On September 18, 2023 Cellectar Biosciences, Inc., a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of targeted drugs for the treatment of cancer, reported that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to iopofosine I 131, the company’s lead small-molecule drug candidate, for Waldenstrom’s macroglobulinemia (WM) in patients who have received two or more prior treatment regimens (Press release, Cellectar Biosciences, SEP 18, 2023, View Source [SID1234637602]).

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The PRIME program aims to optimize development plans and speed up evaluation of medicines that may offer a major therapeutic advantage over existing treatments or benefit patients without treatment options. These medicines are considered priority medicines by the EMA and are intended to reach patients earlier. To be accepted for PRIME, new therapies must demonstrate the potential to significantly address an unmet medical need in clinical trials.

"PRIME designation from the EMA further underscores our confidence in iopofosine I 131 to provide a differentiated and highly needed new treatment option for patients with WM," said James Caruso, president and CEO of Cellectar. "We expect to release top-line data from the CLOVER-WaM pivotal trial in the fourth quarter of 2023 and submit our NDA in March, 2024. With PRIME designation now in hand we look forward to advancing our EU strategy to bring this potential targeted treatment option to patients in the US and EU as quickly as possible."

The U.S. Food and Drug Administration (FDA) has granted Cellectar’s lead asset iopofosine I 131, a small-molecule Phospholipid Drug Conjugate (PDC) designed to provide targeted delivery of iodine-131 (radioisotope), Fast Track Designation for WM patients having received two or more prior treatment regimens, as well as relapsed (or refractory) multiple myeloma and relapsed (or refractory) diffuse large B-cell lymphoma (DLBCL). The company expects to complete our ongoing Phase 2b WM pivotal trial (NCT02952508) in the second half of 2023 and assuming an FDA Priority Review and approval, remains on target for a 2024 US product launch.

On September 18, 2023 Vividion Therapeutics, Inc. (Vividion), reported that it has initiated dosing of patients in a Phase I oncology clinical trial of its investigational oral Kelch-like ECH Associated Protein 1 (KEAP1) activator, VVD-130037 (Press release, Bayer, SEP 18, 2023, View Source [SID1234635305]). Vividion is a biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision therapeutics for devastating cancers and immune disorders, and a wholly owned and independently operated subsidiary of Bayer AG. The start of the trial represents a major milestone for Vividion’s innovative chemoproteomics platform.

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"The initiation and dosing of this clinical trial marks a major inflection point for Vividion as we advance to a clinical stage company. We are proud of the progress we have made in a relatively short amount of time with our novel pipeline of previously undruggable protein targets for prominent oncology and immunology diseases," said Aleksandra Rizo M.D., Ph.D., Chief Executive Officer of Vividion. "We are energized by the future, as we work to deliver multiple programs to the clinic starting in 2023."

"We are leveraging Vividion’s innovative chemoproteomics technology to develop new therapies with the potential to stop or reverse the progression of diseases," said Christian Rommel, Ph.D., Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of Research and Development. "For millions of patients and their families, cancer continues to be a devastating disease, and new treatments are needed to address key drivers of tumor cell survival and growth. The start of Vividion’s first clinical trial takes us a step closer to a potentially meaningful new oncology treatment for various forms of cancer."

Vividion’s proprietary chemoproteomic approach, which allows the company to unlock high value, traditionally undruggable target biology with precision therapeutics for cancers and immune disorders, has been thriving following the company’s acquisition by Bayer in August 2021. The transaction allows Vividion to operate at arm’s length in a best-of-both-worlds’ model, preserving its innovative, entrepreneurial culture while also leveraging Bayer’s deep expertise in small molecule development, global capabilities and financial strength.

"We are excited to announce the initiation and dosing of Vividion’s first drug in clinical development from our chemoproteomic platform," said Jenna Goldberg, M.D., Chief Medical Officer of Vividion. "This is a first-in-class clinical candidate, aimed to target cancers with activation of the KEAP1-NRF2 pathway. This would be a novel opportunity in cancer treatment."

The company is advancing multiple novel biology programs toward the clinic and has more than a dozen similar pipeline opportunities emerging in early discovery in the fields of oncology and immunology. The Phase I clinical trial will evaluate the safety, pharmacokinetics and pharmacodynamics and preliminary efficacy of VVD-130037 in patients with advanced solid tumors. Trial participants will have a histologically confirmed metastatic or unresectable solid tumor. Participants will receive ascending doses of VVD-130037, orally, once daily in 21-day treatment cycles.

