Greetings. Welcome to Actinium Pharmaceuticals update call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. The information presented herein contains expressed and implied forward-looking statements regarding the current intentions, expectations, estimates, opinions, and beliefs of Actinium Pharmaceuticals that are not historical facts. These forward-looking statements include statements regarding Actinium's expectations for its product candidates, including their therapeutic and commercial potential, anticipated future development activities, anticipated timing of development activities, including initiation of clinical trials and presentations of clinical data and indications Actinium and its collaborators plan to pursue.
Future results of operations and financial position, business strategy, strategic collaborations, any royalty or milestone payments on Actinium's ability to obtain and maintain intellectual property protection for its product candidates. Such forward-looking statements may be identified by such words as believes, may, will, expects, endeavors, anticipates, intends, plans, estimates, projects, should, objective, and variations of such words and similar words.
These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other government agencies, regulatory clearances, responses to regulatory matters, the market demand for acceptance of Actinium's products and services, performance of clinical research organizations, and other risk details from time to time in Actinium's filings with the Securities and Exchange Commission, including, without limitation, its most recent annual report on Form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. I would now like to turn the conference over to Sandesh Seth , Actinium's Chairman and CEO. Thank you. You may begin.
Thank you, operator. Good evening. Thank you for joining us on your Saturday of President's Day weekend. We are in Orlando for the Tandem Meetings, the largest bone marrow transplant and cellular therapy-focused conference globally. I am delighted to be joined by key members of the Actinium team, including Dr. Madhuri Vusirikala, Actinium's Vice President, Clinical Development, Transplant, and Cell Therapy, Dr. Avinash Desai, our Chief Medical Officer, and Christine Yarbrough, Actinium's Chief Commercial Officer. This is an exciting and transformative moment for Actinium. We are pleased to have this opportunity to highlight the full results from the pivotal phase III SIERRA trial of Iomab-B, which were just presented in a late-breaker session here at TCT and received very positively by the BMT community.
I am pleased to report today that SIERRA results support Iomab's value proposition of enabling both improved access and improved outcomes to a potentially curative bone marrow transplant. As previously announced, the primary endpoint of six month durable complete remission was met with a high degree of statistical significance, as evidenced by the P value of 0.0001. Our presentation today will reveal that Iomab provided patients with active AML, a population largely not transplanted under the treatment paradigm currently, with unprecedented access to a BMT and is highly relevant to the outcomes of this trial. Our results today show that Iomab-B treatment improved outcomes in these patients in terms of survival. Specifically, trial results for Iomab-B showed significantly improved event-free survival, doubled both median and one year overall survival, as well as enabling meaningful long-term survival, especially in patients who received the primary endpoint.
Iomab-B patients also had lower rates of sepsis than GVHD. We believe the combination of improved access and improved outcomes of a bone marrow transplant achieved with a Iomab-B regimen provides a significant curative option for relapsed refractory patients. This segment today comprises approximately 50% of all AML patients, and the majority of them are not transplanted. Based on these results and their potential benefits to patients, physicians, and payers, we believe commercial dynamics are aligning favorably for Iomab. Key market factors such as the lack of visible direct competition and concentration of centers are also favorable. By virtue of the SIERRA trial, we have established operations at over 20 centers that together represent about 30% of transplant volume in the United States.
We look forward to leveraging our proven operational experience as the bedrock foundation from which we can bring Iomab-B to market with a focused and lean commercial organization that is not expected to be a massive drain on our balance sheet while delivering on its mission to make Iomab-B a commercial success. The SIERRA results support Iomab-B becoming a new standard of care, offering patients of last resort a chance for longer survival and cure via a bone marrow transplant. The results also represent a practice-expanding opportunity for physicians who have little to currently offer these patients in terms of treatments, let alone one with curative potential. To tell you about these results, I would like to introduce my colleague, Dr. Madhuri Vusirikala. Dr.
Vusirikala comes to Actinium from UT Southwestern Medical Center in Dallas, where she was a Professor of Medicine in the Division of Hematologic Malignancies and also Director of the Allogeneic Stem Cell Transplant Program. She has over 20 years of experience and has performed hundreds of bone marrow transplants with many hematologic cancers. Madhuri serves on several national committees, including the National Comprehensive Cancer Network or NCCN panels for stem cell transplant, acute lymphoblastic leukemia on BMT InfoNet and the Aplastic Anemia and MDS International Foundation. Madhuri plays and will play a vital role in conveying the value of Iomab to her BMT peers and shape the expansion of our Iomab-B and Iomab-ACT programs as we seek to fill the unmet need for better approaches to improve access and outcomes in BMT, CAR-T, and gene therapy. We're thrilled to have Dr. Vusirikala as part of the core team.
Madhuri, over to you.
Thank you, Sandesh. I am thrilled to share the SIERRA trial results. When I was introduced to Iomab-B and Actinium's targeted radiotherapy approach, I immediately recognized the potential for this technology. When I first reviewed the available SIERRA data, I was struck by the profound impact Iomab-B was having on significantly increasing BMT access and improving outcomes for patients we would never consider for transplant. I was even more confident in Iomab-B's potential, given its strong scientific pedigree and clinical results from the prior work at Fred Hutchinson Cancer Center. To date, about 400 patients have received Iomab-B across 12 trials for multiple hematologic malignancies. I believe my contributions to Iomab's development will allow me to have a greater impact on patients.
