On December 19, 2024 Modiblast GmbH, a preclinical-stage biopharmaceutical company developing novel immunomodulatory cancer therapies, reported the publication of novel preclinical in vivo data and initial human data validating its therapeutic strategy in the peer-review International Journal of Molecular Sciences. The data sets demonstrate the therapeutic potential of the patented approach aimed at the in vivo reprogramming of myeloid leukemic blasts into antigen-presenting dendritic cells of leukemic origin (DCleu) to boost adaptive and innate anti-cancer immunity. The full publication is available for download via the IJMS website.

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"The preclinical data sets published today further substantiate our previous work and validate our novel approach from various angles. Even more so, the addition of first patient data from off-label use significantly derisks the further development path and provides us with strong guidance for designing the upcoming clinical trial," commented Prof. Dr. rer. nat. Helga Schmetzer, Managing Director and Founder of Modiblast. "Overall, we continue to make steady progress in advancing our lead program MB101 towards an IND-ready state and plan to accelerate the development towards the initiation of clinical trials once backed by a new financing round in 2025."

Modiblast’s therapeutic approach combines two synergistic factors to turn ‘foe’ into ‘friend’. A myeloid differentiation factor fosters the creation of dendritic cell progenitor cells and hematological recovery. The combination with a danger signal and maturation factor drives the formation of dendritic cells (DCs). Both signals combined trigger the reprogramming of cancer blast into DCleu’s and boost the creation of healthy DCs. The first program, MB101, aims for a fixed-dose combination of granulocyte-macrophage colony stimulation factor (GM-CSF), and prostaglandin E1 (PGE1) as a ‘danger signal’.

In the preclinical portion of the new publication, MB101’s therapeutic effects were evaluated in an established animal acute myeloid leukemia (AML) model. After 9 days of treatment, DCleu and memory-like T cells increased in the peripheral blood, whereas regulatory T cells and especially blasts decreased in treated as compared to untreated control animals. A significant reduction of blasts compared to the control group was seen in both spleen and blood following treatment with GM-CSF and PGE1.

Based on the confirmatory preclinical data package generated for MB101’s drug combination to date, two heavily pre-treated and refractory AML patients received MB101 treatment on an individualized basis over a 4-week period. A third, untreated patient with similar clinical parameters served as a control. The treatment was shown to be safe, leading to neutrophil recovery without increasing blast counts. At the same time, immune cells of the adaptive and innate lines were activated and gave rise to memory as well as to antileukemic cells. One of two patients treated showed a rapid recovery of platelets, a postulated synergistic effect of the combination of GM-CSF and PGE1, which made the patient independent of platelet transfusions.

The full publication "In vivo Induction of Leukemia Specific Adaptive and Innate Immune Cells By Treatment of AML-Diseased Rats and Therapy-Refractory AML-Patients with Blast Modulating Response Modifiers" can be downloaded on the IJMS website or via our Publications section.

(Press release, Modiblast, DEC 19, 2024, https://www.modiblast.com/modiblast-publishes-preclinical-in-vivo-data-and-initial-human-data-on-novel-cancer-cell-reprogramming-approach-in-aml/ [SID1234662150])

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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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."