On January 15, 2025 XENOTHERA reported the securing of a €4 million financing from the public investment program France 2030 to develop its PALT24 project (Polyspecific Antibodies in Lymphoproliferative T cell disorders) (Press release, Xenothera, JAN 15, 2025, View Source [SID1234649743]). This project aims a particularly agressive onco-hematologic disease with high unmet medical needs : PTCL, as the five year survival rate remains at only 30%.

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This financing will enable us to launch the PALT1 clinical trial and pursue early access authorization in France and Europe by 2027. XENOTHERA’s polyclonal glyco-humanized antibody (GH-pAb) is unique in its ability to target tumor cells selectively without affecting healthy lymphocytes, a major advancement in PTCL treatment. Already recognized as an "orphan drug" by both the FDA and EMA, it brings unprecedented hope for patients.

On January 14, 2025 Pasithea Therapeutics Corp. (NASDAQ: KTTA) ("Pasithea" or the "Company"), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other cancer indications, reported it has opened three clinical trial sites in Eastern Europe (Press release, Pasithea Therapeutics, JAN 14, 2025, View Source [SID1234649712]). These sites in Romania and Bulgaria are actively recruiting patients along with the four open sites in the United States, for Pasithea’s PAS-004 Phase 1 trial.

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In Eastern Europe, Pasithea is working with Arensia Exploratory Medicine, Institute of Oncology Bucharest, Arensia Exploratory Medicine, Institute of Oncology Cluj-Napoca, and Arensia Exploratory Medicine, Multiprofile Hospital for Active Treatment Sveta Sofia- EOOD.

In addition, Pasithea has completed initial dosing of three patients in Cohort 4A (15mg capsule). Patient recruitment for Cohort 4B is ongoing (4mg tablet). The Company plans to present interim safety and pharmacokinetic (PK) data from Cohorts 4A and 4B in Q1 2025.

Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea stated, "We are pleased to be working with Arensia in Eastern Europe, allowing PAS-004 to be tested in patients with tumor types more sensitive to single agent MEK treatment or patients who have previously failed first-generation MEK inhibitors."

The ongoing Phase 1 clinical trial is a multi-center, open-label, dose-escalation 3+3 study design to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of PAS-004 in patients with MAPK pathway-driven advanced solid tumors with a documented RAS, NF1 or RAF mutation or patients who have failed BRAF/MEK inhibition (NCT06299839).

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]).

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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 9, 2025 Sanofi reported results from the investigational, randomized, open-label IRAKLIA phase 3 study demonstrated that Sarclisa administered at a fixed dose subcutaneously (SC) via an on-body delivery system (OBDS) in combination with pomalidomide and dexamethasone (Pd) met its co-primary endpoints of non-inferior objective response rate (ORR) and observed concentration before dosing (C trough) at steady state compared to intravenous (IV) Sarclisa administered at a weight-based dose in combination with Pd in patients with relapsed or refractory multiple myeloma (R/R MM) (Filing, 6-K, Sanofi, JAN 14, 2025, View Source [SID1234649713]). Key secondary endpoints, including very good partial response (VGPR), incidence rate of infusion reactions and C trough at cycle 2 were also achieved. The study is ongoing, and the full results will be presented at a forthcoming medical meeting.

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Sikander Ailawadhi, MD

Professor of Medicine, Division of Hematology/Oncology at Mayo Clinic Florida and principal investigator of the study

"The consistent overall response rate and comparable efficacy and safety profile observed in the IRAKLIA study for subcutaneous Sarclisa represent an exciting advancement, offering insight into a potential new administration option for patients. The results from IRAKLIA, in patients with relapsed or refractory multiple myeloma, support the potential of an on-body delivery system to help ease the delivery of a new formulation without impacting patient outcomes."

The IRAKLIA study was conducted using Enable Injections’ enFuse hands-free OBDS, which was designed to administer high-volume medicines subcutaneously through an automated drug delivery technology. The enFuse device leverages a hidden and retractable needle that is thinner compared to commonly used SC injection needles.

Houman Ashrafian, MD, PhD

Executive Vice President, Head of Research and Development at Sanofi

"We are fueled by our focus on innovation and finding best-in-class solutions to help ease the burden of disease for patients. The IRAKLIA study results are a prime example of what’s driving our scientific engine. Being able to possibly bring a novel option that helps reduce time in a healthcare facility is driven by our patient and provider-centric mindset. We look forward to sharing full results and working to bring this new advancement to the multiple myeloma community."

Additional studies evaluating Sarclisa SC formulations across different combinations and lines of therapy are ongoing. The safety and efficacy of Sarclisa SC and the enFuse device have not been evaluated by any regulatory authority outside of their approved indications. Regulatory submissions in the US and in the EU are planned during the first half of 2025.

About the IRAKLIA study

IRAKLIA is a randomized, open-label, pivotal phase 3 study evaluating the non-inferiority of Sarclisa SC formulation administered at a fixed dose subcutaneously via an OBDS versus weight-based dosed Sarclisa IV in combination with Pd in adult patients with R/R MM. The study enrolled 531 patients across 252 global sites, who were equally randomized to receive Sarclisa SC or IV in combination with Pd for 28-day cycles until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever came first. In the SC arm, Sarclisa was administered at a fixed dose SC weekly for four weeks during the first cycle and every two weeks for subsequent cycles. In the IV arm, Sarclisa was administered at a weight-based dose via IV infusion weekly for four weeks during the first cycle and every two weeks for subsequent cycles. The study enrolled adult patients with MM who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor.

The co-primary outcomes being assessed are ORR, defined as the proportion of patients with stringent complete response, complete response, VGPR, and partial response (PR) according to the 2016 IMWG criteria assessed by Independent Review Committee (IRC), and observed C trough at steady state, defined as observed Sarclisa plasma concentrations.

About Enable Injections

Based in the US (Cincinnati, Ohio), Enable Injections is a global healthcare innovation company committed to improving the patient treatment experience through the development and manufacturing of enFuse. enFuse is an innovative wearable drug delivery platform that is designed to deliver large volumes of pharmaceutical and biologic therapeutics via subcutaneous administration, with the aim of improving convenience, supporting superior outcomes, and advancing healthcare system economics. For more information, visit View Source

About Sarclisa

Sarclisa (isatuximab) is a CD38 monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US FDA.

Currently, Sarclisa is approved in more than 50 countries, including the US and EU, across two indications; Sarclisa is approved under an additional indication in the US. Based on the ICARIA-MM phase 3 study, Sarclisa is approved in combination with Pd for the treatment of patients with R/R MM who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor, and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with R/R MM who have received 1–3 prior lines of therapy and in the EU for patients with MM who have received at least 1 prior therapy. In the US, Sarclisa is approved in combination with bortezomib, lenalidomide, and dexamethasone (VRd) as a front-line treatment option for adult patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for autologous stem cell transplant (ASCT), based on the IMROZ phase 3 study. On November 14, 2024, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of Sarclisa-VRd in this patient population. A final decision is expected in the coming months.

Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum spanning six potential indications. Further clinical studies evaluating a subcutaneous administration method for Sarclisa are ongoing.

In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat often rare cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

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.

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"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.