On November 18, 2024 AstraZeneca reported that Tagrisso (osimertinib) has been recommended for approval in the European Union (EU) for the treatment of adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy (CRT) (Press release, AstraZeneca, NOV 18, 2024, View Source [SID1234648466]).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on the results from the LAURA Phase III trial, which were published in The New England Journal of Medicine.

Results showed Tagrisso reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio [HR] 0.16; 95% confidence interval [CI] 0.10-0.24; p<0.001) as assessed by blinded independent central review. Median progression-free survival (PFS) was 39.1 months in patients treated with Tagrisso versus 5.6 months for placebo.

Overall survival (OS) results remain immature at this current analysis. The trial continues to assess OS as a secondary endpoint.

Each year in Europe, there are more than 450,000 people diagnosed with lung cancer.1 Among those with NSCLC, the most common form of lung cancer, about 10-15% of patients in Europe have tumours with an EGFR mutation.2,3 Additionally, nearly one in five people with NSCLC has an unresectable tumour.4

Manuel Cobo, MD, Specialist Physician of the Medical Oncology Service at the Carlos Haya University Hospital, Malaga, Spain, and investigator for the trial, said: "The LAURA results build on the established efficacy of osimertinib and support the approval of the first targeted therapy for patients with unresectable, EGFR-mutated lung cancer. Today’s positive recommendation marks an important step towards offering patients in Europe a targeted treatment option that can extend the time before their disease progresses by more than three years."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Today’s news reinforces Tagrisso as the backbone therapy in EGFR-mutated non-small cell lung cancer, meeting the critical unmet need for an effective targeted treatment option in the unresectable setting. Tagrisso has now demonstrated its benefit across all stages of EGFR-mutated lung cancer, representing a pivotal step in transforming care for patients who are urgently in need of innovative therapies that can help extend their lives."

The safety and tolerability of Tagrisso in the LAURA trial was consistent with its established profile and no new safety concerns were identified.

Tagrisso following CRT was recently approved for the treatment of adult patients with unresectable, Stage III EGFRm NSCLC in the US. Regulatory applications are also currently under review in China, Japan and several other countries based on the LAURA trial.

Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC. Tagrisso is also approved in combination with chemotherapy in the US, China and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

Notes

Lung cancer
Each year, an estimated 2.4 million people are diagnosed with lung cancer globally.5 Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and small cell lung cancer.3 The majority of all NSCLC patients are diagnosed with advanced disease.6

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.7-9 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.10

LAURA
LAURA is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum-based CRT. Patients were treated with Tagrisso 80mg once-daily oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with Tagrisso.

The trial enrolled 216 patients in more than 145 centres across more than 15 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of Tagrisso as standard of care in EGFRm NSCLC. Tagrisso improved patient outcomes in early-stage disease in the ADAURA Phase III trial, Stage III, unresectable disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the neoadjuvant setting in the NeoADAURA Phase III trial and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.
The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso plus savolitinib as well as other potential new medicines.

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On November 18, 2024 Intensity Therapeutics, Inc. (Nasdaq: INTS), ("Intensity" or "the Company") a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that Christian F. Meyer M.D., Ph.D., Assistant Professor of Oncology and lead medical oncologist for adult sarcoma patients at Johns Hopkins University’s Sidney Kimmel Cancer Center, presented final safety and efficacy data from the Company’s Phase 1/2 clinical trial of INT230-6 that was used as a monotherapy in patients with relapsed, refractory, and metastatic sarcomas, along with an overview of the Company’s ongoing INVINCIBLE-3 Study design (NCT06263231) (Press release, Intensity Therapeutics, NOV 18, 2024, View Source [SID1234648482]). Dr. Meyer shared the information during an oral podium presentation in a late-breaking session at the 2024 Connective Tissue Oncology Society ("CTOS") on November 16, 2024, at 9 AM PST. The abstract’s lead author was Albiruni Razak, MB BCh, BM BCh, Clinician Investigator, Princess Margaret Cancer Centre at the University Hospital Network in Toronto, Ontario, Canada. Both Drs. Razak and Meyer, enrolled patients in the Phase 1/2 clinical trial. This year’s annual CTOS conference was held in San Diego from November 13 to 16, 2024 at the Grand Hyatt.

