On November 28, 2023 Novocure (NASDAQ: NVCR) reported a series of actions to strengthen and optimize business operations to support near-term growth drivers and long-term value creation (Press release, NovoCure, NOV 28, 2023, View Source [SID1234638027]). The plan includes an expected reduction in residual operating expenses of approximately $60 million, enabling the Company to fund future growth priorities without an associated increase in expected forward operating cash burn. Novocure continues to focus resources on its global commercial infrastructure and launch preparation ahead of its anticipated indication in metastatic non-small cell lung cancer and on high-potential research and development programs.

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"Decisions like these are deeply personal and challenging, because of the impact on our employees and their families," said Novocure’s Chief Executive Officer, Asaf Danziger. "To those departing Novocure, I want to express my sincere gratitude for your hard work. Your contributions have influenced the lives of many cancer patients and your legacy will forever be intertwined with Novocure."

"The initiatives announced today prioritize growth and maintain financial health and flexibility as we position our company for future profitability," said Novocure’s Chief Financial Officer, Ashley Cordova. "These decisions were difficult, yet essential. With a more focused organization, we are confident that these initiatives will bolster Novocure’s position, enabling us to unlock our long-term potential and fulfill our mission."

Key elements of the plan include:

Portfolio prioritization
Novocure has taken a holistic review of operating expenses and has focused resources on the areas of greatest anticipated value creation, intended to balance near-term and long-term growth opportunities.

Novocure continues to invest in launch readiness, including field-based commercial and field-based medical team hiring, for the anticipated approval of Tumor Treating Fields therapy for the treatment of metastatic non-small cell lung cancer following progression on or after platinum-based therapies.
Novocure will deliver two phase 3 randomized clinical trial readouts in brain metastases from non-small cell lung cancer (METIS) and locally advanced pancreatic cancer (PANOVA-3) anticipated in 2024.
Novocure has prioritized development investments on a sharply focused list of randomized clinical trials – TRIDENT, KEYNOTE D58 and LUNAR-2 – which have the potential to drive the greatest value in solid tumors where Tumor Treating Fields therapy has established efficacy.
Strategic restructuring
In conjunction with its portfolio prioritization, Novocure is streamlining its operational expenses.

Novocure’s plan to reduce residual operating expenses by approximately $60 million includes a planned reduction in headcount of approximately 200 colleagues, 13% of its current workforce. Field-based commercial and field-based medical employees are minimally affected. Novocure expects to incur one-time costs related to the workforce reduction of approximately $7 million in the fourth quarter of 2023.
The anticipated cost savings are expected to offset growth investments and accelerate Novocure’s path to profitability.

On November 28, 2023 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, reported the publication of results of a post-hoc analysis assessing the impact of urinary activity on the interpretation of POSLUMA (flotufolastat F 18) injection (formerly known as 18F-rhPSMA-7.3) PET/CT in prostate cancer (Press release, Blue Earth Diagnostics, NOV 28, 2023, View Source [SID1234638026]). The analysis was based on data from Blue Earth Diagnostics’ prospective Phase 3 LIGHTHOUSE1 and SPOTLIGHT2 studies that evaluated the diagnostic performance and safety of POSLUMA in newly diagnosed and recurrent prostate cancer. Majority read results from 3 blinded readers assessing 712 evaluable POSLUMA scans showed that urinary activity in the bladder and ureters did not influence disease assessment for the vast majority (96%, 682/712) of patients. Halo artifacts, which can inhibit image assessment, were very rare, and were absent in 99.7% (710/712) of patients by majority read. Ureteric activity, which can also limit assessment of lymph nodes distant to the bladder, was also absent in a majority of patients (56%, 401/712). FDA-approved POSLUMA is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.

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The results, "Quantitative and qualitative assessment of urinary activity of 18F-flotufolastat-PET/CT in patients with prostate cancer: A post-hoc analysis of the LIGHTHOUSE and SPOTLIGHT studies," were published online in Molecular Imaging and Biology (2023), View Source and will also appear in an upcoming print issue. Authors are Phillip H. Kuo, Departments of Medical Imaging, Medicine, and Biomedical Engineering, University of Arizona, Tucson, AZ, USA, and Southern Arizona Veterans Administration Healthcare System; Rick Hermsen, Department of Nuclear Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands; Ross Penny and Ernst J. Postema, Blue Earth Diagnostics Ltd, Oxford, UK.

