SHANGHAI Epimab Biotherapeutics Inc., of Shanghai, inked its first licensing deal for its bispecific antibody platform technology to one of China's rising biopharma stars, Innovent Biologics Inc., of Suzhou. Epimab's technology, called Fabs-In-Tandem Immunoglobulin (FIT-Ig), approaches the creation of new bispecific antibodies making use of existing monoclonal antibodies (MAbs) with proven biology.
The deal gives Innovent the ability to develop an unspecified number of bispecific antibodies for the China market and to out-license those candidates globally using FIT-Ig technology. In return, Epimab received an undisclosed up-front payment and stands to gain milestone payments and royalties valued at a potential $120 million.
Epimab intends to develop its own bispecific antibody pipeline assisted by the revenues it generates from licensing deals like this one.
Epimab was established in February 2015, coming out of stealth last month in May. Founder Chengbin Wu is an experienced biotech leader in China known for his role at CP Guojian Pharmaceutical Co., as chief scientific officer and president of R&D, and for establishing advanced biologics capabilities at CRO, Shanghai Chempartner. But the idea behind Epimab stems from Wu's even earlier work at Abbott Laboratories, of Chicago, where he was the primary inventor of DVD-Ig technology, a bi-specific antibody platform for developing next generation biologics therapies.
When Wu invented FIT-Ig as a new format for bispecific antibodies, he did so "knowing the limits of the format he had invented previously," Stephan Lensky, CBO and COO of Epimab, told BioWorld Asia.
"This new format is very simple, it is allows one to cut and paste two known antibodies together and the amazing thing the properties of the antibodies conserve their original features. It makes it extremely viable that these molecules can reach the clinic," explained Lensky. "Wu cracked a major problem in the bispecific arena: how to make a bispecific antibody go into the body like one, be soluble like one, but is able to function like each of them simultaneously."
Wu raised $2.5 million from angel investors in the U.S., China and Europe on the strength of his FIT-Ig platform. The main angel investor, Robert Kamen currently entrepreneur-in-residence at Third Rock Ventures knows Wu well having worked with him back in their Abbott days where Kamen oversaw the Humira program.
Bispecific antibodies have been around for over a decade and hold numerous advantages over monoclonal antibodies, with the potential to be more cytotoxic binding to two antigens as opposed to monoclonal antibodies which bind to one and cheaper to manufacture since their enhanced effectiveness requires lower doses and thus less antibodies to manufacture. But constructing a successful bispecific antibody with drug-like qualities has been a challenge. To date only Amgen Inc.'s Blincyto (blinatumomab) for Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (ALL) has been approved by the FDA.
Even minor modifications to an antibody can significantly alter its binding properties, pharmacokinetics, stability, solubility or the ability to manufacture the molecule in sufficient amounts. Many bispecific technologies rely on significant modifications to the basic structural elements of an antibody. They may insert mutations to the Fc-domain, or omit it entirely, and they may add less stable single chain fragments (scFv's), or linkers, that can change the overall stability or enhance immunogenicity.
SIMPLE DNA APPROACH
Epimab's FIT-Ig technology uses another approach. By re-arranging the DNA sequences of two existing monoclonal antibodies into three constructs and co-expressing them in mammalian cells, Epimab generates bispecific FIT-Igs that fully retain the biological function of their parental monoclonal antibodies. This approach is characterized by simplicity and allows for flexibility. It does not require Fc mutation, does not use scFv elements or linker or peptide connectors. The Fab-domains in each arm work in tandem forming a tetravalent bispecific antibody with four active and independent antigen binding sites.
With simplicity comes speed and also ease of use. "You need the sequence information of the original two antibodies. . . . Any experienced molecular biologist with a bit of knowledge in this area can actually use this format to make bispecific antibodies," said Lensky. "We actually can get up to 100 mg or more of bispecific antibody within four to six weeks if we know the sequence of the original antibody. In the bispecific antibody space this is unheard of."
Innovent is hoping this speed will also work for them.
Last year, Innovent moved into bispecifics in a big way with a $1 billion deal with Eli Lilly and Co. involving three anti-PD1 based bispecific antibody molecules for cancer. (See BioWorld Today, Oct. 14, 2015.)
The deal with Epimab is not connected to this deal but "will be an independent approach to develop bispecific molecules," said Blake Salisbury, vice president of business development at Innovent.
The Epimab technology "accelerates our ability to develop new entities. Innovent seeks to discover improved molecules compared to existing treatments and bispecifics are one good approach to achieve this innovation goal," he added.
PLANS TO EXPAND QUICKLY
Epimab, which has adopted the Cayman-registration model common for foreign invested companies in China, has set up its lab in Shanghai's Zhangjiang Hi-tech park, a bustling hub of biopharma activity. The company plans to raise a series A financing by the end of this year. Currently, a two-man show, Epimab looks set to grow quickly. (See BioWorld Today, March 23, 2016.)
According to Lensky, the main goal is to discover bispecific antibodies based on their proprietary format then to develop at least two molecules to clinical proof of concept (early phase II) in oncology and inflammation and then exit the assets either by licensing, selling or IPO.
Bispecifics have a role to play in combination therapies making them especially attractive in immuno-oncology trials. The opportunities further multiply given that Epimab can potentially partner numerous assets given the sheer quantity of possible bispecific antibodies they can discover.
"[FIT-lg] is an extremely powerful tool to explore the bispecific world. Imagine you have 50 therapeutic antibodies: You can actually make 50 multiplied by 49 bispecific antibodies. Just imagine each will have different types of properties you can explore it is opening up a new era," said Lensky. "It is important for us to acknowledge we cannot do them all. Our intention is to find capable partners that can bring more molecules to IND to validate the platform. The more molecules that get out there, the better it is for patients at the end of the day."
However, one concern will be navigating the complicated world of IP when combining two existing MAbs. The antibody patent is determined on the binding sequence regardless of the format which could mean that Epimab bispecifics will only be able to marketed at the end of the original antibodies patent life.