Cellectar Biosciences Inc (NASDAQ: CLRB)
Cellectar Biosciences is a Madison, WI based oncology company that is generating a tremendous amount of industry interest, with an increasing amount of attention being placed on the company's Phosphopipid Drug Conjugate (PDC), a proprietary platform that enables delivery of diverse oncologic payloads through its phospholipid ether cancer-targeting vehicle. Importantly, not only does CLRB's unique PDC platform provide a targeted therapeutic treatment, it also increases the therapeutic payload of the drug directly to cancer cells, which enhances effectiveness and reduces drug exposure to healthy cells, potentially reducing adverse events. These technological advantages within the company's PDC platform may act as the “secret sauce” that can open tremendous opportunity for both the company and its investors.
Since first writing about CLRB, investors have pinged me on several occasions, asking for a review of the most recent phase I data of their Multiple Myeloma drug, CLR 131, and to provide some analysis as to where I believe the already impressive data may ultimately lead. But, if I were to do so, and not include the opinion that the PDC technology generating these impressive results was the most seducing part of the Cellectar Biosciences equation, I would be selling the investment world short. And short, by the way, is not a position that I would currently recommend in regard to CLRB stock ownership.
PDC, It's Better Than A Basket Of Wings
With many investors wanting to skip through the appetizers and get straight to the meat and potatoes of an investment thesis, let me offer them this, which should build them with enough confidence to allow themselves to grasp a full appreciation of the absolute potential behind those results. Here it is, impatient friends: CLRB is providing striking results in treating both relapsed or refractory multiple myeloma, combined with a safety and tolerability profile that is extremely encouraging when compared to current standards of care. The overall survival rate and patient tolerability results already demonstrated with single, lower dose treatments, may ultimately put CLR 131 toward the top of the efficacy list.
With the essential basics out of the way, it’s time to dig deep into this PDC platform that Cellectar Biosciences is developing. It's a crucial component to what they are doing, and while the PDC platform is currently being used to generate some mouthwatering results in its current clinical trials, the applications to which it can be applied are much broader than treating multiple myeloma, although such an accomplishment will be a great way to put an exclamation point on its proof of concept.
CLRB And Strategy
Cellectar is deep into the process of providing proof of concept for its PDC platform, continuing its CLR-131 franchise, and advancing early stage development chemotherapeutic conjugates so that when applied through the PDC process, they can achieve significantly higher therapeutic benefit to patients.
Unlocking the power that is exuding from the platform is the key, because once established as a breakthrough technology, its use in delivering a targeted therapeutic dose of treatment will be applicable through a wide range of cancer-targeting therapies. This is the "protein" within the company, and like all good high protein meals, it could make CLRB extremely strong.
The basis for the PDC delivery platform is to deliver a phospholipid ether cancer targeting vehicle, exploiting selective cancer and cancer stem cells, allowing for the uptake and prolonged retention in malignant cells. By being able to attach to a diverse set of oncologic payloads, the PDC platform may prove to have the ability to treat a broad range of cancer indications.
While I want you to take my word as to the platforms merit, it's worthy to acknowledge the two peer reviewed publications that offered extensive research and scientific validation of PDC. In an article published by Nature Reviews Clinical Oncology titled, "Beyond The Margins: Real Time Detection of Cancer Using Targeted Fluorophores", the review team evaluated the current use of fluorescent molecules in cancer diagnostics, as well as the fluorescence-guided surgical resection of tumors. The paper focused on the need for the use of targeted delivery of molecules to malignant tissue. The peer reviewed data in both reports was consistent in several conclusions, but one clearly stands out to benefit CLRB: both journals provided insight, review and validation of the unique potential and varied utility of Cellectar's PDC platform. And, with this validation comes the increased likelihood of partnership and licensing opportunities as the company continues to mature the pipeline.
What Are PDC's?
Okay, so some of the hard part is done, but not all of it. Many still don't understand what the PDC platform is, and why it could be such a huge asset to CLRB in both the near and long term.
To break it down in simplest terms, the company's product candidates are built upon its patented cancer cell-targeting and retention platform of optimized phospholipid ether-drug conjugates (PDC's). The company was deliberate in designing its phospholipid ether carrier platform to be coupled with a variety of cancer fighting payloads, and to be both therapeutic and diagnostic in function.
