Silexion Therapeutics’ SIL-204 Shows Groundbreaking Synergy in Preclinical Data, Boosting Hope for KRAS-Driven Cancer Treatments

On January 16, 2025 Silexion Therapeutics (NASDAQ: SLXN), a clinical-stage biotech advancing RNA interference (RNAi) therapies for KRAS-driven cancers, reported compelling new preclinical data for SIL-204, its next-generation siRNA candidate (Press release, Silexion Therapeutics, JAN 16, 2025, View Source [SID1234649764]). These findings reaffirm the company’s innovative approach to addressing some of the most challenging cancers, including pancreatic cancer, which is marked by KRAS mutations in over 90% of cases.

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The newly released data reveal significant synergy between SIL-204 and first-line chemotherapy agents, including 5-fluorouracil, irinotecan, and gemcitabine. In human pancreatic tumor cell models harboring KRAS G12D mutations, SIL-204 amplified the efficacy of these standard therapies, resulting in greater reductions in cancer cell confluence compared to chemotherapy alone. This underscores SIL-204’s potential to enhance treatment regimens for pancreatic cancer and other KRAS-driven cancers, potentially addressing a substantial unmet medical need.

Building on the success of its first-generation LODER platform, which improved overall survival in Phase 2 trials, SIL-204 takes Silexion’s RNAi approach further by targeting a broader spectrum of KRAS mutations. With toxicology studies set to begin soon and Phase 2/3 trials planned for 2026, Silexion remains on track to advance its groundbreaking candidate into the clinic.

Shortly releasing this new data, Silexion also announced the pricing of a $5 million public offering to support its preclinical and clinical efforts. While this may introduce near-term dilution, if the offering is to close, the additional capital seems to bolster the company’s ability to drive innovation and achieve key clinical milestones as it moves forward.

As KRAS-driven cancers continue to be among the most aggressive and elusive to treat, Silexion’s progress with SIL-204 positions it as an important innovator to watch in the precision oncology space, offering hope for transformative therapies that could redefine cancer care.

Chromatin Bioscience’s synthetic promoter supports EsoBiotec’s ESO-T01 CAR-T therapy as it enters the clinic

On January 15, 2025 Chromatin Bioscience reported its ongoing collaboration with EsoBiotec, which has successfully advanced its ESO-T01 in vivo CAR-T candidate into clinical trials (Press release, EsoBiotec, JAN 15, 2025, View Source [SID1234649749]). ESO-T01 is the first in vivo B-cell maturation antigen (BCMA) CAR-T candidate to reach the clinical stage and utilises a synthetic promoter designed using Chromatin Bio’s proprietary promoter design platform, chromatinLENS, exclusively for EsoBiotec as part of its innovative approach to immunotherapy.

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EsoBiotec’s ESO-T01, developed using its ENaBL platform, is a T cell targeted lentiviral vector expressing a BCMA-targeted CAR construct for the treatment of multiple myeloma. This construct is regulated by a Treg-specific synthetic promoter developed in collaboration with Chromatin Bioscience. Early studies demonstrated highly effective in vivo transduction, with the BCMA CAR transgene expressed specifically in T cells, leading to the generation of a large population of circulating BCMA CAR-T cells that persisted throughout the study. These results highlight the long-term durability and efficacy of the engineered T cells, marking an important milestone for the therapeutic.

"ESO-T01 is the first in vivo BCMA CAR-T candidate to advance to the clinical stage, showcasing the capabilities of our ENaBL platform technology that reprograms immune cells within the body to combat cancer," stated EsoBiotec CEO Jean-Pierre Latere, Ph.D. "While various treatments exist for multiple myeloma, including ex vivo CAR-T options, many come with severe side effects and are limited by manufacturing capacity, logistical challenges, and high costs. We are excited to collaborate with Chromatin Bioscience to integrate this innovative synthetic promoter, aiming to enhance the safety and efficacy profile of ESO-T01."

