On July 6, 2023 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for the company’s Biologics License Application (BLA) for zolbetuximab, a first-in-class investigational Claudin 18.2 (CLDN18.2)-targeted monoclonal antibody, for first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive (Press release, Astellas, JUL 6, 2023, View Source [SID1234633047]). If approved, zolbetuximab would be the first CLDN18.2-targeted therapy available in the U.S. for these patients.

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Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of January 12, 2024. The FDA reviewed the application under its Real-Time Oncology Review (RTOR) program, which aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.

In the U.S., it is estimated that 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023.1 Early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, often resulting in gastric cancer diagnosis in the advanced or metastatic stage, or once it has spread from the tumor’s origin to other body tissues or organs.2 The five-year relative survival rate for patients at the metastatic stage is 6.6%.1

"Astellas is committed to bringing innovative therapies to patients with hard-to-treat cancers, including gastric cancer. While rare in the U.S., gastric cancer can be deadly when diagnosed in the late stages," said Moitreyee Chatterjee-Kishore, PhD, MBA, Senior Vice President and Head of Immuno-Oncology Development, Astellas. "The FDA’s acceptance of the Biologics License Application filing and Priority Review designation for zolbetuximab confirms the urgent therapeutic need and brings us one step closer to delivering on this commitment to patients, families and caregivers."

The BLA is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6. The GLOW study evaluated zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX.

In both SPOTLIGHT and GLOW, approximately 38% of patients screened for the trials had tumors that were CLDN18.2-positive (≥75% of tumor cells with moderate-to-strong membranous CLDN18 staining intensity), as determined by a validated immunohistochemistry assay.3,4

Astellas has already reflected the impact from this acceptance in its financial forecast of the current fiscal year ending March 31, 2024.

About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer
Gastric cancer, also commonly known as stomach cancer, is the fifth most commonly diagnosed cancer worldwide.5 In the U.S., it is estimated that 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023.1 Signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, diarrhea or constipation, bloating of the stomach after meals, loss of appetite, and sensation of food getting stuck in the throat while eating.2 Signs of more advanced gastric cancer can include unexplained weight loss, weakness and fatigue, and vomiting blood or having blood in the stool.6 Risk factors associated with gastric cancer can include older age, male gender, family history, H. pylori infection, smoking and gastroesophageal reflux disease (GERD).2,7 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor’s origin to other body tissues or organs.2 The five-year relative survival rate for patients at the metastatic stage is 6.6%.1 Gastroesophageal junction (GEJ) adenocarcinoma is a cancer that starts at the area where the esophagus joins the stomach.8

About Zolbetuximab
Zolbetuximab is an investigational, first-in-class chimeric IgG1 monoclonal antibody (mAb) that targets and binds to Claudin 18.2 (CLDN18.2), a transmembrane protein. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).9 Zolbetuximab has not been approved by any regulatory bodies for the treatment of patients with gastric and GEJ cancers, and there is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated.

INVESTIGATIONAL STUDIES

About SPOTLIGHT Phase 3 Clinical Trial
SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2-positive. The study enrolled 565 patients at 215 study locations in the U.S., Canada, United Kingdom, Australia, Europe, South America and Asia. The primary endpoint is progression-free survival (PFS) in participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability and quality-of-life parameters.

Data from the SPOTLIGHT clinical trial were presented during the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium in an oral presentation on January 19 and were subsequently published in The Lancet on April 14.3

For more information, please visit clinicaltrials.gov under Identifier NCT03504397.

About GLOW Phase 3 Clinical Trial
GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2-positive. The study enrolled 507 patients at 166 study locations in the U.S., Canada, United Kingdom, Europe, South America and Asia. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include OS, ORR, DOR, safety and tolerability and quality-of-life parameters.

Data from the GLOW study were initially presented at the March 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series with an updated oral presentation at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting on June 3.4

For more information, please visit clinicaltrials.gov under Identifier NCT03653507.

Investigational Pipeline in CLDN18.2
An expanded Phase 2 trial in metastatic pancreatic adenocarcinoma is in progress. The trial is a randomized, multi-center, open-label study, evaluating the safety and efficacy of investigational zolbetuximab in combination with gemcitabine plus nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic adenocarcinoma with CLDN18.2-positive tumors (defined as ≥75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163.

