NEUROD1

SUZHOU, China, March 21, 2024 /PRNewswire/ -- NeuExcell Therapeutics, a leading biotechnology company focused on in vivo neural regenerative therapies, announces the successful dosing of the first patient with the first-in-class NeuroD1 gene therapy product NXL-004. This milestone represents significant progress in the development of new treatment for malignant glioma patients. Led by Professor Yulun Huang and his team at the Fourth Affiliated Hospital of Soochow University in Suzhou, China, the investigator-initiated trial (IIT) will evaluate the safety and tolerability of NeuExcell's AAV-NeuroD1 gene therapy product NXL-004 in patients with glioblastoma. This clinical study marks the first clinical use of AAV-NeuroD1 gene therapy to treat patients worldwide. Glioblastoma is a highly aggressive form of brain cancer with limited treatment options and poor prognosis. NXL-004, based on NeuExcell's revolutionary in vivo trans-differentiation technology platform, aims to inhibit tumor cell proliferation and promote their transformation into neural cells through the overexpression of the NeuroD1 transcription factor. The advantage of this glioma cell trans-differentiation approach is minimal side-effect on other brain cells, which is distinct from radiation or chemotherapy that has collateral damage on healthy cells. Promising preclinical results from animal model studies have paved the way for this groundbreaking clinical trial, offering hope for many patients suffering from debilitating brain disorders such as malignant glioma. "We are very excited about completing the dosing of the first patient using NeuroD1 gene therapy product NXL-004 in this exploratory clinical study," said Dr. Yulun Huang, the study's lead investigator. "This milestone underscores the dedication of our team to try innovative approaches in addressing unmet medical needs such as glioblastoma. We are committed to closely monitor the patient and evaluate the safety and efficacy of NXL-004 in this trial." Professor Gong Chen, the inventor of in vivo neural regenerative gene therapy and the founder of NeuExcell Therapeutics, expressed his gratitude: "We are grateful to Professor Yulun Huang and his team for their outstanding work. This first-in-human trial sets an important milestone for our first-in-class NeuroD1 gene therapy that has the potential to treat millions of patients suffering from severe neurological disorders. We are dedicated to developing game-changing treatments for neurodegenerative diseases using in vivo neural regenerative therapies." About NeuExcell Therapeutics: NeuExcell Therapeutics is a leading biotechnology company focused on developing innovative neural regenerative therapies to address unmet medical needs in the field of neurodegenerative diseases and cancers. NeuExcell is committed to revolutionizing the field of CNS drug development and improving outcomes for patients worldwide.

Researchers have discovered that turning brain immune cells into neurons successfully restores brain function after stroke-like injury in mice. These findings suggest that replenishing neurons from immune cells could be a promising avenue for treating stroke in humans. Researchers at Kyushu University have discovered that turning brain immune cells into neurons successfully restores brain function after stroke-like injury in mice. These findings, published on October 10 in PNAS, suggest that replenishing neurons from immune cells could be a promising avenue for treating stroke in humans. Stroke, and other cerebrovascular diseases, occur when blood flow to the brain is affected, causing damage to neurons. Recovery is often poor, with patients suffering from severe physical disabilities and cognitive problems. Worldwide, it's one of the most common causes for needing long-term care. "When we get a cut or break a bone, our skin and bone cells can replicate to heal our body. But the neurons in our brain cannot easily regenerate, so the damage is often permanent," says Professor Kinichi Nakashima, from Kyushu University's Graduate School of Medical Sciences. "We therefore need to find new ways to replace lost neurons." One possible strategy is to convert other cells in the brain into neurons. Here, the researchers focused on microglia, the main immune cells in the central nervous system. Microglia are tasked with removing damaged or dead cells in the brain, so after a stroke, they move towards the site of injury and replicate quickly. "Microglia are abundant and exactly in the place we need them, so they are an ideal target for conversion," says first author, Dr. Takashi Irie from Kyushu University Hospital. In prior research, the team demonstrated that they could induce microglia to develop into neurons in the brains of healthy mice. Now, Dr. Irie and Professor Nakashima, along with Lecturer Taito Matsuda and Professor Noriko Isobe from Kyushu University Graduate School of Medical Sciences, showed that this strategy of replacing neurons also works in injured brains and contributes to brain recovery. To conduct the study, the researchers caused a stroke-like injury in mice by temporarily blocking the right middle cerebral artery -- a major blood vessel in the brain that is commonly associated with stroke in humans. A week later, the researchers examined the mice and found that they had difficulties in motor function and had a marked loss of neurons in a brain region known as the striatum. This part of the brain is involved in decision making, action planning and motor coordination. The researchers then used a lentivirus to insert DNA into microglial cells at the site of the injury. The DNA held instructions for producing NeuroD1, a protein that induces neuronal conversion. Over the subsequent weeks, the infected cells began developing into neurons and the areas of the brain with neuron loss decreased. By eight weeks, the new induced neurons had successfully integrated into the brain's circuits. At only three weeks post-infection, the mice showed improved motor function in behavioral tests. These improvements were lost when the researchers removed the new induced neurons, providing strong evidence that the newly converted neurons directly contributed to recovery. "These results are very promising. The next step is to test whether NeuroD1 is also effective at converting human microglia into neurons and confirm that our method of inserting genes into the microglial cells is safe," says Professor Nakashima. Furthermore, the treatment was conducted in mice in the acute phase after stroke, when microglia were migrating to and replicating at the site of injury. Therefore, the researchers also plan to see if recovery is also possible in mice at a later, chronic phase.

