Technology

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Mangifygen, Inc owns worldwide exclusive rights to the “immunogenicity-abolished anti-ROR1 immunotoxin” technology for treatment of various kinds of cancer, especially Triple-negative breast cancer or TNBC.

ROR1 - a novel universal marker for cancer therapy.

Most cancer markers are also present on normal cells in small quantity, making drugs targeting those markers toxic to normal cells. ROR1 is one exceptional marker because: (1) It is only expressed at embryonic stage and is not present in any adult tissues. (2) It is highly expressed by almost any type of cancer. So in theory, a highly effective drug targeting ROR1 could be used to treat most types of cancers without noticeable side effects.

For example, ROR1 is highly expressed by TNBC, the most difficult-to-treat breast cancer type.

ROR1-staining
ROR1 is highly expressed in TNBC (B) but not in normal breast tissue (A).

Immunotoxins back to life.

Immunotoxin is a kind of therapeutic drug comprising an antibody linked to a toxin. The antibody part binds to cancer markers such as ROR1 and brings the toxin part to cancer cells. The toxin enters cancer cells and kills them. Its mechanism is analogous to a missile: the antibody is the guiding system and the toxin is the warhead. They work together to demolish targets (cancer cells) precisely and effectively.

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Anti-ROR1 Immunotoxin targets ROR1-expressing cancer cells similar to a missile.

Immunotoxin is an “old” technology that has been around for many years. The biggest challenge for immunotoxin technology is immunogenicity of the toxin part. The toxin protein is “foreign” to human body and can illicit neutralizing antibodies that reduce the drugs’ half-lives. This technical issue has been solved with Magnifygen’s state-of-the-art “immunogenicy-abolished” toxin. Magnifygen's next-generation immunotoxins containing the new version of toxin are NONE immunogenic, which “revives” the immunotoxin technology, similar to “humanization” revived therapeutic mouse monoclonal antibody technology.

ROR1-targeing drug candidate IT-4 for treatment of TNBC.

About 15-20% of breast cancer patients are TNBC type. Currently there is no effective therapy for TNBC, making it the most deadly type of breast cancer.

The anti-ROR1 immunotoxin drug candidate IT-4 developed by Magnifygen showed excellent anti-TNBC activity both on TNBC cancer cells and in TNBC mouse models. When a few additional IND-enabling experiments are finished, IT-4 will be ready for human clinical trials.

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Drug candidate IT-4 kills ROR1+ TNBC cell line HS578T effectively, but spares ROR1- breast cancer cell line BT474.

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Mice with TNBC xenograft are treated with IT-4 or a negative control immunotoxin. Tumor in control group keeps growing, while IT-4 treated group shows apparent tumor recess.

Market Potential of IT-4

We predict market potential of IT-4 is about $1.7 billion per year in the US alone. IT-4 can also be used to treat other cancer types, such as lung, prostate, colon, ovary and pancreatic cancers, total market potential is over $10 billion per year in the US alone.