CELLECTAR BIOSCIENCES, INC. Overview
We are a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer. We are developing proprietary drugs independently and through research and development collaborations. Our core objective is to leverage our proprietary phospholipid drug conjugate™ (PDC™) delivery platform to develop PDCs that are designed to specifically target cancer cells and deliver improved efficacy and better safety as a result of fewer off-target effects. Our PDC platform possesses the potential for the discovery and development of the next generation of cancer-targeting treatments, and we plan to develop PDCs both independently and through research and development collaborations. The COVID-19 pandemic has created uncertainties in the expected timelines for clinical stage biopharmaceutical companies such as us, and because of such uncertainties, it is difficult for us to accurately predict expected outcomes at this time. We have not yet experienced any significant impacts as a result of the pandemic and have continued to enroll patients in our clinical trials. However, COVID-19 may impact our future ability to recruit patients for clinical trials, obtain adequate supply of CLR 131 and obtain additional financing.
Our lead PDC therapeutic, CLR 131 is a small-molecule PDC designed to provide
targeted delivery of iodine-131 directly to cancer cells, while limiting
exposure to healthy cells. We believe this profile differentiates CLR 131 from
many traditional on-market treatment options. CLR 131 is the company's lead
product candidate and is currently being evaluated in a Phase 2 study in
relapsed/refractory (r/r) B-cell malignancies, including multiple myeloma (MM),
chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),
lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LPL/WM), marginal
zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell
lymphoma (DLBCL).CLR 131 is also being evaluated in a Phase 1 dose escalation
study in pediatric solid tumors and lymphoma. The
Our product pipeline also includes one preclinical PDC chemotherapeutic program (CLR 1900) and several partnered PDC assets. The CLR 1900 Series is being targeted for solid tumors with a payload that inhibits mitosis (cell division) a validated pathway for treating cancers.
We have leveraged our PDC platform to establish four collaborations featuring five unique payloads and mechanisms of action. Through research and development collaborations, our strategy is to generate near-term capital, supplement internal resources, gain access to novel molecules or payloads, accelerate product candidate development and broaden our proprietary and partnered product pipelines.
Our PDC platform provides selective delivery of a diverse range of oncologic payloads to cancerous cells, whether a hematologic cancer or solid tumor, a primary tumor, or a metastatic tumor and cancer stem cells. The PDC platform's mechanism of entry does not rely upon specific cell surface epitopes or antigens as are required by other targeted delivery platforms. Our PDC platform takes advantage of a metabolic pathway utilized by all tumor cell types in all stages of the tumor cycle. Tumor cells modify specific regions on the cell surface as a result of the utilization of this metabolic pathway. Our PDCs bind to these regions and directly enter the intracellular compartment. This mechanism allows the PDC molecules to accumulate over time, which enhances drug efficacy, and to avoid the specialized highly acidic cellular compartment known as lysosomes, which allows a PDC to deliver molecules that previously could not be delivered. Additionally, molecules targeting specific cell surface epitopes face challenges in completely eliminating a tumor because the targeted antigens are limited in the total number on the cell surface, have longer cycling time from internalization to being present on the cell surface again and available for binding and are not present on all of the tumor cells in any cancer. This means a subpopulation of tumor cells always exist that cannot be targeted by therapies targeting specific surface epitopes. In addition to the benefits provided by the mechanism of entry, PDCs offer the ability to conjugate payload molecules in numerous ways, thereby increasing the types of molecules selectively delivered via the PDC.
The PDC platform features include the capacity to link with almost any molecule, provide a significant increase in targeted oncologic payload delivery and the ability to target all types of tumor cells. As a result, we believe that we can generate PDCs to treat a broad range of cancers with the potential to improve the therapeutic index of oncologic drug payloads, enhance or maintain efficacy while also reducing adverse events by minimizing drug delivery to healthy cells, and increasing delivery to cancerous cells and cancer stem cells.
We employ a drug discovery and development approach that allows us to efficiently design, research and advance drug candidates. Our iterative process allows us to rapidly and systematically produce multiple generations of incrementally improved targeted drug candidates.
