On June 18, 2024 REVEAL GENOMICS, S.L., a pioneering biotechnology start-up based in Barcelona set to revolutionize precision oncology through biomarker innovation, reported the start of a prospective study in collaboration with the Dana-Farber Cancer Institute (Dana-Farber) (Press release, REVEAL GENOMICS, JUN 18, 2024, View Source [SID1234644433]). This trial will evaluate the turnaround time of the HER2DX genomic test to determine its feasibility in clinical practice in the US.

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HER2DX test results are currently generated and managed in Barcelona, Spain, with an average turnaround time of 8.1 business days, according to data presented at the ESMO (Free ESMO Whitepaper) Breast Conference last May. This study at Dana-Farber aims to additionally evaluate the turnaround time of HER2DX conducted at Brigham and Women’s Center for Advanced Molecular Diagnostics (CAMD, Boston, MA, USA) in tumor samples of patients with newly diagnosed HER2+ early-stage breast cancer.

The study will also examine how the HER2DX test results influence therapeutic decisions by Dana-Farber physicians for patients with stage I-III HER2+ breast cancer, and the confidence levels of both patients and physicians before and after the test.

Patricia Villagrasa, REVEAL GENOMICS’ CEO, says, "We are excited to see the HER2DX test being used in the United States to improve clinical decision-making and patient outcomes. This collaboration with the Dana-Farber Cancer Institute is a significant milestone in our mission to enhance precision oncology through innovative biomarker solutions."

Sara M. Tolaney, MD, MPH, Chief of Division of Breast Oncology and Associate Director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber, adds, "The HER2DX test has the potential to significantly influence therapeutic decisions for patients with HER2+ breast cancer. We are excited to be the first center in the United States to incorporate HER2DX and to explore its practical application in diverse clinical environments."

Adrienne G. Waks, MD, and Principal Investigator of the study at Dana-Farber, notes: "In addition to its potential incorporation into clinical practice, the fact that the study analyzes decision-making and collects information on physician and patient opinions makes the results of this study very powerful data for the routine use of the test."

The study will include patients with newly diagnosed stage I-III HER2+ breast cancer. In addition to assessing turnaround time, the study will provide questionnaires to patients to assess their basic understanding of their disease and the HER2DX assay, and to physicians to assess their pre-assay treatment choice and confidence in the results. The study team will record the physician researcher’s choice of treatment before and after the HER2DX results.

About HER2DX

HER2DX is the world’s first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS since January 2022, the HER2DX is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e., tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX predicts:

Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2+ breast cancer.
About HER2+ breast cancer

HER2+ breast cancer accounts for 20% of all diagnosed breast tumors. This represents more than 390,000 new cases diagnosed worldwide every year, meaning that, on average, 3 women are diagnosed with HER2+ breast cancer every 4 minutes. HER2+ breast cancer is clinically, and biologically heterogeneous, and standard clinical-pathological assessment has proven insufficient in capturing this heterogeneity. Understanding this biological heterogeneity is key to identifying the prognosis of each patient and the benefit from systemic therapies that target HER2.

On June 18, 2024 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, reported updates on its oncology pipeline at an investor meeting. At several major international oncology annual meetings this year, Innovent presented clinical data on multiple cancer drug candidates, including 10 oral reports and over 15 posters (Press release, Innovent Biologics, JUN 18, 2024, View Source [SID1234644432]). In a conference call with investors on June 17, Innovent interpreted the clinical data for these drugs in detail. The company also outlined its current R&D strategy centered on global innovation, as well as the early research mechanisms, development strategies and future directions for multiple mid- and early-stage molecular candidates in its pipeline. Innovent’s Chief Financial Officer Rachel You, Senior Vice President of Oncology Development Dr. Hui Zhou, and Vice President of Oncology Biology and ADC Drug Research Dr. Kaijie He attended the meeting and made reports.

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Oncology pipeline development strategy: extensively deploy "IO + ADC" to solve unmet clinical needs worldwide

Scientific and technological advancements have steadily increased cancer patient survival rates and quality of life. However, many unmet clinical needs persist in cancer treatment. These include the limited response rates to immunotherapies like PD-1, with most responses resulting in relapse or resistance. Additionally, the effectiveness of current mainstream treatment, such as anti-angiogenic drugs, remains limited. Significant unmet needs continue to drive further innovation in oncology drug development.

Innovent has built a product pipeline of 36 new drug candidates, including 22 in oncology. Utilizing a world-leading antibody technology platform, differentiated linker-payloads and deep scientific expertise in oncology, Innovent has extensively deployed a combination of immune-oncology (IO) and antibody-drug conjugates (ADCs). This comprehensive "IO + ADC" approach aims to drive global innovation and enhance the brand positioning for the Company’s oncology pipeline, which strives to "further life’s possibilities."

Key product milestones: PoC + MRCT driving the globalization of innovative therapies

The Company is progressing its innovative oncology pipeline through clinical proof-of-concept (PoC) studies and global multi-regional clinical trials (MRCT). Several high-potential molecules have now entered clinical development, including the three novel candidates IBI363, IBI343 and IBI389, which were discussed in detail on the call. Innovent also has additional bispecific antibody and ADC candidates advancing in early global clinical development.

