Boehringer Ingelheim plans to develop new immuno-oncology treatments for an undisclosed number of targets using PureTech Health’s lymphatic targeting technology for immune modulation, through a collaboration that PureTech said today could generate for it more than $226 million.
The companies will initially focus on applying PureTech’s internally-developed lymphatic targeting platform to an unspecified Boehringer Ingelheim immuno-oncology candidate for gastrointestinal (GI) cancers that is administered directly to the gut lymphatics, PureTech said.
PureTech specializes in developing novel medicines for dysfunctions of the Brain-Immune-Gut (BIG) axis. The company’s platform is designed to harness the gut’s lipid transport mechanisms to enable oral administration and transport of drug candidates directly through the gut-draining lymphatic vasculature, also bypassing first pass metabolism in the liver.
Specifically, the company’s therapeutic candidates are directed to the mesenteric lymph nodes, which program as many as 70% of circulating adaptive immune cells. By targeting the lymphatic system directly, PureTech reasons, its proprietary technology could achieve more effective and precise immunomodulation of local tissues, while sparing patients from the risks of extensive systemic exposure to the drug.
PureTech’s lymphatic targeting approach is based on the research of Chris Porter, PhD, director of the Monash Institute of Pharmaceutical Sciences (MIPS) at Monash University.
According to its website, Porter’s lab aims to use drug delivery technologies:
- To overcome limitations to drug absorption resulting from low drug solubility
- To target drugs to the lymphatics (a site rich in immune cells and tissues and therefore a site of action for many immunotherapeutics)
- To better understand the mechanisms by which drugs are trafficked specifically to critical organelles within the cell
- To design nanomaterials to better target drug delivery to a range of diseases, including cancer
Promise beyond cancer
The targeting approach developed by Porter’s lab can potentially be applied to therapeutic molecules across a range of physiochemical properties and holds promise for the development of novel therapeutics for gastrointestinal, central nervous system, and autoimmune diseases as well as cancer, according to the company.
In cancer, PureTech presented two posters at the recent 2019 American Association for Cancer Research (AACR) Annual Meeting in Atlanta detailing the company’s development of two immuno-oncology candidates targeting solid tumors—first-in-class, fully-human monoclonal antibodies targeting Galectin-9 (LYT-200) and immunosuppressive γδ1 (gamma delta) T cells (LYT-210).
LYT-200 and LYT-210 are designed to target foundational, novel mechanisms of tumoral immune escape and immunosuppression in cancer. The two candidates have been tested as monotherapy, as well as in combination with PD-1 inhibitors in preclinical murine and human-derived ex vivo models, PureTech said.
During AACR, Boehringer Ingelheim highlighted several of its cancer candidates, including: BI 905677, a novel highly potent and selective LRP5/6 antagonist now in a Phase I trial (NCT03604445) in patients with advanced cancers; BI 907828, a novel MDM2-p53 antagonist also in a Phase I trial involving patients with advanced or metastatic solid tumors (NCT03449381); and BI 905711, a novel CDH17-targeting TRAILR2 agonist for which preclinical results were presented at the meeting.
Access to tumor targets
On March 29, Boehringer Ingelheim also signaled growing interest in cancer drug development by acquiring Berlin-based ICD Therapeutics for an undisclosed price. The deal gave Boehringer Ingelheim rights to ICD’s MacroDelbiologics-delivery platform, believed to facilitate access to targets inside tumor cells, for use in novel therapeutics in collaboration with a former ICD shareholder, nanoPET Pharma.
Boehringer Ingelheim has agreed to pay PureTech up to $26 million in upfront payments, research support, and preclinical milestone payments—as well as more than $200 million in payments tied to achieving development and sales milestones, plus royalties on product sales.
Once product candidates enter the development stage, Boehringer Ingelheim has agreed to assume full responsibility for development, PureTech added.
Headquartered in Boston with labs in Cambridge, MA, PureTech has launched partnerships with more than 70 research investigators based at numerous institutions and eight biopharma giants, including Amgen, Eli Lilly, Johnson & Johnson, Merck KGaA, Novartis, Pfizer, Roche, and Shire (now Takeda Pharmaceutical). PureTech plans to release full-year 2018 results on April 24.
“This collaboration signals the exciting potential of another proprietary platform from our internal R&D to enable novel immunotherapy approaches by harnessing the lymphatic system’s capacity for immune cell trafficking and immunomodulation,” PureTech co-founder and CEO Daphne Zohar said in a statement. “We look forward to working with the excellent scientific teams at Boehringer Ingelheim to advance this important program, which has the potential to greatly expand therapeutic options for patients with cancer.”