GBM Therapeutics Clinical Landscape Analysis

An interactive learning atlas by mindal.app

Launch Interactive Atlas

Create a competitive landscape analysis for Glioblastoma (GBM) therapeutics currently in clinical development. The structure should first break down the pipeline by major therapeutic modalities, and then list the key companies and specific drugs

Glioblastoma (GBM) is an aggressive brain tumor with limited efficacy from conventional therapies, driving intensive research into novel modalities. Major therapeutic approaches in clinical development include Oncolytic Viruses (OVs), CAR T-cell therapy, and molecularly targeted therapies/immunotherapy. The landscape features numerous companies and drugs aiming to improve the poor patient outcomes in GBM.

Key Facts:

  • Candel Therapeutics is developing CAN-3110, an oncolytic virus gene therapy based on the herpes simplex virus type 1, for glioblastoma.
  • Mustang Bio, in collaboration with City of Hope, is developing a CAR T-cell therapy targeting IL13Rα2 for recurrent glioblastoma.
  • Plus Therapeutics is developing REYOBIQ™ (rhenium Re186 obisbemeda), a targeted radiation therapy, currently in the FDA-approved Phase 2 ReSPECT-GBM clinical trial.
  • Kazia Therapeutics is advancing paxalisib, a blood-brain barrier-penetrant PI3K/mTOR inhibitor, for newly diagnosed Glioblastoma Multiforme, with an FDA Type C meeting scheduled for December 2024.
  • Bristol-Myers Squibb Co. has a significant pipeline for GBM, including Marizomib (NPI-0052) in Phase III for glioma and trials for checkpoint inhibitors like Relatlimab and Nivolumab.

Candel Therapeutics

Candel Therapeutics is a company focused on developing novel oncolytic virus gene therapies. Their lead candidate for glioblastoma is CAN-3110, an oncolytic virus derived from the herpes simplex virus type 1, which has shown extended survival and appeared safe in early clinical trials for glioblastoma patients.

Key Facts:

  • Candel Therapeutics is developing CAN-3110 for glioblastoma.
  • CAN-3110 is a novel oncolytic virus gene therapy based on herpes simplex virus type 1.
  • Early results from a first-in-human clinical trial of CAN-3110 showed extended survival and safety in glioblastoma patients.

Batavia Biosciences

Batavia Biosciences is collaborating with Candel Therapeutics to accelerate the development and production of CAN-3110. Their primary focus in this partnership is on establishing a scalable and robust manufacturing process for the oncolytic virus, critical for its future clinical and commercial availability.

Key Facts:

  • Batavia Biosciences is a collaborator with Candel Therapeutics.
  • Their collaboration focuses on accelerating the development and production of CAN-3110.
  • Batavia Biosciences' specific role is establishing a scalable manufacturing process.
  • They are responsible for ensuring robust manufacturing of the oncolytic virus.
  • This partnership supports the future availability of CAN-3110.

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CAN-2409

CAN-2409 is another promising product candidate in Candel Therapeutics' pipeline, utilizing an adenovirus platform. It has demonstrated robust efficacy in other difficult-to-treat cancers, including prostate, pancreatic, and lung cancer, with significant survival gains reported.

Key Facts:

  • CAN-2409 is a product candidate from Candel Therapeutics' pipeline, distinct from their glioblastoma lead.
  • It is based on an adenovirus platform.
  • CAN-2409 has shown robust efficacy in prostate cancer.
  • Significant survival gains were reported for CAN-2409 in pancreatic cancer.
  • The candidate also demonstrated efficacy in lung cancer.

CAN-3110

CAN-3110 is Candel Therapeutics' lead candidate for glioblastoma, a first-in-class replication-competent oncolytic viral immunotherapy based on the herpes simplex virus type 1 (HSV-1). It is engineered to directly destroy cancer cells through oncolysis and stimulate an immune response against the tumor, showing promise in clinical trials for recurrent high-grade glioma (rHGG).

