Cellectar Biosciences, Inc. (CLRB) Q4 2017 Earnings Report, Transcript and Summary

Welcome to the Cellectar Biosciences 2017 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. Following management’s prepared remarks, we’ll hold a Q&A session. [Operator Instructions] As a reminder, this conference is being recorded March 22, 2018. I would now like to turn the conference over to Anne Marie Fields. Please go ahead, ma’am.

Thank you. Good morning. This is Anne Marie Fields, Senior Vice President at LHA Investor Relations. Thank you all for participating in today’s call. Joining me from Cellectar Biosciences are Jim Caruso, Chief Executive Officer; John Hamill, Interim Chief Financial Officer; Dr. John Friend, Chief Medical Officer; and Jarrod Longcor, Chief Business Officer. After the close of the U.S. financial market yesterday, Cellectar issued a news release and filed its annual report on Form 10-K with the SEC disclosing its financial results for the fiscal year ended December 31, 2017. Before we begin, I would like to remind you that comments made by management during this conference call will contain forward-looking statements that involve risks and uncertainties regarding the operations and future results of Cellectar. I encourage you to review the company’s SEC filings, including without limitation the company’s form 10-K, 10-Q and 8-K, which identify specific factors that may cause actual results or events to differ materially from those described in the forward-looking statements. Furthermore, the contents of this conference call contain time-sensitive information that is accurate only as of the date of the live broadcast, March 22, 2018. Except as required by law, Cellectar indicates no obligation to revise or update any statement to reflect events or circumstances after the date of this conference call. With that said, I will turn the call over to Jim Caruso. Jim?

Thank you, Anne Marie. Good morning, everyone, and thank you for joining us. Cellectar made significant progress throughout 2017 to transition our company from its origins in imaging and diagnostics to a purely therapeutic company leveraging our phospholipid drug conjugate or PDC platform across a number of important oncology indications, both on our own and in partnership with others. The accomplishments we’ve made in 2017 position us well to achieve a number of value creating milestones throughout the balance of 2018. We are implementing a multifaceted development strategy focused on building proof-of-concept datasets in large oncology markets, where we can partner with third parties that have the resources to conduct the large studies required for market approval and that have the commercial infrastructure to promote them. In tandem, we are pursuing niche hematologic and orphan pediatric oncology indications, where we can conduct studies with smaller patient enrollment numbers in scalable markets, where we can compete on our own. Towards that end, we initiated the fifth cohort of our Phase 1 study in relapsed/refractory multiple myeloma. We advanced and expanded our Phase 2 clinical trial in a variety of B-cell malignancies. We filed an investigational new drug application for a Phase 1 study in rare pediatric cancers and we initiated research activities on two wholly-owned PDC programs. These programs are advancing rapidly and further demonstrate the breadth of molecule types or PDC delivery platform can utilize. We also continue to advance our PDC platform through third-party research collaborations, such as the ones we have with Avicenna Oncology, Onconova Therapeutics and Pierre Fabre. 2018 has gotten off to a strong start with progress across a number of important areas, both clinical and corporate that we will discuss in greater detail later in this call. Now let me turn the call over to John Hamill, for a review of our 2017 financial results. John?

