On January 4, U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to telisotuzumab vedotin (Teliso-V) , an antibody conjugate drug (ADC), for the treatment of patients with advanced/metastatic epidermal growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer (NSCLC) with high levels of c-Met overexpression whose disease has progressed on or after platinum-based therapy.

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c-Met ADC Receives FDA Breakthrough Therapy
Designation
On January 4, U.S. Food and Drug Administration (FDA) granted Breakthrough
Therapy Designation (BTD) to telisotuzumab vedotin (Teliso-V) , an antibody
conjugate drug (ADC), for the treatment of patients with advanced/metastatic epidermal
growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer
(NSCLC) with high levels of c-Met overexpression whose disease has progressed on or
after platinum-based therapy.
Telisotuzumab vedotin (ABBV-399), Image Source: https://www.abbvie.com/
Lung cancer is the leading cause of cancer-related deaths worldwide, with NSCLC
accounting for approximately 85% of lung cancer. Patients with lung cancer whose
disease has progressed after standard of care therapy, including prior platinum, have
limited treatment options and a poor prognosis.
Teliso-V is an ADC drug that targets c-Met, a receptor tyrosine kinase (RTK) that is
overexpressed in a variety of tumors, including NSCLC. Currently, no cancer therapies
have been approved specifically for patients with c-Met overexpressed NSCLC.
This BTD determination is supported by data from LUMINOSITY (M14-239), an ongoing
phase 2 study designed to identify c-Met overexpressing NSCLC populations best suited

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to receive Teliso-V monotherapy in second- or third-line therapy, and then further evaluate
efficacy in selected populations. The primary endpoint of the study is the overall remission
rate (ORR) in patients with ≥12 weeks of follow-up.
Previously published interim analysis showed an ORR of 53.8% in the c-Met high
expression group and 25.0% in the c-Met intermediate expression group in patients with
EGFR wild-type non-squamous NSCLC. Teliso-V was also evaluated in combination with
osimertinib in the ongoing Phase 1 study M14-237 in previously treated patients with
c-Met overexpressing NSCLC. In addition, it will be further evaluated as monotherapy in
previously treated c-Met overexpressing NSCLC patients in the randomized Phase 3
study TeliMET NSCLC-01 (M18-868).
c-MET: a novel target for anticancer therapy
c-Met is a protein product encoded by the c-Met proto-oncogene, a hepatocyte growth
factor receptor with tyrosine kinase activity. c-Met is associated with a variety of oncogene
products and regulatory proteins, and is involved in the regulation of cellular information
transduction, cytoskeletal rearrangement, and is an important factor in cell proliferation,
differentiation, and motility.
It is now believed that c-Met is closely associated with the development and metastasis of
many types of cancer. Studies have shown that many tumor patients have c-Met
overexpression and gene amplification during their tumorigenesis and metastasis. c-Met
has become another important molecular therapeutic target for NSCLC after EGFR and
ALK.
➤ Monoclonal antibodies
To date, several companies have ventured into monoclonal antibodies targeting c-Met,
such as ARGX-111 from argenx, Emibetuzumab from Lilly, Onartuzumab from Genentech,

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and HLX55 from Henlius. Unfortunately, the first three drugs have been discontinued from
clinical trials due to their poor efficacy.
HLX55 specifically binds to the Sema/PSI domain of human c-MET, and has a dual
mechanism of action by blocking the binding of c-MET to its ligand HGF, thereby blocking
c-MET activation, and promoting c-MET degradation. Currently, HLX55 has been licensed
for clinical trials in Taiwan and China, and clinical trials are in progress.
➤ Bispecific Antibodies
Compared to monoclonal antibodies, bispecific antibodies have been more well
researched in c-MET targets. Among them, the fastest progress is Johnson &
Johnson/Janssen's bispecific antibody Amivantamab targeting c-Met/EGFR. on May 21,
2021, the FDA accelerated the approval of Amivantamab for patients with metastatic
NSCLC with EGFR exon 20 insertion mutation progressing after platinum-based
chemotherapy.
➤Polyclonal Antibody
GB263T is the first tri-specific antibody (EGFR/cMET/cMET) developed by GENOR
BIOPHARMA. On December 20, 2021, GENOR BIOPHARMA has submitted a clinical
trial application to the Bellberry Human Research Ethics Committee (Bellberry HREC) in
Australia for GB263T for the treatment of advanced malignancies. It is expected to file
IND applications in China and the United States in 2022.
➤ ADCs
c-Met is also one of the targets for ADC drug development. In addition to teliso-V, two
other anti-cMet ADCs (TR1801-ADC and SHR-A1403) are currently under investigation
for use against solid tumors with promising preclinical activity.

4. Biopharma PEG https://www.biochempeg.com
Biopharma PEG is dedicated to being your most reliable partner to provide a chemical
synthesis and high-quality ADC linkers & PEG linkers. We are committed to promoting the
progress of your ADC discovery and development projects.
Reference:
[1] AbbVie Announces U.S. FDA Granted Breakthrough Therapy Designation (BTD) to
Telisotuzumab Vedotin (Teliso-V) for Previously Treated Non-Small Cell Lung
Cancer https://news.abbvie.com/news/press-releases/abbvie-announces-us-fda-granted-
breakthrough-therapy-designation-btd-to-telisotuzumab-vedotin-teliso-v-for-previously-tre
ated-non-small-cell-lung-cancer.htm
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