On January 15, 2025 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, reported that Germany’s medical regulatory body, the Paul-Ehrlich-Institute (PEI), has approved the continuation of patient enrollment into Cohort 5 of the GOBLET study (Press release, Oncolytics Biotech, JAN 15, 2025, View Source [SID1234649740]). This cohort is evaluating pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab (Tecentriq) in newly diagnosed pancreatic ductal adenocarcinoma (PDAC) patients.

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Following a positive safety review by the independent Data Safety Monitoring Board (DSMB), which recommended continuation, the PEI’s approval allows Cohort 5 to progress to full enrollment. Early safety data will be presented at the upcoming 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium later this month, with initial efficacy results expected in the second half of the year.

"Pelareorep has the potential to meaningfully improve outcomes for patients with metastatic pancreatic cancer," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer for Oncolytics Biotech. "Encouraging tumor response rates observed in an earlier cohort of the GOBLET study underscore pelareorep’s promise in this disease. GOBLET Cohort 5 extends our evaluation by testing pelareorep with a different chemotherapy regimen, mFOLFIRINOX, which broadens the range of pancreatic cancer patients who may benefit from this innovative therapy. Positive results from this cohort may ultimately enable pelareorep to benefit the large majority of metastatic pancreatic patients for whom improved treatment options are badly needed."

About GOBLET Cohort 5
The mFOLFIRINOX cohort of the Phase 1/2 GOBLET study is designed to evaluate newly diagnosed metastatic PDAC patients treated with pelareorep + mFOLFIRINOX with or without atezolizumab. A three-patient safety run-in was incorporated to evaluate the safety and tolerability of each treatment arm: pelareorep + mFOLFIRINOX + atezolizumab and pelareorep + mFOLFIRINOX. A total of fifteen evaluable patients will be randomized to each arm in Stage 1 of this Simon two-stage study. The co-primary endpoints are objective response rate and safety. If Stage 1 success criteria are met, one or both treatment arms may be expanded to Stage 2, in which 17 additional evaluable patients per arm will be enrolled. Blood and tumor samples will also be collected for translational evaluations.

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 17 centers in Germany and is being managed by AIO-Studien-gGmbH. The co-primary endpoints of the study are objective response rate (ORR) and/or disease control rate and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers. The study comprises five treatment groups:

1.Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line advanced/metastatic PDAC patients;

2.Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients;

3.Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients;

4.Pelareorep in combination with atezolizumab in 2nd line or later advanced and unresectable anal cancer patients; and

5.Pelareorep in combination with mFOLFIRINOX with and without atezolizumab in newly diagnosed metastatic PDAC patients.

Any cohort meeting pre-specified efficacy criteria in Stage 1 may be advanced to Stage 2 and enroll additional patients.

About AIO
AIO-Studien-gGmbH (AIO) emerged from the study center of the medical oncology working group within the German Cancer Society (DKG). AIO operates with a non-profit purpose of promoting science and research with a focus on medical oncology. Since its foundation, AIO has become a successful sponsor and study management company and has established itself both nationally and internationally.

PHYRAGO Represents the First and Only Improved Version of SPRYCEL That Can Be Safely Co-administered With Gastric Acid-Reducing Agents

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On January 15, 2025 Handa Pharmaceuticals, Inc. ("Handa") (6620.TWO) announced that its U.S. subsidiary, Handa Therapeutics, LLC (the "Company"), has acquired PHYRAGO (dasatinib) tablets, a U.S. Food and Drug Administration ("FDA") approved chronic myeloid leukemia treatment that was developed by Nanocopoeia, LLC (Press release, Nanocopoeia, JAN 15, 2025, View Source [SID1234650016]). PHYRAGO is the first and only dasatinib product that can be co-administered with gastric acid-reducing agents. An estimated one-third of patients who require SPRYCEL treatment may also take gastric acid-reducing agents1, which can reduce dasatinib’s drug exposure by more than 40% when taken with a proton pump inhibitor and more than 60% when taken with an H2 receptor antagonist2.

PHYRAGO was granted Orphan-Drug Designation and has received three (3) years of data exclusivity that will expire December 5, 2026. Should PHYRAGO be granted Orphan-Drug Exclusivity, it may be eligible for seven (7) years of exclusivity, until December 5, 2030. PHYRAGO is protected by several issued patents, including those listed in the FDA’s Approved Drugs and Therapeutic Equivalents publication (the "Orange Book") that expire January 22, 2041.

