On April 8, 2022 BroadenBio Co., Ltd. (BroadenBio) reported the completion of PreA+ round of financing of tens of millions (CNY) (Press release, BroadenBio, APR 8, 2022, View Source [SID1234640198]). The financing was led by the original shareholder Tao Capital, followed by Minkang Health Technology, and the original shareholder Lapam Capital continued to increase investment.

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The funding will primarily be used for the Phase 1 clinical trial of the potentially Best-in-Class (BIC) investigational drug BB102. In addition, the investment will also be used in the development of international cutting-edge small molecule inhibitors of intracellular immune checkpoint, and the preclinical study of globally First-in-Class (FIC) small molecule drug candidates that play immune activation and tumor suppression dual functions, as well as establishing a top-level immunology and small molecule coupling technology platform.

"We are very grateful to all investors, to Lapam Capital and Tao Capital, the well-known investment institutions in the industry, for their long-term support and companionship," said Xingmin Zhang, M.D., Ph.D., founder and Chief Executive Officer of BroadenBio. "BroadenBio has always been adhering to the original intention of its establishment, Gathering Talents, For Innovation, applying our unique technology platforms in the discovery and development of FIC and BIC innovative drugs, benefiting human health with immune technology."

Since its foundation, the company’s R&D pipeline has covered various fields such as oncology, autoimmune disease, and infection. Characteristic technology platforms are becoming increasingly perfect, and the R&D center has begun to take shape.

On April 8, 2022 AbClon reported that the company has partnered with the National Cancer Center (NCC) to develop a CAR-T (Chimeric Antigen Receptor-T) cell therapy for solid cancer and target Claudin (CLDN)-18.2 antigen (Press release, AbClon, APR 8, 2022, View Source [SID1234638630]).

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According to the company, the recent breakthrough success of CAR-T cell therapy for blood cancer has accelerated CAR-T research to treat intractable solid cancer. However, due to various difficulties, such as the micro-tumor environment of solid cancer, there have been no positive clinical results shown in the blood cancer field.

The two sides agreed to fully mobilize each other’s proprietary platform technology to develop a CAR-T cell therapy to treat intractable solid cancer.

The NCC research team plans to develop a platform technology that activates the killing ability of T cells only against cancer cells and a source technology for gene therapy using CAR-T cells that target antigens that exist only in cancer cells.

Abclon plans to develop a CAR-T cell therapy targeting the specific antigen Claudin-18.2 based on NCC’s technology.

The two parties plan to apply the developed method in treating solid metastatic cancer that is refractory to existing treatment.

AbClon stressed that Professor Jung Jun-ho at Seoul National University College of Medicine, an authority in antibody-drug and CAR-T cell therapy research, will participate in developing antibodies among the constituents of CAR that will act on the Claudin-18.2 antigen.

"Since Claudin-18.2 is overexpressed in gastric and pancreatic cancers, we have judged the antigen as a potential target to solve the unmet needs of patients with intractable solid cancer," Professor Jung said.

An AbClon official said, "In addition to the blood cancer treatment currently in clinical trials, the company plans to provide various treatment opportunities to patients by successfully developing a solid cancer CAR-T cell treatment."

The joint research project with NCC will serve as an opportunity for the company to leap forward as a global leader in CAR-T cell therapy, he added.

On April 8, 2022 The board of directors (the "Board") of Sino Biopharmaceutical Limited (the "Company", together with its subsidiaries, the "Group") reported that "TQ-B3525", an innovative drug self-developed by the Group, has been included by the Center for Drug Evaluation (the "CDE") of the National Medical Products Administration of China in the list of breakthrough therapy drugs (Press release, Sino Biopharmaceutical, APR 8, 2022, View Source(e)_0407_1829(2).pdf [SID1234633501]). The indication is relapsed/ refractory follicular lymphoma that has failed at least two prior lines of therapy.

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TQ-B3525 is a novel and selective oral PI3K (phosphatidylinositol 3-kinase) α/δ inhibitor. Studies have shown that PI3K is closely associated with tumours. TQ-B3525 is a dual inhibitor of PI3K catalytic subunits α/δ. It can not only overcome the drug resistance problem caused by the increase of PI3Kα subunit activity when inhibiting PI3Kδ subunit alone, but also significantly reduce the toxicity compared with PI3K pan-inhibitors. Currently, the Group has initiated a number of clinical studies on TQ-B3525 in China, mainly targeting haematological tumours, and some of them have entered Phase II clinical trials.

The CDE has established the Procedure for Breakthrough Therapy Drugs to encourage research and development of new drugs to meet clinical needs and to expedite the review and approval of new drug varieties. Follow-up communication and review and approval of the innovative drugs that have been included as breakthrough therapy drugs can be carried out in accordance with the accelerated procedures.

On April 8, 2022 BlueSphere Bio, a T-cell receptor (TCR) T-cell therapy company developing a powerful TCR discovery platform and novel therapeutic candidates for patients with hematologic malignancies and solid tumors, reported that it presented preclinical data demonstrating the potential of its novel high throughput TCXpress platform to efficiently identify TCRs against minor histocompatibility antigens (miHAs) for the future clinical development of adoptive TCR T cell therapy aimed at improving the efficacy of allogeneic stem cell transplant (alloSCT) treatments for patients with hematologic malignancies, including acute myeloid leukemia (AML), during the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 8 – 13, 2022 (Press release, BlueSphere Bio, APR 8, 2022, View Source [SID1234616064]).

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This work enabled the discovery of BlueSphere’s first clinical candidate, a TCR T-cell therapy directed against the miHA HA-1. The company anticipates filing its first IND by the end of 2022. In addition, the TCXpress platform has enabled the discovery of a TCR panel reactive against other relevant miHAs, which BlueSphere plans to soon announce this year.

