On August 30, 2024 IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, off-the-shelf, immune-modulating therapeutic cancer vaccines based on its T-win platform, reported that an Independent Data Monitoring Committee (IDMC) recommended continuation of the company’s pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) of its lead investigational therapeutic vaccine, IO102-IO103, following a per-protocol interim analysis (Press release, IO Biotech, AUG 30, 2024, View Source [SID1234646234]). The trial is evaluating IO102-IO103 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, as a first-line treatment for patients with unresectable or metastatic (advanced) melanoma. Based on their review of the safety and efficacy data, the IDMC recommended that the trial continue without modifications and noted that no new safety signals were observed. The primary endpoint of progression-free survival (PFS) is projected to be reached in the first half of 2025.

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The per-protocol interim analysis was performed one year after 225 patients were randomized in the trial. The interim efficacy analysis was intentionally set with a high statistical bar (p≤0.005), and based on the analysis, the IDMC determined that the data did not meet the criteria to declare superiority of ORR. The trial was designed to preserve most of the statistical alpha for the trial’s primary endpoint of PFS. The PFS analysis is event-driven and will be conducted when 226 events (disease progression or death) have been reported in the trial with independent central review. With 407 patients randomized, the trial is powered at 89% to detect a 35% reduction in the risk of an event.

"To date, none of the approved immunotherapeutic combinations for the treatment of advanced melanoma demonstrated statistical significance in ORR in large Phase 3 trials; nevertheless, these trials achieved statistical significance on PFS," said Mai-Britt Zocca, PhD, President and CEO of IO Biotech. "Based on the 25.5 months median PFS we observed in the Phase 1/2 trial of IO102-IO103 in combination with a PD-1 inhibitor in advanced melanoma, with no added significant systemic toxicity than that typically seen with anti-PD-1 monotherapy, we remain optimistic about meeting the primary endpoint of PFS, projected to occur in the first half of 2025."

Igor Puzanov, MD, MSCI, FACP, Director, Center for Early Phase Clinical Trials, Chief, Division of Melanoma, Department of Medicine and Investigator for the Phase 3 Study at Roswell Park Comprehensive Cancer Center, Buffalo, New York commented, "The incidence of melanoma is on the rise and new treatments are needed. This is a novel investigational immune-modulatory therapeutic cancer vaccine combined with an anti-PD-1 therapy that has the potential to transform the treatment paradigm with a new and better option for people battling advanced melanoma. I am eagerly awaiting the PFS primary endpoint readout of this Phase 3 trial that could further validate this novel cancer vaccine’s ability to help patients with advanced melanoma who are seeking more efficacious, low treatment-induced toxicity therapy options."

Jessica Hassel, MD, Head of the Section for Dermato-Oncology at the University Hospital Heidelberg, investigator and lead enroller for the Phase 3 trial added, "We have been seeing promising results using combination immunotherapeutic treatments and I remain confident that IO102-IO103 in combination with pembrolizumab could offer new hope for treating patients with advanced melanoma. I look forward to the full readout of data at the end of this trial to further understand the full potential of this investigational therapeutic cancer vaccine combined with an anti-PD-1 agent."

Dr. Zocca continued, "We continue to be enthusiastic about the encouraging preliminary data from our Phase 2 basket trial evaluating IO102-IO103 in combination with pembrolizumab for the treatment of metastatic non-small cell lung cancer (NSCLC) or recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Data from the SCCHN cohort has been accepted for poster presentation at the ESMO (Free ESMO Whitepaper) congress, and data from the NSCLC cohort has been accepted to another medical meeting in the fall. We believe these data could provide further evidence to support the broader potential of therapeutic cancer vaccines for the benefit of patients in additional cancer indications."

About the IOB-013/KN-D18 Clinical Trial

IOB-013/KN-D18 (Clinical Trials.gov: NCT05155254) is an open label, randomized Phase 3 pivotal clinical trial of IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. A total of 407 patients have been enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study is progression-free survival, an event-driven analysis conducted when 226 events, defined as disease progression or death, have been reported in the study. Secondary endpoints include overall response rate (ORR), overall survival (OS), durable objective response (DRR), complete response rate (CRR), duration of response (DoR), time to complete response (TTCR), disease control rate (DCR), and incidence of AEs and SAEs (safety and tolerability). Biomarkers in the blood and tumor tissue will also be assessed. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab.

