On December 18, 2024 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 1 clinical trial has unanimously approved opening of the third cohort of patients based on its favorable review of Cohort 2 safety data (Press release, TransCode Therapeutics, DEC 18, 2024, https://www.prnewswire.com/news-releases/transcode-therapeutics-announces-safety-review-committee-approval-of-opening-third-cohort-and-preliminary-results-from-first-cohort-in-phase-1-ttx-mc138-clinical-trial-302334447.html [SID1234649203]). The therapeutic candidate being evaluated, TTX-MC138, is TransCode’s lead candidate designed to inhibit microRNA-10b, or miR-10b, a microRNA critical to the emergence and progression of many metastatic cancers. The dose administered to the third cohort will be approximately double the dose administered to the second cohort.

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Several patients in the first and second cohort remain on study for continued treatment. No significant safety or dose limiting toxicities have been reported. Analysis of Cohort 1 data for pharmacokinetic (PK) and pharmacodynamic (PD) activity is ongoing and to date suggests that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical results and results from the previous Phase 0 clinical trial. Specifically, results from Cohort 1 confirmed the Phase 0 observation that TTX-MC138 shows evidence of pharmacodynamic activity in the presence of high baseline expression of miR-10b, reaching a 66% inhibition at 24 hours after infusion. Additionally, the concentration of TTX-MC138 in blood plasma as a function of dose in humans was found to be higher than achieved in nonclinical studies, suggesting a favorable pharmacokinetic profile.

"An SRC is a group of clinicians and experts that oversee patient safety during the conduct of a clinical trial. The SRC determines whether and how a study should proceed, including dose escalation and de-escalation decisions in accordance with the study design. The recommendations of the SRC are used to decide whether a clinical trial should be continued as designed, changed, or terminated," 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 patients may now be screened and scheduled in Cohort 3 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 microRNA 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 phase followed by a dose-expansion phase. The primary objective of the dose-escalation phase is to evaluate the safety and tolerability of escalating dose levels of TTX-MC138. In the dose-expansion phase, 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 phase.

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

On December 18, 2024 Blueprint Medicines Corporation (Nasdaq: BPMC) reported that Kate Haviland, Chief Executive Officer, will present a corporate overview and 2025 outlook at the 43rd Annual J.P. Morgan Healthcare Conference on Monday, January 13, 2025, at 9:00 a.m. PT (12:00 p.m. ET) (Press release, Blueprint Medicines, DEC 18, 2024, View Source [SID1234649202]).

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A live webcast of the presentation will be available by visiting the Investors & Media section of Blueprint Medicines’ website at View Source A replay of the webcast will be archived on Blueprint Medicines’ website for 30 days following the presentation.

On December 18, 2024 Abilita Therapeutics, Inc. ("Abilita") reported a global licensing and multi-target research collaboration with Finnish Orion Corporation ("Orion") focused on the discovery, development and commercialization of next generation antibody therapeutics in the areas of oncology and pain (Press release, Orion, DEC 18, 2024, View Source [SID1234649201]). The companies will leverage Abilita’s proprietary Enabled Membrane Proteins (EMP) platform to unlock challenging MMP targets. Abilita will be responsible for discovery and lead optimization efforts. Orion will have an exclusive option to license development candidates to each target for continued development and commercialization.

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"This collaboration combines Abilita’s strength in discovering breakthrough antibody therapeutics for challenging membrane protein targets with Orion’s proven expertise in oncology, pain, clinical development, and commercialization," said Mauro Mileni, Ph.D., founder and CEO of Abilita. "We are excited to leverage our EMP platform, the most advanced directed evolution approach, to unlock targets to generate high-value therapeutics. The partnership with Orion allows us to accelerate promising therapeutics into the clinic as part of our broader plan to advance our pipeline."

"We are looking forward to this exciting collaboration with Abilita. Orion is dedicated to improving the lives of the patients through innovative R&D and gaining access to Abilita’s proprietary EMP technology provides us new opportunities on our path to develop novel therapies," said Outi Vaarala, Senior Vice President, Innovative Medicines and Research & Development at Orion.

