ON November 18, 2023 Servier reported that new data from clinical development program for vorasidenib in IDH-mutant diffuse glioma, presented at the 28th Annual Meeting of the Society for Neuro-Oncology (SNO) in Vancouver, Canada, showed that vorasidenib reduced tumor growth as measured by a blinded independent radiology committee (Press release, Servier, NOV 18, 2023, View Source [SID1234637797]). Additional data from the INDIGO study being presented at SNO include health-related quality of life data, indicating patients receiving vorasidenib experience preservation of quality of life, stable neurocognitive function, and seizure control, as well as translational data demonstrating vorasidenib’s efficacy across IDH-mutant diffuse gliomas with various additional mutations.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These data further add to the growing body of evidence in vorasidenib as a potential first-in-class treatment option in IDH-mutant diffuse glioma, and we look forward to the opportunity to deliver vorasidenib as the first targeted treatment option in this disease space to patients across the globe," said Susan Pandya, M.D., Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "With these analyses now complete, we are moving forward with the submission of a new drug application for vorasidenib in IDH-mutant diffuse glioma to the U.S. Food and Drug Administration by the end of 2023. We are honored and excited at the prospect of ushering in a new era of targeted treatment options for patients living with this devastating disease."

Vorasidenib has been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA). Servier plans to submit a new drug application (NDA) for vorasidenib to the FDA by the end of 2023 and the European Medicines Agency (EMA) in early 2024, with commercial availability for the drug to be available at launch.

Impact of vorasidenib treatment on mutant IDH1 or IDH2 diffuse glioma tumor growth rate (Abstract # LTBK-06; late-breaker)

In the pivotal randomized, double-blind Phase 3 INDIGO[1],[2] clinical trial, vorasidenib demonstrated a remarkable improvement in progression-free survival (PFS) with a median of 27.7 months for vorasidenib vs. 11.1 months for placebo in patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. In a late-breaking new analysis, treatment with vorasidenib reduced tumor growth rate (TGR) and shrunk tumor volume, whereas continued growth in tumor volume was observed in patients randomized to the placebo arm.

"Tumor growth rate is an innovative and advanced analysis that requires significant rigor to capture the impact of vorasidenib on these tumors beyond delaying disease progression," said Patrick Wen, Chief, Division of Neuro-Oncology, Dana Farber Cancer Institute. "These data from the INDIGO study offer the first prospective volumetric dataset in IDH-mutant gliomas and provide robust evidence that treatment with vorasidenib not only delays or prevents tumor growth, but also lead to tumor shrinkage."

In patients randomized to the vorasidenib arm, tumor volume decreased by a mean of 2.5% (TGR of -2.5%; 95% CI: -4.7 to -0.2) every 6 months, while tumor volume increased by a mean of 13.9% (TGR of 13.9%; 95% CI: 11.1 to 16.8) every 6 months for patients randomized to the placebo arm, as measured by a blinded independent radiology committee.

Phase 1 safety lead-in and randomized open-label perioperative study of vorasidenib combined with pembrolizumab in recurrent or progressive enhancing IDH1-mutant astrocytomas (Abstract # CTIM-14; oral)

In the first results from the safety lead-in of a new Phase 1 study, vorasidenib 40 mg orally once daily plus KEYTRUDA (pembrolizumab), Merck & Co., Inc., Rahway, NJ., USA’s anti-PD-1 therapy, 200 mg intravenously once every three weeks was safe and tolerable among seven patients with recurrent or progressive enhancing IDH1-mutant grade 2/3 astrocytoma.

As of April 2023, patients received a median of two (range, 2–5) cycles of combination treatment, with six ongoing and one discontinuation due to disease progression. No dose-limiting toxicities, adverse events (AE) leading to study drug discontinuation, or AEs of special interest were reported. Six patients (86%) experienced a treatment-related AE, none of which were higher than grade 2.

