On June 10, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that updated preclinical data on its IPH6501 tetra-specific ANKET (Antibody-based Natural Killer cell Engager Therapeutics) are presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 congress (Press release, Innate Pharma, JUN 10, 2023, View Source [SID1234632625]). IPH6501 is a first-in-class CD20-targeting tetra-specific ANKET that co-engages two activating receptors (NKp46 and CD16), the interleukin-2 receptor (without involvement of the IL-2Rα subunit) with a human IL-2 variant and CD20 target antigen on malignant B cells.

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In preclinical settings, IPH6501 was shown to induce NK cell proliferation and to trigger high NK cell cytoxicity against CD20+ target cells in in vitro assays, in ex vivo assays with relapse/refractory (R/R) B-NHL patient samples who received at least one prior treatment, as well as in in vivo studies in non-human primates. A surrogate of IPH6501 mediated a potent anti-tumor activity in vivo in CD20+ tumor models in mice. In addition, in ex vivo assays with R/R B-NHL patient samples, IPH6501 was shown to be more efficient than a T cell engager targeting CD20.

Pr. Eric Vivier, PhD, DVM, Chief Scientific Officer at Innate Pharma "As the lead in this new class of tetra-specific NK-cell engager, IPH6501 represents an innovative option for the treatment of R/R B-cell non-Hodgkin’s lymphomas after multiple lines of treatment, who are still in need of therapies. By providing proliferation and activation signals targeted to NK cells, the tetra-specific NK Cell Engager based on our ANKET platform leverages the advantages of harnessing NK cell effector functions against cancer cells. With a low systemic cytokine release profile, IPH6501 represents a promising alternative strategy to T cell therapies. IPH6501 continues to progress towards a Phase 1 clinical trial and we look forward to share further updates on other ANKET assets as they enter clinic."

About ANKET

ANKET is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer. This fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.

Innate’s latest innovation, the tetra-specific ANKET, is the first NK cell engager technology to engage activating receptors (NKp46 and CD16), a tumor antigen and the interleukin-2 receptor (via an non-alpha IL-2 variant, IL-2v) via a single molecule. By providing proliferation and activation signals targeted to NK cells, tetra-specific ANKET leverages the advantages of harnessing NK cell effector functions against cancer cells.

On June 10, 2023 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, reported highlights from a clinical update event held today, June 10, 2023, in conjunction with EHA (Free EHA Whitepaper) 2023 International Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Frankfurt, Germany (Press release, Aptose Biosciences, JUN 10, 2023, View Source [SID1234632619]). The event included an up-to-date review of clinical data for Aptose’s two investigational products under development for hematologic malignancies: tuspetinib, an oral, myeloid kinase inhibitor in the Phase 1/2 APTIVATE trial in patients with relapsed or refractory acute myeloid leukemia (AML); and luxeptinib, an oral, dual lymphoid and myeloid kinase inhibitor in Phase 1 a/b stage development for the treatment of patients with relapsed or refractory hematologic malignancies. The webcast of the presentation is available on Aptose’s website here.

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Aptose provided updated clinical findings with tuspetinib, a potent suppressor of FLT3, SYK, JAK 1/2, mutant forms of cKIT, and the RSK1/2 kinases operative in AML:

Completed tuspetinib dose escalation and dose exploration Phase 1/2 trial in 77 R/R AML patients.
Tuspetinib demonstrated a favorable safety profile.
Tuspetinib delivered monotherapy responses across four dose levels with no DLT in mutationally diverse and difficult to treat R/R AML populations, including TP53-mutated patients with a CR/CRh = 20% and RAS-mutated patients with a CR/CRh = 22%.
Completed successful End of Phase 1 (EOP1) Meeting with US FDA for tuspetinib, and a monotherapy RP2D was selected as 80mg daily, and all development paths remain open, including the single arm accelerated path.
Initiated tuspetinib APTIVATE expansion trial with R/R AML patients.
Tuspetinib is being administered as a monotherapy and as a combination doublet with tuspetinib + venetoclax (TUS/VEN), and enrollment has been brisk.
TUS/VEN doublet has been well tolerated, all patients remain on study, and preliminary CR activity has already been reported in patients previously treated with VEN.
Aptose also reviewed clinical findings with the new G3 formulation of luxeptinib (Lux):

50mg G3 formulation with continuous dosing achieves roughly equivalent PK profile as 900mg original G1 formulation.
Expect to dose escalate G3 formulation with continuous dosing in patients soon.
"We are delighted to have finalized our dose escalation and dose exploration Phase 1/2 trial with tuspetinib (TUS), to have demonstrated single agent responses across four dose levels that had no DLTs and across a range of R/R AML populations with a diversity of adverse mutations," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "As part of our EOP1 meeting with the FDA, we designated 80mg daily as our monotherapy recommended phase 2 dose (RP2D), and now we focus all attention on our APTIVATE expansion trial to place monotherapy TUS in more patients with highly adverse mutations and to evaluate TUS in combination with venetoclax (VEN) as a doublet in R/R AML patients. Notably, to date, the doublet appears to be well tolerated, with all patients remaining on study, including a preliminary CR in a R/R AML patient who previously failed venetoclax. We look forward to accelerating testing of the doublet, adding MDS patients to our APTIVATE trial, and with the aim of moving into triplet therapy (TUS/VEN/HMA) in 1L AML patients."