In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1 trial for people with gastric, GEJ or pancreatic adenocarcinoma. The safety and efficacy of the agent under investigation have not been established for the uses being considered. For more information, please visit clinicaltrials.gov under Identifier NCT05365581.

There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated.

On July 5, 2023 Boostimmune reported on the 5th that ‘BIO-101’, a translationally-controlled tumor protein (TCTP) antibody with a mechanism targeting immunosuppressive cells, was selected as a candidate material stage support project by the National New Drug Development Agency (KDDF) (Press release, Boostimmune, JUL 5, 2023, View Source [SID1234634477]).

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According to this task selection, BoostImmune will receive R&D support of 900 million won (based on government subsidies) over the next two years with the goal of deriving preclinical candidate substances.

TCTP is known to originally function as a cytosolic protein, but when it is released to the outside through apoptosis such as necrosis of tumor cells, myeloid derived suppressor cells (MDSC) are recruited within the tumor. The company judges that it contributes to cancer growth by inducing an immunosuppressive tumor microenvironment (TME). Conversely, when TCTP was inhibited by a knock-out mouse model or drug, it was observed that the ratio of MDSC in tumors decreased and cancer growth was suppressed through TLR2.

Immunologist Tadatsugu Taniguchi, emeritus professor at the University of Tokyo, who expressed interleukin (IL-2), interferon beta (IFN-β), HMGB1, and IRF, identified the possibility of TCTP as a drug target, and in 2021, Nature Immun Two papers have been published in Nology (doi: 10.1038/s41590-021-00967-5, 10.1038/s41590-021-00986-2).

Kwang-Hee Lee, CEO of BoostImmune, said, "We plan to accelerate the development of TCTP target antibodies using the selection of this national new drug development project support project as a stepping stone to confirm preclinical candidate materials in a short time."

Boost Immune plans to jointly research and develop blood biomarkers for the TCTP task in cooperation with the oncology research team at Asan Medical Center in Seoul.

Boost Immune is a biotech company that develops new anti-cancer drugs co-founded in 2021 by CEO Lee Kwang-hee and Professor Tadatsugu Taniguchi. Boost Immune is conducting tasks such as immuno-oncology drugs targeting myeloid cells, antibody drug conjugates (ADC), and immune-activating antibodies (ISAC).

On July 5, 2023 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immune-oncology technologies addressing hard to treat oncology indications, reported that Jeffrey Eisenberg, Chief Executive Officer and Curtis A. Lockshin, PhD, Chief Scientific Officer of Xenetic Biosciences will participate in the Virtual Investor Summer Spotlight Series on Wednesday, July 12, 2023 at 10:00 AM ET (Press release, Xenetic Biosciences, JUL 5, 2023, View Source [SID1234633072]).

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A live video webcast of the presentation will be available on the Events page in the Investors section of the Company’s website (www.XeneticBio.com). A webcast replay will be available two hours following the live presentation and will be accessible for 90 days.

On July 5, 2023 Oncoinvent AS, a clinical stage company advancing alpha emitter therapy to treat cancers, reported the appointment of Anders Månsson as Chief Executive Officer (CEO), effective September 1st, 2023 (Press release, Oncoinvent, JUL 5, 2023, View Source [SID1234633071]).

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"Following a comprehensive search process, it was determined that Anders was the preferred candidate to lead Oncoinvent forward. Anders’s extensive leadership experience in various positions within the pharmaceutical industry, including large multinationals, start-ups, and companies listed on the stock exchange, will add immeasurable value to Oncoinvent, as we advance towards providing best in class therapies to patients in serious need," said Roy Larsen, Ph.D., Chairman of Oncoinvent’s Board of Directors. "On behalf of the Board and everyone at Oncoinvent, I would like to thank Jan Alfheim for his leadership and contributions to our company. We appreciate his commitment to ensuring a seamless transition and we wish him all the best."

"I am honored to join Oncoinvent at this pivotal time in the company’s development, specifically with the continued very promising advancement of Radspherin. I look forward to collaborating with the Oncoinvent board and management team to develop novel and unique radiopharmaceutical treatments for peritoneal carcinomatosis originating from colorectal and ovarian cancers," said Anders Månsson, newly appointed Chief Executive Officer of Oncoinvent.

