ITGB6

SOUTH SAN FRANCISCO, Calif., Sept. 10, 2024 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), a late-stage biotechnology company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases, announced its presentations at the European Respiratory Society (ERS) International Congress 2024 taking place in Vienna, Austria September 7 - 11, 2024. “Presentations made by Pliant colleagues and investigators at the 2024 ERS Congress include additional clinical data from our recently announced type 1 collagen PET imaging study, an integrated safety summary from our INTEGRIS clinical programs and non-clinical data from our bexotegrast development program. Taken together, these data provide further support for the late-stage development of this novel therapeutic as part of our ongoing BEACON-IPF trial,” said Éric Lefebvre, M.D., Chief Medical Officer at Pliant Therapeutics. Bexotegrast reduces type 1 collagen deposition in participants with idiopathic pulmonary fibrosis (IPF) after 12 weeks of therapy In a late-breaker oral presentation, Sydney B. Montesi, M.D., Assistant Professor of Medicine at Massachusetts General Hospital, Havard Medical School presented results from the first interventional Phase 2, single-center, randomized, double-blind, placebo-controlled trial (NCT05621252) evaluating type 1 collagen deposition by positron emission tomography (PET) imaging in the lungs of participants with IPF. Following 12 weeks of treatment, bexotegrast demonstrated a reduction in type 1 collagen in contrast to an increase on placebo, supporting bexotegrast’s antifibrotic effects and suggesting favorable lung remodeling. In addition, treatment with bexotegrast showed numerical improvements in forced vital capacity, cough severity, and prognostic biomarkers, suggesting its potential for disease modification in idiopathic pulmonary fibrosis (IPF). Lastly, measurements by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), bexotegrast demonstrated an increased peak enhancement and a faster contrast washout rate, suggesting improvements in lung microvasculature and decreased extravascular extracellular volume, further supporting the PET imaging findings. Safety and tolerability of bexotegrast in Phase 2 trials of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC) In an oral presentation, Gregory Cosgrove, M.D. FCCP, Vice President of Clinical Development at Pliant Therapeutics presented an integrated safety summary of bexotegrast from the INTEGRIS Phase 2a trials in IPF and primary sclerosing cholangitis (PSC). Results showed that, at 12 weeks of treatment, bexotegrast was well tolerated with no related serious adverse events with most adverse events being mild to moderate with low discontinuation rates across both trials. Bexotegrast is antifibrotic in precision cut-lung slices prepared from fibrotic interstitial lung disease explants In a late-breaker oral presentation, Johanna Schaub, Ph.D., Principal Scientist II, Translational Sciences at Pliant Therapeutics, presented a study assessing the antifibrotic effects of bexotegrast, a dual αvβ6/αvβ1 integrin inhibitor, in precision cut-lung slices from patients with progressive fibrosing interstitial lung diseases (ILD) other than IPF. Results showed that integrin αvβ6 levels were increased in lungs from patients with a diverse set of fibrotic ILDs and that bexotegrast decreased profibrogenic gene expression in lung slices generated from a wide range of ILD lung explants. In addition, the antifibrotic activity of bexotegrast was found to be similar in slices from IPF and non-IPF explants. These data support the further investigation into the antifibrotic activity of bexotegrast in ILD-associated progressive pulmonary fibrosis (PFF). Post-hoc biomarker analysis in participants with IPF receiving bexotegrast over 12-weeks in INTEGRIS-IPF In a poster presentation, Martin Decaris, Ph.D., Senior Director, Translational Sciences at Pliant Therapeutics, presented results from a post-hoc proteomic analysis of plasma samples from the INTEGRIS-IPF Phase 2a clinical trial of bexotegrast in patients with IPF. Results showed that plasma levels of several previously identified biomarkers of ILD progression, including integrin beta-6, were reduced in participants receiving bexotegrast at the 320 mg dose versus placebo. Plasma integrin beta-6 levels were also found to negatively correlate with changes in lung function as determined by percent predicted forced vital capacity (FVCpp). Further analyses of plasma biomarkers are included as part of the ongoing global Phase 2b/3 BEACON-IPF trial. Posters presented at the ERS International Congress 2024 are available on Pliant’s website under the Publications section at https://pliantrx.com/publications. About Pliant Therapeutics, Inc. Pliant Therapeutics is a late-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indications for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in IPF and PSC and Orphan Drug Designation from the European Medicines Agency in IPF and PSC. Pliant has initiated BEACON-IPF, an adaptive Phase 2b/3 trial of bexotegrast in IPF. Pliant is conducting a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that is being developed for the treatment of solid tumors. In addition, Pliant has received regulatory clearance for the conduct of a Phase 1 study of PLN-101325, a monoclonal antibody agonist of integrin α7β1 targeting muscular dystrophies. For additional information, please visit: www.PliantRx.com. Follow us on social media: X, LinkedIn, and Facebook. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding the potential for the future development of bexotegrast. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including any delays in our ongoing or planned preclinical or clinical trials, the impact of current macroeconomic and marketplace conditions, including the effects of COVID-19, on our business, operations, clinical supply and plans, our reliance on third parties for critical aspects of our development operations, the risks inherent in the drug development process, the risks regarding the accuracy of our estimates of expenses and timing of development, our capital requirements and the need for additional financing, including the availability of additional term loans under our loan facility, and our ability to obtain and maintain intellectual property protection for our product candidates. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Quarterly Report on Form 10-Q for the period ended June 30, 2024 which we filed with the SEC on August 7, 2024, and is available on the SEC's website at www.sec.gov. Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. Investor and Media Contact:Christopher KeenanVice President, Investor Relations and Corporate CommunicationsPliant Therapeutics, Inc.ir@pliantrx.com

12-week treatment with Bexotegrast 160 mg resulted in reduction of total lung collagen as measured by PET imaging, compared to an increase on placebo Improvement in FVC and​ reduction in cough severity reported in bexotegrast-treated patients at all timepoints compared to placebo Bexotegrast 160 mg was well tolerated over 12 weeks of treatment with no serious adverse events and no discontinuations SOUTH SAN FRANCISCO, Calif., May 14, 2024 (GLOBE NEWSWIRE) -- Pliant Therapeutics, Inc. (Nasdaq: PLRX), today announced topline data from a 12-week, randomized, double-blind, placebo-controlled trial of bexotegrast (PLN-74809) conducted at Massachusetts General Hospital evaluating change in total collagen levels in the lungs of patients with idiopathic pulmonary fibrosis (IPF). IPF is a disease characterized by excessive collagen deposition in the lung. Bexotegrast-treated patients showed reduced total lung collagen post treatment as measured by positron emission tomography (PET) imaging, compared to increased total lung collagen in the placebo group, suggesting potential reversal of fibrosis. Bexotegrast-treated patients demonstrated improvements in forced vital capacity (FVC) and reduction in cough severity across all timepoints compared to placebo. Bexotegrast 160 mg was well tolerated over 12 weeks with no drug-related serious adverse events (SAEs) and no discontinuations. The trial evaluated bexotegrast at a once-daily dose of 160 mg versus placebo, and measured change in total lung collagen in 10 patients with IPF after 12 weeks of treatment. Patients underwent PET imaging with a collagen-binding radiotracer at baseline and Week 12. The trial enrolled 7 patients in the active arm and 3 in the placebo arm. Eight out of 10 enrolled patients were on standard of care with the majority of those on nintedanib. Bexotegrast 160 mg-Treated Patients Showed Reduced Total Lung Collagen Levels After 12 Weeks of Treatment, Suggesting Potential Reversal of Fibrosis The primary endpoint of the trial was an evaluation of the change in standardized uptake value (SUV) of 68GA-CBP8, a PET ligand that binds to type 1 collagen. Type 1 collagen is the predominant collagen type produced in the lungs as a result of IPF.1 An increase in SUV of in the lung indicates increased total lung collagen and potential progression of disease. IPF patients have been shown to exhibit higher SUV values compared to healthy subjects.2 Additionally, patients with increased total lung collagen as measured by PET imaging had an increased risk of death.3 After 12 weeks of treatment, bexotegrast-treated patients showed a reduction in SUV in the lung compared to an increase seen in placebo. This reduction in SUV indicates reduced total lung collagen in the treated group, suggesting potential reversal of fibrosis. Figure 1. Mean