The PDC pipeline includes promising product candidates for cancer therapy and cancer diagnostic testing, highlighted by its lead therapeutic agent, CLR131, which is currently being evaluated under an orphan drug designated Phase I clinical study in patients with relapsed or refractory multiple myeloma. In addition to that study, CLRB is planning to initiate a Phase II clinical study in the first quarter of 2017 to assess efficacy in a range of B-cell malignancies. To reach deeper into the 2017 initiatives, Cellectar Biosciences is further planning to develop PDC's for targeted delivery of chemotherapeutics, advance its existing collaboration with Pierre Fabre and to expand its PDC pipeline through both in-house and collaborative efforts.
Basically, it's as simple as this: CLRB can take a phospholipid ether, add a linking molecule, attach the specified drug to be delivered, and it becomes a PDC with the ability to deliver a fortified and targeted payload using fluorophores, radioisotopes, chemotherapeutic agents and potentially other classes of molecules.
Some have compared the PDC platform to ADC targeting and delivery, but the benefits of PDC still stand clear. The PDC's method of delivery is through the cell cytoplasm and has no immunogenic properties, compared to ADC, which targets the cell surface and holds potential immunogenic qualities. This differentiating feature allows Cellectar Biosciences' platform to exploit an unalterable metabolic pathway.
In fact, beyond those two measures, PDC offers a host of additional benefits by using its small molecule approach. The CLRB platform offers direct cancer targeting, cancer stem cell targeting, metastases targeting, ability to overcome resistance, and a solid safety profile. Additionally, PDC delivers a cytoplasm payload delivery that brings payload diversity, linking options, and a far easier method for manufacturing, improving cost efficiencies. The company is clearly fulfilling its mission step by step by using its PDC platform to represent a new class of cancer targeting and payload delivery system, one that is clearly demonstrating its benefit.
OK, Now The Science
While the company posseses a number of product assets, focusing in on its most advanced trial will work to demonstrate the potential throughout the entire pipeline. Remember, while the payload being delivered is certainly an integral part of the therapeutic process, it’s the platform that drives the results.
In addressing multiple myeloma, CLRB is demonstrating what many industry insiders consider to be toward the top of the class in terms of efficacy and safety with a single drug dose. In its Phase I trial targeting both relapsed and refractory multiple myeloma, CLR 131 demonstrated its targeted and precision radiotherapeutic value, along with the platform's novel execution of action. Additionally, during its Phase 1 maximum dose study, CLR 131 provided early signs of both efficacy and patient tolerability.
CLR 131 demonstrated significant improvement from Cohort 1 to Cohort 2, with a progression free survival rate increase of 43%. Additionally, there were less adverse events at higher doses, and the average grade of adverse events overall increased only slightly. But, to be clear, even though there was a slight uptick in average grade of adverse events, these reported issues were not considered materially severe or unexpected.
The Phase II trial will initiate in the first quarter of 2017, advancing the development of the r/r multiple myeloma therapy and further expanding into other hematologic malignancies. Importantly, patients may receive two 25.0 mCi doses of CLR 131, at baseline and between day 75 – 180. Only one dose is being delivered in the Phase 1.
The decision to advance the CLR 131 trial is due to the benefits associated with delivering a potential best in class therapy. The current trial has demonstrated overall clinical success, and CLR 131 holds the potential to be used in combination with approved therapies and , in a multi-dose schedule to further improve performance.
Impressive Phase I Results
The Phase I trial was a multi-center, open label, dose escalation study initiated in the second quarter of 2015. The primary objective was to characterize safety and tolerability, with secondary objectives designed to establish a dosing regimen and to assess therapeutic activity. The study began with a single 12.5 mCi dose in Cohort 1 and progressed past 18.75 mCi to a single 25.0 mCi dose in Cohort 3, which represents a 100% increase in drug dose and potential therapeutic value from Cohort 1.
The participating patients’ had an average age of 68, 4 prior lines of treatment, including the latest approved drugs and 50% had also undergone stem cell transplant procedures representing a difficult to treat patient population. Theses demographics remained consistent through the initial two cohorts, which will serve to validate the consistency in the trial design and results.