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"The data in the Phase 1/2 study has shown that INT230-6 causes cell death leading to tumor necrosis, improved cancer recognition by immune cells, and an ignition of a systemic anti-cancer immune response that results in T-cells entering the tumor microenvironment and has shown a favorable safety profile in soft tissue sarcomas," said Dr. Razak. "Systemically delivered chemotherapies have severe side effects, including cardiotoxicity, and most sarcoma subtypes have only a minimal response to immunotherapies. In addition, most sarcoma patients remain on current therapies for only a few months prior to progression, death or excessive toxicity. Demonstrating statistically significant improvement in median overall survival for the INT230-6 treatment arm compared to the standard of care arm in the INVINCIBLE-3 Study would be a major step forward in treating patients with these deadly soft tissue sarcomas."

Phase 1/2 Study (Sarcoma Subset Data: 15 Patients):

Demographics:

Median (min, max) lines for prior drug therapies: 3 (1.00, 7.00)
Mean (SD) age: 62.8 (8.1) years and ranged from 41.9 to 76.1 years
ECOG performance status at screening was 0, 1 and 2 for 2 (13.3%), 12 (80.0%), and 1 (6.7%) subjects respectively
The sarcoma diagnoses of the Phase 2 patients included liposarcoma, pleomorphic sarcoma, leiomyosarcoma, chondrosarcoma, osteosarcoma (chondroid syringoma), myofibroblastic, osteosarcoma, Kaposi sarcoma and chordoma
Efficacy:

The mOS in the mixed sarcoma population: 21.3 months for INT230-6
The mOS had not been reached with 21.4 months of median follow-up for patients who received a cumulative INT230-6 dose volume that was greater than 40% of their total tumor burden
INT230-6 extended overall survival in refractory sarcoma subjects by nearly 15 months as monotherapy when compared to a synthetic control group based on the Royal Marsden Hospital scoring method
Sarcoma population’s overall disease control rate (DCR): 93.3% (95% CI: 68.1, 99.8) at 2 months
Median duration of response (DOR): 4.0 months (95% CI: 1.7, NA) and 11.3 months (95% CI: 2.8, NA) for subjects who received a cumulative dose of ≥ 40% of the total incoming total tumor burden
INT230-6 demonstrated an increase in T-cells within the tumors
27% of patients had uninjected tumors shrink (abscopal effects), though tumors less than 1 cm were uninjected, untracked and unreported by investigators, so the true abscopal percentage is unknown; further radiomics work is on-going
Safety

INT230-6 demonstrated a favorable safety profile and was well-tolerated
3 subjects (20%) had one or more drug regimen-related Grade ≥ 3 Treatment Emergent Adverse Events (TEAE); all were grade 3 (there were no grade 4 or 5 TEAEs)
INVINCIBLE-3 Study Overview
The INVINCIBLE-3 Study is designed to evaluate INT230-6 administered intratumorally by an interventional radiologist or an equivalently trained physician using image guidance compared to systemically dosed standard of care ("SOC") chemotherapy. The study endpoints are overall survival and safety, along with an exploratory quality of life (QoL) assessment using the EORTC-30 survey. This is a global randomized Phase 3 study comparing the efficacy and safety of INT230-6 intratumoral (IT) injection with any of three standard of care therapies (pazopanib, trabectedin, or eribulin) in approximately 333 adult participants with locally recurrent, inoperable, or metastatic soft tissue sarcoma ("STS") patients who had disease progression prior to study enrollment following standard therapies, which must have included an anthracycline-based regimen unless contraindicated. Participants may also have received a maximum of one additional regimen. Randomization will occur after screening and eligibility confirmation. As this is a survival study, there is no crossover allowed between SOC and INT230-6. Disease progression will be determined by the World Health Organization (WHO) criteria. Participants will be prospectively stratified into 1 of 3 histologically defined STS strata:

