Waldenstrom Macroglobulinemia

iStock, leolintang Wegovy and Zepbound are just the latest drug dyads to face-off in the competitive pharma market, continuing a legacy of rivalry that includes blockbuster drugs Keytruda, Humira and Eliquis. Obesity is the most competitive space in biopharma right now. The two frontrunners, Novo Nordisk and Eli Lilly, are locked in a very tight fight for leadership in a market that by some estimates could reach a jaw-dropping $150 billion in the next few years. Novo moved first. Its GLP-1 analog semaglutide was first cleared by the FDA in 2017 as Ozempic for type 2 diabetes. Some four years later, in July 2021, semaglutide won another approval as Wegovy , this time specifically indicated for chronic weight management. Lilly’s weight-loss blockbuster tirzepatide, in comparison, is a relative late-comer, first reaching the U.S. market in 2022 as Mounjaro for type 2 diabetes Then in November 2023, the FDA approved the drug as Zepbound for obesity , setting up the head-to-head battle with Wegovy in the massive and swiftly growing weight loss market. Despite being years behind, Lilly is chipping away at Novo’s lead. Costanza Alciati, pharma analyst at GlobalData, told BioSpace in an email that tirzepatide’s efficacy edge has helped Lilly catch up. Broadly speaking, according to Alciati, the safety profiles of Zepbound and Wegovy are similar, with both drugs sharing common side effects like nausea and vomiting. Both products are also matched in terms of the route and frequency of administration. However, Zepbound’s “weight loss efficacy seems to be higher than Wegovy’s,” Alciati said, adding that “according to trials, there seems to be less muscle mass loss associated with Zepbound’s treatment than Wegovy’s.” Currently, Novo’s first-mover advantage and sprawling global footprint has allowed it to maintain a slight lead over Lilly. Last year, the Danish pharma logged roughly $26 billion in sales for Ozempic and Wegovy worldwide, while Lilly’s tirzepatide franchise brought in nearly $16.5 billion globally. But with an aggressive commercial strategy, Lilly is quickly gaining ground. “Eli Lilly’s drug has now been launched in all major markets,” Alciati said. Last month, the Indianapolis pharma launched Mounjaro in India, beating Novo to tap the market of the world’s most populous country. Aside from Wegovy and Zepbound, pharma has witnessed many other dramatic drug rivalries play out over the years, from Keytruda’s comeback and subsequent dominance over Opdivo and the burgeoning competition between Leqembi and Kisunla. In this article, BioSpace looks at some of the biggest pharma face-offs. Cancer: Merck’s Keytruda vs BMS’ Opdivo In the oncology arena, few drugs can hope to stand up against Merck’s blockbuster PD-1 inhibitor Keytruda, which has become a cornerstone of cancer care since its first approval in September 2014. As of writing, Keytruda has more than 41 approvals under its belt. These include several forms of melanoma, hepatocellular carcinoma, breast cancer and, crucially, lung cancer. For the last two years, it has also been the pharma’s top-selling product , bringing in $29.5 billion in 2024. But it wasn’t always that way. Keytruda once played second fiddle to Bristol Myers Squibb’s PD-1 blocker Opdivo. Approved in December 2014, just months behind Keytruda, Opdivo initially took a sizeable lead in the market, bringing in $942 million in 2015 versus Keytruda’s $566 million. “Initially, Bristol Myers Squibb was dominating that race,” William Blair partner Matt Phipps told BioSpace in an interview last month. “They had broader approvals and bigger indications.” Merck, according to Phipps, “completely overtook” BMS due to better trials and crucial approvals in lung cancer. Opdivo never recovered. Last year, the drug brought in $9.3 billion —less than a third of Keytruda’s sales. Still, BMS continues to carve out a cancer niche for Opdivo. In January, BMS won the race to bring a subcutaneous PD-1 treatment to the market, with the FDA signing off on a new formulation of Opdivo that can be delivered with an injection under the skin. Merck’s application for subcutaneous Keytruda is still under review. Meanwhile, an NSCLC approval in October 2024 made Opdivo the first PD-1 blocker that can be used both before and after surgery. Cardio: BMS, Pfizer’s Eliquis vs Bayer, J&J’s Xarelto Two blood thinners brought by four of the biggest pharmas are battling it out in cardiovascular disease. Bristol