On January 14, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported it has exercised early the option to license from GenFleet Therapeutics VS-7375 (also known as GFH375), a potential best-in-class oral and selective KRAS G12D (ON/OFF) inhibitor (Press release, Verastem, JAN 14, 2025, View Source [SID1234649730]). In addition, the Company announced preliminary clinical data from the Phase 1 study being conducted by GenFleet in China.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As previously announced by GenFleet, 26 patients have been treated with VS-7375 in a Phase 1 dose-escalation study being conducted in China. Both confirmed and unconfirmed partial responses have been observed, including patients with metastatic pancreatic cancer and advanced non-small cell lung cancer. In addition, six dose cohorts have been cleared with no dose-limiting toxicities (DLTs) observed. In the study, oral dosing of VS-7375 has achieved plasma levels in patients that correlate with efficacious exposures that induced deep tumor regressions across all preclinical KRAS G12D tumor models as presented in collaboration with GenFleet at the AACR (Free AACR Whitepaper) 2024 annual meeting.

Enrollment in the Phase 1 dose-escalation study in China is ongoing. Verastem remains on track to file a U.S. investigational new drug (IND) application for VS-7375 during the first quarter of 2025 and expects to initiate a Phase 1/2a study in mid-2025. The Companies expect to share updated preclinical and clinical data at upcoming medical meetings in mid-2025.

"Bringing VS-7375 formally into our pipeline allows us to leverage our scientific and development expertise in the RAS/MAPK-pathway to target KRAS G12D – the most prevalent KRAS mutation in human cancers," said Dan Paterson, chief executive officer at Verastem Oncology. "Our decision to exercise the option early for VS-7375 was based on the safety, pharmacokinetics and efficacy data to date in the Phase 1 study in China, which are in line with our expectations and, importantly, indicate that patients are generally achieving oral bioavailability with exposures that correlate with strong tumor regressions across KRAS G12D mutant preclinical models. We look forward to building on the work GenFleet has started in China to bring VS-7375 to the clinic in the U.S. in mid-2025."

In August of 2023, Verastem entered into a discovery and collaboration agreement with GenFleet to advance three oncology discovery programs targeting RAS pathway-driven cancers. The collaboration was designed with a risk-sharing structure and flexibility for Verastem to exclusively license up to three compounds selected for collaboration after the successful completion of pre-determined milestones in Phase 1 trials. Under the terms of the license for VS-7375, Verastem receives an exclusive global license to VS-7375 outside of the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan.

About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor

VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024.

The Phase 1 portion of the study is being conducted in approximately 20 hospitals in China and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The Phase 1 study will determine the recommended Phase 2 dose (RP2D) and the Phase 2 will further evaluate the efficacy and safety of VS-7375 in patients with advanced solid tumors, such as pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer.

Preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2024 demonstrated oral bioavailability across preclinical species, strong anti-tumor activity as a single agent, and potent efficacy in an intracranial tumor model suggesting the potential to treat brain metastases.

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%) and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration targeting KRAS G12D.

On January 14, 2025 Vistagen (Nasdaq: VTGN), a late clinical-stage company dedicated to pioneering neuroscience based on nose-to-brain neurocircuitry, reported positive results from an exploratory Phase 2A study of PH284 in cancer cachexia (Press release, VistaGen Therapeutics, JAN 14, 2025, View Source [SID1234649729]). PH284 is an investigational pherine nasal spray differentiated from all current treatments for the loss of appetite associated with chronic disorders, such as cancer. In the study, PH284 demonstrated higher mean subjective feeling of hunger as compared to placebo and appeared safe and well-tolerated with an adverse event profile similar to placebo in a population compromised by terminal cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are highly encouraged by the potential of PH284 to improve the quality of life for those challenged by the debilitating impacts of cancer cachexia," stated Shawn Singh, President and Chief Executive Officer of Vistagen. "Loss of appetite from cancer and other illnesses not only negatively impacts overall health and quality of life, but can also reduce the effectiveness of critical therapies, such as chemotherapy in cancer patients. PH284 is our fifth novel investigational pherine, each supported by positive Phase 2 or later clinical data and placebo-like tolerability, underscoring the breadth, diversity and potential of our neuroscience pipeline to address multiple significant unmet needs."