Thanks, Jim, and good morning, everyone. As Jim noted, we are pleased with the meaningful progress we’re making toward achieving our strategic objectives. We continue to apply disciplined financial management in order to conserve our resources for investment in our very promising development programs. Before I review our financial results for 2017, let me touch on a prior period presentation change we made to our 2016 statement of operations. In the 2016 10-K, we allocated the proceeds of the November 2016 underwritten offering between the Series A preferred stock and the Series C warrants based on fair value and correctly recorded the Series A preferred stock is equity. However, the embedded beneficial conversion feature associated with the Series A preferred stock was not properly considered. As a result, we were required to reflect a deemed dividend of approximately $3.2 million in the presentation of our 2016 financial results. Additionally, in 2016, the number of shares used in computing basic and diluted net loss per common share were overstated by approximately 0.2 million shares. The net effect of these two changes was to increase the 2016 net loss attributable to common shareholders per share by $0.78. These prior period adjustments had no effect on cash, cash flow or shareholders equity during 2016, and also had no effect on cash, cash flow, net loss or stockholders equity for any subsequent period. After considering the quantitative and qualitative effects to the 2016 annual financial statements, as well as the quarterly period financial statements within 2016 is not material to assessing the financial condition or operations of the company. Now let’s turn to our operating results for 2017. Research and development expenses for 2017 were approximately $9.5 million compared with approximately $4.8 million for 2016. The increase is primarily due to higher support for the ongoing Phase 2 clinical trial in hematologic malignancies, as well as expanded preclinical development cost. Also, 2017 R&D expenses include one-time non-cash depreciation expense associated with discontinuing a small scale manufacturing operation at the company’s facility in Madison, Wisconsin, including approximately $1.0 million for leasehold improvements and approximately $0.2 million for equipment. Investment in the company’s ongoing Phase 1 relapsed/refractory multiple myeloma trial remained relatively consistent for both years. General and administrative expenses were approximately $4.1 million for 2017, down from approximately $4.7 million in 2016. The net loss attributable to common stockholders for 2017 was approximately $15.0 million, or $1.7 per share based on 14.0 million shares outstanding. This compares with a net loss attributable to common stockholders for 2016 of approximately $9.4 million, or $2.14 per share based on 4.4 million shares outstanding. The results include non-cash, stock-based compensation expense of approximately $0.8 million in 2017 and $0.5 million in 2016, as well as non-cash deemed dividends of $0.10 per share in 2017 and approximately $0.70 per share in 2016. Cash, cash equivalents as of December 31, 2017 were approximately $10 million, compared with approximately $11.4 million as of December 31, 2016. During the fourth quarter of 2017, we raised net proceeds of approximately $7.1 million in a registered direct offering of common stock and Series B preferred stock, as well as a private placement of Series D warrants. Throughout 2018, we will continue to invest in our core clinical programs and will remain opportunistic regarding potential grants, partnerships and licensing opportunities. We believe that carrying cash and cash equivalents are sufficient to fund budgeted operations into the first quarter of 2019. With that financial overview, let me turn the call over to John Friend for discussion of our clinical programs.