Myers Squibb and Pfizer’s oral anticoagulant Eliquis is the stronger competitor. Despite being approved more than a decade ago, Eliquis’ market presence continues to grow, surging 9% year-on-year to bring in $13.3 billion in 2024. Meanwhile, its closest competitor is a distant second. Though it won the FDA’s blessing a year ahead of Eliquis in 2011 , Bayer and Johnson & Johnson’s Xarelto has fallen behind its competitor in terms of market share. The drug peaked in 2021 when it earned J&J $2.44 billion in the U.S. and Bayer just over $5 billion in international markets, for a total of around $7.5 billion. Last year Bayer reported roughly $3.85 billion in international sales for Xarelto, while J&J recorded $2.37 billion in the U.S.—a total of over $6.2 billion. There are likely several reasons for why Eliquis has cleanly outperformed Xarelto, and one of them might be a question of clinical value. A 2021 study published in JAMA showed that in a Medicare population of more than 580,000 patients with atrial fibrillation, Xarelto was associated with significantly elevated risks of major ischemic or hemorrhagic events, such as fatal bleeding, as compared with Eliquis. Total mortality was also worse with Xarelto. Similarly, a 2023 study in Circulation found that Xarelto significantly heightened the risk of ischemic stroke and major bleeding versus Eliquis in patients in the Optum Clinformatics Data Mart database. There have been no well-designed and well-controlled head-to-head trials to compare the drugs. Alzheimer’s: Biogen, Eisai’s Leqembi vs Lilly’s Kisunla Decades of dispiriting clinical failures have finally produced two winners in Alzheimer’s disease. A tough market showdown has followed. In one corner is Biogen and Eisai’s embattled Leqembi and on the other is Eli Lilly’s newer challenger Kisunla. The anti-amyloid antibody Leqembi first won regulatory clearance in January 2023 under the FDA’s accelerated pathway before becoming the industry’s first fully approved Alzheimer’s therapy in July 2023. The buzz around Leqembi was strong, despite questions about the strength of the efficacy results and whether the benefits outweighed the risks. Phase III data presented in September 2022 helped revitalize the anti-amyloid theory, experts said at the time. In June 2023, an FDA advisory committee unanimously endorsed Leqembi’s full approval. Meanwhile, Kisunla’s path to approval was more fraught. In January 2023, the FDA turned down Lilly’s bid for accelerated approval, citing the need for more data from patients who had been treated for at least 12 months. The drug eventually won the regulator’s blessing in July 2024 , almost a year to the day behind Leqembi. Now, however, Leqembi’s edge doesn’t seem so large. Biogen and Eisai have struggled to get the drug off the ground and have been forced at least twice to lower their sales projection for the asset. In March, for instance, Eisai revealed that it expects Leqembi to bring in from ¥250 billion to ¥280 billion (approximately $1.7 billion to $1.9 billion) in its fiscal year 2027—a roughly 50% decline from a prior projection. For fiscal year 2024, which ends this month, the Japanese firm expects full-year sales of around $280 million for Leqembi. Lilly has already launched Kisunla in the U.S. but has yet to report sales figures. But both drugs have faced concerns about side effects called ARIA, which can signal bleeding or swelling in the brain. They have also faced slow uptake as physicians and health systems struggle to adapt to the new treatment paradigm. I&I: AbbVie’s Humira vs J&J’s Stelara Two pharma giants are duking it out in the immunology space with blockbuster drugs that are past their prime. AbbVie’s Humira was for six straight years the world’s best-selling drug. The biologic peaked in 2022 , bringing in $21.2 billion. But since losing key patent protections in 2023, its sales have declined steeply : last year, Humira made just under $9 billion . On the other hand, J&J’s Stelara never reached the same sales heights as Humira. At its peak in 2023, Stelara raked in $10.86 billion before dipping 4.6% to $10.34 billion last year. Like AbbVie’s biologic, Stelara is contending with copycat competitors. After it lost market exclusivity in 2023, several biosimilars have entered the U.S. market, including Amgen’s Wezlana and Sandoz’s Pyzchiva . Both Humira and Stelara work by tamping down the inflammatory response and share a substantial overlap in their indications, including