NBE-Therapeutics AG

On July 29, Boehringer Ingelheim announced a major acquisition, with plans to buy Nerio Therapeutics for $1.3 billion. Nerio Therapeutics, a pharmaceutical company focused on phosphatase research, has successfully developed highly selective phosphatase PTPN2/N1 inhibitors for an innovative regimen of tumor immunotherapy. With a leading position in the global oncology market, Boehringer Ingelheim has continuously strengthened its strategic presence in oncology in recent years. According to preliminary statistics, the company has established cooperative relationships with a number of well-known pharmaceutical companies in recent years to accelerate the construction of tumor research and development pipelines: In December 2020, Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros to acquire novel antibody-coupled drugs to address the challenge of refractory solid tumors. In the same month, Boehringer Ingelheim acquired Labor Dr. Merk & Kollegen to increase its research and development and clinical manufacturing capabilities to support its next generation cancer immune drug development program. In January 2021, the company entered into a strategic partnership with Enara Bio to develop innovative cancer immunotherapies using its Dark Antigen™ platform. In September 2021, Boehringer Ingelheim acquired Abexxa Biologics to gain expertise in targeting cancer-specific proteins within cells, expanding the range of potential cancer antigen targets. In June 2022, the company entered into A global licensing agreement with the Agency for Science, Technology and Research of Singapore (A*STAR) to acquire the development and commercialization rights for A*STAR's series of innovative tumor-specific antibodies. In January 2023, Boehringer Ingelheim and 3T Biosciences entered into a strategic collaboration and licensing agreement to jointly explore and develop the next generation of cancer therapies. In March 2023, the company partnered with Covant Therapeutics to develop a covalent drug candidate for the ADAR1 cancer target. In November 2023, Boehringer Ingelheim acquired T3 Pharmaceuticals for CHF 450 million (approximately $508 million), which specializes in innovative therapeutic platforms that enhance immunotherapy with live bacteria. In the same month, Boehringer Ingelheim established a strategic collaboration and licensing agreement with Phenomic AI to jointly discover key targets in rich stromal cancers. In February 2024, Boehringer Ingelheim and CBmed entered into a long-term strategic partnership to accelerate the development of first-of-its-kind oncology drugs using translational medicine to improve the lives of patients. In May 2024, Boehringer Ingelheim and OSE expanded their collaboration to jointly develop first-of-its-kind therapies for tumor and cardio-renal metabolic diseases, including the anti-SIRRP α tumor Immunity program and the cis targeted anti-PD1 / cytokine platform. While Boehringer Ingelheim does not yet have a significant oncology product in the market, its oncology pipeline includes several promising candidates, such as Zongertinib(Phase 1), Brigimadlin (Phase two-thirds) and BI-764532 (Phase 2). Zongertinib is an innovative covalently bound, orally effective and selective HER2 small molecule inhibitor. It covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including exon 20 mutations, while preserving the wild-type signal of EGFR, thereby demonstrating good tolerability and safety while ensuring efficacy. Data from the Phase 1a/1b clinical study of Zongertinib monotherapy for HER2-variant advanced solid tumors (NCT04886804), presented at the ASCO meeting in 2024, showed that Zongertinib demonstrated superior efficacy and was well tolerated in patients with HER2-mutation-positive advanced NSCLC. Brigimadlin is a mouse dual microhomologous gene 2 (MDM2) -p53 antagonist targeting MDM2-amplified tumors such as biliary adenocarcinoma, non-small cell lung cancer, and pancreatic cancer. Currently, Brigimadlin's first-line treatment of dedifferentiated liposarcoma (DDLPS) has entered phase 2/3 of clinical trials. New results from the Phase 1a/1b study (NCT03449381) presented at the ASCO Meeting in 2024 show that Brigimadlin induces proteomic changes in DDLPS that may serve as potential biomarkers for predicting