First and foremost, the SIERRA results are highly impactful, with Iomab-B producing unprecedented efficacy and safety in a patient population that has seen little improvement in outcomes in decades. As previously announced, SIERRA met the primary endpoint of 6-month durable complete remission with a high statistical significance and a P value less than 0.0001. Iomab-B significantly improved event-free survival with a hazard ratio of 0.22 and P value less than 0.0001. Put another way, patients receiving Iomab-B had a 78% lower probability of experiencing an event. In addition, Iomab-B doubled median overall survival and one year survival when compared with patients in the control arm who did not receive Iomab-B. In these older high-risk patients, Iomab-B produced a one year survival similar to what one would expect in younger patients with active disease.
More importantly, 90% of Iomab-B patients achieving a six-month DCR were alive at one year and 60% at the two-year mark, a significant clinical milestone following BMT. In my experience, such an outcome in this patient population is unprecedented. Finally, Iomab-B was well-tolerated and had a favorable safety profile with 4x lower rates of sepsis, a major post-BMT complication, and lower rates of acute graft versus host disease compared to the control arm. I'm very excited by these results, and the totality of the SIERRA data support Iomab-B's potential to become a new standard of care that can provide broader access to BMT for patients with relapsed refractory AML. Here are some facts about AML. It is an aggressive heterogeneous disease of older patients with an incidence of greater than 20,000 patients per year.
Approximately 30% of patients fail to respond to frontline therapy. Those who do respond have a high relapse rate. As a result, more than half of all AML patients will ultimately develop relapse refractory disease, which is incredibly difficult to treat with dismal outcomes. No significant improvements have been demonstrated despite approval of 10 therapies since 2017. Bone marrow transplant remains the only potential curative option. However, less than 20% of AML patients receive a BMT, most of whom are younger and fitter. For the remaining 80%, transplant remains out of bounds. During the past 25 years of my experience as a transplanter, I have seen AML patients having to overcome several challenges related to access and outcomes to have a successful transplant. The first access challenge for the patient is to be in complete remission prior to BMT.
The current clinical practice is not to transplant patients with active AML, as outcomes are poor due to high relapse rates. The NCCN guidelines also recommend treatment to achieve remission prior to transplant in patients with relapsed AML. The second challenge to access is tolerance to current conditioning regimens. For older patients, myeloablative regimens are not an option due to intense toxicity and mortality. The third challenge deals with achieving post-BMT remission and successful engraftment. Inadequate conditioning can lead to graft failure, which is associated with very high mortality. Patients who fail to achieve a CR post-transplant have extremely poor outcome and a survival of few weeks. Finally, the fourth challenge relates to BMT tolerability and post-BMT complications. The conditioning and immunosuppressive regimens given to these patients put them at high risk for infectious complications and toxicity.
While it may seem daunting, overcoming these challenges result in long-term survival and curative outcomes. Unfortunately, 30% of patients with AML have primary refractory disease, while 50% relapse quickly after achieving initial remission. Getting these patients with primary refractory and relapsed AML into remission is very challenging due to characteristics such as age, comorbidities, and disease features such as high-risk mutations, which contribute to lack of response to salvage therapies and limit treatment options. In the absence of a remission, AML patients with active disease are not offered BMT due to poor outcomes. Iomab-B overcomes this challenge as patients with active disease can directly proceed to transplant with positive outcomes. A vital component of BMT is the conditioning regimen given prior to infusion of stem cells to facilitate engraftment and, in some instances, disease control. Currently available regimens are all non-targeted and chemotherapy-based.
Intensity of regimen is inversely proportional to disease relapse, suggesting myeloablation is critical for disease control. Myeloablative regimens are associated with high mortality, especially in older patients, and reduced intensity regimens are associated with high relapse rates. This highlights the need for novel and targeted conditioning regimens such as Iomab-B, which are not only effective but well-tolerated. Iomab-B is a radioconjugate targeting CD45, which is universally expressed on all AML cells as well as the immune cells and stem cells in the marrow. Given its targeted nature, high doses of radiation up to 15-16 gray are delivered to the bone marrow while sparing the healthy organs such as lungs, heart, and GI tract, thereby producing myeloablative outcomes with the safety profile and tolerability of a reduced intensity regimen.
Iomab-B thus allows patients with active AML to proceed to transplant, eliminating the need for multiple lines of therapy to get them to remission. Importantly, Iomab-B works rapidly as it does not need to be internalized in order to produce cell kill. In a highly proliferative disease such as AML, the ability to get the patient to transplant quickly is critical, and Iomab-B enables this. The strong phase I, II data from Fred Hutch, where this drug was developed and studied, was used to design the phase III SIERRA trial, which is the first randomized phase III trial in this patient population. SIERRA enrolled patients who were aged 55 or over with blast counts of 5% or greater in the marrow or circulating blast suggestive of active AML. Simply put, older patients with advanced active disease, a patient population not considered for BMT in current practice.
The control arm allowed treatment per physician's choice from over 20 different available chemotherapy and targeted agents, including Cytarabine, Venetoclax, FLT3 inhibitors, IDH inhibitors, and Mylotarg, in an attempt to get patients to CR. Recently approved AML therapies were added to the SIERRA protocol as they became available, hence, the control arm truly reflected concurrent AML best practice. A crossover arm was designed in SIERRA for an equipoise that offered Iomab-B to patients failing to achieve a CR on the control arm with an intent to rescue them by taking them to transplant. Of note, SIERRA allowed a highly restricted optionality for post-transplant maintenance, which we will discuss later. Approximately 40% of the patients enrolled on the SIERRA trial had received Venetoclax in addition to a variety of other targeted agents, including FLT3 inhibitors, IDH inhibitors, and Mylotarg.