The Company is in the process of selecting a U.S. commercialization partner and expects PHYRAGO to be available to patients in Q1-2025.

PHYRAGO is indicated for adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase and adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who no longer benefit from, or did not tolerate, other treatments.

"PHYRAGO represents a novel dasatinib formulation that delivers equivalent efficacy to SPRYCEL, with the additional benefit of allowing patients to take dasatinib with gastric acid-reducing agents", said Bill Liu, Chairman and CEO of Handa. "Unlike SPRYCEL, PHYRAGO allows concomitant use with a proton pump inhibitor or H2 receptor antagonist."

The effect of co-administration of gastric acid-reducing agents on SPRYCEL is significant. The SPRYCEL label warns that the "co-administration of SPRYCEL with a gastric acid-reducing agent may decrease the concentration of dasatinib. Decreased dasatinib concentrations may reduce efficacy. Do not administer H2 agonists or proton pump inhibitors with SPRYCEL."3

The FDA approved PHYRAGO with a label that allows co-administration with gastric acid-reducing agents, stating that "No clinically significant differences in the pharmacokinetics of PHYRAGO were observed following concomitant use with omeprazole (proton pump inhibitor) or famotidine (H2 receptor antagonist)."4 and "Avoid concomitant use of PHYRAGO with antacids. If concomitant use of an antacid cannot be avoided, administer the antacid at least 2 hours prior to or 2 hours after the dose of PHYRAGO."5

According to Bristol Myers Squibb’s annual report, net sales of SPRYCEL in 2023 totaled $1.44 billion. For full prescribing information about PHYRAGO, please visit www.phyrago.com.

Sources:

IQVIA longitudinal prescription and medical claims data, January 2013-March 2021, identified 7,419 patients receiving dasatinib treatment of which 31.8% were concomitantly prescribed a proton pump inhibitor and/or H2 receptor antagonist
SPRYCEL Prescribing Information (Rev. 7/2024), Section 12.3, Pharmacokinetics – Drug Interaction Studies – Gastric Acid Reducing Agents
SPRYCEL Prescribing Information (Rev. 7/2024), Section 7.1, Drug Interactions – Effect of Other Drugs on Dasatinib – Gastric Acid Reducing Agents
PHYRAGO Prescribing Information (Rev. 12/2024), Section 12.3, Pharmacokinetics – Drug Interaction Studies – Gastric Acid Reducing Agents
PHYRAGO Prescribing Information (Rev. 12/2024), Section 2.2, Dosage Modifications – Antacids

On January 15, 2025 Orna Therapeutics, Inc. ("Orna") and Shanghai Simnova Biotech Co., Ltd. ("Simnova") reported the expansion of their strategic collaboration to include BCMA (B-cell maturation antigen) as a designated biological target for RNA-based therapeutics development (Press release, Orna Therapeutics, JAN 15, 2025, View Source [SID1234649741]). This partnership leverages Orna’s groundbreaking circular RNA (oRNA) technology and Simnova’s expertise in cell therapy to deliver transformative treatments for patients worldwide.

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Under the agreement, Simnova will pursue the research and development and commercialization of in vivo panCar cell therapies targeting BCMA in greater China and Orna will retain all rights for development and commercialization in the rest of the world. Each party will have the right to receive an upfront payment within their respective licensed territories and is eligible for clinical development, regulatory, and commercialization milestones as well as royalties on any approved products derived from the collaboration.

In January 2023, Simnova and Orna announced a collaboration agreement granting Simnova exclusive rights to develop and commercialize Orna’s in vivo cell therapy products in the Greater China region. This includes Orna’s lead isCAR project targeting CD19, "ORN-101."

"We are excited to deepen our partnership with Simnova to bring an in vivo BCMA panCAR therapy to patients with multiple Myeloma," said Ansbert Gadicke, M.D., Chairman of Orna and Managing Partner of MPM BioImpact. "Orna’s panCAR approach holds the potential to introduce a novel class of in vivo CAR therapies that overcomes the limitations of current ex vivo cell therapies. The exciting pre-clinical and non-human primate data that Orna has generated continues to reinforce our commitment in this area. We look forward to advancing our programs towards the clinic."

