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- Initiation of CX-2051 Phase 1 clinical study in EpCAM positive tumors including colorectal cancer anticipated in 1H 2024 - - Initiation of CX-801 Phase 1 clinical study in solid tumors including melanoma, renal, and head and neck squamous cell carcinoma also anticipated in 1H 2024 - Jan. 24, 2024 -- CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, today announced that it has received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) applications for the conditionally activated Probody® therapeutics CX-2051, an EpCAM-directed ADC, and CX-801, a dually-masked version of interferon-alpha 2b. CX-2051 has been cleared for the initiation of Phase 1 dose escalation in solid tumors with known EpCAM expression and CX-801 has been cleared for the initiation of Phase 1 dose escalation in solid tumors including melanoma, renal, and head and neck squamous cell carcinoma. Both programs are expected to start Phase 1 studies in the first half of 2024. “CX-2051 and CX-801 have the potential to address major unmet needs in oncology and we are excited to advance these programs into Phase 1 clinical studies. CX-2051 is an ADC conjugated to a next-generation topoisomerase-1 inhibitor payload that we believe is tailored to certain EpCAM-expressing tumors, including colorectal cancer,” said Wayne Chu, M.D., chief medical officer of CytomX Therapeutics. “CX-801 is designed to overcome previous limitations of interferon-directed therapies due to systemic toxicity and establish CX-801 as a cornerstone of combination regimens, including with checkpoint inhibitors, across a wide range of tumor types,” continued Dr. Chu. “The parallel advancement of these programs toward the clinic demonstrates the continued high productivity of the CytomX team and the versatile, multi-modality nature of our Probody® platform. The product design principles behind CX-2051 and CX-801 integrate over a decade of continuous innovation and experience at CytomX,” said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX Therapeutics. “We look forward to the clinical initiation of these programs as we enter a potentially milestone-rich period for the company in 2024 and 2025.” EpCAM is a high potential oncology target that has been clinically validated by locally administered, previously approved cancer therapies. However, to date, efforts to generate systemically administered anti-EpCAM therapeutics have not been successful due to toxicities in certain epithelial tissues, notably in the gastrointestinal tract. CX-2051, a conditionally activated ADC, is tailored to optimize the therapeutic index for EpCAM-expressing cancers. The cytotoxic payload utilized in CX-2051 is a derivative of camptothecin, a topoisomerase-1 inhibitor, a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets. CX-2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer. Phase 1 clinical initiation in EpCAM expressing solid tumors is expected in the first half of 2024. Further details on the design and preclinical optimization of CX-2051 can be found here: Interferon-alpha 2b is an immunotherapeutic cytokine that has demonstrated clinical activity and gained regulatory approval previously in multiple cancer types, including metastatic melanoma, renal cancer and bladder cancer. IFNα2b provides a potentially superior approach to activating anti-tumor immune responses compared to other cytokines. CX-801 is a dually masked, conditionally activated version of IFNα2b that has the potential to become a cornerstone of combination therapy for a wide range of tumor types, including in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. Phase 1 initiation for CX-801 solid tumors including melanoma, renal, and head and neck squamous cell carcinoma anticipated in the first half of 2024. Further details on the design and preclinical optimization of CX-801 can be found here: CytomX is a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel conditionally activated biologics designed to be localized to the tumor microenvironment. By pioneering a novel pipeline of localized biologics, powered by its Probody® therapeutic platform, CytomX’s vision is to create safer, more effective therapies for the treatment of cancer. CytomX’s robust and differentiated pipeline comprises therapeutic candidates across multiple treatment modalities including antibody-drug conjugates (“ADCs”), T-cell engagers, and immune modulators such as cytokines and checkpoint inhibitors. CytomX’s clinical pipeline includes the cancer immunotherapeutic candidates CX-904 and BMS-986288. CX-904, partnered with Amgen, is a conditionally activated T-cell-engaging antibody targeting the epidermal growth factor receptor (EGFR) on tumor cells and the CD3 receptor on T cells. BMS-986288, partnered with Bristol Myers Squibb, is a conditionally activated CTLA-4-targeting antibody that is a non-fucosylated version of ipilimumab. In addition, CytomX has a diverse, emerging portfolio of wholly-owned drug candidates including CX-2051, a conditionally activated ADC directed toward epithelial cell adhesion molecule, EpCAM, with potential applicability across multiple EpCAM-expressing epithelial cancers, and CX-801, an interferon alpha-2b Probody cytokine with broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive tumors. CytomX has established strategic collaborations with multiple leaders in oncology, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna. For more information about CytomX and how it is working to make conditionally activated treatments the new standard-of-care in the fight against cancer, visit www.cytomx.com and follow us on LinkedIn and Twitter. The content above comes from the network. if any infringement, please contact us to modify.

