NBE Therapeutics and SOTIO Collaborate in the Development of the Next-Gen ADC

Capped vials on an analysis autosampler - selective focus

NBE Therapeutics, a privately owned Swiss, Basel-based Biotech company, and SOTIO, a biotechnology company located in Prague, Czech Republic, with facilities in Europe, the United States, China and Russia and a focus on the development of new Active Cellular Immunotherapy based on activated dendritic cells for the treatment of cancer and autoimmune diseases as well as other targeted therapies, have entered into a strategic collaboration for the development of next-generation antibody-drug conjugates or ADCs for improved cancer therapy.

Under the terms of the agreement, NBE Therapeutics and SOTIO collaborate on the discovery, non-clinical development and manufacturing of novel ADC products against several undisclosed targets. The ADC products will be based on NBE’s proprietary antibody discovery and conjugation platforms, including NBE’s Transpo-mAb™ antibody platform, its site-specific SMAC-Technology™ (sortase- mediated antibody conjugation technology) and its novel ultra-potent anthracycline-based toxin platform. SOTIO will have global responsibility for clinical development, registration and commercialization of the novel ADC products.


“…this partnership validates our antibody-drug conjugate platform and will allow us to further expand our ADC product pipeline…”


A different approach
With two approved antibody-drug conjugates (brentuximab vedotin /Adcetris®; Seattle Genetics approved in 2011 and ado-trastuzumab emtansine or T-DM-1/Kadcyla® approved in 2013) and 60 investigational ADCs in clinical trials industry-wide, researchers have been successful in the development of novel, effective ADCs.  Being highly potent anti-tumor drugs, ADCs typically exceed the efficacy of traditional chemotherapy or conventional antibodies.

ADC Bio
MabPlex
Lonza
 

However, it still remains a significant challenge to conjugate small molecule cytotoxins to monoclonal antibodies. For optimal therapeutic effect, the small molecular weight cytotoxic payload needs to be tightly coupled to an antibody while at the same time requiring specific release upon binding and internalization into the targeted tumor cells.[1]

In the currently approved ADCs and ADCs in clinical development, the attachment is effected by chemical conjugation involving linkers that attach to a small-molecule cytotoxin to the antibody through lysine or cysteine side chains. Because antibodies contain many lysine and cysteine residues this results in a heterogeneous mixture of ADCs.[1]

One of the problems researchers encounter is that this approach does neither allow for the control of coupling site nor coupling ratio. This, in turn, results in challenges in characterization, analytics, manufacturing and regulatory approval. One reason, analytics has shown, is that this process generates mixtures of antibody-drug conjugates with variations in coupling site and number of cytotoxins coupled to individual antibodies.[1]

Furthermore, variations in coupling site and number of cytotoxins coupled to individual antibodies can potentially negatively impact efficacy and integrity of the antibody function in an antibody-drug conjugate. Researchers have recognized this and are working on a variety of approaches to better control of chemical conjugation of cytotoxic payloads to antibodies. However, the majority of these approaches still rely on optimized chemical conjugation.[1]

In an attempt to change this, researchers at NBE-Therapeutics have developed a unique enzyme-technology platform based on the S. aureus sortase A-mediated transpeptidation reaction.  This technology platform allows for the efficient generation of ADCs with small molecule cytotoxins conjugated to pre-defined sites at pre-defined drug-to-antibody ratios (DAR).  The enzymatic reaction used allows for mild conjugation conditions and keep the structure of the antibody fully intact. [1]

Strategic Collaboration
“We are excited about entering a strategic collaboration with SOTIO. This partnership validates our ADC platform and will allow us to further expand our ADC product pipeline. SOTIO’s proven clinical development expertise will help us to develop our ADC platform to the next level,” noted Ulf Grawunder, Ph.D, CEO of NBE Therapeutics.

“NBE Therapeutics’ product platform addresses the key issues of today’s antibody-drug conjugates. With the very strong preclinical data generated by NBE Therapeutics that show superiority in terms of potency, safety and product homogeneity, as well as strong immunotherapeutic effects, this platform has the potential to provide new superior treatment options for cancer patients,” Ladislav Bartoníček, MBA, CEO of SOTIO, added.

Partnership
As part of the agreement, the PPF Group, the owner of SOTIO with assets exceeding EUR 21.6 billion, has committed to invest CHF 10 million in the next financing round of NBE Therapeutics. The company is also financially backed by the Boehringer Ingelheim Venture Fund and additional private investors.

Upon exercise of the target options, NBE Therapeutics will be eligible for an option exercise fee, as well as milestone payments and royalties based on global net sales of the products. In addition, NBE will be reimbursed for its R&D expenses incurred in connection with the development of the product in collaboration with SOTIO.