Thank you, John. Let me begin with a review of our Phase 1 clinical trial with CLR 131 to treat relapsed or refractory multiple myeloma. As announced, we have completed the first part of this study, which was to determine the safety and tolerability of a single 30-minute infusion of CLR 131 and highly pretreated relapsed/refractory multiple myeloma patients. 15 patients were enrolled across four cohorts, receiving doses from 12.5 millicurie per meter squared up to 31.25 millicurie per meter squared. Each cohort dosing was evaluated by an independent data monitoring committee and determined all four dose levels to be safe and tolerable. Looking at the safety profile across all 15 dosed patients, we remain highly encouraged that our phospholipid ether [indiscernible] selectively delivers iodine-131 to cancer cells, while minimizing the off-target effects commonly seen with chemotherapy and other radiotherapeutics. We did not observed any liver function abnormalities GI toxicities or neurological toxicities in the Phase 1 study to date. Based on this, as well as efficacy signals observed, including reductions in m-protein and pre-light chain, the fact that we have not reached median overall survival at this time and the pooled all 15 patients overall survival to date of 15 months, we modified the protocol to begin the second part and a cohort 5, the main objective of which is to determine an optimal dose range for CLR 131. Cohort 5 is actively enrolling and should complete by the end of the second quarter. In this cohort, we split the 31.25 millicurie per meter squared dose into two 30-minute infusions of 15.625 millicurie per meter squared doses, given approximately one week apart. We are extremely encouraged about the potential for this multi-dose regimen based on extensive preclinical animal models that have demonstrated improved overall survival and tumor reduction compared with a single dose. We have observed these significant benefits with every animal study we’ve looked at to date and the available literature supports this dosing regimen as well. We have recently converted the Phase 1a clinical data to pool data for presentation of the total performance of the results to date as the pool data is more likely to be reflective of larger Phase 2/3 clinical studies. We have recently provided preliminary pool data from the first four cohorts and plan to share additional updates sometime over the course of this year. Currently, the lead investigators are working on the manuscript for the single dose dataset from the first four cohorts. We look forward to updating you on the progress with this lead program. Turning now to our Phase 2 clinical trial with CLR 131 to treat a variety of B-cell malignancies. The Phase 2 study is being conducted approximately 10 leading U.S. cancer centers in patients with relapsed or refractory B-cell hematologic cancers. The hematologic cancer is being studied include multiple myeloma, chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma or DLBCL. The studies primary endpoint is clinical benefit response with additional endpoints of progression-free survival, median overall survival, and other markers of efficacy following a single 25.0 millicurie per meter squared dose of CLR 131 with the option for a second 25.0 millicurie per meter squared dose approximately 75 to 180 days later. In addition to CLR 131, multiple myeloma patients will receive 40 milligrams of oral dexamethasone weekly for up to 12 weeks. Efficacy responses will be determined by the latest International Multiple Myeloma Working Group criteria for all multiple myeloma patients and the Lugano criteria for all lymphoma patients. In December, we announced that we are increasing the targeted patient enrollment in the relapsed/refractory multiple myeloma cohort of the study, as data from this cohort demonstrated that the treatment exceeded pre-specified criteria for clinically meaningful benefit. As a result, the cohort will be expanded to as many as 40 patients. We are very excited about this as these initial results highlight the potential for CLR 131 to benefit these heavily pre-treated and relapsed patients. We recently announced the initiation of the DLBCL cohort, which represents the fourth and final cohort of this study. Similar to other B-cell cohorts, we expect to enroll up to 10 patients and perform an interim analysis. If these interim data are positive, the DLBCL cohort could be expanded by an additional 10 to 20 patients. DLBCL is a rare hematologic cancer with few treatment options and fits well with our strategy to pursue orphan indications. In addition, the study is being supported by $2 million grant from the National Cancer Institute. Turning now to our upcoming studies. We’re looking forward to initiating our Phase 1 clinical study of CLR 131 in pediatric cancers. We have already submitted the IND application with the FDA and expect to initiate the trial in the first-half of 2018. The Phase 1 clinical trial will be an open-label, sequential-group, dose-escalation study to evaluate the safety and tolerability of a single IV administration of CLR 131 in up to 30 children and adolescents with relapsed/refractory cancers, including neuroblastoma, sarcomas, lymphomas and malignant brain tumors. Secondary objectives of the study are to determine preliminary antitumor activity of CLR 131 and to identify the recommended Phase 2 dose of CLR 131. The study is being conducted by pediatric oncologists and Nuclear Medicine/Radiology Group at The University of Wisconsin. This world renowned group of clinicians have extensive experience in pediatric cancers and are considered leaders in the field. Last week, we were delighted to receive FDA orphan drug designation for CLR 131 as a treatment for neuroblastoma. This is the third most common childhood cancer and there are currently no approved treatments for children with relapsed or refractory disease. There are a number of benefits related to orphan drug designation, which includes seven years of market exclusivity, increased engagements and assistance from the FDA, tax credits for certain research grants and a waiver of the new drug application user fee. Currently, highly toxic multimodality therapies, such as 131I-MIBG are being used with limited success. Clearly, there’s an urgent need for new drugs, including targeted radiopharmaceuticals with cancer specific update such as CLR 131. Next month, an oral presentation at the World Federation of Nuclear Medicine and Biology will highlight results from a Phase 1 study of CLR 124 demonstrating its ability to cross the blood brain barrier and a cheap uptake in human brain tumors. CLR 124 is the company’s cancer selected PDC radiolabeled with iodine-124. This molecule is analogous to CLR 131, which delivers therapeutic iodine-131 rather than the diagnostic iodine-124 to the tumors. The demonstration of our PDC’s ability to access the brain with a systemically administered compound and achieve strong uptake in brain tumors underscored the potential of our PDC platform technology to selectively deliver oncologic payloads to highly restricted compartments within the body. These data along with a number of preclinical studies supporting this approach may have a read through for CLR 131, which is very encouraging for this Phase 1 pediatric study, particularly as it relates to treating malignant brain tumors. Additionally, an approval in any pediatric indication may provide a Priority Review Voucher and potential for NCCN Compendium listing for other tumor types. A Priority Review Voucher is awarded by the FDA to sponsors of rare pediatric disease product applications. Under this program, a sponsor who receives an approval for a drug or biologic for a rare pediatric disease may qualify for a voucher that can be redeemed to receive a Priority Review of a subsequent marketing application for a different product. Four such vouchers were traded in 2017, two sold for $125 million and two for $135 million. Clearly, this could be a very valuable asset for Cellectar as we advance our technology in a number of rare pediatric cancers. We are also moving forward with our plans for a Phase 1 study of CLR 131 in combination with external beam radiation for the treatments of refractory head and neck cancer, which is also being conducted in collaboration with the University of Wisconsin. This study is 100% funded by the prestigious National Institutes of Health Specialized Program of Research Excellence or SPORE grant to improve treatments and outcomes for head and neck cancer patients. We’re working with the investigators at the UW to finalize the Phase 1 study designed and expect to file an IND with the FDA for this important study in the first-half of this year. In October, preclinical data showing that our PDC molecule, CLR 127, synergizes with external beam radiation were presented at an International Scientific Meeting. The data showed that CLR 127 was taken up and retained in tumor cells at six to 10-fold higher levels than normal tissue and sensitized the tumor cells to external radiation. The study treated adult from pediatric cancer cells and in vivo xenograft-bearing mice with CLR 127 followed by external radiation. The group reported that the effect of the radiation was meaningfully, excuse me, meaningfully increased versus external radiation alone and persisted at higher levels for up to 24 hours post-administration of the external radiation. Additionally, treatment with CLR 127 appears to inhibit DNA repair function that typically occurs in tumor cells following radiation treatment. Here again, we expect to have re-through to CLR 131 treatments in combo with external beam radiation. CLR 131 has been shown to experience high levels of cellular uptake and squamous cell carcinomas of head and neck tumor cells with a single treatment in combination with external beam radiation, resulting in a statistically significant reduction in tumor growth regardless of HPV human papillomavirus steps. We’re encouraged that this combination treatment could result in enhanced efficacy for patients and significantly reduce morbidity associated with external beam radiation. This is another important indication, where we believe Cellectar can have a meaningful impact on the 300,000 Americans living with oral cavity and pharynx cancer and over 80,000 with larynx cancer. The majority of head and neck cancer patients will relapse and reirradiation has a high risk of severe injury to normal tissue structures that maintain long-term recall from the prior radiation exposure. Several studies have examined the role of reirradiation in head and neck cancers. However, the result show that it comes with considerable risk for high grade toxicities, including death. Let me now turn the call over to Jarrod Longcor, for discussion of our business development initiatives and certain of our preclinical activities. Jarrod?