psoriatic arthritis, plaque psoriasis, Crohn’s disease and ulcerative colitis. The specific mechanisms by which the drugs exert their therapeutic effects differ, however. Humira targets TNF-alpha, while Stelara acts on IL-12 and IL-23. All three molecules are crucial parts of the inflammatory cascade and often act synergistically, with slight differences in functionality. IL-12 and IL-23 explicitly encourage inflammation, for instance, while TNF-alpha can have both pro- and anti-inflammatory effects. In May 2021, a head-to-head study showed that despite these mechanistic nuances, Stelara and Humira are largely clinically similar. In patients with Crohn’s disease, Stelara induced a 64.9% clinical remission rate at 52 weeks, while Humira achieved a 61% remission rate at the same time point—a difference that failed to reach statistical significance. Lymphoma: AstraZeneca’s Calquence vs AbbVie’s, J&J’s Imbruvica The blood cancer field is witness to a BTK inhibitor battle between AbbVie and J&J’s Imbruvica, the first-comer, and AstraZeneca’s Calquence, which entered the ring four years later. The bad blood between the two goes way back to the biotech days, when Pharmacyclics developed what would become Imbruvica and rival Acerta Pharma championed Calquence. The rivalry was chronicled in Nathan Vardi’s book For Blood and Money: Billionaires, Biotech, and the Quest for a Blockbuster Drug . Both drugs work by blocking the Bruton’s tyrosine kinase, an enzyme that plays a crucial signaling role in the proliferation and activity of B cells. Because they share a mechanism of action, the two products also have wide overlap in their indications. Imbruvica and Calquence are both approved for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL). Currently, Imbruvica has a slight edge. Last year, AbbVie reported nearly $3.35 billion in worldwide sales for the drug, as opposed to Calquence’s $3.13 billion. Imbruvica also has broader coverage: Aside from the indications that it shares with Calquence, it is also approved for chronic graft versus host disease and the rare blood cancer Waldenström’s macroglobulinemia. But Calquence is quickly gaining ground. In 2024, AstraZeneca’s asset grew 24% year-on-year, while Imbruvica slid 6.9%. Calquence is also catching up clinically. A May 2024 readout showed that AstraZeneca’s drug, when combined with standard chemoimmunotherapy, can boost progression-free survival in untreated patients with mantle cell lymphoma (MCL). AbbVie and J&J had pulled Imbruvica’s accelerated approval in this indication nearly a year before. Calquence remains approved for MCL under the FDA’s accelerated pathway. Meanwhile, real-world data presented at the 2024 Congress of the European Hematology Association showed that patients with CLL or SLL who were treated with Calquence had longer time to discontinuation or death than comparators on Imbruvica. Time to next treatment was also longer in the Calquence group, as reported by OncLive at the time.

Orphan Drug Designation follows positive Phase 1 data presented at the 12th International Workshop on Waldenström Macroglobulinemia First-in-class Bruton’s tyrosine kinase (BTK) degrader NX-5948 assigned nonproprietary name “bexobrutideg” in newly named degrader class of drugs March 17, 2025 -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to bexobrutideg (NX-5948) for the treatment of Waldenström macroglobulinemia (WM). Bexobrutideg is an orally bioavailable, brain penetrant degrader of BTK which is being evaluated in an ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. The FDA's Orphan Drug Designation program provides orphan status to therapies intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the United States. This designation provides certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved. “The FDA’s Orphan Drug Designation for bexobrutideg, also known as NX-5948, represents an important milestone in our regulatory strategy and underscores the significant unmet medical need for improved treatments for Waldenström macroglobulinemia,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “Granting of the designation highlights bexobrutideg’s potential to provide patients with WM a promising new therapeutic option. We are also pleased to announce that our investigational therapy bexobrutideg has been assigned a nonproprietary name reflecting its novel mechanism of action, designated with the unique suffix “deg” for degrader.” In collaboration