On June 7, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the updated results from a Phase Ib/II study of the Bcl-2 inhibitor lisaftoclax (APG-2575) in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) in a Poster Presentation at the 58th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ascentage Pharma, JUN 7, 2022, View Source;ascentage-pharma-releases-updated-data-demonstrating-lisaftoclaxs-apg-2575-therapeutic-potential-in-patients-with-rr-cllsll-301563282.html [SID1234615726]).

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Entering the fifth consecutive year in which company’s abstracts were selected for presentations by the ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including favorable data of lisaftoclax, a key drug candidate of the company’s apoptosis-targeted pipeline, in Chinese patients with R/R CLL/SLL showing an objective response rate (ORR) of 67.4%. Lisaftoclax was well tolerated, and all adverse events were manageable. No dose-limiting toxicity (DLT) were observed at up to 800 mg/day. The risk of clinical tumor lysis syndrome (TLS) in patients on daily dose ramp-up was minimal.

Prof. Jianyong Li, Director of the Hematology Department, Jiangsu People’s Hospital, and the principal investigator of this study, said, "Lisaftoclax is a Bcl-2 selective inhibitor that can induce apoptosis and suppress the growth of tumor cells. In this Phase Ib/II study, lisaftoclax as a single agent showed favorable preliminary efficacy and safety, and a daily ramp-up schedule that is patients’ friendly. We look forward to further evaluating the efficacy of lisaftoclax as a single agent and in combinations in patients with R/R CLL/SLL."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China, also the world’s second and China’s first Bcl-2 inhibitor being investigated in pivotal trials. Data released at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting suggest that lisaftoclax may offer an effective, safe, and more ‘user friendly’ treatment alternative to patients with R/R CLL/SLL. We are taking firm steps forward with this clinical development program to allow patients to benefit from this novel therapeutic as soon as possible. Meanwhile, we are also evaluating lisaftoclax monotherapy and combinations in patients with solid tumors."

Dr. Zhai continued, "Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma’s drug candidates, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on lisaftoclax are as follows:

A phase Ib/II study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).

Abstract: #7543

The aim of this multicenter, open-label study was to evaluate the safety, antitumor activity, PK, and pharmacodynamics (PD) of lisaftoclax in Chinese patients with R/R CLL/SLL.

As of January 25, 2022, 45 patients had been enrolled. Lisaftoclax was administered orally once daily at 3 dose cohorts (400, 600, or 800 mg) in 28-day cycles, with 15 patients in each cohort.

Lisaftoclax monotherapy demonstrated favorable safety profiles in all three dose cohorts, and no DLT was observed during the Phase I study.

The risk of TLS in patients on daily dose ramp-up was extremely low, which was consistent with the observations of the Phase I study. The median duration of treatment was 7 cycles. and the ORR in the 43 efficacy evaluable patients with R/R CLL/SLL was 67.4%, including 1 complete response (CR) and 28 partial responses (PRs).

BCL-2i lisaftoclax was well tolerated up to 800 mg/day. There were no significant new or unmanageable safety findings. The recommended Phase II dose (RP2D) of lisaftoclax was determined as 600 mg. Lisaftoclax may offer a treatment alternative for patients with R/R CLL/SLL, with a daily ramp-up schedule that may be more convenient and "user friendly".
Appendix: A list of Ascentage Pharma’s abstracts selected by this year’s ASCO (Free ASCO Whitepaper) Annual Meeting

On June 7, 2022 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune and inflammatory diseases, reported the appointment of industry veteran Andrew S. Sandler, M.D., as its Chief Medical Officer (Press release, Alpine Immune Sciences, JUN 7, 2022, View Source [SID1234615693]). Dr. Sandler joins Alpine from Kiadis Pharma, a Sanofi Company, where he was Chief Medical Officer. Dr. Sandler’s anticipated start date is August 17, 2022.

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"We are very excited and fortunate to have Andy join the Alpine team. His appointment comes at a time where we are quickly advancing our three development programs across multiple oncology and autoimmune disease indications," said Stanford Peng, M.D., Ph.D., President and Head of Research and Development at Alpine. "Andy is a highly experienced Chief Medical Officer with extensive clinical development expertise, and has a passion for developing novel therapies for patients with life-threatening and debilitating diseases."

