On October 10, 2023 GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, reported that the first subject was dosed in a phase Ib/II trial of GFH009 (a highly selective CDK9 inhibitor) treating relapsed/refractory PTCL (peripheral T-cell lymphomas) patients (Press release, GenFleet Therapeutics, OCT 10, 2023, View Source [SID1234635826]). Designed to enroll a total of 95 patients, this multi-center (close to 40 hospitals in China), open-label, single-arm study will include the prominent Sun Yat-Sen University Cancer Center and the First Affiliated Hospital of Zhengzhou University.

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The phase I, multi-center trial of GFH009 monotherapy for relapsed/refractory hematological malignancies has completed its dose escalation portion in both China and the US. Preliminary results demonstrated favorable safety/tolerability and promising clinical efficacy of GFH009. Complete or partial responses were observed in acute myeloid leukemia and lymphoma patients; 4 PTCL patients were observed with clinical response including one in a continuous treatment for over 48 weeks. The recommended phase II dose (RP2D) has been determined to be 100 mg once per week based on all safety, pharmacokinetics, pharmacodynamics, and efficacy data.

There are approximately 100,000 newly diagnosed non-Hodgkin’s lymphoma（NHL）patients per year in China, with PTCL patients accounting for over 20% of new cases. Within the histologically and clinically heterogeneous group of PTCL, patients in most subtypes (other than ALK-positive ALCL patients) are relatively chemo-resistant and are less responsive to autologous stem cell transplants. There is significant room for improvement in terms of prognosis and overall survival rate in recurrent/refractory PTCL patients after first-line treatment. Based on current studies, the functional dependence on MCL1 and the amplification or copy-number gain of MYC observed in many PTCL cell lines are correlated to poor prognosis. Clinical trials of GFH009 demonstrated significant reduction in the expression of proto-oncogenes such as MYC, MCL1, and PCNA in patients with hematological malignancies including PTCL.

"GFH009 is GenFleet’s first clinical-stage asset for hematological malignancies in a global multi-center trial. Currently there is significant unmet medical need in recurrent/refractory PTCL; studies from GFH009 have confirmed its potential in combating the disease. Following on GFH009’s favorable safety profile and preliminary efficacy in phase I trial, we are planning to explore more studies of GFH009 monotherapy and combination therapies for global patients." stated Yu Wang, M.D., Ph.D., Chief Medical Officer of GenFleet.

GenFleet received IND approval in 2020 for the GFH009 monotherapy (NCT04588922) to proceed into phase I trial treating patients with relapsed/refractory hematological malignancies. In 2022, GenFleet and SELLAS Life Sciences Group (Nasdaq: SLS) entered into an exclusive license agreement across all therapeutic and diagnostic uses. Conducted by SELLAS, the phase IIa clinical trial of SLS009 (GFH009) with venetoclax and azacitidine is ongoing in the US treating r/r AML patients.

References:

1. Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments, 2023, Cancer Biology & Therapy
2. Current status and progress of lymphoma management in China, 2018, International Journal of Hematology
3. SELLAS Announces First Patient Dosed in Phase 2a Clinical Trial of GFH009 in Acute Myeloid Leukemia, 2023
4. VIP152, a Selective CDK9 Inhibitor, Induces Complete Regression in a High-Grade B-Cell Lymphoma Model and Depletion of Short-Lived Oncogenic Driver Transcripts, MYC and MCL1, with a Once Weekly Schedule, 2021, Blood

About CDK9 and GFH009

As a family of serine & threonine kinases, the cyclin-dependent kinase (CDK) family plays an important role in cell cycle regulation and transcription; CDK9 activity is inversely correlated with the overall survival rate of patients with multiple tumors. Data from phase I trial and the preclinical research of GFH009 were posted at the 2002 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper). GFH009 monotherapy is well tolerated with preliminary clinical activity in patients with relapsed/ refractory lymphomas and an AML patient observed with complete remission (with no minimal residual disease) lasting for over 8 months.

According to preclinical research, GFH009 reduces the expression of downstream oncogenes required for rapid cellular division and protein expression through specific inhibition of CDK9. With more than 100 times selectivity over other CDK subtypes, this depletion via GFH009 inhibition of CDK9 likely deprives oncogene-addicted cancer cells of crucial survival signals, leading to senescence and death. GFH009 also exhibits strong anti-proliferative activities in multiple human cell lines, effectively inhibits the growth of tumor in various xenograft models and significantly improves survival of tumor bearing animals.

About PTCL (peripheral T-cell lymphomas)

The incidence of PTCL in Asia is substantially higher compared with western countries. The most common PTCL subtypes in China include NK/T-cell lymphoma (NKTCL), PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL).

Currently, CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP with etoposide remain the most commonly used first-line treatment for PTCL. Autologous stem cell transplantation (AUTO-HSCT) may follow as a consolidation therapy for eligible patients. Based on retrospective studies, ALK-positive ALCL patients have the most favorable prognosis after applying CHOP-based regimens. However, the prognosis of relapsed/refractory PTCL patients was poor, and the median overall survival was less than 6 months. In recent years, the development of targeted drugs provided new options for patients with relapsed and refractory PTCL.