with the national naming authority, United States Adopted Name (USAN) Council, Nurix’s lead BTK degrader, NX-5948, was assigned the nonproprietary name “bexobrutideg.” The U.S. and international drug naming convention is designed to select a single name of worldwide acceptability for each active substance that is intended to be marketed as a pharmaceutical. Most notable with bexobrutideg is the designation of a new suffix, “deg,” which references bexobrutideg’s novel degradation mode of action. Targeted protein degraders are characterized by their bifunctional nature, binding to both a target protein and a ligase to drive ubiquitination and catalytic degradation of the target through the proteasome. The new deg suffix is an important recognition that the mechanism of action, pharmacokinetics and pharmacodynamics of targeted protein degraders are fundamentally different than inhibitors, which all use the “ib” suffix. The central stem of the name, “bruti,” references the target, Bruton’s tyrosine kinase (as used in ibrutinib, zanubrutinib and acalabrutinib). The prefix “bexo” is the unique identifier of a specific agent in the class and is often used for ease of reference to the agent. “We are excited that bexobrutideg has been recognized by the USAN Council as a unique entity and member of a new class of small molecule drugs, targeted protein degraders,” said Gwenn Hansen, Ph.D., chief scientific officer of Nurix. “The catalytic mechanism of action and event driven pharmacology triggering ubiquitination and proteasomal degradation of a target protein is highly differentiated from inhibitors and allows degraders to eliminate the totality of a protein’s function. In our BTK degrader clinical program, we have also established that degraders can eliminate mutant oncoproteins that have proven to be resistant to inhibitor therapy.” Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK that is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported encouraging safety and efficacy data in patients with WM treated in the ongoing Phase 1a/b clinical trial of bexobrutideg demonstrating early promise of clinical benefit with potential for durable outcomes. Nurix continues to enroll patients with WM in an ongoing Phase 1b expansion cohort and anticipates sharing additional clinical data in 2025. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022). Nurix is also developing bexobrutideg for the potential treatment of inflammatory diseases. WM is a rare, slow growing type of non-Hodgkin’s lymphoma that is characterized by the replacement of normal bone marrow cells by malignant lymphocytic cells that produce monoclonal IgM. This replacement leads to anemia, bleeding, and impaired immune function, while the elevated IgM levels may cause neurologic symptoms. The incidence of Waldenström macroglobulinemia ranges from 0.361,2 to 0.573 per 100,000 people in the United States or approximately 1,200 to 1,900 annually. With a median disease duration approaching 10 years, 4 approximately 12,000 to 19,000 patients are living with Waldenstrom’s macroglobulinemia in the United States. Recommended first-line treatments including chemoimmunotherapy and BTK inhibitor (BTKi) therapy. There are no therapies approved to treat WM patients after a BTKi. Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, the next frontier in innovative drug design aimed at improving treatment options for patients with cancer and inflammatory diseases. Nurix’s wholly owned, clinical stage pipeline includes degraders of Bruton’s tyrosine kinase (BTK), a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Nurix also is advancing multiple potentially first-in-class or best-in-class degraders and degrader antibody conjugates (DACs) in its preclinical pipeline. Nurix’s partnered drug discovery pipeline consists of preclinical stage degraders of IRAK4 and STAT6, as well as multiple additional programs under collaboration agreements with Gilead Sciences, Inc., Sanofi S.A. and Pfizer Inc., within which Nurix retains certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates. Powered by a fully AI-integrated discovery engine capable of tackling any protein class, and coupled with unparalleled ligase expertise, Nurix’s dedicated team has built a formidable advantage in translating the science of targeted protein degradation into clinical advancements. Nurix aims to establish degrader-based treatments at the forefront of patient care, writing medicine’s next chapter with a new script to outmatch disease. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com. 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Achieves alignment with U.S. Food and Drug Administration (FDA) on regulatory path for potential accelerated approval of iopofosine I 131 as a treatment for Waldenström macroglobulinemia (WM) Evaluating timing for Phase 1 solid tumor studies; Auger-emitting radioconjugate prepared for Phase 1b; plans to submit an IND for alpha-emitting radioconjugate; Company to host webcast and conference call at 8:30 AM ET today FLORHAM PARK, N.J., March 13, 2025 (GLOBE NEWSWIRE) -- Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development, and commercialization of drugs for the treatment of cancer, today announced financial results for the year ended December 31, 2024, and provided a corporate update. “In 2024 the company showcased the efficacy and safety of iopofosine I 131 for the treatment of relapsed/refractory Waldenström macroglobulinemia. We recently completed a productive meeting with the FDA that established a clear regulatory pathway for the accelerated approval of this promising drug. Based upon this regulatory clarity, the quality of the CLOVER-WaM data, and a robust global market opportunity, we continue to evaluate inbound inquiries regarding a range of collaborations for iopofosine I 131, which we view as an attractive, non-dilutive funding approach.” said James Caruso, president and CEO of Cellectar. “In addition, the company received clearance for an IND for our Auger-emitting radioconjugate and will be submitting an IND application for our alpha-emitting radioconjugate. By the middle of 2025 we will be prepared to advance into phase 1 clinical studies for both compounds, in triple negative breast cancer and pancreatic cancer indications, respectively.” 2024 and Recent Corporate Highlights Finalized confirmatory study design and regulatory pathway for potential FDA accelerated approval of iopofosine I 131, the Company’s targeted radiotherapeutic candidate for the treatment of relapsed/refractory WM. The study will be a randomized, controlled trial of iopofosine I 131 versus a comparator arm, with 100 patients per arm.Two-stage approval process includes conditional accelerated approval based on a major response rate (MRR) endpoint with full approval based upon achieving a progression-free survival endpoint.Company expects to complete full patient enrollment within 24 months of the first patient admitted to the study.Total study cost is expected to be between $40M-$45M, with approximately $30M to full enrollment. Presented data from the Phase 2 CLOVER-WaM study in an oral session at the 66th American Society of Hematology Annual Meeting and Exposition (ASH 2024) in December. The oral presentation highlighted that treatment with iopofosine I 131 in patients suffering from relapsed/refractory WM demonstrated: overall Response Rate (ORR) was 83.6%;major Response Rate (MRR) was 58.2%, which exceeded the FDA agreed-upon primary endpoint of 20% MRR;durable efficacy in previously treated WM patients, with no current standard of care therapy;well tolerated with a manageable toxicity profile across broad biologic and clinical subgroups. An article published in the journal eBioMedicine, volume 111, 2025, 105496, ISSN 2352-3964 from a SPORE Grant-supported, investigator-led study utilizing iopofosine I 131 (also known as CLR 131) in combination with external beam radiation, reported the best overall response from 11 evaluable patients included seven participants with a complete response (63.6%), one with a partial response (9%), one with stable disease (9%), and two with disease progression (18%), further supporting iopofosine I 131’s therapeutic benefit in solid tumors.Continued development of CLR 121225 and CLR 121125, the Company’s pre-clinical radioconjugate assets, to support Phase 1 solid tumor studies: The company is prepared to initiate a Phase 1b/2a dose-finding study with CLR 121125 in triple-negative breast cancer. CLR 121125 is the company’s lead Auger-emitting (iodine-125) Phospholipid Radioconjugate™ (PRC) that provides the greatest precision in targeted radiotherapy as emissions only travel a few nanometers.The company plans to file an IND application in the first half of 2025 for CLR 121225. CLR 121225 is Cellectar’ s lead alpha-emitting (actinium-225) PRC, which has demonstrated activity in multiple solid tumor animal models, including pancreatic and colorectal cancer. 