On October 10, 2023 Signifying a monumental step forward in the domain of powered antibody therapies, the SparX Group reported its strategic alliance with Arovella Therapeutics Ltd (ASX: ALA) (Press release, Arovella Therapeutics, OCT 10, 2023, View Source [SID1234635831]). This collaboration emphasizes the utilization of SPX-101, an innovative monoclonal antibody (mAb) that targets the Claudin 18.2 (CLDN18.2) tumor specific antigen, as an exciting component in Arovella’s CLDN18.2-CAR-iNKT cells as a leading off-the-shelf CAR-iNKT cell therapy.

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Dr. Gui-Dong Zhu, CEO of the SparX Group, elucidated on the significance of this collaboration: "Our partnership with Arovella represents a transformative phase in advancing mAb-based therapies. Invariant Natural Killer T (iNKT) cells, distinguished by their recognition of lipid antigens via the CD1d molecule, have emerged as potent therapeutic vectors. Arovella’s cutting-edge CAR-iNKT platform, encapsulating advanced techniques for in-vitro expansion and post-infusion persistence of iNKT cells, underscores their leadership in this domain. We profoundly acknowledge CLDN 18.2-iNKT cell therapy as a groundbreaking paradigm in oncological therapeutics."

Echoing the enthusiasm, Dr. Michael Baker, CEO of Arovella, remarked, "Licensing the CLDN18.2 mAb sequence from SparX represents a seminal phase in our therapeutic trajectory. SparX’s sophisticated work, spotlighting the unparalleled attributes of their CLDN18.2 monoclonal antibody, coupled with its safety and specificity, accentuates the global attention this molecular target is garnering. We’re uniquely positioned as the only global entity developing a CAR-iNKT cell therapy aimed at CLDN18.2. The synergistic combination of iNKT cells with the CLDN18.2 CAR paves an exciting avenue to develop novel cancer therapeutics."

CLDN18.2 manifests predominantly in gastric cancers (GC), gastroesophageal junction cancers (GEJC), pancreatic cancers (PC), and a spectrum of other solid tumors. Both GC and GEJC represent formidable clinical challenges, registering over a million new cases annually worldwide and culminating in 770,000 fatalities. This places them as the fourth leading cause of cancer-related deaths globally. Spearheaded by SparX, SPX-101 embodies a pinnacle of molecular engineering, stemming from SparX’s sophisticated SAILINGTM discovery platform. This mAb is designed for optimized therapeutic efficacy, offering the potential to be recognized as a best-in-class molecular entity targeting claudin 18.2.

Expounding on the cellular dynamics, Invariant Natural Killer T (iNKT) cells are a specialized T cell subset known for recognizing lipid antigens via the CD1d molecule. These cells possess inherent attributes like tissue infiltration capabilities, counteracting tumor-promoting cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and orchestrating a robust immune response by recruiting auxiliary immune cells against tumor sites. The pathological architecture of tumor development often exposes the CLDN18.2, rendering it accessible to novel treatments such as CAR-iNKT cell therapies. Preliminary clinical findings indicate that iNKT cell therapies might proffer a superior safety profile relative to alternative T cell therapies, notably displaying a reduced propensity for cytokine release syndrome, a prevalent and potential adverse reaction observed in certain cell therapies.

On October 10, 2023 XNK Therapeutics AB ("XNK") reported that it has applied for and been granted funding by Sweden’s innovation agency Vinnova (Press release, XNK Therapeutics, OCT 10, 2023, View Source [SID1234635830]). The grant consists of SME support through the Competence Center for Next-generation NK Cell-based Cancer Immunotherapy (NextGenNK). The competence center is coordinated by the Karolinska Institutet and XNK has been a member since the center’s inception in 2020. The funding amounts to up to 1.7 million SEK over two years and will be used in a specific preclinical program in XNK’s project portfolio.

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On October 10, 2023 Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH), a discovery and development stage specialty pharmaceutical company focused on improving the outcomes of cancer patients treated with radiation therapy (RT), reported that Dr. Anatoly Dritschilo, Chief Executive Officer, will present and host one-on-one meetings with investors at the Lytham Partners Fall 2023 Investor Conference, taking place virtually on October 17, 2023 (Press release, Shuttle Pharmaceuticals, OCT 10, 2023, View Source [SID1234635828]).