Key Facts:

  • CAN-3110 is derived from herpes simplex virus type 1 (HSV-1) and targets glioblastoma.
  • It is currently in an ongoing Phase 1b clinical trial for recurrent high-grade glioma (rHGG), which includes glioblastoma patients.
  • Early results published in Nature indicate a nearly doubling of expected median overall survival (mOS) to approximately 12 months for rHGG patients.
  • The FDA has granted CAN-3110 Fast Track Designation and Orphan Drug Designation for rHGG.
  • Pre-existing immunity to HSV-1 was associated with better response, with mOS reaching over 14 months for HSV-1 serology positive patients.

enLIGHTEN™ Discovery Platform

The enLIGHTEN™ Discovery Platform is an iterative HSV-based platform utilized by Candel Therapeutics to create new viral immunotherapies. This platform is designed for the development of novel oncolytic viruses for solid tumors, building upon the company's expertise with herpes simplex virus.

Key Facts:

  • The enLIGHTEN™ Discovery Platform is an iterative HSV-based technology.
  • It is used by Candel Therapeutics to create new viral immunotherapies.
  • The platform is specifically designed for developing treatments for solid tumors.
  • It leverages expertise with the herpes simplex virus for novel oncolytic therapies.
  • The platform underpins the development of Candel's pipeline candidates like CAN-3110.

CAR T-cell Therapy

CAR T-cell therapy for glioblastoma involves engineering a patient's immune cells to target specific tumor-associated antigens, then re-infusing them to destroy cancer cells. A significant challenge is the blood-brain barrier, often requiring direct injection, but early phase 1 trials have shown promising clinical activity for recurrent glioblastoma.

Key Facts:

  • CAR T-cell therapy engineers patient immune cells to target tumor-associated antigens.
  • The blood-brain barrier is a significant challenge for CAR T-cell delivery in brain cancer.
  • Mustang Bio and City of Hope are developing a CAR T-cell therapy targeting interleukin-13 receptor alpha 2 (IL13Rα2).
  • This IL13Rα2-targeting CAR T-cell therapy showed promising clinical activity in a phase 1 trial for recurrent glioblastoma.

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CAR T-cell delivery methods

CAR T-cell delivery methods for glioblastoma address the challenge of bypassing the blood-brain barrier (BBB). Investigated routes include intratumoral injection, intraventricular infusion, and combined intratumoral and intraventricular administration, with localized methods gaining traction over intravenous delivery.

Key Facts:

  • The blood-brain barrier (BBB) is a significant hurdle for CAR T-cell therapy in glioblastoma.
  • Intratumoral injection involves directly injecting CAR T-cells into the tumor site.
  • Intraventricular infusion delivers CAR T-cells into the cerebrospinal fluid (CSF).
  • Combined intratumoral and intraventricular administration has shown potential in improving outcomes.
  • Localized delivery methods are gaining traction for their potential to bypass the BBB and improve tumor infiltration.

Glioblastoma tumor microenvironment challenges

The glioblastoma tumor microenvironment (TME) presents significant obstacles for CAR T-cell therapy, including heterogeneous antigen expression, limited T-cell infiltration, and immunosuppression. These factors inhibit CAR T-cell function and persistence, necessitating strategies like multi-targeted approaches.

Key Facts:

  • Challenges include heterogeneous expression of target antigens within the tumor.
  • Limited infiltration of T-cells into the tumor is a significant hurdle.
  • The immunosuppressive tumor microenvironment (TME) can inhibit CAR T-cell function and persistence.
  • Strategies to overcome these challenges involve developing CAR T-cells that can better penetrate the tumor and enhance their persistence.
  • Multi-targeted approaches are utilized to address antigen heterogeneity and improve efficacy.

