On February 21, 2022 Mission Therapeutics ("Mission"), a drug discovery and development company focused on protein homeostasis by selectively inhibiting deubiquitylating enzymes (DUBs), reported that its CEO, Anker Lundemose, will attend and present at the next event in the BMO Biopharma Spotlight Series: Protein – Degraders and Other Next Gen Technologies, on Thursday, 24 February 2022 (Press release, Mission Therapeutics, FEB 21, 2022, View Source [SID1234608353]).

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The virtual event will focus on the therapeutic area of protein degraders and other emerging technologies, with an agenda consisting of fireside chats, expert presentations, and topical panels.

Dr Lundemose will be available for one-to-one meetings as well as presenting as part of the Private Company Spotlights panel and Q&A at 11.20 ET.

This will be the sixth event in the BMO Biopharma Spotlight series of webinars, which explore different therapeutic areas and enable KOLs, public companies, and key players in the private sector to discuss their scientific research and technological approaches.

On February 21, 2022 AIGEN Sciences, an artificial intelligence-based new drug development biotech, reported that it signed a joint research agreement with Incurix to develop new anticancer drugs based on artificial intelligence (AI) (Press release, AIGEN Sciences, FEB 21, 2022, View Source [SID1234643551]).

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This contract applies artificial intelligence technology based on transcriptome profiles based on Eisen Science’s protein structure to develop new anticancer drugs based on transcription factor inhibitors, which are attracting attention as major anticancer targets but are known to be difficult to develop. The goal is joint development.

Eisen Science plans to derive new substances that can regulate transcription factors based on its artificial intelligence platform. Afterwards, Incurix will be responsible for verification of effective substances and lead substances and follow-up development of final candidate substances by utilizing the new substances derived from Eisen Science using the transcription factor direct inhibitor new drug development technology platform. The terms of the contract will be kept confidential as agreed between the two companies, and the profits secured through commercialization, such as third-party technology transfer, will be shared in a certain ratio according to the stage of candidate material development at the time of profit generation.

Accordingly, AIGEN Science uses its platform ‘AIGEN Discovery’ to initially select about 10,000 ‘focused library’ compounds that show the effect of regulating transcription factors at the cellular level from a library of 3 billion compounds. Next, we plan to use the protein structure of the transcription factor to discover effective substances that bind with high affinity, and then proceed with optimization using ‘AIGEN Optimizer’ to discover leading substances.

Kang Jae-woo, CEO of Eisen Science, said, "Through joint development with Incurix, which specializes in developing anticancer drugs that directly inhibit transcription factors, we will successfully lead the development of new drugs for transcription factor targets (difficult-to-target) that were difficult to access through traditional methods. "As Eisen Science’s artificial intelligence platform is a model based on transcriptome data, synergy is expected with Incurix, which has expertise in developing transcription factor inhibitors, and we have high expectations for future joint development."

On February 21, 2022 Published in Cancer Research Communications (1), a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), findings reported by investigators of the Vall d’Hebron Institute of Oncology’s (VHIO) Models of Cancer Therapies Group (Vall d’Hebron Barcelona Hospital Campus), and VHIO-born spin-off Peptomyc S.L., show that MYC inhibition is anti-metastatic in breast cancer (Press release, Peptomyc, FEB 21, 2022, View Source [SID1234608354]).

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The deregulation of the pleiotropic and ubiquitous MYC oncoprotein is implicated in almost all human cancers, and while its role as a promoter of tumorigenesis is beyond doubt, its function in the process of metastasis remains controversial. Contrasting reports suggest both a pro-metastatic and anti-metastatic function of MYC have largely precluded research assessing MYC inhibitors in the metastatic setting.

Thanks to two decades of research pioneered by Laura Soucek and her team, as well as the dedicated work of other groups, MYC inhibition is gaining pace in entering the clinic. Historically considered as an undruggable target, MYC now officially occupies a top spot on the most-wanted list of targets in cancer therapy.

Having shown potent anti-tumor activity of the MYC inhibitor Omomyc in multiple cancer cell lines and mouse models, regardless of their tissue of origin or driver mutations, Laura’s group and her Peptomyc team are developing viable, non-toxic pharmacological options for MYC targeting in the clinic.

