HER2-Expressing Endometrial Carcinoma

近日，映恩生物在港股的IPO申请获得受理，摩根士丹利，瑞富金融集团，中信里昂证券以及中金公司为联席保荐人。 映恩生物是一家比较年轻的BioTech公司，创立于2020年。 成立两个月后，映恩生物便完成了3000万美元的A轮融资，次年5月再度完成9000万美元的B轮融资。 映恩生物的投资方名单可谓明星资本云集，包括礼来亚洲基金、药明生物产业基金、华盖资本、松禾资本等。药明生物产业基金是映恩生物重要的支持者，不仅战略投资A轮，在B轮仍继续加持。 在ADC的研发技术上，映恩生物对标于第一三共的Dxd技术，在第三代ADC技术平台的基础上开发了DITAC、DIMAC、DISAC、DIBAC等多个具有自主知识产权的技术平台，DITAC是映恩生物最主要的技术平台。 在ADC管线的布局策略上，映恩生物设计了三大研发梯队。 其中第一梯队选择已有临床验证的靶点，主要是基于DITAC平台开发的DB1303（HER2 ADC）和DB1305（Trop2 ADC），DB-1303已经推进到临床Ⅲ期阶段，首个适应症HER2表达子宫内膜癌预计最早于2025年向FDA申请加速批准。DB-1305处在临床I/II期开发阶段。 第二梯队开发和第三梯队开发best-in-class和first-in-class产品，预计在2025年之后进行推进。 有赖于其专有的平台技术，映恩生物的技术/管线授权合作在2023年开始爆发涌现。先后和Adcendo、BioNTech、百济神州海内外药企达成多项授权合作。 即便尚未有药品批准上市，但是凭借这些对外授权合作，映恩生物已经拿到了24.27亿元收入，其中最大的贡献来自BioNTech，2023年至2024年Q1季度以来，映恩生物以已经收到BioNTech的21.22亿元付款。 目前，映恩生物在研发上的投入比较大，2022和2023年2024Q季度，研发投入分别为3.39亿元、5.58亿元、3.1亿元。 参考出处： https://www1.hkexnews.hk/app/sehk/2024/106751/documents/sehk24082601406_c.pdfADC中的"最强黑马"，映恩生物为何受追捧 本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

Duality Biotherapeutics pulled back the curtain on its wide-reaching antibody-drug conjugate (ADC) pipeline this week, revealing new information on its 12-production portfolio as part of a filing declaring the biotech’s intent to go public on the Hong Kong stock exchange.  The document also provided more details on the candidates partnered with Germany-based drugmaker BioNTech, which first linked up with DualityBio in 2023 in an effort to diversify beyond its flagship mRNA vaccine business. For more on their collaboration, see BioNTech jumps on the ADC bandwagon. Between the BioNTech tie-up and other partnerships with BeiGene and Adcendo, DualityBio said its current deals represent more than $4 billion in total value. The Shanghai-based firm said it anticipates its late-stage ADCs to reach commercialisation in the next few years.Bispecifics and autoimmune diseases Altogether, DualityBio said it has developed 12 ADCs, of which half are already in the clinic — though several more are close to reaching that milestone, including DB-2304, the firm’s only autoimmune disease programme.The ADC targets blood dendritic cell antigen 2 (BDCA2), a receptor expressed on a specific cell type — plasmacytoid dendritic cells — that has been linked to the pathogenesis of lupus erythematosus (LE). DualityBio plans to file investigational new drug (IND) applications for both systemic and cutaneous LE this half. Other notable preclinical programmes include two bispecific ADCs, a newer iteration of the popular modality that enables the targeting of two different epitopes on either the same or different antigens, with the goal of reducing off-target toxicities, overcoming drug resistance and boosting ADC internalisation. For more on the latest advances in the space, see Spotlight On: Bispecific ADCs are gaining traction.The most advanced bispecific ADC is DB-1419, which targets both B7-H3 and PD-L1. According to DualityBio, the candidate is designed to simultaneously deliver a toxic DNA topoisomerase I inhibitor payload while also modulating T-cell activation. The first patient in a Phase I/IIa global trial is expected to be dosed this half. BioNTech collaborationThe filing also delved into a trio of programmes partnered with BioNTech. At the head of the pack is BNT323 (formerly DB-1303), a HER2-targeting ADC in three potentially registrational trials. DualityBio said it expects next year to file with the FDA seeking accelerated approval for the lead indication of HER2-expressing endometrial cancer.The candidate uses a stable, cleavable linker and topoisomerase-based payload to lower off-target toxicities and improve antitumour activity. Outside of endometrial cancer — for which BNT323 is the most advanced HER2-targeting ADC — the candidate has also shown activity against several solid tumours including breast, ovarian, colorectal and esophageal cancers.  