Patient Overall Survival performance, likely the biggest factor in getting this therapy to market, was exceedingly impressive. As of 11-22-16, median overall survival in Cohort 1 was 11.9 months and Cohort 2 was already at 4.9 months. It's important to note that all 8 evaluable patients from the first 2 cohorts are still alive and the overall survival duration continues to increase.
Equally impressive is the PFS. Patients receiving the 12.5 mCi Cohort 1 dose achieved 89 days of PFS and Cohort 2 patient PFS increased by 43% to 127 days.
Comparing Overall Survival Performance
Investors want to see the side by sides, especially when they are being exposed to a company that may be laying claim to becoming best in class for therapeutic value. For the drugs most recently approved to treat multiple myeloma - Carfilzomib, Pomalidomide and Daratumumab, the mOS was 11.9, 11.9 and 18.6 months respectively.
Compare this to the CLRB’s CLR 131, whose Cohort 1, low dose results already surpasses two of the recently approved drugs, and is rapidly closing in on the third. The CLRB data listed is as of 11-22-16 and is increasing as all patients continuing to survive.
Progression Free Survival, which may be a marker for Overall Survival, has already cleared 127 days in cohort 2, and represents at least a 43% increase from cohort 1.
Overall survival is key, but the FDA looks at a host of additional factors prior to approval of a drug, and thankfully, I like the company's chances even greater in this category. We know that the treatment is at least as equally effective to date, but how is the drug tolerated by patients?
The answer is simple. Strikingly well.
CLR 131 has a positive safety profile through 2 cohorts as well as an overall data set of 28 patients. Within the profile, there are no neuropathies, no nephrotoxicity and no cardiotoxicities. Additionally, CLR 131 has demonstrated no GI toxicities and no deep vein thrombosis. The therapy’s most common adverse events are hematological in nature.
Importantly, CLRB plans to provide cohort 3 results and PFS and mOS updates for cohort 1 and 2 in the first half of 2017.
Even with additional chapters still being written, the CLRB story is shaping up to be a tremendous value to investors who gauge the probability for imminent success. CLRB will be addressing a significant market upon treatment approval. There are approximately 90,000 multiple myeloma cases diagnosed per year in the U.S., with a potential market estimated to eclipse $22.4 billion in 2023. That is an estimated increase of 151% increase in global market opportunity within the next 10 years.
The benefits of an approved CLR131 extend to both patient and provider, with CLR 131 being considerably more cost effective, and allowing a patient to receive as little as one dose to achieve targeted results.
CLRB is in a strong position to capitalize on their momentum, with approximately $13.9 million on hand, as well as a fully diluted capitalization picture of only 22.6 million shares on a fully diluted basis. Currently, CLRB has roughly 11.5 million shares outstanding, with additional warrants and preferred stock options making up the difference. But, if investors exercise those options, it brings capital into the business, and while the company is financially stable at the moment, having arrows in the quiver to attract additional funding will provide security for investors.
Those who follow CNA Finance understand that we hold tremendous interest in finding emerging companies that may offer transformative and curative treatments in both the service and medical industries. While Cellectar does need a bit more time to generate its final phase 2 data, the results from the phase I trial are both compelling and remarkable from a therapeutic standpoint. With the stock trading at roughly $2.00 per share, investors may be facing down an opportunity to catch a rising star still in its intermediate development phase. Recall that Cellator, upon its buyout from Jazz Pharmaceuticals, went from $1.60 to over $30.00 in a matter of three months,based on an overall survival rate increase of slightly over 3 months. CLRB is in a similar position, whereby they are rapidly closing in on survival data that may serve to be equally, if not more, impressive. With a low share structure, combined with a solid balance sheet and extremely promising trial data in hand, the company possesses the right ingredients for investor consideration and action.
Disclosure: This article was written by Kenny Soulstring, and it reflects my own opinions and unique articulation. This article is not intended to offer investing advice, guarantee 100% accurate predictions or to be interpreted as providing a personal recommendation. What I can guarantee, though, is accurate research, thoughtful analysis and an enthusiasm about any stock that I cover.
I wrote this article myself and it includes my own research and expresses my own opinions. I am not receiving compensation for it (other than from CNA Finance). I have no business relationship with any company whose stock is mentioned in this article.
Additional Disclosure: I have no position in any stock mentioned, but may initiate a long position in CLRB within the next 72 hours.
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