On April 14, 2022 Akeso, Inc. (9926.HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, reported the publication of preclinical results of its PD-1/CD73 bi-specific antibody (AK131) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Akeso Biopharma, APR 14, 2022, View Source [SID1234612264]). AK131 has demonstrated to have potent in-vitro and in-vivo anti-tumor activities.

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Abstract: AK131, an anti-PD1/CD73 bispecific antibody for cancer immune therapy

View Source!/10517/presentation/17745

AK131 is a bi-specific antibody derived from Penpulimab (Akeso’s marketed PD-1 antibody ) and AK119 (Akeso’s CD73 antibody in clinical stage). AK119 is a dual mechanism antibody (2021 SITC (Free SITC Whitepaper) poster #750) that both blocks the generation of adenosine and stimulates antigen specific B cell activation. Adenosine is a key immune suppressive molecule contributing to the resistance of PD-1 antibody therapy. Both CD73 and PD-1 are with high expression in the tumor microenvironment. Moreover, a growing body of literature evidence supports an important role of B cells in anit-tumor immunity. Thus the company developed a bi-specific PD-1/CD73 antibody with the capacity to relieve immune checkpoint control of T cells, activate B cells, and eliminate immune suppression by adenosine, for immune therapy of cancer.

The results and observations in AK131’s preclinical study support the development of AK131 as an anti-tumor agent in the clinic：

AK131 effectively bound to human PD-1 and CD73 with high affinity. The interaction between PD-1 and its ligand PD-L1 was blocked by AK131 in reporter gene assay.
In cellular assays, AK131 effectively promoted the secretion of IFN-γ and IL-2 by T cells in co-culture of PBMCs and Raji-PDL1 cells.
Moreover, AK131 inhibited CD73 enzymatic activity and induced endocytosis of CD73. AK131 enhanced the expression of CD69, CD83, HLA-DR and IgM which are markers of B cell activation in an adenosine-independent manner.
In in-vivo assay, AK131 successfully inhibited tumor growth in C57BL/6-hPD1/hPDL1/hCD73 transgenic mice MC38-hPDL1-hCD73 tumor syngeneic model.
Reference

[1] Huang S, Apasov S, Koshiba M, Sitkovsky M. Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion. Blood. 1997; 90:1600-10.

[2] [2] Novitskiy SV, Ryzhov S, Zaynagetdinov R, Goldstein AE, Huang Y, Tikhomirov OY, Blackburn MR, Biaggioni I,Carbone DP, Feoktistov I, et al. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood. 2008; 112:1822-31.

On April 14, 2022 Akeso, Inc. (9926.HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, reported the publication of preclinical results of its anti-TIGIT monoclonal antibody (AK127) showing potent preclinical anti-tumor activities at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Akeso Biopharma, APR 14, 2022, View Source [SID1234612263]).

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Abstract：AK127, a novel monoclonal antibody (mAb) targeting T cell immunoreceptor (TIGIT)

View Source!/10517/presentation/17743

AK127 is a novel humanized immunoglobulin (Ig) G1 monoclonal antibody (mAb) targeting T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT). AK127 specifically binds to TIGIT and blocks the interaction of TIGIT with its ligands, thus relieving immune suppression and promoting anti-tumor immune response.

Immune checkpoint blocking antibodies achieved great clinical success, yet a large fraction of cancer patients receive minimum benefit from current immunotherapies targeting PD-1 and CTLA-4. As a new multifunctional immune checkpoint molecule, TIGIT holds promise to become an important cancer immune therapy target.

The observations in AK127’s preclinical study support the development of AK127 as an anti-tumor agent in the clinic：

AK127 blocked the immune inhibitory signal mediated by TIGIT, resulting in enhanced IL-2 secretion.
AK127 exhibited binding to FcγRIa, FcγRIIIa and C1q, and eliciting ADCC, ADCP and CDC.
In animal models, both AK104 (0.5 mg/kg) and AK127 (4 mg/kg) significantly inhibited tumor growth.
The combination of AK127 and AK104 produced a significantly enhanced anti-tumor effect than either monotherapy, demonstrating the synergistic anti-tumor activity of AK127 combined with AK104.

On April 14, 2022 Akeso, Inc. (9926.HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, reported the publication of preclinical results of its PD-1/LAG-3 bi-specific antibody (AK129) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Akeso Biopharma, APR 14, 2022, View Source [SID1234612262]). Both in vitro and in vivo preclinical data demonstrated that AK129 has enhanced T cell activation activity with robust anti-tumor activity compared to PD-1 and LAG-3 antibody combo.