Under the agreement, Orion will have an exclusive option to license an undisclosed Abilita discovery program upon identification of a development candidate. Orion will have the option to nominate two additional MMP targets under the same option to license arrangement. In addition to the upfront payments for each target, Orion will also fund all joint discovery efforts. In total, Abilita has the potential to earn up to $785 million in milestone payments for all three targets plus royalties on commercial sales.

On December 18, 2024 Applied DNA Sciences, Inc. (NASDAQ:APDN) ("Applied DNA" or the "Company"), a leader in PCR-based DNA technologies, reported that the State Institute for Drug Control of the Czech Republic (SÚKL) approved an application for a Phase I clinical trial of an investigational CD123-specific autologous CAR T-cell therapy by the Institute of Hematology and Blood Transfusion (ÚHKT/Eng: IHBT) in Prague for the treatment of relapsed and/or refractory acute myeloid leukemia (AML) (Press release, Applied DNA Sciences, DEC 18, 2024, View Source;id=331355&p=2353954&I=1206939-c7Z3G6f3m8 [SID1234649200]). UHKT-CAR123-01 utilizes Applied DNA’s synthetic DNA, Linea DNA, as a critical component in its manufacture.

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AML is a hematologic malignancy with a high rate of treatment failure for which current treatment options are often restricted to palliative approaches. Novel emerging methods leveraging advancements in genetic medicines, such as CAR T-cell therapies, can potentially improve outcomes of patients after relapse but have been difficult to establish for clinical use due to high costs and long manufacturing times predominantly attributable to the use of viral vectors.

UHKT-CAR123 seeks to address these issues by generating CD123-specific CAR T-cells in a non-viral workflow utilizing Linea DNA to reduce manufacturing costs and timelines. Preclinical data showed that ÚHKT’s Linea DNA-empowered non-viral workflow resulted in the rapid production of substantial and cost-efficient CAR T-cell yields with high potency[1].

"The use of Linea DNA illustrates our innovative approach to finding new and best-in-class treatments for patients with relapsed or refractory AML," stated Dr. Jan Vydra, principal investigator of the UHKT-CAR123 clinical trial.

Added Pavel Otáhal, Ph.D., scientific project leader at ÚHKT, "The Linea DNA platform enables the very rapid abiotic production of expression vectors usable for highly effective electroporation-based CAR-T manufacturing compared to plasmid-based vectors. The decreases in complexities and costs of developing autologous CAR-T technologies offer an innovative approach for the rapid clinical testing of novel types of CAR-T products. This is an incredible milestone for ÚHKT and one that we could not have achieved without the commitment of the Applied DNA team."

Applied DNA CEO Dr. James A. Hayward, said, "We congratulate ÚHKT on their progress into the clinic. Their accomplishment is also a significant milestone for Linea DNA as we look to support additional customers expected to initiate clinical trials in calendar 2025."

About Linea DNA

Linea DNA is an enzymatically produced, linear DNA manufactured by the Company’s proprietary, large-scale polymerase chain reaction ("PCR") based manufacturing platform, the Linea DNA platform. As an alternative to plasmid-based DNA, Linea DNA can be used to manufacture of a wide range of nucleic acid-based therapies and in vitro diagnostics, including mRNA therapies, DNA vaccines, cell and gene therapies, and molecular and genetic diagnostic tests.

On December 18, 2024 Krystal Biotech, Inc. (the "Company") (NASDAQ: KRYS), a commercial-stage biotechnology company, reported initial clinical results from its ongoing KYANITE-1 study evaluating inhaled KB707 in patients with solid tumors of the lung (Press release, Krystal Biotech, DEC 18, 2024, View Source [SID1234649199]). KB707 administered via inhalation demonstrated early evidence of monotherapy activity that was most pronounced in patients with advanced non-small cell lung cancer (NSCLC), where an objective response rate (ORR) of 27% and disease control rate (DCR) of 73% were observed as of data cut-off on December 6, 2024.

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"The inhaled local delivery of cytokine that maximizes efficacy and limits systemic toxicity is truly innovative," said Wen Wee Ma, MBBS, Vice Chair of Research and Director of the Novel Cancer Therapeutics Center at Cleveland Clinic. "To see potential benefit as a monotherapy in NSCLC patients who have progressed after standard of care treatments is very encouraging and provides much needed hope."

