On June 22, 2023 Kite Pharma, Inc., a Gilead Company (Nasdaq: GILD), reported that the Marketing Authorization in Japan for Yescarta (axicabtagene ciloleucel), a chimeric antigen receptor (CAR) T-cell therapy, has been transferred from Daiichi Sankyo Co., Ltd. to Gilead Sciences K.K., the Japan subsidiary of Gilead Sciences, Inc (Press release, Gilead Sciences, JUN 22, 2023, View Source [SID1234632855]).

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This follows the announcement made by Daiichi Sankyo and Kite Pharma, Inc. in December 2022 about changes to their initial 2017 partnership whereby Daiichi Sankyo obtained the Marketing Authorization for Yescarta. With this completion of the Marketing Authorization transfer, the sales and promotion activities of Yescarta in Japan now will be managed by the Kite Cell Therapy Business Unit of Gilead Sciences K.K.

"As the global leader in cell therapy, we appreciate the opportunity and responsibility of bringing this innovative treatment to as many eligible patients as possible who may benefit," said Cindy Perettie, Executive Vice President and Global Head of Kite. "We are pleased that we are able to fully leverage our manufacturing expertise and commercialization capabilities to meet increasing demand and maximize the potential of this important therapy for patients in Japan."

The first Yescarta treatment center in Japan was authorized in December 2021, and there are now a total of six hospitals in Japan authorized to administer the therapy with many more anticipated by the end of the year. Kite’s manufacturing facility in El Segundo, California, U.S. has been approved by Japanese regulatory authorities to manufacture Yescarta for the Japanese market, and commenced its supply of the product earlier this year.

"We are rapidly building a diverse pipeline in oncology, from antibody-drug conjugates and small molecules to cell therapy-based approaches," said Kennet Brysting, General Manager of Gilead Sciences K.K. "We look forward to advancing new treatments in oncology with the potential to positively impact the lives of people with cancer in Japan."

About YESCARTA

Yescarta (axicabtagene ciloleucel) is a CAR T-cell therapy directed against CD19 (a cell membrane protein), which harnesses a patient’s own immune system to fight cancer. Axicabtagene ciloleucel is made by removing a patient’s T cells from their blood and engineering them in the lab to express chimeric antigen receptors so that they can recognize and destroy cancer cells when they are infused back into the patient’s body. The CAR T-cell therapy is manufactured specifically for each patient and administered only once.

Axicabtagene ciloleucel received Orphan Drug Designation from the Japan Ministry of Health, Labour, and Welfare in 2018 for the treatment of diffuse large B-cell lymphoma (LBCL), primary mediastinal B-cell lymphoma, transformed follicular lymphoma and high-grade B-cell lymphoma. Yescarta was approved in Japan for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphomas, a type of non-Hodgkin lymphoma, who are previously treated with two or more lines of treatment including chemotherapy or an autologous stem cell transplant, in January 2021. In December 2022, Yescarta was approved for the initial treatment of patients with R/R LBCL in Japan.

Yescarta is approved in more than 20 countries, including the U.S., Canada, Europe, Great Britain, Switzerland, Brazil, Singapore, Israel, Japan, and Australia, for patients with certain types of relapsed or refractory B-cell lymphoma. It is developed and manufactured by Kite and commercialized by Kite in the U.S. and outside the U.S. by the respective Gilead affiliate.

Please see full U.S. Prescribing Information, including BOXED WARNING and Medication Guide.