The previously unreported double-blind, placebo-controlled exploratory Phase 2A study was designed to evaluate the efficacy, safety, and tolerability of intranasal administration of PH284 in female patients diagnosed with cachexia (induced by chronic loss of appetite) due to terminal cancer (n=40). PH284 nasal spray (0.4 µg/50 µL) was administered intranasally, one spray in each nostril (total daily dose = 3.2µg), four times daily before meals (breakfast, mid-morning snack, lunch, and dinner). From Day 1 through Day 4, all subjects were administered placebo 30 minutes prior to each meal. Beginning on Day 5 through Day 11 subjects were randomized in a 1:1 fashion to receive either PH284 or placebo.

Efficacy

Patients measured Subjective Feeling of Hunger (SFH) ten minutes before each meal. PH284, as compared to placebo, induced a cumulative effect on mean SFH scores, with scores increasing from breakfast to lunch and lunch to dinner throughout the treatment period. Specifically, prior to dinner on Day 7 of treatment, PH284 subjects reported a 71% improvement in SFH versus baseline, while placebo subjects reported a less than 1% improvement.

Safety and Tolerability

No unusual changes in body weight were observed in either the PH284 or placebo groups, though on average, there was a small gain in body weight for PH284 versus a small loss in placebo. PH284 demonstrated no serious adverse events, and adverse events reported for the PH284 group were similar to those reported in the placebo-treated group. All the adverse events reported were attributed to the underlying medical condition (cancer) and were not deemed to be related to the administration of PH284 or placebo.

About Cachexia

Cachexia, also known as wasting syndrome, is a complex metabolic syndrome that causes a gradual loss of muscle and body weight. Cachexia is associated with chronic diseases like cancer, AIDS, heart failure, chronic obstructive pulmonary disease (COPD), anorexia nervosa, multiple sclerosis, tuberculosis, and anemias. The current definition of cancer cachexia is a loss of 5% or more of body weight over the preceding six months, accompanied by any of a handful of other symptoms, including fatigue and reduced strength. According to the National Cancer Institute, cachexia is estimated to occur in up to 80% of people with advanced cancer, depending on the type of cancer and how well they respond to cancer treatment. Cachexia is thought to directly cause up to 30% of cancer deaths, often because of heart or respiratory failure related to muscle loss. Maintaining nutritional support and alleviating cachexia has the potential to improve the underlying condition of cancer. Currently, there are no effective medical interventions or approved drugs proven to alleviate cachexia.

This previously unreported Phase 2A exploratory study of PH284 was sponsored by Pherin Pharmaceuticals (Pherin), now a wholly owned subsidiary of Vistagen, and conducted at the National Institute of Oncology (INCAN) and National Institute of Nutrition (INNSZ) in Mexico City, Mexico, in 2005. Vistagen gained access to the results of this study in connection with its acquisition of Pherin in February 2023. Hector Burges, MD, former Director, Institute of Nutrition; Marcos Cano Guardiana, MD, Associate Professor, National Institute of Oncology, Mexico City; and Ricardo Plancarte Sanchez, MD, Head of the Pain Clinic, Institute of Oncology, Mexico City, served as the Principal Investigators of the study.

About PH284

PH284 is an investigational neuroactive pherine nasal spray with a novel, rapid-onset potential mechanism of action (MOA) that is fundamentally differentiated from the MOA of all current treatments for the loss of appetite associated with chronic disorders, such as cancer or heart disease. PH284 is thought to act by regulating olfactory to mediobasal-hypothalamus neural circuits involved in appetite control. PH284 has demonstrated an excellent safety profile in all clinical trials completed to date. Vistagen is currently evaluating the potential path forward for PH284, including an assessment of completed studies and studies we believe are necessary to support a U.S. Investigational New Drug application for potential further Phase 2 clinical development of PH284 for the treatment of cachexia.

On January 14, 2025 BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, and Georgetown University’s Lombardi Comprehensive Cancer Center reported a collaboration to explore the effectiveness of immune system profiling to monitor patients with gastrointestinal (GI) cancers receiving combinations of immunotherapy and anti-VEGF inhibitors in the microscopic residual disease (MRD) setting (Press release, BostonGene, JAN 14, 2025, View Source [SID1234649728]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Currently, surveillance for GI cancer patients having undergone curative-intent procedures relies on radiologic imaging and non-specific lab tests with poor sensitivity, often detecting relapse only after it has advanced. Biomarkers, such as circulating tumor DNA (ctDNA), have emerged as non-invasive blood tests with the ability to identify the earliest signs of cancer relapse, or MRD. This multi-institution feasibility study aims to identify high-risk patients with GI cancers who have completed standard of care curative-intent therapies but have MRD in the surveillance setting, defined by detectable ctDNA but no evidence of radiographic relapse. These high-risk patients are then treated with combination of atezolizumab (immune checkpoint blockade) and bevacizumab (anti-VEGF therapy) while assessing ctDNA serially for MRD clearance. The study aims to obtain pilot data on ctDNA as a new tool to detect early signals of therapeutic efficacy within months of starting treatment.

