Boehringer Ingelheim Looks to Expand Targeted Therapies Portfolio

Pipeline Report | <b>Pipeline Report: December 2020</b>

January 5, 2020 - Boehringer Ingelheim will add to its cancer cell-directed therapies portfolio with the acquisition of NBE-Therapeutics, the developer of NBE-002, an anti-ROR1 antibody-drug conjugate.

Boehringer Ingelheim will add to its cancer cell-directed therapies portfolio with the acquisition of NBE-Therapeutics, the developer of NBE-002, an anti-ROR1 antibody-drug conjugate (ADC). The deal is expected to be completed in the first quarter of 2021 and is valued at $1.4 billion.1

As a result of the deal, Boehringer Ingelheim will gain access to NBE-Therapeutics’ immune-oncology development pipeline, including its proprietary enzymatic conjugation platform. This technology allows for the site-specific attachment of small molecule drugs to monoclonal antibodies.

NBE-Therapeutics’ next-generation ADCs comprise a highly potent derivative of the anthracycline toxin PNU-159682. The novel ADCs are equipped with stable peptide linkers that connect the highly potent payload to the antibody, which is only released upon binding to the cognate target in tumor cells and internalization and intracellular linker cleavage.2

“I am extremely proud of the NBE-Therapeutics’ team and delighted that our world class ADC expertise is being recognized by Boehringer Ingelheim. This transaction is a validation of our platform and its potential for the next-generation cancer therapies,” Bertrand Damour, CEO of NBE-Therapeutics, stated in a press release. “We look forward to progressing NBE-002, our lead program and best-in-class anti-ROR1 ADC, and to continuing the fight against cancer alongside Boehringer Ingelheim with its strong clinical development capabilities.”

The leading agent offering from the company is NBE-002, an ADC that was designed to target ROR1, which plays a fundamental role in cardiorespiratory, neurological, and skeleton development;3 it is more commonly detected in the absence of normal adult tissue and is observed during embryonic and fetal development. However, type-I transmembrane protein has been identified in several hematologic and solid malignancies, with a significant prevalence in various solid tumors, making it a promising immunotherapeutic target.

The agent demonstrated preclinical activity in patient-derived xenograft models of triple-negative breast cancer (TNBC), lung adenocarcinoma, ovarian carcinoma, and other sarcomas.4 Specifically, the ADC was found to have the highest efficacy in the TNBC model, resulting in complete tumor regression at the lowest dose level examined, which was 0.33 mg/kg. Investigators noted that combining NBE-002 with checkpoint inhibition, such as α-PD1 or α-CTLA4, significantly enhanced tumor eradication following initial treatment.

In October 2020, NBE-Therapeutics announced the commencement of the first-in-human clinical study of the novel anti-ROR1 agent, NBE-002.5 The phase 1/2 trial (NCT04441099) will evaluate 100 patients with advanced solid tumors to determine the recommended phase 2 dose of the agent based on dose-limiting toxicity data as well as antitumor activity.

To be eligible for participation on the phase 1 study, patients must have histologically or cytologically confirmed advanced solid tumor (carcinoma or sarcoma), have progressive disease, have undergone systemic therapy for advanced disease, and have no standard therapy available to them. NBE-002 will be administered intravenously on day 1 of repeated 21-day treatment cycles.

Expansion cohort criteria for phase 2 of the study will include patients with histologically or cytologically confirmed advanced TNBC, who have progressive disease, and have received no more than 3 prior lines of systemic therapy for advanced disease. A second expansion cohort will include all other patients with histologically or cytologically confirmed advanced solid tumor other than TNBC.

The trial has already treated a patient at the third dose level, according to press release issued by NBE-Therapeutics. Initial study results are expected in 2021.5

References

1. Boehringer Ingelheim to Acquire NBE-Therapeutics for $1.4 Billion. BioPharm International. December 11, 2020. Accessed December 17, 2020. https://www.biopharminternational.com/view/boehringer-ingelheim-to-acquire-nbe-therapeutics-for-1-4-billion

2. Immune oncology. NBE-Therapeutics. Accessed December 17, 2020. https://www.nbe-therapeutics.com/technology/immune-oncology

3. Schiavone G, Epistolio S, Martin V, et al. Functional and clinical significance of ROR1 in lung adenocarcinoma. BMC Cancer. 2020;20(1):1085. doi:10.1186/s12885-020-07587-6

4. Beerli RR, Waldmeier L, Gébleux R, Pretto R, Grawunder U. NBE-002, an anthracycline-based immune-stimulatory antibody drug conjugate (iADC) targeting ROR1 for the treatment of triple-negative breast cancer. Cancer Res. 2019;79(suppl 13):LB-197. doi:10.1158/1538-7445.AM2019-LB-197

5. NBE-Therapeutics commences first clinical study of anti-ROR1 antibody-drug conjugate for patients with solid tumors. News release. NBE-Therapeutics. October 26, 2020. Accessed December 17, 2020.