On October 10, 2023 Accent Therapeutics, a biopharmaceutical company pioneering a new class of small molecule precision cancer therapies, reported that it will present data unveiling a novel, previously undisclosed program in two poster presentations at the 35th AACR (Free AACR Whitepaper)-NCI-EORTC Symposium held October 11-15, 2023 in Boston, Massachusetts (Press release, Accent Therapeutics, OCT 10, 2023, View Source [SID1234635825]). The company will also present data supporting development of its ADAR1 and DHX9 programs in two additional poster presentations.

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5′→3′ exoribonuclease 1 (XRN1) is an enzyme that degrades single- and double-stranded RNA, playing roles in extracellular mRNA turnover and innate immunity through prevention of dsRNA accumulation and subsequent MDA5 and PKR-mediated immune signaling. Accent has identified XRN1 as a key vulnerability for therapeutic targeting of tumors with elevated type I interferon signaling and is developing small molecule inhibitors of this compelling oncology target, for which there are none currently disclosed.

Two of the company’s presentations at the meeting describe the preclinical validation of XRN1 as an oncology target and the subsequent characterization of selective inhibitors of XRN1. XRN1 knockout resulted in cell death due to accumulation of dsRNA and downstream activation of the MDA5 and PKR innate immune pathways in cells with intrinsically elevated type I interferon signaling, but not in those with low interferon signaling. Accent has identified novel, potent, and selective allosteric inhibitors that bind XRN1 with nanomolar target affinity without binding to XRN2.

"We are excited to share our progress advancing our portfolio and to introduce our XRN1 inhibitor program as a potentially impactful approach to helping cancer patients," said Robert Copeland, Ph.D., President and Chief Scientific Officer of Accent Therapeutics. "These data demonstrate the versatility and promise of pursuing critical intracellular dependences of cancer biology to identify novel oncology targets with the potential to benefit broad patient populations."

ADAR1 has emerged as a promising, yet challenging-to-drug, oncology target for which inhibition has been shown to induce downstream immune activation and subsequent cell death in cancer cells with high intrinsic type 1 interferon signaling—a trait that 15-30% of primary tumors share. Accent will also present its innovative suite of in vitro and cellular assays that enable identification of small molecule inhibitors of ADAR1. The resulting compounds are shown to potently inhibit cell growth in a cancer cell line with high interferon type 1 signaling.

The company’s final presentation at the meeting will highlight its progress developing small molecule inhibitors of the novel oncology target DHX9, an RNA helicase that has been reported to play important roles in the maintenance of genomic stability in multiple cancer types. The presentation will demonstrate that DHX9 inhibition in microsatellite instable tumors exhibiting defective mismatch repair induces replication stress and subsequent cell death.

The poster presentations will be archived on the Accent website following the meeting.

Details for the presentations are as follows:

Title: Exoribonuclease XRN1 is a Therapeutic Vulnerability in Tumors with Intrinsically Elevated Type I Interferon Signaling
Abstract Number: A163
Session & Location: Poster Session A – Exhibit Hall D
Session Date & Time: Thursday, October 12, 12:30 pm – 4:00 pm ET
Presenter: Maureen M. Lynes, Ph.D.

Title: Discovery of Small Molecule Inhibitors of ADAR1
Abstract Number: A170
Session & Location: Poster Session A – Exhibit Hall D
Session Date & Time: Thursday, October 12, 12:30 pm – 4:00 pm ET
Presenter: Shane M. Buker, Ph.D.

Title: Characterization of Selective, Allosteric Inhibitors of Human XRN1
Abstract Number: B073
Session & Location: Poster Session B – Exhibit Hall D
Session Date & Time: Friday, October 13, 12:30 pm – 4:00 pm ET
Presenter: Gordon J. Lockbaum, Ph.D.

Title: DHX9 Inhibition as a Novel Therapeutic Modality in Microsatellite Instable Colorectal Cancer
Abstract Number: C087
Session & Location: Poster Session C – Exhibit Hall D
Session Date & Time: Saturday, October 14, 12:30 pm – 4:00 pm ET
Presenter: Jennifer Castro

About XRN1
XRN1 is an RNA exonuclease that plays important roles in innate immunity by preventing double-stranded RNA (dsRNA) accumulation. Tumors with intrinsic type I interferon signaling are acutely sensitive to XRN1 loss, making it a strong oncology target. Inhibitors of XRN1 have potential for use as monotherapy and in combination with immuno-oncology therapeutics. Accent is applying structure-based design approaches to develop potent and selective small molecule inhibitors of XRN1 to address cancer indications with high unmet medical need.