Immune system profiling, a non-invasive blood-based tool can detect unique and specific cancer-driven changes in a patient’s immunity often not detected by conventional methods. In this trial, the investigators hope to characterize the baseline and on-treatment changes in the peripheral blood immune profiles of patients with MRD receiving immunotherapy. Evaluating peripheral blood immune profiles as predictive biomarkers is promising in the MRD setting where tumor biopsies are not feasible and systemic immune surveillance is relevant in eradicating micrometastases.

The pioneering study will explore immune system profiling as a new predictive marker of therapeutic response. By tracking immune system profiling and ctDNA trends post-treatment, it aims to generate pilot data on immune system profiling’s feasibility in guiding treatment and improving outcomes in GI cancer patients.

"We need new approaches for improving outcomes for patients with gastrointestinal cancers," said principal investigator John L. Marshall, MD, director of the Ruesch Center for the Cure of GI Cancers at Georgetown Lombardi. "If we can validate immune system profiling as a reliable early marker of MRD, it would be a pivotal step towards enhancing early detection, optimizing treatment strategies, and ultimately preventing relapse." Marshall treats patients at MedStar Georgetown University Hospital.

"If we can demonstrate feasibility of enrolling patients and clearing ctDNA with immunotherapy in this pilot study, it could lead to future validation studies of novel therapeutics in the MRD setting and ctDNA as a surrogate for survival with the hopes of expediting drug discovery in the adjuvant and post-adjuvant settings," said co-principal investigator Reetu Mukherji, MD, assistant professor of medicine at Georgetown and co-writer of the study. "Additionally, our study will incorporate correlative science to study the yet unknown peripheral blood immune profiles of patients with MRD using the BostonGene peripheral blood profiling assay. Most ICI biomarkers studied to date are based on molecular or immune profiling of tumor tissue or molecular testing of ctDNA. However, liquid immunoprofiling is an emerging technology that holds ICI biomarker promise and warrants further study. This study has the potential to identify novel predictive biomarkers and hopefully one day transform current approaches to improve survival rates for patients who have undergone curative treatment."

Marshall and Mukherji both treat patients at MedStar Health, Georgetown’s academic health system partner.

Using advanced molecular and immune profiling capabilities, BostonGene will characterize each patient’s immune environment, providing detailed insights into how immune system profiling trends correlate with therapeutic outcomes. This analysis will facilitate the identification of predictive biomarkers, potentially informing future clinical applications of immune system profiling for MRD monitoring. By utilizing advanced multiomic data analysis and immune system profiling technology, BostonGene will also deliver essential insights into how a patient’s immune changes during and after therapy.

"We are excited to collaborate with Georgetown Lombardi," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "Our expertise in molecular and immune profiling, combined with immune system analysis, has the potential to revolutionize how MRD is detected and managed in GI cancers. By providing critical insights into immune system dynamics, we empower clinicians to make more informed, timely treatment decisions, thereby improving patient outcomes and reducing relapse rates."

On January 14, 2025 Bayer reported progress in its pharmaceutical growth strategy with multiple regulatory filing submissions underway for key growth drivers darolutamide, finerenone, and elinzanetant on the occasion of the 43rd J.P. Morgan Healthcare Conference in San Francisco (Press release, Bayer, JAN 14, 2025, View Source [SID1234649727]).

"We are successfully delivering on our ambitious business goals despite significant headwinds. At the same time, the value of our pipeline is growing by accelerating breakthrough innovations," said Stefan Oelrich, Member of the Board of Management, Bayer AG, and President of Bayer’s Pharmaceuticals Division. "Our new operating model is visibly becoming a key enabler to drive growth and efficiency gains."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Topline improved and poised for future growth

Bayer continues to strengthen its leadership position in prostate cancer with the anticipated launch of a third indication in 2025 for the oral androgen receptor inhibitor (Ari) darolutamide, marketed under the brand name NUBEQA, supported by data from the ARANOTE trial. Darolutamide plus androgen deprivation therapy (ADT) now has positive data both with and without chemotherapy (docetaxel) based on two pivotal Phase III studies (ARASENS and ARANOTE) in metastatic hormone-sensitive prostate cancer (mHSPC). Bayer recently submitted an application to the Center of Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for this third indication for darolutamide in addition to filings in the U.S. and the EU earlier in 2024. NUBEQA achieved global blockbuster status in September 2024 after crossing the threshold of one billion euros in annual sales. Additionally, NUBEQA is now the fastest growing androgen receptor inhibitor in the U.S., with nearly 45,000 patients in the U.S. and 100,000 patients globally treated as of the end of 2024. For important risk and use information about NUBEQA, please see the full Prescribing Information.