leiomyosarcoma
liposarcoma (dedifferentiated, myxoid, round cell and pleomorphic)
undifferentiated pleomorphic sarcoma
The comparator agents used are all U.S., Europe, Canadian and Australian-approved agents for sarcomas: pazopanib tablets, trabectedin, and eribulin mesylate. Authorizations for the INVINCIBLE-3 Study have been obtained from the U.S. FDA, Health Canada, the European Medicines Agency, and Australia’s Therapeutic Goods Administration. Sites will be opened in 8 countries and the study is presently recruiting participants in the U.S., Canada, and Europe.

"The safety and efficacy data of our lead drug candidate, INT230-6, generated for sarcomas was quite encouraging. Many insights were gained from the over 200 patients treated before initiating the INVINCIBLE-3 study and applied to the ongoing study. Our approach uses sophisticated interventional radiology technologies to guide needles into tumors to inject our novel cytotoxic drug, which is highly absorbed by tumors, and showed a potential meaningful impact on lengthening metastatic sarcoma patient lives, reducing toxicities and improving quality of life compared to current treatments in our first clinical trial," said Lewis H. Bender, Intensity’s President and Chief Executive Officer. "Our unique chemistry enables water-based products to diffuse throughout tumors and into cancer cells, causing immunologic cell death."

About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine sulfate, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 causes a release of a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy.

On November 18, 2024 Avenzo Therapeutics, Inc. ("Avenzo"), a clinical-stage biotechnology company developing next-generation oncology therapies for patients, reported it has entered into an exclusive option agreement with VelaVigo for an exclusive license to develop, manufacture and commercialize a potential first-in-class Nectin4/TROP2 bispecific antibody-drug conjugate (ADC), globally (excluding Greater China) (Press release, Avenzo Therapeutics, NOV 18, 2024, View Source [SID1234649419]). Nectin4 and TROP2 are highly co-expressed in multiple solid tumor types, including metastatic urothelial cancer.

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In addition, Avenzo has closed the final tranche of an oversubscribed Series A/A-1 financing, adding three new investors. The prior syndicate of investors, namely OrbiMed, Foresite Capital, SR One, Lilly Asia Ventures, Surveyor Capital (a Citadel company), New Enterprise Associates (NEA), Deep Track Capital, Sofinnova Investments, Sands Capital, INCE Capital, TF Capital, Delos Capital, and Quan Capital participated in this tranche, bringing the total capital raised to approximately $386 million.

"Since the formation of Avenzo, we have focused on building a pipeline of potential best- or first-in-class oncology assets. Today’s announcement brings us one step closer to our goal, and is based on the tremendous work from Scott Lipman, Chief Business Officer, and our entire team over the past 18 months," said Athena Countouriotis, M.D., Co-founder, President and CEO of Avenzo. "We continue to build our team to support our expected multiple clinical stage assets in mid-2025 and are excited to close our Series A/A-1 financing and add three new investors to our syndicate."

Under the terms of the exclusive option agreement, VelaVigo will receive an upfront fee and be entitled to receive upon the option exercise by Avenzo, an option exercise payment and potential development, regulatory, and commercial milestone payments, totaling up to approximately $800 million, as well as tiered royalties on sales in Avenzo’s territory.

An Investigational New Drug application for the Nectin4/TROP2 ADC is planned for submission to the U.S. Food and Drug Administration in mid-2025.