On June 10, 2023 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported presentations highlighting preliminary data based on a November 2022 data cut-off from its Phase 1 dose escalation clinical trial of NKX019 at two scientific conferences: the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Hybrid Congress and the 17TH International Conference on Malignant Lymphoma (17-ICML) (Press release, Nkarta, JUN 10, 2023, View Source [SID1234632614]). NKX019 is an allogeneic, off-the-shelf NK cell therapy candidate derived from healthy donors and engineered to target CD19.

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Seven of ten patients with relapsed/ refractory non-Hodgkin lymphoma (NHL) treated at the higher dose levels showed a complete response (70% CR), including two patients with aggressive large B cell lymphoma (LBCL) as well as other difficult histologies, including mantle cell lymphoma (MCL), high-risk follicular lymphoma (FL) and marginal zone lymphoma (MZL). No dose limiting toxicity, neurotoxicity / ICANS, graft versus host disease (GvHD), or >Grade 3 cytokine release syndrome (CRS) were observed in the study.

"Autologous CAR-T cell therapies set a standard for responses in patients with relapsed/ refractory B-cell malignancies. However, potential for toxicity and logistic challenges have limited access to these therapies, and many patients could still benefit from a safe, on-demand treatment," said Michael Dickinson, M.D., Lead, Aggressive Lymphoma disease group, Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, and investigator in the NKX019 trial. "In this early evaluation of an allogeneic CAR-NK cell therapy candidate, NKX019 had a manageable safety profile with encouraging anti-tumor activity as well as the option for retreatment after relapse. Based on these early data, NKX019 merits further study as a potential outpatient cell therapy approach."

"These data highlight the encouraging safety profile and clinical activity across different histologies in the dose escalation portion of the NKX019 study," said David R. Shook, M.D., Nkarta’s Chief Medical Officer. "We continue to explore the potential of allogeneic CAR NK cells, leveraging their biology to create a differentiated cellular therapy, and we look forward to the next update on the NKX019 program later this year."

Nkarta’s presentation materials from EHA (Free EHA Whitepaper) and ICML will be available for download on the Nkarta website (View Source). The presentations will ensure that the broader clinical and academic community has the opportunity to assess the NKX019 clinical data in a peer-reviewed format. All data were previously disclosed at a company event in December 2022. Nkarta plans to provide an update from the NKX019 program, including data from dose expansion cohorts, in 2023.

About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.

On June 9, 2023 Theolytics, a biotechnology company harnessing viruses to combat disease, reported data presentations at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which was held 2 to 6 June, 2023 in Chicago and at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Congress, which is being held 8 to 11 June in Frankfurt (Press release, Theolytics, JUN 9, 2023, View Source [SID1234635716]).

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ASCO Abstract

Title: Evaluation of THEO-260 as a novel oncolytic virus therapy for treating stromal rich tumours

LINK to abstract

Stromal rich cancers pose a challenge to many cancer therapies due to the abundance of cancer associated fibroblasts (CAFs). This compartment of the tumour microenvironment physically blocks the penetration of drugs, immune cells and promotes resistance to many therapies. THEO-260 is a new oncolytic virus in development that is intrinsically capable of targeted killing of both cancer cells and CAFs.

The efficacy and safety of THEO-260 was assessed in multicellular spheroids, in patient-derived ex vivo fresh ovarian samples and in mouse models of human stromal tumours. Unpassaged ascites and tumour samples collected from cytoreductive surgeries for advanced ovarian cancer were treated with a clinically-relevant dose of THEO-260. THEO-260 effectively killed the cancer cell and CAF populations, being efficacious in treatment-naive and platinum-resistant patient samples. Importantly, the T cell population in these patients, in addition to primary normal fibroblasts from healthy donors, were not damaged. Ex vivo studies show THEO-260 stimulates effector T cell responses upon tumour lysis and demonstrates suitability as an IV

delivered agent. THEO-260 excels in low nutrient, low proliferative environments, typical of human solid tumours and has been developed with a view to persist in the tumour microenvironment without the need for repeated cycles of delivery. In ovarian cancer murine models containing human CAFs and cancer cells, THEO-260 shows antitumor efficacy, with a complete reduction in tumour volume in subcutaneous and intraperitoneal systems, and superiority to standard of care. Virus activity is not restricted to ovarian cancer, with cell line data demonstrating killing in additional solid tumour types, including pancreatic, colorectal, lung, and breast cancer. THEO-260 exhibits genetic and temperature based stability, and GMP manufacturing to high yields is underway.