The second programme is BNT324 (DB-1311), which targets B7-H3, a protein that plays a key role in tumour progression and metastasis and is overexpressed in several tumour types such as non–small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), castration-resistant prostate cancer (CRPC) and esophageal squamous cell carcinoma (ESCC). Currently in a Phase I/IIa trial for solid tumours including SCLC and CRPC, DualityBio plans to test the candidate as monotherapy and in immunotherapy combinations. BNT324 has fast track designation from the FDA for CRPC, as well as orphan drug designation for ESCC. Rounding out its BioNTech collaboration is BNT325 (DB-1305), a TROP2-targeting programme for “under-explored” indications such as ovarian cancer. The company said the compound also has combination potential for NSCLC, cervical cancer and triple-negative breast cancer, which may position it as “a potential backbone therapy in the TROP2 ADC landscape.” BNT325 is in a Phase I/IIa study for advanced solid tumours, including NSCLC, where “encouraging preliminary efficacy signals” have been observed.Unpartnered assetDualityBio’s most advanced wholly owned programme is DB-1310, a HER3-targeting ADC candidate the firm believes has “untapped opportunities to cover a broad patient population with limited reliance on biomarker-based patient selection and overcome resistance to standard of care.” Currently in Phase I testing, DualityBio expects to explore the asset in KRAS-mutant NSCLC, as well as in combination with AstraZeneca’s Tagrisso (osimertinib) for patients with EGFR-mutated NSCLC who are resistant to tyrosine kinase inhibitors.

CULVER CITY, Calif.--( BUSINESS WIRE )--Immunotherapy company ImmunityBio, Inc. ( NASDAQ: IBRX ), today announced the opening of a clinical trial to study ANKTIVA® (nogapendekin alfa inbakicept-pmln) together with the investigational AdHER2DC vaccine (autologous dendritic cells transduced with HER2 expressing adenovirus), in individuals with HER2-expressing endometrial cancer. It marks the latest trial involving ANKTIVA, the company’s IL-15 superagonist immune enhancer, to evaluate ANKTIVA as an agent to replace the short-term activity of checkpoint inhibitor immunotherapies with long-term effectiveness. ANKTIVA was recently approved by the FDA for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumors. This Phase 1/2 QUILT 502 trial ( NCT06253494 ) sponsored by the National Cancer Institute, part of the National Institutes of Health, will study whether the AdHER2DC vaccine in combination with ANKTIVA, pembrolizumab (checkpoint inhibitor), and lenvatinib (kinase inhibitor) can be safely administered in combination and provide preliminary clinical efficacy before a larger, more definitive study. Endometrial cancer is the most common gynecological cancer in the U.S., and affects more than 65,000 women each year with incidence peaking around 50-60 years of age. The 5-year overall survival rate in patients with metastasis is around 20 percent; treatment options after the second-line treatment are limited. The AdHER2DC vaccine targets the HER2 protein, which is elevated in 30% of patients with endometrial cancer and in more than 50% of high risk subtypes. The AdHER2DCs are autologous, using each participant’s own blood cells obtained through apheresis, a “loop” where blood is removed from one vein, passed through a machine to filter out target cells and then returned to the patient through another vein. The AdHER2DC is a proprietary agent of the NCI and it will be manufactured at the NIH Clinical Center for each study participant. The single agent AdHER2DC demonstrated safety profile and immunogenicity in a phase 1 clinical trial conducted by the NCI. The first treatment cycle is 28 days and each cycle after that will be 21 days. All participants will receive the vaccine and the two FDA approved drugs pembrolizumab and lenvatinib, and some participants will receive ANKTIVA. Phase 1 of the open-label, two-arm Phase 1/2 study will determine recommended dose of pembrolizumab, lenvatinib, ANKTIVA and AdHER2DC in participants with HER2 positive endometrial cancer. The Phase 2 portion of the study will assess the efficacy of the combination of pembrolizumab, lenvatinib, ANKTIVA and the AdHER2DC vaccine in qualified participants as determined by the proportion of participants without disease progression at six months. The study will enroll 60 subjects and is expected to be completed in 2026. “We are pleased to partner with the NCI on this important cancer control study involving ANKTIVA, which has demonstrated in clinical trials that activation of memory T cells may help deliver long-duration response well beyond that of checkpoint inhibitors alone,” said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “We are hopeful that the AdHER2DC investigational vaccine plus ANKTIVA will ‘rescue’ the checkpoint inhibitor pembrolizumab and kinase inhibitor lenvatinib and lead to an improved