Mark Shlomchik, M.D., Ph.D., co-founder and chief scientific officer of BlueSphere Bio commented that "The data from this presentation highlight the potential of our platform technology for the development of novel cellular therapies targeting miHAs that can be used to improve treatment outcomes in alloSCT. These data also demonstrate the remarkable efficiency of our high throughput discovery platform to robustly identify TCRs with potential applications that are not limited to a single class of targets or therapeutic strategy. We look forward to continuing to advance our internally developed candidates and fully realizing the potential of this platform to transform TCR discovery."

Presentation Highlights

Title: High throughput single cell based cloning reveals functional diversity of T-cell receptors targeting minor histocompatibility antigen

Presenter: Sawa Ito, M.D., Ph.D., hematologist/oncologist at UPMC Hillman Cancer Center and Assistant Professor, Division of Hematology Oncology and of Immunology at the University of Pittsburgh School of Medicine.

Data Highlights:

• TCXpress successfully identified a diverse set of novel TCRs with activity against the miHA, HA-1, from a single donor, naturally immunized to HA-1 through pregnancy.

• TCXpress yielded this set of TCRs with a broad functional affinity from a single donor, demonstrating its rapid and efficient discovery capabilities.

• When re-expressed in primary CD8-positive T cells, a high affinity TCR against HA-1 mediated specific killing of HA-1 positive target cells.

• The data also highlight the wide range of TCR affinities that can arise from a natural immune response against a single allopeptide/HLA complex, underscoring the potential to identify and characterize TCRs against other targets with this technology.

About TCXpress

TCXpress is a proprietary high-throughput and efficient T-cell receptor (TCR) capture, expression and functional screening platform capable of processing thousands of single T cells directly into functionally expressed TCRs within a matter of days, thereby creating extensive libraries without the need for lengthy sequencing.

On April 8, 2022 Applied Pharmaceutical Science reported that disclosed for the first time the critical preclinical data of the next-generation RET inhibitor APS03118 at AACR (Free AACR Whitepaper) 2022 annual meeting (Press release, Applied Pharmaceutical Science, APR 8, 2022, View Source [SID1234613105]). The data shows that APS03118 is a highly selective next-generation RET inhibitor that strongly inhibits multiple RET aberrances in vitro and in vivo, and can be used in patients with acquired resistance to the first-generation RET inhibitors.

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APS03118 is an innovative drug developed by APS for unlimited cancers with global independent intellectual property rights. Potential indications include non-small cell lung cancer(NSCLC), thyroid cancer, breast cancer, colorectal cancer and other metastatic solid tumors with RET aberrances.

RET aberrances contain fusions and mutations that lead to over-activation of RET signaling pathways and uncontrolled cell growth. As RET oncogene is present in a variety of cancers，it has become an important target of "unlimited cancer" therapies. Tumors with RET alterations primarily rely on abnormal activation of this kinase to promote proliferation and growth, therefore RET positive tumors are sensitive to RET inhibitors.

Although RET oncogene is closely related to various of cancers, only selpercatinib and pralsetinib were approved recently as the selective RET inhibitors. Selective RET inhibitors are effective in RET positive patients but followed by acquired drug resistance and progress disease. On-target resistances include the acquisition of solvent front mutations (SFMs) RET G810 R/S/C that have been identified as a predominant mechanism to both selpercatinib and pralsetinib. The roof RET L730I/M, gate keeper RET V804M/L/E, and hinge RET Y806 mutations are also important resistance mutations to current MKI and selective RET inhibitors. Therefore, a next-generation RET inhibitor should potently against SFMs and a broad range of other mutations.

APS03118 is the highly selective and potent next-generation RET inhibitor

• APS03118 was highly selective against a panel of 468 kinases at 100 nM compound concentration (performed at Eurofins).

• No concerning off-target finding in Eurofins Safety47 panel at the 10 μM compound concentration.

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APS03118 is potent against RET alterations in vitro

• APS03118 is potent against wild-type (WT) and a board range of mutant RET in comparison with selpercatinib and pralsetinib in the enzymatic and cell-based assays, especially the SFMs RET G810 R/S/C, gate keeper RET V804M/L/E, roof RET L730I/M and hinge RET Y806 mutations that induced the resistance to RET inhibitors.

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APS03118 shows potent antitumor efficacy in xenograft mouse tumor models

• APS03118 is highly active in xenograft tumor models including KIF5B-RET PDX, KIF5B-RET V804M CDX and KIF5B-RET G810R CDX models.

• Tumors completely subsided in orthotopic brain PDX model harboring CCDC6-RET with a 100% survival rate in APS03118 treated group.

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RET is closely related to the occurrence of a variety of human tumors. Lung cancer is the malignant tumor with the highest morbidity and mortality in China, and NSCLC is the most common type of lung cancer. NSCLC patients with RET gene alterations are not uncommon in clinic. In addition, the incidence of brain metastasis is high in lung cancer patients, which is closely related to the positive RET fusion with the cumulative incidence of more than 60% in 24 months. APS03118 may provide a better therapeutic option for NSCLC and thyroid cancer induced by RET aberrances.

Dr. Jun Zhong, vice president of R&D of APS, stated: "APS03118 has proved its great potential in the treatment of cancers with RET aberrances in preclinical studies. By participating the AACR (Free AACR Whitepaper) meeting, We hope the RET-targeted therapy would attract more attention, and provide optimized options for the patients with acquired resistance to the first-generation selective RET inhibitors in response to the global unmet medical needs in this field."

Investigational New Drug (IND) application of APS03118 was approved by FDA early this year, and APS03118 was also granted the Fast Track Designation by FDA. APS03118 released key preclinical data on AACR (Free AACR Whitepaper) meeting would add more confidence to ongoing global clinical trial.