IBI363: First-in-class PD-1/IL-2 α-bias bispecific antibody fusion protein shows promising anti-tumor efficacy across multiple cancer types, including in immunotherapy-treated and ‘cold’ tumors, signaling the emergence of a potential next-generation IO therapy

IBI363 represents Innovent’s continuous research and innovation in immuno-oncology. At this meeting, Innovent reported for the first time on IBI363’s novel mechanical of action and provided updates on its clinical development progress.
Regarding its molecular design, ICI363 creatively employs an α-biased approach while weakening β and γ signaling, significantly improving the therapeutic window of IL-2. Through specific binding to PD-1, it can selectively stimulate and amplify tumor-specific T cells that co-express PD-1 and CD25, thereby exerting an anti-tumor effect. The novel design leverages the cytokine’s activating potential while mitigating systemic toxicity.
IBI363 exhibits excellent drug-like properties, demonstrating antibody-like pharmacokinetics (IgG-like PK) and low immunogenicity. This allows for unprecedented dosing levels of IBI363 while maintaining a favorable safety profile, overcoming the toxicity concerns typically associated with IL-2 therapy.
In the Phase 1 clinical trials involving over 300 subjects, IBI363 demonstrated encouraging anti-tumor efficacy across multiple representative cancer types, including immunotherapy-treated driver gene wild-type non-small cell lung cancer, immunotherapy-treated melanoma, immunotherapy treatment-naïve mucosal melanoma, and the immunologically ‘cold’ colorectal cancer. These results highlight IBI363’s broad-spectrum anti-tumor potential across diverse tumor types and treatment settings.
Building on the encouraging clinical data, Innovent is further expanding IBI363’s clinical development, including continued evaluation of the 3mg/kg high dose cohort to determine the optimal dose for subsequent studies, initiating Phase 2 trials in the United States, and exploring additional combination therapy opportunities to broaden IBI363’s potential applications.
Two CLDN18.2-target based innovative technology modalities, IBI343 and IBI389, showed initial breakthrough efficacy

IBI343: Innovative TOPO1i CLDN18.2 ADC, the world’s first ADC drug to show initial breakthrough efficacy in pancreatic cancer

IBI343 is a world-leading innovative TOPO1-inhibitor CLDN18.2 ADC that features an excellent molecular design utilizing world-class specific glycoconjugate technology for high in vivo stability. IBI343 binds to the Claudin 18.2-expressing tumor cells, which causes Claudin 18.2-dependent ADC internalization to occur. Meanwhile, the high potency payload (exatecan) is used with strong bystander killing effect. Notably, its Fc-silenced design mitigates ADCC-mediated gastrointestinal toxicity, ensuring a high safety profile. This integrated design positions IBI343 at the forefront of innovative CLDN18.2-targeted ADCs.
The world’s first ADC single agent to show breakthrough efficacy in pancreatic cancer: Preliminary Phase 1 data of IBI343 in pancreatic cancer patients who had received at least one line of treatment showed that the objective response rate (ORR) was 40% in CLDN18.2 IHC1/2/3+≥60% pancreatic cancer patients (n=10) who received 6 mg/kg IBI343.
In addition to pancreatic ductal adenocarcinoma (PDAC), IBI343 has shown strong anti-tumor effects in the treatment of late-line gastric cancer, and its Phase 3 MRCT clinical trial is under preparation.
IBI389 (anti-CLDN18.2/CD3 bispecific antibody): First-in-class T-cell engager with anti-tumor activity observed in pancreatic cancer

IBI389 is an anti-CLDN18.2 T cell-engaging bispecific antibody developed by Innovent. It induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the surfaces of tumor cells. IBI389 stimulates T-cell activation, resulting in cytolytic protein production, inflammatory cytokine release and further T-cell proliferation, which eventually leads to durable anti-tumor effects. Preclinical results show that even in cell lines with low expression of CLDN18.2, IBI389 can still bind to tumor cells and show significant anti-tumor efficacy.
IBI389 has shown promising efficacy signals in advanced gastric and pancreatic cancers, including cases with low to medium CLDN18.2 expression. Notably, as the world’s first bispecific antibody targeting CLDN18.2/CD3 to publish clinical data, IBI389 has shown significant initial anti-tumor effects in pancreatic cancer, marking a breakthrough for this innovative drug form in the field of difficult-to-treat cancers.
ASCO clinical data showed that among 27 pancreatic cancer subjects who received 600μg/kg IBI389 and underwent at least one post-baseline tumor assessment, the objective response rate (ORR) was 29.6%, the confirmed objective response rate (cORR) was 25.9%, and the disease control rate (DCR) was 70.4%. Among the 18 subjects with CLDN18.2 IHC 2/3+≥40%, the cORR reached 38.9%.
Based on the unique advantages of IBI343 and IBI389 demonstrated in early clinical trials, Innovent is advancing the development of IBI343 for the MRCT Phase 3 clinical trial in gastric cancer. Additionally, the Company is moving forward with proof-of-concept clinical studies of both IBI343 and IBI389 in the difficulty-to-treat pancreatic cancer.
Looking ahead, Innovent will continue to advance the high-quality clinical development of its oncology product line, address unmet medical needs in cancer treatment and promote global innovation guided by its "IO + ADC" strategy.

Dr. Hui Zhou, Senior Vice President of Oncology Development at Innovent Biologics, said: "As one of the few biopharmaceutical companies with leading R&D capabilities in both IO and ADC, we possess a unique competitive advantage in next-generation oncology treatment innovations. We will adhere to our mission of empowering patients worldwide with affordable, high-quality biopharmaceuticals, aiming to benefit even more patients and support the Healthy China 2030 initiative."

Detailed sharing materials can be downloaded from the company’s official website, link: View Source

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.