Thank you, John, and good morning, everyone. As Jim said earlier, 2017 was a year of substantial progress that has laid the foundation for an exciting year ahead at Cellectar. Nowhere has this been more evidenced than the progress we’ve made in collaborations. Collaborations and strategic partnerships are core to our strategy for leveraging the power of our PDC platform by broadly and efficiently expanding the number of PDC product candidates. During 2017, we were delighted to report the initiation of two new research and development partnerships with Avicenna Oncology and Onconova Therapeutics, and in addition to extend our existing research collaboration with Pierre Fabre. As a recap, Avicenna Oncology is a leading precision medicine company developing antibody drug conjugates that is based in Basel, Switzerland. We are in collaboration with them for the development of new PDCs that combine out patented phospholipid ether delivery platform with their novel cytotoxic anti-cancer small molecules. These cytotoxic molecules have previously been attached to antibodies and tested as antibody drug conjugates or ADCs. We also have a strategic collaboration to develop new PDCs combining Cellectar patented phospholipid ether delivery platform with select proprietary compounds or payloads from Onconova’s early-stage product pipeline to create a new and precisely targeted anti-tumor agents. These molecules have not been attempted as ADCs and based upon their chemical structures could not be conjugated to antibodies. Both of these partnerships show the diversity of payloads that we can be – that can be attached and delivered via our phospholipid ether platform. They are both moving forward according to plan. We are hopeful that in conjunction with our partners, we will be reporting data from these collaborations during coming year, and look forward to events and these very promising programs to our clinical studies. Last fall, we expanded our ongoing collaboration with Pierre Fabre, one of France’s leading pharmaceutical companies on the development of novel PDCs for oncology applications. The mutual decision to extend the partnership was based on a review of the encouraged preclinical data seen with these PDC compounds across a multiple solid tumor types, which demonstrated a clear cancer targeting advantages over the unconjugated payload and the potential to create a significant improvement in the therapeutic index. We are very encouraged by the potential of this collaboration to produce a new class of novel targeted chemotherapeutics and again, we look forward to providing updates on the progress of this very promising partnership. In tandem with these research collaborations, we have initiated development of two internal proprietary programs, CLR 1700 and CLR 1900 series. These programs expand Cellectar’s proprietary pipeline with the delivery of these molecules. CLR 1700 uses a Burton’s tyrosine kinase or BTK inhibitor as the payload. This class of modules has been shown to be a very effective treatment for various hematologic cancers, where BTK is overexpressed. BTK is expressed in all hematologic cell lineages, which is why a number of significant adverse events are associated with this unconjugated payload. The CLR 1900 series is a novel class of compound that is being used as payload. The class targets a known and validated pathway that inhibit cell mitosis or cell division, while very effective against barrier solid tumors. When not conjugate, this class of payload is not tolerated. We continue to advance our preclinical support work in support of our PDC platform and we’re very pleased to report that some of our preclinical work related to CLR 131 and our PDC platform were accepted as late-breaking posters for presentation at the upcoming Annual Meeting of the American Association for Cancer Research. The first poster titled phospholipid drug conjugates shows specificity for a broad range of tumor cells and provide a novel approach for targeted and precision therapy, will further elucidate the mechanism of targeting and uptake into the molecule, sorry, uptake of the molecules into the cells, as well as the cell trafficking the intracellular trafficking of these molecules. This is important new data as it replicates earlier preclinical work and supports our thesis regarding the very specific targeting of our PDC platform. The second poster entitled efficacy of fractionated injections of CLR 131 in an OPM SCID nude mouse model suggest a more optimized multi-dose scheme. It is particularly exciting to share efficacy data of fractionated injections of CLR 131 and the preclinical multiple myeloma model, as it supports the multi-dose strategy we are implementing in cohort 5 of our Phase 1 clinical study underway as a treatment for relapsed or refractory multiple myeloma and our ongoing Phase 2 clinical study of CLR 131, as a treatment for select B-cell malignancies. I look forward to presenting these data at AACR next month. And I encourage any of you attending the meeting stop by our poster presentations. With that overview, let me turn the call back over to Jim. Jim?

