On March 11, 2024 Ono Pharmaceutical Co., Ltd. (Osaka, Japan; President and CEO: Gyo Sagara; "Ono") reported that it entered into a five-year, university-wide strategic research alliance agreement with Harvard University (Cambridge, MA, USA; "Harvard") aiming at validating novel therapeutic targets (Press release, Ono, MAR 11, 2024, View Source [SID1234641031]).

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In this alliance, as part of our ongoing open innovation initiative to collaborate with external partners, the request for proposals will be for research projects focused on the validation of novel therapeutic targets from labs across Harvard University in Ono’s priority research areas of oncology, immunology, neurology, and specialty with high unmet medical needs. Working together with Harvard’s Office of Technology Development (OTD), Ono will support and fund research projects that are jointly selected. With the combined expertise and resources of both Ono and Harvard, this strategic alliance will promote our innovative drug discovery efforts.

Ono has been dedicated to the drug discovery and development of innovative drugs, focusing on priority areas of oncology, immunology, neurology, and specialty areas to fulfill unmet medical needs. Ono has generated a number of innovative medicines, by proactively promoting "open innovation" by working with external partners. Through our unique drug discovery approach based on open innovation, we will be committed to creating innovative drugs.

"We are pleased to work together with Harvard University, a leading institution developing cutting-edge technologies and advancing research through strategic alliances such as this one," stated Toichi Takino, Senior Executive Officer / Executive Director, Discovery & Research at Ono Pharmaceutical. "Our alliance with Harvard University leverages the complementary strengths to accelerate the validation of novel therapeutic targets that would lead to the discovery of new drugs. We will continue to work hard to deliver innovative drugs for patients with unmet medical needs."

"Harvard’s alliance with Ono underscores the university’s commitment to advancing our understanding and treatment of some of today’s most pressing health issues," stated Vivian Berlin, Executive Director, Harvard Medical School in Harvard’s Office of Technology Development. "The alliance will support research projects that pave the way for a future where complex diseases are better understood and more effectively treated."

"Strategic alliances bring together academic discovery with industrial capabilities," stated Isaac Kohlberg, Senior Associate Provost and Chief Technology Development Officer at Harvard University. "Not only accelerating the translation of groundbreaking discoveries into tangible innovations but also enriching academic research with real-world applications."

On March 11, 2024 TiumBio Co., Ltd. (KOSDAQ: 321550), a clinical-stage biopharmaceutical company focused on discovering and developing innovative therapeutics for patients with rare and incurable diseases, reported that it has submitted Investigational New Drug (IND) application to the Korean Ministry of Food and Drug Safe (MFDS) for a Phase 2a study of TU2218, an oral immuno-oncology drug, in late February, 2024 and that preclinical results of TU2218 will be presented at the upcoming 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, TiumBio, MAR 11, 2024, View Source [SID1234641029]).

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TU2218 is a novel oral dual inhibitor targeting transforming growth factor beta receptor 1 (TGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2). TGF-ß and VEGF pathways are known to be factors that interfere with the activity of immuno-oncology drugs, so TU2218 is expected to maximize the efficacy of immuno-oncology drugs by blocking them. TiumBio is currently conducting a Phase 1b clinical trial of TU2218 in combination with Keytruda (pembrolizumab) in advanced solid tumors in the U.S.

For the Phase 2a trial, TiumBio has selected indications in biliary tract cancer (BTC), head and neck squamous cell carcinoma (HNSCC), and colorectal cancer (CRC). The study will enroll up to 116 evaluable participants across three cohorts (up to 40 participants for BTC, up to 36 participants for HNSCC, and up to 40 participants for CRC, respectively) and will evaluate the efficacy and safety of TU2218 administered in combination with pembrolizumab.

BTC, HNSCC, and CRC have historically shown low treatment response rates to existing therapies. TiumBio expects that the combination of TU2218 and Keytruda will improve response rates in these tumors.