The pivotal Phase 3 trial with BNT323/DB-1303 follows positive Phase 1/2 safety and efficacy data in patients with Human Epidermal Growth Factor Receptor 2 (“HER2”)-expressing advanced solid tumors with early signs of anti-tumor activity in heavily pretreated patients with HER2-low and HER2-positive breast cancer The trial is expected to enroll 532 patients with Hormone Receptor-positive (“HR+”) and HER2-low metastatic breast cancer progressing on hormone therapy at clinical trial sites worldwide, initially in China, followed by sites in the United States, Europe, and additional regions The clinical milestone is in furtherance of BioNTech’s and DualityBio’s strategic objective to advance BNT323/DB-1303 into late-stage development in multiple high unmet medical need cancer indications January 22, 2024 – BioNTech SE (Nasdaq: BNTX, “BioNTech”) and Duality Biologics (Suzhou) Co., Ltd. (“DualityBio”) today announced that the first patient with metastatic breast cancer has been treated in a pivotal Phase 3 trial evaluating the efficacy and safety of the next-generation antibody-drug conjugate (“ADC”) candidate BNT323/DB-1303 targeting the Human Epidermal Growth Factor Receptor 2 (“HER2”), a cancer cell surface protein. Breast cancer is the most commonly diagnosed cancer worldwide and the leading cause of death from malignant tumors in women globally.1,2 The breast cancer subtype, which is defined by the expression of hormone receptors ("hormone receptor-positive”, "HR+") and a low expression level of the HER2 protein ("HER2-low") on the cancer cell surface, accounts for approximately 40 % to 45 % of patients in advanced, metastatic disease stage.3 HER2 has been shown to be a suitable target structure for the treatment of breast cancers with intermediate and high HER2 expression.4 HER2-directed therapies have been ineffective in the past in patients with tumors with low expression levels of the protein.5 Recent studies have indicated that next-generation ADCs may have the potential to transfer the impact of HER2-directed therapies to HER2-low tumors.6 The global, multi-center, open-label, randomized Phase 3 trial (NCT06018337) will assess the efficacy and safety of BNT323/DB-1303 compared to standard-of-care single-agent chemotherapy in chemotherapy-naïve patients with HR+ and HER2-low metastatic breast cancer that have progressed on hormone therapy. The trial is expected to enroll 532 patients at more than 223 clinical sites worldwide, initially in China, followed by sites in the United States, Europe, and additional regions. The study’s primary endpoint is progression-free survival. Secondary endpoints include overall survival, objective response rate, duration of response, and safety. “For patients with advanced HR+/HER2-low breast cancers who progressed after primary therapy, single-agent palliative chemotherapy is the most common regimen to control the disease and reduce mortality. BNT323/DB-1303 has been designed with the aim to combine the selectivity of antibodies with the cancer cell-killing properties of chemotherapy, thereby aiming to minimize the toxicity of the chemotherapeutic agents for patients,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. “Our objective is to further expand the impact of HER2-targeted ADC therapies to chemotherapy naïve patients in metastatic disease stage who express HER2 at low levels at earliest possible treatment lines, seeking to extend the therapeutic window and improve outcomes for these patients.” “The initiation of the Phase 3 trial marks an important step in the development of our next-generation ADC candidate with the first indication progressing into pivotal evaluation,” said Vivian Gu, M.D., Chief Medical Officer at DualityBio. “Results from our Phase 1/2 clinical study indicate a robust mechanism of action of BNT323/DB-1303 and have demonstrated preliminary efficacy and a manageable safety profile. We look forward to further advancing this differentiated ADC candidate.” The Phase 3 trial is based on positive safety and efficacy data from a Phase 1/2 study (NCT05150691) with BNT323/DB-1303 in patients with advanced/metastatic solid tumors. Data presented at ASCO 2023 demonstrated encouraging anti-tumor activity in heavily pretreated patients with HER2-low breast cancer with an objective response rate of 38.5% and a disease control rate of 84.6%. BNT323/DB-1303 was well tolerated with a manageable safety profile across all evaluated patients with advanced/metastatic solid tumors. The milestone is in furtherance of BioNTech and DualityBio’s strategic objective to advance the product candidate into late-stage development in multiple high unmet medical need cancer indications. The Phase 3 trial initiation marks a major landmark in BioNTech’s and DualityBio’s strategic collaboration initiated in April 