On November 7, 2024 Cellenkos Inc., a clinical-stage biotechnology company focused on developing allogeneic, off-the-shelf, T regulatory (Treg) cell therapies for inflammatory disease areas of high unmet needs and autoimmune disorders, reported that its CK0804 Phase 1b study data in myelofibrosis has been selected for oral presentation at the 66th Annual Meeting & Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), December 7-10, 2024, in San Diego, California (Press release, Cellenkos, NOV 7, 2024, View Source [SID1234647984]).

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The oral presentation will feature the safety and efficacy data from Cellenkos’ Phase 1b trial evaluating CK0804 in patients with myelofibrosis who have suboptimal responses to prior therapies, including ruxolitinib. CK0804 is an off-the-shelf, allogeneic, non-HLA matched, CXCR4-enriched Treg cell therapy and is administered in fixed dose of 100 million cells infused every 28 days for 6 doses. CK0804 has shown early promise in addressing this high unmet medical need.

Oral Presentation Details (View Source)

Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Advancing MPN Care: Innovative Therapies and Clinical Breakthroughs in Myelofibrosis
Date: Monday, December 9, 2024
Time: 5:00 PM (Presentation)
Location: Manchester Grand Hyatt San Diego, Harbor Ballroom DEFG
Publication Number: 999
Title: A Phase Ib, Open-Label Study of Add-on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib
Submission ID: 211587
The study data to be presented demonstrates the safety and efficacy of CK0804 in patients with myelofibrosis who had previously failed standard treatments. Key findings from the trial include significant improvements in symptom burden, spleen volume reduction, blood transfusion dependence, and systemic inflammatory cytokine levels. Importantly, CK0804 was well-tolerated, with no significant drug-related adverse events observed, aside from one patient with a sulfa drug allergy who had an infusion reaction.

Study Highlights

Nine patients, with a median of two (range, 1-6) prior lines of treatment, were treated with CK0804.
Improvements in fatigue and overall symptom burden were reported by all patients, with four out of six evaluable patients showing spleen volume reduction (SVR).
Two patients who were transfusion-dependent showed a reduction in their monthly need for transfusions by the end of the treatment period.
Longitudinal data indicates sustained benefits, including improvements in hemoglobin levels and inflammatory markers.
Following the initial success of the Phase 1b trial, the Data Safety Monitoring Board has approved an expansion cohort to further explore the safety and efficacy of CK0804. This expansion includes an induction phase of four weekly doses, followed by five monthly doses, and active participant enrollment is ongoing (NCT05423691).

About Myelofibrosis
Myelofibrosis is a rare, chronic, and progressive blood cancer that causes scar tissue to form in the bone marrow, disrupting the production of normal blood cells. Patients with myelofibrosis often experience debilitating symptoms such as fatigue, spleen enlargement, and night sweats. Approximately 16,000 to 18,500 people in the U.S. are living with myelofibrosis, and those who fail to respond adequately to current treatments including ruxolitinib, face limited options and a poor prognosis. Inflammation is a key driver for disease pathogenesis and progression in myelofibrosis.

About CK0804
CK0804 is an investigational, allogeneic, off-the-shelf Treg cell therapy that leverages the CXCR4/CXCL12 axis to suppress inflammatory cytokines implicated in myelofibrosis pathogenesis. CXCR4 enriched Tregs home faster to bone marrow compared to unmanipulated Tregs. Derived from clinical-grade umbilical cord blood and manufactured using Cellenkos’ proprietary CRANE process, CK0804 does not require HLA matching, making it an ideal therapeutic option for patients in need of prompt intervention. The therapy is administered intravenously and can be infused in an outpatient setting.

On November 7, 2024 cTRL Therapeutics, a biotechnology company advancing next-generation cell therapies for solid tumors, reported that it will present new data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2024, taking place November 6-10 in Houston, TX (Press release, CTRL Therapeutics, NOV 7, 2024, View Source [SID1234647983]). The company will showcase two poster presentations that underscore the therapeutic potential of circulating tumor-reactive lymphocytes (cTRLs), enabled by the company’s proprietary IsoQore cell isolation platform.