Thank you for those updates, John and Jarrod. Moving forward in 2018, we continue to execute our plan and expect to achieve a number of important milestones that will further advance our PDC platform in a variety of important oncology indications. To summarize, we expect to complete the multi-dose fifth cohort of our Phase 1 study of CLR 131 to treat relapsed/refractory multiple myeloma by the end of the second quarter and to have preliminary data in the first-half of 2018. To report cohort performance updates from our Phase 2 clinical trial at CLR 131 for multiple myeloma in a variety of large market, as well as niche B-cell hematologic malignancies. To advance the research of our PDC delivery platform, both independently and in collaborations and to further develop PDC conjugates possessing a variety of cytotoxic payloads in preclinical and other IND-enabling studies. To initiate the Phase 1 study of CLR 131 in children and adolescents with rare and orphan cancers and to commence the Phase 1 study of CLR 131 in combination with external beam radiation in head and neck cancer. We have an exciting year ahead as we advance our clinical programs to these important data points, while being opportunistic about grant partnership and collaborative opportunities. We remain steadfast in our mission to advance our proprietary product pipeline and to further leverage our innovative PDC platform to design and develop a portfolio of safe and effective targeted cancer treatments to realize our PDC technologies powerful potential and to create substantial shareholder value. On behalf of the Cellectar management team and Board of Directors, I thank you for your support, as we continue to build Cellectar into a leading targeted oncology company bringing potentially life saving therapies to patients with limited treatment options. Now before we open the call for your questions, I want to address a question we received from investors on the sale of a modest number of shares by Jarrod Longcor and myself. These sales were executed under a 10b5-1 program sale instituted in 2017 for the sole – the sole purpose of covering the income tax liability for our restricted shares. Of course, this in no way reflects our enthusiasm for the stock or the company. In fact, as I sit here today, I have never felt. I have never felt more confident in Cellectar’s future and the promise of our PDC platform. With that overview, operator, we are ready to take questions.

[Operator Instructions] One moment please for the first question. And your first question comes from the line of Wangzhi Li with Ladenburg.

Hey, good morning. Thanks for taking my questions and congratulations for the progress through the year. Maybe few questions, starting with the cohort 5, I think, you mentioned you’re going to finish the enrollment in the second quarter and potentially provide preliminary data in the first-half of 2018. So I assume is the second quarter, too?

That is correct.

Right. And also at the upcoming AACR, I think, you’re going to provide the preclinical data for the – the fractionated doses. Any color on that? What type of – you mentioned many different tumor types should benefit of the secondary doses versus your – versus a single dose? Maybe additional – any additional color in terms of what tumor types and what – how many tumor types you’re going to see from the presentation of the AACR?

Absolutely, Wangzhi. Before I turn that over to Jarrod for his response, I think, it’s also important to say that, as you know, with our single dose we’ve observed some very, very nice activity. With a 30-minute infusion, we really like where we sit, both from an activity perspective and an AE profile we’ve observed minimal or off-target effects further validating the targeted nature of our PDC delivery platform. And based on our own preclinical 131 research and what we’ve observed in the literature, we believe that a multi-dose or set another way potentially a fractionated dose may further advance the 131 product profile beyond as it currently sits. Jarrod and team have done significant work in this area. And I’ll turn it over to him for some additional color.

Sure. Thank you, Jim, and thank you, Wangzhi. Just to give some color to this, in general, I’m not going to list all the different tumor types. But I will say, we tested this in over 20 different in vivo animal models looking at a number of both solid and hematologic malignancies. And in all cases, we have to see this benefit that we refer to, as John alluded to in his prepared remarks, I would say that, what we see is a statistically significant benefit, both in tumor reduction – tumor volume reduction and survival of the animals, as compared to any other dose paradigm. We expect to be sharing that data, I will say, the data that will definitely be in that will be related to the multiple myeloma experience that we have, but we will also be putting in other animal model data to support what we’re seeing there.

