusion industry. In simplest terms, home infusion is a specialized service that allows patients to receive intravenous medications at home, replacing the need to remain hospitalized or in a skilled nursing facility. Home infusion providers are specialized closed-door pharmacies with expertise in sterile compounding and clinical management of IV therapies. And they utilize a multidisciplinary approach to patient management. Common conditions treated with home infusion include serious infection, cancer, heart failure, immune deficiency, various GI diseases as well as numerous other rare diseases. Home infusion begins with a physician referral in order for an IV medication. And for about 65% of all home infusion patients, they're referred after a recent hospitalization. Once the referral is made, the home infusion provider verifies the insurance coverage, performs an assessment to ensure the patient has a safe home environment and coordinates the nursing services, which can be provided directly by the home infusion provider or in an arrangement with a separate home health company. The clinical team then works with the prescribing physician to develop the plan of treatment and offers recommendations for modification if necessary to ensure the proper monitoring plan is in place to prevent adverse events. Once on service, the home infusion provider purchases, prepares and delivers the medications, which in most cases, requires aseptic preparation in an ISO 5 cleanroom environment, and performs ongoing assessments for efficacy and adverse events. Finally, the payers are then billed for all services. A typical home infusion claim has 3 lines: Providers receive a bundled payment for each day of home administration. Drugs are billed separately, and nursing is also billed by the visit on a separate line. It's important to note that most patients become independent with administering their IV therapy and that nurses are generally visiting once a week. Several studies have found that patients receiving home infusion report a higher quality of life, including improved feelings of control and fewer days of missed work or school. In the Polinski study, the authors described a wide range of benefits, including shorter hospital or skilled facility stays, lower rates of depression and fatigue and less opioid use. Another benefit of home infusion is -- that is particularly relevant today is the reduced risk for hospital-acquired infections. Home infusions have experienced a surge in demand during the public health emergency from patients who are trying to avoid exposure to COVID-19. Finally, in the largest study to date of patient satisfaction in home infusion, NHIA found that more than 97% of patients agreed or strongly agreed with the statement, "I was satisfied with the overall quality of the services provided." Providers also scored extremely well in specific tasks such as patient instruction with learning to administer the IV medication. The vast majority of home infusion today occurs in patients under the age of 65 due to commercial payers embracing the cost savings and higher quality of life associated with home infusion therapy. Commercial plans typically include home infusion in the major medical benefit as opposed to covering the services part of the prescription drug benefit. Unfortunately, Medicare lags the private sector in coverage for home infusion. There is partial coverage for home infusion under the Medicare Part B durable medical equipment benefit for approximately 30 drugs that require the use of an infusion pump for administration. For patients with traditional fee-for-service Medicare and who are also enrolled in the Part D plan, they may have coverage for the drug but lack a benefit for the services and supplies that are required to make patients successful. If the patient, however, is enrolled in a Medicare Advantage Plan, they may have a home infusion benefit as many of these plans are modeled after the commercial sector. The same is true for patients with Medicaid as, again, commercial payers have embraced home infusion as a lower-cost, higher-quality -- high-quality site of care. The home infusion and specialty infusion marketplace is experiencing explosive growth and provides a favorable reimbursement opportunity for suitable drugs. NHIA recently published a study based on a robust survey of over 220 home infusion providers and compared the results to a similar study published in 2010. The industry as a whole has grown by over 300% in terms of the number of patients served annually. NHIA estimates that provider-generated revenue in 2019 was approximately $19 billion, up from $7 billion in 2010. Anti-infective agents are the most commonly prescribed home infusion therapy. However, there was substantial growth across all product categories. Based on recent trends and current market conditions, we see positive signs for continued growth in home infusion. Key drivers of this growth are high rates of patient demand and satisfaction with services, site of care optimization programs driven by commercial payers, legislation that is pending to close the coverage gaps for Medicare beneficiaries and a robust pipeline of specialty IV drug treatments. It's also worth mentioning that the COVID-19 pandemic has heightened the demand for all home-based care, including home infusion. Additionally, home infusion providers are beginning to utilize technology to expand nursing capacity with virtual visits. We are also seeing an increase in oncology in home infusion, particularly for therapies that are immunologic and have previously been given in hospital outpatient clinics or physician offices. This shift is primarily due to commercial payer site of care optimization programs, the need to reduce capacity in oncology clinics and to accommodate patients that prefer to avoid risking exposure to COVID-19. Now I want to talk a little bit about parenteral nutrition patients as they're commonly treated with home infusion and are at a particularly high risk for iron deficiency anemia. IDA falls into the category of a condition that is relatively simple to identify but challenging to treat with current IV formulation. IDA is estimated to occur in 40% to 55% of all patients on long-term parenteral nutrition. Patients receiving parenteral nutrition for conditions such as short bowel syndrome, fistula or Crohn's disease are prone to IDA and can exhibit symptoms of fatigue, shortness of breath, rapid or irregular heartbeat and glossitis, all of which can affect quality of life. The American Society for Parenteral and Enteral Nutrition, or ASPEN, recommends that patients receiving home parenteral nutrition be screened regularly for anemia and treated with parenteral iron when iron deficiency is recommended by the physician. These patients, it is important to note, are unlikely to respond to oral supplementation. Patients dependent on parenteral nutrition can be challenging to treat for IDA as inadequate response may be related to continued blood loss, inflammation, ineffective absorption or poor adherence to therapy. While IDA is most common in patients with parenteral nutrition needs, many patients on home infusion therapy suffer from diseases which -- in which iron deficiency anemia is commonly associated, but currently, treatment patterns are inadequate. While IV supplementation is more effective than oral formulations, often, home infusion clinicians are reluctant to recommend home therapy due to the formulation options that are available today. Home infusion of traditional IV iron is limited due to risk of hypersensitivity and concerns about incompatibility with other infused drugs the patient may be receiving. As a result, patients may be referred to the physician for an IV iron infusion, which may be costly, inconvenient and may not be available from that physician's particular practice model. Limitations with the current approach can lead to a vicious cycle of late diagnosis and inconsistent treatment. Parenteral nutrition patients, in particular, would likely benefit from a more structured approach to IDA management similar to what is available in end-stage renal disease. The home infusion nutrition support team could then work with physicians to develop established protocols for identification and monitoring of patients requiring IV iron. This type of process coupled with an iron product that has a better safety profile could be utilized in home infusion to improve outcomes in parenteral nutrition patients with IDA. In summary, home infusion therapy is a rapidly growing area of medicine with over 3.2 million patients served every year. The growth trend is likely to continue driven by cost savings versus office-based or hospital care, an improving reimbursement landscape under Medicare and emerging standards resulting in the global -- resulting from the global pandemic. Iron deficiency anemia is a persistent comorbidity, and a feasible, effective treatment regimen remains a significant medical unmet need for many patients receiving home infusion. Overall, management of IDA is inconsistent for home infusion patients, in part driven by limitations with the currently available iron replacement products. Thank you, and I'll turn it over to Tim Chole to talk about market opportunities. Thank you.

