On March 13, 2025 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported that the Safety Review Committee (SRC) monitoring its Phase I clinical trial has unanimously approved opening of the fourth cohort of patients based on the SRC’s favorable review of Cohort 3 safety data (Press release, TransCode Therapeutics, MAR 13, 2025, View Source [SID1234651139]). The therapeutic candidate being evaluated, TTX-MC138, is a first-in-class therapeutic designed to treat multiple metastatic cancers using antisense technology. The dose administered to the fourth cohort, as originally planned in the clinical protocol, will be approximately fifty percent higher than the dose administered in the third cohort.

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Under the clinical protocol, patients may remain on study absent safety events or disease progression. Out of 9 patients treated with TTX-MC138 in the first three cohorts, 6 remain on study for continued treatment since there have been no dose limiting toxicities or disease progression with these patients. The patient that has remained on study the longest has, to date, received 7 doses each approximately 28 days apart over the approximately 7 months that this patient has been on study. In addition to approving opening the fourth cohort, the SRC approved enrollment of additional patients in Cohort 3 to build upon the safety profile of TTX-MC138. Further, Cohort 1 and 2 data analysis for both pharmacokinetic (PK) and pharmacodynamic (PD) activity is ongoing and suggests that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical results and results from TransCode’s Phase 0 clinical trial. Preliminary results from Cohort 2 confirmed observations from the Phase 0 trial and from Cohort 1 that the drug candidate shows evidence of activity in patient blood. Preliminary PK analysis suggests that dose levels 0.8-1.6 mg/kg, the levels administered to Cohorts 1 and 2, could represent an efficacious range.

"SRC approval to open the fourth cohort and expand enrollment in Cohort 3 is an important advancement for the clinical trial. It will provide an opportunity to obtain additional safety and PK/PD data, inform the dose expansion stage of the clinical trial and may allow us to obtain initial evidence of clinical activity" commented Sue Duggan, TransCode’s Senior Vice President of Operations. Duggan added, "Enrollment into the study continues based on the cumulative safety data review. Eligible subjects may now be screened and scheduled in Cohort 4 for treatment with the next dose level of TTX-MC138 while preliminary data analysis continues."

About TTX-MC138

TTX-MC138 is a first-in-class therapeutic candidate that targets microRNA-10b, a micro-RNA widely believed to be a driver of metastatic disease. TransCode’s 2023 Phase 0 clinical trial produced evidence of delivery of a radiolabeled version of TTX-MC138 to metastatic lesions and pharmacodynamic activity, even at a microdose of the drug candidate, suggesting a broad therapeutic window for TTX-MC138.

About the Trial

TransCode’s Phase 1 clinical trial is a multicenter, open-label, dose-escalation and dose-expansion study, designed to generate critical data to support evaluation of the safety and tolerability of TTX-MC138 in patients with a variety of metastatic solid cancers. While not an endpoint, the trial may provide early evidence of clinical activity of TTX-MC138. The trial comprises an initial dose-escalation stage followed by a dose-expansion stage. The primary objective of the dose-escalation stage is to evaluate the safety and tolerability of escalating dose levels of TTX-MC138. In the dose-expansion stage, the safety, tolerability and anti-tumor activity of TTX-MC138 will be further evaluated in certain tumor types selected based on preliminary results from the dose-escalation stage.

Further information is available at www.clinicaltrials.gov NCT Identifier: (NCT06260774).

On March 13, 2025 Blue Earth Therapeutics reported further promising developments for its radiohybrid lutetium labelled, PSMA targeted, investigational radioligand therapy (Press release, Blue Earth Therapeutics, MAR 13, 2025, View Source [SID1234651138]). Radiation dosimetry and pharmacokinetic data from the 13 metastatic castrate resistant prostate cancer patients enrolled in the Phase 1 portion of a Phase 1/2 clinical trial (NCT05413850) of Lutetium (177Lu) rhPSMA-10.1 Injection showed proportionately higher absorbed radiation doses in tumours than in critical healthy tissues such as the kidneys. The data compares favourably to published data on first-generation PSMA-targeted radioligand therapies.1,2

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The Phase 1 data shows that Lutetium (177Lu) rhPSMA-10.1 Injection has high ratios for absorbed radiation dose to tumours vs. dose to healthy tissues, with a measured mean tumour to salivary gland ratio of 73 and tumour to kidney ratio of 32. Median absorbed radiation dose to tumours defined by SPECT imaging was 8.9 Gy for each GBq of administered radioactivity. Mean absorbed radiation dose to the kidneys was 0.27 Gy/GBq; to salivary glands, 0.13Gy/GBq.

Underlying these results, the mean biological half-life in tumors for the Lutetium (177Lu) rhPSMA-10.1 Injection was 338 hours. When paired with the 6.7-day physical half-life of 177Lu, this gives an effective mean half-life of 91.4 hours. This allows delivery of radiation to tumors over many days: one and a half to twice the reported data for established agents in this class1. This prolonged retention of the drug in tumors without proportionate increases to retention in normal tissues helps to explain the positive radiation dosimetry data.