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. (1.1)
Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. (1.1)

Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). (1.2)
For the full European Prescribing Information, please visit: View Source

On June 22, 2023 Tvardi Therapeutics, Inc., a privately held, clinical-stage biopharmaceutical company focused on the development of STAT3 inhibitors, reported that the first patients have been dosed in each arm of its ongoing REVERT LIVER CANCER trial (Press release, Tvardi Therapeutics, JUN 22, 2023, View Source [SID1234632854]). The trial is evaluating safety and clinical activity of TTI-101 as monotherapy and in combination with standard of care therapy in patients with locally advanced or metastatic, and unresectable hepatocellular carcinoma (HCC)

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The REVERT LIVER CANCER trial is currently enrolling HCC patients at top US cancer research institutes and is designed to evaluate TTI-101 across multiple lines of therapy:
• TTI-101 alone for patients previously treated with up to three prior lines of systemic therapy
• TTI-101 in combination with pembrolizumab (Keytruda) for patients previously treated with immunotherapy
• TTI-101 in combination with atezolizumab (Tecentriq) and bevacizumab (Avastin) for treatment naïve patients

Liver cancer is the sixth most commonly diagnosed cancer and the third most common cause of cancer death. HCC is the most common form of liver cancer; however, treatment options for the disease are limited and overall prognosis for survival is poor, with a 5-year survival rate of 18%. TTI-101’s target, STAT3, is a key regulatory protein which plays a critical role in the pathogenesis of HCC by initiating tumorigenesis as well as promoting an immunosuppressive tumor microenvironment. TTI-101 is an orally delivered, small molecule, direct inhibitor of STAT3.

"Enthusiasm for our HCC study continues to expand with recently presented clinical data demonstrating TTI-101 monotherapy has robust efficacy in heavily pretreated patients with HCC, published preclinical work highlighting TTI-101’s synergy with immunotherapy, and the FDA’s Fast-Track Designation for TTI-101 in HCC," said Imran Alibhai, PhD, CEO of Tvardi Therapeutics. "This is the second of three Phase 2 trials Tvardi has initiated to address diseases driven by STAT3."

For more information about the REVERT LIVER CANCER trial currently enrolling at sites throughout the US, please visit ClinicalTrials.gov (NCT05440708).

On June 22, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the first patient has been dosed in a Phase 2a study of its novel and highly selective CDK9 inhibitor, GFH009, in combination with venetoclax and azacitidine (aza/ven) in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML) who did not respond or stopped responding to venetoclax-based therapies (Press release, Sellas Life Sciences, JUN 22, 2023, View Source [SID1234632853]). Topline data is expected during the fourth quarter of this year.

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The Phase 2a clinical trial is an open label, single arm, multi-center study that is designed to evaluate safety, tolerability, and efficacy at two dose levels of GFH009 (once weekly 45 mg or 60 mg) in combination with aza/ven. The study will enroll up to 20 r/r AML patients, 10 patients per dose level, all of whom will receive standard doses of aza/ven after they became unresponsive to venetoclax combinations including aza/ven, with the addition of GFH009. Treatment will continue for as long as there are no dose limiting toxicities and no progression of disease. Bone marrow will be assessed after the first two infusions of GFH009: at day 14 and day 28. Thereafter, bone marrow assessments will be made every 28 days.

In addition to safety and tolerability of GFH009 in combination with aza/ven, the primary endpoints are composite complete response rate (CRc) and duration of response (DOR). Additional endpoints include event free survival (EFS), overall survival (OS), and pharmacokinetic (PK) and pharmacodynamic (PD) assessments.

"We are excited to advance GFH009 to the next phase of clinical development, which we believe holds great promise for patients who continue to suffer with advanced and difficult to treat AML," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "As far as we know, GFH009 is the only CDK9 inhibitor in development that, as a single agent, has shown such unique and very encouraging clinical data which is the reason our hematology experts see high promise in this Phase 2a study. Treatment of the first patient in this study represents successful completion of one of several near-term potential value enhancing milestones."

