PTPN2

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.

INGELHEIM, Germany and LA JOLLA, CA, USA I July 29, 2024 I Today marks a significant step for Boehringer Ingelheim’s immuno-oncology pipeline as the company is adding an innovative preclinical program with the acquisition of Nerio Therapeutics Inc. (“Nerio”) for a total of up to USD 1.3 billion. Boehringer Ingelheim aims to develop this program as a potential key centerpiece component for its immuno-oncology portfolio to achieve its aim of improving cancer patient outcomes. Nerio’s small molecules inhibit the protein tyrosine phosphatases N1 and N2 (PTPN1 and PTPN2), which act as immune checkpoints. Through this mechanism, PTPN1/2 inhibition can activate the immune system to fight cancer cells. Immune checkpoint blockade with current checkpoint inhibitors has transformed the cancer treatment landscape. However, while this approach works for some patients, it does not provide a therapeutic benefit for all.  Boehringer Ingelheim is committed to changing this paradigm and extending the benefits of immuno-oncology to more cancer patients with a comprehensive portfolio of therapies based on immune checkpoint blockade to boost the immune system and direct it toward cancer cells. Nerio’s small molecule inhibitors will be an important addition to Boehringer Ingelheim’s portfolio with the potential to act as a single agent therapy and, importantly, in combination with many cancer therapies already being developed in-house. “Securing the rights to Nerio Therapeutics’ novel checkpoint inhibitors creates a broad panel of exciting new cancer treatment combination opportunities. This brings us a major step closer to our vision of transforming the lives of people living with cancer,” said Paola Casarosa, Member of the Board of Managing Directors at Boehringer Ingelheim with responsibility for the Innovation Unit. Sanford Madigan, partner at Avalon BioVentures, L.P. and co-founder and CEO of Nerio Therapeutics, shares this excitement stating, “We believe Nerio’s small molecule PTPN1/N2 inhibitors have superior drug-like properties and provide a first-in-class opportunity. We are excited to expand Boehringer Ingelheim’s pipeline and commend their commitment to unlock the full potential of our compounds and their mechanistically unique approach to fighting cancer.” This acquisition is a bold step toward transforming cancer care. It further strengthens Boehringer Ingelheim’s oncology pipeline of cancer cell-directed and immuno-oncology investigational therapies for smart combinations that may offer the greatest benefit for people living with cancer. About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at. www.boehringer-ingelheim.com . About Nerio Therapeutics Nerio Therapeutics, Inc. is a drug discovery and development company focused on phosphatases, a notoriously difficult class of potentially high-value therapeutic protein targets. Nerio has developed novel, potent, and highly selective PTPN2/N1 inhibitors with excellent drug-like properties. Nerio’s first-in-class PTPN2/N1 inhibitors enhance immune function and sensitize tumors to pro-inflammatory signals, promoting robust anti-tumor activity. Nerio was founded by Avalon Ventures and had additional financial support from a syndicate including Bregua Corporation, Correlation Ventures, Alexandria Venture Investments and Viva BioInnovator.  Nerio was developed in the Avalon BioVentures accelerator, benefiting from their resident expertise in early-stage drug development and comprehensive company support. SOURCE: Boehringer Ingelheim

Boehringer Ingelheim has acquired California biotech Nerio Therapeutics, picking up a preclinical novel immune checkpoint inhibitor in what the drugmaker is calling a "significant step" for its immuno-oncology pipeline. In a deal that Boehringer says is worth a total of $1.3 billion, the German drugmaker will secure the rights to Nerio’s small molecules, which inhibit the protein tyrosine phosphatases N1 and N2 (PTPN1 and PTPN2), which act as immune checkpoints. Through this mechanism, PTPN1/2 inhibition can activate the immune system to fight cancer cells. According to Boehringer, the company aims to develop the program as a "potential key centerpiece component for its immuno-oncology portfolio" in order to improve cancer patient outcomes. Boehringer Ingelheim laid out bold goals for the company in its 2023 earnings report, shared this past April , aiming for 25 new treatment launches by 2030. Back in June , the drugmaker revealed positive results from a phase 2 trial of survodutide, co-invented with Zealand Pharma, in metabolic dysfunction-associated steatohepatitis (MASH). The drug is being evaluated in five phase 3 trials for obesity, but the partners are betting on it becoming a best-in-class treatment for MASH/NASH.