Following recent consultation with regulatory authorities, and sharing of the preliminary data, this now opens the way for the Phase 2 portion of the Phase 1/2 trial to test innovative dosing regimens, with the goal of optimising outcomes for patients. This Phase 2 portion of the study will explore the following dosing concepts:

Administration of significantly higher overall injected radioactivity in comparison to recent Phase 3 clinical trials of other PSMA-targeted radioligand therapies
Front loading of administered radioactivity in early cycles; and
Extending the duration of administration of radioactivity beyond 36 weeks to provide longer time on treatment.
In combination with the promising Phase 1 data for Lutetium (177Lu) rhPSMA-10.1 Injection, these design factors should further support the aim of maximizing treatment response and therefore may enable delivery of better outcomes for patients. The Phase 2 portion of the study is expected to start this quarter.

David Gauden DPhil, CEO of Blue Earth Therapeutics said, "The Phase 1 data provides strong validation of the innovative approach taken on optimizing radioligand therapy by Blue Earth Therapeutics and the inventors of the rhPSMA technology. The relative ratios of tumour to healthy organ absorbed radiation doses are key metrics in establishing a better profile of the risks and potential benefits of radioligand therapies. With radioligand therapies, normal organ toxicity considerations gate the total amount of radioactivity that can be administered, so the more of the radioactivity that accumulates in tumours, the better. Our goal is to substantially increase the potential for prostate cancer patients to benefit compared to available radioligand therapy, and completion of this study moves us closer to making that goal a reality."

About metastatic prostate cancer
In 2025 it is estimated that there will be 50,055 new cases of metastatic prostate cancer in the United States (de novo diagnoses plus recurrence from earlier stage diagnoses).3 Five-year survival for newly diagnosed metastatic prostate cancer is low, 36.6%.4 While death rates from prostate cancer have declined over the past three decades4, there is still considerable room to improve patient outcomes.

About Radiohybrid Prostate–Specific Membrane Antigen (rhPSMA)
rhPSMA compounds are referred to as radiohybrid ("rh"), as each molecule possesses four distinct domains. The first consists of a Prostate–Specific Membrane Antigen–targeted receptor ligand. It is attached to two labelling moieties which may be radiolabeled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy, all of which are joined together by a modifiable linker which can be used to modulate important pharmacokinetic characteristics. Radiohybrid PSMA offers the potential for targeted treatment for men with prostate cancer and originated at the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics.

On March 13, 2025 Immorta Bio Inc., a scientific longevity company focused on "Treating Diseases of Aging and Treating Aging as Disease," reported that its Chairman and CEO, Dr. Boris Reznik, presented the latest findings from its SenoVax Program at the LSX Investival Showcase on March 11th at the Miami Beach Convention Centre (Press release, Immorta Bio, MAR 13, 2025, View Source [SID1234651137]).

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The presentation disclosed advancements in the Company’s oncology pipeline, highlighting animal studies showing the regression of brain, lung, skin, pancreas, and breast cancers by SenoVax, the Company’s lead product. Additionally, cellular mechanisms by which this "longevity therapeutic" targets a broad range of cancers were discussed.

"It has been widely demonstrated that senescent cells play a critical role in initiating, promoting and protecting cancer," said Dr. Thomas Ichim, President and Chief Scientific Officer of the Company. "By amplifying the body’s natural immunological activities to kill senescent cells, SenoVax induces regression of tumors."

The Company, together with the University of California San Diego, George Washington University, Calidi Biosciences, and Cedars Sinai, demonstrated in a peer-reviewed publication that SenoVax kills cancer in part by inducing antibody and T cell responses that eliminate senescent cells¹.

"We are developing multiple programs focused on radical extension of human healthspan including our senolytic immunotherapy platform," said Dr. Boris Reznik, Chairman and CEO of Immorta Bio. "Our development strategy is to apply longevity-associated technologies to address unmet medical needs that can provide answers in months not decades."

On March 13, 2025 Enliven Therapeutics, Inc. (Enliven or the Company) (Nasdaq: ELVN), a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapeutics, reported financial results for the fourth quarter and full year ended December 31, 2024, and provided a business update, including highlights of pipeline progress (Press release, Enliven Therapeutics, MAR 13, 2025, View Source [SID1234651136]).

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"We are very pleased with the ongoing progress we are making as a Company. We continue to hear significant enthusiasm and excitement from investigators on both of our programs. The momentum of ELVN-001 has accelerated since the data presentation at the ESH-iCMLf conference," said Sam Kintz, Co-founder and Chief Executive Officer of Enliven. "2025 is a big year for Enliven and we are excited for the upcoming program updates. We are focused on continued clinical execution and preparing for the potential start of a pivotal trial for ELVN-001 in 2026."

