On July 29, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for revumenib for the treatment of adults and pediatric patients with relapsed or refractory (R/R) KMT2Ar acute leukemia (Press release, Syndax, JUL 29, 2024, View Source [SID1234645137]).

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The FDA notified Syndax on July 26, 2024 that they required additional time to conduct a full review of supplemental information provided to the FDA in response to their requests. The submission of additional information to the FDA was determined to constitute a Major Amendment to the NDA and resulted in a standard three-month extension to the original PDUFA action date of September 26, 2024. No additional trials or manufacturing information have been requested by the FDA.

"Revumenib, upon approval, will be the first drug indicated to treat patients with KMT2A-rearranged acute leukemia, a population with significant unmet need," said Michael A. Metzger, Chief Executive Officer. "We are confident that the data from the AUGMENT-101 trial, as well as the additional information provided to the FDA, support approval and continue to demonstrate the meaningful benefit revumenib brings to patients with this devastating disease. We look forward to continuing our engagement with the FDA as they complete their review of the NDA by December 26, 2024."

The NDA for revumenib was granted Priority Review and is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program. The FDA previously granted Breakthrough Therapy, Fast Track and Orphan Drug designations for revumenib.

About Revumenib
Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation for the treatment of AML and ALL by the FDA and for the treatment of AML by the European Commission, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About the Real-Time Oncology Review Program (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

On July 29, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to avutometinib, a RAF/MEK clamp, in combination with defactinib, a selective FAK inhibitor, for the treatment of pancreatic cancer (Press release, Verastem, JUL 29, 2024, View Source [SID1234645138]).

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"At the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting, we reported positive initial interim results from the ongoing RAMP 205 trial evaluating avutometinib and defactinib in combination with standard of care chemotherapy in first-line metastatic pancreatic cancer," said Dan Paterson, president and chief executive officer of Verastem Oncology. "The FDA Orphan Drug Designation for the combination of avutometinib and defactinib for the treatment of pancreatic cancer recognizes the substantial unmet treatment need for patients with pancreatic cancer. We believe avutometinib and defactinib in combination with standard of care has an opportunity to provide a different approach in treating this challenging cancer. We look forward to reporting updated data from across dose cohorts in the ongoing RAMP 205 trial in the first quarter of 2025."

At the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2024, Verastem presented initial interim safety and efficacy results from the ongoing RAMP 205 trial of avutometinib and defactinib in combination with current standard of care gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer. As of the data cutoff of May 14, 2024, 41 patients had been treated in one of four dose cohort regimens and only patients in dose cohort 1 had a minimum follow up of six months. In the dose level 1 cohort, 83% (5/6) of patients achieved a confirmed partial response with more than six months of follow up at the time of data cutoff. One dose-limiting toxicity (DLT) was observed in the dose level 1 cohort, and the dose level was subsequently cleared after additional patients were enrolled. Of the 26 patients in all cohorts who have had the opportunity to have their first scan while on treatment, 21 have experienced a reduction of the change in target lesion sum of diameters. Read the press release here.

FDA Orphan Drug Designation is granted to certain investigational treatments for diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation provides benefits to drug developers, including tax credits for qualified clinical trials, exemptions from certain FDA user fees and the potential for seven years of market exclusivity upon approval.

About Metastatic Pancreatic Cancer

Pancreatic cancer is the third leading cancer in the U.S. and seventh leading cause of cancer-associated mortality worldwide. Metastatic pancreatic cancer is defined as stage IV cancer, where the cancer spreads to other organs. In the U.S., over 30,000 patients are diagnosed with metastatic pancreatic cancer each year, for which the five-year survival rate is 3%. Globally, over 240,000 patients are diagnosed with metastatic pancreatic cancer each year. More than 90% of pancreatic cancers have a KRAS mutation. The standard of care consists of surgery, chemotherapy, radiation or a combination of these approaches.

About RAMP 205 Phase 1/2 Study

RAMP 205 is a multicenter, open-label, single arm Phase 1b/2a study designed to evaluate the safety, tolerability and efficacy of avutometinib and defactinib in combination with standard of care chemotherapy (gemcitabine and Nab-paclitaxel) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma. Part A of the study will evaluate different dose and schedule combinations to determine the recommended Phase 2 dose for expansion into Part B. RAMP 205 is supported by a PanCAN Therapeutic Accelerator Award.

About the Avutometinib and Defactinib Combination

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/MAPK pathway inhibition. In contrast to currently available MEK-only 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 MEK-only inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib, a selective 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. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. RAMP 301 (NCT06072781) is an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed in each of the dose optimization and expansion phases and the low-dose evaluation. Verastem has initiated a rolling NDA submission for avutometinib and defactinib combination in adults with recurrent LGSOC and expects to complete its NDA submission in the second half of 2024 with a potential FDA decision in the first half of 2025.

Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. The RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award.

On July 29, 2024 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, reported participation in two investor conferences in August: BTIG virtual Biotechnology Conference, August 5-6, 2024, and Canaccord Genuity (CG) 44th Annual Growth Conference, August 13-14, 2024 in Boston (Press release, Akebia, JUL 29, 2024, View Source/news-releases/news-release-details/akebia-therapeutics-present-upcoming-investor-conferences-1" target="_blank" title="View Source/news-releases/news-release-details/akebia-therapeutics-present-upcoming-investor-conferences-1" rel="nofollow">View Source [SID1234645139]).