The company also announced the promotion of Scott Lipman, MBA to Chief Business Officer. Mr. Lipman joined Avenzo in March 2023 as Senior Vice President, Corporate Development and has led the company’s business development and strategy functions. Previously, he was on the leadership team at Turning Point Therapeutics and played an integral role in its acquisition by Bristol Myers Squibb for $4.1 billion in 2022. Mr. Lipman also worked in Healthcare Investment Banking at Goldman Sachs and started his career as a management consultant at ZS Associates. He received his B.S. in Chemical Engineering from the University of California, Los Angeles and his M.B.A. from the Kellogg School of Management at Northwestern University.

On November 18, 2024 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, reported financial results for the quarter ended September 30, 2024, and provided a corporate update (Press release, Cellectar Biosciences, NOV 18, 2024, View Source [SID1234648467]).

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"We achieved important clinical, operational and commercial corporate objectives during the quarter. We reported topline results from the CLOVER-WaM pivotal study in WM and look forward to filing our NDA submission with a request for accelerated regulatory approval in the coming months," said James Caruso, president and CEO of Cellectar Biosciences. "In addition to our lead iopofosine I 131 program, we plan to further advance the value of our phospholipid radioconjugate pipeline and are preparing alpha and Auger PRCs for initiation of solid tumor clinical studies as business conditions allow."

Third Quarter and Recent Corporate Highlights

· Reported positive results from the Phase 2 CLOVER-WaM pivotal study evaluating iopofosine I 131, the company’s potentially first-in-class, targeted radiotherapeutic candidate, for the treatment of relapsed/refractory Waldenstrom’s macroglobulinemia (WM). These results support the company’s planned filing of the New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the near term.

· Selected to present data from the CLOVER-WaM study evaluating iopofosine I 131 in patients with WM at the upcoming 66th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition (ASH) (Free ASH Whitepaper), in an oral presentation session. Details of the oral presentation are as follows:

o Abstract Title: Iopofosine I 131 in Previously Treated Patients with Waldenström Macroglobulinemia (WM): Efficacy and Safety Results from the International, Multicenter, Open-Label Phase 2 Study (CLOVER-WaM)

o Session Name: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Clinical Trials for Marginal Zone Lymphoma, Waldenstrom’s Macroglobulinemia and Hairy Cell Leukemia

o Session Date: Monday, December 9, 2024

o Presentation Time: 3:15 PM PST

· Delivered oral and poster presentations at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM) in October 2024 that highlighted the activity of iopofosine I 131 in WM.

o Oral presentation: Session XXII Clinical Trials in Progress for WM: Multi-center trial of iopofosine I-131 in relapsed/refractory WM

o Poster presentation: Treatment With iopofosine I 131 in a Patient With Bing-Neel Syndrome, A Rare Manifestation of Waldenström Macroglobulinemia: A Case Report

· Advanced sales, marketing and medical planning activities to support iopofosine I 131 commercialization

· Partnered with key national and regional community cancer networks to better understand the WM disease landscape, to advance iopofosine I 131 for WM patients in the community setting

· Established collaboration with the City of Hope Cancer Center to evaluate iopofosine I 131 in mycosis fungoides, a cutaneous T-cell lymphoma

· Executed supply and manufacturing agreements, further strengthening our multi-sourced supply network:

o Commercial finished product supply of iopfosine I 131 with SpectronRx

o Pre-clinical and clinical supply of alpha-emitting actinium 225 isotope with Northstar Medical Radioisotopes

· Raised $19.4 million through warrant exercises and issued new milestone-based warrants with the potential to raise up to an additional $73.3 million. Funds generated from the execution of these new warrants will further advance the company’s commercialization plans for iopofosine I 131 in the treatment of WM and support future clinical development.

Third Quarter 2024 Financial Highlights

· Cash and Cash Equivalents: As of September 30, 2024, the company had cash and cash equivalents of $34.3 million, including 19.4 million ($17.5 million, net) raised through investor exercises of Tranche B warrants and the purchase of new warrants in July 2024, compared to $9.6 million as of December 31, 2023. The company believes its cash balance as of September 30, 2024, is adequate to fund its basic budgeted operations into the second quarter of 2025.