Thank you very much, Connie. So considering the expanding home infusion therapy sector of medical care and the opportunity for improvement in treating iron deficiency anemia for patients at home, we believe there is a significant market opportunity for FPC as a home infusion therapy. For home parenteral nutrition patients, specifically, we believe that FPC can meet an unmet need for effective, proactive iron replacement therapy. There are over 110,000 unique patients annually in the U.S. who receive home parenteral nutrition, or HPN, approximately 30% of whom are on long-term, year-round therapy. HPN patients receive daily infusions, each lasting between 8 and 12 hours per day. And according to experts in the field, an estimated 40% to 55% of HPN patients are iron deficient, while the vast majority of them have a negative iron balance due to low or no iron absorption. HPN patients are also prone to inflammation, which can further restrict absorption of iron and result in a functional iron deficiency, where body iron stores are sequestered in the liver. Evidence shows that the negative iron balance in HPN patients results in a deficit between 1 and 2 milligrams per day. Oral iron is rarely an appropriate therapy as patients are most often requiring HPN due to their inability to absorb nutrients through the GI tract. Currently available parenteral iron products are infrequently provided in the home due to perceived risk of hypersensitivity reactions and concerns related to incompatibility with parenteral lipid formulations. Because of the excellent safety profile of FPC and the fact that it is expected to be compatible with PN solutions such as lipids, we believe it is uniquely suited to be the iron replacement therapy of choice for these patients. The maximum market opportunity for FPC as a treatment for iron deficiency anemia in HPN patients for both replacement and maintenance of iron stores is estimated to be near $200 million per year. While we have identified a very clear unmet need for an alternative treatment for IDA in the HPN population, we have also considered the possibility that a similar need exists in patient populations receiving other types of home infusion therapy. The following patients are receiving therapies at home for diseases that are commonly associated with iron deficiency anemia. For example, over 130,000 oncology patients received chemotherapy at home, and published literature confirms that half of chemotherapy patients are iron deficient. This is also a population that is characterized by high inflammation and, therefore, is at a high risk of functional iron deficiency and anemia. We believe FPC could be a desirable alternative for iron repletion or iron maintenance therapy in a subset of these patients due to its tolerability, iron bioavailability and suitability for home infusion. The applicability of FPC in these additional patient groups will depend on the rate and risk of iron deficiency anemia, the length of infusion time of the primary therapy and the acceptability of alternative therapies such as traditional IV iron loading or oral iron. However, as Connie Sullivan mentioned earlier, we believe that the issue of IDA across the entire home infusion population is not effectively managed. And this in large part is due to limitations with the currently available iron replacement therapy options. The general indication we intend to pursue for treatment of IDA in home infusion would allow us to access this broader market opportunity beyond just the opportunity with home parenteral nutrition patients. In some cases where home infusion therapy providers may not play as active of a role in patient care planning, it may be necessary to leverage direct-to-prescriber, peer-to-peer education programs or to find partners for co-promotion to gain adoption of FPC in these additional patient populations. The additional FPC market opportunity associated with these other home infusion patient populations is estimated at $400 million. This chart explains in general terms how traditional high-dose IV iron is currently provided for patients receiving home infusion therapy and how the proposed application of FPC would compare. So as we've mentioned, patients diagnosed with iron deficiency anemia may require a loading dose of iron to replace body iron stores, otherwise known as iron repletion therapy, and iron repletion course can be given with traditional IV iron in 2 to 5 infusions of 15 to 30 minutes each. However, due to concerns aforementioned, the therapy is rarely given at home, and patients must visit a physician office, infusion center or a hospital to receive it. FPC as an alternative would need to be infused at a slower rate over the course of 1 to 3 weeks, depending on the iron needs of the patient. But there could be distinct advantages, no office visit will be required, and in some cases, therapy could be administered concurrently with other home infusion drugs. We've also explained how home infusion patients at risk of IDA would benefit from a more proactive maintenance approach to iron therapy. Parenteral iron maintenance therapy is not routinely provided in home infusion with the currently available traditional IV iron products. FPC as an alternative could enable ongoing iron maintenance dosing safely at home in small regular infusions. With a flexible dosing schedule and excellent safety profile, FPC would be uniquely positioned to support the home infusion services model. Too often, novel biopharmaceutical products are introduced and approved for use in the U.S., and market access for those products is poor due to restrictive reimbursement policies. In this case, we have thoroughly investigated the home infusion reimbursement landscape in advance with the support of experts from the NHIA, and we believe a market access pathway is in place for FPC. It's likely that FPC would be eligible for favorable reimbursement from commercial payers, who have a well-established and universal coverage approach in place for home infusion therapy, which includes separate ASP plus reimbursement for drugs. Drugs are reimbursed via a buy-and-bill process for home infusion service providers. Coverage for home infusion drugs is also available under the Medicare Part B durable medical equipment benefit. And although there's a narrow pathway for approval under this benefit, we believe FPC could meet the criteria. To ensure optimal pricing and reimbursement, we believe FPC needs to meet the additional criteria shown: must be approved with an NDA, be presented as a product differentiated from previously approved formulations of FPC, receive a unique J-code and have a product label which describes delivery with an infusion pump. As Dr. Hoffman will explain, our clinical and regulatory development strategy will be carefully designed to ensure that these criteria are met. And we intend to design the product presentation for FPC in a way that will be optimized for the home infusion therapy services model with the objective of streamlining care so that providers will be comfortable recommending it to prescribers based on the opportunity to improve patient outcomes. I would now like to hand the call over to Dr. Marc Hoffman, Rockwell's Chief Medical Officer, who will take us through the development plan for FPC in home infusion. Dr. Hoffman?