Recent Research and Development Highlights and Upcoming Milestones

ELVN-001 is a potent, highly selective, small molecule kinase inhibitor designed to specifically target the BCR::ABL gene fusion

In 2024, the Company announced positive initial data from the ongoing Phase 1 clinical trial that compared favorably to the precedent Phase 1 trials for the approved BCR::ABL1 tyrosine kinase inhibitors (TKIs).
The U.S. Food and Drug Administration (FDA) granted orphan drug designation to ELVN-001 for the treatment of chronic myeloid leukemia (CML).
The first patient was dosed in the Phase 1 trial evaluating ELVN-001 in Japanese patients with CML (NCT06787144).
The Company plans to report additional data from the ongoing Phase 1a/b trial in the middle of 2025.
ELVN-002 is a potent, highly selective, central nervous system (CNS) penetrant and irreversible HER2 inhibitor with activity against wild type HER2 and various HER2 mutations

Enliven continued to enroll patients in its Phase 1 trial evaluating ELVN-002 as a monotherapy agent in patients with HER2+ and HER2 mutant tumors and its exploratory cohort in combination with Kadcyla (an approved HER2 antibody drug conjugate) in patients with HER2+ metastatic breast cancer (MBC) (NCT05650879).
Additionally, the Company continued to enroll patients in its Phase 1 trial evaluating ELVN-002 in combination with trastuzumab +/- chemotherapeutic agents in patients with HER2+ MBC and colorectal cancer (CRC) and began dosing patients in the Phase 1b trial specifically evaluating patients with CRC (NCT06328738).
Enliven plans to report data from the ongoing Phase 1 trials in the second half of 2025.
Fourth Quarter and Full Year 2024 Financial Results

Cash Position: As of December 31, 2024, the Company had cash, cash equivalents and marketable securities totaling $313.4 million, which is expected to provide cash runway into mid-2027.
Research and development (R&D) expenses: R&D expenses were $20.7 million for the fourth quarter of 2024, compared to $17.9 million for the fourth quarter of 2023. R&D expenses were $80.8 million for the full year 2024, compared to $64.6 million for the full year 2023.
General and administrative (G&A) expenses: G&A expenses for the fourth quarter of 2024 were $6.2 million, compared to $4.8 million for the fourth quarter of 2023. G&A expenses were $23.8 million for the full year 2024, compared to $19.0 million for the full year 2023.
Net Loss: Enliven reported a net loss of $23.2 million for the fourth quarter of 2024, compared to a net loss of $19.4 million for the fourth quarter of 2023. Total net loss for the full year 2024 was $89.0 million, compared to $71.6 million for the full year 2023.

On March 13, 2025 Medigene AG (Medigene, FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported the submission of a patent for a novel natural killer (NK) cell-specific TCR construct to the European Patent Office. With that, Medigene is advancing its TCR-guided strategy by expanding the application of its proprietary 3S (sensitive, specific, and safe) TCRs into NK cells (Press release, MediGene, MAR 13, 2025, View Source [SID1234651135]). This patent application marks a major expansion of Medigene’s intellectual property portfolio, broadening its therapeutic reach and reinforcing its commitment to developing innovative, off-the-shelf immunotherapies for cancer treatment.

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To enable this innovation, Medigene combined TCR-guided precision targeting with innate NK cell killing. The Company has developed a proprietary universal scaffold that allows its 3S TCRs to function in NK cells without requiring CD3 co-expression. This novel NK-TCR system enhances NK cell production and therapeutic potential by facilitating the efficient transfer of all 3S TCRs into NK cells, streamlining the manufacturing process for future allogeneic TCR-NK therapies. By eliminating CD3 dependency, this approach overcomes a critical limitation in TCR-based NK cell therapy development, delivering a scalable, clinically viable solution that accelerates therapeutic timelines and reduces costs.

"This innovative approach supports our strategy to apply Medigene’s 3S TCRs into new TCR-guided modalities, such as TCR-TCEs and now TCR-NKs, to create additional value for both patients and our shareholders," said Selwyn Ho, CEO of Medigene. "Expanding our TCR-guided therapies to include NK cells aligns with our commitment to developing off-the-shelf, highly specific, and effective immunotherapies for cancer treatment."

The global NK cell therapeutics market is rapidly expanding, driven by rising cancer prevalence, an aging population, and demand for innovative immunotherapies. Valued at ~$0.55B in 2024, it is projected to reach $2.13B by 2033 (Source:Business Research Insights). Medigene’s proprietary TCR-NK technology is well-positioned to drive this growth with highly specific, scalable NK cell-based therapies.

Medigene continues to strengthen its intellectual property portfolio through the generation of new 3S TCRs, development of advanced technologies, and strategic expansion of existing patents across additional geographies. With over 29 unique patent families worldwide, Medigene safeguards its proprietary TCR and End-to-End Platform technologies, ensuring a strong competitive position in the immunotherapy space.