On December 19, 2024 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer drugs, reported that the first patient has been successfully enrolled in the global multi-center Phase 1b clinical trial of CS5001 (ROR1 ADC), a key product in its 2.0 pipeline (Press release, CStone Pharmaceauticals, DEC 19, 2024, View Source [SID1234656224]).

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To date, CS5001 has demonstrated a favorable safety profile and significant anti-tumor activity across 10 dose cohorts in a Phase 1a dose-escalation trial. CS5001 has been well-tolerated in patients with multiply pretreated advanced B-cell lymphoma and solid tumors, with no dose-limiting toxicities (DLTs) observed across all 10 dose cohorts. At the initially selected Phase II recommended dose (RP2D) of 125 μg/kg, CS5001 achieved ORRs of 70% and 100% in advanced B-cell non-Hodgkin’s lymphoma and Hodgkin’s lymphoma, respectively . Furthermore, significant efficacy signals have been observed in advanced solid tumors such as non-small cell lung cancer and pancreatic cancer.

Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said, "This year, the clinical results of CS5001 have been presented at numerous international conferences and have garnered widespread attention within the industry. The latest clinical data demonstrate that CS5001 monotherapy achieves a higher ORR than competing agents in both aggressive and indolent advanced lymphomas, and the efficacy data have stabilized with increasing patient enrollment. Therefore, we believe CS5001 has the potential for accelerated registration and marketing, as well as the potential to impact the frontline combination therapy landscape . We are very pleased to see the initiation of a Phase 1b dose optimization and expansion trial of CS5001, which is expected to be further expanded into a Phase 2, single-arm, registration-enabling trial in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) . Concurrently, we will continue to explore the safety and efficacy of CS5001 in Phase 1b, either as a monotherapy or in combination with frontline standard therapies, across a variety of hematologic malignancies and solid tumors, with the goal of bringing innovative therapies with even greater survival benefits to cancer patients worldwide."

About the CS5001 (ROR1 ADC)

CS5001 is an antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). CS5001 features a unique design, utilizing a tumor-specifically activated pyrrolobenzodiazepine (PBD) protoxin payload and a linker. CS5001 is delivered only after tumor cell internalization. Within the lysosome, the linker is cleaved by a specific enzyme highly expressed in tumor cells, releasing the PBD protoxin, which is then activated and killed within the tumor cell. This "dual-control" mechanism of linker plus protoxin effectively mitigates the toxicity issues associated with traditional PBD payloads, resulting in a wider safety window. CS5001 has demonstrated complete tumor inhibition in several preclinical cancer models and exhibits favorable serum half-life and pharmacokinetic properties. All of this indicates that CS5001 has significant clinical development potential and broad application prospects in a variety of solid tumors and hematological malignancies. Furthermore, CS5001 utilizes directed conjugation technology to achieve a precise drug-antibody ratio (DAR), facilitating homogeneous production and large-scale production.

In October 2020, CStone Pharmaceuticals and LigaChem Biosciences, Inc. (LCB) entered into a licensing agreement for the development and commercialization of CS5001. CS5001 was originally synthesized by LCB and ABL bio, two leading Korean biotech companies. Under the terms of the agreement, CStone Pharmaceuticals obtained exclusive development and commercialization rights for CS5001 worldwide, excluding Korea.

Data from the first-in-human study of CS5001 in patients with advanced solid tumors and lymphomas were presented as a poster at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Furthermore, updated clinical data on CS5001 as a monotherapy for advanced lymphomas were recently presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

On December 19, 2024 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer drugs, reported that the first patient has been successfully enrolled in the global multi-center Phase 1b clinical trial of CS5001 (ROR1 ADC), a key product in its 2.0 pipeline (Press release, CStone Pharmaceauticals, DEC 19, 2024, View Source [SID1234656224]).

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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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To date, CS5001 has demonstrated a favorable safety profile and significant anti-tumor activity across 10 dose cohorts in a Phase 1a dose-escalation trial. CS5001 has been well-tolerated in patients with multiply pretreated advanced B-cell lymphoma and solid tumors, with no dose-limiting toxicities (DLTs) observed across all 10 dose cohorts. At the initially selected Phase II recommended dose (RP2D) of 125 μg/kg, CS5001 achieved ORRs of 70% and 100% in advanced B-cell non-Hodgkin’s lymphoma and Hodgkin’s lymphoma, respectively . Furthermore, significant efficacy signals have been observed in advanced solid tumors such as non-small cell lung cancer and pancreatic cancer.

Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said, "This year, the clinical results of CS5001 have been presented at numerous international conferences and have garnered widespread attention within the industry. The latest clinical data demonstrate that CS5001 monotherapy achieves a higher ORR than competing agents in both aggressive and indolent advanced lymphomas, and the efficacy data have stabilized with increasing patient enrollment. Therefore, we believe CS5001 has the potential for accelerated registration and marketing, as well as the potential to impact the frontline combination therapy landscape . We are very pleased to see the initiation of a Phase 1b dose optimization and expansion trial of CS5001, which is expected to be further expanded into a Phase 2, single-arm, registration-enabling trial in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) . Concurrently, we will continue to explore the safety and efficacy of CS5001 in Phase 1b, either as a monotherapy or in combination with frontline standard therapies, across a variety of hematologic malignancies and solid tumors, with the goal of bringing innovative therapies with even greater survival benefits to cancer patients worldwide."