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Abstract: AK129, an anti-PD1/LAG-3 bi-specific antibody for cancer therapy

View Source!/10517/presentation/17739

AK129, a bi-specific antibody, acts by co-blocking two immune checkpoint molecules co-expressed on T cells, PD-1 and LAG-3. Signaling through PD-1/PD-L1 exerts major effects on cytokines production by T cells, inhibiting the production of IFN-γ and IL-2. LAG-3 is a cell surface molecule expressed on effector T cells and Tregs, which plays a vital role in regulating T cell function to promote tumor immune escape. LAG-3 and PD-1 mediate different signaling pathways, but they may act synergistically to cause effector T cells inactivation and exhaustion. AK129 is being investigated as a cancer immunotherapeutic agent.

Results and observations from AK129’s preclinical study support the development of AK129 as a cancer immunotherapeutic agent in the clinic：

AK129 showed good antigen binding to PD-1 and LAG-3. Coinsidently, AK129 potently inhibited the binding of LAG-3 to its ligand MHC-II, and the binding of PD-1 to its ligand PD-L1, thus blocking downstream immune suppression.
At the individual target level, AK129 demonstrated a similar PD-1 blocking activity compared to penpulimab, and similar LAG-3 blocking activity compared to relatlimab. Importantly, at the whole cell level, the enhancement effect of AK129 is stronger than the combination of penpulimab and relatlimab, as evidenced by significantly higher level of IL-2 and IFN-γ secretion from PBMCs.
AK129 showed favorable anti-tumor activity in BALB/c-hPD1/hLAG3 mice CT26.WT tumor model, with tumor growth inhibition values reaching 99.27% and 89.48% in high dose (20 mg/kg) and low dose (4 mg/kg) group of AK129, respectively.
Reference

[1] Kraman M, Faroudi M, Allen N, Kmiecik K, Gliddon D, Seal C, Koers A, Wydro M, Winnewisser J, Young L, Tuna M, Doody J, Morrow M, Brewis N. FS118, a bispecific antibody targeting LAG-3 and PD-L1, Enhances T-Cell activation result_x0002_ing in potent antitumor activity. Clin Cancer Res 2020; 26:3333–3344

[2] Maruhashi T, Sugiura D, Okazaki IM, Okazaki T. LAG-3: from molecular functions to clinical applications. J Immunother Cancer. 2020 Sep;8(2):e001014. doi: 10.1136/jitc-2020-001014. PMID: 32929051; PMCID: PMC7488795. [3] Long L, Zhang X, Chen F, Pan Q, Phiphatwatchara P, Zeng Y, Chen H. The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes Cancer. 2018 May;9(5-6):176-189. doi: 10.18632/genesandcancer.180. PMID: 30603054; PMCID: PMC6305110.

On April 14, 2022 West Pharmaceutical Services, Inc. (NYSE: WST), a global leader in innovative solutions for injectable drug administration, reported that it will release first-quarter 2022 financial results before the market opens on Thursday, April 28, 2022, and will follow with a conference call to discuss the results and business expectations at 9:00 a.m. Eastern Time (Press release, West Pharmaceutical Services, APR 14, 2022, View Source [SID1234612261]). To participate on the call, please dial 877-930-8295 (U.S.) or 253-336-8738 (International). The conference ID is 6690124.

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A live broadcast of the conference call will be available at the Company’s website, www.westpharma.com, in the "Investors" section. Management will refer to a slide presentation during the call, which will be made available on the day of the call. To view the presentation, select "Presentations" in the "Investors" section of the Company’s website.

An online archive of the broadcast will be available at the site three hours after the live call and will be available through Thursday, May 5, 2022, by dialing 855-859-2056 (U.S.) or 404-537-3406 (International). The conference ID is 6690124.

On April 14, 2022 Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported that its abstract providing the follow-up clinical data of GC012F in the treatment of relapsed/refractory multiple myeloma (RRMM) has been selected for oral presentation as part of an Oral Abstract Session at 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Gracell Biotechnologies, APR 14, 2022, View Source [SID1234612260]).

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GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19. It is developed using Gracell’s proprietary FasTCAR platform which enables next-day manufacturing, and is currently being evaluated in investigator-initiated trials (IITs) in China including in RRMM. In November 2021, GC012F was granted Orphan Drug Designation for the treatment of multiple myeloma by the U.S. Food and Drug Administration.

The complete title of the abstract will be released on meetings.asco.org on April 27, 2022 and the text of abstract will be posted on May 26, 2022 at 5:00 PM EDT. 2022 ASCO (Free ASCO Whitepaper) Annual Meeting will take place on June 3 – June 7, 2022 at the McCormick Place Convention Center in Chicago, Illinois.

About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma (MM) and B-cell non-Hodgkin’s lymphoma (B-NHL). GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can improve efficacy and reduce relapse in MM and B-NHL patients.

About FasTCAR

CAR-T cells manufactured on Gracell’s proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next-day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, increasing the accessibility of cell therapies for cancer patients.