Thank you, Tim. Home infusion clinicians are hesitant to recommend IV iron supplementation due to the potential for severe hypersensitivity risk, however rare. This is particularly concerning in the unsupervised home environment. As you heard earlier, several of the current IV iron preparations come with specific warnings and contraindications for use as well as requiring some formal monitoring period in the instructions for use. In both clinical trials and in post-approval use, FPC has demonstrated an excellent safety profile in more than 1.2 million users and, as a result, is not encumbered with any of these restrictions. Treatment with traditional IV iron therapy can temporarily address iron deficiency, but iron deficiency may persist due to inflammation and sequestration of the iron, whereas FPC is immediately bioavailable and does not increase hepcidin nor is it impacted by it. As a result of the aforementioned concerns, managing iron deficiency with traditional IV iron is inconsistent for home infusion patients. The amount of effective or bioavailable iron will depend on a number of these factors versus management with FPC, which can be delivered as a predictable physiologic maintenance dose to address an ongoing negative iron balance and prevent iron deficiency anemia. Our clinical development strategy for home infusion leverages data that has previously been generated for the FPC molecule, primarily in the preclinical areas of toxicology and pharmacology. This data is foundational for our dosing and pharmacokinetic modeling. Rockwell will need to file a new IND for these indications. The remainder of the data that would be required to be generated in support of this NDA will be new and unique in these indications and primarily clinical in nature. The NDA will be for a novel indication home infusion, resulting in a new presentation to be determined by further feasibility and market research and a new dosing regimen. Therefore, the regulatory filing for this indication will be an NDA as opposed to an sNDA and is expected to yield new NDC and J-codes for these indications and presentation of FPC. From there, we will take a largely conventional approach to the development of this indication, leveraging previously established data on safety and efficacy. After consultation with thought leaders in this space, both clinical and commercial, we will request a Type C meeting with FDA to present our clinical plan. Type C meeting is any meeting other than a Type A or B meeting between CBER and CDER and a sponsor or applicant regarding the development and the review of a product. Type C meetings are scheduled to occur within 75 days of FDA receipt of the written meeting request. Our goal would be to schedule this meeting with the FDA toward the end of 2020 or early in the first quarter of 2021. Official minutes of the meeting will be issued by FDA within 30 days of the meeting. In our briefing package to FDA, Rockwell would lay out the intended clinical development plan for FPC for the treatment of iron deficiency anemia in adult patients receiving home infusion therapy regardless of the underlying cause for the home infusion treatment. As with any other clinical development plan, we will establish efficacy of FPC in this setting and generate additional safety data in a new population. Because of the large safety database that we have in a fragile patient population, we have not eliminated but greatly mitigated any safety risk that would otherwise be present at this stage of development. We are confident in this strategy as there are strong precedents even within this class of drug for the development of a broad label claim based upon clinical studies in narrower, undifferentiated populations. Feraheme, Injectafer and, most recently, Monoferric are indicated for the treatment of iron deficiency anemia in adult patients who have an intolerance to oral iron or who have had unsatisfactory response to oral iron. In the Feraheme label, there are no specific disease states identified in their clinical trial section. For Injectafer, primary causes of iron deficiency anemia were heavy uterine bleeding and gastrointestinal disorders. Monoferric studied a heterogeneous population of adult patients with iron deficiency anemia caused by different etiologies. Additionally, none of these labels, who are the labels of our major competitor products, touched on our target areas of therapy. An advantage of our development strategy is that it incorporates previously established pharmacology, toxicology and a robust safety database with more than 1 million users. As a result, we are able to launch directly into Phase II development. We have envisioned a relatively simple and straightforward development plan for this indication, leveraging our extensive knowledge of anemia management. As we've just heard from Connie, the treatment paradigm for anemia in home infusion populations is broken, and this is a problem that is both underdiagnosed and undertreated. As a result, we would use an observational approach to determine practice patterns, levels of iron deficit, treatment targets and dosing strategies across patient segments. Once these have been identified, Rockwell plans to conduct a more traditional dose scheduling study in several patient segments, for example, patients receiving parenteral nutrition or long-term inotropes. At the conclusion of these 2 programs, we would have validated endpoints and confirmed dose response, for example, the amount and time required to increase hemoglobin by 1 gram per deciliter. We would also gather additional safety data in the new patient populations as well as additional data on inflammatory markers. Together, these studies should establish our proof-of-concept for this indication in the home infusion setting and our first go/no-go decision point, which would be achieved in 13 to 18 months from the initiation of the program. Both of these studies are relatively small, short and, by drug development standards, inexpensive but should meaningfully reduce clinical and safety risk to the program and inform the design of the Phase III clinical study. Prior to initiating a Phase III program, we will take advantage of an end of Phase II meeting with FDA to present our findings and validate our Phase III study design, patient selection criteria and endpoints. An important benefit of our plan, as constructed, is that it takes a stepwise approach to answering these important clinical questions with the opportunity to assess and report our findings after each study is completed. Here, you see a schematic for a proposed Phase III study in home parenteral nutrition. A similar study design would be employed for an additional patient population. This is a randomized, double-blind standard of care controlled study of 200 to 300 patients receiving home parenteral nutrition with the concurrent diagnosis of iron deficiency anemia. The study would involve 3 periods: run-in, whereby we would establish eligibility for the study; a treatment phase; and then long-term follow-up. During the treatment phase of the study, we will establish the safety and efficacy of FPC in the treatment of iron deficiency anemia. In the long-term follow-up phase, the study will establish the safety and efficacy of FPC as maintenance therapy for the replacement of iron to maintain hemoglobin in adult patients receiving home infusion therapy. The primary endpoints would be safety and change in hemoglobin from baseline. The secondary endpoints would include standard iron parameters, such as TSAT, ferritin and serum iron as well as inflammatory markers and quality of life measures. The regulatory strategy would be to submit an NDA for treatment at the conclusion of this phase of the study and then follow this with a supplemental NDA for the maintenance indication at the end of the long-term follow-up. In this way, we would not delay market access until the conclusion of the long-term follow-up. With that, I will turn the call over to Dr. Russell Ellison to summarize this new FPC indication opportunity for us. Russell?