2024 Financial Highlights Cash and Cash Equivalents: As of December 31, 2024, the company had cash and cash equivalents of $23.3 million, compared to $9.6 million as of December 31, 2023. In 2024, Cellectar executed multiple financial transactions, including investors’ exercise of warrants in January 2024 that generated $44.1 million, and an inducement financing in July 2024, which included the exercise of existing warrants and the purchase of new warrants for an additional $19.4 million. The company believes its cash balance as of December 31, 2024, is adequate to fund its basic budgeted operations into the fourth quarter of 2025.Research and Development Expenses: R&D expenses for the year ended December 31, 2024, were approximately $26.1 million, compared to approximately $27.3 million for the year ended December 31, 2023. The decrease was primarily a result of the timing of expenditures for our WM Phase 2 study to support final patient visits, partially offset by the extensive analytic work necessary to prepare for a planned regulatory submission, product sourcing, manufacturing, and logistics infrastructure costs to support multi sourcing for each aspect of iopofosine I 131 production.General and Administrative Expenses: G&A expenses for the year ended December 31, 2024, were approximately $25.6 million, compared to approximately $11.7 million for the same period in 2023. The increase was primarily driven by costs associated with the development of infrastructure necessary to support potential commercialization, including the related marketing and personnel costs.Other income and expense: Other income and expense, net, was approximately $7.3 million of income in 2024, as compared to approximately $3.9 million of expense in the prior year. These amounts are almost exclusively non-cash and driven by the issuance and valuation of equity securities in conjunction with financing activities. The only cash impact was interest income, which for 2024 improved to approximately $1.2 million from $0.4 million in the prior year.Net Loss: Net loss for the full year ending December 31, 2024, was $44.6 million or $1.22 per basic share and $1.40 per diluted share, compared with $42.8 million or $3.50 per basic and diluted share during 2023. Conference Call & Webcast DetailsCellectar management will host a conference call and webcast today, March 13, 2024, at 8:30 AM Eastern Time to discuss these results and answer questions. Stockholders and other interested parties may participate in the conference call by dialing 1-800-717-1738. A live webcast of the conference call can be accessed in the “Events & Presentations” section of Cellectar’s website at www.cellectar.com. A recording of the webcast will be available and archived on the Company’s website for approximately 90 days. About Cellectar Biosciences, Inc.Cellectar Biosciences is a late-stage clinical biopharmaceutical company focused on the discovery and development of proprietary drugs for the treatment of cancer, independently and through research and development collaborations. The company’s core objective is to leverage its proprietary Phospholipid Drug Conjugate™ (PDC) delivery platform to develop the next-generation of cancer cell-targeting treatments, delivering improved efficacy and better safety as a result of fewer off-target effects. The company’s product pipeline includes its lead assets: iopofosine I 131, a PDC designed to provide targeted delivery of iodine-131 (radioisotope); CLR 121225, an actinium-225 based program being targeted to several solid tumors with significant unmet need, such as pancreatic cancer; and CLR 121125, an iodine-125 Auger-emitting program targeted in solid tumors, such as triple negative breast, lung and colorectal, as well as proprietary preclinical PDC chemotherapeutic programs and multiple partnered PDC assets. In addition, iopofosine I 131 has been studied in Phase 2b trials for relapsed or refractory multiple myeloma (MM) and central nervous system (CNS) lymphoma, and the CLOVER-2 Phase 1b study, targeting pediatric patients with high-grade gliomas, for which Cellectar is eligible to receive a Pediatric Review Voucher from the FDA upon approval. The FDA has also granted iopofosine I 131 six Orphan Drug, four Rare Pediatric Drug, and two Fast Track Designations for various cancer indications. For more information, please visit www.cellectar.com or join the conversation by liking and following us on the company’s social