About IO102-IO103

IO102-IO103 is an investigational off-the-shelf therapeutic cancer vaccine designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase (IDO) positive and/or programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating IO102-IO103 in combination with pembrolizumab as first line treatment in patients with solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating IO102-IO103 in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors.

The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck, which is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103.

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

On August 30, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported that it has voluntarily withdrawn its supplemental New Drug Application ("NDA") in China for fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric or gastroesophageal junction adenocarcinoma and will evaluate a new route forward (Press release, Hutchison China MediTech, AUG 30, 2024, View Source [SID1234646233]). Following an additional internal review of the current data package, in light of recent discussions with the National Medical Products Administration of China ("NMPA"), HUTCHMED has determined that the submission is unlikely to support an approval in China at this time.

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This supplemental NDA for fruquintinib was based on data from the Phase III FRUTIGA study, which was declared positive due to a statistically significant improvements in many clinically meaningful endpoints, including progression-free survival ("PFS"), which served as one of two primary endpoints. However, while an improvement was also observed in the second primary endpoint of median overall survival ("OS"), it was not statistically significant. Extensive subsequent analyses conducted indicate that, although the high and imbalanced proportion of patients receiving subsequent antitumor therapies confounded the OS effect, fruquintinib plus paclitaxel demonstrated meaningful clinical benefit and favorable OS trends through a variety of models. Furthermore, no new safety signals were observed, and fruquintinib plus paclitaxel showed a tolerable safety profile. However, it became clear from dialogue with the Centre for Drug Evaluation (CDE) of the NMPA and its external committee members that the current understanding and interpretation of the OS results could not serve as the basis of the supplemental NDA approval, and that further work needs to be undertaken.

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, commented, "Whilst disappointed by this outcome, we remain optimistic about the utility of fruquintinib in the treatment of gastric cancer. The data set from FRUTIGA demonstrates that fruquintinib plus paclitaxel could offer a promising new treatment option to certain patients in future, and we are driven to investigate this possibility thoroughly. We look forward to evaluating a path forward and would like to thank both the patients and principal investigators who took part in this study for contributing to a better understanding of this devastating disease."

Dr Rui-Hua Xu, Professor at the Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, added, "Gastric cancer is the fifth most common cancer worldwide and patients in China are currently underserved by available treatment options. Although the current data package would not support approval on this occasion, the Phase III study demonstrated clear benefits of this fruquintinib combination across many clinically meaningful endpoints and the team are committed to evaluating all options. Promising subgroup analyses are helping us to better understand how we can effectively combat this disease, and we remain hopeful that this study forms part of an important journey to a much-needed new therapy."

Fruquintinib is approved in China, the US and Europe for the treatment of previously-treated patients with metastatic colorectal cancer ("CRC"), and regulatory applications for this indication are progressing as expected in over a dozen jurisdictions. It works as an anti-cancer therapy by blocking tumor angiogenesis, a proliferation of blood vessels that is critical for cancer growth. It is a selective oral inhibitor of vascular endothelial growth factor receptors ("VEGFRs") 1, 2 and 3, and this pathway plays a key role in the pathogenesis of many solid tumors including gastric cancer.

An NDA in China for fruquintinib in combination with sintilimab in endometrial cancer was accepted with priority review status in April 2024, and a Phase III trial in China of fruquintinib in combination with sintilimab in renal cell carcinoma was fully enrolled in December 2023.

About the Phase III FRUTIGA Trial
FRUTIGA (NCT03223376) was a 1:1 randomized, double-blind, Phase III study conducted across 35 sites in China. It evaluated fruquintinib in combination with paclitaxel chemotherapy, compared with paclitaxel monotherapy, for second-line treatment in 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma. The study was declared positive due to a statistically significant improvement in progression-free survival ("PFS"), one of two dual primary endpoints. Median PFS for patients who received fruquintinib plus paclitaxel was 5.6 months, compared to 2.7 months for those who received paclitaxel monotherapy (stratified hazard ratio ["HR"] = 0.569; p < 0.0001). An improvement was also observed in the dual primary endpoint of median overall survival (OS), (9.6 months vs. 8.4 months) but this was not statistically significant. Fruquintinib plus paclitaxel demonstrated statistically significant improvements in multiple other endpoints including objective response rate (ORR), disease control rate (DCR) and duration of response (DoR). It was well tolerated, with a safety profile consistent with expectations and previously reported studies.