IL13Rα2-targeting CAR T-cell Therapy

This therapeutic modality involves engineering T-cells to express a Chimeric Antigen Receptor (CAR) that specifically recognizes and binds to the Interleukin-13 receptor alpha 2 (IL13Rα2) protein, which is often overexpressed on glioblastoma cells.

Key Facts:

  • IL13Rα2 is a key target for CAR T-cell therapy in GBM due to its high expression in over 75% of GBM patients and limited expression in normal tissue.
  • Mustang Bio's MB-101 is an example of an IL13Rα2-targeting CAR T-cell therapy.
  • This approach aims to leverage the immune system to specifically attack cancer cells expressing the IL13Rα2 antigen.
  • Clinical trials involving IL13Rα2-targeting CAR T-cells for recurrent glioblastoma have shown promising safety and clinical activity.
  • Administration methods include direct injection into the tumor and infusion into the cerebrospinal fluid.

City of Hope

City of Hope is a leading research institution with an extensive CAR T-cell therapy program. They have been pivotal in the development of CAR T-cell therapies for glioblastoma, including the IL13Rα2-targeting therapy licensed by Mustang Bio, and have numerous ongoing CAR T clinical trials for solid tumors like glioblastoma.

Key Facts:

  • City of Hope is a leading research institution with a comprehensive CAR T-cell therapy program.
  • They developed the IL13Rα2-targeting CAR T-cell therapy licensed by Mustang Bio.
  • City of Hope has numerous ongoing CAR T clinical trials, including for solid tumors like glioblastoma.

AOH1996

AOH1996 is an investigational targeted chemotherapy developed by City of Hope scientists. It is designed to selectively disrupt DNA replication and repair in cancer cells, while sparing healthy cells.

Key Facts:

  • Developed by City of Hope scientists, AOH1996 is a targeted chemotherapy.
  • It selectively disrupts DNA replication and repair in cancer cells.
  • Preclinical research suggests it can annihilate all solid tumors, including breast, prostate, brain, and ovarian cancers.
  • AOH1996 is currently in a Phase 1 clinical trial in humans.

California Institute for Regenerative Medicine (CIRM)

The California Institute for Regenerative Medicine (CIRM) is involved in collaborative research efforts with City of Hope. They provided a $10.2 million grant to advance CAR T-cell therapy.

Key Facts:

  • CIRM provided a $10.2 million grant for collaborative research.
  • The grant supports advancing CAR T-cell therapy for melanoma and other solid tumors.
  • This collaboration includes City of Hope, Stanford, and UCLA.
  • The focus is on solid tumors that express the IL13Rα2 protein.

IL13Rα2-targeting CAR T-cell Therapy

This therapeutic modality involves engineering T-cells to express a Chimeric Antigen Receptor (CAR) that specifically recognizes and binds to the Interleukin-13 receptor alpha 2 (IL13Rα2) protein, which is often overexpressed on glioblastoma cells.

Key Facts:

  • IL13Rα2 is a key target for CAR T-cell therapy in GBM due to its high expression in over 75% of GBM patients and limited expression in normal tissue.
  • Mustang Bio's MB-101 is an example of an IL13Rα2-targeting CAR T-cell therapy.
  • This approach aims to leverage the immune system to specifically attack cancer cells expressing the IL13Rα2 antigen.
  • Clinical trials involving IL13Rα2-targeting CAR T-cells for recurrent glioblastoma have shown promising safety and clinical activity.
  • Administration methods include direct injection into the tumor and infusion into the cerebrospinal fluid.

Kazia Therapeutics

Kazia Therapeutics is advancing paxalisib, a blood-brain barrier-penetrant PI3K/mTOR inhibitor, for the treatment of newly diagnosed Glioblastoma Multiforme. The company is actively pursuing potential registration pathways for paxalisib, with an FDA Type C meeting scheduled for December 2024 to discuss these plans.

Key Facts:

  • Kazia Therapeutics is advancing paxalisib for newly diagnosed Glioblastoma Multiforme.
  • Paxalisib is a blood-brain barrier-penetrant PI3K/mTOR inhibitor.
  • An FDA Type C meeting is scheduled for December 2024 to discuss potential registration pathways for paxalisib.