In my experience, as well as based on published literature, patients with these characteristics often have an expected survival of two to three months with very few therapeutic options. My practice, I typically would not recommend bone marrow transplant for them, given extremely poor survival. Patients on this trial had a median age of 68, with the oldest patient being 77 years old. These patients were high risk, with over 90% having intermediate or adverse cytogenetics or molecular features. Over 50% of patients treated were primary induction failure, 1/4 were in first early relapse, and the remaining were relapse refractory or in second relapse. All the patients enrolled on SIERRA had highly active disease at the time of randomization, with some having greater than 90% blast.
Patients were heavily pretreated with a median of three lines of prior therapy, and some had as many as 8 lines of therapy. Before moving on to the results, I want to quickly highlight the comparison of patients on the Iomab-B control arm, which will show that the study arms were well-balanced, reflecting SIERRA's randomization. Again, these were all heavily pretreated older patients with active disease and high-risk features and dismal expected outcomes who would not be offered BMT in standard practice outside of a clinical trial. Here we describe the disposition of the 153 patients randomized to the SIERRA trial. Of the 76 patients on the Iomab-B arm, 66 received therapeutic dose, all of whom proceeded to transplant. 59 of these patients were included in the per protocol analysis, the number used to assess primary endpoint.
Per protocol analysis excluded patients who had major protocol deviations, missed disease assessment, or failed to complete primary therapy, as these would impact interpretation of the primary endpoint. Of the 77 patients on the control arm, 14 achieved a CR and proceeded to allogeneic transplant, 44 crossed over to Iomab-B arm, and 18 had no further treatment. Of the 77 control arm patients, 64 were included in the per protocol analysis. As shown throughout the study and now confirmed with the final results, 100% of patients receiving Iomab-B were able to access transplant without a need to achieving a CR and were able to do so in half the time compared to control arm. We expect this to be even shorter in the real world as barriers for clinical trial enrollment would not exist.
The SIERRA control arm correlates with published data that less than 20% of relapsed refractory AML patients are able to access BMT with currently available therapies. In the control arm, only 14 of the 77 patients were able to achieve remission and able to proceed transplant. This clearly demonstrates that Iomab-B addresses the first two challenges by eliminating the need to achieve a CR prior to transplant and an unprecedented access to BMT. We are excited to present the post-BMT complete remission rates in SIERRA. As shown here, 75% of patients receiving Iomab-B were in complete remission approximately 30 days after BMT. This compares highly favorably to the control arm, where only 6% of patients were in remission after BMT. If you consider BMT access and engraftment with these post-CR rates, Iomab-B's value continues to evolve.
This clearly shows that Iomab-B addressed the third challenge of BMT by producing higher rates of post-BMT CR and engraftment. Before moving to the endpoint results, I want to highlight Iomab-B's excellent safety profile. Iomab-B is well-tolerated given its targeted nature, especially when compared to the non-targeted chemotherapy agents and total body irradiation that are mainstays of current BMT practices. The 4x reduction in sepsis rate is a significant finding as this is potentially fatal post-BMT complication. In addition, patients receiving Iomab-B had lower rates of febrile neutropenia, mucositis, and acute graft versus host disease. All the above results confirm that Iomab-B addresses all the challenges that prevent a substantial number of AML patients from accessing BMT.
As previously announced, Iomab-B met the primary endpoint of six months durable complete remission with a high degree of statistical significance and a P value less than 0.0001. We are excited to report that 22% of the patients receiving Iomab-B maintained durable CR lasting 180 days or more, while none on the control arm achieved a DCR. This demonstrates the difficulty of maintaining durable remissions in this patient population despite being in a complete remission pre-transplant as evident in the control arm. Durable CR in this population where life expectancy is about two to three months is highly meaningful. Patients on Iomab-B arm were restricted to a limited optionality for post-transplant maintenance in order to isolate the effect of Iomab-B.
The standard practice in the real world is to start post-transplant maintenance therapy to reduce chances of relapse in such high-risk AML patients. What's even more exciting is the survival of patients who achieved a DCR with Iomab-B. At one year, 92% of Iomab-B responders were alive and 60% at the two year mark, which is a significant milestone in this patient population and is highly indicative of long-term survival and a possible curative outcome. I also want to point out that median overall survival in this patient population has not yet been... Event-free survival or EFS is a secondary endpoint in SIERRA and is really a pristine endpoint given the SIERRA trial crossover design and accurately represents survival outcomes.
Iomab-B reduced the probability of an event by 78% compared to the control arm with a hazard ratio of 0.22 and a P-value of less than 0.0001. The separation of these curves illustrates the difference. In SIERRA trial, an event is defined as one of the following: a patient not achieving CR or CR with incomplete platelet recovery or crossing over, patient not receiving BMT, and a patient relapsing or unfortunately dying. Due to the SIERRA crossover arm, you see the initial steep drop as patients who experience any of these defined events are treated as if the event happened at time of randomization or day zero.
Overall survival is the other secondary endpoint in SIERRA, and as shown here, Iomab-B doubles median overall survival from 3.2 months- 6.4 months when compared to the control arm excluding crossover patients. one year survival was also doubled with Iomab-B from 13% - 26%. Despite the confounding effect of the crossover design on the overall survival statistics, positive results were noted. As you can see, we have included survival curves for patients randomized to Iomab-B and those that received Iomab-B after crossover. The one year survival for these groups is right around that 30%, which is highly meaningful in this patient population. Just to remind you, expected median overall survival for these patients is two to three months without a BMT. Here I want to share information regarding the patients who crossed over to the Iomab-B arm.