"The ability to gather actionable information from PSMA PET scans is important for physicians to make informed decisions about patient management for men with prostate cancer," said Phillip Kuo, MD, Ph.D., Departments of Medical Imaging, Medicine, and Biomedical Engineering. "Activity in the urinary bladder and ureters is a common feature of PSMA-PET radiopharmaceuticals. It can potentially obscure tumors and lymph nodes in the prostate region – the most common site of recurrence – as well as pelvic and retroperitoneal lymph nodes distant to the prostate region, interfering with accurate image interpretation. In early clinical experience, POSLUMA demonstrated a high binding affinity for PSMA, with low urinary activity, providing enhanced image evaluation in the prostate and regions near the ureters for patients with prostate cancer. Results from this large dataset, based on images from two Phase 3 prospective trials, build on that experience and demonstrate that POSLUMA urinary activity is low and rarely impacts disease assessment."

"This analysis of FDA-approved POSLUMA marks the first and only published assessment of urinary activity for a PSMA-targeted PET/CT prostate cancer agent, and we are pleased that the results have been published in Molecular Imaging and Biology where they can be widely shared with the imaging community," said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Diagnostics. "POSLUMA represents a new class of PSMA-targeted PET radiopharmaceuticals based on novel radiohybrid technology. It is engineered to advance clinical decision-making by providing clinically precise information for treatment planning in men with prostate cancer, which can lead to changes in patient management. We believe that POSLUMA’s diagnostic performance, high-affinity PSMA binding and low urinary activity characteristics make it a valuable diagnostic tool that is radiolabeled with 18F for high image quality and readily available patient access."

Published results were based on 712 evaluable POSLUMA scans (348 newly diagnosed patients and 364 patients with recurrent prostate cancer from LIGHTHOUSE and SPOTLIGHT, respectively). Of the 718 eligible scans, 6 were excluded on the basis of cystectomy, renal failure or presence of a urinary catheter. Findings included quantitative analyses of activity in the urinary bladder, based on maximum and mean standardized uptake values (SUVmax and SUVmean, respectively). Qualitative analyses conducted by 3 blinded, independent PET readers examined the impact of any urinary activity on the ability to assess the prostate/prostate bed and pelvic lymph nodes using a 3-point scale.

The median bladder SUVmax and SUVmean for POSLUMA were 17.1 and 12.5, respectively. For the qualitative metrics, by majority read, it was possible to distinguish urinary activity from disease uptake in 96% (682/712) of patients. Halo artifacts impacting assessment around the ureters and bladder were only observed in 0.3% (2/712) of patients.

There were several limitations to the study. It was not designed as a head-to-head comparison with other PSMA-PET radiopharmaceuticals and any comparisons with other radiopharmaceuticals reported in the literature should be made with caution. Another limitation was that reader agreement was not formally tested, however the authors noted that patient-level inter-reader agreement has been previously reported as ≥ 95%3 and ≥ 75%4 for LIGHTHOUSE and SPOTLIGHT respectively. Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer.

Blue Earth Diagnostics’ LIGHTHOUSE Phase 3 clinical trial (NC04186819) was a prospective, Phase 3, multi-center, single-arm, imaging study conducted in the United States and Europe to evaluate the safety and diagnostic performance of POSLUMA PET in men with newly diagnosed prostate cancer. Results from the SPOTLIGHT study were published in European Urology DOI.org/10.1016/j.eururo.2023.06.0181. The SPOTLIGHT trial (NCT04186845) was a Phase 3, multi-center, single-arm imaging study conducted in the United States and Europe to evaluate the safety and diagnostic performance of POSLUMA PET imaging in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy. Results from the SPOTLIGHT study were published in the Journal of Urology: DOI: 10.1097/JU.0000000000003493.2

About POSLUMA (flotufolastat F 18)

POSLUMA (flotufolastat F 18) injection (formerly referred to as 18F-rhPSMA-7.3) is an optimized, targeted radiohybrid diagnostic imaging agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. Precision PET imaging with POSLUMA can help identify the location and extent of prostate cancer, providing clinically valuable information to guide patient management. POSLUMA represents a new class of high-affinity PSMA-targeted PET radiopharmaceuticals based on novel radiohybrid technology and is labeled with the radioisotope 18F to provide readily available patient access and leverage the high image quality of 18F-labeled PSMA PET imaging to facilitate effective detection of disease. POSLUMA was approved by the U.S. Food and Drug Administration in May 2023.

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) compounds consist of a radiohybrid ("rh") Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells, and they may be radiolabeled with imaging isotopes for PET imaging, or with therapeutic isotopes for therapeutic use – providing the potential for creating a true theranostic technology. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Diagnostics received U.S. Food and Drug Administration approval for its radiohybrid PET diagnostic imaging product for use in prostate cancer in 2023. rhPSMA compounds for potential therapeutic use are investigational and have not received regulatory approval.

