On April 28, 2025 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported research data on TALEN-mediated non-viral transgene insertion for advancing cellular and gene therapies, and advancements in genetic editing using base editors (TALEB), at the Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) annual meeting, that will be held on May 13-17, 2025 in New Orleans (Press release, Cellectis, APR 28, 2025, View Source [SID1234652224]).

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The data are presented in two posters:

Title: TALEN- Mediated non-viral Transgene Insertion for the Advancement of Cellular and Gene Therapies.

Cell and gene therapy approaches can use gene-editing tools and introduce transgenes to modify disease-associated genes, thus providing a potential therapeutic solution for a wide array of diseases.

In this work, Cellectis combines TALEN-mediated gene editing with non-viral delivery of transgene for advancing cellular and gene therapies, and explores gene insertion-efficacy and cellular health using single-stranded DNA (ssDNA) for payload delivery in different cell types.

This innovative approach has the potential to address the challenges associated with traditional lentiviral viral methods or AAV-mediated transgene insertion such as manufacturing constraints, potential genomic toxicities or limited payload size.

Research data show:

Non-viral methods for gene editing: TALEN mediated gene editing combined with non-viral templates (linear and circular ssDNA) can be used for highly efficient gene insertion in T-cells as well as hematopoietic stem and progenitor cells (HSPCs) promoting viability and insertion specificity
Advantages of Circular ssDNA over viral vectors: Transcriptomic analysis and in vivo data demonstrate that CssDNA-mediated cell engineering allows better maintenance of HSPC fitness as well as more stable gene editing, compared to traditional viral donor template-mediated transgene delivery.
« The implementation of these gene-editing techniques holds significant potential for the development of next-generation therapies, aiming to provide alternative efficient, and safe therapeutic options for patients with cancer, autoimmune diseases, monogenic disorders, and various other conditions. » said Beatriz Aranda Orgilles, Ph.D., Associate Director – IO and business development analyst at Cellectis.

Title: High fidelity C-to-T editing with base editors

TALE base editors (TALEB) are fusions of a transcription activator-like effector domain (TALE), split-DddA deaminase halves, and a uracil glycosylase inhibitor (UGI). The C-to-T class of TALEB edits double-stranded DNA by converting a cytosine (C) to a thymine (T) and does not involve DNA strand nick.

Cellectis has developed a method to characterize the efficiency of this conversion and examined various factors influencing TALEB activity. This method also takes advantage of a highly precise and efficient knock-in of ssODN in primary T cells to develop an assay to assess how the composition and spacer variations of target sequences affect TALEB activity/efficiency.

Research data show:

Efficiency of C-to-T editing: TALEB enables efficient conversion of C to T. Variations in target sequences and surrounding bases affecting editing efficiency. An educated choice of the TALEB architecture further allows to control the editing outcome.
Assessment of off-target editing risks: Studies have been conducted to evaluate off-target editing, showing no detectable editing in primary cells at previously described sites, highlighting the specificity of TALEB for potential therapeutic applications.
«It is inspiring to see the advancement of Cellectis’ TALE technology into a new tool that is available in our gene editing toolbox. Our ability to understand and fine-tune the editing capacity of TALE base editors has equipped us with another efficient and specific approach that can be used to support novel gene editing and gene therapy applications. » said Louisa Mayer, Ph.D., Scientist II and Supervisor – Innovation & Gene Editing at Cellectis.

Overall, the results of this study enhance the control and use of TALEB, allowing for the design of highly efficient and specific TALEB compatible with future therapeutic applications.

The abstracts are live on the ASGCT (Free ASGCT Whitepaper) website. The posters will be available on Cellectis’ website the first day of the event.

On April 28, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the presentation of a poster at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, highlighting preclinical data on ORIC-944, a potent, highly selective, orally bioavailable allosteric inhibitor of PRC2, which demonstrated synergistic activity and improved progression-free survival (PFS) when combined with androgen receptor pathway inhibitors (ARPIs) in models of prostate cancer (Press release, ORIC Pharmaceuticals, APR 28, 2025, View Source [SID1234652240]).

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"We are excited by the potential of ORIC-944 to be a best-in-class PRC2 inhibitor for the treatment of prostate cancer," said Lori Friedman, PhD, chief scientific officer. "The data presented at AACR (Free AACR Whitepaper) demonstrate the strong synergy of ORIC-944 when combined with standards of care, reversing the evolution of prostate cancer, and improving progression-free survival in both castration-resistant and castration-sensitive prostate cancer models – validating the clinical exploration of ORIC-944 across the continuum of prostate cancer."