2023. The collaboration aims to accelerate the development of differentiated antibody-drug conjugate therapeutics for solid tumors. BioNTech will hold commercial rights globally (excluding Mainland China, Hong Kong Special Administrative Region, and Macau Special Administrative Region), while DualityBio will retain commercial rights for Mainland China, Hong Kong Special Administrative Region, and Macau Special Administrative Region. BNT323/DB-1303 is a third-generation topoisomerase-1 inhibitor-based ADC targeting HER2 which was built from DualityBio’s proprietary Duality Immune Toxin Antibody Conjugates (“DITAC”) platform. HER2 is a surface-expressed protein on solid tumors and has been linked to the aggressive growth and spread of cancer cells, making it a potential target for innovative cancer therapeutics. The candidate has exhibited antitumor activity in both HER2-positive and HER2-low tumor models as well as in several solid tumor indications, including patients with breast, gastric, endometrial, biliary tract cancers, and other advanced solid tumors. Preclinical data and preliminary clinical data for BNT323/DB-1303 indicate its potential to target HER2 receptors on solid tumors irrespective of expression level with a manageable safety profile and a potentially expanded therapeutic window. BNT323/DB-1303 is currently being evaluated in an ongoing Phase 1/2 study (NCT05150691) in patients with advanced/metastatic solid tumors and in a pivotal Phase 3 study (NCT06018337) in patients with Hormone Receptor-positive (“HR+”) and Human Epidermal Growth Factor Receptor 2 (“HER2”)-low, metastatic breast cancer that have progressed on hormone and/or cyclin-dependent kinase 4/6 (“CDK4/6”) therapy. The BNT323/DB-1303 program received the Fast Track designation and Breakthrough Therapy designation from the U.S. Food and Drug Administration (“FDA”) for the treatment of endometrial cancer in 2023. Biopharmaceutical New Technologies (BioNTech) is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (“CAR”) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (“ADC”) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, OncoC4, Regeneron and Pfizer. DualityBio is a clinical-stage company focusing on the discovery and development of the next generation ADC therapeutics for patients with cancer and autoimmune diseases. DualityBio has successfully established a number of next generation Antibody-Drug Conjugate (ADC) technology platforms with global intellectual property rights. Building upon deep understanding of disease biology and translational capability, DualityBio has advanced 4 assets into global clinical studies, and developed more than 10 innovative product candidates which are currently in preclinical stage. Additionally, DualityBio is continuing evolving its novel protein engineering and ADC technology platforms for the next wave of “super ADC” molecules including diverse payload classes, bispecific ADCs and dual payload ADCs. 1 Arnold M, Morgan E, Rumgay H et al. Breast. 2022 Dec; 66: 15–23. 2 Smolarz B, Nowak AZ, Romanowicz H. Breast Cancer—Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). Cancers. 2022; 14(10):2569. 3 Harbeck N, et al. Nat Rev Dis Primers. 2019 Sep 23;5(1):66. 4 Tarantino P, Hamilton E, Tolaney SM, et al. J Clin Oncol. 2020 Jun 10;38(17):1951-1962. 5 Modi S, Jacot W, Yamashita T, et al. N Engl J Med. 2022 Jul 7;387(1):9-20. 6 Mark C, Lee JS, Cui X, Yuan Y. Int J Mol Sci. 2023 Sep 6;24(18):13726. 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Designation is based on Phase 1/2 safety and efficacy data in patients with Human Epidermal Growth Factor Receptor 2 (“HER2”)-expressing advanced endometrial cancer with encouraging early signs of anti-tumor activity Breakthrough Therapy designation will allow for an expedited development and regulatory review of BNT323/DB-1303 Endometrial or uterine cancer is the second most common gynecologic cancer globally with over 400,000 cases occurring each year BioNTech SE (Nasdaq: BNTX, “BioNTech”) and Duality Biologics (Suzhou) Co. Ltd. (“DualityBio”) today announced that the U.S. Food and Drug Administration (“FDA”) granted Breakthrough Therapy designation for BNT323/DB-1303 for the treatment of advanced endometrial cancer in patients who progressed on or after treatment with immune checkpoint inhibitors. BNT323/DB-1303 is a next-generation antibody-drug conjugate (“ADC”) candidate targeting the Human Epidermal Growth Factor Receptor 2 (“HER2”), a cell surface protein which is expressed in a range of tumor types. The designation is based on encouraging topline data from a Phase 1/2 study (NCT05150691) with BNT323/DB-1303 in patients with HER2-expressing advanced endometrial cancer. Endometrial or uterine cancer is the second most common gynecologic cancer globally, with over 400,000 cases occurring each year1,2 and both incidence and mortality are increasing3,4. While localized, early disease stages can be cured via surgery, the five-year survival rate for patients with advanced, metastatic or recurrent disease is only 18.4%5. “The Breakthrough Therapy designation for BNT323/DB-1303 shows the potential of our ADC candidate to address current treatment challenges for patients with advanced HER2-expressing endometrial cancer who progressed under several lines of