Chromatin Bioscience’s chromatinLENS platform allows for the identification of highly specific, cell-type selective gene regulatory elements from the dark genome, offering significant advantages in minimising off-target effects while ensuring robust and durable therapeutic efficacy. These promoters are critical in ensuring the success of advanced therapies like ESO-T01, where targeted expression in T cells is paramount for the safety and efficacy of the treatment.

"EsoBiotec’s progress to the clinic is an exciting development in the field of gene therapy," said Michael Roberts, CEO and Founder of Chromatin Bioscience. "Our synthetic promoters are designed to provide precision and durability in gene expression, and we are pleased that they are playing a role in ensuring the success of ESO-T01. This collaboration represents the power of combining cutting-edge gene therapy with targeted gene expression technologies to offer new treatment options for patients."

AIM ImmunoTech Highlights Key 2024 Achievements and Outlines Upcoming 2025-26 Value-Driving Milestones

On January 15, 2025 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company") reported key clinical, regulatory and corporate milestones achieved over 2024 and outlined its expected upcoming milestones (Press release, AIM ImmunoTech, JAN 15, 2025, View Source [SID1234649733]).

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"It is clear that 2024 was a foundational year for AIM on the clinical, regulatory and corporate fronts. Without a doubt, our team continued to drive our strategy forward and deliver results. We believe this progress has positioned AIM for an exciting 2025 and the opportunity to drive value for our stockholders," stated Thomas K. Equels, Chief Executive Officer of AIM ImmunoTech. "Looking ahead, we believe we are poised for an exciting 2025 with a number of key milestones expected over the next 18 months across important clinical trials addressing major unmet medical needs. Certain of these trials are being funded in part by major oncology interests such as the National Cancer Institute, AstraZeneca and Merck, which we believe emphasizes their great potential to change lives for the better. Our team is committed to the seamless execution of our clinical development programs and, if successful, we believe each holds the potential to drive significant value in the near and long term."

2024 Clinical Achievement Highlights

Metastatic Pancreatic Ductal Adenocarcinoma Program

Commenced enrollment and dosing in DURIPANC Phase 1b/2 study combining Ampligen with AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor Imfinzi (durvalumab) for the treatment of late-stage pancreatic cancer;
Announced that the first dose level was generally well-tolerated in the DURIPANC Phase 1b/2 study of Ampligen and Imfinzi as a combination therapy for late-stage pancreatic cancer; and
Reported positive preliminary data from Phase 1b/2 study of Ampligen and Imfinzi as a combination therapy for late-stage pancreatic cancer.
Phase 2 Locally Advanced Pancreatic Adenocarcinoma Program

Received authorization from the Erasmus Medical Center Ethics Committee to open a European site for the ongoing Phase 2 study ("AMP-270") of Ampligen as a therapy for locally advanced pancreatic cancer; and
Announced the publication of new positive data analysis from a long-term Early Access Program studying Ampligen for the treatment of advanced pancreatic ductal adenocarcinoma.
The Company sought FDA guidance on expansion of inclusion criteria and treatment arms, and then subsequently amended the study protocol. The study is recruiting patients. These adjustments are also expected to result in substantial reductions in clinical costs.
Phase 2 Recurrent Ovarian Cancer Program

Reported positive top-line, protocol-planned interim report data from the study of Ampligen combined with pembrolizumab for the treatment of recurrent ovarian cancer.
Phase 2 Post-COVID Conditions Program

Reported positive topline results from the Company’s Phase 2 study evaluating the efficacy and safety of Ampligen as a potential therapeutic for people with the post-COVID condition of fatigue ("AMP-518"); and
Reported an analysis of the AMP-518 clinical trial, based upon statistically significant data, which supports the Company’s belief in Ampligen as a potential therapeutic for people with the moderate-to-severe post-COVID-19 condition of fatigue, and that this would be the likely subject population for AIM’s planned follow-up clinical trial.
Grants of Intellectual Property in 2024
Further, the Company was also granted two important patents covering Ampligen for the treatment of:

Endometriosis, a painful chronic condition that affects nearly 10% of women of reproductive age, or approximately 6.5 million women in the United States. This patent was granted in the United States.
The Post-COVID Condition of Fatigue. This method and compositions patent was granted in the Netherlands.
Additionally, AIM successfully completed cGMP manufacturing of 9,042 clinical vials of Ampligen. The Company announced the publication of new pre-clinical data of Ampligen as part of a combinational therapy in the treatment of melanoma.

