Our goal of transforming DLL3-positive carcinomas

Neuroendocrine carcinomas (NECs) are highly aggressive cancers that can occur in multiple organs including the lung, gastrointestinal tract, urogenital tract, and skin. These cancers are associated with a poor prognosis and 5-year survival rate ranging between 3-13% in advanced stages^1,2.

Small cell lung cancer (SCLC) is the most common form of NEC and accounts for 13% of all lung cancer cases¹. Both SCLC and extrapulmonary NEC (epNEC) share key attributes which set them apart from many other tumors. These include: late symptom presentation resulting in the majority of patients receiving a late-stage diagnosis, rapid tumor growth rate and progression, and poor prognosis^3,4.

Diagnosis of SCLC and NEC

Receiving a SCLC or NEC diagnosis can be lifechanging and a struggle to accept. These cancers can have a detrimental physical, psychological, and emotional impact on the daily lives of those diagnosed⁵. Current treatment options for advanced NECs include chemotherapy and immunotherapy⁶.

Danielle Hicks, Chief Patient Officer at GO2 for Lung Cancer, commented, “Industry, healthcare professionals, and patient organizations have an opportunity to partner more closely to prioritize SCLC and NECs to ensure that those impacted by these more aggressive cancers get the care they need. There is an urgent need for additional treatment options for the SCLC community as many unmet needs still exist for this population.”

Addressing some of the most challenging, but potentially most impactful areas of cancer research, our robust pipeline comprises homegrown and partnered assets with diverse mode of actions. This includes cancer cell-directed and immuno-oncology investigational therapies. Through this combined approach, we believe that we may offer the greatest benefit for people living with cancer.

Development of a future treatment option

Delta-like ligand 3 (DLL3) is a protein that is expressed specifically on the surface of up to 85% of SCLC tumor cells and around 77% of NECs. In normal tissue, DLL3 is minimally expressed, which makes it an ideal therapeutic target.

In partnership with Oxford BioTherapeutics, we are investigating BI 764532 for the potential treatment of people living with extensive stage small cell lung cancer (ES-SCLC) and epNEC^7,8.  BI 764532 is an investigational T-cell engager that might selectively redirect T cells towards cancer cells expressing the DLL3 protein, potentially resulting in the destruction of SCLC or other NEC tumors by the body’s own immune system.

Evelyn Fahrenkrug, DLL3 Global asset team lead at Boehringer Ingelheim, said, “We are hopeful that we can help bring a targeted immunotherapeutic to people living with SCLC and NEC. As part of our ambition for cancer research, we want to continue to drive progress that delivers life-changing treatments to transform cancer care.”

The Phase I first-in-human dose-escalation trial data were presented during the ASCO 2023 Annual Meeting. In line with our pipeline approach, we have increased our efforts to accelerate its development and recently initiated the DAREON-5 Phase II (ClinicalTrials.gov Identifier: NCT05882058) clinical trial.

As of October 2023, The U.S. Food and Drug Administration (FDA) granted BI 764532 with:

• Fast Track Designations in ES-SCLC with disease progression following at least two prior lines of treatment including platinum-based chemotherapy and for epNEC with advanced or metastatic disease following at least one prior line of treatment including platinum-based chemotherapy.
• Orphan Drug Designation for small cell lung cancer.

This compound is investigational and has not been approved for use by any regulatory authority, including the U.S. FDA. The efficacy and safety of this compound have not been established.

Accelerating progress through strategic collaboration

The successful partnership between Boehringer Ingelheim and Oxford BioTherapeutics was established to discover and develop potential treatment options for cancer. Through the use of Oxford BioTherapeutics' OGAP® platform to identify targets for immunotherapies, we aim to advance therapeutic modalities that depend upon the identification of unique and specific tumor antigens within our cancer immunology portfolio. To learn more about the trial and partnership, read Oxford BioTherapeutics’ press release.

Christian Rohlff, PhD, Chief Executive Officer of Oxford BioTherapeutics, said, “We are delighted about the clinical development for BI 764532 to help address unmet needs for people living with SCLC and NECs. This is an important milestone for our teams and exciting news for the community.”

As part of the broader clinical trial program for BI 764532, additional trials will be initiated in 2023 and 2024.

Read more about our commitment to advancing immuno-oncology and how we are driving innovation in this area.

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¹Lung Cancer Survival Rates. American Cancer Society. Accessed 10.07.23.

²Dasari A, et al. Cancer 2018;4:807-815.

³Robinson MD, et al. Ther Adv Med Oncol 2023;15:17588359231156870.

⁴Basumallik N, et al. StatPearls [Internet] 2023.

⁵Living with Neuroendocrine Cancer. Neuroendocrine Cancer UK. Accessed 30.06.23.

⁶Yao J, et al. Oncologist 2022;27:940-951.

⁷Wermke: BI 764532 ph 1 trial in progress (ASCO 2020 poster) – data on file

⁸Hazini A, et al. J Immunotherapy Cancer 2021

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