Boehringer Ingelheim has further expanded its immuno-oncology pipeline by shelling out up to €325 million ($364.9 million) to acquire Swiss-owned AMAL Therapeutics, a developer of first-in-class cancer vaccines based on its KISIMA® technology platform.

AMAL’s lead vaccine candidate, ATP128, is a chimeric recombinant protein vaccine being developed for stage IV colorectal cancer, and set to begin first-in-human trials later this month.

ATP128 will be studied as monotherapy and in combination with Boehringer Ingelheim’s monoclonal antibody PD-1 antagonist BI 754091, a T-lymphocyte checkpoint inhibitor, using safety and tolerability as primary endpoints.

The study, called KISMA-01, will also measure anti-tumor activity and characteristics of the immune response as secondary and exploratory endpoints. AMAL announced plans for KISMA-01 on May 2.

AMAL’s pipeline also includes a preclinical candidate in lead optimization phase for an undisclosed indication.

“Acquiring AMAL is part of Boehringer Ingelheim’s long-term strategy to enhance our existing position as an innovator of novel cancer therapies, including immuno-oncology treatments,” Michel Pairet, member of Boehringer Ingelheim’s Board of Managing Directors with responsibility for the company’s Innovation Unit, said Monday in a statement.

“We want to pioneer new paradigms of biology-based care for cancer patients, and the technologies and expertise developed at AMAL are critical to our efforts,” Pairet added.

Initial seed investor

Boehringer Ingelheim’s venture fund joined High-Tech Gründerfonds as initial seed investors of AMAL in 2012, when they joined a syndicate of corporate and institutional investors to spin out AMAL in 2012 from the University of Geneva. AMAL is still based at the University’s medical campus.

In acquiring AMAL, Boehringer Ingelheim said it plans to develop new therapies that combine assets from its cancer immunology portfolio with AMAL’s KISIMA platform.

Boehringer Ingelheim said KISMA technology offered a promising therapeutic option for patients with non-inflamed, “cold” tumors, representing cancer types refractory to checkpoint inhibitor drugs and many other treatments. Developing cold-tumor treatments has been complicated by the difficulty of immune targeting—the challenge that Boehringer has sought to overcome through the therapies discovered by its Cancer Immunology group.

KISMA—derived from the Swahili word for “well”— is a self-adjuvanting, peptide/protein-based immunization technology designed to enable the assembly within one chimeric fusion protein of three elements deemed essential to generating potent immunity: a proprietary cell-penetrating peptide for antigen delivery, a proprietary toll-like receptor (TLR) peptide agonist as adjuvant, and a modulable multi-antigenic cargo that can be tailored for various indications.

Boehringer Ingelheim said KISMA will support its focus on developing therapies for hard-to-treat gastrointestinal and lung cancers. While AMAL has focused the platform on oncology, the company has planned to expand beyond cancer into infectious diseases.

One of three “pillars”

Cancer vaccines and oncolytic viruses make up one of three “pillars” of Boehringer Ingelheim’s approach to oncology treatments, Ioannis Sapountzis, PhD, corporate senior vice president, business development & licensing with Boehringer Ingelheim, told GEN in June. The other two are T-cell engagers or TCEs, and new mechanisms for immune regulatory receptors.

The AMAL acquisition is Boehringer Ingelheim’s latest of several deals over the past year that were designed to strengthen its cancer vaccine pillar. In September 2018, the company exercised its option to buy ViraTherapeutics for €210 million ($235.7 million), in a deal that gave Boehringer full control over a preclinical viral-based cancer immunotherapy the companies have been co-developing for two years.

Five months earlier in April 2018, Boehringer Ingelheim launched a potentially more than €1.1 billion ($1.2 billion) collaboration with OSE Immunotherapeutics to develop OSE’s late-preclinical-stage candidate then known as OSE-172 (Effi-DEM), a novel checkpoint inhibitor antibody designed to treat solid tumors.

Boehringer and OSE last month announced the dosing of the first patient in a first-in-human Phase I clinical trial (NCT03990233) assessing the candidate, now called BI 765063. The myeloid checkpoint inhibitor is a first-in-class monoclonal antibody antagonist of SIRPα that is being studied in patients with advanced solid tumors, both as monotherapy and in combination with Boehringer Ingelheim’s monoclonal antibody PD-1 antagonist BI 754091, a T-lymphocyte checkpoint inhibitor.

Boehringer will pay €15 million ($16.8 million) in milestone payments to OSE based on achieving the first-patient dosing and a clinical trial authorization obtained in March.

In acquiring all shares of AMAL, Boehringer Ingelheim agreed to pay €225 million ($252.6 million) consisting of an upfront payment and payments tied to achieving clinical, development, and regulatory milestones—as well as up to €100 million ($112.3 million) tied to achieving commercial milestones.

“Our new relationship with Boehringer Ingelheim will enable us to realize the full potential of our KISIMA platform to fight solid cancers while preserving AMAL’s approach to biotechnology research and our scientific and academic networks,” stated Madiha Derouazi, PhD, founder and CEO of AMAL Therapeutics. “Moreover, sharing resources and capabilities in clinical development will greatly help us to move ATP128 and other assets forward.”

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