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Potential First-in-Class Data from Preclinical Program for STX-003, a Programmable mRNA Therapy to Treat Solid Tumor Cancers

On April 28, 2025 Strand Therapeutics Inc., the programmable mRNA company developing curative therapies for cancer and beyond, reported that it will present preclinical data from its STX-003 program at the 2025 annual meetings of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago April 25-30 and the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in New Orleans May 13-17 (Press release, Strand Therapeutics, APR 28, 2025, View Source [SID1234652280]). The proof-of-concept studies demonstrate that Strand’s programmable mRNA genetic circuits can target the expression of interleukin-12 (IL-12) to cancerous tissue to help achieve the right therapeutic dose while reducing off target side effects. These groundbreaking findings underscore the potential of STX-003 and build on the promise of Strand’s platform and pipeline to address the critical challenges of solid tumor immunotherapy.

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Systemic delivery is an effective way to reach solid tumors that are not surface accessible. However, systemic delivery of potent cytokines such as recombinant IL-12 has been challenging due to toxicity from off-target side effects. STX-003 aims to overcome this limitation by restricting IL-12 expression to the tumor microenvironment.

STX-003 is a systemically delivered, self-replicating mRNA encoding IL-12. Its programmable mRNA genetic circuitry acts as a sophisticated control system, restricting the expression of the IL-12 payload to the tumor microenvironment and preserving its activity within the cancerous tissue. Through its genetic circuits, Strand engineers its mRNA to sense the unique molecular signatures of different cell types, ensuring that the therapeutic payload is primarily produced within the target tumor tissues, while its activity is significantly inhibited in healthy, off-target tissue areas. By precisely controlling the delivery of mRNA and its expression of IL-12, STX-003 offers a promising strategy to unlock the full therapeutic potential of this powerful cytokine in the fight against solid tumors. The early discovery work was supported by funding from Wellcome Leap, a nonprofit organization focused on accelerating breakthroughs in human health.

"The results from the Strand STX-003 preclinical studies are unprecedented. For the first time, systemically delivered programmable mRNA was used to safely target expression of IL-12 into cancerous tissue while inhibiting expression in healthy tissue," said Jacob Becraft, Ph.D., CEO & Co-Founder, Strand Therapeutics. "Our proprietary mRNA platform and genetic circuitry have the potential to make systemic delivery of mRNA and expression of powerful cytokines such as IL-12 safer and more effective for patients in a range of solid tumors, including hard to reach visceral tumors."

STX-003 presentations at AACR (Free AACR Whitepaper) and ASGCT (Free ASGCT Whitepaper) include key findings from preclinical studies regarding the functionality of its genetic circuitry and its impact on the efficacy and tolerability of systemically delivered mRNA expressing IL-12.

AACR
Abstract Title: STX-003: cancer immunotherapy with systemic delivery of mRNA utilizing programmable genetic circuits for precise regulation of IL-12 expression and reduced toxicity
Session Type: Poster
Session Title: PO.IM01.12 Local Treatments, Novel Tools, and Delivery Systems to Manipulate Tumor Immunity
Date and Time: April 28, 2:00-5:00 pm CT
Abstract Number: 3472/11
Location: Section 37

Full abstract is available on the AACR (Free AACR Whitepaper) Annual Meeting website.

ASGCT
Abstract Title: STX-003: A mRNA Cancer Immunotherapy Utilizing Cancer-Selective Programmable Genetic Circuits for Systemic Tumor Control
Session Type: Oral
Session Title: Targeted Gene and Cell Therapy for Cancer
Date and Time: May 17, 8:15-8:30 am CT
Abstract Number: 394
Location: Room 291-292

Full abstract is available on the ASGCT (Free ASGCT Whitepaper) Annual Meeting website.

Strand continues to demonstrate innovation in the field of programmable mRNA therapeutics, marked by significant preclinical and clinical progress for its mRNA platform for solid tumor treatment. In 2023, the company received U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application for STX-001, an investigational multi-mechanistic, synthetic self-replicating mRNA technology that expresses an IL-12 cytokine for an extended duration, directly into the tumor microenvironment via intratumoral delivery. Strand dosed their first patient in a Phase 1 clinical trial in 2024. STX-001 clinical development is ongoing and updates will be shared in the near future. These achievements reflect the company’s ability to translate its innovative mRNA technology from the laboratory into clinical development.

Personalis’ NeXT Personal® Detects 100% of Colorectal Cancer Relapses Ahead of Imaging in VICTORI Cancer Study

On April 28, 2025 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported new interim analysis results of the VICTORI study showing strong performance of its ultra-sensitive NeXT Personal assay in detecting early signs of residual or recurrent colorectal cancer (CRC) (Press release, Personalis, APR 28, 2025, View Source [SID1234652279]).

The study, led by Dr. Jonathan Loree’s team at BC Cancer in Vancouver, Canada, utilized NeXT Personal to look for small traces of circulating tumor DNA (ctDNA) in blood samples from a cohort of 71 patients with resectable Stage I-IV CRC. The data was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois by Emma Titmuss at BC Cancer, in an oral presentation titled Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study.