The Phase 2a study builds on strong data from the group of patients with AML in the Phase 1 study which demonstrated a favorable safety profile with strong early efficacy signals and evidence of anti-tumor activity increasing with higher doses. Durable complete remission (CR) with no minimal residual disease (MRD) was observed in one patient who had failed prior aza/ven therapy and is now lasting for more than six months which, to the Company’s knowledge, is the first CR ever reported for a CDK9 inhibitor in AML. No dose-limiting toxicities were observed at any level, and MCL1 and MYC biomarkers decreased in 97% of patients. Full Phase 1 AML data is expected be presented at a major medical conference in the fourth quarter of 2023.

Based on preclinical results showing synergy between GFH009 and venetoclax, along with the topline Phase 1 data in patients with AML, SELLAS believes that GFH009 has potential to both improve venetoclax effectiveness and convert resistance to venetoclax into a response which, given its high selectivity and high therapeutic index as well as favorable safety profile, could differentiate it from other CDK9 inhibitors currently in development. Strong synergy with venetoclax could also allow it to improve patient response to the current standard of care.

GFH009 leads to suppression of MCL1 expression. As almost all AML patients have heterogenous cancer cells, some cells will depend mostly on BCL2 and will be killed by venetoclax, some will depend on MCL1 and will potentially be killed by GFH009, and some will depend on both BCL2 and MCL1 and the two-fold assault by both anti-apoptotic agents at the same time. In this Phase 2a study, the addition of azacitidine also allows for a NOXA release enhancement, thus increasing pro-apoptotic effect, a triple hit which may potentially increase the response rates in relapse/refractory AML patients.

The Company recently held an expert panel discussion with hematology-oncology specialists who discussed the potential for GFH009 to address unmet medical needs for patients with relapsed and/or refractory AML.

On June 22, 2023 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported pelareorep has been selected for inclusion as a new investigational treatment in Precision PromiseSM, an innovative adaptive Phase 3 clinical trial (Press release, Oncolytics Biotech, JUN 22, 2023, View Source [SID1234632851]). The Precision Promise study is designed to evaluate pelareorep in combination with a checkpoint inhibitor and the chemotherapeutic agents gemcitabine and nab-paclitaxel. If successful, the clinical study is expected to support approval of the studied combination as a treatment for first-line metastatic pancreatic ductal adenocarcinoma (PDAC).

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Precision Promise has a primary endpoint of overall survival and can include multiple investigational treatments as well as control arms evaluating: (1) gemcitabine plus nab-paclitaxel or (2) mFOLFIRINOX. Each investigational therapy is subject to pre-specified interim analyses prior to proceeding to the registrational portion of the trial. This design, which was developed with guidance from the U.S. Food and Drug Administration, minimizes the number of participants needed to generate licensure-enabling data, thereby accelerating late-stage development by up to two years and reducing costs compared to non-platform trials.

"We are delighted at being selected by the Precision Promise panel of experts," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech. "Our next step is to engage with stakeholders to finalize the protocol for Precision Promise’s pelareorep-containing investigational treatment so that we can enter into this study. We are thrilled to have the opportunity to leverage Precision Promise, which we expect will allow us to reduce the time and costs needed to reach a potential approval."

Julie Fleshman, JD, MBA, President and CEO of PanCAN commented, "With a five-year survival rate of 12%, pancreatic cancer patients cannot afford to wait for new treatment options. This urgent unmet need was the driving inspiration behind the Precision Promise platform trial, which was designed specifically to identify, accelerate, and de-risk the development of promising pancreatic cancer treatments. We are thrilled to be bringing pelareorep into Precision Promise as a new investigational therapy to study against the current standard of care."

Dr. Thomas Heineman, Chief Medical Officer of Oncolytics Biotech, commented, "Prior trials in pancreatic cancer show pelareorep-based combinations outperforming historical controls on key metrics such as one and two-year survival and objective response rate. In addition, mechanistic data from these studies highlight how pelareorep’s immunologic mechanism of action allows it to synergize with chemotherapy and checkpoint inhibition in this indication. I look forward to working with the Precision Promise team of investigators to seek to confirm the therapeutic value of pelareorep in a randomized setting so that we can potentially provide pancreatic cancer patients with a new treatment option."