Poster presentation:

ORIC-944, a PRC2 inhibitor with best-in-class properties, restores luminal features and restricts adaptation in prostate cancer models, conferring synergy with AR pathway inhibitors

Key findings of the presentation:

ORIC-944 increased progression-free survival (PFS) when combined with ARPIs in both castration-sensitive and castration-resistant prostate cancer models.
ORIC-944 demonstrated transcriptional synergy and antitumor synergy when combined with ARPIs in prostate cancer cells.
In preclinical prostate cancer models, ORIC-944 demonstrated robust inhibition of PRC2, enhanced luminal cell state, and consistently restricted lineage transcription factor accessibility through chromatin remodeling, ​thereby reenforcing the luminal state and preventing access to plasticity programs.
Results position ORIC-944 as a potential best-in-class PRC2 inhibitor that, through both transcriptional and chromatin mechanisms, blocks prostate tumor adaptation, restores luminal features, and sensitizes tumors to ARPIs.
ORIC-944 is currently being evaluated in combination with ERLEADA (apalutamide) and in combination with NUBEQA (darolutamide) in an ongoing Phase 1b trial for prostate cancer.
About ORIC-944
ORIC-944 is a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the embryonic ectoderm development (EED) subunit that demonstrates best-in-class drug properties in preclinical studies, including potency, solubility, and pharmacokinetics, with half-life supporting once daily dosing. ORIC-944 was initially evaluated as a single agent in a Phase 1b trial in patients with advanced prostate cancer and demonstrated potential best-in-class drug properties, including clinical half-life of approximately 20 hours, robust target engagement and a favorable safety profile. ORIC-944 is currently being evaluated in combination with ERLEADA (apalutamide) and in combination with NUBEQA (darolutamide) in an ongoing Phase 1b trial for prostate cancer (NCT05413421).

On April 28, 2025 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), an oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported poster presentations at the upcoming 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25-30 in Chicago, IL (Press release, Sutro Biopharma, APR 28, 2025, View Source [SID1234652257]). The presentations will cover preclinical activity and safety data for STRO-004, the Company’s novel exatecan Tissue Factor ADC, as well as showcase the unique advantages of Sutro’s XpressCF+ platform in enabling precise and efficient development of dual-payload ADCs.

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"We are excited to share our progress advancing our next-generation ADC pipeline at AACR (Free AACR Whitepaper)," said Jane Chung, Sutro’s Chief Executive Officer. "In preclinical studies, STRO-004 consistently demonstrated potent, dose-dependent anti-tumor activity and a favorable safety profile across all tested doses. Of note, STRO-004, after only a single dose, achieved promising overall response and disease control rates in Tissue Factor-positive patient-derived xenograft models spanning multiple cancer types. We look forward to continuing to investigate the full potential of STRO-004, as we complete IND-enabling studies and prepare to initiate a first-in-human trial later this year."

Ms. Chung continued: "Also, as presented at AACR (Free AACR Whitepaper), our XpressCF+ cell-free platform is uniquely capable of creating revolutionary dual-payload ADCs—differentiated by higher drug-to-antibody ratios, fully site-selective conjugation of two linker payloads and a validated, cell-free ADC manufacturing process. We are excited to showcase these and other key features of our platform, which enable our ADC candidates to overcome limitations of conventional ADCs and the challenges of targeting complex disease biology. These presentations further reinforce our technology leadership and our highly differentiated ADC candidates."

Poster Presentation Details:

Title: Preclinical activity and safety of STRO-004, a novel ADC targeting tissue factor for solid tumors
Abstract: #1572
Session: PO.ET02.01 – Antibody-Based Cancer Therapeutics 1
Date & Time: Monday, April 28, 2025, 9:00 a.m. – 12:00 p.m. CT
Presenter: Alice Yam, Ph.D., Vice President of Drug Discovery at Sutro Biopharma

Title: Enhancing Topo1i ADC efficacy: development of homogeneous dual-payload ADCs combining Topo1i with microtubule inhibitors or PARP inhibitors
Abstract: #2870
Session: PO.ET02.11 – Antibody-Based Cancer Therapeutics 2
Date & Time: Monday, April 28, 2025, 2:00 p.m. – 5:00 p.m. CT
Presenter: Gang Yin, Ph.D., Vice President of Platform Engineering & Process Research at Sutro Biopharma

The abstracts are currently available on AACR (Free AACR Whitepaper)’s website and the poster presentations will be accessible through the News & Events page of the Investor Relations section of the Company’s website at www.sutrobio.com.

