Boehringer Ingelheim's Cancer R&D Journey: From Acquisitions to Innovative Drugs

On July 29, Boehringer Ingelheim revealed plans to acquire Nerio Therapeutics for $1.3 billion. Nerio Therapeutics is known for its research on phosphatases and has developed highly selective phosphatase PTPN2/N1 inhibitors. These inhibitors are part of an innovative tumor immunotherapy regimen.

Boehringer Ingelheim, a leader in the global oncology market, has been expanding its strategic presence in oncology over recent years. The company has formed partnerships with several well-known pharmaceutical companies to boost its tumor research and development pipeline:

- In December 2020, Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros to secure novel antibody-coupled drugs aimed at treating refractory solid tumors.
- Also in December 2020, the company acquired Labor Dr. Merk & Kollegen to enhance its research, development, and clinical manufacturing capabilities for the next generation of cancer immune drugs.
- In January 2021, Boehringer Ingelheim entered a strategic partnership with Enara Bio to develop innovative cancer immunotherapies using Enara Bio's Dark Antigen™ platform.
- In September 2021, the acquisition of Abexxa Biologics brought expertise in targeting cancer-specific proteins within cells, broadening the range of potential cancer antigen targets.
- In June 2022, Boehringer Ingelheim secured a global licensing agreement with the Agency for Science, Technology and Research of Singapore (A*STAR) to develop and commercialize innovative tumor-specific antibodies.
- In January 2023, a strategic collaboration and licensing agreement with 3T Biosciences was established to explore next-generation cancer therapies.
- In March 2023, the company partnered with Covant Therapeutics to develop a covalent drug candidate targeting ADAR1 in cancer treatment.
- In November 2023, Boehringer Ingelheim acquired T3 Pharmaceuticals for CHF 450 million (approximately $508 million), focusing on innovative therapeutic platforms that enhance immunotherapy with live bacteria.
- That same month, a strategic collaboration and licensing agreement with Phenomic AI was formed to discover key targets in rich stromal cancers.
- In February 2024, Boehringer Ingelheim and CBmed entered a long-term strategic partnership to accelerate the development of novel oncology drugs using translational medicine.
- In May 2024, Boehringer Ingelheim and OSE expanded their collaboration to develop therapies for tumor and cardio-renal metabolic diseases, including the anti-SIRRP α tumor immunity program and the cis-targeted anti-PD1/cytokine platform.

Although Boehringer Ingelheim does not yet have a major oncology product on the market, its pipeline includes several promising candidates, such as Zongertinib, Brigimadlin, and BI-764532.

Zongertinib is an innovative, orally effective, and selective HER2 small molecule inhibitor. It binds covalently to the tyrosine kinase domain of both wild-type and mutant HER2 receptors, preserving the wild-type signal of EGFR, thus showing good tolerability and safety. Data from a Phase 1a/1b clinical study of Zongertinib monotherapy for HER2-variant advanced solid tumors presented at the ASCO meeting in 2024, indicated superior efficacy and good tolerability in patients with HER2-mutation-positive advanced NSCLC.

Brigimadlin targets MDM2-amplified tumors such as biliary adenocarcinoma, non-small cell lung cancer, and pancreatic cancer. It is currently in Phase 2/3 clinical trials for the first-line treatment of dedifferentiated liposarcoma (DDLPS). New results from a Phase 1a/1b study presented at the ASCO Meeting in 2024 showed 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 bispecific antibody that induces a patient's own T cells to attack cancer cells expressing DLL3. It has received fast-track approval from the FDA for the treatment of advanced small cell lung cancer (SCLC) and advanced or metastatic extrapulmonary neuroendocrine carcinoma. In both DLL3-positive cell and xenograft models, BI 764532 demonstrated 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. Their inhibition enhances tumor sensitivity to CD8+T cells by increasing the number of activated cytotoxic CD8+T cells in the tumor and improving antigen presentation. Researchers are developing PTPN2/N1 inhibitors such as ABBV-CLS-579 and ABBV-CLS-484 (AC484). AC484, an oral PTPN2/N1 active site inhibitor, enhances response to interferon and promotes immune cell activation. Currently, a Phase 1 clinical trial is evaluating AC484's efficacy in treating advanced or metastatic solid tumors.

Moreover, Insili has developed a novel PTPN2/N1 inhibitor using its generating-AI platform, Chemistry42. This inhibitor has shown drug-like properties, good oral bioavailability, and strong in vivo antitumor activity, demonstrating nanoscale inhibitory efficacy.

Boehringer Ingelheim's relentless pursuit of innovative cancer therapies underscores its commitment to improving patient outcomes and solidifying its leadership in the oncology market.