response compared with the current standard of care in this high risk population.” ImmunityBio is already partnered with the NCI to study the use of ANKTIVA in cases of Lynch syndrome, a genetic condition that is linked with significantly increased incidence of cancers, particularly colon cancer. These studies along with the recent approval of ANKTIVA for bladder cancer signal the advent of the era of cytokines as the next-generation of immunotherapies. To learn more about this study, please visit https://clinicaltrials.gov/study/NCT06253494 . For patients interested in enrolling in this study, please contact NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the website: https://trials.cancer.gov and/or NCIMO_referrals@mail.nih.gov . The AdHER2DC vaccine is investigational. Safety and efficacy of this investigational agent have not been established by any health authority, including the FDA. How ANKTIVA Works The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response. ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. The proliferation of the trifecta of these immune killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo. About ImmunityBio ImmunityBio is a vertically-integrated biotechnology company developing next-generation therapies and vaccines that bolster the natural immune system to defeat cancers and infectious diseases. The company’s range of immunotherapy and cell therapy platforms, alone and together, act to drive and sustain an immune response with the goal of creating durable and safe protection against disease. Designated an FDA Breakthrough Therapy, ANKTIVA ® is the first FDA-approved immunotherapy for non-muscle invasive bladder cancer that activates natural killer cells, T cells, and memory T cells for a long-duration response. The company is applying its science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that we believe sharply reduce or eliminate the need for standard high-dose chemotherapy. These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases. For more information, please visit: www.immunitybio.com Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding commercial launch activities and timing, product demand, patient treatment, data and results from clinical trials and potential implications therefrom, product availability and supply, potential regulatory pathways and approval requests and submissions, the regulatory review process and timing thereof, market and prevalence data, potential benefits to patients, potential treatment outcomes for patients, the described mechanism of action and results and contributions therefrom, information regarding ongoing pre-clinical studies and clinical trials, potential future uses and applications of ANKTIVA and use in cancer vaccines and across multiple tumor types, ImmunityBio’s financial condition, and ImmunityBio’s approved product and investigational agents as compared to existing treatment options, among others. Statements in this presentation that are not statements of historical fact are considered forward-looking statements, which are usually identified by the use of words such as “anticipates,” “believes,” “continues,” “goal,” “could,” “estimates,” “scheduled,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “indicate,” “projects,” “seeks,” “should,” “will,” “strategy,” and variations of such words or similar expressions. Statements of past performance, efforts, or results of our preclinical and clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. Forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of ImmunityBio’s management as well as assumptions made by and information currently available to ImmunityBio. 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More details about these and other risks that may impact ImmunityBio’s business are described under the heading “Risk Factors” in the Company’s Form 10-K filed with the U.S. Securities and Exchange Commission (“SEC”) on March 19, 2024 and the Company’s Form 10-Q filed with the SEC on May 9, 2024, and in subsequent filings made by ImmunityBio with the SEC, which are available on the SEC’s website at www.sec.gov . ImmunityBio cautions you not to place undue reliance on any forward looking statements, which speak only as of the date hereof. ImmunityBio does not undertake any duty to update any forward-looking statement or other information in this press release, except to the extent required by law.