On September 24, 2024 Duke Street Bio Ltd, a precision medicine biotech developing next generation small molecule cancer therapies, reported that the European Medicines Agency (EMA) has granted approval to commence a clinical trial for its highly-selective PARP1 inhibitor, DSB2455 (Press release, Duke Street Bio, SEP 24, 2024, View Source [SID1234646835]). This potentially best-in-class, potent, highly selective and CNS-penetrant agent targets cancers that harbour homologous recombination deficiencies (HRD) including BRCA mutations. The safety profile of first generation non-selective PARP1/2 inhibitors has restricted their application, particularly in combination with chemotherapy and radiotherapy. By selectively inhibiting PARP1, we believe that DSB2455 has the potential to achieve a significantly enhanced therapeutic index, representing a significant advancement in precision medicine cancer treatment. Preliminary data indicate a strong safety profile and compelling efficacy in preclinical studies, paving the way to open our trial in the clinic.

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Alan Wise, CEO of Duke Street Bio, commented, "The approval of the DSB2455 First-in-Human clinical trial by the EMA is a testament to the therapeutic potential of our innovative approach in the DDR space. Duke Street Bio’s mission is to improve patient outcomes and bring new hope to individuals battling cancer. We believe that DSB2455 has the potential for improved efficacy and tolerability versus first-generation PARP inhibitors in patient populations where there is still significant unmet medical need."

On September 24, 2024 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, reported presentations on POSLUMA (flotufolastat F 18) injection (formerly known as 18F-rhPSMA-7.3) at the upcoming American Society for Therapeutic Radiology and Oncology (ASTRO) 2024 Annual Meeting, to be held in Washington, DC, from September 29 – October 2, 2024 (Press release, Blue Earth Diagnostics, SEP 24, 2024, View Source [SID1234646851]). 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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"PET imaging with POSLUMA can reveal clinical information crucial to decision-making for men with prostate cancer, and we are excited to share new results with the radiation oncology community at ASTRO," said Marco Campione, Chief Executive Officer of Blue Earth Diagnostics. "Presentations by our collaborators include additional results from the completed Phase 3 SPOTLIGHT study, which evaluated POSLUMA in recurrent prostate cancer, and results from an investigator-initiated study of POSLUMA PET and MRI in recurrent disease. Blue Earth Diagnostics will also host an Industry-Expert Theater event, ‘Let’s Talk About POSLUMA (flotufolastat F 18)’."

Details of selected oral and poster presentations by Blue Earth Diagnostics and its collaborators are listed below.

HIGHLIGHTED SCIENTIFIC PRESENTATIONS

Sunday, September 29, 2024

Oral presentation

Title:

A Prospective Pilot Study Investigating 18F rhPSMA-7.3 PET/MRI to Detect Disease and Guide Radiotherapy Planning in Patients with Biochemically Recurrent Prostate Cancer Post-Prostatectomy

Presenter:

Devaki Shilpa Surasi, MD, MD Anderson Cancer Center, Houston, Texas

Session Type

Oral

Session Title:

QP 01 – GU 4: GU Quick Pitch

Session Time:

8:00 – 9:00 AM ET

Presentation Time:

8:50 – 9:00 AM ET

Location:

Room 207 B

Presentation No.:

1005

Tuesday, October 1, 2024

Poster presentation

Title:

18F-Flotufolastat Detection Rates in the Pelvis Region for Patients with Prostate Cancer Recurrence after Radical Prostatectomy and PSA Levels <1 ng/mL: Data from the Phase 3 SPOTLIGHT Study

Presenter:

Bridget F. Koontz,* MD, FASTRO, AdventHealth Cancer Institute, Orlando, FL, for the SPOTLIGHT Study Group (*Duke University Medical Center, Durham, NC – affiliation at time of study)

Session Title:

PQA 08 – PQA 08 Genitourinary Cancer, Patient Safety, and Nursing/Supportive Care Poster Q&A

Presentation Time:

2:30 – 3:45 PM ET

Location:

Hall C

Presentation No.:

3210

Blue Earth Diagnostics invites participants at the 2024 ASTRO Annual Meeting to attend the presentations above and visit the company at Exhibit Booth 1949. Blue Earth Diagnostics is hosting an Industry-Expert Theater event, "Let’s Talk About POSLUMA (flotufolastat F 18)," which will feature invited speakers Sean Collins, MD, PhD, Professor, Georgetown University Hospital and Elizabeth Hawk, MS, MD, PhD, DABNM, DABR, University of California San Diego, and be moderated by Todd Cohen, MD, Blue Earth Diagnostics, Inc. The event will be held on Sunday, September 29, 2024, from 12:00 PM to 1:00 PM ET, in Theater 1, Exhibit Hall, of the Walter E. Washington Convention Center. Blue Earth Diagnostics also has a Medical Affairs information booth at ASTRO, where attendees can learn about the Company’s clinical research. For full session details and scientific presentation listings, please see the ASTRO online program here.

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 September 24, 2024 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has obtained manufacturing and marketing approval for fibroblast growth factor receptor (FGFR) selective tyrosine kinase inhibitor "TASFYGO Tablets 35mg" (tasurgratinib succinate) in Japan for the treatment of patients with unresectable biliary tract cancer with FGFR2 gene fusions or rearrangements that progressed after cancer chemotherapy (Press release, Eisai, SEP 24, 2024, View Source [SID1234646836]). In Japan, it has received orphan drug designation from the Ministry of Health, Labour and Welfare (MHLW), and the marketing authorization application was submitted in December 2023.

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This approval is based on data such as the results of a multicenter, open-label, single-arm clinical phase II trial (Study 201) conducted by Eisai in Japan and China. Study 201 enrolled 63 patients with unresectable advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions or rearrangements previously treated with gemcitabine-based combination chemotherapy. The primary endpoint of this study was objective response rate (ORR), and secondary endpoints included safety.1 This study achieved its primary endpoint and exceeded a prespecified tumor response threshold (15%) with statistical significance: ORR of patients treated with TASFYGO was 30.2% (90% confidence interval (CI): 20.7-41.0) as assessed by independent imaging review. Treatment-emergent adverse events (incidence of 25% or more) observed in this study were hyperphosphataemia (81.0%), palmar-plantar erythrodysaesthesia syndrome (44.4%), diarrhoea (36.5%), aspartate aminotransferase increase (31.7%), alanine aminotransferase increase (28.6%) and stomatitis (25.4%).

The estimated number of patients in Japan with biliary tract cancer is approximately 22,0002,3 with approximately 25% of the five-year relative survival rate,2 making it an intractable cancer with the second worst prognosis following pancreatic cancer. Since drug therapy options are limited in comparison with other cancers, it is a disease with significant unmet medical needs. FGFR2 gene fusions or rearrangements are observed in approximately 14% of intrahepatic cholangiocarcinoma, which accounts for 15-30% of biliary tract cancers.4 FGFR genetic aberrations such as the gene fusions are known to be deeply involved in the proliferation, survival and migration of cancer cells as well as tumor angiogenesis and drug resistance. As these genetic aberrations in FGFRs have been observed in various other types of cancers as well as biliary tract cancer, there is growing interest in FGFRs as a promising target for cancer therapy. TASFYGO is thought to show tumor growth inhibition by selectively inhibiting FGFR1, 2 and 3, and blocking those signals.5,6 In non-clinical studies, the antitumor activity of TASFYGO was confirmed in cells expressing the FGFR2-fusion genes, which were identified by the National Cancer Center Japan (Headquarters: Tokyo) through large-scale genomic analysis of Japanese biliary tract cancer. The companion diagnostic test to detect FGFR2 gene fusions or rearrangements for the use of TASFYGO in biliary tract cancer, "AmoyDx FGFR2 Break-apart FISH Probe Kit" by Nihon Stery, Inc. (Headquarters: Tokyo) was approved in August 2024.7

Eisai aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals, by delivering TASFYGO as a new treatment option for biliary tract cancer with FGFR2 gene fusions or rearrangements.