Thank you, Connie, Tim and Marc. In summary, we believe we have a tremendous opportunity to develop FPC as a new treatment for iron deficiency in home infusion patients that will transform care for the patients that need it. As Connie explained, home infusion is an area of medicine that is experiencing explosive growth, a trend that is likely to continue, fueled in part by COVID safety concerns. Iron deficiency anemia in certain subpopulations of patients receiving home infusion therapy is a serious concern, and management of the disease is inconsistent at best. This is in part due to limitations with the currently available IV iron preparations, and we believe FPC is uniquely suited to be a home infusion treatment for IDA due to its excellent safety profile, and compatibility with other commonly prescribed home infusion drugs and nutrients, with a total estimated market opportunity of $600 million. Our clinical development plan for FPC is expected to be relatively streamlined and low cost and could be completed in as little as 27 to 40 months, with an estimated total cost of approximately $9 million to $13 million. A go/no-go decision would be reached at the end of Phase II in 13 to 18 months at a cost of $1.5 million to $2.5 million. This is our top priority development opportunity for FPC as we view it to be a tractable clinical development project with relatively low safety risk given our extensive database on the safety of FPC and a low efficacy risk given our expertise and experience in the use of parenteral iron for the treatment of iron deficiency anemia. We expect to be able to address a significant unmet medical need in a growing area of medicine where market access and reimbursement are favorable, giving us significant pricing power. Now we will switch gears and present you with information on a second new concept for FPC that is being explored by the company. FPC for the treatment of iron deficiency in acute decompensated heart failure and patients who are hospitalized. The use of FPC to treat heart failure would be a truly unique application. Tim Chole will kick things off with a brief overview of the target population and a description of the market opportunity. Tim?

Thank you, Russell. Heart failure is a syndrome characterized by shortness of breath, fatigue, weakness, anxieties and edema. Approximately 5 million patients in the U.S. are diagnosed with heart failure. And of these, almost 80% of patients are greater than 65 years of age. Long and frequent hospitalizations, intensive medical treatment and expensive interventional methods for reducing the morbidity and mortality result in a high cost burden to the health care system in the treatment of heart failure. Heart failure may be categorized using a number of different parameters, which are often overlapping and confusing. Right and left heart failure refer to syndromes presenting predominantly with congestion of the systemic or pulmonary veins, leading to signs of fluid retention with ankle swelling or pulmonary edema, respectively. The most common cause of right ventricular failure is a raised pulmonary artery pressure due to failure of the left ventricle, leading to poor perfusion of the kidney, retention of salt and water, and accumulation of fluid in the systemic circulation. Additionally, heart failure may be characterized by the physiology of the defect. When your heart muscle cannot pump or eject the blood out of the heart very well, this is called systolic heart failure, or heart failure with a reduced ejection fraction, or HFrEF. Inversely, when your heart muscle is stiff and does not fill up with blood easily, this is called diastolic heart failure or heart failure with a preserved ejection fraction, or HFpEF. There's no consensus concerning the cutoff for preserved versus reduced ejection fraction, but commonly accepted guidance in the literature coalesces around 35% to 40%. Many additional words or phrases are used to characterize patients with heart failure. These terms can overlap, and physicians do sometimes use words with a slightly different meaning. The word acute, in the context of acute heart failure, has become confusing because some clinicians use the word to indicate severity, and others use the word to indicate decompensated recent onset or even new onset heart failure. The word has been an indicator of time rather than severity. Based on our initial research and discussions with KOLs, we believe that there may be a place for FPC in the treatment of heart failure patients that are acute, hospitalized, and with a reduced ejection fraction or HFrEF. Let's begin now by taking a look at some of the trends in the heart failure population in the U.S. today. An estimated 5 million people in the U.S. have congestive heart failure, a large population that continues to grow. And each year, over 1 million patients are hospitalized with a diagnosis of acute decompensated heart failure. In recent years, there's been an increased understanding of the role of iron deficiency in this disease, and it is now a recognized comorbidity in all forms of heart failure, affecting over half of patients. We estimate that no fewer than 633,000 acute systolic heart failure patients are iron-deficient. In our expert interviews, the following quote came from an academic cardiologist. Iron deficiency is a predictor of worse outcomes. If you have iron deficiency, your prognosis is poor. In a few minutes, Dr. Inder Anand will tell us more about the role of iron and the impact of iron deficiency in the heart failure patient. Regarding reimbursement for drugs used to treat acute heart failure in the hospital, the majority of patients are insured by Medicare or Medicaid through a well-established approach and a bundled payment structure. If FPC is approved as a drug for acute heart failure and used to treat patients at the hospital, it will likely be covered under the diagnostic reimbursement group, or DRG, bundled payment schema. The DRG payment is provided as a comprehensive reimbursement for hospital care, including more supply, services and drugs. The payment level is determined by disease diagnosis, disease severity, and procedures performed during the hospital stay. But it is a flat payment resulting in a capitated reimbursement to the hospital. Commercial payers have largely adopted this approach as well and commonly used Medicare reimbursement rates as a benchmark. Considering this bundled payment structure, FPC must demonstrate clinical efficacy, which translates into health economic value. For the acute heart failure patient, we believe that FPC has the potential to provide this value by proving clinical outcomes that translate into a reduced hospital length of stay and/or a reduced risk of readmission within 30 days of a hospital discharge. Considering the size of the AHF population each year in the U.S. and a high rate of iron deficiency, we see a significant potential for FPC if it is demonstrated to be an effective treatment for hospitalized AHF patients. FPC is uniquely suited to safely deliver 100% immediately bioavailable iron when administered via slow IV infusion. Patients could receive up to 40 milligrams per day for an average of 4 to 5 days for a total of 160 to 200 milligrams. If it can be demonstrated that this regimen of FPC improves heart muscle energetics and clinical outcomes, the health economic value could support a good price. A 1-day reduction in hospital length of stay for the AHF patient translates into an estimated $2,400 of savings for the hospital and just a 10% reduction in the risk for 30-day readmission translates into a savings for hospitals of about $1,300 per admission. Our estimate then for the total U.S. market opportunity for FPC as a treatment for iron deficiency and acute heart failure is estimated to exceed $1 billion. To tell us more about the importance of addressing iron deficiency in the acute decompensated heart failure patients, it is now my pleasure to introduce Dr. Inder Anand. Dr. Anand has had a long and distinguished career in cardiology with a focus on heart failure. Dr. Anand is a former Professor of Medicine at the University of Minnesota Medical School and the former Director of their heart failure program. He is former adviser to the National Heart, Lung and Blood Institute and NIH, and as well a founding member of the Heart Failure Society of America. He is a current and former editor of numerous cardiology journals and has over 1,000 publications, abstracts and book chapters to his credit. Dr. Anand?