treatment response and adverse events. BI 764532 is a first-in-class T cell-mediated bisspecific antibody developed at Boehringer Ingelheim that induces a patient's own T cells to attack cancer cells expressing DLL3. BI 764532 has received fast track approval from the FDA for the treatment of advanced SCLC and advanced or metastatic extrapulmonary neuroendocrine carcinoma. In both DLL3-positive cell and xenograft models, BI 764532 showed potential preclinical antitumor activity. PTPN2 and PTPN1 (also known as PTP-1B) are phosphatases that negatively regulate multiple cytokine signaling pathways and T cell receptor (TCR) signaling pathways. They inhibit inflammation by dephosphorylation of JAK and STAT family members, and reduce T-cell sensitivity to antigens by phosphorylation of LCK and FYN. PTPN2 deletion was found to increase the number of activated cytotoxic CD8+T cells in the tumor, improve antigen presentation and sensitivity to IFNγ, and thus enhance tumor sensitivity to CD8+T cells. Given the critical role of PTPN2/N1 in tumor and immune cells and its highly conserved active sites, researchers are developing PTPN2/N1 inhibitors. Currently, there are several PTPN2/N1 inhibitors, such as ABBV-CLS-579 and ABBV-CLS-484 (AC484). AC484 is an oral PTPN2/N1 active site inhibitor that enhances the response to interferon and promotes the activation and function of immune cell subsets. In a PD-1-resistant mouse model, AC484 monotherapy showed significant antitumor effects. Currently, a Phase 1 clinical trial of AC484 is underway to evaluate its efficacy alone or in combination with PD-1 inhibitors or VEGFR tyrosine kinase inhibitors (TKI) in the treatment of advanced or metastatic solid tumors. In addition, using Chemistry42, its generating-AI platform, Insili has also developed a novel PTPN2/N1 inhibitor that has drug-like properties, good oral bioavailability in vivo, and strong in vivo anti-tumor activity, demonstrating nanoscale inhibitory efficacy.

PRAGUE, Czech Republlic & BEIJING, China I July 16, 2024 I SOTIO Biotech , a clinical-stage biopharmaceutical company owned by PPF Group, and Biocytogen (HKEX: 02315) , a global biotech company focused on the discovery of novel antibody therapeutics, today announced a research collaboration and exclusive option and license agreement. The agreement grants SOTIO the option to license multiple fully human bispecific antibodies generated with Biocytogen’s proprietary RenLite ® platform, which SOTIO will use to develop next-generation antibody-drug conjugates (ADCs) targeting solid tumors. The agreement also includes an option for SOTIO to leverage Biocytogen’s proprietary ADC platform. Biocytogen will be eligible to receive upfront, development, and commercial milestones and royalties on net sales on a product-by-product basis. “SOTIO’s powerful ADC platform brings together multiple technologies, allowing us to tailor our therapeutics to meet the needs of specific cancer types. Specifically, exploiting bispecific targeting in the context of our ADC approaches to improve precision targeting and overcome tumor heterogeneity is particularly appealing,” said Martin Steegmaier, Ph.D., chief scientific officer of SOTIO. “This agreement with Biocytogen complements our existing collaborations with Synaffix, LigaChem, and NBE-Therapeutics, providing SOTIO with access to fully human antibodies from Biocytogen’s state-of-the-art in vivo discovery platform. With the first targets for a bispecific program already selected, we are well-positioned to expand our ADC pipeline and the therapeutic possibilities for patients with solid tumors.” Under the terms of the agreement, Biocytogen is eligible to receive upfront and potential milestone payments worth up to $325.5 million, plus low single-digit royalties on net sales. SOTIO and Biocytogen will collaborate closely during the research phase of the bispecific programs. SOTIO will be responsible for non-clinical and clinical development, manufacturing, and commercialization of the ADC products. “We are eager to deploy Biocytogen’s cutting-edge tools for antibody discovery to support SOTIO’s exciting ADC development plans,” said Yuelei Shen, Ph.D., president and chief executive officer of Biocytogen. “Our unique RenMice ® platforms allow us to discover fully