On June 20, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that it has commenced its 64Cu/67Cu SAR-Bombesin Phase I/II trial in metastatic castrate resistant prostate cancer (mCRPC) with the opening of the first site at BAMF Health, Inc in Michigan (Press release, Clarity Pharmaceuticals, JUN 20, 2023, https://www.claritypharmaceuticals.com/news/combat_commences-us/ [SID1234632791]).

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COMBAT (Copper-67 SAR Bombesin in metastatic castrate resistant prostate cancer, NCT05633160)1 is a dose escalation and cohort expansion trial for up to 38 participants. The aim for the trial is to determine the safety and efficacy of 67Cu-SAR-Bombesin in participants with gastrin-releasing peptide receptor (GRPr) expressing mCRPC in patients who are ineligible for therapy with 177Lu PSMA-617.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are excited to initiate our first theranostic clinical trial of the SAR-Bombesin product. COMBAT is our third theranostic trial in the US and a second theranostic trial in prostate cancer, an indication that continues to have a high unmet need. In the VISION trial for the recently approved 177Lu PSMA-617, median overall survival increased from approximately 11 months on standard of care therapy to approximately 15 months with 177Lu PSMA-617 plus standard of care. Despite this, around a quarter of men with mCRPC do not have PSMA-expressing lesions, making it impossible to offer PSMA-targeted products as therapy for this group of patients. As a very large proportion of prostate cancers express GRPr, SAR-Bombesin is an exciting new prospect for better treating these patients that have few therapeutic options at present in the face of a devastating diagnosis.

"We look forward to progressing the COMBAT trial and building on the compelling data from our preclinical studies as well as from three diagnostic trials with this product. SAR-Bombesin has already resulted in improvements to the management of prostate cancer for patients with PSMA-negative or low PSMA expressing tumours and we hope to confirm its safety and efficacy in the theranostic trial."

About SAR-Bombesin
SAR-Bombesin is a highly targeted pan-cancer radiopharmaceutical with broad cancer application. It targets the gastrin-releasing peptide receptor (GRPr) present on cells of a range of cancers, including but not limited to prostate, breast and ovarian cancers. GRPr is found in up to 100% of prostate cancers, including prostate cancers that don’t express PSMA (PSMA-negative)2-6. The product utilises Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-Bombesin is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide7. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of prostate cancer in the US and around 34,700 deaths from the disease8.

Approximately 25% of mCRPC patients have low or no uptake of a PSMA-targeting tracer.9 These patients are therefore unlikely to respond to therapeutic PSMA-targeted products and currently have few treatment options available to them. Given the prostate cancer indication is one of the largest in oncology, there is a significant unmet medical need in this segment. The SAR-Bombesin product could offer valuable imaging and therapeutic options for not only PSMA-negative patients, but also the large number of patients that have the target receptor on their cancers.

On June 19, 2023, Kelun-Biotech reported that the innovative TROP2-ADC (SKB264, also known as MK-2870), which is being developed in collaboration with MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA), in combination with pembrolizumab (KEYTRUDA, MSD’s anti-PD-1 therapy) for Phase II clinical studies in select patients with a variety of advanced solid tumors, has been approved for clinical trials in the European Union (Press release, Kelun, JUN 19, 2023, View Source(mk-2870)-is-approved-for-clinical-trials-in-the-european-union [SID1234633517]). This is an international multicenter clinical study which is currently approved in multiple countries and territories, including China, the United States, Canada, Australia, and now the European Union, fully demonstrating the strength of Kelun-Biotech in conducting clinical studies on a global scale. MSD and Kelun-Biotech are working closely to continually advance the international development of SKB264.

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At present, immune checkpoint inhibitors, mainly represented by anti-PD-1/PD-L1 therapies, have played an important role in treating cancer across a variety of tumors. In order to improve outcomes for patients, combination therapies are being explored, including combination with chemotherapy, targeted therapy, radiotherapy, other types of immunotherapy, and more.

ADCs specifically target tumor cells to deliver cytotoxic molecules that induce immunogenic cell death (ICD) and trigger innate and adaptive immune responses, allowing large numbers of T cells to infiltrate tumor cells and thereby improving immunotherapeutic efficacy. Clinical trial data in multiple cancer types have shown that anti-PD-1 therapies in combination with ADCs may be able to improve efficacy compared to either agent alone. TROP2 is highly expressed in a variety of epithelial-derived tumors and can promote tumor cell proliferation, invasion, and metastasis, and is a promising target for broad-spectrum anti-tumor therapy. TROP2-ADCs specifically target TROP2-expressing tumor cells to deliver cytotoxic effects, and have shown encouraging anti-tumor activity as monotherapy in several clinical trials, and has the potential to improve anti-tumor efficacy in combination with immune checkpoint inhibitors such as anti-PD-1/PD-L1 therapies.