media channels: X, LinkedIn, and Facebook. Forward Looking Statements DisclaimerThis news release contains forward-looking statements. You can identify these statements by our use of words such as "may," "expect," "believe," "anticipate," "intend," "could," "estimate," "continue," "plans," or their negatives or cognates. These statements are only estimates and predictions and are subject to known and unknown risks and uncertainties that may cause actual future experience and results to differ materially from the statements made. These statements are based on our current beliefs and expectations as to such future outcomes. Drug discovery and development involve a high degree of risk. Factors that might cause such a material difference include, among others, uncertainties related to the ability to raise additional capital, uncertainties related to the disruptions at our sole source supplier of iopofosine, the ability to attract and retain partners for our technologies, the identification of lead compounds, the successful preclinical development thereof, patient enrollment and the completion of clinical studies, the FDA review process and other government regulation, our ability to maintain orphan drug designation in the United States for iopofosine, the volatile market for priority review vouchers, our pharmaceutical collaborators' ability to successfully develop and commercialize drug candidates, competition from other pharmaceutical companies, product pricing and third-party reimbursement. A complete description of risks and uncertainties related to our business is contained in our periodic reports filed with the Securities and Exchange Commission including our Form 10-K for the year ended December 31, 2024. These forward-looking statements are made only as of the date hereof, and we disclaim any obligation to update any such forward-looking statements. INVESTORS:Anne Marie FieldsPrecision AQ212-362-1200annemarie.fields@precisionaq.com +++ TABLES FOLLOW +++ CELLECTAR BIOSCIENCES, INC.CONSOLIDATED BALANCE SHEETS December 31, December 31, 2024 2023 ASSETS CURRENT ASSETS: Cash and cash equivalents $23,288,607 $9,564,988 Prepaid expenses and other current assets 961,665 888,225 Total current assets 24,250,272 10,453,213 Property, plant & equipment, net 757,121 1,090,304 Operating lease right-of-use asset 436,874 502,283 Other long-term assets 29,780 29,780 TOTAL ASSETS $25,474,047 $12,075,580 LIABILITIES AND STOCKHOLDERS’ (DEFICIT) EQUITY CURRENT LIABILITIES: Accounts payable and accrued liabilities $7,585,340 $9,178,645 Warrant liability 1,718,000 16,120,898 Lease liability, current 84,417 58,979 Total current liabilities 9,387,757 25,358,522 Lease liability, net of current portion 409,586 494,003 TOTAL LIABILITIES 9,797,343 25,852,525 COMMITMENTS AND CONTINGENCIES (Note 10) MEZZANINE EQUITY: Series D convertible preferred stock, 111.11 shares authorized; 111.11 shares issued and outstanding as of December 31, 2024 and 2023 1,382,023 1,382,023 STOCKHOLDERS’ (DEFICIT) EQUITY: Series E-2 preferred stock, 1,225.00 shares authorized; 35.60 and 319.76 shares issued and outstanding as of December 31, 2024 and 2023, respectively 520,778 4,677,632 Common stock, $0.00001 par value; 170,000,000 shares authorized; 46,079,875 and 20,744,110 shares issued and outstanding as of December 31, 2024 and 2023, respectively 461 207 Additional paid-in capital 261,115,905 182,924,210 Accumulated deficit (247,342,463) (202,761,017)Total stockholders’ (deficit) equity 14,294,681 (15,158,968)TOTAL LIABILITIES AND STOCKHOLDERS’ (DEFICIT) EQUITY $25,474,047 $12,075,580 CELLECTAR BIOSCIENCES, INC.CONSOLIDATED STATEMENTS OF OPERATIONS Year Ended December 31, 2024 2023 OPERATING EXPENSES: Research and development $26,136,246 $27,266,276 General and administrative 25,641,452 11,694,367 Total operating expenses 51,777,698 38,960,643 LOSS FROM OPERATIONS (51,777,698) (38,960,643) OTHER INCOME (EXPENSE): Warrant issuance expense (7,743,284) (470,000)Gain (loss) on valuation of warrants 13,794,683 (3,787,114)Interest income 1,210,853 387,147 Total other income (expense), net 7,262,252 (3,869,967)LOSS BEFORE INCOME TAXES (44,515,446) (42,830,610) INCOME TAX PROVISION (BENEFIT) 66,000 (60,000) NET LOSS $(44,581,446) $(42,770,610)NET LOSS PER SHARE — BASIC $(1.22) $(3.50)NET LOSS PER SHARE — DILUTED $(1.40) $(3.50)WEIGHTED-AVERAGE COMMON SHARES OUTSTANDING — BASIC 36,622,474 12,221,571 WEIGHTED-AVERAGE COMMON SHARES OUTSTANDING — DILUTED 37,143,769 12,221,571