Change from Baseline in Uptake of Collagen PET Tracer After 12 Weeks Bexotegrast-Treated Patients Demonstrated Improvements in FVC, Cough Severity, and Fibrosis Biomarkers Across All Time Points The trial's exploratory efficacy endpoints assessed changes in FVC, forced vital capacity percent predicted (FVCpp), patient reported cough severity, and fibrosis biomarkers. Bexotegrast-treated patients experienced improved lung function, as measured by FVC and FVCpp, with a clear separation from placebo across all timepoints. Figure 2. Change in FVC and FVCpp from Baseline of Bexotegrast 160 mg Over 12 Weeks Chronic cough in IPF is often refractory and debilitating.4 It is an independent predictor of disease progression and may predict time to death or lung transplantation.5 Across all timepoints, bexotegrast-treated patients experienced reduced patient-reported cough severity as measured by the cough visual analog scale (VAS) compared to placebo patients who experienced increased cough severity at all timepoints. Figure 3. Mean Change from Baseline in Cough Severity Visual Analog Scale (VAS) of Bexotegrast 160 mg Over 12 Weeks Elevated integrin beta-6 plasma levels have been associated with interstitial lung disease (ILD) progression as defined by mortality, transplant or ≥ 10% relative reduction in FVC (mL) over 12 months.6 PRO-C3, a serum biomarker of type III collagen synthesis, is elevated in patients with IPF and associated with progressive disease.7 At weeks 4 and 12, bexotegrast-treated patients demonstrated a reduction in circulating biomarkers integrin beta-6 and PRO-C3 relative to placebo. The trial’s secondary endpoint was the evaluation of the safety and tolerability of bexotegrast. Bexotegrast was well tolerated at a dose of 160 mg over 12-weeks of treatment with no serious adverse events (SAE) reported. Most frequently reported treatment-emergent adverse events (TEAEs) were mild in severity with no trial discontinuations. “These imaging data continue to demonstrate the antifibrotic mechanism of action of bexotegrast and build on previous results, including from our INTEGRIS-IPF Phase 2a trial,” said Éric Lefebvre, M.D., Chief Medical Officer at Pliant Therapeutics. “Results from this first study using collagen PET imaging to assess a therapeutic intervention highlight the possible utilization of this novel technology to identify potentially disease-modifying antifibrotic IPF therapies in short-term studies,” said Sydney Montesi, M.D., Clinician-Researcher, Division of Pulmonary and Critical Care Medicine at Massachusetts General Hospital and Principal Investigator in the trial. A slide deck with the topline data from this trial is available under the Investors & Media section of the Pliant website at . Phase 2a PET Imaging Trial (NCT05621252) This was a Phase 2a, 12-week, single-center, randomized, double-blinded, placebo-controlled trial that evaluated bexotegrast at a once-daily dose of 160mg or placebo on levels of total collagen deposition in the lungs of participants with IPF. Patients were randomized in a 2:1 ratio of (active:placebo) and stratified based on use of standard of care IPF therapy. Participants underwent positron emission tomography (PET) imaging with a radiotracer, 68Ga-CBP8, that binds to total collagen at Baseline and at Week 12. The trial’s primary endpoint was the assessment of change in Baseline of type 1 collagen in the lung and the secondary endpoint was the evaluation of the safety and tolerability of bexotegrast. The trial's exploratory efficacy endpoints assessed changes in forced vital capacity (FVC) and forced vital capacity percent predicted (FVCpp), changes in patient reported cough severity, and changes in fibrosis biomarkers. Bexotegrast-treated patients demonstrated improvements across all the exploratory efficacy endpoints compared to placebo. About Pliant Therapeutics, Inc. Pliant Therapeutics is a late-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indications for the treatment of idiopathic pulmonary fibrosis, or IPF, and primary sclerosing cholangitis, or PSC. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in IPF and PSC and Orphan Drug Designation from the European Medicines Agency in IPF and PSC. Pliant has initiated BEACON-IPF, a Phase 2b/3 trial of bexotegrast in IPF. Pl Pliant is conducting a Phase 1 study for its third clinical program, PLN-101095, a small molecule, dual-selective inhibitor of αvß8 and αvß1 integrins, that is being developed for the treatment of solid tumors. Pliant has received regulatory clearance for the conduct of a Phase 1 study of PLN-101325, a monoclonal antibody against integrin α7β1 targeting muscular dystrophies. For additional information, please visit: . Follow us on social media X, LinkedIn, Facebook and YouTube. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those regarding the safety, tolerability, pharmacodynamics and therapeutic potential of bexotegrast; our plans for the future development of bexotegrast, PLN-101325 and PLN-101095; bexotegrast’s potential to become a treatment for IPF and the potential future utilization of PET imaging technology to identify IPF therapies. Because such statements deal with future events and are based on our current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Pliant Therapeutics could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including those related to the development and commercialization of our product candidates, including any delays in our ongoing or planned preclinical or clinical trials, the impact of current macroeconomic and marketplace conditions, including the effects of health epidemics and pandemics, such as COVID-19, on our business, operations, clinical supply and plans, our reliance on third parties for critical aspects of our development operations, the risks inherent in the drug development process, the risks regarding the accuracy of our estimates of expenses and timing of development, our capital requirements and the need for additional financing, including the availability of additional term loans under our loan facility, and our ability to obtain and maintain intellectual property protection for our product candidates. These and additional risks are discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K for the period ended December 31, 2023, as updated in our Quarterly Report on Form 10-Q for the period ended March 31, 2024, each available on the SEC's website at Unless otherwise noted, Pliant is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. Investor and Media Contact: Christopher Keenan Vice President, Investor Relations and Corporate Communications Pliant Therapeutics, Inc. ir@pliantrx.com 1 Kuhn C 3rd, et al. 1989. Am Rev Respir Dis. Dec;140(6):1693-703. 2 Montesi SB, et al. 2019. Am J Respir Crit Care Med 200:258–261. 3 Justet, A. et al. 2017. Respir Res 18, 74. 4 van Manen MJG et al. Eur Respir Rev 2016; 25: 278–286. 5 Ryerson CJ et al. Respirology 2011; 16: 969–975. 6 Organ LA et al. Respir Res. 2019 Jul 12;20(1):148. 7 Bowman WS et al. Lancet Respir Med. 2022 Jun;10(6):593-602. Figures accompanying this announcement are available at Figure 1 Mean Change from Baseline in Uptake of Collagen PET Tracer After 12 Weeks Figure 2 Change in FVC and FVCpp from Baseline of Bexotegrast 160 mg Over 12 Weeks Figure 3 Mean Change from Baseline in Cough Severity Visual Analog Scale (VAS) of Bexotegrast 160 mg Over 12 Weeks

Without a doubt, ADC (Antibody Drug Conjugates) is one of the hottest fields in recent years. In 2022, the global sales exceeded 7 billion US dollars, and the sales of these drugs in the first half of this year have already exceeded 5 billion US dollars. It is expected to break the 10 billion dollar mark for the full year. Currently, 15 ADCs have been approved for marketing. Hundreds of ADCs are under investigation worldwide, and in pursuit of differentiation and increased competitiveness, an increasing number of targets are being developed, including popular targets such as HER2, Trop-2, EGFR, and emerging targets like Nectin-4, B7-H3, and B7-H4. Pharmaceutical giants have also joined in the layout of the ADC pipeline. This year, Pfizer has acquired Seagen for as high as 43 billion US dollars, incorporating its ADC pipeline, including Nectin-4 ADC Padcev, CD30 ADC Adcetris, Zinc transporter LIV-1 ADC Ladiratuzumab vedotin, ITGB6 ADC SGN-B6A and B7H4 ADC SGN-B7H4V. Global Phase III Clinical ADCs under InvestigationApart from the approved ADCs, there are hundreds of ADCs under clinical investigation, covering a increasingly diverse range of targets. Not only do they include popular targets like HER2 and Trop-2, but also emerging targets such as B7-H3, FRα, Nectin-4, and so on. There are several drugs globally that have entered phase III clinical stage. The figure below lists some of the ADCs under phase III clinical investigation. A166 A166 is a HER2 ADC developed by Sichuan Kelun-Biotech Biopharmaceutical, a subsidiary of Sichuan Kelun Pharmaceutical, using the OptiDC platform. By stably proteolytic cleavable valine-citrulline linker, it specifically links to the HER2 antibody site and couples it to Duo-5 (an antimicrotubule agent). It has demonstrated its safety and effectiveness in HER2-positive breast cancer patients. Last year, at the ASCO conference, Sichuan Kelun-Biotech Biopharmaceutical announced the results of a phase I trial of A166 (CTR20181301). The best ORR among all patients in the 4.8 and 6.0 mg/kg groups was 73.91% and 68.57%, respectively, with mPFS of 12.30 and 9.40 months, respectively. Among 23 patients treated at a dose level of 4.8 mg / kg, one patient had confirmed and