EVT801

EVT801 is another drug candidate in Kazia Therapeutics' pipeline, distinct from paxalisib. It is described as a small-molecule inhibitor of VEGFR3, indicating its potential role in oncology or other areas where VEGFR3 inhibition is therapeutically relevant.

Key Facts:

  • EVT801 is a drug candidate in Kazia Therapeutics' pipeline.
  • It is a small-molecule inhibitor of VEGFR3.
  • Its mechanism of action suggests potential applications in angiogenesis-related conditions or oncology.
  • EVT801 is mentioned as separate from paxalisib, indicating a broader development portfolio for Kazia Therapeutics.
  • No specific clinical trial data or indications are provided in this summary for EVT801.

Fast Track Designation

Fast Track Designation (FTD) is an FDA process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Paxalisib received FTD for glioblastoma in August 2020 and for solid tumor brain metastases in July 2023.

Key Facts:

  • Paxalisib received Fast Track Designation (FTD) for glioblastoma in August 2020.
  • It also received FTD in July 2023 for solid tumor brain metastases with PI3K pathway mutations in combination with radiation therapy.
  • FTD is intended to facilitate development and expedite the review of drugs for serious conditions with unmet medical needs.
  • This designation allows for more frequent communication with the FDA and potential for rolling review.
  • FTD can accelerate a drug's path to market if criteria are met.

FDA Type C meeting

Kazia Therapeutics scheduled an FDA Type C meeting for December 2024 to discuss potential registration pathways for paxalisib in newly diagnosed glioblastoma multiforme. Following this meeting, the FDA indicated that overall survival data, while generally not suitable for accelerated approval, could support traditional or standard approval.

Key Facts:

  • An FDA Type C meeting was scheduled for December 2024 by Kazia Therapeutics to discuss paxalisib's registration pathways.
  • The FDA stated that overall survival data for paxalisib could support traditional or standard approval, but not accelerated approval.
  • The secondary OS data from the GBM-AGILE study were deemed supportive for planning a pivotal registrational study.
  • Kazia and the FDA agreed on key design aspects for a proposed pivotal Phase 3 study for paxalisib.
  • Updates from this meeting occurred in December 2024 / January 2025.

GBM AGILE Study

The GBM AGILE Study (NCT03970447) is an adaptive Phase 2/3 global trial sponsored by the Global Coalition for Adaptive Research. It evaluated paxalisib, among other therapies, for glioblastoma, with prespecified secondary analysis results in July 2024 showing meaningful improvement in overall survival for newly diagnosed patients with unmethylated MGMT promoter status.

Key Facts:

  • The GBM AGILE Study (NCT03970447) is an adaptive Phase 2/3 global trial.
  • It is sponsored by the Global Coalition for Adaptive Research.
  • In July 2024, secondary analysis results showed paxalisib improved overall survival in newly diagnosed glioblastoma patients with unmethylated MGMT promoter status.
  • The median OS with paxalisib in this population was 15.54 months compared to 11.89 months with concurrent standard-of-care (SOC) therapy.
  • No new safety signals were identified for paxalisib in the study, and it was well-tolerated, though no efficacy signal was found in the recurrent disease population.

Orphan Drug Designation

Orphan Drug Designation is a regulatory status granted to drugs intended to treat rare diseases. Paxalisib received Orphan Drug Designation for glioblastoma in February 2018, which provides incentives to pharmaceutical companies for developing therapies for small patient populations.

Key Facts:

  • Paxalisib received Orphan Drug Designation for glioblastoma in February 2018.
  • This designation is given to drugs developed for rare diseases.
  • It provides incentives such as tax credits for clinical research costs and market exclusivity after approval.
  • Paxalisib also received Orphan Drug Designation for diffuse midline gliomas.
  • This designation typically supports the development of therapies for small patient populations with high unmet medical need.