· Research and Development Expenses: R&D expenses for the three months ended September 30, 2024, were approximately $5.5 million, compared to approximately $7.0 million for the three months ended September 30, 2023. The overall decrease was primarily a result of the conclusion of patient enrollment in our WM pivotal study having occurred earlier in the year, partially offset by increased activity in our ongoing pediatric trial and an increase in personnel.

· General and Administrative Expenses: G&A expenses for the three months ended September 30, 2024, were approximately $7.8 million, compared to approximately $2.4 million for the same period in 2023. The increase was primarily driven by costs associated with the development of infrastructure necessary to support commercialization upon anticipated NDA approval, including the related marketing and personnel cost.

Conference Call & Webcast Details

Cellectar management will host a conference call and webcast today, November 18, 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.

On November 18, 2024 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, reported recent regulatory and development updates for its Iomab-B, Actimab-A and Iomab-ACT ARC clinical programs as well as its financial results for the third quarter ended September 30, 2024 (Press release, Actinium Pharmaceuticals, NOV 18, 2024, View Source [SID1234648483]). Iomab-B is a first in class CD45 targeted conditioning agent to enable bone marrow transplant (BMT) and has been studied in over four hundred patients including the completed Phase 3 SIERRA trial for patients with relapsed or refractory acute myeloid leukemia (r/r AML). Actimab-A is a targeted radiotherapeutic that uses the Actinium-225 (Ac-225) isotope payload directed against CD33 with broad potential for development in AML and other myeloid indications including in collaboration with the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA). Iomab-ACT is a next-generation CD45 targeted conditioning agent being developed for cell and gene therapies for both malignant and non-malignant hematologic indications. Actinium is executing cutting-edge R&D focused on ARCs and other targeted radiotherapies for blood cancer and solid tumor indications leveraging its strong intellectual property portfolio of 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron.

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Sandesh Seth, Actinium’s Chairman and CEO, stated, "During the third quarter and over the last several weeks, we have made significant progress with our three ARC clinical programs. Actinium is now positioned to advance exciting clinical trials for Actimab-A and Iomab-ACT in large indications with high unmet needs that can deliver impactful clinical data in 2025. Actimab-A’s backbone therapy potential is poised to be realized with the operationally seamless Phase 2/3 trial following alignment with the FDA, additional clinical trials being planned under the NCI CRADA including the myeloMATCH program and via our R&D efforts to further elucidate Actimab-A’s mutation agnostic mechanism of action. The clinical data anticipated from Iomab-ACT in 2025 from the commercial CAR-T and sickle cell transplant trials has the potential to establish Iomab-ACT as a best-in-class targeted conditioning agent for both malignant and non-malignant hematology indications. In addition, our recent meeting with the FDA regarding Iomab-B established a clear development pathway, which will be incredibly valuable in securing a U.S. strategic partner. Finally, I am delighted to welcome Dr. June Almenoff to our Board of Directors, who brings over 25 years of biopharma industry experience with a proven track record of leading drug development through approvals and executing value enhancing business development transactions."

Actimab-A Regulatory and Development Update

Actinium met with the FDA in the third quarter and aligned with the FDA on an operationally seamless randomized Phase 2/3 trial to study Actimab-A + CLAG-M
In the Phase 2 portion of the study, the Actimab-A dose will be optimized in combination with CLAG-M
The Phase 3 portion will study the optimized dose of Actimab-A + CLAG-M versus CLAG-M alone in patients with r/r AML
Operationally seamless trial design is expected to reduce the required time and resources compared to separate Phase 2 and Phase 3 trials
Actinium continues to evaluate and develop additional Actimab-A clinical trials under its CRADA with the NCI, investigator initiated, or Actinium sponsored studies
Actimab-A selected by NCI for recently opened myeloMATCH precision medicine program for patients with AML and myelodysplastic syndrome (MDS)
Iomab-ACT Program Update