The safety lead-in was conducted to determine the recommended combination dose for the recently initiated perioperative phase of the study. In this phase, approximately 60 patients will be randomized to the combination treatment, vorasidenib 40 mg once-daily alone, or no treatment prior to surgery.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Glioma3
Gliomas are tumors that arise from glial or precursor cells within the central nervous system (CNS). The 2021 WHO classification recognizes four general groups of gliomas, one of which is adult-type diffuse gliomas. These diffuse gliomas are the most common primary malignant brain tumors in adults. The pathogenesis and prognosis of these tumors are tightly linked to mutations (or lack thereof) in the metabolic enzyme isocitrate dehydrogenase (IDH), and molecular testing is required for proper diagnosis. As of 2021, adult-type diffuse gliomas are sub-divided into only three categories:

Astrocytoma, IDH-mutant (CNS WHO grades 2-4)
Oligodendroglioma, IDH-mutant and1p19q-codeleted (CNS WHO grades 2-3)
Glioblastoma, IDH-wildtype (CNS WHO grade 4)

On November 17, 2023 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated Photo Dynamic Compounds ("PDCs") used for the safe and effective destruction of various cancers, bacteria and viruses, reported that it has commenced a non-brokered private placement of units of the Company ("Units") to raise up to $CAN 1.5 M ("Offering") (Press release, Theralase, NOV 17, 2023, View Source [SID1234637859]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the Offering, each Unit is priced at $CAN 0.22 and consists of one common share of the Company ("Common Share") and one Common Share purchase warrant ("Warrant"). Each Warrant will entitle the holder thereof to purchase one Common Share of the Company ("Warrant Share") for a period of 60 months following the Closing Date (as defined herein) of the Offering at an exercise price of $CAN 0.28 per Warrant Share.

The Company plans to use the proceeds of the Offering to further the Phase II Non-Muscle Invasive Bladder Cancer ("NMIBC") clinical study currently underway and for working capital needs.

All securities issued under the Offering will be subject to a four months and one day hold period from the Closing Date under applicable Canadian and US securities laws.

The Offering is scheduled to close on or about the week of November 20, 2023 and is subject to the receipt of all necessary approvals, including the approval of the TSXV ("Closing Date").

The Offering is being made to accredited investor subscribers resident in each of the Provinces of Canada, pursuant to applicable private placement exemptions, in the United States or to, or for the account of, U.S. persons, on a private placement basis pursuant to an exemption from the registration requirements in Rule 144A or Regulation D of the United States Securities Act of 1933, as amended or other available U.S. registration exemptions and offshore jurisdictions pursuant to relevant prospectus or registration exemptions in accordance with applicable laws.

The Company agrees to pay a finder’s fee to eligible finders for subscribers, introduced by such finder, in connection with the non-brokered private placement, as follows:

A cash commission equal to 7% of the gross proceeds
Non-transferable finder warrants exercisable to acquire that number of Units equal to 5% of the total number of Units issued, at an exercise price of $CAN 0.22. Each finder warrant will be exercisable for one Share at $CAN 0.28 for a period of 60 months following the Closing Date.
No other fee or commission is payable by the Company in connection with the completion of the Private Placement.

The Company also announces that it has mutually terminated the recently announced brokered Listed Issuer Financing Exemption ("LIFE") financing with Research Capital Corporation.

The securities referred to in this news release have not been, and will not be, registered under the United States Securities Act of 1933, as amended ("U.S. Securities Act"), or any applicable securities laws of any state of the United States, and may not be offered or sold within the United States or to, or for the account or benefit of, U.S. persons (as such term is defined in Regulation S under the U.S. Securities Act) or persons in the United States unless registered under the U.S. Securities Act and any other applicable securities laws of the United States or an exemption from such registration requirement is available. This press release shall not constitute an offer to sell or a solicitation of an offer to buy nor shall there be any sale of the securities offered in any jurisdiction in which such offer, solicitation or sale would be unlawful, including the United States.

On November 17, 2023 FORE Biotherapeutics today reported updated safety and efficacy data from the Phase 1/2a clinical trial evaluating plixorafenib (FORE8394; PLX8394), a novel, investigational, small-molecule, next-generation, orally available selective inhibitor of BRAF alterations (Press release, Fore Biotherapeutics, NOV 17, 2023, View Source [SID1234637790]). The results continue to demonstrate promising single-agent activity against BRAF V600-mutated tumors, including primary central nervous system tumors (PCNSTs), as presented at the Society for Neuro-Oncology (SNO) 2023 Annual Meeting, being held November 15-19, 2023, in Vancouver, Canada.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The updated data from our Phase 1/2a study continues to reinforce plixorafenib’s differentiated clinical profile in patients harboring BRAF V600 mutations," said Stacie Shepherd, MD, PhD, and Chief Medical Officer of FORE. "The data presented today at SNO 2023 demonstrate deep and durable confirmed responses in MAPK inhibitor-naïve patients, including a 67% overall response rate in patients with primary central nervous system tumors. I look forward to further elucidating plixorafenib’s potential in our ongoing, global Phase 2 FORTE study."