Thank you, Tim, for your very kind introduction. As you know, becoming aware, anemia and iron deficiency are 2 very common comorbidities in heart failure, and they often coexist. Together or independently, they are associated with worse symptoms and outcomes such as increased hospitalizations and mortality. We now know that treating anemia in heart failure with the erythropoiesis-stimulating agents does not improve outcomes and may well be deleterious and is not recommended. Iron deficiency is seen as 50% of chronic heart failure patients and up to 70% of patients with acute decompensated heart failure. An increasing data suggests that intravenous iron in ambulatory patients with heart failure with reduced ejection fractions, improve symptoms, exercise capacity but their long-term outcomes on hospitalization, mortality and safety are not known. All the studies with IV iron have been made in chronic heart failure patients with reduced ejection fraction. And unfortunately, there are no studies in patients with acute heart failure and in heart failure with preserved ejection fraction. Again, although studies suggest that iron plays an important role in improving the energetics of heart failure with reduced ejection fraction. These patients -- these data are not available in HFpEF patient in acute heart or in acute heart failure patients. Now we now know that iron deficiency is indeed an independent risk factor in heart failure. There is an older study from Poland in -- 546 patients with HFpEF. These investigators found that overall, approximately 1/3 of the patients have iron deficiency. And as expected, this was common -- more common in patients who had anemia, shown in the red bars compared to the non-anemic patient, the blue bar. However, iron deficiency with or without anemia increased the risk of death or of heart failure, heart transplantation by 60% as shown in the gray low capital mark compared to those with iron deficiency in the following page. And this were independent, not only of anemia but also of other risk factors. Similarly, in a more recent international pooled analysis of over 1,500 patients with HFpEF, iron deficiency was found to be more important. And an independent prognostic marker than anemia for all caused mortality. Notice as compared to patients with heart failure and no iron deficiency or anemia in the first column, the presence of anemia alone, but with no iron deficiency shown in the second column, includes the risk of mortality, but this wasn't significant. Whereas iron deficiency without anemia shown in the third column increased mortality significantly by about 42%. So the question arises, how iron deficiency worsens outcomes? The reasons are clearly multifactorial. First, iron is an essential component of all energy-producing mitochondrial enzymes. And iron deficiency reduces cardiac and skeletal muscle iron contents, causing both structural and functional mitochondrial abnormalities, including decrease in high energy stores like ATP and phosphates. These explain why iron deficiency can cause skeletal and cardiac muscle dysfunction and thereby reduce not only exercise capacity, but worsen heart failure, quite independent of anemia. Fortunately, over the last few years, it has been possible for us to measure iron and the high energy phosphates in the skeletal and cardiac muscle non-invasively using magnetic resonance imaging. So if iron deficiency can cause skeletal and cardiac muscle dysfunction, does iron replacement therapy help? Clearly, oral iron replacement is the standard of therapy for iron deficiency. It's not only readily available, it is inexpensive, and it effectively raises serum iron level in patients who are -- haven't got heart failure. But because heart failure is an inflammatory state with elevated levels of cytokines and the peptide hepcidin, these inflammatory markers prevent absorption of iron from the gut, and it's released from iron stores in the body. Moreover, oral iron is also associated with several adverse GI effects. It is not well tolerated by many patients, and therefore, often is not used by a large number of them. Finally, there are only a few studies that actually investigated the effects of oral iron in patients with iron deficiency and heart failure. And because of this, the National Institutes of Health carried out Iron Out, a proof-of-concept Phase II study. There [indiscernible] 225 patients with HFrEF, class 2 to 4 heart failure, median injection fraction 25, who were either anemic or non-anemic and they were randomized to oral iron or to placebo. As you see, unfortunately, the study failed to meet either the primary or any of the secondary end points, leading to the conclusion that oral iron may not be the answer to this population. But well before Iron Out was started, a number of small, uncontrolled and controlled studies were being carried out in Europe. The randomized studies among them found that overall IV iron increased exercise capacity as measured by oxygen, peak oxygen consumption, and 6-minute or walk test, it improved quality of life and improved NYHA class. Reduced NT-proBNP levels, a marker of left ventricle function. Because, however, of their small size the outcomes, such as death and hospitalization to heart failure could not be assessed. And therefore, these same investigators decided to pool their data and carried out a meta-analysis of the combined data from the 4 randomized controlled studies that had used ferric carboxymaltose versus placebo in a very identical -- almost identical protocol and very similar patients with HFrEF. IV iron was associated, as you see, with a 32% lower CV mortality after the hospitalization compared to placebo as shown in the last row, with the blue dot. So how does IV iron improve outcomes? I will try to approach this subject by addressing 3 questions: First, does IV iron restore iron stores in the body and particularly in the heart and skeletal muscle? And how rapid is this effect? Second, are these effects associated with improvement in cardiac and skeletal muscle energetics and outcomes? And finally, are the effects of IV iron observed in both chronic and acute heart failure patients? Now it's well -- it is now well established that IV iron rapidly restores myocardial iron stores. Earlier this year, Nunez and its colleagues randomized patients with HFrEF to placebo, 26 of them; and to IV ferric carboxymaltose 27 of these patients. We measured T2 Star and T1 cardiac magnetic resonance imaging to assess myocardial iron at baseline and repeated it at 7 to 30 days after randomization. Notice that IV iron, as measured by T2 Star, T1 MRI, was rapidly normalized by 7 days. The blue column represent the placebo, and the red represent ferric carboxymaltose. Unlike myocardial iron, levels of iron in the blood, as inflected by serum ferritin and TSAT also normalized at 7 days and well maintained at 30 days. But by 7 days, an increase in myocardial iron was not associated with any significant benefit to cardiac function of symptoms or in quality of life. However, by 30 days, symptoms and quality of life improved, but the improvement on LVEF openly of borderline significance. So does IV iron improve myocardial energetics. The next question I'd like to address. Now this study called Ferric HF-II addressed this very important question. And they tested the hypothesis that in HFrEF patients, IV iron with enhanced skeletal muscle energetics, as reflected in a shorter phosphor creating recovery half time on P31 magnetic resonance across the [indiscernible]. The randomized 40 patients, 50% of them were anemic. They were all HFrEF, NYHF class with more than 2 iron deficiencies were present in every one, and they will randomize even to IV isomaltoside or saline. P31 MRS was assessed at baseline and then 2 weeks after infusion. Notice how skeletal muscle energetics improved significantly in the IV iron group shown in the first column, suggesting better mitochondrial function, with no change seen in the placebo group. These significant improvements in skeletal muscle seen over the 2 weeks, short period by any stretch of imagination, were associated with only modest changes in exercise capacity and saw no significant change in FPE cap. So to summarize then, these iron studies assure that although IV iron rapidly entered myocardial cells and improved skeletal muscle mitochondrial function, the functional changes were modest, and there was no appreciable improvement in cardiac function. Taken together, these findings raise the possibility that the kinetics and bioavailability of ferric carboxymaltose and iron isomaltoside that were used in these studies might be slow and the unique properties of ferric pyrophosphate citrate or FPC, and its rapid kinetics might more quickly improve cardiac function and symptoms. Our proposal is designed to test this hypothesis in patients with acute decompensation heart failure. Thank you.