"I am thrilled to join the Alpine team and continue to advance the clinical strategy and development of the company’s extremely promising pipeline, including acazicolcept, davoceticept, and ALPN-303," said Dr. Sandler. "I look forward to integrating with the development teams to continue to advance these exciting therapies that were built from Alpine’s directed evolution platform and have the potential to improve the lives of many patients."

Dr. Sandler brings over 25 years of industry and clinical practice experience. Prior to his role at Kiadis Pharma/Sanofi, Dr. Sandler was Senior Vice President of Medical Affairs at Medivation (Pfizer). Before that, Dr. Sandler held various roles including Chief Medical Officer, Executive Vice President, Research and Development, Seattle Site Head, and Senior Vice President, Clinical and Medical Affairs at Dendreon Pharmaceuticals. Earlier in his career, Dr. Sandler was Chief Medical Officer at Spectrum Pharmaceuticals and Vice President and Head of Global Medical Affairs for Oncology at Bayer Healthcare Pharmaceuticals. Dr. Sandler also previously held various positions at Berlex Oncology/Schering AG and Seattle Genetics, Inc.

Dr. Sandler holds a B.S. degree in Neuroscience from the University of Rochester. He obtained his M.D. degree and completed his residency in Internal Medicine at Mount Sinai Medical Center, followed by a fellowship in Hematology/Oncology at the University of California, San Francisco. Dr. Sandler also holds a Certificate in Epidemiology and Biostatistics.

On June 6, 2022 Checkpoint Therapeutics, Inc. (Checkpoint) (NASDAQ: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported the presentation of data from its pivotal trial of cosibelimab in metastatic cutaneous squamous cell carcinoma (cSCC) during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Checkpoint Therapeutics, JUN 6, 2022, View Source [SID1234615709]). Positive top-line results were previously announced in January 2022 .

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Poster Presentation Title: Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in patients with metastatic cutaneous squamous cell carcinoma: Results from pivotal cohort

This registration-enabling clinical trial enrolled 78 patients with metastatic cSCC at 24 sites in 8 countries, including Australia/New Zealand (58%), Europe (24%), South Africa (10%), and Thailand (8%), and is being conducted under an Investigational New Drug application with the U.S. Food and Drug Administration. The trial is investigating the safety and efficacy of cosibelimab administered as a fixed dose of 800 mg every two weeks in patients with metastatic cSCC (lymph nodal or distant metastatic disease). Data from this study is expected to support a Biologics License Application for cosibelimab planned for submission in the fourth quarter of 2022.

Data highlights from the poster include:

Efficacy

Confirmed objective response rate (ORR) by independent central review in the modified intent to treat population of 48.7% (95% CI, 37.0-60.4)
13.2% of patients achieved a complete response in target lesions
Median duration of response (DOR) had not yet been reached at time of analysis; 76% of responses were ongoing
The Kaplan-Meier-estimated probability of maintaining a response at six and 24 months was 88.1% and 72.5%, respectively
Safety

Cosibelimab was generally well tolerated with no unexpected safety signals
The most common adverse events associated with cosibelimab were fatigue (11.5%) and rash (10.3%)
Seven patients (9.0%) experienced a grade 3 treatment-related adverse event (TRAE); no grade 4 or 5 TRAEs were reported
A copy of the poster can be found on the Publications page of the Checkpoint Therapeutics website.

Cosibelimab was licensed by Checkpoint in 2015 from the Dana-Farber Cancer Institute.

About Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately one million cases according to the Skin Cancer Foundation. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced and an estimated 15,000 people will die from their disease. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear.

About Cosibelimab
Cosibelimab (formerly referred to as CK-301) is a potential best-in-class, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 (PD-L1) and blocks the PD-L1 interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) for potential enhanced efficacy in certain tumor types.

On June 7, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the results from its Phase I first-in-human (FIH) study of the company’s novel FAK inhibitor and third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) APG-2449 in patients with second-generation TKI-resistant ALK/ROS1+ non-small-cell lung cancer (NSCLC) or mesothelioma in a Poster Presentation at the 58th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ascentage Pharma, JUN 7, 2022, View Source;ascentage-pharma-releases-for-the-first-time-results-of-its-fakalkros1-inhibitor-apg-2449-demonstrating-safety-and-efficacy-in-patients-with-advanced-nsclc-301563283.html [SID1234615727]). APG-2449 is the first China-developed third-generation ALK inhibitor entering clinical studies.