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"We are excited to present data that demonstrate the robust tumor reactivity and therapeutic potential of cTRLs in patients with limited treatment options," said Ruben Rodriguez, PhD, Head of Research at cTRL Therapeutics. "These findings highlight the potential of our IsoQore platform to unlock the therapeutic use of cTRLs, previously thought to be impossible, offering a new way forward for patients with solid tumors."

Poster Presentations:

Abstract 401: Anti-tumor activity of circulating tumor-reactive lymphocytes (cTRLs) isolated from checkpoint-refractory melanoma patients that failed TIL manufacturing.
This poster will present data on cTRLs isolated from melanoma patients who had failed conventional TIL manufacturing. The results demonstrate strong tumor reactivity in cTRLs, with higher frequency of tumor-reactive TCR repertoire compared to TILs, providing a more potent anti-tumor response. The data underscore the potential of cTRLs as a simpler and more effective alternative to traditional cell therapy approaches like TIL therapy.
Poster Presentation: Friday, Nov. 8

Abstract 400: Circulating tumor-reactive lymphocytes (cTRLs) isolated from colorectal cancer (CRC) patients are reactive against autologous tumors and show less exhaustion than tumor-infiltrating lymphocytes (TILs).
This presentation highlights the potential of cTRLs isolated from CRC patients to outperform TILs. The data show that cTRLs exhibit lower levels of exhaustion markers (PD-1, CD39) and higher expression of memory/activation markers (CD27, CD28) and improved functionality and tumor reactivity compared to paired TILs. These findings position cTRLs as a promising new polyclonal T-cell therapy, eliminating the need for surgical tumor resection and expanding patient eligibility.
Poster Presentation: Saturday, Nov. 9
"These data highlight the strong potential of cTRLs as a next-generation approach in cell therapy," said Derrell Porter, M.D., CEO of CTRL Therapeutics. "With a non-invasive blood draw instead of surgical resection, and superior cell fitness compared to traditional cell therapies, cTRLs could offer patients a more accessible, scalable, and effective treatment option. We look forward to sharing these findings with the scientific community at SITC (Free SITC Whitepaper)."

cTRL Therapeutics continues to advance its proprietary IsoQore platform, which isolates and expands high-quality cTRLs from peripheral blood, paving the way for a new era of cell therapies that address key limitations of current modalities.

On November 7, 2024 Nektar Therapeutics (Nasdaq: NKTR) and collaborators at The University of Texas MD Anderson Cancer Center reported late-breaking results from a Phase 2 study evaluating NKTR-255 for the treatment of radiation induced lymphopenia after concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) patients at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting (Press release, Nektar Therapeutics, NOV 7, 2024, View Source [SID1234647982]).

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NKTR-255 is a novel polymer-conjugated IL-15 agonist, designed to activate, proliferate and expand natural killer (NK) and CD8+ T-cells, as well as to promote the survival and expansion of memory CD8+ T cells. NKTR-255 is currently being evaluated in combination with cellular therapies and immune checkpoint inhibitors. Previous pre-clinical and clinical studies have shown that NKTR-255 can proliferate a range of immune cells and augment lymphocyte trafficking.1,2,3

The results from the preplanned interim analysis from the REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE) trial suggest that NKTR-255 effectively reversed radiation induced lymphopenia in patients with locally advanced NSCLC receiving consolidation therapy with durvalumab. Interim pharmacodynamic data demonstrated statistically significant superiority of the eight-week absolute lymphocyte count (ALC) with NKTR-255 post chemoradiation and in combination with durvalumab versus non-contemporaneous control groups who received either chemoradiation alone or chemoradiation in combination with durvalumab.

"Radiation induced lymphopenia is common after chemoradiation therapy and is associated with worse overall survival in multiple solid tumors including lung cancer." said Steven H. Lin, MD, PhD, Professor of Radiation Oncology at MD Anderson. "These interim results showing that NKTR-255 can rapidly restore absolute lymphocyte counts post chemoradiation suggest that NKTR-255 has the potential to confer prognostic benefits and enhanced survival in patients with locally advanced NSCLC."