As you've just heard from Dr. Anand, there's an increasing data of evidence suggesting that IV iron in the ambulatory patients with heart failure with reduced ejection fraction, known as HFrEF, improves symptoms and exercise capacity. But long-term effects on hospitalization, mortality and safety had not been formally established, but have been demonstrated in a meta-analysis of the data. Nunez and colleagues have very elegantly demonstrated reuptake and response of the cardiac tissues to the administration of IV iron. However, the delay and degree of impact may be directly linked to the bioavailability of the macro molecular virus. Our clinical hypothesis for the development of FPC in this acute indication is that iron replacement with 100% bioavailable iron, will get more iron direct to the cardiac muscle and faster. Further, FPC administered acutely will then be available for normal physiologic iron metabolism and return to the circulating iron pool. Thus, be available for weeks to come, less normal physiologic losses of approximately 1 milligram per day. And this increase in intracellular iron would yield an improvement in myocardial energetics, improved function, less ventricular ejection fraction and strain and ultimately, a clinical benefit to the acute heart failure patient. The use pharmacokinetics and pharmacodynamics of the currently available iron oxide nanoparticles, IONPs, vary dramatically. These differences are crucial to the application and utility in the treatment of heart failure. IONPs are delivered in very large bolus doses, ranging from initial doses of 100 to 750 milligrams per dose. As previously described, these large doses and complex carbohydrate structures are known to increase inflammation and increase hepcidin, which paradoxically prevents the release of iron to the tissues that need it most. According to the clinical trial section of the U.S. package insert, or their label, approximately 1 gram of ferumoxytol, given to iron-deficient patients, resulted in a 1.35 gram per deciliter increase in hemoglobin. This is an effective correction of a 207-milligram iron deficit but at 5 weeks. Similarly, in the same study, 1,500 milligrams of ferric carboxymaltose given to iron-deficient patients resulted in a 1.63 gram per deciliter increase in hemoglobin, an effective correction of a 245-milligram iron deficit, again at 5 weeks. The IONPs are currently included on both the European Society of Cardiology and the American Heart Association guidelines for the treatment of heart failure. FPC is ideally suited for this population, which is already receiving IV drugs for extended periods of time in the hospital, some 24/7. FPC is immediately bioavailable, getting iron direct to the tissues, and a 2-milligram per hour infusion would result in 200 milligrams of immediately bioavailable iron within the first 4 days of hospitalization, while having no impact on hepcidin and no additional iron sequestration effect in hepcidin. The target indication being explored is the treatment of iron deficiency with or without anemia, in adult patients with acute heart failure or heart failure with reduced ejection fraction, as you've heard more commonly known in the cardiology community as HFrEF. Over the past 20 years, there's been considerable study and progress in the treatment of chronic heart failure. Yet heart failure is still associated with an annual mortality rate of approximately 10%. The 1-year mortality rate after an acute decompensated heart failure diagnosis is approximately 25% and about 6% to 8% for chronic heart failure in the general population. The search for better treatments in this population is one of the major challenges in cardiology today. This is a high level schematic for a mechanistic proof-of-concept study. This concept was developed in close consultation with our expert cardiologists and clinical pharmacologists and the final study design as well as patient selection criteria and endpoints would be determined after further consultation with the study investigators. The objective of this study would be to replicate the findings of iron uptake in the myocardium that was seen with the IONP drugs in the [ NUNA ] study presented by Dr. Anand. But more acutely by demonstrating both iron uptake and a commensurate increase in cardiac energetics and improvement in function within days of administration because of the bioavailability of FPC. The mechanistic proof-of-concept study would be a first critical go, no-go decision in the development plan. By essentially connecting the dots to demonstrate that the improvement in both feel and function will translate into clinical benefit. Functional improvement would be demonstrated with improved less ventricular function captured by echocardiography and is measured by global longitudinal strain. An improvement in energetics measured from phosphocreatine/creatinine kinase ratio and phosphocreatine flux via NMR spectroscopy, by comparing the timing of changes in phosphocreatine between the 2 doses of IV FPC and the standard of care. This would be a first-in-class finding for IV iron in the acute setting. Functional improvements would be demonstrated by exercise tolerance. I'll now hand the call back to Dr. Ellison for a summary of this exciting opportunity under consideration. Russell?