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A description of our PDC product candidates follows:
Clinical Pipeline
Our lead PDC therapeutic, CLR 131 is a small-molecule, PDC designed to provide
targeted delivery of iodine-131 directly to cancer cells, while limiting
exposure to healthy cells. We believe this profile differentiates CLR 131 from
many traditional on-market treatments and treatments in development. CLR 131 is
currently being evaluated in a Phase 2 study in r/r B-cell lymphomas, and two
Phase 1 dose-escalating clinical studies, one in r/r MM and one in r/r pediatric
solid tumors and lymphoma. The initial Investigational New Drug (IND)
application was accepted by the FDA in
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Phase 2 Study in Patients with r/r select B-cell Malignancies
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Patients with r/r NHL who received ~50mCi TBD and the ~75mCi TBD had a 42% and 43% ORR, respectively and a combined rate of 42%. These patients were also heavily pre-treated, having a median of three prior lines of treatment (range, 1 to 9) with the majority of patients being refractory to rituximab and/or ibrutinib. The patients had a median age of 70 with a range of 51 to 86. All patients had bone marrow involvement with an average of 23%. In addition to these findings, subtype assessments were completed in the r/r B-cell NHL patients. Patients with DLBCL demonstrated a 30% ORR with one patient achieving a complete response (CR), which continues at nearly 24 months post-treatment. The ORR for CLL/SLL/MZL patients was 33%. Current data from our Phase 2 CLOVER-1 clinical study show that four LPL/WM patients demonstrated 100% ORR with one patient achieving a CR which continues at nearly 27 months post-treatment. This may represent an important improvement in the treatment of relapsed/refractory LPL/WM as we believe no approved or late-stage development treatments for second- and third-line patients have reported a CR. LPL/WM is a rare, indolent and incurable form of NHL that is composed of a patient population in need of new and better treatment options.
The most frequently reported adverse events in r/r MM patients were cytopenias, which followed a predictable course and timeline. The frequency of adverse events have not increased as doses were increased and the profile of cytopenias remains consistent. Importantly, these cytopenias have had a predictable pattern to initiation, nadir and recovery and are treatable. The most common grade ?3 events at the highest dose (75mCi TBD) were hematologic toxicities including thrombocytopenia (65%), neutropenia (41%), leukopenia (30%), anemia (24%) and lymphopenia (35%). No patients experienced cardiotoxicities, neurological toxicities, infusion site reactions, peripheral neuropathy, allergic reactions, cytokine release syndrome, keratopathy, renal toxicities, or changes in liver enzymes. The safety and tolerability profile in patients with r/r NHL was similar to r/r MM patients except for fewer cytopenias of any grade. Based upon CLR 131 being well tolerated across all dose groups and the observed response rate, especially in difficult to treat patients such as high risk and triple class refractory or penta-refractory, and corroborating data showing the potential to further improve upon current ORRs and durability of those responses, the study has been expanded to test a two-cycle dosing optimization regimen of CLR 131.
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Phase 1 Study in Patients with r/r Multiple Myeloma
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CLR 131 in combination with dexamethasone is currently under investigation in
adult patients with r/r MM. Patients must have been refractory to or relapsed
from at least one proteasome inhibitor and at least one immunomodulatory agent.
The clinical study is a standard three-plus-three dose escalation safety study
to determine the maximum tolerable dose. Multiple myeloma is an incurable cancer
of the plasma cells and is the second most common form of hematologic cancers.
Secondary objectives include the evaluation of therapeutic activity by assessing
surrogate efficacy markers, which include M protein, free light chain (FLC), PFS
and OS. All patients have been heavily pretreated with an average of five prior
lines of therapy. CLR 131 was deemed by an Independent Data Monitoring Committee
(IDMC) to be safe and tolerable up to its planned maximum single, bolus dose of
31.25 mCi/m2. The four single dose cohorts examined were: 12.5 mCi/m2(~25mCi
TBD), 18.75 mCi/m2 (~37.5mCi TBD), 25 mCi/m2(~50mCi TBD), and 31.25
mCi/m2(~62.5mCi TBD), all in combination with low dose dexamethasone (40 mg
weekly). Of the five patients in the first cohort, four achieved stable disease
and one patient progressed at Day 15 after administration and was taken off the
study. Of the five patients admitted to the second cohort, all five achieved
stable disease however one patient progressed at Day 41 after administration and
was taken off the study. Four patients were enrolled to the third cohort and all
achieved stable disease. In
Following the determination that all prior dosing cohorts were safe and tolerated, we initiated a cohort 7 utilizing a 40mCi/m2 fractionated dose administered 20mCi/m2 (~40mCi TBD) on days 1 and day 8. Cohort 7 was the highest pre-planned dose cohort and subjects have completed the evaluation period. Final study report and study close-out will be completed later this year.
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Phase 1 Study in r/r Pediatric Patients with select Solid tumors, Lymphomas and Malignant Brain Tumors
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Phase 1 Study in r/r Head and Neck Cancer
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Preclinical Pipeline
We believe our PDC platform has potential to provide targeted delivery of a diverse range of oncologic payloads, as exemplified by the product candidates listed below, that may result in improvements upon current standard of care ("SOC") for the treatment of a broad range of human cancers:
· CLR 1800 Series was a collaborative PDC program with Pierre Fabre that
expired in January 2019 . The program has been successful in demonstrating
improved tolerability and efficacy in multiple animal models. The newly
developed PDCs may provide enhanced therapeutic indices to otherwise
highly potent, nontargeted payloads through the targeted delivery of the
chemotherapeutic payload to cancer cells via our proprietary phospholipid
ether delivery platform. The CLR 1800 Series remains under evaluation by
us as a number of PDC molecules have the potential to be progressed toward
and into IND enabling studies.