"These results, combined with the body of evidence previously reported with NKTR-255 in combination with cell therapy, highlight NKTR-255’s potential to enhance clinical benefit in both hematologic malignancies and solid tumors" said Mary Tagliaferri, MD, Senior Vice President and Chief Medical Officer at Nektar.

The Phase 2 single-arm study conducted by MD Anderson is evaluating NKTR-255 (3µg/kg IV) following concurrent chemoradiation and in combination with consolidation therapy with durvalumab. NKTR-255 3µg/kg is administered intravenously every 4 weeks in combination with durvalumab (1500mg IV) for up to 1 year (NCT05632809). The primary objectives of the study are safety and ALC normalization at Week 8 after initiation of NKTR-255 and durvalumab post chemoradiation. Secondary endpoints include progression-free survival and overall survival. The trial is currently ongoing at MD Anderson.

Key details and takeaways from the presentation are as follows:

Late-breaking Abstract (LBA) 1489: " REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE): Preplanned Interim Safety and Efficacy Analysis", Lin, S., et al.

The combination of NKTR-255 and durvalumab post chemoradiation was shown to be safe and tolerable with an AE profile consistent with previously reported clinical trials.
Interim pharmacodynamic data demonstrated statistically significant superiority of the eight-week absolute lymphocyte count with NKTR-255 post chemoradiation and in combination with durvalumab versus non-contemporaneous control groups who received either chemoradiation alone or chemoradiation in combination with durvalumab. Additional pharmacodynamic findings following NKTR-255 administration show increased markers of NK cell proliferation and activation.
About NKTR-255

NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body’s innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory to improve the anti-tumor immune response.

In addition to studies in combination with CAR T cell therapies, NKTR-255 is being studied in a Phase 1 clinical trial sponsored by AbelZeta which is evaluating C-TIL051, a tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant metastatic non-small cell lung cancer (NCT05676749). The JAVELIN Bladder Medley study (NCT05327530), sponsored by Merck KGaA, is also ongoing to evaluate NKTR-255 in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (NCT05327530).

On November 7, 2024 Dragonfly Therapeutics, Inc., a clinical-stage biotechnology company developing novel immunotherapies, reported the company will deliver poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Conference, highlighting preclinical data supporting two clinical-stage assets, DF6215, its engineered IL-2 cytokine, and DF9001, its EGFR-targeting TriNKET, for the treatment of advanced solid tumors (Press release, Dragonfly Therapeutics, NOV 7, 2024, View Source [SID1234647981]).

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Data show that Dragonfly’s DF6215 IL-2 cytokine drives greater therapeutic benefit in vivo than non-alpha IL-2, with no evidence of capillary leak syndrome or cytokine release syndrome . In addition, DF6215 synergizes with PD-1 blockade cancer treatment in the "cold" B16F10 melanoma tumor model, without adding toxicity. "DF6215 is a differentiated IL-2, specifically tuned to potently stimulate anti-tumor CD8 T cells and NK cells without incurring counterproductive Treg expansion or VLS," said Ann Cheung, Chief Scientific Officer of Dragonfly Therapeutics.

Dragonfly’s DF9001 EGFR-targeting TriNKET drives efficacy via both EGFR-signal inhibition and immune-mediated mechanisms. Data show superior anti-tumor activity via EGFR signal inhibition compared to cetuximab in a xenograft mice model, and that DF9001 induces potent in vivo efficacy via immune effector cells, even in cancer models not dependent on EGFR signaling. DF9001 was well-tolerated at ≤50 mg/kg/week in a 4-week GLP study in cynomolgus monkeys. "DF9001 is the only EGFR-targeting agent that allows engagement of both innate and adaptive immune effectors," remarked Cheung, "and does so with a favorable safety profile."

SITC is being held November 6-10, 2024 in Houston, Texas, USA. Dragonfly’s poster presentations will take place on Saturday, Nov. 9, Lunch (12:15–1:45 pm), and Poster Reception (7–8:30 pm) in the George R. Brown Convention Center – Level 1 – Exhibit Halls AB.