KYANITE-1 is an ongoing, open-label, multicenter, dose escalation and expansion study evaluating inhaled KB707 for the treatment of solid tumors of the lung. Treatments of either 108 PFU or 109 PFU of KB707 were evaluated in dose escalation, following which 109 PFU was selected for dose expansion. Frequency of KB707 administration has been consistent throughout dose escalation and expansion, with patients receiving KB707 via inhalation once weekly for the first three weeks, then once every three weeks. Trial objectives include evaluation of safety, tolerability, and tumor response measured using RECIST v1.1 criteria. Additional details of the KYANITE-1 study can be found at www.clinicaltrials.gov under NCT identifier NCT06228326.

The first patient in KYANITE-1 was dosed on April 17, 2024. A total of 37 patients were enrolled and received at least one dose of inhaled KB707, including 17 patients with a diagnosis of advanced NSCLC. All patients had malignant lesions in the lung at baseline.

Inhaled KB707 has been safe and generally well tolerated to date in this diverse, heavily pre-treated patient population with advanced disease, and amenable to administration in an outpatient setting. Treatment-emergent adverse events have been predictable and consistent with both the underlying disease and known adverse event profiles of interleukin-2 and interleukin-12. The majority of treatment-related adverse events have been mild to moderate in severity and transient, with no Grade 4 or 5 adverse events observed.

Clinical activity observed to date in the KYANITE-1 study has shown the most therapeutic benefit in patients with advanced NSCLC. As of the data cut-off, 11 NSCLC patients were evaluable for response with at least one radiographic scan and RECIST v1.1 evaluation. Patients included in the analysis were heavily pre-treated with 4 median lines of prior therapy and all had received at least one line of prior immunotherapy. In this NSCLC patient analysis cohort, an ORR of 27%, with three partial responses, has been achieved. DCR to date has been 73% with 7 out of 11 patients still remaining on treatment. Duration of treatment for patients included in the analysis ranged from 10.3 to 33.3 weeks as of data cut-off.

In addition to preliminary evidence of abscopal effect and treatment benefit outside of the lung, treatment responses in lesions of the lung were especially notable. Among the same 11 evaluable NSCLC patients, the ORR in target lung lesions specifically was 36%, with three partial responses and one complete response, and DCR was 82%.

"Signals of monotherapy activity with inhaled KB707, although early, are an exciting milestone for our program and highlight the significant potential of our vectorized cytokine approach in the treatment of difficult cancers," said Suma Krishnan, President of Research and Development of Krystal Biotech. "These data add to a rapidly growing clinical dataset, generated across multiple programs and patient populations, demonstrating that our HSV-1 platform can safely and repeatedly deliver functional genetic material to the lung and impact the course of disease. We are excited about the implications for our platform and the prospect of delivering meaningful clinical benefit to patients suffering from rare and serious lung diseases."

Based on positive initial results in monotherapy, the Company has amended the KYANITE-1 protocol to add two cohorts evaluating inhaled KB707 for the treatment of advanced NSCLC in combination with either anti-programmed cell death protein 1 (PD-1) therapy or anti-PD-1 therapy and chemotherapy. No patients have been enrolled in the combination expansion cohorts to date.

The Company expects to disclose detailed and updated results of KYANITE-1 at future scientific conference(s).

About IL-2, IL-12, and KB707

IL-2 and IL-12 are secreted cytokines with complementary functions promoting cell-mediated immunity in humans. Both IL-2 and IL-12 have been shown to elicit anti-tumor immune responses in preclinical or clinical models and have been extensively studied for their potential in cancer immunotherapy. Despite promising signs of efficacy, it has proven difficult to effectively harness IL-2 and IL-12 for therapeutic benefit, as systemic administration is often poorly tolerated, and their inherently short half-lives necessitate high dose levels and extremely frequent dose intervals. KB707 is a modified HSV-1 vector designed to deliver genes encoding both human IL-12 and IL-2 directly to a patient’s tumor(s) and promote systemic immune-mediated tumor clearance. KB707 targets solid tumors that are accessible via intratumoral injection or inhalation.