"Considering the results of our previous studies that have clearly demonstrated Omomyc’s efficacy in primary tumors, we hypothesized that targeting MYC could also be efficacious against metastatic breast cancer," said Laura Soucek, corresponding author of this present study, Co-Founder & Chief Executive Officer (CEO) of Peptomyc, and an ICREA Research Professor.

Ringing in MYC inhibition in the metastatic setting
Metastases are genetically unstable. Information from a patient’s primary tumor might not mirror the metastasis, and one metastasis may vary from another, thus hampering the benefits of targeted therapies. Based on their data indicating the efficacy of MYC inhibition independently of the mutational profile of the tumor, the investigators hypothesized that this approach could overcome th challenge.

They also sought to establish if MYC inhibition could revert MYC’s promotion of epithelial-mesenchymal transition (EMT) and dedifferentiation, two important hallmarks of cancer metastasis.

The promise of Omomyc as a potential anti-metastatic therapy in breast cancer
To evaluate Omomyc’s efficacy against breast cancer and metastasis, the researchers used a panel of breast cancer cell lines, representative of all molecular subtypes of the disease. Assessing the transgenically expressed Omomyc first, they observed therapeutic impact in these cell lines and in cell-derived in vivo xenograft models.

They then confirmed that the same therapeutic impact can be achieved pharmacologically using the purified Omomyc mini-protein which demonstrated efficacy in cell lines in vitro, as well as in vivo, in cell-derived and patient-derived xenograft (PDX) models.

Results of this present study (1) shed important light on the efficacy of MYC inhibition in the metastatic setting, with particular focus on triple-negative breast cancer (TNBC). The investigators demonstrate for the first time that MYC inhibition by Omomyc is effective against TNBC by displaying potent anti-metastatic activity in vivo.

"Our results illuminate the relevance of MYC inhibition in metastatic disease, and are particularly timely now that MYC inhibitors, including our first Omomyc-derived compound, OMO-103, are reaching the clinic," added Laura Soucek.

Notably, OMO-103 entered clinical trials in May 2021, and is being tested in patients with various solid tumors in the Phase I/IIa MYCure study (2).

"We have now demonstrated that MYC inhibition by Omomyc exerts a dramatic effect on the metastatic process, from tumor growth, invasion to seeding. Findings evidenced a striking reduction in both primary tumor and metastatic growth. In some cases, metastases were even eradicated," said Daniel Massó-Vallés, first author of this study and a Postdoctoral Researcher and Project Manager at Peptomyc.

This study shows the promise of Omomyc as an anti-metastatic therapy against breast cancer and also challenges the controversial notion that MYC inhibition potentiates, rather than inhibits, tumor cell invasion and metastasis.

Results support the inclusion of metastatic TNBC patients in the ongoing MYCure trial, uphold MYC’s essential role in all aspects of tumorigenesis, and could ultimately lead to improved survival in this patient population.

This research was carried out in collaboration with investigators from other VHIO groups including Violeta Serra (PI, Experimental Therapeutics Group), and Joaquín Arribas (PI, Growth Factors Group), and researchers at CIEMAT (Madrid, Spain), and the Karolinska Institutet (Stockholm, Sweden).

This project was mainly funded by grants received from the Agència de Gestió d’Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants), Spanish Ministry of Science and Innovation, Spanish Ministry of Science and Technology – Institute of Health Carlos III, European Research Council (ERC), and the FERO Foundation.

References:

Daniel Massó-Vallés, Marie-Eve Beaulieu, Toni Jauset, Fabio Giuntini, Mariano F. Zacarías-Fluck, Laia Foradada, Sandra Martínez-Martín, Erika Serrano, Génesis Martín- Fernández, Sílvia Casacuberta-Serra, Virginia Castillo Cano, Jastrinjan Kaur, Sergio López- Estévez, Miguel Ángel Morcillo, Mohammad Alzrigat, Loay Mahmoud, Antonio Luque-García, Marta Escorihuela, Marta Guzman, Joaquín Arribas, Violeta Serra, Lars-Gunnar Larsson, Jonathan R. Whitfield & Laura Soucek. MYC inhibition halts metastatic breast cancer progression by blocking growth, invasion and seeding. Cancer Res Commun. 2022;2:110–30. doi: 10.1158/2767-9764.CRC-21-0103.
Phase 1/2 Study to Evaluate Safety, PK and Efficacy of the MYC-Inhibitor OMO-103 in Solid Tumours (MYCure). ClinicalTrials.gov Identifier: NCT04808362.