Indication and Important Safety Information About POSLUMA

INDICATION

POSLUMA (flotufolastat F 18) injection is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer

with suspected metastasis who are candidates for initial definitive therapy
with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level
IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping. The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended.
Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence: The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region. Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F 18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline.
POSLUMA use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers.
The adverse reactions reported in ≥0.4% of patients in clinical studies were diarrhea, blood pressure increase and injection site pain.
Drug Interactions: androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F 18 in prostate cancer. The effect of these therapies on performance of POSLUMA PET has not been established.
To report suspected adverse reactions to POSLUMA, call 1-844-POSLUMA (1-844-767-5862) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full POSLUMA prescribing information is available at www.posluma.com/prescribing-information.pdf.

On November 28, 2023 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported the clearance of its Investigational New Drug application (IND) by the U.S. Food and Drug Administration (FDA) for CT-0525, an ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2) (Press release, Carisma Therapeutics, NOV 28, 2023, View Source [SID1234638025]). Having received a Study May Proceed notification from the FDA, Carisma expects to initiate a Phase 1 study in the coming months and to treat the first patient in the first half of 2024.

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"Clearance of the IND for CT-0525 is a significant milestone in Carisma’s mission to develop innovative myeloid cell therapies for metastatic solid tumors," said Steven Kelly, President and Chief Executive Officer of Carisma. "Through this Phase 1 study, we aim to advance our understanding of safety, tolerability, manufacturing feasibility and mechanism of action of CT-0525."

Monocytes are the precursor cells to macrophages, and there are numerous potential benefits to a CAR-Monocyte approach to help overcome certain challenges of treating solid tumors. The CAR-Monocyte manufacturing platform enables the ability to manufacture up to 10 billion cells from a single apheresis and utilizes a rapid, single-day manufacturing process. This manufacturing process holds the potential to significantly reduce the future cost of goods and manufacturing turnaround time associated with this autologous cell therapy. Pre-clinical data presented at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting in November 2022 demonstrate that CT-0525 therapy reduced tumor growth in multiple pre-clinical solid tumor models.

"CT-0525 is the first CAR-Monocyte to be evaluated in the solid tumor setting. With a CAR-Monocyte’s in vivo persistence, ability to differentiate into pro-inflammatory CAR macrophages, and multi-modal anti-tumor mechanism of action, along with its high cell yield, CT-0525 has the potential to improve the treatment paradigm for patients with HER2 overexpressing metastatic solid tumors," said Michael Klichinsky, PharmD, PhD, Co-Founder and Chief Scientific Officer at Carisma. "We look forward to the clinical development of CT-0525."

The Phase 1 study for CT-0525 is designed to assess the safety, tolerability, and the manufacturing feasibility of CT-0525. This study will enroll participants with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2 whose disease has progressed on standard approved therapies. The study will consist of two cohorts: Cohort 1 will receive IV administration of up to 3 billion CAR-positive cells, while Cohort 2 will receive IV administration of CT-0525 of up to 10 billion CAR-positive cells.

About CT-0525

CT-0525 is an ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). The CAR-Monocyte approach has the potential to address the challenges of treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity.

On November 28, 2023 Fosun Pharma USA Inc. ("Fosun Pharma USA") reported its abstract on ASTRIDE (NCT05468489), a phase 3 randomized, open-label study of serplulimab vs atezolizumab both in combination with chemotherapy (Carboplatin-Etoposide) in patients with extensive-stage small-cell lung cancer (ES-SCLC), has been accepted for presentation at the International Association for the Study of Lung Cancer’s (IASLC) 2023 North America Conference on Lung Cancer (NACLC), being held in Chicago, Illinois, Dec. 1 – 3, 2023 (Press release, Fosun Pharma, NOV 28, 2023, View Source [SID1234638024]).

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All abstracts accepted for presentation have been published on the NACLC website.

"Our PIs are excited to present their poster on the design of the ASTRIDE Trial in Progress (TiP), which is an important milestone for the lead investigators and authors," said Stan Lechpammer, Vice President, Medical Affairs, Innovative Medicines, Fosun Pharma USA. "This presentation provides greater insight into the ASTRIDE trial that investigates serplulimab as a potentially new therapeutic option for extensive-stage (ES) small-cell lung cancer patients (SCLC). SCLC is an aggressive malignancy, with the majority of patients presenting with extensive-stage disease at initial diagnosis. There is a high unmet need for this patient population. Beyond the potential of our TiP study design, we have committed to recruiting patients from many medically underserved communities, to address health disparities and improve health equity for ES-SCLC patients in the U.S."