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Paxalisib

Paxalisib is an investigational brain-penetrant PI3K/Akt/mTOR inhibitor, formerly known as GDC-0084, developed for treating newly diagnosed Glioblastoma Multiforme (GBM). It is distinguished by its ability to cross the blood-brain barrier, addressing a significant challenge in central nervous system drug delivery.

Key Facts:

  • Paxalisib (formerly GDC-0084) is a brain-penetrant inhibitor of the PI3K/Akt/mTOR pathway.
  • It has shown positive results in a Phase 2 study (NCT03522298) for glioblastoma, with median OS of 15.7 months vs. 12.7 months for temozolomide.
  • In the GBM AGILE Study (NCT03970447), paxalisib improved overall survival in newly diagnosed glioblastoma patients with unmethylated MGMT promoter status (median OS 15.54 months vs. 11.89 months for SOC).
  • Paxalisib received Orphan Drug Designation (February 2018) and Fast Track Designation (August 2020) for glioblastoma.
  • It is also being investigated in other brain cancers, including brain metastases, diffuse midline gliomas, and primary central nervous system lymphoma.

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Mustang Bio

Mustang Bio is a company involved in the development of CAR T-cell therapies, notably licensing and developing an IL13Rα2-targeting CAR T-cell therapy for recurrent glioblastoma in collaboration with City of Hope. This therapy has demonstrated promising clinical activity in phase 1 trials.

Key Facts:

  • Mustang Bio is developing a CAR T-cell therapy targeting IL13Rα2.
  • The CAR T-cell therapy is being developed in collaboration with City of Hope.
  • The IL13Rα2-targeting CAR T-cell therapy showed promising clinical activity in a phase 1 trial for recurrent glioblastoma.

IL13Rα2-targeting CAR T-cell Therapy

This therapeutic modality involves engineering T-cells to express a Chimeric Antigen Receptor (CAR) that specifically recognizes and binds to the Interleukin-13 receptor alpha 2 (IL13Rα2) protein, which is often overexpressed on glioblastoma cells.

Key Facts:

  • IL13Rα2 is a key target for CAR T-cell therapy in GBM due to its high expression in over 75% of GBM patients and limited expression in normal tissue.
  • Mustang Bio's MB-101 is an example of an IL13Rα2-targeting CAR T-cell therapy.
  • This approach aims to leverage the immune system to specifically attack cancer cells expressing the IL13Rα2 antigen.
  • Clinical trials involving IL13Rα2-targeting CAR T-cells for recurrent glioblastoma have shown promising safety and clinical activity.
  • Administration methods include direct injection into the tumor and infusion into the cerebrospinal fluid.

MB-101

MB-101 is Mustang Bio's lead CAR T-cell therapy specifically designed to target the interleukin-13 receptor alpha 2 (IL13Rα2) antigen, which is highly expressed in over 75% of Glioblastoma (GBM) patients.

Key Facts:

  • MB-101 targets the IL13Rα2 antigen, which is highly expressed in over 75% of GBM patients.
  • It was developed by City of Hope and is exclusively licensed to Mustang Bio.
  • A Phase 1 clinical trial for recurrent glioblastoma showed 50% of heavily pretreated patients achieved stable disease or better for at least two months.
  • One patient in the trial achieved a complete response lasting over five years (more than 66 months).
  • MB-101 has received Orphan Drug Designation from the U.S. FDA for recurrent diffuse and anaplastic astrocytomas and glioblastoma.

MB-108

MB-108 is an oncolytic herpes simplex virus (HSV-1) developed by Mustang Bio, designed to infect and kill tumor cells and enhance immune responses, often used in combination with other therapies like MB-101.