On February 21, 2022 United Therapeutics Corporation (Nasdaq: UTHR) reported that it will report its fourth quarter and full year 2021 financial results before the market opens on Thursday, February 24, 2022 (Press release, United Therapeutics, FEB 21, 2022, View Source [SID1234608355]).

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United Therapeutics will host a public webcast Thursday, February 24, 2022, at 9:00 a.m. Eastern Time. The webcast will be accessible via United Therapeutics’ website at View Source A rebroadcast of the webcast will be available for one week and can be accessed at the same location.

On February 20, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported the first patient dosing for its first-in-class IgG-based universal "modular" Claudin 18.2-targeting chimeric antigen receptor T (CAR-T) cell product (development code: IBI345) for the treatment of advanced Claudin18.2-positive solid tumors in an investigator-initiated-trial (IIT) (Press release, Innovent Biologics, FEB 20, 2022, View Source [SID1234608339]). Since Innovent announced its strategic cooperation with Roche on June 9, 2020, this is the first disclosure of the development milestone for the cell therapy products based on Roche’s proprietary innovative technology platform.

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The study (NCT05199519) is an investigator-initiated clinical trial with the primary objective of evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345 in subjects with Claudin18.2-positive solid tumors.

CAR-T cell therapy has established a meaningful role in the treatment of hematological tumors with 5 products approved by the FDA, and 2 by the NMPA in China, respectively; however, antitumor efficacy for solid tumors remains a challenge calling for technological breakthroughs. As the world’s first universal "modular" CAR-T cell product, IBI345 has potentially differentiated advantages over conventional CAR-T cell therapy products, including: 1) leveraging antibody function to target tumor antigens and consequently amplifying the tumor antigen signal to guide CAR-T cells to enter the tumor, thus aiding in the initiation of tumor recognition and killing; 2) controlling the functional activity of the CAR-T cells via concomitantly administered antibodies which act as a bridge between the target cell and CAR-T cell, potentially providing a better safety profile; 3) allows for the sequential or simultaneous administration of more than one antibody targeting different antigen targets without changing CAR-T cells, to treat tumors with highly heterogeneous antigen expression or relapsed tumors due to antigen-loss, thereby improving the accessibility and increasing the flexibility of CAR-T cell therapy for patients.

The principal investigator of the study, Professor Weichang Chen, the Secretary of the Party Committee and Chief Physician of the Department of Gastroenterology of the First Hospital Affiliated to Soochow University, pointed out: "As gastric and pancreatic cancer are highly aggressive tumors with high incidence rates in the world, patients are in urgent need of novel treatment options to improve clinical outcomes. IBI345, with its unique design to control CAR-T functional activity through the antibody bridging, will likely provide improved safety and efficacy. We look forward to the positive results of the safety, tolerability and efficacy data of IBI345 in patients with solid tumors, which will potentially provide a new option for the treatment of patients with advanced gastric or pancreatic cancer."

Dr. Xu Wei, VP of Innovent, R&D Head of Cell Therapy, said: "IBI345 is a highly differentiated CAR-T cell product with a new mechanism of action developed by Innovent based on Roche’s proprietary technology. As a universal "modular" CAR-T cell therapy product, equipped with a precisely targeted antibody switch, it regulates the expansion of CAR-T cells to control side effects, potentially providing an opportunity to switch to another antibody that targets different antigens to prevent recurrence and treat different tumors. Our preclinical studies have validated this "modular" CAR-T technology, which provides us with the sufficient scientific data to initiate clinical studies. In the following clinical studies, we will explore the safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345, and optimize the clinical dosage and regimen to support the subsequent IND application. We firmly believe that Innovent will be able to introduce more innovative cell therapies through platform technology innovation, product transformation and in-depth collaboration with the clinical academic community that will ultimately benefit more patients and families."