About SKB264 (MK-2870)

SKB264 is an innovative ADC targeting TROP2 which was developed by OptiDC, a well-known international ADC R&D platform of Kelun-Biotech, using a proprietary payload-linker strategy (Kthiol design strategy) that achieves an optimized balance of ADC safety and efficacy by combining novel irreversible antibody conjugation chemistry, pH-sensitive payload release mechanisms, and site-specific moderately potent toxin molecules with DAR of 7.4 (novel topoisomerase I inhibitors) [2].

SKB264 (MK-2870) has received 2 Breakthrough Therapy Designations (BTDs) from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic triple-negative breast cancer and locally advanced or metastatic EGFR-mutated non-small cell lung cancer who have failed EGFR-TKI therapy.

SKB264 (also known as MK-2870) is currently conducting Phase II and Phase III clinical trials of monotherapy/combination in multiple solid tumors. In China, the Phase III registrational clinical study of SKB264 monotherapy for patients with advanced or metastatic triple-negative breast cancer (TNBC) who have failed at least second-line therapy is progressing smoothly, and it is expected to become the first domestic TROP2-ADC approved for the Chinese market. Phase III clinical studies of SKB264 monotherapy in patients with TKI-resistant and EGFR-mutated non-small cell lung cancer (NSCLC) are also rapidly advancing. Several Phase II clinical studies of SKB264 in combination with pembrolizumab (KEYTRUDA, MSD’s anti-PD-1 therapy) or KL-A167 (Kelun’s anti-PD-L1 monoclonal antibody) are ongoing. Kelun-Biotech has licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to research, develop, produce and commercialize SKB264 in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

On June 19, 2023, Kelun-Biotech reported that the innovative TROP2-ADC (SKB264, also known as MK-2870), which is being developed in collaboration with MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA), in combination with pembrolizumab (KEYTRUDA, MSD’s anti-PD-1 therapy) for Phase II clinical studies in select patients with a variety of advanced solid tumors, has been approved for clinical trials in the European Union (Press release, Kelun, JUN 19, 2023, View Source(mk-2870)-is-approved-for-clinical-trials-in-the-european-union [SID1234633517]). This is an international multicenter clinical study which is currently approved in multiple countries and territories, including China, the United States, Canada, Australia, and now the European Union, fully demonstrating the strength of Kelun-Biotech in conducting clinical studies on a global scale. MSD and Kelun-Biotech are working closely to continually advance the international development of SKB264.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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At present, immune checkpoint inhibitors, mainly represented by anti-PD-1/PD-L1 therapies, have played an important role in treating cancer across a variety of tumors. In order to improve outcomes for patients, combination therapies are being explored, including combination with chemotherapy, targeted therapy, radiotherapy, other types of immunotherapy, and more.

ADCs specifically target tumor cells to deliver cytotoxic molecules that induce immunogenic cell death (ICD) and trigger innate and adaptive immune responses, allowing large numbers of T cells to infiltrate tumor cells and thereby improving immunotherapeutic efficacy. Clinical trial data in multiple cancer types have shown that anti-PD-1 therapies in combination with ADCs may be able to improve efficacy compared to either agent alone. TROP2 is highly expressed in a variety of epithelial-derived tumors and can promote tumor cell proliferation, invasion, and metastasis, and is a promising target for broad-spectrum anti-tumor therapy. TROP2-ADCs specifically target TROP2-expressing tumor cells to deliver cytotoxic effects, and have shown encouraging anti-tumor activity as monotherapy in several clinical trials, and has the potential to improve anti-tumor efficacy in combination with immune checkpoint inhibitors such as anti-PD-1/PD-L1 therapies.

About SKB264 (MK-2870)

SKB264 is an innovative ADC targeting TROP2 which was developed by OptiDC, a well-known international ADC R&D platform of Kelun-Biotech, using a proprietary payload-linker strategy (Kthiol design strategy) that achieves an optimized balance of ADC safety and efficacy by combining novel irreversible antibody conjugation chemistry, pH-sensitive payload release mechanisms, and site-specific moderately potent toxin molecules with DAR of 7.4 (novel topoisomerase I inhibitors) [2].

SKB264 (MK-2870) has received 2 Breakthrough Therapy Designations (BTDs) from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic triple-negative breast cancer and locally advanced or metastatic EGFR-mutated non-small cell lung cancer who have failed EGFR-TKI therapy.