"These results continue to demonstrate that plixorafenib has a favorable safety and efficacy profile compared to the currently approved BRAF/MEK inhibitors and investigational pan-RAF inhibitors," shared Macarena de la Fuente, MD, Associate Professor and Chief of Neuro-oncology at the University of Miami Sylvester Comprehensive Cancer Center. "I am excited to share these data today with the medical community and I look forward to the further study of plixorafenib to address the high unmet need of patients living with these difficult to treat cancers."

Key Findings from the Phase 1/2a Study

Safety and Tolerability

As of the data cutoff date of September 6, 2023, 113 patients have received plixorafenib under continuous dosing until disease progression and are included in the safety population.

Plixorafenib continues to demonstrate a favorable tolerability profile with a low frequency of symptomatic treatment emergent adverse events (TEAEs) relative to approved BRAF/MEK inhibitors
The safety profile in patients with PCNSTs (N=22) was consistent with that observed in the overall population
Headache was the only symptomatic Grade ≥3 treatment emergent AE occurring in >5% of patients
At the recommended Phase 2 dose (plixorafenib 900mg QD with PK booster: cobicistat 150mg QD), dose optimization maximizes dose intensity early in treatment with:
No DLTs
Most common laboratory abnormality TEAEs are predominantly Grade 1-2
Symptomatic TEAEs were almost all Grade 1
Efficacy

Among the 9 MAPKi-naïve patients with V600-mutated PCNSTs, 6 achieved a response for an ORR of 66.7% (95% CI: 29.9, 92.5), all of which were confirmed responses
mDOR was 13.9 months (range: 3.7, 32.3) with 4/6 (67%) of responders having DOR of 6 months or longer
mPFS was not yet reached in patients with low grade glioma and glioneuronal tumors (range: 1.6, 27.8+ months; n=4) and 6.7 months (range: 2.8, 34.1 months; n=5) in high grade gliomas
Among the 24 MAPKi-naïve patients with V600-mutated advanced solid tumors, 10 had a response for an ORR of 41.7%, all of which were confirmed responses
mDOR was 17.8 months (range: 3.7, 59.2)
Median time to response was 3.5 months in patients with V600-mutated solid tumors, including those treated with prior MAPK inhibitor
About Plixorafenib (FORE8394; PLX8394)

Plixorafenib is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. It was designed to target a wide range of BRAF mutations while sparing wild-type forms of RAF. Preclinical studies and clinical trials have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAF V600 monomers targeted by first-generation RAF inhibitors but also disrupts constitutively active dimeric BRAF class 2 mutants, fusions, splice variants and others. Unlike first-generation RAF inhibitors, plixorafenib does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a "paradox breaker," plixorafenib could therefore treat acquired resistance to current RAF inhibitors and, more generally, yield improved safety and more durable efficacy than first-generation RAF inhibitors.

Plixorafenib was granted Orphan Drug Designation by the U.S. Food and Drug Administration in March 2023 for the treatment of primary CNS malignancies. In September 2022, the Agency granted plixorafenib Fast Track Designation for the treatment of patients with cancers harboring BRAF Class 1 (V600) and Class 2 alterations (including fusions) who have exhausted prior therapies.

Plixorafenib is currently being evaluated in Phase 1/2a clinical trial in patients with advanced solid tumors (including brain and spinal cord tumors) with activating BRAF alterations. Interim clinical data presented at ESMO (Free ESMO Whitepaper) 2022, ASCO (Free ASCO Whitepaper) 2023 and SNO 2023 provided evidence of durable anti-tumor activity in patients with BRAF-altered cancers.