Results were published in Nature Medicine and presented at the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting, concluding that fruquintinib plus paclitaxel could be a promising second-line treatment option for patients with advanced gastric or gastro­esophageal adenocarcinoma, who have failed fluoropyrimidine- or platinum-containing chemotherapy.

About Gastric Cancer
Gastric cancer is a cancer that starts in the stomach. It is the fifth most common cancer worldwide in 2022. It was estimated to have caused approximately 660,000 deaths worldwide.[2] In China, it was estimated that over 359,000 people were diagnosed with gastric cancer, and approximately 260,000 people died from gastric cancer.

About Fruquintinib
Fruquintinib is a selective oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti-cancer therapies.

About Fruquintinib Approval for metastatic CRC in China
Fruquintinib is approved for marketing in China, where it is co-marketed by HUTCHMED and Lilly under the brand name ELUNATE. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch, fruquintinib has benefited over 100,000 patients in China.

On August 29, 2024, bluebird bio, Inc. (the "Company") reported to have entered into an amendment (the "Fourth Amendment") to its Loan and Security Agreement, dated as of March 15, 2024, as amended on April 30, 2024, July 9, 2024 and August 13, 2024 (the "LSA"), by and among the Company, the several banks and other financial institutions or entities party thereto, as lenders (collectively, the "Lenders"), and Hercules Capital, Inc., as administrative agent and collateral agent (the "Agent") (Filing, 8-K, bluebird bio, AUG 30, 2024, View Source [SID1234646232]).

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Pursuant to the Fourth Amendment, the Company, the Agent and the Lenders agreed to, among other things, an extension of the deadlines by which the Company must provide to the Lenders financial statements for the year ended December 31, 2023 and for the quarter ended March 31, 2024. Further, the Fourth Amendment provides that the Company’s late delivery and filing of its Form 10-K for the year ended December 31, 2023 and Form 10-Q for the quarter ended March 31, 2024 shall not be deemed a violation of the Company’s covenant to maintain compliance with applicable law, so long as such documents are filed by the extended deadlines.

The foregoing description of the Fourth Amendment does not purport to be complete and is qualified in its entirety by the full text of the Fourth Amendment, a copy of which is filed as Exhibit 10.1 to this Current Report on Form 8-K and incorporated herein by reference.

On August 30, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing tuspetinib, a highly differentiated oral kinase inhibitor for the treatment of patients with acute myeloid leukemia (AML), reported that it received a $10 million loan through a Facility Agreement with Hanmi Pharmaceutical Co. Ltd. ("Hanmi") (Press release, Aptose Biosciences, AUG 30, 2024, View Source [SID1234646231]). The loan is convertible as prepayment of milestone obligations under the Future Collaboration Agreement (as defined hereinafter) or repayable after the expected completion of a triple drug combination trial with tuspetinib in newly diagnosed AML patients. Aptose will use the proceeds from such loan for the development of tuspetinib.

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Beyond the $10 million Facility Agreement, Aptose and Hanmi have agreed to negotiate a new tuspetinib co-development collaboration agreement (the "Future Collaboration Agreement’), intended to provide additional funding to accelerate clinical development of tuspetinib. Aptose licensed tuspetinib from Hanmi Pharmaceutical in November 2021.

On August 30, 2024 Amgen (NASDAQ:AMGN) reported that it will present at the 2024 Wells Fargo Healthcare Conference at 9:30 a.m. ET on Thursday, Sept. 5, 2024. Peter Griffith, executive vice president and chief financial officer at Amgen, and Jay Bradner, executive vice president of Research and Development and chief scientific officer at Amgen, will present at the conference (Press release, Amgen, AUG 30, 2024, View Source [SID1234646230]). The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

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The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.