About the CS5001 (ROR1 ADC)

CS5001 is an antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). CS5001 features a unique design, utilizing a tumor-specifically activated pyrrolobenzodiazepine (PBD) protoxin payload and a linker. CS5001 is delivered only after tumor cell internalization. Within the lysosome, the linker is cleaved by a specific enzyme highly expressed in tumor cells, releasing the PBD protoxin, which is then activated and killed within the tumor cell. This "dual-control" mechanism of linker plus protoxin effectively mitigates the toxicity issues associated with traditional PBD payloads, resulting in a wider safety window. CS5001 has demonstrated complete tumor inhibition in several preclinical cancer models and exhibits favorable serum half-life and pharmacokinetic properties. All of this indicates that CS5001 has significant clinical development potential and broad application prospects in a variety of solid tumors and hematological malignancies. Furthermore, CS5001 utilizes directed conjugation technology to achieve a precise drug-antibody ratio (DAR), facilitating homogeneous production and large-scale production.

In October 2020, CStone Pharmaceuticals and LigaChem Biosciences, Inc. (LCB) entered into a licensing agreement for the development and commercialization of CS5001. CS5001 was originally synthesized by LCB and ABL bio, two leading Korean biotech companies. Under the terms of the agreement, CStone Pharmaceuticals obtained exclusive development and commercialization rights for CS5001 worldwide, excluding Korea.

Data from the first-in-human study of CS5001 in patients with advanced solid tumors and lymphomas were presented as a poster at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Furthermore, updated clinical data on CS5001 as a monotherapy for advanced lymphomas were recently presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

On December 19, 2024 Palleon Pharmaceuticals, a company pioneering glyco-immunology drug development to treat autoimmune diseases and cancer, reported a collaboration and license agreement with Shanghai Henlius Biotech, Inc. (2696.HK) to develop and commercialize Palleon’s first-in-class human sialidase enzyme therapeutic, E-602, in combination with Henlius’ self-developed HANLIKANG (rituximab) in patients with autoimmune diseases, including lupus nephritis (LN) (Press release, Palleon Pharmaceuticals, DEC 19, 2024, View Source [SID1234649229]).

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Depleting B cells with targeted antibodies such as rituximab (anti-CD20 mAb) is an established treatment for several autoimmune diseases, however, many patients have inadequate response to these drugs. Glyco-immunology provides a new approach to treating autoimmunity by enhancing depletion of activated memory B cells, the pathogenic subset of B cells associated with disease progression and often resistant to antibody-mediated depletion. E-602 enzymatically degrades sialoglycans—immunosuppressive cell surface sugars that protect pathogenic memory B cells from depletion by B cell-targeted antibodies.

Preclinical studies of E-602 in combination with rituximab demonstrate improved outcomes versus rituximab alone without the risk of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) associated with CAR T and T cell engagers. E-602 has demonstrated a favorable safety profile with no dose-limiting toxicities in human clinical trials, which makes it suitable for the outpatient community setting.

"Palleon’s glycan editing therapeutic has the potential to significantly improve treatment outcomes in patients who have autoimmune diseases including lupus nephritis, with a therapy that achieves optimal patient accessibility, including delivery in community outpatient settings," said Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon. "We look forward to continuing our successful partnership with Henlius and expanding glyco-immunology drug development to address a new category of patients in need of better treatment options."

Under the terms of the agreement, Henlius received an exclusive China license to Palleon’s E-602. Palleon is eligible to receive up to $95.3 million in certain predetermined development and commercial milestones, in addition to royalties upon E-602 commercialization in China. Henlius shall perform and fund E-602 development in China in combination with HANLIKANG for the treatment of lupus nephritis. This partnership expands upon Palleon and Henlius’ ongoing collaboration in oncology formed in June 2022 to co-develop targeted sialidase therapies in cancer.

"We are pleased to expand our collaboration with Palleon Pharmaceuticals, the leader in the novel field of glyco-immunology," said Dr. Jason Zhu, Executive Director and Chief Executive Officer of Henlius. "HANLIKANG is the only rituximab approved for an autoimmune indication in China. We are committed to bringing better therapies to patients who suffer from lupus nephritis and other autoimmune conditions for which current treatment options are not always sufficient."

E-602 is a first-in-class human sialidase enzyme therapeutic developed from Palleon’s EAGLE glycan editing platform. HANLIKANG (rituximab) is the first-ever biosimilar developed and approved in China.

On December 19, 2024 Portal Biotechnologies, Inc. ("Portal"), a cell engineering platform company, reported an oversubscribed $7M seed round led by IA Ventures with participation from Pear VC, Undeterred Ventures, Page One VC, IKJ Capital and other current investors (Press release, Portal Biotechnology, DEC 19, 2024, View Source [SID1234649228]).