"After surgery, ctDNA-based liquid biopsies may help identify patients who would benefit most from additional treatment," said Jonathan Loree, MD, MS, a medical oncologist at BC Cancer and the senior investigator of the study. "Alternatively, this may help patients with good prognosis avoid toxicities from unnecessary chemotherapy. By monitoring patients for recurrences, liquid biopsies can continue to support clinical care and allow more patients to undergo second curative intent surgeries to remove early recurrences."

Key findings presented from the interim analysis for VICTORI:

100% of patients who have recurred were detected as ctDNA positive by NeXT Personal prior to detection on imaging.
100% of patients who have been ctDNA negative throughout the study remain disease-free.
87% of clinical recurrences were detectable within the early "landmark window" 2 to 8 weeks after surgery, with 85% detectable by 4 weeks.
64% of detections within the landmark window were in the ultrasensitive range (under 100 ppm).
100% of distant metastatic recurrences were detected prior to imaging, including lung metastasis, an area which has traditionally been more challenging to detect by ctDNA testing.
70% of the first ctDNA detections were in the ultrasensitive range, with a median of 24.4PPM and as low as 2.45 PPM.
Median patient follow-up at the time of the interim analysis was 15.75 months, with the patients continuing to be followed clinically.

"The initial results from our study show the importance of using a highly sensitive MRD assay like NeXT Personal in colorectal cancer," said Dr. Loree.

"We are encouraged by the preliminary results from the VICTORI study, which show the ability of our ultrasensitive ctDNA assay NeXT Personal to detect residual and recurrent colorectal cancer at high rates in the early landmark window after surgery," said Dr. Richard Chen, Chief Medical Officer and Executive Vice President, R&D at Personalis. "We continue to expand this prospective study as we strive towards helping patients with colorectal cancer detect and treat recurrence earlier."

ADC Therapeutics Announces Preclinical Data Highlighted at the American Association for Cancer Research Annual Meeting 2025

On April 28, 2025 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), reported data from preclinical studies of three exatecan-based antibody drug conjugates (ADCs) targeting Claudin-6 (CLDN6), prostate-specific membrane antigen (PSMA), and Alanine, Serine, Cysteine Transporter 2 (ACST2) as presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, ADC Therapeutics, APR 28, 2025, View Source [SID1234652278]).

"We believe these presentations demonstrate the strong potential of our exatecan-based ADCs to treat a wide range of solid and hematologic cancers beyond lymphoma. The data from the oral presentation of our CLDN6-targeted ADC show its potential, both as a single agent and in combination, to treat ovarian and non-small cell lung cancers," said Patrick van Berkel, PhD, Chief Scientific Officer of ADC Therapeutics. "Our additional presentations showcase compelling data validating the potency and tolerability of our PSMA-targeting and ASCT2-targeting ADCs."

Data from the preclinical investigation of ADCT-242, a novel exatecan-based ADC targeting CLDN6, were presented in an oral presentation titled, "Preclinical investigation of ADCT-242, a novel exatecan-based antibody drug conjugate targeting Claudin-6, as single agent or in combination in ovarian and non-small lung cancer models." Key highlights from this presentation include:

ADCT-242 demonstrated potent anti-tumor activity in vivo in PA-1 and OVCAR-3 xenograft models with medium CLDN6 expression
CLDN6-dependent anti-tumor activity of ADCT-242 was observed in lung patient-derived tumor models
ADCT-242 was tolerated in mice or cynomolgus monkeys at doses up to 150 mg/kg or 40 mg/kg, respectively, indicative of a good therapeutic index
Data from the preclinical investigation of ADCT-241, a novel PSMA-targeting ADC, were presented in a poster presentation titled, "Preclinical Development of ADCT-241, a Novel Exatecan-based Antibody-Drug Conjugate Targeting PSMA for the Treatment of Prostate Cancer." The data demonstrated antitumor activity in both xenograft and patient-derived PSMA-expressing prostate cancer models as well as synergy with enzalutamide. ADCT-241 was well tolerated in both rats and cynomolgus monkeys.

Data from the preclinical investigation of HuB14-VA-PL2202, a novel ASCT2-targeting ADC, were presented in a poster presentation titled, "HuB14-VA-PL2202, a novel antibody-drug conjugate targeting ASCT2, a novel ADC target over-expressed in both solid and hematological cancers." The data demonstrated potent and specific in vitro and in vivo antitumor activity of HuB14-VA-PL2202 in ASCT2-positive solid and hematological cancer cell lines, and HuB14-VA-PL2202 was well-tolerated in cynomolgus monkeys.

Elpis Biopharmaceuticals to Present Two "Late-Breaking" Posters Detailing Its Pioneering CAR-T Cell Therapy Technologies at AACR Annual Meeting 2025

On April 28, 2025 Elpis Biopharmaceuticals, a clinical-stage cell therapy company developing bispecific armored CAR-T therapies for solid tumors, reported that it will present two posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Elpis Biopharmaceuticals, APR 28, 2025, View Source [SID1234652277]). The presentations, which were accepted as late-breaking submissions, highlight the company’s latest advances in multi-mechanism, armored CAR-T therapies for the treatment of solid tumors and glioblastoma (GBM).