Thank you, Marc. In summary, over 1 million patients are hospitalized each year with acute decompensated heart failure with iron deficiency, a common comorbidity in 50% to 70% of these patients, representing a significant unmet clinical need. A significant body of evidence exists to support the use of IV iron as replacement therapy. Therapy is intended for improvement of cardiac energetics, not necessarily improvement of hemoglobin. The current therapeutic options are IONPs, which are limited in rapid iron uptake and clinical benefit because of their relative bioavailability, particularly in inflamed patient population such as heart failure. In contrast, FPC would be uniquely suited for the hospitalized acute heart failure patient. A 200-milligram dose of immediately bioavailable iron can be delivered during hospital a stay of 4 days, which is roughly equivalent to the impact of over 1 gram of currently available IV iron products, but without the inflammation. A mechanistic proof-of-concept study would determine if 200 milligrams of FPC over 4 days provides a sufficient influx of iron to cardiac tissue to improve myocardial energetics and improve feel and function in heart failure patients. A positive study would retire significant clinical risk and provide the dose response information required to design later phase studies. A Phase III program would focus on heart failure with reduced ejection fraction in the acute hospital setting, where the clinical endpoints would focus on feel and function, as these translate into length of stay. The development plan is consistent with the FDA's guidance on heart failure for drugs intended for acute use. Moreover, the guidance indicates that if the planned treatment is for short-term use, typically less than 10 days, there is generally no requirement for long-term mortality data. It is this mortality data that generally drives up the size, duration and cost of cardiovascular studies. These acute phase studies usually have primary endpoints at the end of therapy, with follow-up to 30 days post discharge. These assumptions would be validated with FDA during the pre-IND or Type C meeting discussions. To conclude, we have outlined the potential development schedule for the further exploration of the FPC indication for acute heart failure. Proof-of-concept study stopping rules, both positive and negative, would be reviewed at the conclusion of each cohort and reports would be provided. And finally, as our top priority, we present to you a development plan summary for FPC for the home infusion indication. As you can see, there will be multiple opportunities over the course of the development phase to provide readouts of progress and reporting of milestones. Once again, I would like to thank the Rockwell team and our expert guests for developing such an informative program, and I sincerely hope you can share our excitement about the future potential for FPC to improve patient care and impact lives. At this time, the operator will open the line for your questions.

[Operator Instructions] Our first question will come from Ram Selvaraju of H.C. Wainwright.

The first is sort of a logistical one for both Dr. Sullivan as well as Dr. Ellison. Can you comment a little bit, the nature of the distribution channel in the home infusion market setting? In particular, with regard to how similar these are to specialty pharmacy networks? Is it a truly closed system? And what kind of infrastructure is necessary in order to ensure distribution of a product through this system? And is that -- this is a question specifically for Rockwell, is that something that Rockwell would have to build or that Rockwell can access through a distributorship?

Russell, this is Connie, do you want me to go ahead and respond?

Yes, why don't you go ahead, Connie. This is Tim. Go ahead.

Okay. Great, thank you. So I want to -- I hope I understand the question correctly, but I'll start with similarity to specialty pharmacy. So while home infusion providers also engage in the distribution of specialty pharmacy drugs, they're generally limiting that distribution to those specialty drugs that require a catheter to infuse. So there is a distinction between home infusion providers and the typical specialty pharmacy in that home infusion provider specialized in the category of drugs that require slightly more clinical support and nursing resources in order to administer in the home setting. So I would say that they're similar, but not exactly the same. They are a truly closed system. So patients generally are not accessing a home infusion provider through -- coming into the facility. They're generally located in industrial-type zoned areas because they have fully functional clean room facilities as well. So what -- in terms of accessing the home infusion environment, the -- Rockwell with a product such as FPC would simply be working through physicians to learn to prescribe that product, identify appropriate patients and refer them to home infusion pharmacies who then work with their drug distributors through a buy-and-bill process, to obtain the product, do whatever preparation is required and they coordinate with the prescriber on the clinical services component. I'm happy to try to follow-up if I can address your question forward.

Thank you, Connie. Tim, would you want to add to that?

The only thing I would add, Russell, and thank you, Connie, is that, that would be something that Rockwell would be able to handle without the use of specialty distributors, think we can handle it with national distribution, the same way we handle our current business.

Okay. Great. And then I guess the second question would be both for Dr. Anand as well as the Rockwell management team. To what extent are you likely for HFpEF versus HFrEF in the future? It sounded as though HFrEF is really the near-term target indication? And would you pursue HFpEF kind of as an independent development path to HFrEF? To what extent, in other words, is development in the HFpEF indication dependent upon the results you see in the HFrEF indication -- in the HFrEF population?