Meanwhile, to test the feasibility of various combination options with TU2218, TiumBio conducted in vivo efficacy studies in 4T1, MC39, and CT26 syngeneic tumor models. Results will be presented at the 2024 AACR (Free AACR Whitepaper), taking place from April 5-10 in San Diego, California.

The poster abstract highlights the improved efficacy and safety profile of TU2218 in combination with various immuno-oncology drugs. Specifically, the combination of lenvatinib, anti-PD-1 antibody, and TU2218 demonstrated a significant tumor growth inhibition (TGI) of 99% and a complete response (CR) rate of 67% in the CT 26 model, compared to a TGI of 76% and CR of 17% in the control group receiving only lenvatinib and anti-PD-1 antibody. The statistical difference in anti-tumor activity between the two groups was deemed significant (p<0.001).

"We believe that the results of this TU2218 triple combination regimen show substantial potential in enhancing anticancer efficacy. We will explore the commercial potential of the combination," said Hun-taek Kim, Ph.D., MBA, Founder and CEO, TiumBio. "The three indications we selected are diseases characterized by high expression of the target protein TGF-beta within the microenvironment, coupled with a significant unmet medical need attributed to low response rates to anti-PD-1 therapies. We will develop TU2218 as a safer and more effective novel drug to increase clinical benefits of the immune checkpoint inhibitors in this area," he added.

On March 11, 2024 Mabwell (688062.SH), an innovation-driven biopharmaceutical company with entire industry chain, reported that it will present its next generation ADC platform IDDC and the latest study results of multiple novel ADCs (9MW2821, 7MW3711, 9MW2921) developed based on this platform as poster presentation at the 14th World ADC London from March 12-15, 2024 local time (Press release, Mabwell Biotech, MAR 11, 2024, View Source [SID1234641028]).

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The World ADC Event Series is the largest academic event in the global ADC field.

Poster Presentation

Poster Title: Mtoxin Payload Applied in IDDC ADC Platform Significant Increases Therapeutic Index and Overcome MultiDrug Resistance in Various Tumor
Booth No.: 26

About the next generation ADC platform IDDC

IDDC is a next generation ADC site-specific conjugation technology platform independently developed by Mabwell, consisting of multiple systematic core patented technologies including the site-specific conjugation process DARfinity, the site-specific linker IDconnect, the novel payload Mtoxin, and the conditional release structure LysOnly. The next generation ADCs developed based on the above systematic patented technologies have better structural uniformity, quality stability, efficacy, and tolerability.

The IDDC platform has already been validated in multiple drugs under study. It is anticipated that more ADCs based on this platform will enter the clinical development stage in the future.

9MW2821 – novel Nectin-4-targeting ADC:
Mabwell is the first Chinese enterprise to advance 9MW2821 into Phase 3 clinical trials for the treatment of urothelial carcinoma, making it the second globally in terms of progress; 9MW2821 is also the first therapeutic drug in the world with the same target to disclose clinical efficacy data for indications of cervical cancer and esophageal carcinoma.

7MW3711 – novel B7-H3-targeting ADC:
Clinical trials have been conducted for 7MW3711 for the indication of advanced solid tumors in China and it has received FDA approval to conduct clinical trials for patients with advanced malignant solid tumors.

9MW2921 – novel Trop-2-targeting ADC:
Clinical trials have been conducted for 9MW2921 for the indication of advanced solid tumors in China.

On March 11, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that preclinical data on multiple novel bispecific antibodies as well as antibody-drug-conjugates (ADCs) from its oncology pipeline will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (Press release, Innovent Biologics, MAR 11, 2024, View Source [SID1234641027]). The AACR (Free AACR Whitepaper) meeting will take place April 5-10, 2024, in San Diego, California.