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Portal is implementing a simplified approach to intracellular delivery, focused on enabling novel cell engineering and analytical capabilities. The initial product suite for research and clinical scales are based on next generation mechanical delivery technology capable of delivering many different types of cargo into a broad range of cells. This simple approach has been shown to enable delivery of a variety of molecules into cells, including impermeable small molecules, polypeptides, antibodies, RNA and gene editing complexes, both individually and simultaneously, for multiplexed cell function modification.

Since emerging from stealth a year ago, Portal has accumulated over 50 biopharma and academic partners leveraging the platform for applications ranging from novel drug screening assays to engineering cell therapies with circular RNA. Portal’s customer base includes 7 of the top 10 pharmaceutical companies, is a member of the Bayer Co.Lab in Cambridge, and affiliated with the Roche Accelerator in Shanghai. Under the ‘Powered by Portal’ model, the company is also integrating its single-use cartridges with high throughput robotics manufacturers and clinical equipment providers.

"The rapid adoption of Portal’s platform has been a very exciting experience. I am deeply grateful to our investors and early adopters for their faith in us at these early stages as we build on our past experiences at MIT and SQZ to democratize access to this potentially transformative technology. As a scientist, I have loved the creativity of our partners in deploying Portal’s unique capabilities in new ways. As a former cancer patient, I can’t wait to see what novel therapeutics we may enable!" said Armon Sharei, Ph.D., Founder and CEO of Portal.

To further accelerate Portal’s commercial activities, while maintaining a commitment to enabling novel science and patient impact, Anil Narasimha, Ph.D. joined as Chief Commercial Officer. Dr. Narasimha was most recently a co-founder and CEO of Mekonos where he gained a deep understanding of the ex-vivo drug delivery space. Paired with Portal’s CEO, Armon Sharei, Ph.D, and COO, Alec Barclay, the company is well positioned to continue scaling its partnering activities and platform development to enable novel drug discovery and cell therapy capabilities across disease areas.

"I am extremely excited to join the Portal team," said Anil Narasimha. "Delivery is a huge bottleneck for a variety of different applications, and Portal has a product that can solve these issues in a simple, fast, and efficient manner."

On December 19, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported that the first patient has been dosed in the Phase 1 clinical trial evaluating ADI-270 in patients with metastatic/advanced ccRCC (Press release, Adicet Bio, DEC 19, 2024, View Source [SID1234649227]).

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"Dosing the first patient in our Phase 1 trial of ADI-270 in metastatic/advanced ccRCC is a significant milestone for Adicet as we advance our first gamma delta 1 CAR T cell product candidate for the treatment of solid tumors, one of the highest unmet needs in oncology," said Chen Schor, President and Chief Executive Officer at Adicet Bio. "Patients with ccRCC, the most common type of kidney cancer, have a pressing need for safe and effective treatments, as current therapies offer limited benefits for patients with advanced disease. Based on ADI-270’s encouraging preclinical data generated to date, in which ADI-270 demonstrated significant tumor infiltration, resistance to the immunosuppressive tumor microenvironment and potent activity via CAR and innate-mediated targeting, we believe ADI-270 has the potential to offer a promising advancement for solid tumors. We anticipate reporting preliminary clinical data from the trial in the first half of 2025."

About the Phase 1 Trial

The Phase 1 multicenter, open-label clinical trial is designed to investigate ADI-270 as monotherapy in adults with relapsed or refractory metastatic/advanced ccRCC. Following lymphodepletion, patients will be eligible to receive a single dose of ADI-270 with a starting dose level of 3E8 CAR+ cells. Subject to meeting protocol defined criteria, patients enrolled in the trial may be eligible to receive a second dose of ADI-270. The dose escalation and dose expansion portions of the trial will evaluate safety, tolerability, and pharmacokinetics as well as anti-tumor activity as assessed by overall response rate, duration of response and disease control rate.

For more information about becoming a study site, please email [email protected].

About ADI-270

ADI-270 is an armored allogeneic "off-the-shelf" gamma delta CAR T cell therapy candidate targeting CD70-positive cancers. CD70 is a compelling target due to its high expression in both solid and hematological malignancies. ADI-270 is engineered with a third-generation CAR designed to target CD70 using its natural receptor, CD27, as the binding moiety and is further armored with a dominant negative form of the transforming growth factor-β receptor II (dnTGFβRII) to provide functional resilience to the immunosuppressive tumor microenvironment. ADI-270 is also designed to increase exposure and persistence by reducing susceptibility to host vs. graft elimination. These properties of ADI-270 combined with the potent tumor infiltration demonstrated with gamma delta 1 T cells aim to improve clinical responses of RCC patients and other patients with CD70+ tumors.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common tumor of the kidney, constituting 80% to 85% of primary renal neoplasms. Clear cell RCC (ccRCC) is the most common subtype, accounting for 80% of all RCCs. ccRCC is an aggressive subtype arising from renal stem cells commonly arising in the proximal nephron and tubular epithelium, and often metastasizes to the lungs, liver, and bones. Approximately 20% of newly diagnosed cases of RCC are locally advanced or metastatic and up to 30% of patients will develop metastatic disease following nephrectomy. While the 5-year survival rate for localized RCC is 93%, the 5-year survival rate for advanced disease is 15%.