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29 september 2021: Naventus Life Science Summit

On September 29, 2021 Sprint Bioscience reported that it will participate in the Naventus Life Science Summit, September 29, 2021 at the Grand Hôtel and CEO Erik Kinnman will present the company (Press release, Sprint Bioscience, SEP 29, 2021, View Source [SID1234590451]). The event is organized by Naventus Corporate Finance together with Setterwalls, Deloitte, FNCA, Nordnet and Nasdaq.

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Alphamab Oncology and Raygene Pharmaceutical Announced Partnership to Develop Combination Therapy of Bispecific Antibody KN046 and Small Molecule Drug RG001

On September 28,2021 Alphamab Oncology (stock code: 9966.HK) reported, the company has entered a partnership agreement with Hangzhou Raygene Pharmaceutical Co., Ltd (Raygene Pharmaceutical) to jointly develop the combination therapy of the PD-L1/CTLA-4 bispecific antibody KN046 and the small molecule drug RG001 for the posterior line treatment of advanced HCC and liver metastasis CRC (Press release, Alphamab, SEP 28, 2021, View Source [SID1234650400]).

Liver cancer and colorectal cancer are the common types of gastrointestinal cancers. According to the latest global cancer burden data released by the World Health Organization in 2020, liver cancer is the sixth most common cancer worldwide, and the third leading cause of cancer-related death globally. Over 50% of new cases and deaths occurred in China. Colorectal cancer is the third most common cancer worldwide and the second most common tumor in China. 83% of colorectal cancer patients in China were at a middle or advanced stage when diagnosed, and 44% of them had liver/lung metastasis.

KN046 is a bispecific antibody independently developed by Alphamab Oncology, which simultaneously targets PD-L1 and CTLA-4 immune checkpoints and could effectively activate T cells and enhance immune anti-tumor ability. The Phase II clinical data of KN046 combined with Lenvatinib in the first-line treatment of HCC were published at the ESMO (Free ESMO Whitepaper) 2021. KN046 in combination with Lenvatinib in first line HCC achieved 57% and 76% ORR and 95% and 95% DCR by RECISCT 1.1 and imRECIST, respectively. Based on the results from this study, a global phase III clinical study of KN046 in combination with Lenvatinib for the first line treatment of hepatocellular carcinoma is justified and currently in the planning phase.

RG001 (TATE) is a proprietary anti-tumor small molecule drug licensed in from abroad by Ruizhen Pharmaceutical. It could be acted as prodrug and transformed to cytotoxic metabolites in hypoxic tumor cell, and resulted in tumor cells killed. According to pre-study, it could achieve a synergistical effects to enhance anti-cancer capacity when combined with other immune checkpoint inhibitors.

According to the agreement, Alphamab Oncology and Raygene Pharmaceutical will conduct clinical trials evaluating safety and efficacy of KN046 plus RG001 or in sequential combination for the posterior line treatment of advanced HCC, CRC liver metastasis and other indications jointly decided by both parties, and to bring new options to patients who have progressed after receiving chemotherapy, small molecule targeted therapy or PD-1 therapy.

About KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a different mechanism CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg（suppress tumor immunity） clearing function.

There are about 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, thymic cancer, pancreatic cancer, HCC, ESCC and TNBC in Australia and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab has received FDA clearance to enter phase Ⅱ trial of KN046 based on the clinical results in China and Australia. Moreover, KN046 has obtained the U.S. FDA’s orphan drug designation for thymic epithelial tumor in September 2020. Four pivotal clinical trials are currently being conducted.

Research Collaboration between XtalPi Inc and Acerand Therapeutics to develop potential novel anti-cancer therapies using High-precision Physics-based model and Machine Learning

On September 28, 2021 XtalPi, a leading AI drug discovery company, reported a research collaboration with Acerand Therapeutics, a biotechnology company specialized in developing best-in-class and or first-in-class drugs (Press release, Acerand Therapeutics, SEP 28, 2021, View Source [SID1234641762]). The partnership will leverage XtalPi’s highly accurate physics-based models and machine learning models to develop potential novel chemical entities for a cancer target.

The collaboration focuses on facilitating new scaffold identification and lead optimization for a promising oncology target using highly accurate physics-based methods and machine learning models. XtalPi will provide machine learning-based high throughput screening for identification of novel scaffold and new chemical entities on a large-scale cloud computing platform. The proprietary free energy perturbation method in combination with a highly automated design-calculation workflow will be used to predict and analyze the binding affinities and inhibition mechanism during lead optimization. Acerand Therapeutics will provide highly valuable medicinal chemistry expertise and key experimental data to further refine the computational models and improve estimation accuracy.