sustained complete remission for 7+ months[1]. The new drug application for A166 was accepted by the CDE on May 11th, for the treatment of HER2-positive locally advanced, inoperable, recurrent or metastatic breast cancer that has failed second-line and above anti-HER2 treatment. Patritumab deruxtecan Patritumab deruxtecan (HER3-DXd, U3-1402) is the world's first HER3-targeting antibody-drug conjugate (ADC) developed by Daiichi Sankyo, and is currently being investigated for indications such as breast cancer and non-small cell lung cancer (NSCLC). HER3-DXd is created by conjugating the monoclonal antibody patritumab (U3-1287), which targets the extracellular domain of HER3, to the cytotoxic topoisomerase I inhibitor deruxtecan using a maleimidocaproyl-GGFG linker via a cysteine-specific coupling approach, with a drug-to-antibody ratio (DAR) of 8. Structure of HER3-DXdIn an oral presentation at this year's ASCO meeting, Daiichi Sankyo unveiled Part A results of the Phase 2 study of HER3-Dxd in patients with HER2-negative metastatic breast cancer (MBC): the overall response rate (ORR) in the total population was 35%, the clinical benefit rate (CBR) was 48%, and the median duration of response (DOR) was 10.0 months, with a 6-month progression-free survival (PFS) rate of 60%. Clinical results of Part AMore recently, at the 2023 WCLC meeting, Daiichi Sankyo announced the key results of the HERTHENA-Lung01, a pivotal Phase 2 study of HER3-DXd in patients with EGFR-mutated non-small cell lung cancer. Evaluated by blinded independent central review (BICR), in 225 patients with EGFR mutation-positive NSCLC treated with HER3-DXd (5.6mg/kg), a confirmed ORR of 29.8% was observed, including 1 complete response (CR), 66 partial responses (PR), and 99 cases of stable disease (SD). The DOR was 6.4 months, with a disease control rate (DCR) of 73.8%. As of May 18, 2023, the median progression-free survival (PFS) was 5.5 months, and the median overall survival (OS) was 11.9 months. Main results of the HERTHENA-Lung01 trial of HER3-DXdMoreover, Merck (known as MSD outside of the United States and Canada) has recently acquired three ADCs, including HER3-Dxd, with a total purchase price of $22 billion, indicating Merck's significant optimism for the potential of this drug. Datopotamab deruxtecan Datopotamab deruxtecan (Dato-DXd, DS-1062) is a Trop-2-targeted antibody-drug conjugate (ADC) co-developed by AstraZeneca and Daiichi Sankyo. It is constructed by coupling a recombinant humanized anti-Trop-2 IgG1 antibody to a topoisomerase I inhibitor (DXd) via a tetrapeptide-based cleavable linker designed to reduce cysteine residues on the interchain disulfide bonds of datopotamab. The tetrapeptide-based linker is designed to release DXd following proteolytic processing by lysosomal enzymes, such as cathepsin, upon internalization into cancer cells. On average, the goal is to have an average of four drug-to-antibody ratio (DAR) per antibody molecule. Unlike Trodelvy, the first approved Trop-2 ADC for the treatment of breast cancer, AstraZeneca and Daiichi Sankyo plan to focus on advanced non-small cell lung cancer (NSCLC) as the initial indication for Dato-DXd, positioning it as a potential alternative to chemotherapy in the treatment of NSCLC. Structure of Dato-DXdAt this year's ASCO Annual Meeting, AstraZeneca and Daiichi Sankyo presented study results for Dato-DXd in the treatment of advanced NSCLC from the TROPION-Lung02 study: Dato-DXd combined with durvalumab or Dato-DXd combined with durvalumab plus platinum-based chemotherapy resulted in an objective response rate (ORR) of 38% and 49%, disease control rates (DCR) of 84% and 87%, and progression-free survival (PFS) of 8.3 months and 7.3 months, respectively, in the overall advanced NSCLC population. In the first-line treatment population, the ORR for Dato-DXd combined with durvalumab or with durvalumab plus platinum-based chemotherapy was 50% and 57%, respectively, with a DCR of 91% for both combinations, and the median duration of response (DOR) had not yet been reached. These results further confirm the significant efficacy and good safety profile of Dato-DXd combined with durvalumab ± platinum-based chemotherapy in first-line or previously treated advanced NSCLC patients without actionable genomic alterations. However, Dato-DXd has also encountered safety issues. Although the TROPION-Lung01 trial met its primary clinical endpoint, serious safety concerns arose, including cases of interstitial lung disease and Grade 5 adverse events leading to death due to drug-related adverse reactions. This news had a significant impact on both AstraZeneca and Daiichi Sankyo, causing their stock prices to drop by 8% and 15% respectively on the day of the announcement. Global Phase II Clinical ADCs under Investigation DB-1305 DB-1305 