On April 28, 2025 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose limiting toxicity, reported data from its recently completed double-blind, placebo-controlled phase 2 randomized clinical trial of lead therapy, LUT014 gel, demonstrating statistically-significant reductions in dose-limiting acneiform rash in patients treated with epidermal growth factor receptor (EGFR) inhibitor therapy (Press release, Lutris Pharma, APR 28, 2025, View Source [SID1234652272]). This new clinical data, showing that Lutris’ topically-applied novel B-Raf inhibitor gel is optimized for paradoxical MAPK activation, was presented yesterday in an oral presentation at the Clinical Trials Plenary Session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025.

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Presentation Details:

Presentation Title: A double-blind placebo-controlled randomized phase 2 clinical trial to assess the efficacy of a topical BRAF inhibitor for acneiform rash toxicities from anti-EGFR therapies
Presenting Author: Anisha B. Patel, MD, Associate Professor, Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, TX
Abstract Number: CT018
Session Title: New Frontiers in Precision Oncology
"Due to the widespread use of EGFR inhibitors for cancer treatment and the frequent occurrence of dermal toxicities, many patients do not receive optimal cancer therapy. This is often because the toxicity leads to dose reductions or complete discontinuation of treatment," stated Benjamin W. Corn, M.D., Chief Medical Officer of Lutris Pharma. "By reversing the inhibitory effect of anti-EGFR therapy on downstream signaling in skin cells, we firmly believe LUT014 has the potential to be a key therapeutic, offering significant benefits to patients with no other effective treatment options. In the trial, as we expected, LUT014 demonstrated statistically significant improvement in acneiform rash compared to placebo, with highly successful outcomes in both intention-to-treat and per-protocol patient analyses. LUT014 was also shown to be safe and well tolerated, with fewer adverse events reported than in the placebo group, with the majority of adverse events being mild."

"This was the first placebo-controlled randomized clinical trial demonstrating the benefit and safety of an agent for the treatment of the acneiform rash associated with anti-EGFR therapy. Therefore, having these overwhelmingly positive results for LUT014 selected for an oral presentation at the prestigious AACR (Free AACR Whitepaper) Annual Meeting, is a testament to the potential of our lead asset and a significant milestone for the company," added Noa Shelach, Ph.D., Chief Operating Officer of Lutris Pharma. "In addition, our successful $30 million financing, completed in January 2025, allows us to continue advancing our clinical development program as we pursue our goal of commercializing LUT014 which will align with our mission to enhance the effectiveness of anti-cancer therapies and significantly improve the quality of life for patients."

The trial enrolled 118 colorectal cancer patients from 23 clinical sites, all of whom had developed grade 2 or non-infected grade 3 acneiform rash while receiving cetuximab or panitumumab. Participants were randomized in a 1:1:1 ratio to receive either LUT014 gel 0.03%, LUT014 gel 0.1%, or a placebo gel. The gel was applied daily for 28 days.

The primary endpoint was the proportion of patients who achieved treatment success, measured by an improvement of at least one grade in Common Terminology Criteria for Adverse Events (CTCAE) scoring or an improvement of at least 5 points in the Functional Assessment of Cancer Therapy (FACT)-EGFRI-18 HRQoL skin-specific assessment. The study employed both an intention-to-treat (ITT) analysis and a Per-Protocol (PP) analysis (i.e., patients who dropped out or did not discontinue their EGFR inhibitor for reasons unrelated to the rash, such as disease progression were excluded from the analysis). Sample size calculation was based on an expected treatment success of 20% for the placebo group and 50% for one of the treatment groups. A total of 117 patients were required for a two group ꭕ2 test with a 0.05 two-sided significance and 80% power.

Efficacy is shown in the table below. In the ITT as well as the PP, the composite endpoint demonstrated statistically significant rates of success for the high dose LUT014 group, compared to placebo.

Treatment
Arm

N

Success
Rate

(ITT)

P
Value

N

Success
Rate

(PP)

P Value

LUT-014 0.1%

39

69 %

0.0015

25

76 %

0.002

LUT-014 0.03%

40

47.5 %

0.12

29

59 %

0.07

Placebo

39

33 %

29

34.5 %

About EGFR Inhibitor-Induced Rash
EGFR is a receptor on the surface of cells which is expressed in many normal epithelial tissues, including skin. The EGFR signaling pathway is one of the key pathways that regulate growth, survival, proliferation, and differentiation of cells. B-Raf is a protein encoded by the BRAF gene and is a downstream effector component of the EGFR signaling pathway. EGFR has been shown to be over-activated in various human cancers, including colorectal, lung, head and neck, urinary bladder, pancreatic and breast cancers, eliciting downstream phosphorylation and activation of the MAP Kinase pathway.