80% of patients on the control arm failed to achieve a remission, and two-thirds of them were able to cross over and proceed to transplant using Iomab-B-led conditioning. The outcomes of these patients in terms of engraftment, DCR, and survival was comparable to that of patients on the Iomab-B arm. Patients who failed salvage therapy in the relapsed refractory setting have very limited therapeutic options, and the ability to take such patients to transplant successfully using Iomab-B further supports its value proposition. To conclude, due to several challenges I discussed in detail, patients who are older and have active disease are routinely not offered curative BMT in current practice due to extremely poor outcomes. It's very clear that Iomab-B is able to overcome the access and outcome challenges in this patient population.
Using an Iomab-B-led regimen, an unprecedented number of patients have access to transplant and were able to do so with active disease, eliminating need for achieving a pre-transplant CR. With an excellent safety profile, Iomab-B produces 100% engraftment rates and a high post-transplant CR, which translates into durable CR with high statistical significance with a P value of less than 0.0001. The two-year survival of 60% in patients achieving DCR is even more exciting and unprecedented. The secondary endpoints of overall survival and event-free survival in the SIERRA trial clearly favor Iomab-B over the control arm. Iomab-B represents an exciting new paradigm in the management of AML patients and establishes a potential new standard of care in relapsed refractory setting. I would now like to introduce Dr. Avinash Desai, Actinium's Chief Medical Officer.
Avi joined Actinium in November 2020 with 27 years of biopharma industry experience focused on clinical development and medical affairs. As a hematologist oncologist, Dr. Desai has had significant roles in the development of successful hematology products such as Darzalex and Velcade while at Johnson & Johnson. He has participated in multiple successful product approvals, launch readiness, strategy development, and lifecycle management plans. Prior to joining Actinium, Avi was Vice President, Head of U.S. Medical Affairs for Oncology at GSK, where he and his team launched three oncology products in 15 months. Avi, I'll hand it over to you.
Many thanks, Madhuri. Let me provide further context for the long-term outcome results of Iomab-B patients who meet primary endpoints, which Madhuri just presented. Just a reminder, in the routine clinical bone marrow transplant practice, these patients would never be considered for transplant and usually have dismal outcome. Iomab-B provides unprecedented BMT access and improved outcomes with better tolerability, opening the promises of better transplant outcomes for the entire universe of relapsed refractory patients. Remember, these patients are reaching long-term survival outcomes despite trial's strict protocol that limited maintenance therapy optionality. In the routine clinical practice, where maintenance therapy is routinely used, we would expect to see even more patients achieving long-term survival outcomes. These results clearly demonstrate Iomab-B's practice expanding opportunity as more patients will be able to access transplant, and once they reach 100-day post-transplant mark, they can return back to their referring hematologist for long-term care.
My partner, Christine , will touch on the significance of this for commercialization in more detail in just a bit. It is apparent from the table on the slide that despite addressing most difficult patient segment in AML, i.e., older relapsed refractory patients with active high-risk disease, Iomab-B results compare highly favorably to approved AML therapies. Even some of them for early line of treatment and even for younger and fit patients population. Iomab-B's P value of less than 0.0001 for the primary endpoint represents one of the most robust P value ever seen in recent AML drug approvals. Overall survival is a secondary endpoint for Sierra, Iomab-B produced 100% increase in survival and highly statistically significant EFS improvement with a P value of less than 0.0001.
A majority of recently approved AML therapies have been able to produce only a modest survival advantage, again, in earlier line of treatment and in younger and fit patients. These impressive outcomes of such magnitude clearly supports Iomab-B's undisputable value proposition. Here we take a more specific comparison of Iomab-B SIERRA results to recently approved AML therapies that are widely used. You can see that Iomab-B's 100% increase in median oral survival stands out compared to Venetoclax, CPX-351, Vyxeos, and Gilteritinib. It is worth emphasizing that Iomab-B produced this highly favorable increase in median oral survival in most difficult patient population that has the lowest expected survival benefit.
We are not suggesting a direct apples-to-apples comparison, we believe newly approved therapy will increase Iomab-B's addressable patient population as they can keep these patients' disease in control after initial diagnosis, so that they can get a bone marrow transplant with an Iomab-B-led regimen. Most importantly, Iomab-B provides this patient who have a clear unmet medical need and their physicians hope for better outcomes. Once approved, Iomab-B would represent the first available therapy for this patient population with no visible competition in sight. With the strong SIERRA results, it provides a compelling foundation for commercial edge. We presented the full results of SIERRA study at this Tandem Meetings. This year will be full of several exciting milestone and robust activity.
We will continue to build further awareness of SIERRA results and Iomab-B value proposition on a global scale by presenting at various U.S. and international medical conferencing across Atlantic in near future. We are actively working on launching an early access program to make Iomab-B available for physicians who believe their patients could benefit from Iomab-B, who have no other treatment options before it is available commercially, assuming approval. We will be focused on filing strong BLA and begin life cycle planning initiatives right away. Assuming approval, we'll also launch Iomab-B in U.S. while working with our Humana partner, Immedica, to support EMA and other regulatory filings with European Medicines Agency. These significant milestones will help us with our goal in establishing Iomab-B as new standard of care for relapsed/refractory AML.
Our life cycle planning initiatives are supported by significant prior clinical experiences from Iomab-B's development at Fred Hutch, where across generations of leading bone marrow transplant physicians and scientists has worked tirelessly to study Iomab-B in variety of hematological malignancies, including myelodysplastic syndrome, acute lymphocytic leukemia, lymphomas, and multiple myelomas. This indication represent potentially tens of thousands of patients with relapsed refractory disease having similar unmet needs to these AML patients in SIERRA. Across this early trial, Iomab-B demonstrated similar access and improved outcomes. This data, together with strong results from our pivotal phase III SIERRA trial, will be leveraged to execute our comprehensive life cycle management strategy to further expand Iomab-B's role in this variety of malignant and non-malignant hematological disorders. These patients are treated at the same concentrated bone marrow transplant high-volume centers that were in the SIERRA trial.