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Late-Breaking Research: Experimental and Molecular Therapeutics 1
Topic: IBI3001: a potentially first-in-class site-specifically conjugated B7-H3/EGFR bispecific ADC for multiple solid tumors
Abstract Number: LB055
Presentation Form: Poster
Presentation Time：Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

Topic: IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumors
Abstract Number: LB056
Presentation Form: Poster
Presentation Time：Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

Topic: Discovery and preclinical characterization of IBI343, a site-specifically conjugated anti-Claudin18.2 ADC for treating solid tumors
Abstract Number: LB057
Presentation Form: Poster
Presentation Time：Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

Poster Session: Immunology – Single Target and Bispecific Antibodies
Topic: A novel TROP2-targeted immune stimulating antibody conjugate (ISAC) with potent anti-tumoral activity and acceptable safety
Abstract Number: 2718
Presentation Form: Poster
Presentation Time: Monday Apr 8, 2024 1:30 PM – 5:00 PM
Location: Poster Section 6
Poster Board Number: 9
Presenting Author: Dr. Huizhong Xiong

Poster Session: Immunology – Immune Modulation Employing Agonist or Co-Stimulatory Approaches
Topic: Tumor targeted-CD28 bispecific antibody with optimized potency, robust anti-tumoral activity and stringent CD3-dependence
Abstract Number: 5295
Presentation Form: Poster
Presentation Time: Tuesday Apr 9, 2024 1:30 PM – 5:00 PM
Location: Poster Section 3
Poster Board Number: 4
Presenting Author: Dr. Huizhong Xiong

Dr. Kaijie He, Vice President of Innovent, stated: "We aim to tackle drug resistance and enhance treatment outcomes in immunotherapy by developing next-generation bispecific antibodies, multi-specific antibodies and ADCs candidates. To select targets that can address broad-spectrum of tumor types is one of our main research direction. We are pleased to present preclinical data of innovative molecules at the AACR (Free AACR Whitepaper) and accepted as Late-breaking Researches. We hope to benefit more patients with continuous advances in life science and technology. "

On March 11, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a publication in Blood Cancer Journal entitled ‘Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry (Press release, Autolus, MAR 11, 2024, View Source [SID1234641026]).’

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Diagnosing leukemic T-cell malignancies poses challenges due to their resemblance to reactive T-cells. In the paper published by Pedro Horna of Mayo Clinic in collaboration with Autolus, the authors introduce a unique approach for identifying T-cell neoplasms by flow cytometry1. This method adopts the recently described monoclonal antibodies targeting TRBC1 and TRBC22, 3, to assess for TRBC-restriction as a surrogate of clonality. The strategy mirrors the routine and broadly adopted analysis of kappa and lambda immunoglobulin chain restriction for the identification of B-cell malignancies.

This innovative and simple strategy to detect clonal expansion of T-cells by flow cytometry has the potential to facilitate the development of more comprehensive diagnostic panels that can be seamlessly integrated into existing screening protocols, obviating the need for separate T-cell clonality assessments. Autolus is working with world leading flow cytometry companies, including Beckman Coulter Life Sciences, BD (Becton, Dickinson and Company) and Thermo Fisher Scientific, in order to enable the development and distribution of diagnostic panels based on these unique TRBC1 and TRBC2 antibodies.

Advancements in diagnostic approaches for T-cell malignancies, coupled with the development of TRBC1 and TRBC2-directed CAR T cell therapeutics4, may contribute to the improvement of therapeutic strategies in this area of unmet clinical need.

1. Horna et al, Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry. Blood Cancer J. 14, 34 (2024). | doi: 10.1038/s41408-024-01002-0

2. Maciocia et al, Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med 23, 1416–1423 (2017) | doi: 10.1038/nm.4444

3. Ferrari et al, Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies. Nat Commun 15, 1583 (2024) | doi: 10.1038/s41467-024-45854-3

4. Cwynarski et al, First in human study of AUTO4, a TRBC1-Targeting CAR T cell therapy in refractory T cell lymphoma. Hematol Oncol 41, 80–81 (2023) | doi: 10.1002/hon.3163_44