I'll answer -- begin the answer, and Dr. Anand, please fill in. HFpEF is very different than HFrEF. The etiology of HFpEF is different. For example, amyloidosis may be greater than 20%. And so the response of HFpEF to various drug treatments can be different than it is to HFrEF. And there's just many, many failed studies in that indication. So I mean, sitting here today, where we are looking at this, we see a program in HFrEF as being necessary to show efficacy, a meaningful efficacy before we would attempt HFpEF. I mean one could consider, while you're running a Phase III HFrEF study, to do one of these energetics studies with HFpEF. But again, because of the multifactorial or the differences in etiology for this condition, it's hard to say how predictive that would be. So our focus is really going to be on HFrEF. And I'll hand the rest over to Dr. Anand, who can maybe speak more about HFpEF.

So Russell, one of the major concerns in heart failure with reduced ejection fraction is the decrease in the contractile force generated by individual myocytes. And it appears that, that is due to lack of energy compounds, mainly high energy phosphors. And if we believe that giving intravenous iron can cause generation and upregulation of high energy phosphates very quickly, then it's likely that, that would translate into improved contractility. Now if we have seen that in IV iron rapidly goes into the intracellular aspects, into the mitochondria, and that does, over a period of time, translate into high energy phosphates. Does that then translate into increase in contractility? We do not know. How rapid is that effect? We have no idea. But we do know that the IV preparations that are available and approved do not do that, that rapidly. So the question we are addressing is whether this compound, ferric FPC, has the properties of rapidly going in, into the cell and then resulting in beneficial effects on contractility. Now the same cannot be said about preserved ejection fraction because that is not really a contract trial dysfunction. It is a dysfunction of relaxation, which does require high energy compound. But in HFpEF, there are other aspects that prevent the heart from relaxing, such as laying down of collagen tissue which, of course, no high energy compounds will do anything to. So this is why I think we should first go for HFrEF, and then if that does show us promise, then we can certainly do a small study in HFpEF as well.

Okay. That's very helpful. And then just from a market standpoint, can you comment on -- and I think this is a question both for Dr. Anand and the Rockwell management team. If you look at the potential target profile of FPC, is this a place where you would only envisage sort of taking over the market in heart failure from iron oxide nanoparticle? Or are you setting your sights on a significantly broader market opportunity and that, realistically speaking, particularly if we focus, as you just said, on the HFrEF indication?

I'll start. So what we're looking for is, for the use of this product during the hospitalization period, when we think it has unique advantages over the iron oxide nanoparticles because of their slower lead to the liver, especially when hepcidin is elevated, which it is in heart failure. And really, that is where we see the use. Now and so in the IONP studies usually begin with giving the IONP at discharge and then following up monthly, et cetera, with their regimen. So it's a very different setting than what we're going after. And I don't see any indication that the IONP companies are doing studies in the hospital for a hospital-based outcome. So we think we're very separate from that. Now there may be some overlap in the home infusion space because a fair number of chronic heart failure patients are getting drugs at home through home infusion. Now usually, they're inotropic agents. And that might be a setting where FPC could be given to these chronic failure patients at home. However, that may well require a very different program and so on. So it's a possibility, but our -- with respect to heart failure, our focus is absolutely on this white -- this current white space, which is the hospitalized heart failure patient, those 4 to 5 days of hospitalization.

So Russell, I'll take up a little more and expand on what you've just said. So there are 2 aspects here. We have enormous amount of data in patients with chronic heart failure using drugs like ferric carboxymaltose, and they are approved around the world. They have a Class IIa indication in Europe, where they were developed and a Class IIb indication, which means you could give it to them if you feel like, but it's not an essential component. And it's only to improve the subjective aspects of heart failure, I mean, feeling better, working a little more and so on. There is still no data on outcomes of mortality and morbidity. But having said that, there are at least 7 or 8 trials that are going on, thousands of patients. It's very likely that within a few months or even a year or so, you should have data that is likely to suggest that in patients with chronic heart failure, HFrEF patients, this set of agents would probably be approved for the treatment of chronic heart failure to reduce mortality and morbidity. We'll be -- yet to see. On the other hand, in acute heart failure, there is not a single drug available that helps. All the brands that we have available and approved are really for short-term purposes of getting people out of hospitals. These are ionotropic agents. They are either used to keep them out-of-hospital or to bridge before you get on to a transplant program. And continuous use of these drugs, particularly dobutamine and so on, are associated with long-term deleterious effects and mortality. So if you have IV iron that does the same thing, improves contractility without having any side effects, like the one that are associated with the inotropic agents, then I think it is a win-win situation for all of us. But of course, we have to test that hypothesis. Remember that all the inotropic agents which are approved, work by increasing intracellular calcium. And intracellular calcium is really something that destroys the cells over a period of time. And therefore, for chronic use of these agents, the drugs are not -- are actually contraindicated. They are a class III indication in -- even in acute heart failure, if you want to have -- to give them for a long period of time. It's only as a bridge to transplant or just to keep them alive until something else comes up.

Thank you, Dr. Anand.

[Operator Instructions] This concludes our question-and-answer session. I would like to turn the conference back over to management for any closing remarks.

This is Russell Ellison, President and CEO of Rockwell. I just want to close the call by thanking you very much for your attendance and your attention. And we hope and look forward to giving you updates on this program as we go on. And as you can see from the last slide that we presented, particularly on our top priority, which is the home infusion indication. I want to thank very much our participants, Connie Sullivan and Dr. Inder Anand for joining us here today, and my colleagues, Tim Chole and Marc Hoffman for their presentations and participation. And I thank you all very much for taking the time to hear about this from us. And I look forward to giving you future updates. Thank you very much.

The conference has now concluded. Thank you for attending today's presentation, and you may now disconnect.