During the successful execution of Sierra, we developed several core competencies at leading high-volume bone marrow transplant centers. We established and actively manage end-to-end supply chain, and we take a great pride in being able to say that we have never missed a single patient dose. We are able to rise the challenge of treating even 60% more patients than expected due to high number of crossover patients. We focused on operational excellence at the point of care, working in partnership with leading key opinion leaders and their teams to successfully execute Sierra at wide array of centers. As a result, we have broad reach across leading bone marrow transplant centers that account for 30% of bone marrow transplant volume.
I'm not aware of that many trials that touches 30% of targeted commercial market in a phase III trial, which speaks to how concentrated bone marrow transplant market really is. The positive SIERRA results of unprecedented access and outcome, along with our commitment to operational excellence, provided strong foundation for our commercial team. I would like to introduce Christine Yarbrough, our Chief Commercial Officer, who will take you through commercialization strategies. Christine joined Actinium in last October with 25 years. Prior to Actinium, she was the Portfolio General Manager at U.S. Oncology at Novartis, managing more than $1 billion product portfolio. She has strong hematology experience from leading Novartis' chronic myeloid leukemia portfolio, including Scemblix and Tasigna, and led strategic account management to support launch of first approved CAR-T therapy, Kymriah.
She also has a significant prior experience at GSK, BMS, and ViroPharma, and Merck. Christine has a deeper understanding of hematology market and CAR-T and bone marrow transplant center dynamics. Christine?
Thank you, Avi. With multiple years in the industry across a variety of specialty businesses, I've spent my career helping to bring new therapies to patients in need. Having led the CML business at Novartis, I gained significant insights into the hematology space, commercializing drugs such as Scemblix and Tasigna in a highly competitive space. I also led strategic account management for Kymriah, the first approved CAR-T therapy, where the team and I worked with transplant centers and physicians to bring a novel, high-value product to patients. I'm thrilled to join Actinium at this pivotal point in the company's trajectory and apply these highly relevant experiences to the commercialization of Iomab-B.
I was drawn to Actinium because of the potential of Iomab-B to significantly improve outcomes in a patient population that is underserved by current therapies and the future potential of the company's pipeline, such as CAR-T conditioning with Iomab-B, the clinical stage asset Actimab-A, and the emerging solid tumor programs. You've heard from Doctors Vusirikala and Desai about the large segment of AML patients that remain in need of life-saving therapeutic approaches and how the results from the SIERRA trial of Iomab-B demonstrate progress against closing that gap. Iomab-B addresses these challenges by providing increased access to BMT in a therapy that combines the safety and tolerability of reduced with the level of bone marrow ablation required to achieve engraftment and longer-term survival in patients that previously would not even qualify for BMT.
It's an exciting development that allows physicians to deliver more transplants to the relapsed refractory population, which represents at least 50% of all AML patients. This group currently has a much lower expected survival rate without the ability to access this proven therapeutic intervention. Patients can return to their primary oncologist for long-term follow-up care. When we evaluate what is realistic in terms of commercialization, we can summarize the opportunity using the three Ps and two Cs as outlined here. Let's start with the first P, patients. There is a very attractive profile for patients, many of whom are not offered the opportunity to receive a transplant because of their age, fitness, or disease status, particularly once they have relapsed on other therapies. Additionally, the side effect profile is appealing.
In recent market research, patients who had received a transplant emphasized their conditioning regimen for transplant was one if not the worst part of their AML treatment journey. If we think about the needs of physicians, well, there's already a proven treatment paradigm, BMT, that is the ultimate goal for nearly all of their AML patients. Often, this is seen as the only real option for survival. Enabling them to provide that proven intervention at much higher levels than seen previously is a simple fit with existing practice, overcoming one of the most frequent hurdles to commercialization of new therapies, which is unfamiliarity with a totally new approach. There is value for payers in providing access to life-saving therapy with manageable safety and tolerability. The average cost of treatment for an AML patient is around $300,000. When transplant is involved, costs can exceed $1 million.
Iomab-B potentially enables better value to be unlocked through getting more patients safely to effective transplants, increasing the length and quality of life for patients that currently have dismal outcomes using available options. Now let's discuss the two Cs. In the competitive space, there has been a lot of development focus in AML, as you heard, with multiple new product therapies over the last several years. However, they've primarily been focused on addressing genetic mutation with limited current or visible competition in terms of increasing access to BMT through better conditioning. Other programs utilizing ADCs or naked antibodies have recently terminated clinical development. As a consequence, the results of SIERRA are even more important to patients and physicians. Finally, the concentration of treatment of these patients is highly attractive as we can build a streamlined, efficient commercial presence to bring Iomab-B and similar therapies to market.
Transplant is a highly specialized intervention. The top 50 centers in the U.S. perform about 75% of all transplants. A small team of account managers, along with other functional experts, will call on these centers to provide clinical education and support with reimbursement and patient services. With an expectation for a total commercial organization of likely less than 50 people, the overall P&L will be far more attractive than, for example, when patient treatment is spread widely across community oncology. The profile of Iomab-B and AML is a perfect fit for a lean, focused biotech approach. Further support for the opportunity we anticipate for Iomab-B comes from looking at analogous product launches and how they have been received and used in clinical practice. On this slide are a couple of examples of products that successfully address significant unmet needs in hematology, specifically in relapsed refractory patient populations.