human antibodies with high affinity, low immunogenicity, and favorable developability. We look forward to working with SOTIO to advance novel therapeutics that have the potential to improve cancer treatment.” About SOTIO SOTIO Biotech (SOTIO) is shaping the future of targeted cancer therapies by translating compelling science into patient benefit. The SOTIO pipeline includes three clinical-stage programs: SOT102, a next-generation Claudin-18.2-targeted antibody-drug conjugate; BOXR1030, a metabolically-enhanced CAR-T cell therapy targeting GPC3-expressing tumors; and SOT201, a next-generation PD-1-targeting immunocytokine. SOTIO is a member of the PPF Group. SOTIO is a registered trademark of SOTIO Biotech a.s. in selected countries. For more information, please visit the company’s website at www.sotio.com . About Biocytogen Biocytogen (HKEX: 02315) is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Founded on gene editing technology, Biocytogen leverages genetically engineered proprietary RenMice ® (RenMab TM /RenLite ® /RenNano ® /RenTCR-mimic TM ) platforms for fully human monoclonal/bispecific/multispecific antibody discovery, bispecific antibody-drug conjugate discovery, nanobody discovery and TCR-mimic antibody discovery, and has established a sub-brand, RenBiologics TM , to explore global partnerships for an off-the-shelf library of >400,000 fully human antibody sequences against approximately 1000 targets for worldwide collaboration. As of December 31, 2023, 103 therapeutic antibody and multiple clinical asset co-development/out-licensing/transfer agreements and 47 target-nominated RenMice ® licensing projects have been established around the globe, including several partnerships with multinational pharmaceutical companies (MNCs). Biocytogen pioneered the generation of drug target knock-in humanized models for preclinical research, and currently provides a few thousand off-the-shelf animal and cell models under the company’s sub-brand, BioMice ® , along with preclinical pharmacology and gene-editing services for clients worldwide. Headquartered in Beijing, Biocytogen has branches in China (Haimen Jiangsu, Shanghai), USA (Boston, San Francisco), and Germany (Heidelberg). For more information, please visit http://en.biocytogen.com.cn . SOURCE: SOTIO

Sotio has already selected the first targets for a bispecific program. Sotio has struck a deal to fuse bispecifics with its antibody-drug conjugate (ADC) capabilities, agreeing to pay Biocytogen up to $325.5 million in upfront and milestone fees for rights to targeting molecules.  China’s Biocytogen uses transgenic mice to generate bispecific antibodies. Bispecifics made their name as a standalone drug modality but they can also be conjugated to cytotoxic payloads to create ADCs with a twist. Using antibodies that hit two targets could enable the creation of resistance-busting molecules, as well as candidates with reduced off-target toxicity and greater cancer-killing power.  Sotio has built out its ADC capabilities over the past eight years through deals with NBE-Therapeutics, LegoChem Biosciences and Synaffix. The deals gave the Czech biotech access to conjugation technology, payloads and ADC candidates.  Bispecific targeting molecules are the next piece of the puzzle. Sotio has turned to Biocytogen to fill that gap. The collaboration gives Sotio the option to license multiple fully human bispecific antibodies found using Biocytogen’s RenLite mice. Sotio also has an option to use Biocytogen’s ADC platform. The biotechs will work together during the research phase, after which Sotio will take over for development.   Sotio has already selected the first targets for a bispecific program. Assets that emerge from the deal will slot into a pipeline that now skews heavily toward ADCs. Sotio lists five ADCs in its pipeline but only one has a disclosed target, Claudin18.2, and is in the clinic.  The biotech was focused on cytokines when it put itself on the map with a 280 million euros ($305 million) round in 2018. However, the failure of an IL-15 superagonist set back Sotio’s work on cytokines. The biotech is still looking for combination opportunities for the IL-15 candidate—and developing a next-generation asset that fuses a superagonist to an anti-PD-1 antibody— but ADCs are the star turn.