On September 24, 2024 Silexion Therapeutics Corp. (NASDAQ: SLXN) ("Silexion" or the "Company"), a clinical-stage biotech developing RNA interference (RNAi) therapies for KRAS-driven cancers, reported significant new findings from its Phase 2 trial of LODER in patients with non-resectable locally advanced pancreatic cancer (LAPC) which bear the KRAS G12D or G12V mutation (approximately 70% of pancreatic cancer patients) (Press release, Silexion Therapeutics, SEP 24, 2024, View Source [SID1234646852]). Overall the updated analysis reveals a 56% objective response rate (ORR) in patients treated with LODER, with the ORR increasing to 67% in patients whose previously non-resectable tumors became resectable. This marks a significant step forward in potentially improving surgical outcomes for LAPC patients.

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Silexion had previously reported that patients treated with LODER in combination with standard-of-care (SoC) chemotherapy experienced a 9.3-month improvement in overall survival (OS) compared to chemotherapy alone. The new data now underscores LODERs additional potential to increase the resectability of tumors, opening up more surgical options for patients with otherwise inoperable pancreatic cancer.

Silexion is also progressing with the development of its next generation product, SIL-204, which builds upon the efficacy of the LODER. SIL-204 is designed to target a broader range of KRAS mutations, covering pan- G12x and G13D, as well as the previously reported findings of properties which should make it more effective clinically such as improved stability and enhanced ability to get to the site of action for silencing the KRAS oncogene. These improved properties demonstrated in preclinical models position SIL-204 as a promising option for the treatment of difficult-to-treat cancers such as locally advanced pancreatic cancer. Silexion continues to proceed with the development of this optimized candidate.

"We are very encouraged by these new findings, which demonstrate LODER’s ability to significantly improve tumor resectability in patients with non-resectable pancreatic cancer, and the improved profile of SIL-204" said Ilan Hadar, Chairman and CEO of Silexion. "As we advance our broader pipeline to address KRAS-driven cancers, this data further validates our oncogene silencing approach."

About the Phase 2 Trial of LODER

The open-label Phase 2 trial enrolled 48 patients in the mITT population with non-resectable locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC) across the U.S. and Israel. The trial was conducted in two parts:

Cohort 1 (n=29): Patients were randomized 1:1 to receive either LODER with SoC chemotherapy or SoC chemotherapy alone. The primary endpoint was overall survival (OS), with 16 patients confirmed to harbor the KRAS G12D/V mutation.
Cohort 2 (n=19): This cohort enrolled patients with non-resectable tumors, LAPC or BRPC, with the key endpoints focused on ORR and safety. Seven patients in this cohort were confirmed to have KRAS G12D/V mutations.
Objective Response Rate for 23 patients confirmed with KRAS G12D/V (Cohorts 1+2)

On September 24, 2024 Araris Biotech AG ("Araris"), a Swiss oncology biotech company developing next-generation antibody drug conjugates (ADCs), reported it has entered into an Agreement with Innate Pharma ("Innate") (Press release, Araris Biotech, SEP 24, 2024, View Source [SID1234651284]). Under the agreement, Innate will assign its portfolio of patents related to its ADC transglutaminase conjugation technology to Araris.

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"We are excited to acquire Innate’s portfolio of transglutaminase related patents, as this transaction further positions Araris as a leader in the development of ADCs using transglutaminase conjugation technology," said Dragan Grabulovski, Ph.D., CEO and co-founder of Araris. "We look forward to continuing to develop next-generation sitespecific ADCs and believe this acquisition not only expands our intellectual property portfolio, but also strengthens our competitive edge."

The newly acquired patents encompass a broad range of intellectual property that cover use of bacterial transglutaminase in conjugating various linker-payloads to antibodies.