On June 27, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported the grant of a new patent (number 11,684,654) entitled "Combined Preparations for the Treatment of Cancer or Infection" by the United States Patent Office (Press release, Immutep, JUN 27, 2023, View Source [SID1234632938]).

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This United States patent was filed as a second divisional application and follows the grant of the United States parent patent and first divisional patent announced in December 2020 and March 2021, respectively.

The claims of the new patent build on the protection provided by the two previously granted patents, and are directed to methods of treating cancer by administering Immutep‘s lead active immunotherapy candidate eftilagimod alpha ("efti") and a PD-1 pathway inhibitor, specifically BMS-936559, durvalumab, atezolizumab or avelumab. The expiry date of the patent is 15 November 2036 (including 312 days of patent term adjustment).

"We continue to build our patent estate around lead candidate efti, which is a unique biomolecule and shows great promise in being able to ultimately help diverse sets of cancer patients, including those with more complex needs. Here we add another key US patent which is closely aligned with our clinical development pipeline. These key patents support ongoing investment and allow us to confidently push forward across all of our business functions, including clinical, manufacturing, and business development," said Marc Voigt, CEO of Immutep.

A continuation application and a further divisional application have been filed to pursue other embodiments of the invention.

About Eftilagimod Alpha (Efti)

Efti is Immutep’s proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen presenting cell (APC) activator that stimulates both innate and adaptive immunity for the treatment of cancer. Efti binds to and activates antigen-presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy.

Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

On June 27, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a publication in Cancer Immunology Research1 entitled: ‘Enhancing CAR T cell therapy using Fab-Based Constitutively Heterodimeric Cytokine Receptors (Press release, Autolus, JUN 27, 2023, View Source [SID1234632937]).’

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For CAR T cells to be effective, they must engraft in the patient, expand to sufficient numbers and persist at the site of disease. Often this can involve intervals in the absence of cognate antigen, for instance during trafficking, or in the face of a hostile tumor microenvironment. T cells in a physiological immune response are supported by a network of immune cells which provide cytokine signals to stimulate proliferation and survival. CAR T cells must survive in the absence of such networks.

To address this, Righi et al describe dFabCCR, a constitutive cytokine receptor architecture. dFabCCR is a highly versatile T cell engineering component which can transmit arbitrary cytokine signals to a CAR T cell: cytokine signals normally associated with T cells such as IL2 and IL7 can be transmitted, these maintain T cells as IL2/7 exposure would do. When screening a library of different cytokine dFabCCRs, other cytokine signals such as that from IL18 or even GM-CSF had distinct functional effects on CAR T cell biology which may have therapeutic advantages in some settings.

"Achieving sufficient CAR T cell expansion and persistence can be difficult when targeting solid cancer antigens," said Dr Martin Pule, Chief Scientific Officer and Founder of Autolus. "Development of the dFabCCR architecture allows us to supply CAR T cells with versatile constitutive cytokine signals overcoming a barrier to effective CAR T cell therapies for solid cancer and is another powerful entry in our toolkit of T cell engineering components."

On June 27, 2023 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, reported the completion of planned patient enrollment in the Phase 1 dose escalation study evaluating the safety, tolerability, and pharmacokinetics of HPN217 in patients with relapsed/refractory multiple myeloma (Press release, Harpoon Therapeutics, JUN 27, 2023, View Source [SID1234632936]). Additional patients currently in screening will also be allowed to enroll.

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"Completing enrollment in the Phase 1 trial of HPN217 is an important step towards potentially bringing this therapy to patients with advanced disease who have progressed after prior treatments," said Luke Walker, M.D., Chief Medical Officer of Harpoon Therapeutics. "I would like to thank our patients and their caregivers, as well as our clinical partners and dedicated team of employees who have participated in this Phase 1 trial and advanced the development of HPN217."

"We are pleased to have achieved this important milestone for Harpoon, with the enrollment of the first of our two TriTAC clinical compounds having completed dose escalation as planned," said Julie Eastland, President and CEO of Harpoon Therapeutics. "The identification of the recommended dose(s) for Phase 2 and the presentation of Phase 1 data is anticipated by the end of 2023."

About the HPN217 Clinical Trial

HPN217 is being evaluated in an ongoing Phase 1, multicenter, open-label dose escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK) and clinical activity in patients with relapsed/refractory multiple myeloma who have had at least three prior systemic treatments, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody, including patients with prior exposure to BCMA therapy. Primary objectives are characterization of safety, tolerability, PK and determination of the recommended Phase 2 dose.