Abstract Number 962: A novel alpha-active IL-2-Fc has expanded therapeutic index and robust monotherapy efficacy in mouse cancer models and strong synergy with PD-1 blockade. The full DF6215 poster is linked here
Abstract Number 1060: DF9001, an EGFR Targeted Immune Engager, Stimulates Innate and Adaptive Anti-Tumor Immunity with a Distinctive Safety Profile."
The full DF9001 poster is linked here
About DF6215
DF6215 is a modified, monovalent, half-life extended recombinant human IL-2 that biases toward activation of anti-tumor T and NK cells in order to improve upon the benefit-to-risk ratio of historic IL-2 drugs.

DF6215 was found to:

Increase proliferation of immune cells and preferentially expand anti-tumor effector cells compared to non-alpha IL-2 molecules (maximizing the anti-tumor effector:Treg ratio)
Increase granzyme B expression in tumor-infiltrating CD8+ T cells and NK cells
Demonstrate effective therapeutic efficacy in mouse cancer models as a single agent as well as in combination with immune checkpoint blockade
Preferentially expand activated CD8+ T cells in NHP without evidence of capillary leak syndrome or cytokine release syndrome
DF6215 is the second in a pipeline of cytokines that Dragonfly is developing to address unmet need in patients with advanced cancer and other diseases. Dragonfly’s DF6215 Phase 1/1b clinical trial is a first-in-human, multi-part, open-label study to investigate the safety, tolerability, pharmacokinetics, biological, and clinical activity of DF6215 in patients with advanced (unresectable, recurrent, or metastatic) solid tumors (NCT06108479).

About DF9001
DF9001 is an investigational first-in-class multi-specific drug candidate that targets and inhibits EGFR and potently redirects natural killer (NK) cells, gamma-delta T cells, and CD8 T cells by engaging activating receptors NKG2D and CD16.

DF9001 disrupts tumor growth by inhibiting EGFR signaling and promoting anti-tumor immunity. It has been optimized for engagement of immune cell populations that lead to the direct killing of tumor cells, while sparing healthy tissues, as well as the production of chemokines and cytokines that recruit additional effector cells to kill tumor cells. These characteristics make DF9001 a promising therapeutic agent against EGFR+ cancers, particularly those for which EGFR signal inhibition alone is ineffective.

DF9001 was discovered and developed using Dragonfly’s TriNKET platform. DF9001 is being evaluated in adult patients for the treatment of advanced solid EGFR-positive tumors (NCT05597839). DF9001 has the potential to stimulate anti-tumor immunity in patients who are not eligible or not adequately responding to current therapies. It is the second wholly owned drug candidate in a pipeline of TriNKETs Dragonfly is developing to address high unmet needs for patients across a broad range of disease areas.

On November 7, 2024 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," reported it will present additional Phase 1 clinical biomarker data for HST-1011, an investigational oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B), in a poster presentation at the 2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, HotSpot Therapeutics, NOV 7, 2024, View Source [SID1234647980]).

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"These biomarker data emerging from our Phase 1 clinical study of HST-1011 provide strong support for the biological activity and therapeutic potential of CBL-B inhibition, with HST-1011 treatment yielding an increase in immune activation as assessed through both peripheral blood and tumor gene expression," said Alison O’Neill, M.D., Chief Medical Officer of HotSpot Therapeutics. "Moreover, while the data are preliminary and in a small number of patients, baseline immune signature analyses suggest the potential for the prediction of clinical response. Collectively, the insights derived from these data support the further interrogation of biomarkers as HST-1011 advances through future clinical development."

The presentation describes additional clinical biomarker data from the ongoing Phase 1 monotherapy dose-escalation study of HST-1011:

An HST-1011-derived gene response signature showed a consistent dose-dependent increase in patient peripheral blood, with patients who demonstrated clinical benefit showing a higher expression of the signature in on-treatment biopsies.
Preliminary T- and B-cell receptor next-generation sequencing data showed HST-1011 impacted both immune cell populations, with changes observed in several metrics associated with clinical benefit.
At baseline, patients who benefitted from HST-1011 treatment showed higher tumor-infiltrating lymphocyte expression and a higher immune signature score, suggesting a potential for prediction of clinical benefit.