About Claudin 18.2
Claudin protein is a critical component of tight junction complex molecules which play an important role in the life activities of the human body. On the one hand, tight junctions can function as a "barrier" to select the size and charge of substances, thereby regulating the transport of substances in the para-cellular pathway. For example, brain vascular endothelial cells can pass through this barrier, preventing blood from mixing with the extracellular fluid in the brain. On the other hand, tight junctions can also function as "fences", maintaining cell polarity by regulating the free diffusion of lipids and proteins between the apical and the basolateral membrane.

Claudin18.2 is a member of the Claudin protein family, which is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer such as gastric cancer, pancreatic cancer, esophageal adenocarcinoma, and colorectal adenocarcinoma. The unique feature of limited expression in normal tissues and highly specific expression in cancer makes Claudin18.2 an ideal target for developing the immunotherapeutic for solid tumors.

Globally, there is currently no therapy targeting Claudin18.2 approved for marketing, but there are many candidate therapies in clinical development. The drug modalities under development include monoclonal antibodies, bispecific antibodies, antibody-conjugated drugs and CAR-T cell products.

About Gastric and Pancreatic adenocarcinoma
Gastric and pancreatic cancer are both malignant tumors of the digestive system that seriously endanger human life and health. The latest global cancer statistics show that there will be about 1.089 million new cases of gastric cancer worldwide in 2020, accounting for 5.6% of the global cancer incidence, and about 768,000 deaths, accounting for 7.7% of the global cancer deaths. There are about 495,000 new cases of pancreatic cancer, accounting for 2.6% of the global cancer incidence, and about 466,000 deaths, accounting for 4.7% of the global cancer deaths. According to the national cancer statistics released by the National Cancer Center of China in 2019, the incidence of gastric cancer in China in 2015 was about 403,000, accounting for 10.26% of the total cancer incidence, second only to lung cancer at 20.03%, with an incidence rate of 29.31/100,000 people, and about 291,000 deaths, accounting for 12.45% of the total cancer deaths, behind lung and liver cancer, with a mortality rate of 21.16/100,000 people. In 2015, the number of cases and deaths of pancreatic cancer nationwide were 95,000 and 85,000 respectively, ranking the 10th and 6th in the incidence and mortality of malignant tumors. The mortality ratio of pancreatic cancer was 0.89, making it a true "King of Cancer". Despite the treatment progress in recent years, drug resistance, recurrence and metastasis are still inevitable. The 5-year survival rate of patients with advanced gastric cancer is about 5-20%, and the median survival rate is about 10 months. Pancreatic cancer has a worse prognosis, with a 5-year survival rate of only 6 to 8%.

About IBI345
IBI345 is the first universal "modular" CAR-T cell product developed by Innovent based on Roche’s proprietary technology. It is an internationally pioneered highly differentiated CAR-T cell product with a new mechanism of action. Different from conventional CAR-T cells that directly recognize and kill tumor cells, IBI345 comprises of two components, anti-Claudin18.2 antibodies and "modular" CAR-T cells where anti-Claudin18.2 antibody recognizes tumor antigen, thus calibrating and amplifying the antigen signal, and guides "modular" CAR-T cells to enter the tumor to initiate the cytotoxic and antitumor activity of CAR-T cells. Compared with conventional CAR-T cells, IBI345 has a variety of potential advantages, including dual effects of antibodies and CAR-T cells to increase antitumor efficacy, and flexible control of side effects by regulating CAR-T cell activity through antibodies; in addition, as having a universal CAR molecule, "modular" CAR-T cells can be easily switched to different antibodies without changing CAR-T cells, by sequentially or simultaneously administering more than one antibody targeting different antigen targets, to treat tumors with highly heterogeneous antigen expression or antigen-loss relapsed tumors, which holds a great potential to reduce the cost of CAR-T cell therapy and improve the accessibility of CAR-T cell therapy for patients.

Innovent announced that first patient dosing has been completed in February 2022 in the investigator-initiated clinical trial of IBI345 for the treatment of advanced Claudin18.2-positive solid tumors, and enrollment is currently ongoing. The safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345 will be explored, and the clinical dosage and regimen will be explored to provide clinical data support for the subsequent IND application.