On September 18, 2023 NH TherAguix ("NHT"), a research-based biotech company specialized in the development of innovative nanomedicines for the treatment of cancer by radiotherapy, and Jean PERRIN Cancer Center in Clermont-Ferrand reported the completion of phase I recruitment and the entry into Phase II for the Nano-GBM phase I/II trial in newly diagnosed glioblastoma, sponsored by Jean PERRIN Cancer Center and led by Pr Julian Biau, radiation oncologist.

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This phase I/II clinical trial investigates the tolerance and efficacy of the combination of AGuIX intravenous injections with radiotherapy plus concomitant temozolomide in the treatment of newly diagnosed glioblastoma.

Nano-GBM is a multicentric, randomized, open-label and non-comparative Phase I/II trial. The aim of the dose escalation phase I was to determine the recommended dose of experimental drug to be evaluated for the phase II. 3 dose levels of AGuIX (50mg/kg, 75mg/kg and 100mg/kg) have been tested on eight patients treated in Phase I. These patients with unresected or partially resected glioblastoma have received four injections of AGuIX in combination with temozolomide (75 mg/m²/day) and radiotherapy (60 Gy in 30 fractions of 2 Gy), followed by adjuvant temozolomide according to Stupp protocol, as the standard of care. AGuIX injections were well-tolerated. In addition, MRI analysis has confirmed that AGuIX nanoparticles selectively accumulated in glioblastoma. The Data Safety Monitoring Board, an independent group of experts external to the trial, has confirmed the safety profile of AGuIX in combination with chemo-radiotherapy for the treatment of glioblastoma patients, has validated the recommended dose chosen as well as the continuation of the trial into Phase II.

Pr. Julian Biau stated: "We are happy to have successfully completed the phase I at Jean PERRIN Cancer Center. Based on a favorable safety profile of AGuIX in combination with Stupp protocol, we are encouraged to pursue assessment of this nanoparticle efficacy within the phase II of this innovative clinical trial, in collaboration with other investigator centers".

Dr. Olivier de Beaumont, CMO of NHT said: "After first hints of efficacy in brain metastases indication, NHT is pursuing further the clinical assessment of AGuIX in neuro-oncology. Based on a robust scientific package demonstrating efficacy of AGuIX in rodents with glioblastoma, this phase I/II clinical trial was designed with the objective to demonstrate the safety and efficacy of AGuIX in patients with glioblastoma de novo. With the completion of the phase I of the Nano-GBM study, we are confirming the good tolerance of AGuIX administered at 100mg/kg via intravenous infusions and we are extremely proud to enter the phase II randomized part of the study with the objective to show a patient clinical benefit in combination with Stupp protocol as standard of care".

This phase II study will be randomized with two arms: an experimental arm in which patients will be treated with AGuIX at a dose of 100 mg/kg in combination with radio-chemotherapy (40 patients), and a control arm in which patients will be treated with radio-chemotherapy alone (20 patients). To date, the two first patients of the phase II have been included in the control arm.

The primary endpoint of this phase II study is progression-free survival at 6 months. Secondary endpoints include AGuIX distribution in tumors, progression-free survival, overall survival, overall objective response rate and the safety profile of AGuIX in combination with radiotherapy and temozolomide.

On September 18, 2023 LinKinVax, a clinical-stage biotechnology company focusing on innovative protein-based vaccines, and Gustave Roussy, the leading cancer centre in Europe ranked third Best Cancer Hospital in the world, reported the treatment at Gustave Roussy of the first patient in a Phase I/IIa clinical study with CD40HVac, a new therapeutic vaccine candidate for HPV-positive oropharyngeal cancer (Press release, LinKinVax, SEP 18, 2023, View Source [SID1234635227]).

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The objectives of the study (EUCT N° 2022-502930-25-00 – NCT06007092), sponsored by Gustave Roussy, include:

To assess the immunogenicity and safety of CD40HVac with the Poly-ICLC adjuvant (Hiltonol) against oncogenic HPV in patients with HPV-positive oropharyngeal cancer, and
To determine the recommended dose for the Phase II study, based on the vaccine candidate’s safety profile and ability to induce immune responses.
Several exploratory objectives are also planned to estimate progression-free survival and overall survival.

This multicentre study will test 2 doses of CD40HVac using a dose escalation regimen. Up to 24 patients will be recruited in this double-blind, randomised and placebo-controlled study.

Valérie Bouchara, Head of Clinical Operations at LinKinVax, commented: "This first administration is a major milestone in the development of our therapeutic cancer vaccine CD40HVac. Our teams are committed to uniting their efforts to bring significant innovations to patients with limited therapeutic options, particularly those with recurrent and/or metastatic HPV-positive cancers."