In the third quarter, the FDA cleared the investigational new drug (IND) applications for both the commercial CAR-T study led by the University of Texas Southwestern (UTSW) and the sickle cell trial being led by Columbia University
The UTSW commercial CAR-T trial expected to initiate patient enrollment in 1Q 2025 with proof-of-concept clinical data expected by year end
Commercial CAR-T sales exceeded $3.5 billion in 2023 with multiple CAR-T therapies approved for patients with lymphomas, leukemias and multiple myeloma
Columbia University sickle cell transplant trial to study Iomab-ACT for targeted conditioning prior to BMT for the first time in a non-malignant hematology setting, which is a rapidly growing indication for BMT; patient enrollment expected to commence in the first half of 2025
Iomab-B Regulatory Status and Program Update

Actinium is seeking a U.S. strategic partner to advance clinical development of Iomab-B including the Phase 3 trial
Actinium met with the FDA in the fourth quarter and aligned on the patient population for the head-to-head Phase 3 trial to evaluate allogeneic BMT using Iomab-B plus a reduced intensity conditioning regimen of fludarabine and total body irradiation (Flu/TBI) versus allogeneic BMT using reduced intensity conditioning comprised of cyclophosphamide plus Flu/TBI
Head-to-head Phase 3 trial to enroll adult patients aged 18 and above with active AML with blasts counts greater than 5% and less than 20%, representing a broader patient population than that in the SIERRA trial
Dose optimization trial to be completed prior to initiating the head-to-head Phase 3 trial to determine the dose for Iomab-B based on radiation to the bone marrow rather than the maximum tolerable dose of 24 Gy of radiation to the liver as was done in the SIERRA trial based on several interactions with the FDA before starting the SIERRA trial
Mr. Seth added, "We are excited by our recent progress and committed to delivering on several milestones in the near-term and throughout 2025. Our current balance sheet provides strong runway into 2027, which enables us to deliver important clinical data and further realize our vision of being a leading fully integrated specialty radiopharmaceutical company."

Third Quarter 2024 Financial Results

Cash and cash equivalents of approximately $78.6 million as of September 30, 2024. Based on Actinium’s current operating plan, cash and cash equivalents are expected to fund operations into 2027.

Research and Development Expense, net of reimbursements

Research and development expenses of $9.8 million for the three months ended September 30, 2024 decreased $1.8 million from $11.6 million for the three months ended September 30, 2023. The decrease is primarily a result of a decline in Chemistry, manufacturing and controls, or CMC, expenses of $5.5 million and lower consulting expenses of $0.5 million, both due to lower activity in 2024 related to Iomab-B. These declines were partially offset by increased preclinical expenses of $3.9 million.

General and administrative expense

General and administrative expenses of $2.8 million for the three months ended September 30, 2024 increased by $0.1 million from $2.7 million for the three months ended September 30, 2023, primarily due to higher non-cash stock compensation expense of $0.5 million, partially offset by lower compensation expense of $0.3 million due to lower headcount.

In the third quarter of 2024, our overall headcount reduced by approximately twenty percent, with a majority of these former employees being from our clinical and CMC groups. As a result of these departures, we expect our personnel expenses to be reduced by approximately $3.7 million in 2025, which may be offset by additional hires or consultants. We do not expect these departures to have a material impact on our operations or ability to execute our operating plan and we are actively seeking a strategic partner for Iomab-B in the U.S. to advance the clinical development activity for Iomab-B including the planned Phase 3 trial.

Other income

Other income is comprised of net interest income in both reporting periods. The amount for the three months ended September 30, 2024 and 2023 of $1.0 million in each reporting period was virtually unchanged from the same time period in the prior year.

Net loss

Net loss of $11.6 million for the three months ended September 30, 2024 decreased by $1.7 million from $13.3 million for the three months ended September 30, 2023 due to lower research and development expenses partially offset by higher general and administrative expenses.