is a Trop-2 targeted ADC developed by Yingen Biopharmaceutical based on its proprietary Duality ImmunoToxin Antibody Conjugate (DITAC) platform, coupling a Trop-2 antibody to an innovative topoisomerase I inhibitor, P1021, through an enzymatically cleavable tetrapeptide linker. In June 2022, DB-1305 initiated an open-label, multi-center, multi-dose, phase 1/2a study (NCT05438329), which included a dose-escalation phase 1 in pretreated patients with advanced solid tumors and a dose-expansion phase 2a. As of December 19, 2022, 20 patients have participated in the dose-escalation portion of the study. Currently, Yingen Biopharmaceutical is co-developing, producing, and commercializing DB-1305 in partnership with BioNTech. This collaboration follows BioNTech's acquisition of two ADC products from Yingen Biopharmaceutical for $1.67 billion in April 2023, making DB-1305 the third product the two companies are jointly advancing. 9MW2821 9MW2821 is an ADC (Antibody-Drug Conjugate) targeting Nectin-4, developed by Jiangsu Maiweikang New Drug Research and Development Co. It received domestic clinical approval in China in October 2021, with indications including urothelial carcinoma, breast cancer, lung cancer, and several other solid tumors. 9MW2821 is produced by employing inter-chain disulfide drug conjugation technology to link a humanized antibody with the cytotoxic payload monomethyl auristatin E (MMAE). Structure and Mechanism of Action of 9MW2821The ADC 9MW2821 is currently undergoing Phase 1/2 clinical trials (NCT05216965 and NCT05773937) in patients with advanced solid tumors, aiming to evaluate the safety, tolerability, pharmacokinetics, preliminary antitumor activity, and immunogenicity of 9MW2821 administered intravenously. Global Phase I Clinical ADCs under Investigation Mirzotamab clezutoclax  Mirzotamab clezutoclax (ABBV-155; Mirzo-C) is a B7-H3-targeted Antibody-Drug Conjugate (ADC) developed by AbbVie, comprising three components: an anti-B7-H3 monoclonal antibody, a cleavable linker, and a BCL-XL inhibitor payload. Specific targeting of BCL-XL has demonstrated synergy with other anticancer drugs in preclinical models. At this year's ASCO conference, AbbVie released the results of a Phase 1 open-label study (NCT03595059) for ABBV-155, evaluating the efficacy of ABBV-155 in combination with taxane-based chemotherapy. As of November 18, 2022, a total of 78 patients had been enrolled (small cell lung cancer n=14; non-small cell lung cancer n=36; breast cancer n=28). In terms of efficacy, the confirmed objective response rate (cORR) for the SCLC cohort was 0%, with a 0% partial response (PR) rate; the NSCLC cohort had a cORR of 11% and a PR rate of 36%; the breast cancer cohort exhibited a cORR of 18% and PR rate of 36%. Overall, ABBV-155, whether used as a monotherapy or in combination with docetaxel, displayed favorable tolerability. Clinical Results of ABBV-155SGN-B6A SGN-B6A is an antibody-drug conjugate (ADC) developed by Seagen, targeting integrin β-6 (ITGB6) to deliver the clinically validated potent payload monomethyl auristatin E (MMAE) to cancer cells. The antibody component of SGN-B6A is specific for integrin β-6 and does not bind to other members of the α-v family. SGN-B6A mediates anti-tumor activity through MMAE-induced cytotoxicity, bystander effects, and immunogenic cell death. Structure and Selectivity of SGN-B6AAt this year's ASCO meeting, Antoine and colleagues presented the results of a phase 1 clinical trial (NCT04389632) for SGN-B6A. As of December 14, 2022, 148 patients were treated with SGN-B6A, including 88 patients in part A and 60 patients in part B of the study, with enrollment for part A completed. SGN-B6A demonstrated a manageable safety profile and showed encouraging preliminary anti-tumor activity with dose-escalated durability of response in a heavily pretreated population. Dose-expansion cohorts of part B for non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), and head and neck squamous cell carcinoma (HNSCC) are currently ongoing. Phase 1 Clinical Trial Results of SGN-B6ANumerous antibody-drug conjugate (ADC) therapies have been successfully developed to date, benefiting tens of thousands of cancer patients. As of now, there are 15 ADCs that have been globally approved for marketing. The market presence of these ADCs, along with the impressive clinical performance of various ADCs, has garnered increased attention in this field. In addition, there are several hundred ADCs currently under research around the world, targeting markers such as HER2, Trop-2, B7-H3, c-Met, and EGFR, among others. This article summarizes a portion of the ADCs in clinical research and briefly introduces some of the typical compounds among them, with the belief that more ADCs will be approved and reach the market in the near future.