For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT04184050.

About HPN217

HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient’s own immune cells to kill tumor cells. HPN217 is being evaluated in an ongoing Phase 1, multicenter, open-label dose escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK) and clinical activity in patients with relapsed/refractory multiple myeloma who have had at least three prior systemic treatments.

In November 2019, Harpoon Therapeutics and AbbVie announced a licensing agreement and option to advance HPN217 and expand an existing discovery collaboration. Under the terms of the agreement, AbbVie may exercise its option to license HPN217 after completion of the Phase 1 clinical trial.

In March 2022, the FDA granted Fast Track designation to HPN217, underscoring its potential to address a serious unmet medical need for patients with relapsed, refractory multiple myeloma.

On June 26, 2023 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company advancing novel, oral, non-systemically absorbed biotherapeutics to transform the care of serious diseases, reported that its management team will participate in the SVB Securities Healthcare Therapeutics Forum, being held in New York, July 11-12, 2023 (Press release, Synlogic, JUN 27, 2023, View Source [SID1234632935]). The Synlogic team will be available for one-on-one investor meetings. To register for the conference or request one-on-one meetings, please contact your SVB Securities representative.

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On June 27, 2023 ONK Therapeutics Ltd, an innovative NK cell therapy company, reported that the European Patent Office (EPO) has granted its licensed patent covering CISH knockout (KO) in NK cells, irrespective of the source of the NK cells, including human cord blood-derived, peripheral blood-derived, and NK cells derived from induced pluripotent stem cells (iPSCs) (Press release, ONK Therapeutics, JUN 27, 2023, View Source [SID1234632933]).

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The patent granted to ONK’s licensor, WEHI (Walter and Eliza Hall Institute of Medical Research), by the EPO is part of a portfolio which includes granted US, Australian, New Zealand and Japanese patents as well as pending applications in several other countries.

ONK licensed the patent family relating to the KO of CISH in NK cells in an exclusive global patent license agreement from WEHI in 2021. CISH KO has been shown to improve the persistence, metabolic profile, and cytotoxicity of NK cells. The patent granted by EPO specifically covers CISH KO NK cells per se, and cancer therapies that utilize NK cells with CISH KO as well as NK cells engineered with the foundational CISH KO in combination with IL-15 (soluble or engineered), TGFβR2 KO, or TGFβR2 KO and IL-15 (soluble or engineered).

ONK and WEHI continue to prosecute the CISH patent portfolio in a way to maximize its depth and breadth of scope. It forms part of ONK’s broad and growing IP estate covering the optimization of persistence, metabolic profile and cytotoxic potential of its NK cell therapy platform.

ONK Therapeutics’ CEO Chris Nowers said, "Editing of NK cells to knockout CISH has the potential to improve the potency and persistence of NK cell-based therapies and provide greater benefit to patients. We are actively exploring the merits of CISH KO alone or in combination with other gene edits such as TGFβR2 KO and IL-15 knock-in. We believe this is the foundational CISH KO patent, based on the earliest scientific discoveries and covers CISH KO NK cells from any source. We are excited to have this broad and evolving patent estate which underpins our scientific efforts in the field."

WEHI’s Head of Biotechnology and Commercialisation Dr Anne-Laure Puaux said, "Cell-based therapies have demonstrated their enormous potential as disease-modifying therapies in oncology. Partnerships and collaborations are key to advancing WEHI’s drug discovery and development programs, to help us take our research from the lab to the clinic. Through this license agreement with ONK Therapeutics, we are excited to support the opportunity to develop more potent cell-based therapies for the future benefit of cancer patients."

-Ends-

About CISH and the WEHI patent

CIS (encoded by the gene CISH) is a member of the suppressor of cytokine signaling (SOCS) family of proteins. When NK cells are stimulated with growth factors, such as interleukin 15 (IL-15), which encourage their growth, survival, and killing capability, there is an increase in the activity of CIS protein, which acts as a brake or checkpoint, on further NK cell growth and function.

The WEHI team found that when CIS was removed from NK cells by deleting the CISH gene, the NK cells were more responsive to growth factors and had improved survival and killing capacity(1). Later studies found that removing CIS improved the metabolic fitness of NK cells, optimizing their ability to kill tumor cells(2-3).

1. Delconte, R., Kolesnik, T., Dagley, L. et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol 17, 816–824, 2016

2. Daher et al., Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells, Blood 137(5), 624-636, 2021

3. Zhu et al., Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity, Cell Stem Cell 27(2), 224-237.e6, 2020