On June 18, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has released updated data of the Bcl-2 inhibitor lisaftoclax (APG-2575), one of the company’s key drug candidates, combined with novel therapeutic regimens in patients with relapsed/refractory (R/R) multiple myeloma (MM) or immunoglobulin light-chain (AL) amyloidosis, in a poster presentation at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress (EHA 2024), taking place in Madrid, Spain (Press release, Ascentage Pharma, JUN 18, 2024, View Source;ascentage-pharma-releases-updated-data-of-lisaftoclax-in-patients-with-rr-mm-and-al-amyloidosis-highlighting-marked-improvement-in-orr-302175033.html [SID1234644431]).

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Building on results from the study released for the first time at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the updated data presented at EHA (Free EHA Whitepaper) 2024 continued to show impressive efficacy and favorable safety of lisaftoclax-based combinations, particularly the combination with pomalidomide and dexamethasone in R/R MM. Moreover, the study reported an incidence of Grade 3 or higher treatment-related neutropenia of 14.3%, which underscored the regimens’ potential in offering patients a safe new treatment option.

Prof. Sikander Ailawadhi, MD, from Mayo Clinic and the principal investigator of this study, commented, "This is a study of lisaftoclax combined with novel therapeutic regimens in patients with R/R MM or AL amyloidosis. From the primary analysis, it demonstrated that lisaftoclax + pomalidomide in R/R MM could achieve ≥very good partial response (VGPR) rate of 33.3%, and higher VGPR along with increasing lisaftoclax dosage. Moreover, lisaftoclax based therapy in both R/R MM and amyloidosis is very well tolerated with Grade 3/4 neutropenia of 14.3%. This convincing data could provide an alternative treatment option to patients with MM and amyloidosis."

"It is our pleasure to release the updated data of lisaftoclax in patients with R/R MM or AL amyloidosis at this year’s EHA (Free EHA Whitepaper) Hybrid Congress," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "These data underscore the outstanding safety and efficacy profiles of the combination therapies, once again demonstrating these regimens’ global best-in-class potential. We will actively advance this clinical development program to bring patients a safe and effective new treatment option as soon as possible."

The EHA (Free EHA Whitepaper) Hybrid Congress is the largest gathering of the hematology field in Europe. It showcases the most cutting-edge research and state-of-the-art innovative therapies, attracting over 10,000 clinical experts and researchers from more than 100 countries every year. This year, in addition to the latest data of lisaftoclax, Ascentage Pharma also released those of the third-generation BCR-ABL1 inhibitor olverembatinib (HQP1351) and the EED inhibitor APG-5918.

Highlights of the data on lisaftoclax presented at EHA (Free EHA Whitepaper) 2024 are as follows:

Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (Pts) with Relapsed or Refractory (R/R) Multiple Myeloma (MM) or Immunoglobulin Light-Chain (AL) Amyloidosis

Abstract#: P917
Presentation Type: Poster presentation
Topic: Myeloma and other monoclonal gammopathies – Clinical
Date & Time: Friday June 14, 2024, 18:00 – 19:00 CEST
Presenting Author: Prof. Sikander Ailawadhi, Mayo Clinic Florida
Highlights:

Background: R/R MM is incurable, with virtually inevitable relapse without appropriate therapeutic intervention. AL amyloidosis is a rare disease that may cause serious organ damage or death. Lisaftoclax is a novel, potent, selective BCL-2 inhibitor with clinical benefits in hematologic malignancies and solid tumors and a low reported incidence of adverse events (AEs).
Introduction: The aim of this multicenter study was to evaluate the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Arms A and C) or daratumumab, lenalidomide, and dexamethasone (Arm B) in patients with R/R MM (Arms A and B) or R/R AL amyloidosis (Arm C).
Patient enrollment and methods: Patients with an Eastern Cooperative Oncology Group (ECOG) performance status≤2 were administered lisaftoclax daily in repeated 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use. Dexamethasone was administered at 40 mg/day, and patients aged>75 were administered at the reduced dose of 20 mg/day.
As of January 25, 2024, 44 patients that included 36 patients with R/R MM and 8 patients with R/R AL amyloidosis were enrolled in the 3 arms of the study (Arms A, B, and C) to receive lisaftoclax at various doses.
The median (range) age of patients was 70.5 (24-88) years, 68.2% were male, and 65.9% were older than 65 years.
The median (range) number of lines of prior therapies was 3 (1-19), median (range) time from diagnosis to the first dose of study drug was 5.5 (1-29) years, and median (range) number of treatment cycles was 4 (1-26).
Efficacy results:
In Arm A, 27 patients with R/R MM were efficacy evaluable. Among them, 10 had partial response (PR), 7 had very good PR (VGPR), and 2 had complete response (CR). The overall response rate (ORR [PR+VGPR+CR]) was 70.4%.
In Arm B, 2 patients with R/R MM achieved CR.
In Arm C, 7 patients with R/R AL amyloidosis were efficacy evaluable, and the ORR was 85.7% (4 VGPRs, 2 CR).
Safety results:
Of the 42 patients included in safety analysis, 10 patients experienced Grade ≥3 treatment-related adverse events (TRAEs), including neutropenia (14.3%), febrile neutropenia (2.4%). 3 patients experienced serious TRAEs that included febrile neutropenia, acute kidney injury, and diarrhea with electrolyte imbalance (1 each).
A total of 24 patients discontinued treatment because of disease progression (n=15), treatment-emergent AE (TEAE, n=3), nonadherence (n=1), or investigator/patient decision (n=5).
Conclusions: Lisaftoclax plus novel therapeutic regimens was well tolerated and demonstrated preliminary antitumor activity in patients with either R/R MM or AL amyloidosis.
*Lisaftoclax is an investigational drug that has not been approved in any country and region.

On June 18, 2024 Calliditas Therapeutics AB (Nasdaq: CALT) (Nasdaq Stockholm: CALTX) ("Calliditas") reported that the United States Patent and Trademark Office (USPTO) has issued a patent for application no. 16/760,910 entitled "Use of NOX Inhibitors for Treatment of Cancer (Press release, Calliditas Therapeutics, JUN 18, 2024, View Source [SID1234644430])."

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The patent covers a method of treating a solid tumor presenting resistance to PD-1 inhibitor immunotherapy by administering setanaxib in combination with a PD-1 inhibitor. The patent will have an expiration date in 2039. Calliditas has corresponding applications and patents in several additional territories around the world, including a pending patent application in Europe.

"We are delighted that the product protection of setanaxib in the area of oncology is extended by way of this patent, and we look forward to expanding this to other geographies", said Renee Aguiar-Lucander, CEO.

Calliditas read out positive topline results of its Phase 2 head and neck cancer trial with setanaxib in May 2024. The analysis showed statistically significant improvements in progression-free survival (PFS), as well as in overall survival (OS), with statistically significant changes in tumor biology consistent with the mechanism of action of setanaxib.

On June 18, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported the company plans to report new data from the global randomized Phase 1b/2 combination study of amezalpat (TPST-1120) with atezolizumab and bevacizumab in first-line treatment of hepatocellular carcinoma (HCC) in a premarket press release followed by a webcasted conference call with associated slide presentation on Thursday, June 20, 2024 at 8:30 a.m. ET (Press release, Tempest Therapeutics, JUN 18, 2024, View Source [SID1234644429]).

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To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the investor section of the Tempest website at View Source The webcast will be available for replay for 30 days.

On June 18, 2024 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported that Paul Peter Tak, MD, PhD, FMedSci, Candel’s President and Chief Executive Officer, will participate in a fireside chat at the H.C. Wainwright 2nd Annual Immune Cell Engager Virtual Conference on Tuesday, June 25, 2024 at 3:00 p.m. ET (Press release, Candel Therapeutics, JUN 18, 2024, View Source [SID1234644428]).

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A live webcast of the fireside chat will be available by selecting Events and Presentations under the News & Events tab in the Investors section on candeltx.com. A replay of the webcast will be archived for up to 90 days following the session date.

On June 18, 2024 XBiotech (NASDAQ: XBIT) reported data from its Phase 1/Phase 2 randomized, double-blind, placebo-controlled multi-center study for advanced pancreatic cancer (Press release, XBiotech, JUN 18, 2024, View Source [SID1234644427]). Known as 1-BETTER, the study examined Natrunix (anti-interleukin-1alpha) antibody in combination with an established chemotherapy regimen (ONIVYDE (ON) + 5-Fluorouracil (5FU) + Leucovorin (LV), a regimen that is already widely used for treating pancreatic cancer but is associated with difficult toxicities and less then ideal survival outcomes. Natrunix was being evaluated as an anti-cancer agent for use in cytotoxic chemotherapy combinations where the Company believes it might potentially also improve tolerability of the chemotherapy.