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Entering the fifth consecutive year in which its abstracts were selected for presentations by the ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including the first-time results of APG-2449 highlighting the company’s promising pipeline in solid tumors. APG-2449 demonstrated preliminary efficacy in TKI-naïve patients or those whose disease was resistant to second-generation TKIs, with 4 partial responses (PRs) observed in the 14 patients with second-generation-TKI resistant and ALK-positive NSCLC. In the 10 TKI-naïve ALK/ROS1+ patients, the objective response rate (ORR) was 80%, and the disease control rate (DCR) was 100%.

Discovered and developed by Ascentage Pharma, APG-2449 is a novel, orally-available FAK/ALK/ROS1 inhibitor and the first China-developed third-generation ALK inhibitor entering clinical studies.

Prof. Hongyun Zhao of Sun Yat-sen University Cancer Center, who is the principal investigator of this study, said, "APG-2449 is a potent FAK/ALK/ROS1 inhibitor that can address drug resistance to second-generation ALK TKIs. In this FIH study, APG-2449 demonstrated favorable safety and antitumor activity in patients with advanced NSCLC, and showed on-target pharmacodynamic effects. Building on results from this Phase I study, we look forward to further evaluate APG-2449’s efficacy in advanced NSCLC patients resistant to second-generation ALK inhibitor.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "APG-2449 is one of our key drug candidates, outside our pipeline of apoptosis-targeting assets. The data presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting demonstrated APG-2449’s therapeutic potential in patients with advanced NSCLC and are indicative of our progress in the field of solid tumors. We will continue to take firm steps to advance this clinical development program. Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma’s drug candidates at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on APG-2449 are as follows:

First-in-human phase I results of APG-2449, a novel FAK and third-generation ALK/ ROS1 tyrosine kinase inhibitor (TKI), in patients (pts) with second-generation TKI-resistant ALK/ROS1 non-small-cell lung cancer (NSCLC) or mesothelioma.

Abstract: #9071

This dose-escalation and dose-expansion study was designed to assess the safety, tolerability, recommended Phase II dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of APG-2449 in patients with second-generation TKI-resistant ALK/ROS1+ NSCLC or mesothelioma.
As of December 30, 2021, 84 Chinese patients with NSCLC or mesothelioma enrolled were treated with APG-2449 at doses ranging from 150 to 1,500 mg. APG-2449 was administered orally once daily on a 28-day cycle using a "3+3" dose escalation design.
4 PRs were observed in 14 ALK+ patients resistant to second-generation TKIs treated at the RP2D. Among 8 patients with brain metastases, 1 complete response (CR) and 3 PRs were observed intracranially. In 10 TKI-naïve patients, the ORR was 80% (ALK+, 6/8; ROS1+, 2/2) and the DCR was 100%.
In addition, AGP-2449 demonstrated a favorable safety profile. The preliminary biomarker data showed decreased FAK phosphorylation in peripheral blood mononuclear cells and increased IFN-γ levels in serum after multiple doses of APG-2449.
Conclusions: APG-2449 has a favorable safety and PK profile. Preliminary efficacy was observed in patients whose disease was resistant to second-generation or TKI-naïve. Biomarker data indicated potential target engagement on FAK and the immunomodulatory effects of APG-2449.

On June 7, 2022 Ashvattha Therapeutics ("Ashvattha"), a clinical stage company developing novel hydroxyl dendrimer therapeutics, reported a poster presentation of preclinical data demonstrating its hydroxyl dendrimer-based therapeutics reduce toxicity in targeted delivery to plexiform neurofibroma, a slow growing tumor associated with neurofibromatosis type 1 (NF1), at the 2022 Neurofibromatosis (NF) Conference hosted by the Children’s Tumor Foundation and taking place at Loews Philadelphia Hotel in Philadelphia, PA, June 18 – 21, 2022 (Press release, Ashvattha Therapeutics, JUN 7, 2022, View Source [SID1234615694]).

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Poster presentation details can be found below:

Title: Hydroxyl Dendrimer Therapeutics Reduce Toxicity in Targeted Delivery to Plexiform Neurofibroma
Presenter: Emma C. Mazurek
Date: Sunday, June 19, 2022
Time: 5:40 – 7:40 p.m. ET
Location: Loews Philadelphia Hotel, Millennium Hall, Second Floor