Antibody Therapeutics for Life

Products

TTAC-0001

In the absence of oxygen, the tumor pours an excess of VEGF into the surrounding tissuestumor microenvironment for survival.
Excess VEGF released from the tumor cells is then removed moves to pre-existing vessels and binds to from the vascular endothelial
growth factor receptor (VEGF receptor), especially VEGFR2 on vascular endothelial cells (VEGF receptor, VEGFR2), and eventually
generates new vessels surrounding tumor, which is a member of the vascular endothelial growth factor receptor 2 (VEGFR2).
We call this a series of angiogenesis processes called tumor angiogenesis. These blood vessels function as a transport pathway for
nutrients and oxygen necessary for tumor growth, and later provide a so-called metastasistic pathway in which some cells that have
detached from the growing tumor migrate to other organs and induce growth.

TTAC-0001 is a kind of anti-angiogenic antibody therapeutics neutralizing the VEGF/VEGFR2 signal transduction, thus inhibiting
tumor growth and metastasis.

TTAC-0001 Mode of Action (MOA)

    Notes

    Responses to VEGFR-2 / KDR, the major mediator of tumor angiogenic angiogenesis mechanisms among the three VEGF receptors.

    TTAC-0001 blocks the binding of VEGF to the receptor, thereby blocking inhibiting the Antiogenesis angiogenesis signaling mechanism through VEGFR-2 activation.

According to its mode of action, TTAC-0001 may have extensive usage in oncology. Theoretically, all solid tumors forms new blood
vessels for their growth and VEGFR2 mediates the tumor angiogenesis during the growth. Therefore, TTAC-0001 may have chance
to use for all kind of solid tumor treatments, which is a good advantage among angiogenic inhibitors. In contrast to angiogenic
inhibitors, antibody therapeutics (ex. Herceptin, Vectibix) that directly suppress tumor growth by targeting antigens on specific
cancers, are relatively limited to use due to applying for specific cancer treatments.

TTAC-0001 is the only antibody therapeutics that has cross-species cross reactivity to VEGFR2 in rodents, enabling transnational
research using mouse models among VEGFR2 targeting antibody therapeutics under development.
The anti-cancer therapy successfully ended in Australia in June 2017 for recurrent glioblastoma (rGBM)r patients. Additionally, we are planning to conduct clinical trials for Avastin refractory rGBM patients in global regions, including the United States and Australia this year, and we already started to conduct combination trials with Keytruda of MSD for both rGBM and metastatic Triple-negative breast cancer (mTNBC) patients

TTAC-0001 has some track records regarding out-license; China-based companyCompany 3Sbio has exclusive rights only for oncology
indication in the territory of China, Thailand, Russia, and Brazil. Global exclusive rights for eye diseases indication was out-licensed to
transferred to Korean pharmaceutical company. Thus, out-license opportunities for oncology indication of TTAC-0001 in major markets
including US, Europe and Japan, MENA areas and Latin America are still open.

PMC-001

PMC-001 is a pipeline in which our DIG-body technology, one of our dual target antibody platform technology is applied.
It is composed of TTAC-0001 as a backbone molecule and Tie2 binding domain as a, second binder, is linked to light chain N-terminal of TTAC-0001 through linker peptides. Both antigens that PMC-001 targets are VEGFR2 and Tie2, respectively and therefore Iit inhibits
tumor angiogenesis more efficiently than single target antibody does.

PMC-001 is an antibody therapeutics targetingts both VEGFR2 and Tie2 receptors which are involved in the tumor angiogenesis.
It is tetravalent antibody therapeutics, and possible to conduct translational research on mice and monkeys as it has cross-species
cross-reactivity in both VEGFR2 and Tie2.

It has been confirmed that tumor angiogenesis, tumor growth and metastasis are effectively inhibited in animal models bearing various types of cancer, and that the single target antibody therapy or combination therapy for each target has not shown more excellent cancer activity compared with dual target antibody therapeutics. Development of PMC-001 is currently underway in the optimization phase prior to full-scale development.

Although PMC-001 is a relatively early pipeline at the development stage, PharmAbcine was able to make overseas out-license in 2014 as a next-generation antibody , therapeutics and as a result 3SBio has gained exclusive rights in Chin and Korea markets.

Various growth factors derived from tumor microenvironment (TME) rapidly amplify immature bone marrow cells. It is reported that myeloid- derived suppressor cells (MDSCs) promote distant metastasis by inhibiting actions of tumor specific T-cells and increasing the
malignancy of tumor cells.

Pipeline List

Name Target(s) Develoment Status Modality Teaser
TTAC-0001 VEGFR2 Phase IIa mAb Attached
PMC-001 VEGFR2, Tie2 Preclinical Bispecific mAb Attached
PMC-005B EGFRvIII In vivo efficacy ADC
CAR-T/NK
Attached
PMC-122 PD-L1, CD47 In vivo efficacy Bispecific mAb Attached
PMC-201 VEGFR2, DLL4 In vivo efficacy Bispecific mAb Attached
PMC-309 VISTA In vivo efficacy mAb Attached
PMC-401 ANG2 In vivo efficacy mAb Attached
PMC-404 ANG2, VEGF-C In vivo efficacy Bispecific mAb
PMC-901 VEGF-A Preclinical Biosimilar Attached
PMC-902 VEGF-A, VEGF-B, PlGF Preclinical Biosimilar
PMC-903 TNF alpha Preclinical Biosimilar
PMC-904 IgE Preclinical Biosimilar

PMC-309

PMC-309 is an antibody that binds with VISTA (V-domain Ig suppressor of cell activation) expressing on the surface of MDSC, and is an immunosuppressive agent that ultimately induces immunological activity by impeding the immune suppression function induced
by VISTA.

The importance of myeloid- derived suppressor cells (MDSCs) present in tumor microenvironment (TME) continues to be reported in
terms of the resistance mechanism against PD-1/PD-L1 inhibitors. Therefore, we expect to significantly increase the effectiveness of treatmentefficacy if we use immune checkpoint inhibitor and PMC-309 together, which primarily regulate the immunological activity
of T-cells such as Pembrolizumab.