Blincyto, which is indicated for CD19 positive, MRD positive B-cell precursor ALL, and often used as a bridge to transplant, was launched at a price of $178,000 per year and has seen continuous growth since launch. Yescarta, a CAR T-cell therapy initially launched in third line plus relapsed refractory large B-cell lymphoma and recently expanded into second line plus, was launched at a cost of $373,000 for a one-time infusion and now exceeds $1 billion in annual sales. Another example not on the slide is a recent one that I was involved with, which was the Novartis launch of Scemblix in third line plus CML. Despite CML being relatively well satisfied with multiple events, patients still lose response or struggle with tolerability. The brand reached 49% new patient share in this population within just the first few months of launch.
Based on the favorable profile of Iomab-B in a patient indication with high unmet needs and my experience in hematology and cellular therapy, I have great enthusiasm for this product launch, assuming approval. To wrap up our call, I'd like to reintroduce our CEO, Sandesh Seth.
Thank you, Christine, for providing your insights on the commercial opportunity for Iomab-B, and to Madhuri and Avi for taking us through the positive SIERRA results and for putting them into context and elaborating on next steps. We could not be more excited for the future of Iomab-B and Actinium. We're excited that the SIERRA trial has produced results that can transform the lives of AML patients of last resort by clearly demonstrating that an Iomab-B-enabled bone marrow transplant can be a viable life-extending or even curative option. Based on these results, it is clear that Iomab-B can address the needs of the largest segment of AML, namely those with relapsed/refractory disease who comprise over 50% of all patients.
The unprecedented access to an engraftment after a transplant, coupled with the safety benefits of Iomab-B's targeted approach, translate to a patient journey that can extend and produce long-term survival outcomes. These results are a major way station in our mission to bring this potentially life-saving treatment to patients. I wish to take a brief moment to thank our entire company for their yeoman work conducting this first of its kind trial featuring a just-in-time personalized medicine in a complex treatment setting. For the entire duration of this trial, we never numbered more than 30 people, and we never spent more than $20 million a year, except for last year, where we spent $25 million. We also executed four other phase I and phase II trials outside of Iomab-B for Actimab-A during this period.
For Iomab-B, we established a network of trial sites at major transplant centers that account for about 30% of volume and never missed a dose. Our operational excellence, coupled with the boost from these results, give us the confidence that we can avail of the highly favorable commercial dynamics in terms of the three Cs and two Cs that my partner Christine alluded to in order to make Iomab-B available to the largest segment of AML population, patients who cannot currently benefit from a bone marrow transplant, both in the United States and also the EUMENA region via our partnership with Immedica. The SIERRA trial results convinced us of Iomab-B's paradigm-changing profile as a high-value commercial opportunity with highly favorable commercial dynamics.
As Iomab-B is the most developed late-stage radiotherapy asset and could be the next commercial radiotherapy drug, we thought it might be a useful exercise to compare ourselves, broadly speaking, to some recently launched radiotherapies. Unquestionably, the radiotherapy field is receiving great interest with nearly $10 billion worth of M&A and investments in the past few years, in addition to what seems like mushrooming new company formations. From the table, you will see that Iomab-B compares favorably with successful radiotherapeutics like Xofigo, Lutathera, and Pluvicto in terms of on-label market opportunity and future expansion potential. In addition, both Iomab-B as a product and Actinium as a company compare favorably versus many other radiotherapy companies based on our development stage and differentiation of our programs, which are not focused in highly competitive areas such as PSMA, SSTRs, and FAP.
We are excited about our low-dose Iomab-ACT program and our Actimab-A program, whose development prospects have recently been bolstered by our collaborative agreement with the National Cancer Institute. We are excited about our recently announced CRADA with the NCI. This is a broad collaboration that can boost our development efforts with Actimab-A, as the NCI will sponsor all clinical trials with our company only having to supply drug. The intent of this collaboration is very much to develop Actimab-A, our CD33 targeting Actinium-225 labeled radiotherapy, in combination with other regimens, including chemotherapy and various targeted therapies. The ability to produce better outcomes by combining with a mutation-agnostic agent like Actimab-A in an extremely heterogeneous disease like AML, characterized by high relapse rates, presents a viable and attractive development opportunity when one considers the results of our Actimab-A combination trial with the chemotherapy-based regimen CLAG-M.
No doubt, the NCI took these results into account as the outcomes of this study seen to the left of the slide show impressive improvement in overall and longer-term survival in very difficult to treat relapsed refractory AML patients. Going forward, Actimab-A development will not only benefit from the NCI's vast network of over 2,000 clinical trial sites and their MyeloMatch program, but also from significant benefits to the balance sheet, as our company has to only supply drug while the NCI is responsible for all development expenses. Importantly, Actinium has the right to review and approve all protocols and has full rights to all data. We look forward to updating on this program's progress later this year as we move into late-stage development with Actimab-A and CLAG-M, as well as other developments with our Venetoclax combination trial as part of our backbone development strategy.
Let us close by pointing to what Actinium will be focused on in AML, given the strong results from the Iomab-B SIERRA trial and the recent CRADA with NCI for Actimab-A. Iomab-B and Actimab-A remain the only targeted radiotherapies in AML, a disease that is known to be radio-radiation sensitive, and our clinical trials validate the merits of our approach. We believe these two programs together offer us the opportunity to transform the treatment of AML in a complementary fashion, especially in the relapsed and refractory segment, which is over 50% of patients on a prevalence basis. The segment is characterized by dismal outcomes and has an outsized economic impact in relation to its population size. The addressable patient population for our therapies is treated primarily in the top 100 quaternary care centers.
