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.

On September 18, 2023 Leading CRISPR gene editing companies Integrated DNA Technologies and Aldevron reported to have inked a new global distribution agreement to expand key CRISPR solutions for cell and gene therapy customers (Press release, Aldevron, SEP 18, 2023, View Source [SID1234635225]). Effective today, IDT will stock and sell three additional research use only (RUO) and current good manufacturing practice (cGMP) CRISPR nucleases with unique performance characteristics, manufactured by Aldevron, to provide researchers with an accelerated path to the clinic.

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Orders for new CRISPR enzymes can be placed at www.idtdna.com/AldevronCRISPRnucleases.

"IDT and Aldevron are united in accelerating CRISPR research worldwide by working together to deliver key solutions for translational medicine, increasing our shared value to the entire CRISPR community," said Sandy Ottensmann, VP/GM, Gene Writing and Editing & Core/PCR Business Units at IDT. "Expanding access to best-in-class gene editing reagents and tools to enable customers to rapidly innovate and translate their projects from research breakthroughs to potential life-saving treatments is key to advancing the future of genomic medicine, and we’re proud to work alongside Aldevron to realize this important work."

"Successful clinical translation requires high quality reagents and consistent performance from proof-of-concept through patient dosing. We are thrilled to partner with IDT and bring together their expertise in CRISPR chemistry and oligo production with Aldevron expertise in cGMP CRISPR nuclease and ribonucleoprotein (RNP) manufacturing," said Tom Foti, Vice President and General Manager of Aldevron’s Protein Business Unit. "By combining manufacturing strengths, from day one, IDT clients now can access Aldevron CRISPR proteins which are designed for clinical translation."

Customers investigating genetic and inherited diseases can now purchase both research grade and full cGMP CRISPR nucleases from IDT. cGMP products accelerate researchers’ path to the clinic by including cGMP quality documentation required for regulatory filings.

The following Aldevron-manufactured enzymes, engineered to be used in a variety of applications including electroporation, transfection, and microinjection, are now available through IDT:

SpyFi Cas9 Nuclease—designed for greater editing efficiency and reduced off-target effects. When used in conjunction with an effective guide RNA, target site, and double-stranded DNA cut strategies, this can deliver higher-fidelity editing with less off-target activity than wild-type SpCas9 nuclease. A Drug Master File (DMF) is on file with the U.S. Food and Drug Administration to streamline regulatory filings. Aldevron’s SpyFi Cas9 Nuclease is sold under license of patents and/or patents pending from IDT.
Eureca-V Nuclease—a Class 2, Type V nuclease based on novel MAD7 protein licensed from Inscripta that targets a T-rich PAM domain and creates a staggered double-strand break at the target locus. This enzyme supports research and development in the allogeneic cell therapy space.
SpCas9 Nuclease—a wildtype SpCas9 nuclease for use in development work as well as standard cGMP products for clinical studies. SpCas9 is supported by an extensive QC panel at research grade and GMP product levels. A Drug Master File (DMF) is on file with the U.S. Food and Drug Administration to streamline regulatory filings.

On September 18, 2023 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company developing targeted and transformative cancer therapies using its proprietary AI and machine learning (ML) platform, RADR, with multiple clinical stage drug programs, reported that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for LP-284 (Press release, Lantern Pharma, SEP 18, 2023, View Source [SID1234635224]). LP-284 is being developed for the treatment of relapsed or refractory non-Hodgkin’s lymphoma (NHL), including mantle cell lymphoma (MCL) and double hit lymphoma (DHL) and other high-grade B-cell lymphomas (HGBL). Lantern expects to commence enrollment of patients for the first-in-human Phase 1 trial for LP-284 during the fourth quarter of 2023.

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"This is now our second novel drug candidate to receive IND clearance from the FDA in the past 100 days, further validating our approach of leveraging AI and machine learning to accelerate the development of our pipeline," stated Panna Sharma, Lantern’s President and CEO. "LP-284 holds blockbuster potential, and we have been able to expedite its journey from a concept to a first-in-human clinical trial in a highly efficient and cost-effective manner – less than 2.5 years and under approximately $2.7 million – underscoring the power and potential of our AI platform RADR to accelerate oncology drug discovery and development. RADR was used to unravel the mechanism of action of LP-284, prioritize its cancer indications, and generate machine-learning biomarker signatures that may be pivotal in selecting patients for future phases of the clinical trials. Our success-to-date with LP-284 reaffirms our commitment to harnessing the power of AI to transform cancer treatment and save lives."

LP-284 is a novel small molecule with a synthetically lethal mechanism of action that preferentially damages cancer cells that harbor mutations in DNA damage repair pathways. Lantern’s LP-284 program has been accelerated and focused using AI insights and biological modeling powered by RADR.

NHL is the leading hematological malignancy in the US and remains one of the leading causes of cancer deaths globally, with an estimated 500,000 new cases annually worldwide. Despite advances in NHL using combination and targeted therapies, nearly 20% to 40% of patients with certain subtypes still relapse after treatment. In aggressive subtypes of NHL, like MCL, nearly all patients relapse from standard-of-care (SOC) therapies. Globally, the annual market potential of LP-284 in NHL is estimated to be approximately $4 billion USD.