Expected Upcoming, Value-Driving Milestones

Metastatic Pancreatic Ductal Adenocarcinoma
Phase 1b/2 Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab with TLR-3 Agonist Ampligen in Patients with Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy (DURIPANC) (NCT05927142); Funded through collaboration of AstraZeneca and Erasmus Medical Center

Q1 2025: Complete Phase 1b
Early Q2 2025: Launch of Phase 2
Q2/Q3 2026: Last patient enrolled in Phase 2
Locally Advanced Pancreas Cancer (LAPC)
Phase 2 Ampligen Combined with Standard of Care (SOC) versus SOC Alone Following First-Line Therapy in Subjects with LAPC (NCT05494697); AIM funded

Q1 2025: Buffet Cancer Center expected to enroll first subject
H1 2025: first subject dosed
Refractory Melanoma
Phase 2 Polarized Dendritic Cell (aDC1) Based Treatment, Interferon Alpha-2, Ampligen, and Celecoxib for the Treatment of HLA-A2+ Refractory Melanoma (NCT04093323); Grant funded by National Cancer Institute

H1 2025: First patient dosed
Stage 4 Triple Negative Breast Cancer
Phase 1/2a Study of Ampligen, Celecoxib and Interferon Alpha 2b with Pembrolizumab for the Treatment of Patients with Metastatic or Unresectable Triple Negative Breast Cancer (NCT05756166); Grant funded by Merck and National Cancer Institute

Q2 2026: Expected completion of enrollment
Advanced Recurrent Ovarian Cancer
Phase 2 Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer (NCT03734692); Grant funded by Merck

H1 2025: Expected last patient dosed and completion of study
Advanced Recurrent Ovarian Cancer
Phase 2 Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines (NCT02432378); Grant funded by the National Cancer Institute

H1 2025: First patient dosed
Post COVID Chronic Fatigue Conditions / Long Covid
Phase 2 Study to Evaluate the Efficacy and Safety of Ampligen in Patients with Post-COVID Conditions (NCT05592418); AIM funded

Q1 2025: Final approved study results to be published on clinicaltrials.gov

OS Therapies Announces Phase 2b Clinical Trial of OST-HER2 Achieves Primary Endpoint with Statistical Significance in the Prevention of Recurrent, Fully Resected, Lung Metastatic Osteosarcoma

On January 15, 2025 OS Therapies, Inc. (NYSE-A: OSTX), a clinical-stage biotechnology company advancing immunotherapies and targeted drug conjugates for cancer treatment, reported positive data from a Phase 2b clinical trial (NCT04974008) of OST-HER2 (OST31-164) – the Company’s HER2-targeted immunotherapy candidate in the rare pediatric-designated indication of prevention of recurrent, fully resected, lung metastatic osteosarcoma (Press release, OS Therapies, JAN 15, 2025, View Source [SID1234649750]). The data demonstrate statistically significant results in the primary endpoint of the study, 12-month event free survival (‘EFS’), where an event is defined as the recurrence of metastatic osteosarcoma, in OST-HER2-treated patients when compared with the leading published historical comparable control group. Further as of the most recent follow up, the data show a strong trend in favor of OST-HER2-treated patients in overall survival (‘OS’, remaining alive) at the 1-year and 2-year interim timepoints of the ongoing 3-year overall survival secondary endpoint. Notably, all patients who achieved the primary 12-month EFS endpoint remain alive.