SKB264 (also known as MK-2870) is currently conducting Phase II and Phase III clinical trials of monotherapy/combination in multiple solid tumors. In China, the Phase III registrational clinical study of SKB264 monotherapy for patients with advanced or metastatic triple-negative breast cancer (TNBC) who have failed at least second-line therapy is progressing smoothly, and it is expected to become the first domestic TROP2-ADC approved for the Chinese market. Phase III clinical studies of SKB264 monotherapy in patients with TKI-resistant and EGFR-mutated non-small cell lung cancer (NSCLC) are also rapidly advancing. Several Phase II clinical studies of SKB264 in combination with pembrolizumab (KEYTRUDA, MSD’s anti-PD-1 therapy) or KL-A167 (Kelun’s anti-PD-L1 monoclonal antibody) are ongoing. Kelun-Biotech has licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to research, develop, produce and commercialize SKB264 in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

On June 19, 2023 Curocell Inc, a Korea-based clinical-stage CAR-T cell therapy company, reported updated Phase 2 interim results for Anbalcabtagene-autoleucel (anbal-cel) on June 15, 2023, at ICML (International Conference on Malignant Lymphoma), Lugano, Switzerland (Press release, Curocell, JUN 19, 2023, View Source [SID1234632805]).

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The anbal-cel is the next-generation OVISTM technology applied to anti-CD19 CAR-T using the 4-1BB domain as a co-stimulation domain as and also it consists of a dual knockdown system for two immune checkpoint receptors, PD-1 and TIGIT, in CAR-T cells.

The Phase 2 study of anbal-cel was conducted to evaluate the efficacy and safety in patients with r/r LBCL. Patients with relapsed or refractory LBCL were enrolled in six Korean investigator sites to receive anbal-cel at a dose of 2×106 CAR-T cells/kg.

41 patients with r/r LBCL were infused with anbal-cel. All patients received two or more prior lines of therapy and 10% (4 of 41) received ≥4 prior lines of treatment before the study.

84% ORR (32/38), 71% CR (27/38) were reached, and durable complete response was monitored as CR at 1 month was 68% (26/38), CR at 3 months was 61% (19/31) and CR at 6 months was 60% (12/20) where median follow-up as 6.3 months.

Grade 3 CRS and ICANS were reported from 14.6% (6/41), and 7.3% (3/41) respectively. No grade 4 CRS and ICANS were observed. Prolonged neutropenia, cytopenia, and serious infection were observed in 31.7% of patients (13/41), 49% of patients (20/41), and 10% of patients (4/41) respectively.

Curocell is planning on submitting an NDA to MFDS in mid-2024 and recently completed the construction of the largest commercial GMP facility for CAR-T production in Daejeon, Korea.

About anbalcabtagene autoleucel (anbal-cel)

Anbal-cel, recognized CD19 and is based on OVIS, a first-in-class CAR-T platform. OVIS technology downregulates PD1 and TIGIT expression on CAR-T cells. Through overcoming the immune suppression by PD-1 and TIGIT ligands, OVIS CAR-T has superior cytotoxicity to tumor cells in the tumor microenvironment. Anbal-cel is in a Phase II clinical trial in patients wit DLBCL in South Korea.

On June 19, 2023 Molecular Targeting Technologies, Inc. (MTTI) reported favorable findings of a 3-year follow-up of EBTATE (3 cycles, 3.7 GBq/cycle) against metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (Press release, Molecular Targeting Technologies, JUN 19, 2023, View Source [SID1234632784]). Results from this study were published in Theranostics.

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EBTATE is the first patented long-acting peptide targeting radiotherapeutic drug. It selectively targets somatostatin receptor 2 (SSTR2) on GEP-NETs, which are then killed by the radionuclide payload. The Evans blue moiety in EBTATE binds to serum albumin, extending in vivo circulatory half-life and residence time, enabling effective but lower radioactivity and fewer dosing cycles vs. the current standard of care (SOC). These findings confirm the safety and efficacy of the previous EBTATE results in 62 NET patients.

Professor Zhaohui Zhu, MD, principal investigator, said "Low occurrence of short and long-term toxicity proved EBTATE is safe (N=29). None of the patients developed leukemia or bone marrow disease during the 3-year follow-up. We observed low incidence of grade 3 hematoxicity (3.4% vs 15% of reported SOC) and no nephrotoxicity of any grade in long-term safety evaluation. Using EBTATE at lower radioactivity (37%) was as effective as SOC in disease control and achieved higher objective response based on RECIST criteria."

Chris Pak, President & CEO of MTTI commented: "It is rewarding to see how EBTATE helped these patients. We look forward to the same benefits from EBTATE trials in small cell lung cancer, nasopharyngeal cancers, Hürthle cell thyroid and others."