Key Facts:

  • MB-108 is an oncolytic herpes simplex virus (HSV-1).
  • It is designed to infect and replicate within tumor cells, leading to their direct lysis.
  • MB-108 also aims to create an inflamed tumor microenvironment, making 'cold' tumors 'hot' by recruiting immune cells.
  • It is a component of Mustang Bio's MB-109 combination therapy for glioblastoma.
  • MB-108 has received Orphan Drug Designation from the FDA for malignant glioma treatment.

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MB-109

MB-109 is a combination therapy being developed by Mustang Bio, which pairs their MB-101 CAR T-cell therapy with an oncolytic herpes simplex virus (HSV-1), known as MB-108, to enhance efficacy in glioblastoma.

Key Facts:

  • MB-109 combines MB-101 (IL13Rα2-targeting CAR T-cell therapy) with MB-108 (oncolytic HSV-1).
  • The oncolytic virus (MB-108) is designed to kill tumor cells directly and make 'cold' tumors 'hot' by recruiting immune cells.
  • This combination aims to improve the efficacy of MB-101 by creating a more inflamed tumor microenvironment.
  • Mustang Bio plans to initiate a Phase 1 clinical trial to evaluate the safety and efficacy of MB-109 for recurrent glioblastoma.
  • Both MB-101 and MB-108 have received Orphan Drug Designation, supporting the combination approach.

Orphan Drug Designation

Orphan Drug Designation is a regulatory status granted to drugs intended to treat rare diseases. Paxalisib received Orphan Drug Designation for glioblastoma in February 2018, which provides incentives to pharmaceutical companies for developing therapies for small patient populations.

Key Facts:

  • Paxalisib received Orphan Drug Designation for glioblastoma in February 2018.
  • This designation is given to drugs developed for rare diseases.
  • It provides incentives such as tax credits for clinical research costs and market exclusivity after approval.
  • Paxalisib also received Orphan Drug Designation for diffuse midline gliomas.
  • This designation typically supports the development of therapies for small patient populations with high unmet medical need.

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Oncolytic Viruses

Oncolytic Viruses (OVs) are genetically engineered viruses designed to selectively infect and destroy cancer cells while leaving healthy cells unharmed. Beyond direct tumor lysis, OVs also stimulate an anti-tumor immune response, converting the immunosuppressive tumor microenvironment into an immunologically "hot" one, enhancing susceptibility to other immunotherapies.

Key Facts:

  • Oncolytic Viruses are engineered to selectively infect and lyse cancer cells.
  • OVs stimulate an anti-tumor immune response.
  • OVs reprogram the immunosuppressive tumor microenvironment into an immunologically "hot" one.
  • Candel Therapeutics is developing CAN-3110, an oncolytic virus gene therapy based on herpes simplex virus type 1.

Adenovirus (AdV)

Adenovirus (AdV) is another type of oncolytic virus that has been investigated for glioblastoma (GBM) treatment. Like other oncolytic viruses, AdV is designed to selectively infect and destroy cancer cells while also activating an immune response.

Key Facts:

  • Adenovirus (AdV) is a type of oncolytic virus investigated for GBM treatment.
  • AdV works by selectively infecting and replicating within cancer cells.
  • AdV also contributes to stimulating an anti-tumor immune response.
  • Clinical trials involving Adenovirus for GBM have demonstrated safety and efficacy against glioma cells.
  • The use of AdV aims to turn the immunosuppressive tumor microenvironment into an immunologically active one.

Herpes Simplex Virus (HSV)

Herpes Simplex Virus (HSV) is one type of oncolytic virus being investigated for glioblastoma (GBM) treatment. These genetically engineered viruses can selectively infect and destroy cancer cells while also stimulating an anti-tumor immune response.

Key Facts:

  • HSV is an oncolytic virus type investigated for glioblastoma (GBM) treatment.
  • Candel Therapeutics' CAN-3110 is a replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy.
  • CAN-3110 is engineered with dual activity for oncolysis and immune activation, conditional on Nestin expression in cancer cells.
  • Clinical trials for GBM with HSV-based oncolytic viruses have shown safety and efficacy against glioma cells.
  • A positive HSV-1 serology was a predictor of response in CAN-3110 clinical trials.