Got it. Would you also expect it to see improvement in the adverse events profile, or most of you think is the improvement efficacy the survival in tumor reduction?

I would say, we don’t know for sure one way or the other. However, based on prior literature research of looking at different dosing paradigms of some other aspects, there’s a potential that what you’re – what you would see from sort of a PK/PD modeling effect is that you would see an improved – potential improvement in adverse event profile. However, that will be played out in cohort 5 and/or additional cohorts in the Phase 1 study.

Okay, got it. And related to the second question for that is, for the pediatric program, I look at your design for the Phase 1, looks like obviously, you can do potentially try the multi-dose, too, right? So assuming that those pediatric tumor types also included in your preclinical study in that what is rationale to also potentially try to multi-dose in the pediatric – upcoming pediatric trial?

So we have to your point based on the preclinical data that we have presented and some data that we have not, you are correct. We’re looking at sarcomas, malignant brain tumors, lymphomas, things of high-grade gliomas and things of that nature. We are – I’m going to turn it over to John for a review of the Phase 1 pediatric trial and our study design, but it will be single dose early on. Maybe we will not initiate with the multi-dose treatment there. John?

Yes. Hi, Wangzhi, good morning. That’s exactly right. Just based on those study design, it’s important to, at least, demonstrate safety and tolerability of the single dose and then potentially moving into multi-dose later on. So as it stands right now, the Phase 1 study will be a single dose and fusion of CLR 131 30-minute infusion assess safety, as well as efficacy over approximately 85 days thereafter. As you can tell, Wangzhi, we’re extremely excited about initiating this study for multiple reasons. Number one, because obviously, we’ve demonstrated some pretty clear safety with CLR 131, both in the hematologic studies ongoing now, but also in solid tumors. So as you recall, the initial INDs were opened up with CLR 131 in solid tumor. So we have exposure of both 131, but also some of our imaging agents and diabetic agents in solid tumors demonstrating a nice safety and tolerability. We also are excited about this upcoming oral presentation at the World Nuclear Medicine and Biology Meeting, whereby we’re demonstrating the PDC, our delivery platform able to cross the blood bank barrier again, potential carry through of the analogous CLR 131 in high-grade glioma. Obviously, the pre-clinical xenograft studies that the University of Wisconsin have done extensive xenograft mouse models and the sarcomas, are really exciting in terms of reductions in tumor burden, as well as overall survival with single dose of CLR 131 in these mice. And lastly, the MIBG, which we’ve spoken about the 131 MIBG is essentially a off-label standard therapy utilized in neuroblastoma patient. So this is what initially discovered in the 1980s at the diagnostic for both neuroblastoma, but also pheochromocytoma, and has been over the past couple of decades used off-label for the treatment of neuroblastoma patients with some success. But obviously, there is some significant room for improvement in terms of overall responses in the 10% to 30% range that we’re seeing with MIBG. So we’re extremely excited to get this kick this study off and determine the potential value of CLR 131 in these rare orphan pediatric patients.

And I think, it’s also important to say, Wangzhi, that this fits very, very nicely with our overall strategy relative to our focus on like niche B-cell malignancies. This is a rear disease. It represents an accelerated pathway to market small and in terms of study design and patient population, not a competitive space in terms of competition for patients to enroll once on the market there is significant high unmet medical need and they are highly scalable spaces. So these are – this is an area, where we clearly feel as if – it’s a very nicely suited for CLR 131 and it’s a same box that we believe we could win both from a clinical perspective and from a commercial marketing perspective in a highly scalable space.

Got it. So just follow-up on John’s comments for the neuroblastoma you mentioned MIBG I want to be warned, that that’s going to segmentary, I mean, there’s off-label right?

That’s correct, Wangzhi. Yes, it is off-label not been approved.

Got it.

As a matter of fact, there’s nothing approved for our relapsed/refractory neuroblastoma patients at this time. And as you probably know, the dosing of the ITAM 131 associated with this nonselective delivery to MIBG platform is that these children are being dosed with extremely high doses of ITAM 131, whereas and we’re dosing 10, 25 millicurie per meter squared. These kids are receiving essentially total doses up to 1 curie worth of [ITAM 131. So there obviously some issues in adverse events associated with MIBG and the non-selective delivery all over with these kids. So we’re highly encouraged. And encouraged also that it does see some benefits or some efficacy, but again, the – as I mentioned, the response rates are quite low. So we think we have some room in terms of winning from an efficacy perspective as well.