We have established best practices in clinical operations and an efficient supply chain in nearly half of these by virtue of our Actimab-A and most importantly, Iomab-B trials. With commercial dynamics favorably aligning for a successful Iomab-B launch and with a lean commercial organization and with late-stage development costs for Actimab-A expected to be significantly defrayed by the NCI, our mission is to deliver on the promise of both these drug candidates to modify AML outcomes materially, and in doing so, create a differentiated specialty radiotherapeutics company focused on the large hospital. With that, I'd like to thank everyone for joining us this evening. Operator, please open the call for questions.
Thank you. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question is from Kristen Kluska with Cantor Fitzgerald. Please proceed.
Hi, good afternoon, everybody. Congrats on the data and the presentation slot you received today. The first question I had for you is, given that you're already working with the trial with roughly 30% or so of who might be your applicable commercial audience, I'm wondering if they've provided any context or tidbits to you about whether or which patients they may likely to use this if it's approved. Also any thoughts or read-through that you think could be important for targeting the other 70% or so of the market.
Yeah. I think, you know, we just. Thanks, Kristen, for that question. I think the first, you know, part of the question is very easy. You know, as a company, we certainly think that, on-label use is, you know, is going to be widespread, especially based on some of the remarks we heard at the late-breaking abstract by Sergio Giralt, who presented the Iomab-B data. You know, while we certainly cannot speak to off-label use, there were remarks in that late-breaking session, which I believe is online, you know, which indicate that the mindset of physicians is really, you know, disease control. Iomab-B achieves that disease control. It achieves targeted myeloablation without the side effects. And it warrants use, I think, you know, for many patients that would qualify.
We've shown that in the trial that we can get patients to a transplant in half the time. As my colleague Madhuri mentioned, some of that half the time had to do with some of the artifacts of the trial. In real life, that might be a lot shorter, right? I think that's kind of the answer we have for you. You know, while we are focused on getting the BLA approved and expect, you know, the on-label market is pretty significant for IMab, I would sort of refer you to the comments made by our presenters. They reflect the medical community.
Okay. Thank you for that. You know, given your comments on the call, you can't make apples to apples comparisons across trials and real-life utilization. Just curious if you could maybe elaborate a little bit more about how patient populations differ here with the SIERRA trial, perhaps, related to like the ASAP trial, for instance, or other studies that have been evaluated?
Great. With that, I think I'm gonna have Madhuri, our head of transplant, respond to that. Madhuri.
Great. Thank you for that question, it's a very important question. Just like you said about comparison of apples to apples, the patients enrolled on the ASAP trial and the SIERRA trial had very different characteristics, hence the results are not comparable. ASAP patients did not have as advanced a disease. For example, 50% had primary induction failure or so-called poor response to induction, the rest had relapsed one, while patients on the SIERRA trial were heavily pretreated with median three lines of therapy and as many as eight. Patients on the ASAP trial were relatively younger, with a median age of 61, compared to the SIERRA, where the median age was 64.
All the patients on the ASAP trial received only chemotherapy for induction. None received targeted agents, which as you might know, has become standard of care. On the other hand, more than 60% of patients on the SIERRA trial had failed some form of targeted therapy or the other, suggesting a much more higher risk patient population compared to ASAP. Also what the ASAP trial required something called sequential conditioning regimen, which was pretty high intensity. A lot of the patients on the SIERRA trial were heavily pretreated and not eligible for such intensive conditioning. Really, you know, in a nutshell, these patients were very different. It's hard to compare them across trials.
Just to sort of elaborate a little further, Kristen, other than the fact that Iomab patients are just sicker, more advanced. I think, you know, the whole issue of access and the time to transplant for Iomab would be much faster than ASAP. We look forward to hearing, you know, what we hear from the transplant communities. There's a lot of confusion in terms of how ASAP conducted the patient selection, what kind of patient selection issues there might have been. Practice for BMT is very different in Europe than the United States, and clearly some of the regimens they used were less advanced than what we have here today with ven and Ven-Aza combinations. Net-net, there's no real overlap between the two trials, they're different populations.
We're very happy with the Iomab results because this is a Hail Mary for people who die in about three months. Right?
Great. Thank you. Congratulations again.
Thank you.
Our next question is from Joseph Pantginis with H.C. Wainwright. Please proceed.
Everybody, good evening, and let me add my congratulations a second time following the October top line data. This is great to see the numbers. A couple questions, if you don't mind. First, the slide wasn't on today's presentation, but when you actually look at the Tandem slides, it's a very powerful set of forest plots here. I just wanted to ask about, you know, it seems a little out of place based on the rest of the data, but when you look at the initial AML disease status, the relapse refractory population, even though it was only 13 patients, favored conventional care. I'm just wondering, when you compare it to everything, is that appears to be just an artifact. I was just curious if you have any comment.
I'm honestly a little bit confused. Are you talking about the? Yeah, Madhuri, do you wanna take that question?
What specific question did you have regarding the forest plot?
In the forest plot, everything except the relapse refractory status for initial AML disease status favors the conventional care, but it's only 13 patients. I was just curious, you know, whereas all of the other populations for initial AML favor IOMab, I'm just curious your comment on that.
It's actually other way around, Joe, because all the subgroup patient populations favors IOMab, because as you can see, anything less than one, which are the favorable outcome, and that's exactly how you interpret this forest plot, that all the subgroup analysis with you are actually in the favor of IOMab.
Okay. Also very nice to see the safety data with regard to sepsis and GVHD. That's very striking. I was curious, and also the fact that these patients on SIERRA didn't see maintenance therapy. I'm just curious, your, you know, of course, these are just projections, you know, any potential impact if you then go back and add back maintenance therapy for both sepsis and GVHD, you know, any impacts there? Also any efficacy projections, 'cause it appears that you could further improve outcomes for patients there.