"The positive THEO-260 data presented at ASCO (Free ASCO Whitepaper) come at an exciting time for Theolytics as we progress this lead product towards the clinic in a first-in-human study in ovarian cancer," said Charlotte Casebourne Stock, Chief Executive Officer and Co-Founder of Theolytics. "THEO-260 is a virotherapy that potentially could demonstrate something that neither chemotherapy, nor immunotherapeutic approaches have been capable of to date and has the potential to deliver a step-change for the oncolytic virus field."

EHA Poster Presentation

Title: Development of a Novel Oncolytic Virus – THEO-310 – Specialised for Targeting the Bone Marrow Tumour Microenvironment of Multiple Myeloma Patients

LINK to abstract

Session Title: 24. Gene therapy, cellular immunotherapy and vaccination – Biology & Translational Research

Poster ID: P1362

Session date and time: Friday, 9 June, 18:00 – 19:00 CEST

Session room: Poster area

Presenting Author: Dr Margaret Duffy

THEO-310 is an oncolytic virus developed for tackling the bone marrow tumour microenvironment (TME) of advanced late-stage myeloma patients. THEO-310 demonstrates efficacy in >80% of ex vivo bone marrow aspirates, across newly diagnosed, relapsed and refractory myeloma patients. In these experiments, TME immune modulation and superiority to ‘best-in-class’ oncolytic virus strains for myeloma, including the measles virus, was observed.

"These exciting set of results differentiates Theolytics’ approach to other oncolytic virus candidates. In addition to showing increased efficacy in patients ex vivo, the candidate demonstrates systemic safety as shown by cytokines levels post IV injection in vivo, whilst exhibiting >40-fold better circulation compared to a clinically validated oncolytic virus strain, thus supporting effective intravenous delivery," said Margaret Duffy, Chief Scientific Officer and Co-Founder of Theolytics. "Taken together, THEO-310 represents a new therapeutic option, with a highly differentiated mechanism independent of BCMA, for myeloma patients with relapsed refractory disease.

On June 9, 2023 NovalGen Ltd ("NovalGen"), a biopharmaceutical company developing disruptive therapies, based on a proprietary autoregulation (AR) platform, reported the presentation of preclinical data on this novel technology in two separate indications at the International Society on Thrombosis and Haemostasis Congress (ISTH), 24-28 June, 2023 in Toronto and the Immuno-Oncology Summit Boston 2023, 7-9 August, 2023 in Boston (Press release, NovalGen, JUN 9, 2023, View Source [SID1234633763]).

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"We are delighted to be showcasing our proprietary platform, which has the potential to improve the safety profile and therapeutic index of a range of immunotherapies. Preclinical data with NVG-444 shows a reduction in thrombotic complications with a bispecific Factor VIII mimetic. These data will be presented in an oral presentation at ISTH. The AR platform is target agnostic as illustrated by its application to an extended half-life T cell engager (TCE) targeting ROR1, resulting in a dramatic reduction in toxicity, thus addressing the "Achilles heel" of TCEs allowing more patients to benefit from this off the shelf, T cell activating technology. The AR technology can be applied to a wide range of immunotherapies and heralds a new and exciting class of self-regulating drugs that respond to biological cues to avoid life-threatening toxicities," said Professor Amit Nathwani, Founder and CEO of NovalGen.

Both abstracts will be delivered as oral presentations at the conferences.

Abstracts to be presented:

Conference: ISTH 2023 Congress
Abstract Title: Thrombin-mediated autoregulation restores sensitivity to the coagulation feedback loop and reduces the risk of prothrombotic events associated with FVIII mimetic antibodies.

Abstract Presentation Number: OC 69.1

Session Title: Hemophilia – Novel therapies II

Session Date: Wednesday, 28 June, 2023
Presentation Time: 10:15 am – 10:30 am

Presenting Author: Vincent Muczynski

Conference: Immuno-Oncology Summit Boston 2023
Abstract Title: NVG-222: A ROR1-Targeting T Cell Engager with Integral Autoregulating Capability Designed to Reduce the Risk of Serious Adverse Events Related to T Cell Activation

Session Title: Bispecific Antibodies for Cancer Immunotherapy: Overcoming Obstacles to Efficacy

Session Date: Tuesday, 8 August, 2023

Presentation Time: 8:05am – 8:35am

Presenting Author: David Granger