· CLR 1900 Series is an internally developed proprietary PDC program
leveraging a novel small molecule cytotoxic compound as the payload. The
payload inhibits mitosis (cell division) and targets a key pathway
required to inhibit rapidly dividing cells that results in apoptosis. We
believe that this program could produce a product candidate targeted to
select solid tumors. Currently, the program is in early preclinical
development and if we elect to progress any molecules further, we will
select preferred candidates.
· CLR 2000 Series is a collaborative PDC program with Avicenna Oncology, or
Avicenna, that we entered into in July 2017 . Avicenna is a developer of
antibody drug conjugates ("ADCs"). The objective of the research
collaboration is to design and develop a series of PDCs utilizing
Avicenna's proprietary cytotoxic payload. Although Avicenna is a developer
of ADCs, this collaboration was sought as a means to overcome many of the
challenges associated with ADCs, including those associated with the
targeting of specific cell surface epitopes. The CLR 2000 Series has
demonstrated improved safety, efficacy and tissue distribution with the
cytotoxic payload in animal models. A candidate molecule and a back-up
have been selected for further advancement.
· CLR 2100 and 2200 Series are collaborative PDC programs with Onconova
Therapeutics, Inc., or Onconova, that we entered into in September 2017 .
Onconova is a biotechnology company specializing in the discovery and
development of novel small molecule cancer therapies. The collaboration is
structured such that we will design and develop a series of PDCs utilizing
different small molecules that Onconova was developing as payloads with
the intent to show improved targeting and specificity to the tumor. At
least one of the molecules was taken into Phase 1 clinical studies
previously by Onconova. We would own all new intellectual property
associated with the design of the new PDCs, and both companies will have
the option to advance compounds.
· CLR 12120 Series is a collaborative PDC program with Orano Med for the
development of novel PDCs utilizing Orano Med's unique alpha emitter, lead
212 conjugated to our phospholipid ether; the companies intend to evaluate
the new PDCs in up to three oncology indications. Currently this series
has shown efficacy in the first two animal models tested.
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Results of Operations
Research and development expense. Research and development expense consist of costs incurred in identifying, developing and testing, and manufacturing product candidates, which primarily include salaries and related expenses for personnel, cost of manufacturing materials and contract manufacturing fees paid to contract manufacturers and contract research organizations, fees paid to medical institutions for clinical trials, and costs to secure intellectual property. The Company analyzes its research and development expenses based on four categories as follows: clinical project costs, preclinical project costs, manufacturing and related costs, and general research and development costs that are not allocated to the functional project costs, including personnel costs, facility costs, related overhead costs and patent costs.
General and administrative expense. General and administrative expense consists primarily of salaries and other related costs for personnel in executive, finance and administrative functions. Other costs include insurance, costs for public company activities, investor relations, directors' fees and professional fees for legal and accounting services.
Three Months Ended
Research and Development. Research and development expense for the three months
ended
The following table is an approximate comparison summary of research and
development costs for the three months ended
Three Months Ended
June 30,
2020 2019 Variance
Clinical project costs $ 992,000 $ 504,000 $ 488,000
Manufacturing and related costs 384,000 752,000 (368,000 )
Pre-clinical project costs 71,000 170,000 (99,000 )
General research and development costs 1,018,000 384,000 634,000
$ 2,465,000 $ 1,810,000 $ 655,000
The overall increase in research and development expense of
General and administrative. General and administrative expense for the three
months ended
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Six Months Ended
Research and Development. Research and development expense for the six months
ended
The following table is a comparison summary of research and development costs
for the six months ended
Six Months Ended
June 30,
2020 2019 Variance
Clinical project costs $ 1,883,000 $ 1,313,000 $ 570,000
Manufacturing and related costs 1,263,000 1,645,000 (382,000 )
Pre-clinical project costs 157,000 246,000 (89,000 )
General research and development costs 1,779,000 914,000 865,000
$ 5,082,000 $ 4,118,000 $ 964,000
The overall increase in research and development expense of approximately
General and Administrative. General and administrative expense for the six
months ended
Liquidity and Capital Resources
As of
Our cash requirements have historically been for our research and development
activities, finance and administrative costs, capital expenditures and overall
working capital. We have experienced negative operating cash flows since
inception and have funded our operations primarily from sales of common stock
and other securities. As of
We believe that the cash balance is adequate to fund our basic budgeted
operations for at least 12 months from the filing of these financial statements.
However, our future results of operations involve significant risks and
uncertainties. Our ability to execute our operating plan beyond that time
depends on our ability to obtain additional funding via the sale of equity
and/or debt securities, a strategic transaction or otherwise. We plan to
actively pursue all available financing alternatives; however, there can be no
assurance that we will obtain the necessary funding. Other than the
uncertainties regarding our ability to obtain additional funding, there are
currently no known trends, demands, commitments, events or uncertainties that
are likely to materially affect our liquidity. Because we have had recurring
losses and negative cash flows from operating activities, and in light of our
expected expenditures, the report of our independent auditors with respect to
the financial statements as of
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