Cellectar Biosciences, Inc. (NASDAQ:CLRB) is a late-stage clinical biopharmaceutical company focused on the discovery, development, and commercialization of drugs for the treatment of cancer. The company's lead product candidate, iopofosine I 131, is a small-molecule phospholipid drug conjugate (PDC) designed to provide targeted delivery of iodine-131 directly to cancer cells, while limiting exposure to healthy cells. This unique approach differentiates iopofosine from many traditional on-market treatments and radiotherapeutics.

Cellectar's Q1 2024 Highlights

In the first quarter of 2024, Cellectar reported several key accomplishments. The company announced positive topline data from the CLOVER-WaM pivotal study, evaluating iopofosine I 131 for the treatment of relapsed/refractory Waldenstrom's macroglobulinemia (WM). The study met its primary endpoint with a major response rate of 61%, exceeding the agreed-upon statistical hurdle of 20%. Additionally, the overall response rate in evaluable patients was 75.6%, and 100% of patients experienced disease control. Responses were durable, with a median duration of response not yet reached and 76% of patients remaining progression-free at a median follow-up of eight months.

To support the potential launch of iopofosine I 131, Cellectar secured approximately $44 million in January 2024 through a private placement, with the potential to receive an additional $34 million upon approval of the WM new drug application (NDA). The company also announced a strategic partnership with the American Oncology Network (AON), a physician-led, community-based oncology platform, to advance the treatment of WM in the community setting and ensure patient access to iopofosine I 131.

Cellectar's Promising Preclinical Pipeline

In addition to the progress with iopofosine I 131, Cellectar reported promising preclinical data for three unique internally developed alpha-emitting radiotherapeutics, including the proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate, CLR 121225, an actinium-labeled phospholipid ether. The company plans to initiate a Phase I study for one of these solid tumor assets no later than Q1 2025.

Financials

Cellectar's financial performance in Q1 2024 reflects the company's focus on advancing its pipeline and preparing for the potential commercialization of iopofosine I 131. As of March 31, 2024, the company had a cash and cash equivalents balance of $40.0 million, compared to $9.6 million as of December 31, 2023. The increase in cash was primarily due to the exercise of warrants, which generated net proceeds of $43.9 million.

Research and development (R&D) expense for the quarter was approximately $7.4 million, compared to $6.7 million in the first quarter of 2023. The increase was driven by the company's efforts to ensure a robust supply chain and production sourcing to mitigate potential disruptions, as well as ongoing clinical trials. General and administrative (G&A) expense for the quarter was $4.6 million, up from $2.1 million in the same period last year, primarily due to the development of infrastructure and personnel to support the expected commercialization of iopofosine I 131.

The company reported a net loss of $21.6 million, or $0.74 per share, for the first quarter of 2024, compared to a net loss of $8.6 million, or $0.76 per share, in the same period of 2023. The increase in net loss was largely attributable to the non-cash charge related to the revaluation of warrants.

Liquidity

As of March 31, 2024, Cellectar had a consolidated cash balance of approximately $40.0 million, which the company believes is adequate to fund its basic budgeted operations into the fourth quarter of 2024. The company's ability to execute its current operating plan beyond that time depends on its ability to obtain additional funding through the sale of equity and/or debt securities, a strategic transaction, or other sources of capital.

Iopofosine I 131: A Promising Radiotherapeutic for Waldenstrom's Macroglobulinemia

Iopofosine I 131 is Cellectar's lead PDC therapeutic, designed to provide targeted delivery of iodine-131 directly to cancer cells, while limiting exposure to healthy cells. The compound has received Fast Track Designation from the FDA for the treatment of lymphoplasmacytic lymphoma (LPL) and Waldenstrom's macroglobulinemia (WM) in patients who have received two or more prior treatment regimens, as well as for relapsed/refractory multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL).

The CLOVER-WaM pivotal study, which completed enrollment in the fourth quarter of 2023, evaluated iopofosine I 131 in WM patients who had received at least two prior lines of therapy, including those who had failed or had a suboptimal response to Bruton tyrosine kinase inhibitor (BTKi) therapy. The study met its primary endpoint, with a major response rate of 61% in the modified intent-to-treat population, exceeding the agreed-upon statistical hurdle of 20%. Iopofosine I 131 was well-tolerated, with a safety profile consistent with the company's previously reported data.