systemic therapy. For these patients the survival rates are still low and the medical need for new and more effective treatments remains high,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. “With the designation and support by the FDA, we seek to expedite further development of BNT323/DB-1303.” “The FDA's decision is an important milestone in the development of our novel differentiated ADC candidate directed at HER2. The HER2 protein overexpression and/or gene amplification is present in approximately 17% to 38%6 of patients with endometrial cancer and more than 50%7 of patients in late disease stage exhibit HER2 overexpression. We believe BNT323/DB-1303 has the potential to serve as a new therapeutic option for patients with HER2 expressing advanced endometrial carcinoma including both patients with high and low expression levels of HER2,” said Vivian Gu, M.D., Chief Medical Officer at DualityBio. “We are committed to advancing BNT323/DB-1303 with the aim to improve outcomes for patients in late disease stages.” Breakthrough Therapy designation is an FDA program designed to expedite the development and regulatory review of investigational therapies that are designed to address serious or life-threatening conditions. To receive the designation, the candidate needs to demonstrate preliminary clinical evidence that indicates that it may offer substantial improvement over existing therapies on one or more clinically significant endpoints. With the Breakthrough Therapy designation, the development of BNT323/DB-1303 may benefit from more frequent engagement with the FDA, which will support the collection of appropriate data needed to accelerate development and may also allow for priority review if the relevant criteria are met. Data presented from the ongoing Phase 1/2 study at ASCO 2023 and ESGO 2023 demonstrated encouraging anti-tumor activity in heavily pretreated patients with advanced endometrial cancer with an unconfirmed objective response rate of 58.8% and an unconfirmed disease control rate of 94.1%. BNT323/DB-1303 was well tolerated with a manageable safety profile across all evaluated patients with advanced/metastatic solid tumors. BNT323/DB-1303 is a third-generation topoisomerase-1 inhibitor-based ADC targeting HER2 which was built from DualityBio’s proprietary Duality Immune Toxin Antibody Conjugates (“DITAC”) platform. HER2 is a surface-expressed protein on solid tumors and has been linked to the aggressive growth and spread of cancer cells, making it a potential target for innovative cancer therapeutics. The candidate has exhibited antitumor activity in both HER2-positive and HER2-low tumor models as well as in several solid tumor indications, including patients with breast, gastric, endometrial, biliary tract cancers, and other advanced solid tumors. Preclinical data and preliminary clinical data for BNT323/DB-1303 indicate its potential to target HER2 on solid tumors irrespective of expression level with a manageable safety profile and a potentially expanded therapeutic window. BNT323/DB-1303 is currently being evaluated in an ongoing Phase 1/2 study (NCT05150691) in patients with advanced/metastatic solid tumors and in a pivotal Phase 3 study (NCT06018337) in patients with Hormone Receptor-positive (“HR+”) and HER2-low metastatic breast cancer that have progressed on hormone and/or cyclin-dependent kinase 4/6 (“CDK4/6”) therapy. Biopharmaceutical New Technologies (BioNTech) is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (“CAR”) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (“ADC”) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, OncoC4, Regeneron, Sanofi and Pfizer. DualityBio is a clinical-stage company focusing on the discovery and development of the next generation ADC therapeutics for patients with cancer and autoimmune diseases. DualityBio has successfully established a number of next generation Antibody-Drug Conjugate (ADC) technology platforms with global intellectual property rights. Building upon deep understanding of disease biology and translational capability, DualityBio has advanced 4 assets into global clinical studies, and developed more than 10 innovative product candidates which are currently in preclinical stage. Additionally, DualityBio is continuing to evolve its novel protein engineering and ADC technology platforms for the next wave of “super ADC” molecules including diverse payload classes, bispecific ADCs and dual payload ADCs. ---- 1 Sung H, Ferlay J, Siegel RL et al. CA Cancer J Clin. 2021 May;71(3):209-249. 2 World Cancer Research Fund International. Endometrial cancer statistics, 2020. Available under: https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics/ (Last access: 19.12.2023) 3 Lortet-Tieulent J, Ferlay J, Bray F, Jemal A. J Natl Cancer Inst. 2018 Apr 1;110(4):354-361 4 Rahib L, Smith BD, Aizenberg R et al. Cancer Res. 2014 Jun 1;74(11):2913-21 5 National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER). Cancer Stat Facts: Uterine Cancer. Available under: https://seer.cancer.gov/statfacts/html/corp.html (Last access: 19.12.2023) 6 Livasy C A, et al. Gynecol Oncol. 2005; 100 (2006):101-106. 7 Grushko TA. Gynecol Oncol. 2008 Jan;108(1):3-9. The content above comes from the network. if any infringement, please contact us to modify.