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"We are extremely pleased with these results of our Phase 2b clinical trial because they show that OST-HER2-treated patients achieved the primary endpoint of 12-month EFS in a statistically significantly higher ratio than comparable historical controls, in addition to increasing the likelihood of 1-year and 2-year survival as compared with comparable historical controls," commented Dr. Robert Petit, Chief Medical & Scientific Officer of OS Therapies. "The strong safety profile shown in this study also supports the use of OST-HER2 in this incredibly difficult-to-treat population that has no currently approved therapies."

"The achievement of the primary endpoint in the OST-HER2 phase 2b is a tremendous success that opens the possibility, for the first time, of meaningful therapy for patients suffering from osteosarcoma with lung metastases after resection. This is a leap forward in the development of OST-HER2 and we are pleased that our regulatory strategy is consistent with the FDA’s recent draft guidance update for accelerated approvals. With these positive data in hand, we are preparing to engage with U.S. FDA on an accelerated pathway for approval in this extremely challenging indication," said Paul Romness, MHP, Chair & CEO of OS Therapies. "We do not expect to have to treat additional patients as part of this process with FDA."

Phase 2b Clinical Trial Data

Enrollment Criteria:

12-39 years old
Recurred, fully resected lung only metastatic (METS) Osteosarcoma
39 evaluable patients at 21 centers, single treatment arm
52 Weeks on Study: Dosed 16 times every 3 weeks for 48 weeks with 4-week follow-up final visit
Primary Endpoint of 12-month EFS:

33% for OST-HER2 vs. 20% for historical control1 (p = 0.0158)
Interim Analysis of Ongoing Secondary Endpoint, OS:

1-year OS: 91% for OST-HER2 vs. 80% for historical control2 (p = 0.0700)
2-year OS: 61% for OST-HER2 vs. 40% for historical control2 (p = 0.0576)
Post-Hoc Analyses

12-months EFS Subgroup Analysis in the OST-HER2 Treatment Group:

Gender (Males vs Females), n = 39:

Females (n=19) = 47%
Males (n= 20) = 20%
(p= 0.0604)
Number of lung resections (1 Prior Resection vs. 2+ Prior Resections), n= 39:

1 Prior Resection (n= 28) = 25%
2+ Prior Resections (n= 11) = 55%
(p = 0.1366)
12-month EFS Responders using a Non-Concurrent Control Group from the only existing US osteosarcoma database with patients qualified for disease-free status following a fully-resected lung-only metastasis of osteosarcoma origin:

OST-HER2, n=39
12-month EFS Responders = 13/39 (33%)
NCCG, n=9
12-month EFS Responders = 1/9 (11%)
(p = 0.1848)
Time to recurrence in patients who did not achieve 12-month EFS:

OST-HER2, n=26 = 5.9 months
NCCG, n=8 = 4.7 months
(p = 0.1454)
About OST-HER2

OST-HER2 is an innovative immunotherapy using a HER2 bioengineered form of the bacteria Listeria monocytogenes (Lm) to trigger a strong immune response against cancer cells expressing HER2. This off-the-shelf immunotherapy treatment is designed to prevent metastasis, delay recurrence, kill primary tumors expressing HER2 alone and potentially in combination with existing approved therapies, and increase overall survival. OST-HER2 has received Rare Pediatric Disease Designation (RPDD) from the FDA and Fast Track and Orphan Drug Designations from the FDA and European Medicines Agency (EMA).