Abstract accepted for presentation’s details and key points about the study design:

Medicine

Abstract Title

Presentation Details

Serplulimab

Serplulimab vs atezolizumab added to chemotherapy in patients with treatment-naive ES-SCLC in the United States – ASTRIDE Trial in Progress

Abstract #: PP01.35

Poster available:

December 2 at 5:40 PM CST/6:40 PM EST

Key Highlights about Study Design

Trial will include approximately 200 adult patients with treatment-naïve ES-SCLC
Study participants are being recruited from over 90 sites across the United States
About Serplulimab
Serplulimab is a novel anti–PD-1 (programmed cell death-1) monoclonal antibody (mAb), with a unique mode of recognition of the PD-1 receptor compared with currently available anti–PD-1 mAbs (Issafras et al. Plos One. 2021).

About the ASTRIDE Phase 3 Trial
ASTRIDE is a randomized, open-label study of serplulimab plus chemotherapy (carboplatin-etoposide) compared with atezolizumab plus chemotherapy in previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC) in the United States. The primary objective for ASTRIDE is to confirm the applicability of the results of ASTRUM-005 (a global, randomized, phase 3 trial) to patients in the United States, with the current standard-of-care as the control arm, based on comments from the U.S. Food and Drug Administration (Serplulimab study protocol 2.0 final. Shanghai Henlius Biotech, Inc.; July 18, 2022).

About Small-cell Lung Cancer
Approximately 30,000-35,000 people are diagnosed with small-cell lung cancer (SCLC) each year in the United States. It is the most aggressive form of lung cancer with approximately 70% of patients presenting with extensive-stage disease (ES-SCLC), with a median overall survival of approximately 12.5 months with standard-of-care treatment.

On November 28, 2023 Orlance, Inc., a Seattle biotech developing next-generation DNA and RNA vaccines and therapeutics, reported that the company has been awarded a National Institutes of Health (NIH) Phase I Small Business Innovation Research (SBIR) grant to use its needle-free MACH-1 platform for creating a vaccine regimen that induces strong tumor specific immune responses and protection from melanoma (Press release, Orlance, NOV 28, 2023, View Source [SID1234638023]).

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The MACH-1 platform is a high-performance microparticle ‘gene gun’ technology that efficiently and uniquely delivers DNA or RNA vaccine-coated microparticles directly into cells in the epidermis, the uppermost layer of the skin. The epidermis is rich in immune-stimulating cells. MACH-1 delivery harnesses this environment and the natural machinery of its immune cells to deliver DNA and RNA vaccines or therapeutics; these encode proteins that trigger potent immunity including generation of antibodies to block an infection and activation of T cells that can either eliminate infected cells or kill tumor cells. Unlike current licensed mRNA vaccines, MACH-1-delivered vaccines are stable at room temperature, are painless and needle-free, and can trigger protective levels of immunity or efficacy with much lower doses.

While personalized cancer antigens have been identified from patients’ tumors, effective methods to deliver these antigens and stimulate specific immune responses are still lacking. MACH-1 stable, painless, targeted, and lose-dose DNA and RNA vaccines show promise for addressing these shortcomings in melanoma treatment, based upon MACH-1 data in other relevant models. Researchers aim to enhance MACH-1’s effectiveness by exploring combinations of genetic enhancers (adjuvants) and DNA or RNA formulations in comparison to other delivery methods in mice.

"Orlance is thrilled that our MACH-1 technology has broad applicability in both infectious disease and oncology. Our preclinical accomplishments in vaccines for viral infections have caught the eye and generated rapid enthusiasm among multiple cancer collaborators, including the National Cancer Institute (NCI) via this SBIR award," stated Kristyn Aalto, Orlance CEO. "Overall, we’re seeing the field recognize the attributes of targeting the skin itself, rather than deeper tissues, as the ideal immunologic tissue and dosing site for DNA and RNA vaccines. We are confident that MACH-1’s standalone ability to delivery specifically into the epidermis will continue to yield strong results across multiple disease targets. Melanoma is an exciting first crossover into cancer for us due both to unmet need and its perfect skin-targeting opportunity." This new SBIR grant, led by Orlance’s Dr. Hannah Frizzell, PhD, will enable Orlance to complete proof of concept, formulation, and adjuvant incorporation necessary to advance lead candidates into later-stage preclinical development activities and IND readiness. If successful, program output will be a vaccine candidate shown to induce significantly slower tumor outgrowth in preclinical models that also incorporates all MACH-1 stability, dose-sparing, tissue targeting, and needle-free advantages.

This award brings Orlance’s SBIR funding total to $12.9M to advance next-generation DNA and RNA vaccines and therapeutics. Orlance was founded as a University of Washington spin out company in 2016 to develop the MACH-1 platform based on technology invented by Deborah Fuller, PhD, Professor of Microbiology at the University of Washington School of Medicine. Orlance plans to initiate Phase 1 clinical trials for the company’s lead infectious disease asset in 2025.