Dr. Zhuoxiao CAO, CEO of Simnova, added, "Our shared commitment to advancing immunotherapies and oncology treatments opens new opportunities to address unmet medical needs through the development of BCMA-targeted therapeutics."

On January 14, 2025 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported that the first patient in Cohort 3 of its Phase 1 clinical trial has been dosed with TTX-MC138, its lead candidate (Press release, TransCode Therapeutics, JAN 14, 2025, View Source [SID1234649726]). The Safety Review Committee monitoring the clinical trial unanimously approved opening of the third cohort based on its favorable review of Cohort 1 and 2 safety and pharmacokinetic (PK) data. Additional Cohort 3 patients have been scheduled. The dose administered to patients in the third cohort is approximately double the dose administered to those in the second cohort.

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Several patients in the first and second cohort remain on study for continued treatment, receiving additional doses of TTX-MC138. No significant safety or dose limiting toxicities have been reported. Analyses of PK data and pharmacodynamic (PD) activity from Cohorts 1 and 2 is ongoing. To date, the analyses suggest that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical results and results from TransCode’s previous Phase 0 clinical trial. Specifically, results from Cohort 1 confirmed the Phase 0 observation that TTX-MC138 shows evidence of pharmacodynamic activity in the presence of high baseline expression of miR-10b, reaching a 66% inhibition at 24 hours after infusion, similar to that seen in the Phase 0 trial. Additionally, TTX-MC138 activity increased with the escalated dose administered in Cohort 2 and was consistent at subsequent administrations of TTX-MC138, suggesting a favorable pharmacokinetic profile.

"An SRC is a group of clinicians and other experts that oversee patient safety during a clinical trial. The SRC determines whether and how a study should proceed, including dose escalation and de-escalation decisions in accordance with the study design. Enrollment into this study continues based on the SRC’s cumulative safety data review. We are very pleased with the commitment from our clinical sites which may enable quick completion of the third cohort," commented Sue Duggan, TransCode’s Senior Vice President of Operations.

About TTX-MC138

TTX-MC138 is a first-in-class therapeutic candidate designed to inhibit microRNA-10b, or miR-10b, a microRNA widely believed to be critical to the emergence and progression of many metastatic cancers. TransCode’s 2023 Phase 0 clinical trial produced evidence of delivery of a radiolabeled version of TTX-MC138 to metastatic lesions and pharmacodynamic activity, even at a microdose of the drug candidate, suggesting a broad therapeutic window for TTX-MC138.

About the Trial

TransCode’s Phase 1 clinical trial is a multicenter, open-label, dose-escalation and dose-expansion study designed to generate critical data to support evaluation of the safety and tolerability of TTX-MC138 in patients with a variety of metastatic solid cancers. While not an endpoint, the trial may provide early evidence of clinical activity of TTX-MC138. The trial comprises an initial dose-escalation stage followed by a dose-expansion stage. The primary objective of the dose-escalation stage is to evaluate the safety and tolerability of escalating dose levels of TTX-MC138. In the dose-expansion stage, the safety, tolerability and anti-tumor activity of TTX-MC138 will be further evaluated in certain tumor types selected based on preliminary results from the dose-escalation phase.

Further information is available at www.clinicaltrials.gov NCT Identifier: (NCT06260774).

On January 13, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported pipeline progress and outlined key anticipated milestones towards its first potential U.S. Food and Drug Administration (FDA) approval under its "OnTarget 2026" operating plan (Filing, 8-K, Nuvalent, JAN 14, 2025, View Source [SID1234649711]).

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As part of this plan, Nuvalent anticipates the following 2025 milestones:

• Report pivotal data for tyrosine kinase inhibitor (TKI) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from its ARROS-1 Phase 1/2 trial of zidesamtinib in the first half of 2025;

• Submit a New Drug Application (NDA) for zidesamtinib with initial target indication of TKI pre-treated patients with advanced ROS1-positive NSCLC by mid-year 2025;

• Report pivotal data for TKI pre-treated patients with advanced ALK-positive NSCLC from its ALKOVE-1 Phase 1/2 trial of neladalkib (NVL-655) by year-end 2025;

• Initiate the ALKAZAR Phase 3 randomized, controlled trial of neladalkib for TKI-naïve patients with ALK-positive NSCLC in the first half of 2025; and

• Progress the HEROEX-1 Phase 1a/1b trial of NVL-330 for patients with advanced HER2-altered NSCLC.