In Cardiovascular, Bayer submitted a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) and CDE of China’s NMPA for finerenone, marketed as KERENDIA, for the treatment of patients with heart failure (HF) with a left ventricular ejection fraction (LVEF) of ≥40%, initiating a major step forward in expanding its reach. Further regulatory filings are planned with a potential market launch by the end of 2025. Filing submissions are based on positive results from the Phase III FINEARTS-HF trial that showed finerenone achieved a statistically significant reduction of the composite of cardiovascular death and total (first and recurrent) HF events, defined as either an unplanned hospitalization for HF or an urgent HF visit, by 16% in patients with HF and a LVEF of ≥40% compared to placebo in addition to a patients’ prescribed treatment regimen. The robust data from Kerendia’s clinical development program underscore its potential to become a pillar of therapy for patients with chronic kidney disease associated with Type 2 Diabetes and patients with heart failure with an LVEF of ≥40%. For important risk and use information about KERENDIA, please see the full Prescribing Information.

In Women´s Healthcare, another significant clinical milestone for investigational compound elinzanetant was secured in early 2025 following three positive Phase III readouts in 2024 (OASIS 1,2,3). OASIS 4, which was conducted outside of the U.S., is a Phase III study evaluating elinzanetant as a non-hormonal treatment for moderate to severe vasomotor symptoms caused by adjuvant endocrine therapy in women with breast cancer or at high risk of developing breast cancer. Elinzanetant successfully met the primary endpoints of the study demonstrating statistically significant reductions in the frequency of moderate to severe vasomotor symptoms (VMS, also known as hot flashes) from baseline to week 4 and 12 compared to placebo. The study also achieved all secondary endpoints demonstrating reductions in severity of VMS at week 4 and 12, VMS frequency reduction at week 1 as well as maintaining the effects over the study period. The detailed results from OASIS 4 are planned to be presented at an upcoming scientific congress. Elinzanetant is the first dual neurokinin-1 and 3 (NK-1 and 3) receptor antagonist in late-stage clinical development for the non-hormonal treatment of moderate to severe VMS associated with menopause.

In Radiology, Bayer is advancing its pipeline. A significant milestone was achieved with its Phase III QUANTI clinical development program, which evaluated the investigational compound gadoquatrane. The first data from the program showed that gadoquatrane successfully achieved its primary endpoint, highlighting its potential to offer a low dose contrast agent option to patients. The QUANTI program showcases Bayer’s leadership in radiology and its commitment to advancing innovation in medical imaging.

Pipeline value improved and early lead positions strengthened

Bayer is making significant progress with its cell and gene therapy platform, achieving important clinical trial milestones, especially in the field of Parkinson´s disease.

Bemdaneprocel will directly advance to Phase III clinical development in Parkinson’s disease, based on positive data from the Phase I exPDite trial. Bemdaneprocel is an investigational stem cell-based therapy that surgically implants dopamine-generating nerve cell precursors into the brain. The FDA granted bemdaneprocel Regenerative Medicine Advanced Therapy (RMAT) designation for its innovative potential in treating Parkinson’s disease.

AB-1005 is advancing in Phase II with the randomization of participants in the REGENERATE-PD clinical trial focusing on patients with moderate-stage Parkinson’s disease. AB-1005 is an investigational AAV-based gene therapy that delivers the human glial cell line-derived neurotrophic factor (GDNF) transgene to the brain to potentially protect and restore dopamine-generating neurons. AB-1005 has received U.S. FDA Fast Track and UK Medicines and Healthcare products Regulatory Agency (MHRA) Innovation Passport designations, highlighting its potential to address significant unmet medical needs.

As part of its transformation, Bayer has sharpened its focus in R&D to build a highly differentiated pipeline for long-term growth in oncology, cardiology and renal diseases, neurology and rare diseases, and immunology. Through rigorous assessment and prioritization, Bayer Pharmaceuticals is now fully focused on the areas of greatest unmet need and highest value potential.

Targeted investments in R&D and platform companies in recent years are already strengthening Bayer’s early and late pipelines. With Vividion´s acquisition of the precision oncology platform company Tavros Therapeutics, Bayer continues to leverage its chemoproteomics platform technology to unlock traditionally undruggable targets with precision small-molecule therapeutics. It has initiated Phase I trials with oral KEAP1 activator in solid tumors and oral STAT3 inhibitor in solid and hematologic malignancies and has IND-enabling programs including a RAS-P13KCA program for RAS-driven cancers.