EGFR inhibitors can block the EGFR signal responsible for cell growth. Among the various types of pharmacological therapies for cancer, EGFR inhibitors are increasingly being used both as primary therapy as well as in patients who have progressed on prior chemotherapy treatments. Although effective as an anti-cancer therapy leading to tumor shrinkage, EGFR inhibitors have many adverse reactions associated with their use. The majority of patients treated with EGFR inhibitors will experience adverse dermatological side effects typically manifested as a papulopustular skin rash, also known as acneiform lesions, which can impact quality of life and affect adherence to therapy.

About LUT014
LUT014 is a novel B-Raf inhibitor which is applied topically to the skin. When the B-Raf protein is mutated, as is the case in some human cancers such as melanoma, blocking this pathway leads to apoptosis of the cells and tumor shrinkage. However, when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAPK pathway is activated, and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses the paradoxical effect of B-Raf Inhibitors in order to enhance cell proliferation and balance cell destruction, typical to radiation dermatitis.

On April 28, 2025 Ankyra Therapeutics, a leading clinical-stage company developing anchored drug conjugates for the treatment of cancer, reported preliminary data highlighting the safety and biologic activity of their lead asset, tolododekin alfa (ANK-101), an anchored interleukin-12 (IL-12) drug conjugate (Press release, Ankyra Therapeutics, APR 28, 2025, View Source [SID1234652288]). The data was derived from Part 1 of the first-in-human (FIH) ANCHOR Phase 1 clinical trial. The study was designed to evaluate the safety and feasibility of tolododekin alfa, as monotherapy in patients with advanced solid tumors. Dr. Howard Kaufman, Ankyra President and CEO stated that "We are extremely pleased with the data which provided support for the potential of the anchored drug conjugate platform." He added "The study demonstrates for the first time that IL-12 can be delivered to tumors at therapeutic doses higher than previously achievable without systemic toxicity." Systemic delivery of IL-12 has been evaluated in previous clinical studies, but development was halted after a maximum tolerated dose of 500 ng/kg prevented further dose escalation of IL-12 in cancer patients. Dr. Joe Elassal, Ankyra Chief Medical Officer added that tolododekin alfa "Phase 1 data are encouraging and we have seen that IL-12 anchoring has resulted in 6-fold higher local IL-12 delivery to established cancers compared with what has been achieved with systemic administration." Furthermore, biomarker analysis of tumor-treated biopsies showed increased CD8+ T cell infiltration and induction of local PD-L1 expression. Dr. Elassal added "The high levels of PD-L1 seen provide strong justification for our expansion cohort combining tolododekin alfa with immune checkpoint blockade." Ankyra reports that on March 25, 2025 the first patient with advanced cutaneous squamous cell carcinoma was treated with a combination of tolododekin-alfa and Regeneron’s PD-1 inhibitor, Libtayo (cemiplimab), in an expansion cohort to the current Phase 1 trial.

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Results from Part one of the Phase 1 FIH study are being presented on Monday, April 28, 2025 at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL.

Abstract Title: Results of a first-in-human phase 1 trial of anchored IL-12 drug conjugate (ANK-101).

Session Title: Phase 0 and Phase I Clinical Trials
Session Start: 4/28/2025 9:00:00 AM
Session End: 4/28/2025 12:00:00 PM
Location: Poster Section 49
Poster Board Number: 18
Abstract Presentation Number: CT039
The poster will be available on the publications section of Ankyra’s website after the meeting at View Source

Key Study Findings

Fifteen (15) patients with metastatic solid tumors who had progressed on standard therapy and had accessible lesions for injection were enrolled across four study sites in the U.S. and Canada
Primary tumor histology included melanoma (n=7), head and neck cancer (n=4), breast cancer (n=2), bladder cancer (n=1), and apocrine adenocarcinoma (n=1)
ANK-101 monotherapy was well-tolerated at doses up to 250 µg/mL with no DLTs or Grade 3 or greater treatment-related treatment-emergent adverse events (TEAEs)
Highly efficient tumor retention with low (generally <1%) systemic IL-12-ABP
ANK-101 induced CD8+ T cell recruitment, PD-L1 expression, and inflammatory gene signatures consistent with biologic IL-12 activity
Initial results suggest clinical activity with 2 PRs and a disease control rate of 80% by modified RECIST v1.1
About Tolododekin alfa (ANK-101)
Tolododekin alfa (ANK-101) is an anchored drug conjugate composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment and retention of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents. The first-in-human, open-label clinical trial of ANK-101 as a monotherapy (NCT:06171750) consists of a dose escalation portion that will evaluate the safety and tolerability of ANK-101, followed by dose expansion cohorts. Additional clinical trials are being planned in different cancer types.

ANK-101 will be prominently featured on an upcoming documentary "The Cancer Pioneers" as part of the Public Broadcasting System (PBS) series "Shelter Me". The program will air nationally on local PBS television stations on May 1, 2025 and more information can be found at View Source