About ADAR1
Adenosine deaminase acting on RNA 1 (ADAR1) is an enzyme that edits double-stranded RNA (dsRNA) to prevent recognition and downstream immune signaling. In tumor cells with high interferon signaling, small molecule inhibitors of ADAR1 have been shown to induce selective cell killing and immune sensitization, making it a highly attractive target for monotherapy and combination approaches with immunotherapies, such as checkpoint inhibitors. Accent is developing ADAR1 targeted therapies to address many solid tumor indications with significant unmet need, including non-small cell lung cancer, triple-negative breast cancer, ovarian cancer, and head and neck squamous cell carcinomas.

About DHX9
Accent’s lead program is a first-in-class DHX9 inhibitor with the potential to address high unmet need indications that lack targeted therapies; these include colorectal, endometrial, gastric, and other high microsatellite instable (MSI-H) cancers. Several additional undisclosed cancer types representing large patient populations are also being explored based on their sensitivities to DHX9 inhibition. DHX9 is a DNA/RNA helicase that has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability. Hence, this enzyme represents a compelling novel oncology target as inhibition of DHX9 exploits key tumor vulnerabilities, resulting in cancer-specific death. Accent is currently conducting IND-enabling studies evaluating its DHX9 inhibitor.

On October 10, 2023 Lunit (KRX:328130.KQ), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics, reported the presentation of 9 studies featuring its AI pathology research at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2023 Congress, scheduled to be held in Madrid, Spain, from October 20 to October 24, 2023 (Press release, Lunit, OCT 10, 2023, View Source [SID1234635824]).

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This year’s collection of abstracts delves into multifaceted research, including the use of AI-powered analysis to predict treatment outcomes in different cancer types, assess HER2 expression in breast and biliary tract cancer, and streamline clinical workflows for treatment decisions in lung cancer, all utilizing the Lunit SCOPE suite.

The highlighted abstracts for ESMO (Free ESMO Whitepaper) 2023 include:

Lunit investigates AI’s potential to predict multiple druggable mutations in non-small cell lung cancer from H&E stained images, paving the way for more efficient clinical workflows and treatment decisions.
In a collaborative study, Lunit SCOPE IO distinguishes MMR-D (Mismatch repair deficiency) from MMR-P (Mismatch repair proficiency) colon cancers by analyzing features in whole slide images, offering insights with implications for prognosis and subtype-based interventions.

Lunit evaluates the efficacy and safety of avelumab plus gemcitabine in leiomyosarcoma patients who failed first-line chemotherapy, demonstrating encouraging results in terms of response rates, duration of response, and overall survival.

Analyzing HER2 expression with Lunit SCOPE HER2 in breast cancer cases proves effective in predicting FISH (Fluorescence In Situ Hybridization) positivity and therapy response, offering valuable insights for targeted therapy.
In another study utilizing Lunit SCOPE HER2, Lunit assesses HER2 expression and TIL (Tumor-infiltrating lymphocyte) density in biliary tract cancer, providing valuable insights into the tumor microenvironment’s role in treatment strategies.

Lunit’s AI-powered spatial analysis of TIL in advanced biliary tract cancer patients, who are planning to be treated with anti-PD-1 therapy, demonstrates the potential of immune phenotypes to predict therapy outcomes.
Using Lunit SCOPE IO, a study explores the predictive role of immune phenotypes and Inflamed Score in metastatic colorectal cancer patients, providing insights into immunogenicity as a biomarker.
Lunit’s AI-powered TIL density analysis in recurrent/metastatic head and neck squamous cell carcinoma patients treated with ICI reveals favorable treatment outcomes, especially in those with higher intratumoral TIL density.
"These groundbreaking abstracts showcase the power of the Lunit SCOPE suite in unraveling complex insights across various cancer types, from distinguishing tumor subtypes to predicting treatment responses," said Brandon Suh, CEO of Lunit. "We’re on our way towards making the Lunit SCOPE suite an essential biomarker for cancer immunotherapy – contributing to the advancement of personalized oncology through innovative AI solutions."

For inquiries or to schedule a meeting with the Lunit team, please contact [email protected].

On October 10, 2023 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company developing targeted and transformative cancer therapies using its proprietary AI and machine learning (ML) platform, RADR, with multiple clinical stage drug programs, reported that Lantern management will be presenting at the ThinkEquity Conference on Thursday, October 19, 2023, at the Mandarin Oriental in New York, NY (Press release, Lantern Pharma, OCT 10, 2023, View Source [SID1234635823]).

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Lantern Pharma is scheduled to present at the conference at 1:30 p.m. ET on October 19.

Webcast Link: View Source
Conference Registration Link: View Source
Lantern Pharma management will be available for one-on-one meetings to be held throughout the conference.

On October 10, 2023 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported that the company plans to report new and updated data from the global randomized Phase 1b/2 combination study of TPST-1120 with atezolizumab and bevacizumab in first-line treatment of hepatocellular carcinoma (HCC) in a premarket press release on Wednesday, October 11, 2023, followed by a webcasted conference call with associated slide presentation at 8:30 a.m. ET on Wednesday, October 11, 2023 (Press release, Tempest Therapeutics, OCT 10, 2023, View Source [SID1234635820]).

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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.