Anders has nearly three decades of extensive experience in strategic leadership, business development, and commercialization in the pharmaceutical industry. He has most recently served as CEO of LIDDS, a technology platform company specialising in depot formulations for intra-tumoral injections with its NanoZolid technology. Prior to LIDDS, Anders served as CEO of RhoVac (now CHOSA Oncology AB), a biopharmaceutical company developing immuno-therapeutic treatments for metastatic cancers. Before this, he was CEO and served on the board of directors at Amniotics AB, a clinical stage biotechnology company developing therapies based on stem cells.

Anders has also held several senior management roles in business development in multinational companies such as LEO Pharma and Ferring Pharmaceuticals, spanning close to two decades. Anders currently serves on the board of directors for EQL Pharma AB and Immetric AB, and he has previously held several other board director and advisor positions. Anders holds an M.B.A. from Business School Lausanne and a bachelor’s degree in Business and Economics from Lund University.

On July 5, 2023 Verastem Oncology (Nasdaq: VSTM) (the "Company"), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that it has finalized with the U.S. Food and Drug Administration (FDA) the design of its confirmatory Phase 3 trial to evaluate the combination of avutometinib and defactinib for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) (Press release, Verastem, JUL 5, 2023, View Source [SID1234633069]). RAMP 301, a randomized global confirmatory trial, will evaluate the efficacy and safety of avutometinib and defactinib versus standard of care (SOC) chemotherapy and hormonal therapy in patients with recurrent LGSOC. RAMP 301 is expected to begin enrollment in the second half of this year.

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RAMP 301 is the follow-up confirmatory study for full approval in recurrent LGSOC. The Company intends to file for Accelerated FDA Approval for the combination of avutometinib and defactinib based on mature data from the Company’s Phase 2 registration-directed RAMP 201, together with the results of the investigator-initiated FRAME trial. The Company recently reported results of Part A of RAMP 201 including confirmed objective response rates (ORR) by blinded independent central review of 45% (13/29; 95% CI: 26%,64%) with a tolerable safety profile.​

"We are pleased to partner with GOG and ENGOT and announce the final study design for RAMP 301, another important milestone in advancing our avutometinib and defactinib program and bringing us closer to addressing the unmet needs of patients living with LGSOC," said Brian Stuglik, Chief Executive Officer, Verastem Oncology. "This trial builds on the encouraging results of Part A of the RAMP 201 trial and our breakthrough therapy designation, after one or more prior lines of therapy, and we are committed to bringing the first FDA-approved therapy for LGSOC to patients as quickly as possible."

RAMP 301 is an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) sponsored by Verastem Oncology. The trial will enroll approximately 270 patients who will be randomized to either the combination of avutometinib and defactinib or SOC chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole). Selection of the SOC regimen will be based on the preference of the investigator. The primary endpoint is progression free survival (PFS) by Blinded Independent Central Review. Secondary endpoints include overall response rates, duration of response​, disease control rate, safety and tolerability, patient reported outcomes and overall survival. The RAMP 301 trial will be led globally and in the U.S. by Rachel Grisham, MD, Section Head, Ovarian Cancer and Director, Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center in Westchester, NY. Susana Banerjee, MBBS, MA PhD, FRCP, global and lead investigator of the RAMP 201 study, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London, will be leading the RAMP 301 trial in Europe.

Financial Update

As of March 31, 2023, Verastem Oncology had cash and short-term investments of $111.2 million. With the net proceeds from the underwritten public offering completed in June 2023 of approximately $91.5 million after deducting estimated underwriting discounts and commissions and estimated offering expenses, the Company has pro-forma cash and short-term investments as of March 31, 2023 of approximately $202.7 million.

Recent historical operating expenses have ranged between $16.0M — $20.0M per quarter, which the Company does not anticipate will change significantly in the near term as the RAMP 301 trial commences.

Dr. Banerjee and Dr. Grisham have consulting relationships with Verastem Oncology.

About Avutometinib (VS-6766)

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Avutometinib is currently in late-stage development.

In contrast to other MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 201 is a registration-directed trial of avutometinib alone and in combination with defactinib in patients with recurrent LGSOC. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.