XtalPi’s automated calculation platform built with high accuracy free energy calculations can precisely depict the interaction between ligands and their targets. The utilization of this technology increases the success rate of lead optimization and novel scaffold identification, and reduces the time required for lead optimization.

XtalPi CEO Dr. Ma Jian’s remark:

The nature of lead optimization is a long and highly complex process involving optimizing molecule physical chemical, ADME, and PK properties. High speed and accurate prediction of ligand affinity and ADMET can significantly reduce the time and cost associated with the development of drugs, especially, the first-in-class drugs. XtalPi can simultaneously evaluate many molecules and speed up the design cycle using the in-house high precision computational chemistry and machine learning technologies combined with our high-capacity cloud computing platform. It is our pleasure to work with Acerand Therapeutics. By collaborating with Acerand Therapeutics, we take advantages of their medicinal chemistry and biology expertise in drug discovery combined with our stength in AI and computational chemistry to more effectively develop potential novel anti-cancer drugs to the patients across the globe.

Acerand Co-Founder and SVP Dr. Genshi Zhao’s remark:

We are thrilled to join forces with XtalPi to develop potential novel anti-cancer therapies for the patients. As we all know, the drug discovery and development is a long and expensive process and there is an urgent need for the efficiency in the development of novel therapies. By leveraging XtalPi’s leading physics-based models and machine learning capabilities, we can rapidly evaluate many molecules with high precision regarding their binding affinities and ADMET properties, which will significantly shorten the lead optimization process, thereby accelerating our drug discovery & development. Learnings from this target should apply to other targets. We believe this is a beginning of a long term and productive collaboration between Acerand Therapeutics and XtalPi.

BioRay Infliximab for Injection (Anbaite®) received marketing authorization

On September 28, 2021 Hisun Biopharmaceutical Co., Ltd. (hereinafter referred to as "HisunBio"), a wholly-owned subsidiary of BioRay Pharmaceutical Co., Ltd. (hereinafter referred to as "Bioray") reported that the National Medical Products Administration (NMPA) of China approved the application for marketing of its own human-mouse chimeric monoclonal antibody targeting human tumor necrosis factor-α (TNF-α), Infliximab for Injection (Anbaite) on September 24 (Press release, Zhejiang Hisun Pharmaceutical, SEP 28, 2021, View Source;a=index&classid=43&id=5 [SID1234634621]). The National Medicine Permission Number (NMPN) of Anbaite is S20210039.

The indications of Anbaite include rheumatoid arthritis, Crohn’s disease in adults and children over 6 years old, fistulizing Crohn’s disease, AS (ankylosing spondylitis), psoriasis, and adult ulcerative colitis. Anbaite is the second biosimilar for infliximab to enter China market. It also becomes the third commercialized biologics from BioRay following the launch of Anbainuo and Anjianning (Adalimumab). Including Anshuzheng (Tofacitinib Citrate Tablets), BioRay has entered the ‘Four-An’ era, expanding its leadership in the treatment of immune diseases.

Anbaite is a recombinant human-mouse chimeric monoclonal antibody targeting TNF-α. As an important cytokine, TNF-α is indispensable for immune homeostasis and fighting against various pathogens. However, it has also been found that the overexpression of TNF-α plays a great role in the pathogenesis of autoimmune diseases. The expression level of tumor necrosis factor-α is relatively low in healthy tissues. When its concentration increases pathologically, TNF-α could impair immune homeostasis by promoting excessive inflammation, resulting in damages to tissues and organs. Anbaite can specifically bind to both soluble (sTNF-α) and transmembrane tumor necrosis factor-α (tmTNF-α) with high-affinity, which blocks the binding of tumor necrosis factor with its receptor to alleviate inflammation and autoimmune disease.

Anbaite is the biosimilar of infliximab for injection (Remicade). Remicade was granted marketing authorization in China in 2006. The efficacy and safety of Remicade have been fully verified by its extensive clinical use. Its peak sale reached $9.24 billion. According to the data from Fierce Pharma, the global sale of Remicade was $4.196 billion in 2020, ranking among top 20 worldwide. The infliximab for injection has been recommended as one of the options to treat related diseases by guidelines such as those in the "Chinese experts’ consensus on the treatment of psoriasis with biological agents (2019)". Additionally, it has also been enlisted on the negotiated drug catalog by "China National Drug Catalog for Basic Medical Insurance, Work-Related Injury Insurance, and Maternity Insurance (2020 Edition)" to further guarantee the drug’s accessibility.