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BTIG Biotechnology Conference
John Butler, Chief Executive Officer, will participate in a fireside chat on Tuesday, August 6, at 8:00 am EST.

CG 44th Annual Growth Conference
Mr. Butler will present on Wednesday, August 14 at 8:30 a.m. EST. A webcast of the presentation can be accessed through the "Investors" section of Akebia’s website at View Source following the conference.

On July 29, 2024 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported a presentation on its ovarian cancer CAR-T therapy clinical trial at the International Gynecologic Cancer Society (IGCS) 2024 Annual Global Meeting being held October 16-18, 2024, in Dublin, Ireland (Press release, Anixa Biosciences, JUL 29, 2024, View Source [SID1234645123]).

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The presentation, titled "Phase I Clinical Trial of Autologous T-cells Genetically Engineered with a Chimeric Receptor to Target the Follicle Stimulating Hormone Receptor (FSHR) in Recurrent Ovarian Cancer (OVCA)," will be presented by the study’s principal investigator, Dr. Robert Wenham, Chair of Gynecologic Oncology at Moffitt Cancer Center, Anixa’s collaboration partner.

About Anixa’s CAR-T Approach (Follicle Stimulating Hormone Receptor-Mediated CAR-T technology)
Anixa’s chimeric antigen receptor T-cell (CAR-T) technology approach is an autologous cell therapy comprised of engineered T-cells that target the follicle stimulating hormone receptor (FSHR). FSHR is found at immunologically relevant levels exclusively on the granulosa cells of the ovaries. Since the target is a hormone (chimeric endocrine) receptor, and the target-binding domain is derived from its natural ligand, this technology is known as CER-T (chimeric endocrine receptor T-cell) therapy, a new type of CAR-T. Anixa’s FSHR-mediated CAR-T technology was developed by Jose R. Conejo-Garcia, M.D., Ph.D., Professor of Immunology in the Department of Integrative Immunobiology at the Duke University School of Medicine. Anixa holds an exclusive world-wide license to the technology from The Wistar Institute.

On July 29, 2024 Akeso (9926.HK) reported that the supplemental biologics license application (sBLA) for its independently developed, world’s first-in-class PD-1/VEGF bispecific antibody drug, 依达方 (generic name: ivonescimab Injection), as a monotherapy for first-line treatment of PD-L1 positive (PD-L1 TPS≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC), has been accepted by the China National Medical Products Administration (NMPA) (Press release, Akeso Biopharma, JUL 29, 2024, View Source [SID1234645140]).

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Ivonescimab is the world’s first bispecific antibody drug approved for the "tumor immunotherapy + anti-angiogenesis" mechanism. The first-line monotherapy treatment of PD-L1 positive (PD-L1 TPS ≥1%) locally advanced or metastatic NSCLC is ivonescimab’s second indication, following its approval for the treatment of EGFR-mutant non-squamous NSCLC that has progressed after EGFR-TKI therapy. Ivonescimab is also expected to become a new standard of care treatment option for both first-line and second-line lung cancer therapy.

This new indication application for ivonescimab is based on the HARMONi-2 (AK112-303) study. The Independent Data Monitoring Committee (IDMC) conducted a pre-specified interim analysis of the HARMONi-2 study, showing highly positive results. In the intent-to-treat (ITT) population, ivonescimab monotherapy significantly prolonged progression-free survival (PFS) compared to pembrolizumab monotherapy, with a hazard ratio (HR) significantly better than expected.

"As a researcher and clinician, we eagerly anticipate ivonescimab becoming the new standard treatment for first-line lung cancer, providing a superior ‘chemotherapy-free’ option for patients," said Professor Zhou Caicun, principal investigator of the HARMONi-2 study and director of the Oncology Department at East Hospital Affiliated To Tongji University. "The success of the HARMONi-2 study underscores the immense value of ivonescimab’s synergistic dual anti-tumor mechanism of ‘tumor immunotherapy + anti-angiogenesis.’"

Professor Zhou also emphasized that clinicians are looking forward to Akeso seizing the opportunity to establish ivonescimab as the new standard treatment for first-line lung cancer. He encouraged continuous exploration of combination therapies and ongoing global upgrades to standard treatment options, aiming to provide patients with better therapeutic choices.

Dr. Michelle Xia, Founder, Chairwoman, President, and CEO of Akeso, said: "We are thrilled that ivonescimab has achieved a significant milestone in first-line lung cancer therapy shortly after its approval for second-line treatment. We sincerely thank all our colleagues at Akeso for their decade-long dedication and craftsmanship, the experts for their meticulous contributions, and all the participants involved in the projects."

According to Dr. Xia, the approval of ivonescimab for second-line lung cancer therapy and its potential as a superior, chemotherapy-free new standard for first-line treatment fills a clinical unmet need in global lung cancer immunotherapy with bispecific antibodies, providing a more effective solution for patients and fulfilling Akeso’s commitment.

Dr. Xia also emphasized that the HARMONi-2 study showcases ivonescimab’s superior efficacy and safety, further solidifying its potential as a cornerstone product in tumor immunotherapy (IO). This includes its broad clinical development value and market prospects when used in combination with ADC drugs or other novel anti-cancer drugs. "We look forward to sharing ivonescimab’s robust clinical research data with global regulatory agencies to achieve worldwide approval and provide more effective solutions for patients around the globe."

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro.1 This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days,1 is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials, HARMONi and HARMONi-3.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.