I'll have Madhuri answer that, Joe.
Again, a great question, Joe. This trial was designed as a pristine experiment to demonstrate the effect of Iomab-B versus conventional care in guidance with the FDA. Under this guidance, maintenance was highly restricted on the Iomab-B arm. Post-transplant maintenance is a hot research topic, and there are several ongoing studies using more novel targeted agents in this setting, which are a lot more effective than what we have right now for maintenance. We anticipate maintenance will improve outcomes in the future. Standard of practice is to provide early post-transplant maintenance in eligible patients, especially those who are high risk for relapse, such as the patients under SIERRA. Allowing post-transplant maintenance following Iomab-B led therapy will potentially further improve these outcomes.
Oh, great.
Same is-
Go ahead, sorry.
Same is true for the NTGVHD profile access also.
Sure, sure. Thank you. I guess, logistical questions, and I'm gonna leave my regulatory question to the last. I just wanted to see, you know, what the plans are around EAP. That's the second part of the question. The logistical question that I have first is, are there any milestones associated with the presentation of these data from Immedica?
Joe, we don't comment on the specifics of the Immedica agreement outside of what has been publicly disclosed.
Okay. From a commercial standpoint, I know you mentioned about potential about looking for EAPs and what other next steps are and any sort of discussion of a summary or summary of interactions or early interactions with the FDA thus far.
Yeah, again, I think this is something that the company, you know, discloses, as appropriate at this point in time. We are, you know, moving ahead with the BLA filing, which is the next major regulatory event. We are moving ahead full speed in that regard as well as, you know, moving ahead with messaging exactly the, you know, I think the, not just the intent of the EAP, but then, more details at the appropriate time.
Got it. Thanks a lot. Congratulations again. Very nice data.
Thank you.
As a reminder, to star one on our telephone keypad if you would like to ask a question. Our next question is from Yuan Zhi with B. Riley Securities. Please proceed.
Congrats on the CR results. I have a couple of questions, if I may. Between day 100 and month 6, there was a rapid drop of event-free survival. Is that expected? Can you describe what happened there and what was the likely cause of those relapses?
Madhuri?
Sure. Again, great question. I wanna draw your attention to the patient population. These patients had very highly proliferative disease resistant to treatment. The very fact that a CR of 75% was achieved in these patients is unprecedented and is expected that most of these patients will quickly relapse. Despite this achieving DCR rate of 22% compared to none in the control arm, I think is really remarkable. That's what we anticipated.
Got it. I also want to hear if you have any thoughts on those crossover patients who appears to be performing better than Iomab-B only arm, even though they had delayed bone marrow transplant. Understand they received additional chemo to control the disease to some degree.
Avi?
If you can see the impact of crossover arm on the survival, it is within the, like, in range of the confidence interval. Practically, the idea is to show that if you even crossover and in the crossover arm also, you have survival benefit. That means Iomab-B, whether early or late, you still get benefit. That's the whole idea.
Got it. Thank you for that color. One last question from us. Can you maybe describe some common baseline characteristics of those patients who had complete response in the Iomab-B arm? Is it basically every patient, or with different background or they have some common baseline characters?
Hello, are you guys, please check the speaker line to see if it is muted. Our next question is from Justin Walsh with JonesTrading. Please proceed.
Hey, thanks. A couple questions from me. I'm wondering if you can comment on some general differences in patient experiences for those in the Iomab-B arm versus control arm? To put it another way, were patients generally amenable to treatment with Iomab-B? Were there any noticeable differences in their hospital stays or quality of life in the context of lower incidents of sepsis, other AEs, and more rapid time to BMT?
We are now having technical difficulties. Thank you for your patience. We are having technical difficulties. We will be beginning momentarily. I believe our technical difficulties have been fixed. We can proceed.
Great. We can continue with Yuan. I believe he had asked two questions. We can take the following one, if he's still on.
We now have a Justin Walsh with Jones Trading.
Great.
Hi. Yeah, thanks. I'll sneak a couple in here while we can. I was just wondering if you can comment on general differences in the patient experiences for those in Iomab-B versus the control arm. Like, to put it another way there, were the patients like amenable to Iomab-B therapy? Were there any noticeable differences in hospital stay or quality of life in the context of the lower sepsis and other AEs and more rapid time to BMT?
Great. I will have Avinash Desai, our Chief Medical Officer, answer that.
In general, actually, all the physician sites, all the bone marrow transplanters are extremely excited to offer the Iomab-B to patients. The experience of patients with Iomab-B was seamless. They were actually because of the less side effects and tolerability, and the quality of life was much better in this patient population. Also compared to the outcome that we received, obviously, they were superly excited to be part of Iomab-B trial.
Got it. Thank you. And yeah-
In terms of more specific data, Justin, you know, there will obviously be subgroup analysis that we will disclose at the appropriate time at medical meetings.
Great. Looking forward to that. I'm sure that'll be an important point for physicians and patients down the line. My last question here, just wondering if you can provide any color on what the common selections were for physician's choice in the control arm, and wondering if any of these performed better than others and if there was a difference in outcomes for the patients who received some of the newer therapies that were added to the protocol later on.
Great. Madhuri?
Patients in the conventional care arm, as you heard, had option of several other therapies, including chemotherapy and targeted agents. When we looked at the data, more than 50% of the patients had received some form of combination of hypomethylating agent in combination with venetoclax, plus or minus cytarabine.
Got it. Congratulations on the data, and have a great night.
Thank you.
That is all the time we have for today for the question and answer session. We can close today's conference. You may disconnect your lines at this time, and thank you for your participation.