So – got it. So a follow-up to that. So your strategy is going to maybe talking to second line or are there refractory/relapsed the neuroblastoma, if you can share better or equal performance over MIBG, I want to know, and if you get FDA approval then you should be – the doctor will be more willing to take your the CLR 131 with MIBG, I want to know, is that a strategy?

It is. I think for now that we would be looking that, at least, the Phase 1 is going to be in relapsed or refractory rare pediatric tumors, including neuroblastoma. So I would assume that most of the neuroblastoma patients would have had MIBG exposure. So that would probably be our first strategy moving forward, but it leaves open. I mean, there’s a huge unmet need even in the first line with these rare pediatric tumors.

Got it. Okay, last question on this is, for neuroblastoma, sarcomas and like osteosarcoma, as you assume by different doctors or they all seem by the – maybe the same doctor pediatrics or oncology sustain all these indications [indiscernible] if it is same thing or by the same kind of doctor maybe you can leverage that and plus you get into neuroblastoma can either expand into other indication for, I mean, in the community setting?

Right. So in general, these patients are all seen in large academic centers across the world. So we’ll talk in terms of the U.S. So I would say, yes. In general, these across the sarcomas and even potentially in the high-grade glioma, the malignant brain tumors, these kids are seen by the very similar pediatric oncologists at these large cancer centers.

And so to your point, Wangzhi, it’s 12 to 15 centers of excellence attachment centers that filter through the majority of these patients at one point or another. So when you think about key opinion leadership, it’s a very limited group. And when you think about the cost to drive trial use and adoption and sustain share growth in this space, it’s very limited, because it’s so scalable. I think, this is an opportunity for premium pricing with limited levels of marketing investment in order to really move the needle from a top line perspective. And most importantly, there’s a significant amount of high unmet medical need and we really have an opportunity to do something great for patients and the communities we serve here, as well as drive shareholder value.

Okay, got it. Maybe one last question. I noticed you had the thickening program BTK, the CLR 1700, right? Maybe a little color what you try to differentiate there, given the multiple BTKs on the market and maybe what the position of your molecule and what’s your hope to achieve and differentiate from or develop already?

So, Wangzhi, we’re obviously, we really like what we see with our PDC delivery platform. We like the broad utility that it’s demonstrated to date. We’ve used a variety of compounds with different mechanisms of action. And in all cases, we’ve been able to target pretty specifically a wide variety of both hematologic malignancies and solid tumors. And Jarrod and his team have done a great job leading the research here. So I’ll turn it over to him for some detail.

Sure. And I think, just, Wangzhi, maybe a bit more on where Jim was going with some of that. One of the beauties of whether it’s the BTK program or the other programs is the information we learn with regard to our linker chemistry our ability to not only have novel linkers that use novel mechanism of releasing cleavage. But that also gives us the ability to attach various payloads. If you think about what’s in the marketplace about 45% to 50% of all molecules out there are small molecules. And unlike with an ADC, we have the potential to attach various versions of that and various versions of small molecules in addition to other molecules to our PDC delivery vehicle. The important thing there is and that’s sort of what we’re showing with the BTK inhibitor, because that would normally not be able to be targeted via an ADC or other delivery vehicles. So that’s one aspect. The aspect that we’re really attempting to do with that molecule, however, is to overcome a number of the adverse event profiles that are seen with BTK inhibitors. The various BTK inhibitors, as you refer to, Wangzhi, represent over $4 billion market space. So for – on one aspect, it’s very attractive for a company like us. Second, as mentioned, they are BTK has a tyrosine kinase is overexpressed in B-cell malignancies in general, hematologic malignancies in general. However, the Burton tyrosine kinase is also expressed in all healthy B-cell lineage cells as well. And obviously, that means that significant amounts of cytopenia and other events, such as bleeding and hemorrhaging are also associated with those compounds. And so to be able to specifically target those molecules just the tumor cells and avoid those off-target effects that are seen with the other BTK inhibitors whether they’re, what I want to say, permanent inhibition or not to be overcome those adverse events would be a significant benefit to the patient population. And we see that as a key aspect in addition to potentially increasing the potential efficacy of these molecules overall.

Got it. Okay, that’s helpful. Thank you very much and then congratulations again on the year.

All right. Terrific, Wangzhi. Thank you for your questions.

Our next question is from Sean Lee with H. C. Wainwright. Please go ahead with your question.

Hi, guys. This is Sean from HCW stepping in for RK and thank you for taking my questions. My first question…

Thank you for being on the call.