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The Phase 1 portion was a dose escalation study in metastatic pancreatic cancer patients to determine if dose limiting toxicities (DLTs) occurred in combination with the ON+5FU+LV regimen in second- or third-line setting. DLTs were not expected with Natrunix and none were seen. The Natrunix dose in the Phase 2 portion was thus the highest dose used in the Phase 1 portion.

Sixty-five subjects were randomized into the Phase 2 study on a 1:1 basis to receive either Natrunix+ ON+5FU+LV (Arm1) or Placebo +ON+5FU+LV (Arm2). There were 33 subjects enrolled into Arm1 and 32 into Arm2. The Phase 2 treatment period was 24-weeks with subjects receiving therapy once every other week for a total of 12 cycles.

Subjects included in the study had confirmed metastatic, unresectable, or recurrent pancreatic adenocarcinoma of exocrine pancreas and were required to have had disease progression after one prior gemcitabine-based therapy or one FOLFIRINOX and gemcitabine containing therapy. All patients were required to have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1).

The primary endpoint for the Phase 2 study was to assess the safety and tolerability of Natrunix when used with the ON+5FU+LV combination. Overall, there were fewer adverse events (AEs) of any kind during the 24-week treatment period for the Natrunix arm compared to placebo (297 vs 336), with markedly fewer events in specific categories of adverse events during that time. There was a 28% reduction in the number of subjects experiencing significant adverse events (SAEs) in the Natrunix arm (9 out of 33) versus placebo (12 out of 32) that occurred during the 24-week treatment period. Subjects receiving the Natrunix ON+5FU+LV regimen also had about a 33% reduction in hospitalization (80 days versus 120 days) during the 24-week treatment period compared to subjects receiving placebo + ON+5FU+LV combination.

Subjects receiving the Natrunix combination also reported a 22% reduction in fatigue (28 vs 36), 32% improved appetite (19 vs 28) and 41% reduction in pain (17 vs 29) as of the last day of the 24-week treatment period compared to subjects receiving the placebo ON+5FU+LV combination.

Severe diarrhea that can be life -threatening is a significant complication for the ON+5FU+LV regimen. There was a two-fold reduction (9% versus 19%) in the incidence of severe diarrhea during the 24-week treatment regimen for patients receiving the Natrunix + ON+5FU+LV combination compared to placebo + ON+5FU+LV.

Overall Survival (OS), one of the secondary endpoints for the Phase 2 study, was conventionally defined in as time from randomization to death. The sample size for the study included intent-to-treat analysis of 33 subjects randomized into the Natrunix + ON+5FU+LV arm versus 32 subjects in Placebo + ON+5FU+LV arm. A Kaplan-Meier Survival Curve using a product limit comparison method was performed. This data highlights the observation that no subjects in the placebo ON+5FU+LV group (n=32) survived for longer than 330 days, whereas 8 subjects in the Natrunix ON+5FU+LV arm (n=33) were still alive as of day 330. Considering the small sample size, the borderline statistically significant p-value of p = 0.096 suggests prolonged survival for subjects receiving the Natrunix regimen.

The lead investigator for the study, David J. Park, MD Medical Oncologist, Medical Director for the providence St. Jude Crosson Institute, Fullerton, CA stated "Treatment of advanced pancreatic cancer in the second and third line settings presents significant challenges in terms of toxicity as well as efficacy. To observe these trends for reduced toxicity and potential survival benefit is remarkable, particularly given the limited sample size. The potential interaction between reduced toxicity, more time on treatment and improvement in survival makes intuitive sense for clinicians who treat these patients. These findings are extremely important."

While there was a relatively small number of pancreatic cancer patients enrolled in the Phase 2 portion of the study, in the Company’s opinion, the findings show better outcomes for the Natrunix + ON+5FU+LV group as compared to the control arm. The Company believes that the reduced number of serious and adverse events, the significant reduction in hospitalization, and improved OS during the respective time periods described above for each of these metrics suggest that Natrunix could represent a breakthrough advance for the treatment of pancreatic cancer.