Dr Caroline Even, Head of the Head and Neck Medical Oncology Unit at Gustave Roussy added: "The CD40HVac therapeutic vaccine candidate will provide a promising addition to the existing therapeutic arsenal, once its benefit and safety have been demonstrated in patients with HPV-positive oropharyngeal cancer. We are delighted to be conducting this study."

About CD40HVac

LinKinVax develops CD40HVac, a therapeutic vaccine for HPV-associated malignancies, based on an innovative technology directly targeting dendritic cells (DC), which play a crucial role in the immune system by stimulating and regulating immune responses. A recent U.S. population-based study conducted by the Centers for Disease Control and Prevention (CDC) showed that 66% of cervical cancers, 55% of vaginal cancers, 79% of anal cancers, and 62% of oropharyngeal cancers are attributable to HPV 16 and 18.

Although many HPV-induced tumors can be cured with modern multidisciplinary treatment approaches, it is important to develop new and effective therapeutic vaccines against HPV-associated malignancies to better address the needs of patients.

On September 18, 2023 Boundless Bio, a clinical stage, next-generation precision oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported that it has entered into a clinical trial collaboration and supply agreement with Taiho Oncology, Inc. (Taiho) for Taiho’s pan-FGFR inhibitor LYTGOBI (futibatinib) for use in combination with BBI-355 in a clinical trial of patients with locally advanced or metastatic solid tumors with oncogene amplifications (Press release, Boundless Bio, SEP 18, 2023, View Source [SID1234635226]). BBI-355 is an orally administered, novel, selective small molecule inhibitor of CHK1 and represents what Boundless Bio believes is the first ecDNA-directed therapy (ecDTx) in development for oncogene amplified cancers.

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"This clinical trial collaboration and supply agreement with Taiho marks an important step in the continued execution of our clinical strategy and the next step in realizing the transformative potential of BBI-355, which we believe is the first ecDNA-directed therapy in development for patients with cancer that harbor oncogene amplifications on ecDNA," said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. "FGFR inhibitors given as monotherapy have to date demonstrated less clinical benefit in patients with cancer harboring FGFR amplifications than in patients with other FGFR driver alteration types. We believe that BBI-355, when combined with Taiho’s futibatinib, has the potential to demonstrate meaningful anti-tumor activity for patients with cancer and FGFR amplifications. We look forward to assessing this novel combination in our ongoing Phase 1/2 POTENTIATE trial."

Under the terms of the agreement, Taiho will provide futibatinib clinical drug supply at no cost for Boundless Bio’s ongoing Phase 1/2 clinical trial (POTENTIATE), which will assess BBI-355 in combination with certain selected targeted therapies, including futibatinib, in patients with specific oncogene amplified solid tumors.

About the POTENTIATE Trial

BBI-355 is being evaluated in a first-in-human Phase 1/2 clinical trial ("POTENTIATE": Precision Oncology Trial Evaluating Novel Therapeutic Interrupting Amplifications Tied to ecDNA) in patients with locally advanced or metastatic solid tumors with oncogene amplifications, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.

The open-label, non-randomized, 3-part trial involves: BBI-355 single agent dose escalation and expansion in cancer patients with oncogene amplification, dose escalation of BBI-355 in combination with certain selected targeted therapies in cancer patients with specific oncogene amplifications, and dose expansion of BBI-355 in combination with certain selected targeted therapies in cancer patients with specific oncogene amplification on ecDNA. BBI-355 is administered orally every other day. In part 3 of the trial, an ecDNA diagnostic clinical trial assay (CTA), which we call ECHO (ecDNA Harboring Oncogenes), will be implemented to determine the presence of oncogenes amplified on ecDNA in patient tumor samples. ECHO is a proprietary bioinformatic diagnostic algorithm designed by Boundless Bio and developed into a CTA in collaboration with SOPHiA GENETICS to detect oncogenes amplified on ecDNA from tumor biopsy samples using routine clinical NGS assays.

About BBI-355

BBI-355 is an orally administered, novel, selective checkpoint kinase 1 (CHK1) inhibitor and, what we believe, is the first ecDNA-directed therapy (ecDTx) being investigated to treat patients with oncogene amplified cancer. CHK1 is a master regulator of the cellular response to DNA replication stress (RS), which frequently arises from oncogene amplification on ecDNA. By disrupting proper CHK1 function in oncogene amplified cancer cells, we believe BBI-355 facilitates catastrophic RS, and preferentially kills cancer cells relative to healthy cells. CHK1 was identified as an ecDNA essential target via Boundless Bio’s proprietary Spyglass research platform.