The first poster, LB363, titled, "Multi-mechanism human B7H3 CAR-T effectively overcome tumor microenvironment resistance in treatment of solid tumors," details research involving EPC-002, Elpis’s novel human B7H3-targeted CAR-T cell therapy developed with a proprietary, precision-engineered multi-mechanism armor to simultaneously overcome multiple tumor microenvironment (TME) resistant mechanisms. B7H3 is overexpressed on a wide range of solid tumors, including skin, pancreatic, lung, breast, colon, kidney, ovarian, and other cancers. As presented at AACR (Free AACR Whitepaper), EPC-002 demonstrated an ability to reduce regulatory T cell proliferation, modulate CAR-T and bystander immune cell activation, enhance TIL infiltration, overcome TME suppression, and mediate anti-tumor activity. These mechanisms were highlighted in preclinical mouse models in which EPC-002 enabled complete tumor regression and long-term persistence with very low dose of 0.3M CAR-T cells in tumor rechallenging studies.

The second poster, LB360, titled, "Discovery and development of fully human IL13Ra2/B7H3 bispecific armored CAR-T for treatment of glioblastoma," describes the ongoing development of EPC-003, Elpis’s first-in-class human bispecific CAR-T cell therapy targeting IL13Ra2 and B7H3, two antigens co-expressed in a majority of GBM tumors. Engineered with Elpis’s proprietary mRNADis and mSCAFold platforms, EPC-003 integrates dual antigen targeting with a secreted multi-functional armor to enhance CAR-T cell persistence, block immune suppression, and penetrate the blood-brain barrier (BBB). As presented at AACR (Free AACR Whitepaper), in an orthotopic GBM mouse model, EPC-003 induced tumor regression as early as day 6 following intracranial injection of 2 × 10⁶ CAR-T cells. Moreover, intravenous injected CAR-T cells successfully penetrated the BBB, achieving significant tumor regression by day 13 post-treatment.

"Having two presentations detailing our lead product candidates, EPC-002 and EPC-003, accepted as late-breaking submissions at AACR (Free AACR Whitepaper) is tremendous validation of Elpis’s technologies and the potential that each offers in the treatment of solid tumors and glioblastoma, which have thus far proven resistant to most CAR-T therapies," said Yan Chen, MD, Ph.D., CEO of Elpis Biopharmaceuticals. "Our multi-mechanism approach is designed to address the challenges of tumor microenvironment resistance and antigen heterogeneity, unlocking the full potential of CAR-T in solid tumors and hard-to-treat cancers like glioblastoma. We now look forward to advancing each product into the clinic, including a soon-to-be initiated proof of concept, investigator-initiated trial of EPC-003 in resistant/relapsed glioblastoma patients."

Presentation Details:

Session Title:

Late-Breaking Research: Clinical
Research 3(LB363)

EPC-002: Multi-mechanism human B7H3
CAR-T effectively overcome tumor
microenvironment resistance in treatment
of solid tumors

Session:

4/29/2025 2:00-5:00 PM

Location:

Poster Section 53

Poster Board Number:

Session Title:

Late-Breaking Research: Clinical
Research 3(LB360)
EPC-003: Discovery and development of
fully human IL13Ra2/B7H3 bispecific
armored CAR-T for treatment of
glioblastoma

Session:

4/29/2025 2:00-5:00 PM

Location:

Poster Section 53

Poster Board Number:

AffyImmune Announces Plenary Oral Presentation on ICAM-1 Directed CAR T Therapy AIC100 at AACR 2025

On April 28, 2025 AffyImmune Therapeutics, Inc., a clinical-stage biopharmaceutical company, reported an abstract detailing its affinity-tuned CAR T therapy AIC100 will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held April 25-30, 2025 at McCormick Place Convention Center in Chicago, IL (Press release, AffyImmune Therapeutics, APR 28, 2025, View Source [SID1234652276]).

"We look forward to presenting our updated Phase 1 data at AACR (Free AACR Whitepaper), and to provide interim safety and efficacy results from our Phase 1 Dose Escalation trial evaluating AIC100 CAR T therapy in patients with advanced thyroid cancers," said Daniel Janse, CEO, AffyImmune. "These results mark progress, as we plan the next steps for our affinity-tuned CAR T therapies for patients with unmet medical need."

Presentation Details:

Title: ICAM-1 directed chimeric antigen receptor (CAR) T cells (AIC100) in patients with Advanced Thyroid cancers: Clinical and translational data from the phase 1 dose escalation study

Presenter: Dr. Samer Ali Srour, University of Texas MD Anderson Cancer Center, Houston, TX

Session Type: Oral Presentation – Clinical Trials Plenary Session

Abstract Number: CT206

Date and Time: April 29, 2025 10:15AM – 12:15PM CST

Location: McCormick Place Convention Center in Chicago, Illinois