PharmaMar (MSE:PHM) has announced today four new abstracts from clinical trials of its compounds Zepzelca® (lurbinectedin), ecubectedin (PM14) and PM534 at the Annual Meeting of the American Association for Cancer Research (AACR), being held in Orlando, Florida (USA) from April 14-19. Among the studies to be presented, the abstract entitled " Lurbinectedin shows potent activity in all four molecular subtypes of small cell lung cancer (SCLC) and POU2F3 and SFLN11 are biomarkers for a better response", presents lurbinectedin activity results obtained in a panel of tumor cells that express the four transcription factors (ASCL1, NEUROD1, YAP1, POU2F3) which permit the molecular classification of SCLC. Moreover, in both in vitro and in vivo studies, as well as in biopsies obtained from patients, a possible predictive biomarker of response to lurbinectedin is identified, SLFN11. Two abstracts will be presented at the congress on PharmaMar's new marine-derived anti-tumor compound, PM534, which is obtained by chemical synthesis and is currently in Phase I clinical development. The first of the abstracts, entitled "PM534 is a novel microtubule-destabilizing agent with high affinity and potent antineoplastic properties", demonstrates by X-ray crystallography that PM534 binds to its target, tubulin, inducing a strong antitumor effect in vitro and in vivo. This research has been carried out in collaboration with CSIC (Spanish National Research Council) researchers. The second, entitled "The novel antitubulin agent PM534 exhibits potent antitumoral and antiangiogenic properties in vivo and in vitro", shows that, as a result of its high affinity for tubulin, it acts by destabilizing the microtubular network in the tumor cell, resulting in potent antitumor activity in vitro and in vivo. In addition, PM534 is a potent inhibitor of angiogenesis, which prevents the formation of blood vessels necessary for tumor growth. Finally, PharmaMar will present the abstract "Ecubectedin is a novel transcriptional inhibitor that displays potent antitumor effects in vivo and in vitro". This antitumor compound induces tumor cell death through apoptosis by inhibiting the activated transcription. This mechanism of action results in a very potent antitumor activity in vitro and in vivo models. Ecubectedin is currently in Phase II clinical development. PharmaMar’s abstracts at AACR 2023 PRODUCTTITLELEAD AUTHORABSTRACTZepzelca® (lurbinectedin)Lurbinectedin shows potent activity in all four molecular subtypes of small cell lung cancer (SCLC) and POU2F3 and SFLN11 are biomarkers for a better responseEva María Garrido-Martín, PhDABSTRACT: 6247 POSTER SESION: Experimental and Molecular TherapeuticsPM534PM534 is a novel microtubule-destabilizing agent with high affinity and potent antineoplastic propertiesEva María Garrido-Martín, PhDABSTRACT: 6239 POSTER SESION: Experimental and Molecular TherapeuticsPM534The novel antitubulin agent PM534 exhibits potent antitumoral and antiangiogenic properties in vivo and in vitroEva María Garrido-Martín, PhDABSTRACT: 6243 POSTER SESION: Experimental and Molecular TherapeuticsEcubectedin (PM14)Ecubectedin is a novel transcriptional inhibitor that displays potent antitumor effects in vivo and in vitroEva María Garrido-Martín, PhDABSTRACT: 1622 POSTER SESION: Experimental and Molecular Therapeutics