Yes. My first question is on your partnerships with Onconova and Pierre Fabre. Could you provide a little more color on what the focus of each partnership is and what the structure is in terms of cost sharing and ownership of the new molecules that you develop?

Sure. Before we – I pass this over to Jarrod to secure his thoughts, I also want to share with the group Sean that, we believe we’re really on the front-end of the opportunity associated with our collaboration model or platform. We have been working very, very quickly to advance that program and create a proof-of-concept. And each and every car that we continue to turn is turning positive for us, and that’s in terms of our capacity to modify therapeutic index for compounds that potentially are very effective and unfortunately also highly toxic. So this validation continues with some really interesting preclinical data. And I think the most important message that I want to leave you with before I transition to Jarrod is, we really believe we’re on the front-end of optimizing our delivery vehicle. And it makes us very unique as a micro-cap company, where we have the potential to generate revenue through collaborations in the near-term to prevent and reduce further shareholder dilution over time.

Thank you. So let me take it. So the call I’m going to say this and please feel free to correct me if I don’t capture everything that you’re looking for in the question. But as I heard it, you want to understand the goal of Pierre Fabre and Onconova collaborations. Those goals are…

That’s correct, yes.

In the Pierre Fabre collaboration, Pierre Fabre is developing a novel class compounds. That class of compounds was very interesting to them. It showed tremendous efficacy and potential treatment for that class of molecules. However, they did experience significant toxicities associated with molecule and we’re unable to continue the development of the molecule as a generalized and fusible therapeutic. They did attempt through their own in-house programs to make an antibody drug conjugate of the molecule. However, here again, the molecule was not successful in folks that tolerability seen with it, as well as getting to an efficacious dose associated with it. So in our collaboration, the goal was first to show that we could deliver the molecule. Second, show that we can get to a tolerable dose that could be meaningfully utilized to show efficacy and then show efficacy upon that potentially move that program forward. As you asked with regard to ownership or the rights associated with the program, in all cases, select our own all of the IP related to the new PDC molecules that are being created. So that’s new composition of matter associated with this and obviously, all subsequent and intellectual property associated with that. Our partners whether Onconova, Pierre Fabre or Avicenna, have an option right that they get the exercise associated with any individual series, molecule – maybe follow-up molecule associated with that, that make an option. If they elect not to exercise that option, Cellectar owns the rights and has the authorization to move those programs forward if we so choose. On the Onconova, the goal was slightly different. The Onconova compounds were actually advanced further. Their quest was to again, improve the targeting and thereby reduce some other tolerability, but these molecules were both efficacious and, at least, somewhat tolerable and able to be taken much further into preclinical and a handful in one case into the clinical studies. And so the goal there is a little bit different and really just to improve that target. Does that answer the question?

Yes, that’s great. Thank you for the additional color. My second question is on additional international collaborations. I’ve noticed that you guys have filed quite a few patents in Japan recently – in the last quarter. Are there any solid plans for a partnership or a business development deal in that region in 2018?

So, Sean, I’ll say this. We are always opportunistic right. So we have a very – we believe a very interesting portfolio of assets as we further advance these assets and create further proof-of-concept both from a clinical and preclinical perspective. Obviously, we will continue to market and merchandise those data in the hopes of attracting larger partners that could help us accelerate our programming through the clinic and further advance the value and of our delivery vehicle. In terms of specific planning from a collaboration perspective or partnership, we certainly don’t share that at this time. Jarrod any – I don’t – we haven’t – Sean, we haven’t really put anything out on the public domain any other comments. I would only say that we are active – we actively seek partnerships in various territories and globally with any – all the parties that you would naturally expect us to be in discussions with. I do appreciate your understanding of the work that we’ve done from an intellectual property portfolio perspective, because one of the things we truly understand is that the value of our assets of the NPV said another way are really a function of the runway we have commercially with these. So one, I’m appreciative that you’ve identified that we’ve built out a very robust intellectual property portfolio. And like – just like collaborations, I think, you can look forward to us continuing to work hard to create further picket fences for our assets.

Great. Congratulations again, on a successful year, and thank you for taking my questions.

Sean, thanks for being on the call and for the questions. Very much appreciate it.

There are no further questions at this time. Mr. Caruso, please proceed with your presentation or any closing remarks.

Thank you, operator. Certainly, I appreciate all of you on the call today for your participation. And we also look forward to making continued progress, executing our business strategy and to provide timely updates on our achievements. We certainly appreciate your continued interest in Cellectar and look forward to reporting our progress, first quarter of 2018 on our business update conference call. Thank you. Have a good day.

Ladies and gentlemen, that concludes your conference call for today. We thank you for your participation and ask that you please disconnect your lines.