Cellectar plans to submit the NDA for iopofosine I 131 in the treatment of WM to the FDA in the second half of 2024. Assuming the company is granted priority review associated with the Fast Track designation, the FDA review period is expected to be approximately 6 months from the date of NDA submission.

Iopofosine I 131 in Other Indications

In addition to the WM pivotal study, Cellectar is evaluating iopofosine I 131 in other indications. The company has initiated a Phase Ib clinical study of iopofosine I 131 in pediatric patients with high-grade gliomas, a patient population with limited treatment options. Cellectar plans to provide an update on this study in the second half of 2024.

Furthermore, the company reported promising data from an investigator-initiated Phase I study of iopofosine I 131 in combination with external beam radiotherapy in patients with recurrent head and neck cancer. The study demonstrated a 64% complete remission rate and a 73% overall response rate in a highly refractory patient population, with durable clinical activity.

Cellectar's Preclinical Pipeline

Cellectar's preclinical pipeline includes several promising assets, including the company's proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate, CLR 121225, which utilizes actinium-225 as the payload. The company has reported positive preclinical data for CLR 121225 in pancreatic cancer models and plans to evaluate the asset in additional solid tumor models, such as ovarian and triple-negative breast cancer. Cellectar intends to initiate a Phase I study for one of its alpha-emitting radiotherapeutic programs no later than Q1 2025.

Cellectar's Commercialization Strategy

Cellectar is actively preparing for the potential commercialization of iopofosine I 131 in the treatment of WM. The company's market research has shown a high intent to prescribe iopofosine I 131 among hematologists, as well as enthusiasm from radiation oncologists and nuclear medicine physicians regarding the product's features, such as the lack of required dosimetry, short infusion time, long storage life, and ease of administration.

Cellectar is selectively building a commercial team to support its go-to-market model in WM, with the goal of establishing market leadership. The company plans to leverage claims data to drive decision-making, support radiotherapy site activation, and ensure a positive first treatment experience for both patients and providers.

The WM market is highly attractive for Cellectar, with no established standard of care, significant unmet need, and limited competition. The company's analysis of third-party claims data shows that nearly 50% of patients in the third line or greater setting are retreated with the same or similar treatment from an earlier line due to the lack of options. Cellectar believes iopofosine I 131, with its novel mechanism of action and strong clinical profile, can capture significant market share in this setting.

Cellectar's Scalable and Flexible Manufacturing and Distribution Strategy

Cellectar has implemented a flexible, modular manufacturing strategy to address the challenges typically faced by targeted radiotherapeutics, such as limited finished product manufacturing locations, constrained isotope availability, and short shelf life. The company's approach utilizes a network of overlapping suppliers and contractors, reducing the overall footprint and operating costs while mitigating supply chain issues.

Currently, Cellectar can supply over 200 doses per week of iopofosine I 131, with the capability to quickly scale up to over 1,000 patient doses per week without expanding its existing infrastructure. The company's modular supply chain also allows for further expansion to nearly double current supplies, with plans in place for over a 50% increase in supplies with the addition of at least one more facility.

Cellectar's distribution strategy aims to provide broad access to iopofosine I 131, working closely with both community-focused oncology networks and hospital systems to ensure availability for their patients.

Conclusion

Cellectar Biosciences is a late-stage clinical biopharmaceutical company with a promising radiotherapeutic pipeline, led by its lead asset, iopofosine I 131. The positive topline data from the CLOVER-WaM pivotal study in Waldenstrom's macroglobulinemia, along with the company's advanced commercial preparations and scalable manufacturing and distribution strategy, position Cellectar for potential success in the radiotherapeutics market.

The company's preclinical pipeline, including the novel alpha-emitting radiotherapeutic conjugate CLR 121225, further demonstrates Cellectar's innovative approach to cancer treatment. With a strong cash position and a clear path forward, Cellectar appears well-equipped to advance its pipeline and capitalize on the significant opportunities in the Waldenstrom's macroglobulinemia and broader oncology markets.