As a drug supported by National Science and Technology Programs, Anbaite has been approved for all indications of Remicade in China. The number of people suffering from those indications exceeds 10 million in China and keeps increasing. With its approval by National Medical Products Administration, Anbaite will help alleviate the huge unmet medical needs. BioRay will also take this opportunity to enrich its product pipelines for the treatment of immune diseases, sharpen its leading edge in the field, and continue to develop affordable high-quality products, bringing more treatment options to patients and helping them improve their health and life quality.

Cue Biopharma Announces Publication in Nature Journal, Scientific Reports, of Immunotherapeutic Platforms Immuno-STAT and Neo-STAT

On September 28, 2021 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells directly within the patient’s body, reported the publication of research titled "Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells" in the peer-reviewed Nature journal, Scientific Reports (Press release, Cue Biopharma, SEP 28, 2021, View Source [SID1234608270]). The article describes Cue Biopharma’s IL-2 based CUE-100 series technology platforms, Immuno-STAT (Selective Targeting and Alteration of T cells) and Neo-STAT, being leveraged for the development of first-in-class biologics that enable selective activation of cancer-killing immune T cells within the patient’s body.

"We believe our platforms address a significant challenge in immunotherapy of ensuring selective targeting of activation signals to anti-tumor T cells in the patient while sparing the indiscriminate systemic activation of the immune system," said Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma. "Adoptive cell therapy such as chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated highly encouraging results for some patients but remain limited by the need of cellular ex-vivo manipulation and manufacturing challenges. Similarly, systemic approaches with immunostimulatory molecules, such as interleukin 2 (IL-2) or bispecific molecules, activate T cells indiscriminately and are associated with common severe adverse events, significantly limiting clinical benefit and applicability. Cue Biopharma’s approach and resulting platform, represents a potential breakthrough in the ability to selectively and safely modulate the immune system in a highly controlled and targeted manner directly in the patient’s body with the potential to create life-changing therapeutics with demonstrated improved efficacy and reduced toxicities."

Key aspects of Cue Biopharma’s technologies discussed in the article include:

The Immuno-STAT platform enables development of first-in-class off-the-shelf biologic molecules designed to selectively engage and activate disease-relevant T cells via the T cell receptors (TCR), mimicking the natural immune process, through the presentation of complimentary and synergistic signals, or "cues." An Immuno-STAT is engineered to include:
A first signal, or "cue" involving the presentation of a targeted and specific epitope, via a major histocompatibility (MHC)-peptide complex, to T cell receptors, or TCRs, of disease-specific T cells, to selectively engage a repertoire of T cells relevant to a particular disease such as cancer.
A corresponding second signal, or "cue" comprising the immunostimulant IL-2 molecule engineered with particular modifications for activation and expansion of CD8+ cytotoxic T cells, the relevant type of T cells with cancer-killing activity and minimize off-target binding and activation.
The Immuno-STAT is constructed upon a portion of a human antibody (the "Fc portion") that serves as the molecule’s backbone or scaffold and provides manufacturability and structural stability.
Through this design, Immuno-STATs enable disease specificity, targeted selective activation of CD8+ T cells and a larger therapeutic window for IL-2 effectiveness.
Neo-STAT is a plug-and-play variation of the Immuno-STAT platform designed with an empty "pocket" for the peptide presentation signal, enabling easy integration of disease-specific antigens a-posteriori to target a variety of cancers and infectious diseases.
The modular Immuno-STAT framework is compatible with diverse co-modulators, including immuno-suppressive molecules, with potential to address a variety of autoimmune diseases.
Ken Pienta, M.D., acting chief medical officer of Cue Biopharma, added, "We have identified a potential solution to safety and scalability challenges based on natural signals governing T cell function: peptide-HLA and costimulatory ligands, embodied in the Immuno-STAT and Neo-STAT immunotherapy platforms. The versatility and modularity of the platform as described in the paper, in addition to the clinical data to date supports the premise that our approach could be the next-generation solution to utilizing IL-2 as a targeted and selective immune activator for treating multiple cancers."

Cue Biopharma’s lead Immuno-STAT asset, CUE-101 has already shown encouraging results as a monotherapy in a Phase 1 dose escalation trial in late stage second line and beyond patients with HPV+ recurrent/metastatic head and neck cancer, which included a confirmed partial response with approximately 65% durable and ongoing tumor reduction and eight confirmed stable disease responses, controlling tumor growth for at least 12 weeks.

The Company is preparing for an Investigational New Drug filing for their next Immuno-STAT clinical candidate, CUE-102, which targets Wilms Tumor 1 (WT1), expressed in numerous solid tumors and hematological cancers.