On November 17, 2023 Avistone Biotechnology Co. Ltd. ("Avistone" or "the Company"), an innovative biotechnology company focused on precision oncology therapeutics, reported that they received conditional approval from the National Medical Products Administration (NMPA) to commercialize Vebreltinib (also referred to as PLB1001, APL-101, Bozitinib, CBT-101) to treat patients with MET exon 14 skipping non-small cell lung cancer (NSCLC) in China (Press release, Avistone Pharmaceuticals, NOV 17, 2023, View Source [SID1234637789]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The development of drugs for indications related to MET targets has always been a difficult one. With the NMPA approval of Vebreltinib, we look forward to providing this new treatment option to patients with MET exon 14 skipping NSCLC in China"

Post this
The conditional approval was based on results from a pivotal Phase II KUNPENG study with an objective response rate (ORR) of 75.0% and median progression-free survival (PFS) in patients with advanced METex14 mutations to 14.1 months with a good safety profile as was recently presented at the 2023 European Society for Clinical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Madrid, Spain (Poster# 1379P).

MET signaling is implicated in cell proliferation, migration, invasion, and survival. Genomic alterations in MET can manifest in driving oncogenesis in the form of MET exon 14 skipping (METex14) or other activating mutations, MET gene amplification, gene fusion and MET protein overexpression. METex14 is an independent prognostic factor associated with poorer survival rates in patients with NSCLC.

"The development of drugs for indications related to MET targets has always been a difficult one. With the NMPA approval of Vebreltinib, we look forward to providing this new treatment option to patients with MET exon 14 skipping NSCLC in China" said Dr. Hepeng Shi, Chairman, CEO, and Founder of Avistone.

Avistone holds the exclusive rights to Vebreltinib in China, Hong Kong and Macau.

On November 17, 2023 Phase Genomics, Inc., a global innovator for industry-leading genomic solutions, reported the presentation of new data from the proximity ligation sequencing-based OncoTerra cytogenomics platform on the leading-edge AVITI next-generation sequencing system (Press release, Phase Genomics, NOV 17, 2023, View Source [SID1234637788]). The platform offers a revolutionary leap toward rapid risk stratification for acute myeloid leukemia (AML).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Traditional cytogenetics has relied on a battery of assays for comprehensive evaluation, including karyotyping, FISH, and CMA, identifying large-scale structural alterations in chromosomes. Not only do these tests often fail to detect clinically relevant sub-microscopic variations, the cascade approach prolongs the time from sample collection to actionable insight.

Phase Genomics addresses these legacy challenges with the combination of its OncoTerra technology and Element’s AVITI system for next-generation sequencing, providing a high-resolution alternative for comprehensive, streamlined risk stratification in the research setting. OncoTerra on AVITI has demonstrated detection of the full range of chromosomal abnormalities observed in cancer from sample to cytogenomic insights.

"Our results speak to the real potential of OncoTerra on the AVITI sequencer. The next-generation cytogenomics all-in-one approach is primed to replace fragmented legacy tests with a single, rapid assay," said Ivan Liachko, founder and CEO of Phase Genomics. "The ability to uncover previously undetected structural alterations in AML opens the exploration for new avenues for targeted therapies and personalized medicine. OncoTerra on AVITI represents a major stride toward accelerating cancer diagnoses and improving patient outcomes."

The research leveraged OncoTerra for de novo risk assessment of 32 AML patient samples in the retrospective setting. Utilizing proximity ligation sequencing, OncoTerra delivered exceptional proficiency in detecting structural aberrations directly within AML samples, as well as seven variants of known clinical significance not detected by standard-of-care cytogenetic testing. These alterations included sub-microscopic inversions, terminal translocations, insertions, and copy-neutral loss of heterozygosity. The increased resolution and integrated analysis of the genome using OncoTerra yielded additional findings in eleven cases without previously detected chromosome abnormalities.

The study also highlighted the improved efficiency and read quality of the AVITI sequencer compared to other platforms. Benchmarking AVITI against Illumina NovaSeq platforms revealed a 20% enhancement in the fraction of effective read pairs, indicating greater sequencing efficiency and coverage.

Phase Genomics, the recent recipient of the Biotech Breakthrough Award for Metagenomics Innovation Of The Year, will highlight the power of OncoTerra for AML in poster G025, "Next-generation cytogenomics using proximity ligation technology on the AVITI genome sequencing platform" on November 18. Discover more about next-generation cytogenomics powered by proximity ligation technology in four presentations at AMP23, or connect with the Phase Genomics team at Booth 810.

OncoTerra is available for research use only and is not for use as a clinical diagnostic.