Oncolytics expects to finalize the definitive agreements within the next 90 days and open the Precision Promise investigational treatment of pelareorep, checkpoint inhibitor, gemcitabine, and nab-paclitaxel in early 2024.

Pelareorep in Pancreatic Cancer
Pelareorep’s inclusion in Precision Promise is supported by prior clinical data in pancreatic cancer that suggests it synergizes with checkpoint inhibition and chemotherapy. These prior data include phase 1/2 results showing a 69% objective response rate (ORR, n = 13) in a cohort of first-line advanced/metastatic PDAC patients treated with pelareorep combined with atezolizumab, gemcitabine, and nab-paclitaxel.

This compares to an average ORR of ~25% reported in relevant historical control trials1-4. In addition, a phase 2 study of pelareorep plus gemcitabine that included 29 evaluable chemotherapy-naïve pancreatic cancer patients showed a median overall survival (mOS) of 10.2 months and a one-year survival rate of 45%, compared to historical control trials showing mOS of approximately 6.7 months and one-year survival rates of approximately 20 – 22%, respectively1,5-6. A subsequent phase 2 study of pelareorep plus checkpoint inhibition without chemotherapy in pancreatic cancer patients who progressed after first-line treatment showed a 42% disease control rate (n = 12), post-treatment increases in PD-L1+ cells, and a correlation between clinical response and increased activation of anti-cancer CD8+ T cells.

On June 22, 2023 Nerviano Medical Sciences Srl (NMS), a member of NMS Group and a clinical stage company discovering and developing innovative therapies for the treatment of cancer, reported that the FDA Clearance of Investigational New Drug (IND) Application for NMS-03592088 (NMS-088), a novel, potent FLT3 inhibitor (Press release, Nerviano Medical Sciences, JUN 22, 2023, View Source [SID1234632850]).

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NMS-088 is poised to transform the landscape of FLT3 inhibitor by addressing a critical unmet medical need. It offers a breakthrough solution that has the potential to improve patient outcomes and significantly enhance quality of life. The IND approval enables NMS to advance to the next stage of clinical development, initiating critical trials to evaluate the safety, efficacy, and therapeutic potential of this next-generation FLT3 inhibitor.

"We are incredibly proud of this IND approval, which underscores our commitment to innovation and improving patient care," said Lisa Mahnke, MD, PhD, CMO of NMS. "This milestone is a testament to the hard work, dedication, and scientific expertise of our talented team. We remain steadfast in our mission to bring forth groundbreaking solutions that make a real difference in the lives of patients."

The forthcoming clinical trial will be conducted in partnership with renowned medical centers and institutions as part of NMS’s global program. This collaborative approach ensures the rigorous evaluation and comprehensive assessment of NMS-088’s safety, efficacy, and potential benefits across diverse patient populations.

As NMS moves forward with clinical trials, the company remains committed to adhering to the highest ethical and regulatory standards. Patient safety and well-being will remain paramount throughout the entire process, with careful monitoring and adherence to strict protocols.

About Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a rapidly progressing hematologic malignancy that most frequently develops in older adults. FLT3 mutations occur in approximately 30% of AML patients and are associated with aggressive disease, higher relapse rates and worse survival. Despite the approval of FLT3 inhibitors midostaurin and gilteritinib the prognosis of patients with relapsed or refractory disease is poor.

About NMS-03592088
NMS-03592088 is a novel, potent inhibitor of FLT3, KIT and CSF1R, all relevant targets in AML. NMS-03592088 showed superior preclinical activity compared with approved FLT3 inhibitors in different FLT3-driven models. In addition, NMS-03592088 is active on FLT3 gatekeeper mutation F691L causing resistance to first generation FLT3 inhibitors. NMS-03592088 is being developed in AML with two studies currently recruiting (MKIA-088-001 and MKIA-088-002)