Measles Virus (MV)

Measles Virus (MV) is an oncolytic virus that has been explored for glioblastoma (GBM) treatment. Genetically modified MV strains selectively infect and destroy cancer cells, while also stimulating an anti-tumor immune response.

Key Facts:

  • Measles Virus (MV) is an oncolytic virus investigated for GBM treatment.
  • MV selectively infects and replicates within cancer cells.
  • The virus leads to the destruction of tumor cells.
  • MV also plays a role in stimulating an anti-tumor immune response.
  • Clinical trials for GBM with oncolytic viruses, including MV, have generally demonstrated their safety and efficacy against glioma cells.

Mechanism of Action of Oncolytic Viruses

Oncolytic Viruses (OVs) function through a dual mechanism involving direct oncolysis and immune system activation. They selectively infect and destroy cancer cells while simultaneously stimulating an anti-tumor immune response.

Key Facts:

  • OVs selectively infect and replicate within cancer cells, leading to direct cellular lysis.
  • OVs trigger immune system activation by releasing tumor-associated antigens (TAAs), pathogen-associated molecular patterns (PAMPs), and danger-associated molecular patterns (DAMPs).
  • The immune activation attracts immune cells like dendritic cells, T lymphocytes, and natural killer cells to the tumor microenvironment.
  • OVs effectively 'reprogram' the immunosuppressive tumor microenvironment into an immunologically active one.
  • Direct oncolysis is dependent on unique characteristics of cancer cells, such as defects in antiviral defense pathways.

Newcastle Disease Virus (NDV)

Newcastle Disease Virus (NDV) is an oncolytic virus explored for glioblastoma (GBM) treatment. NDV, similar to other oncolytic viruses, targets and destroys cancer cells while also stimulating the immune system to fight the tumor.

Key Facts:

  • Newcastle Disease Virus (NDV) is an oncolytic virus being investigated for GBM treatment.
  • NDV selectively infects and replicates within cancer cells, leading to their destruction.
  • NDV is known to stimulate an anti-tumor immune response.
  • Clinical trials for GBM using NDV have shown safety and efficacy against glioma cells.
  • NDV contributes to modulating the immune response within the brain tumor microenvironment.

Reovirus

Reovirus is an oncolytic virus under investigation for glioblastoma (GBM) treatment. This virus naturally targets and replicates in cancer cells that have activated Ras signaling pathways, leading to cell lysis and immune activation.

Key Facts:

  • Reovirus is an oncolytic virus being investigated for GBM treatment.
  • Reovirus selectively infects and replicates in cancer cells, often those with activated Ras pathways.
  • The virus leads to direct cellular lysis of tumor cells.
  • Reovirus also triggers an anti-tumor immune response.
  • Clinical trials for GBM using oncolytic viruses, including reovirus, have demonstrated safety and efficacy against glioma cells.

Plus Therapeutics

Plus Therapeutics is developing REYOBIQ™ (rhenium Re186 obisbemeda), a targeted radiation therapy for central nervous system cancers such as recurrent glioblastoma. This drug is currently being evaluated in the FDA-approved Phase 2 ReSPECT-GBM clinical trial, representing a novel approach to delivering radiation directly to the tumor.

Key Facts:

  • Plus Therapeutics is developing REYOBIQ™ (rhenium Re186 obisbemeda).
  • REYOBIQ™ is a targeted radiation therapy for central nervous system cancers, including recurrent glioblastoma.
  • REYOBIQ™ is being evaluated in the FDA-approved Phase 2 ReSPECT-GBM clinical trial.

Leptomeningeal Metastases

Leptomeningeal Metastases (LM) is a severe complication of advanced cancer where cancer cells spread to the cerebrospinal fluid and surrounding membranes. REYOBIQ™ is also being developed for LM, having received Orphan Drug and Fast Track Designations from the FDA, and is being evaluated in the ReSPECT-LM trial.