With the achievement of these milestones, the company anticipates that the first potential approval from its pipeline of novel kinase inhibitors will be for zidesamtinib for the treatment of TKI pre-treated ROS1-positive NSCLC in 2026.

"2025 marks our opportunity to transition to becoming a fully integrated commercial-stage biopharmaceutical company. Throughout this period of growth and evolution, our strategy remains rooted in our commitment to our core value of Patient Impact, and our responsibility to the patients and treating physicians who continue to support our clinical trials," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "Enrollment momentum in the Phase 2 portions of our ARROS-1 and ALKOVE-1 clinical trials has further accelerated following our presentation of updated Phase 1 data at ESMO (Free ESMO Whitepaper) 2024, reinforcing our plan to report pivotal data from both programs this year. We believe this enthusiasm is a clear demonstration of the medical need for patients with ROS1- and ALK-positive NSCLC, and of our responsibility to bring new treatment options to TKI pre-treated patients as quickly as possible."

"Parallel development paths are in place towards our ultimate goal to provide new, potential best-in-class treatment options to all patients with ROS1- or ALK-positive NSCLC," said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent. "For zidesamtinib, we plan to submit an NDA this year with an initial target indication for TKI pre-treated patients with ROS1-positive NSCLC, where we believe zidesamtinib has demonstrated the potential to address a medical need. We expect to report topline pivotal data from this population in the first half of 2025. In parallel, we continue a collaborative dialogue with the FDA on accelerated opportunities towards a potential line-agnostic indication supported by our ongoing TKI-naïve cohort in the Phase 2 portion of our ARROS-1 trial."

Ms. Noci continued, "Similarly for neladalkib, we expect our initial NDA submission to be for TKI pre-treated patients with ALK-positive NSCLC, supported by topline pivotal data from the ALKOVE-1 trial that we expect to report by year-end 2025. Additionally, we remain on-track to initiate the Phase 3 randomized, controlled ALKAZAR trial for TKI-naïve patients in the first half of this year, a critical step towards our ultimate goal of moving neladalkib up the treatment paradigm."

"We believe we have the right team in place and are well resourced with cash runway into 2028 to support the advancement of our clinical programs and ongoing buildout of a commercial infrastructure," said Alexandra Balcom, Chief Financial Officer at Nuvalent. "Beyond our parallel-lead programs, we remain committed to advancement of our HEROEX-1 Phase 1a/1b trial and robust discovery pipeline for sustainable long-term growth."

Enrollment Updates for ARROS-1 and ALKOVE-1

ARROS-1 for ROS1-positive NSCLC

•As of December 31, 2024, a total of 430 Phase 1 and Phase 2 patients had been enrolled in the ongoing ARROS-1 Phase 1/2 trial of zidesamtinib for patients with advanced ROS1-positive NSCLC and other solid tumors, which is designed with registrational intent for TKI pre-treated and TKI-naïve patients with advanced ROS1-positive NSCLC. Updated Phase 1 data were presented in September 2024 at the ESMO (Free ESMO Whitepaper) Congress.

ALKOVE-1 for ALK-positive NSCLC

•As of December 31, 2024, a total of 596 Phase 1 and Phase 2 patients had been enrolled in the ongoing ALKOVE-1 Phase 1/2 trial of neladalkib for patients with advanced ALK-positive NSCLC and other solid tumors, which is designed with registrational intent for TKI pre-treated patients. Updated Phase 1 data were presented in September 2024 at the ESMO (Free ESMO Whitepaper) Congress.

Presentation at 43rd Annual J.P. Morgan Healthcare Conference

Dr. Porter will present at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco on Tuesday, January 14, 2025 at 9:00 a.m. PT. A live webcast will be available in the Investors section of Nuvalent’s website at www.nuvalent.com, and will be archived for 30 days following the conference.

About Zidesamtinib

Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, zidesamtinib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy. Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ROS1 tyrosine kinase inhibitors and orphan drug designation for ROS1-positive NSCLC.

About Neladalkib (NVL-655)

Neladalkib is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.

About NVL-330

NVL-330 is a novel brain-penetrant HER2-selective tyrosine kinase inhibitor designed to address the combined medical need of treating HER2-mutant tumors, including those with HER2 exon 20 insertion mutations, avoiding treatment related adverse events due to off-target inhibition of wild-type EGFR, and treating brain metastases.