Additionally in the field of precision oncology, investigational BAY 2927088, an oral, small molecule, tyrosine kinase inhibitor as a potential new targeted therapy for patients with non-small cell lung cancer (NSCLC) harboring HER2 activating mutations, showed promising results as a second line therapy in the ongoing Phase I/II SOHO-01 study evaluating safety and efficacy. Its potential is underscored by Breakthrough Therapy Designations from both the FDA and Chinese CDE. Beyond the SOHO-01 trial, BAY 2927088 is also being assessed for its potential as a first-line therapy in patients with advanced non-small cell lung cancer (NSCLC), whose tumors have activating HER2 mutations in the SOHO-02 trial. Further, a Phase I clinical trial with BAY3498264, an investigational oral selective Son of Sevenless Homologue 1 (SOS1) inhibitor, has recently been initiated (outside of the US). The open-label, first-in-human, dose escalation study will evaluate patients with KRAS G12C-mutated metastatic cancer. This innovative approach has the potential to enhance the treatment options available for patients, offering the possibility to reduce or stop tumor progression.

Targeted Radionuclide Therapy (TRT) is a strategic area of focus in Oncology precision drug development at Bayer, building on more than 10 years of real-world experience with radium Ra 223 dichloride injection therapy, marketed as XOFIGO, for patients with metastatic castration-resistant prostate cancer. Bayer´s evolving TRT portfolio includes novel targeting approaches which combine alpha radionuclides such as actinium-225 with different targeting moieties, including antibodies, small molecules or peptide-based molecules. 225Ac-pelgifatamab (BAY 3546828) and 225Ac-PSMA-Trillium (BAY 3563254), two candidates targeting PSMA (prostate specific membrane antigen), are currently in Phase I clinical trials in patients with advanced metastatic castration resistant prostate cancer (mCRPC). For important risk and use information about XOFIGO, please see the full Prescribing Information.

In the field of cardiovascular diseases, Bayer is making progress with its Phase II assets. With BAY3283142, an investigational soluble guanylate cyclase (sGC) activator in patients with chronic kidney disease (CKD), Bayer has entered into a Phase II clinical study. By modulating sGC via a heme-independent pathway, the investigational sGC activator now represents a new class of potential future drugs that could offer an advantage in conditions of high oxidative stress such as in diabetic nephropathy.

With the anti-alpha2 antiplasmin antibody program, Bayer is developing a new modality and mechanism of action-based thrombolytic agent. Based on investigational research, the antibody works by specifically blocking the endogenous plasmin inhibitor, α2AP, potentially leading to the lysis of acute embolic or thrombotic clots with a tolerable safety profile. The investigational antibody is currently being evaluated in Phase II in patients with deep vein thrombosis and could be used for indications of high medical relevance.

On January 14, 2025 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported that the first patient in Cohort 3 of its Phase 1 clinical trial has been dosed with TTX-MC138, its lead candidate (Press release, TransCode Therapeutics, JAN 14, 2025, View Source [SID1234649726]). The Safety Review Committee monitoring the clinical trial unanimously approved opening of the third cohort based on its favorable review of Cohort 1 and 2 safety and pharmacokinetic (PK) data. Additional Cohort 3 patients have been scheduled. The dose administered to patients in the third cohort is approximately double the dose administered to those in the second cohort.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Several patients in the first and second cohort remain on study for continued treatment, receiving additional doses of TTX-MC138. No significant safety or dose limiting toxicities have been reported. Analyses of PK data and pharmacodynamic (PD) activity from Cohorts 1 and 2 is ongoing. To date, the analyses suggest that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical results and results from TransCode’s 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, similar to that seen in the Phase 0 trial. Additionally, TTX-MC138 activity increased with the escalated dose administered in Cohort 2 and was consistent at subsequent administrations of TTX-MC138, suggesting a favorable pharmacokinetic profile.

"An SRC is a group of clinicians and other experts that oversee patient safety during 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. Enrollment into this study continues based on the SRC’s cumulative safety data review. We are very pleased with the commitment from our clinical sites which may enable quick completion of the third cohort," commented Sue Duggan, TransCode’s Senior Vice President of Operations.

About TTX-MC138

TTX-MC138 is a first-in-class therapeutic candidate designed to inhibit microRNA-10b, or miR-10b, a microRNA widely believed to be critical to the emergence and progression of many metastatic cancers. 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 phase.

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