Key Facts:

  • Leptomeningeal Metastases is a severe complication of advanced cancer involving spread to the cerebrospinal fluid and membranes.
  • REYOBIQ™ has received Orphan Drug Designation for LM in lung cancer.
  • REYOBIQ™ also has Fast Track Designation from the FDA for LM.
  • The Phase 1 ReSPECT-LM trial evaluated safety and efficacy of REYOBIQ™ via an intraventricular route.
  • Neuroimaging from ReSPECT-LM showed a clinical benefit rate of 76%.

ReSPECT-GBM

The ReSPECT-GBM clinical trial is an FDA-approved Phase 2 study evaluating REYOBIQ™ for recurrent glioblastoma. Initial Phase 1/2 results showed promising safety and efficacy, including an improved median overall survival for treated patients.

Key Facts:

  • ReSPECT-GBM is a Phase 2 clinical trial for recurrent glioblastoma.
  • Initial Phase 1/2 results demonstrated promising safety and efficacy, with no dose-limiting toxicity observed.
  • The median overall survival (OS) for all treated patients was 11 months, exceeding the standard of care of 8 months.
  • Patients receiving >100 Gy absorbed dose showed a median OS of 17 months.
  • The trial is a multi-center, sequential cohort, open-label, dose-escalation study.

ReSPECT-LM

The ReSPECT-LM trial (NCT05034497) is a Phase 1 study evaluating REYOBIQ™ for leptomeningeal metastases (LM). This trial demonstrated a dose-dependent increase in absorbed radiation to the subarachnoid space and showed a clinical benefit rate of 76%, leading to a dose optimization trial.

Key Facts:

  • ReSPECT-LM is a Phase 1 trial for REYOBIQ™ in leptomeningeal metastases (LM).
  • The trial demonstrated a dose-dependent increase in absorbed dose to the cranial and spinal subarachnoid space.
  • Neuroimaging results showed a clinical benefit rate of 76% (CR + PR + SD).
  • A significant reduction in circulating tumor cells was observed in some patients.
  • A dose optimization trial has been initiated for ReSPECT-LM, following FDA's Project Optimus.

ReSPECT-PBC

The ReSPECT-PBC trial is a planned Phase 1/2a clinical trial cleared by the FDA to evaluate REYOBIQ™ in pediatric patients with high-grade glioma and ependymoma. This trial is funded by a $3.0 million grant from the U.S. Department of Defense.

Key Facts:

  • ReSPECT-PBC is a Phase 1/2a clinical trial for pediatric brain cancer.
  • The trial will evaluate REYOBIQ™ in pediatric patients with high-grade glioma and ependymoma.
  • The FDA has cleared an Investigational New Drug (IND) application for this trial.
  • Funding for the trial includes a $3.0 million grant from the U.S. Department of Defense.
  • The trial will enroll children aged 6 to 21, with potential for patients up to 25.

REYOBIQ™ (rhenium Re186 obisbemeda)

REYOBIQ™ (rhenium Re186 obisbemeda) is Plus Therapeutics' lead drug candidate, a novel targeted radiation therapy utilizing rhenium-186 encapsulated in a nanoliposome carrier. It is delivered directly to the tumor via Convection Enhanced Delivery (CED) to precisely target cancer cells while minimizing damage to healthy tissue.

Key Facts:

  • REYOBIQ™ uses rhenium-186, a radioisotope, within a nanoliposome carrier.
  • Delivery to the tumor is achieved through Convection Enhanced Delivery (CED).
  • This method allows for 15-20 times greater radiation dosing compared to external beam radiation therapy (EBRT).
  • Rhenium-186 has a short half-life and provides both beta energy for destruction and gamma energy for imaging.
  • The nanoliposome carrier is non-toxic and naturally degrades in the body.