The US FDA granted OST-HER2 rare pediatric disease designation for osteosarcoma in 2021. The US FDA rare pediatric disease PRV program aims to incentivize drug development for rare pediatric diseases. Under this voucher program, a sponsor who receives an approval for a drug or biological product for a rare pediatric disease qualifies for a voucher that can be redeemed to receive priority review for a different product. The sponsor may also transfer or sell the voucher to another sponsor. OS Therapies intends to sell the PRV it would earn upon receiving an approval of OST-HER2 for recurrent, fully resected, lung metastatic osteosarcoma. The most recent publicly disclosed sale price of a PRV was on November 27th, 2024 when PTC Therapeutics announced selling its PRV to Kebilidi for $150M. With emerging scarcity in the PRV market, the Company expects the value of PRVs to increase going forward. The maximum sale price of a PRV was in 2015 when AbbVie bought a priority review voucher from United Therapeutics for $350 million.

The most recent continuing resolution (CR) negotiations in the US House of Representatives failed to reauthorize the PRV program for pediatric cancers such as osteosarcoma. Despite this, as a result of OS Therapies’ having been granted OST-HER2’s rare pediatric disease designation prior to December 20, 2024 in addition to the Company’s aim to receive an approval for OST-HER2 in the rare pediatric disease osteosarcoma in 2025, prior to the September 30, 2026 deadline, OS Therapies remains eligible to receive the PRV upon approval of OST-HER2 in recurrent, resected metastatic osteosarcoma.

The osteosarcoma treatment market was estimated at $1.2 billion in 2022 according to Data Bridge Market Research. Approximately 50% of patients are diagnosed with a lung metastasis at some point following surgical resection and chemotherapy. 3-year survival rates in patients who were not diagnosed with a metastasis are 59%. 3-year survival rates in patients who were diagnosed with pulmonary metastasis were 30%. The Company believes the market opportunity for OST-HER2 in the prevention of lung metastases is over $500 million.

Imagenomix Corp. Partners with Alterome Therapeutics Inc. to Enhance Precision Oncology Clinical Trials with AI

On January 15, 2025 Imagenomix Corp., a leader in AI-driven precision medicine, reported a groundbreaking partnership with Alterome Therapeutics Inc., a pioneering oncology drug development company (Press release, Alterome Therapeutics, JAN 15, 2025, View Source [SID1234649734]). This collaboration will leverage Imagenomix’s cutting-edge artificial intelligence technologies to optimize clinical trial efficiency, improve patient stratification, and accelerate the development of Alterome’s targeted cancer therapies.

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The partnership represents a convergence of Imagenomix’s advanced AI expertise with Alterome’s innovative approach to precision oncology. Together, the companies aim to set a new standard for using AI to transform clinical trials and deliver life-saving treatments to patients faster.

Travis Wold, CEO of Imagenomix Corp., emphasized the transformative potential of the partnership:
"We are honored to collaborate with Alterome Therapeutics Inc., a trailblazer in precision oncology. At Imagenomix, we are committed to leveraging AI to advance medicine, and this partnership exemplifies the extraordinary impact of combining state-of-the-art technology with innovative therapeutic development."

Dr. Andrew Chi, Chief Medical Officer of Alterome Therapeutics Inc., shared his perspective on the collaboration:
"We are excited to integrate Imagenomix’s AI-powered analytics into our clinical trials., Together, we have an opportunity to redefine the way precision oncology clinical trials are conducted. By developing methods to rapidly identify critical patient selection biomarkers with unparalleled efficiency and scale we can potentially pave a new path to faster, more effective precision oncology trials. This approach could easily translate into routine patient care and ultimately improve patient outcomes."

Key Highlights of the Partnership:

Accelerated Drug Development: The Imagenomix Predict AI platform will streamline clinical trial timelines and improve cost-effectiveness.
Enhanced Precision: Advanced analytics aims to identify critical biomarkers with unprecedented speed, scale, and efficiency to ensure targeted patient selection for Alterome’s targeted therapy trials.
Industry Innovation: The partnership represents a paradigm shift in leveraging AI for oncology clinical trials, setting a new benchmark for the field.
This strategic collaboration underscores the shared commitment of Imagenomix Corp. and Alterome Therapeutics Inc. to harness the power of innovative technologies in delivering precision medicine breakthroughs.