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Company Webcast

The Company’s webcast presentation will be available for viewing at 7:00am ET on Tuesday, October 17, 2023, on the Company’s website at View Source or View Source The webcast will also be archived and available for replay.

1×1 Meetings

Management will be participating in virtual one-on-one meetings throughout the event. To arrange a meeting with management, please contact Lytham Partners at 1×[email protected] or register at View Source

On October 10, 2023 Scorpion Therapeutics, Inc. ("Scorpion"), a pioneering clinical-stage oncology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, and Pierre Fabre Laboratories reported that the first patient has been dosed in a Phase 1/2 first-in-human dose escalation and expansion clinical trial evaluating STX-721, Scorpion’s highly differentiated, orally bioavailable, irreversible highly selective tyrosine kinase inhibitor ("TKI") targeting epidermal growth factor receptor ("EGFR") and ERBB2 (HER2) Exon 20 insertion ("ex20ins") mutations, well-known, clinically validated oncogenic drivers in non-small cell lung cancer ("NSCLC") (Press release, Scorpion Therapeutics, OCT 10, 2023, View Source;301949595.html [SID1234635827]). The Phase 1/2 clinical trial will evaluate STX-721 as a monotherapy in participants with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations.

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NSCLC is the most common sub-type of lung cancer and various EGFR mutations are the most frequent drivers of NSCLC, occurring in up to 38% of tumors, depending on geography.[1],[2],[3] Of this population, up to 10% have ex20ins mutations.[4]

"We are excited to begin the clinical evaluation of STX-721, our mutant-selective EGFR ex20ins inhibitor with a potentially best-in-class profile, for the treatment of non-small cell lung cancer," said Axel Hoos, M.D., Ph.D., Chief Executive Officer of Scorpion. "The initiation of our second clinical trial this year underscores our research team’s productivity and execution, as well as the confidence that Scorpion and Pierre Fabre Laboratories have in the quality, selectivity, and potential clinical differentiation of this compound. Based on preclinical data to-date, we believe that STX-721 is more selective and can provide a wider therapeutic window than other therapies currently on the market or in development and, as a result, has the potential to deliver superior efficacy to this highly underserved patient population."

"We are pleased to see STX-721 enter the clinic, and the overall progress we’ve achieved since we announced the partnership with Scorpion six months ago," said Eric Ducournau, Chief Executive Officer of Pierre Fabre Labor­­­­­­atories. "Our two teams have been working closely on both of the EGFR candidates and we look forward to seeing how patients may benefit from this targeted therapy."

STX-721 is an oral treatment designed to be mutant-selective and optimized for tolerability and efficacy when compared to currently available commercial treatments. Existing therapeutic options face significant limitations that are associated with the inhibition of wild-type EGFR in healthy tissues, including serious adverse events often leading to dose reductions or interruptions.

"STX-721 is a wild-type-sparing, oral inhibitor of EGFR ex20ins mutations with a compelling preclinical selectivity profile," said Michael Streit, M.D., Chief Medical Officer of Scorpion. "In this Phase 1/2 trial, we will aim to demonstrate how these unique qualities translate into a potentially best-in-class product profile that increases response rates as a result of its optimized design. We look forward to partnering with study investigators, as well as our colleagues at Pierre Fabre Laboratories, to evaluate STX-721 in patients with EGFR ex20ins-mutated NSCLC."

About STX-721 Phase 1/2 Trial

Scorpion’s Phase 1/2 clinical trial, in collaboration with Pierre Fabre Laboratories, is a multi-center, open-label study designed to evaluate the safety and tolerability of STX-721 in multiple ascending doses for patients with locally advanced or metastatic NSCLC driven by EGFR mutations. The goal of the trial is to characterize the safety profile of STX-721 and determine a maximum tolerated dose or a lower optimal-biologically active dose, if appropriate, as the recommended Phase 2 dose ("RP2D") as a monotherapy for NSCLC driven by EGFR exon20ins mutations. Once the RP2D is established, Scorpion intends to continue to evaluate the safety, tolerability and overall efficacy of STX-721. Secondary objectives for this Phase 1/2 trial include assessing the pharmacokinetic profile, pharmacodynamic effects and clinical response as measured by Response Evaluation Criteria In Solid Tumors ("RECIST") version 1.1. To learn more about the first-in-human trial of STX-721, please visit this page.

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.