On October 31, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that the U.S. Food and Drug Administration ("FDA") lifted the clinical holds on clinical trials of zevorcabtagene autoleucel (zevor-cel, CT053, an autologous CAR-T product against BCMA), satricabtagene autoleucel (satri-cel, CT041, an autologous CAR-T product against Claudin18.2), and CT071 (an autologous CAR-T product against GPRC5D) in the United States (Press release, Carsgen Therapeutics, OCT 31, 2024, View Source [SID1234647613]).

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On October 31, 2024 Akeso Biopharma (9926.HK) reported the successful enrollment of the first patient in the HARMONi-GI-01/AK112-309 study, a randomized, controlled, multicenter Phase III registration study for biliary track tumor (Press release, Akeso Biopharma, OCT 31, 2024, View Source [SID1234647612]). This trial is designed to compare the ivonescimab combined regimen, a PD-1/VEGF bispecific antibody internally developed by Akeso, with the durvalumab (PD-L1) combined regimen for the first-line treatment of advanced biliary tract cancers (BTC). The primary endpoint of the AK112-309 study is overall survival (OS).

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This study represents the sixth registrational Phase III clinical trial featuring ivonescimab, with a PD-1/L1 monoclonal antibody as the comparator. It underscores Akeso’s commitment to advancing the field of cancer immunotherapy and establishing a global standard of care for cancer treatment. Furthermore, it highlights Akeso’s capability to maximize the number of cancer patients globally that can benefit from its product portfolio through a strategic approach to clinical development.

Previously, the positive results from a Phase II clinical study of ivonescimab in combination with chemotherapy for the first-line treatment of BTC were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The findings demonstrated that the ivonescimab regimen exhibits significant antitumor activity and a good safety profile in BTC.

The objective response rate (ORR), as assessed by investigators, was 63.6%, with an ORR of 77.8% specifically for patients with gallbladder cancer. The disease control rate (DCR) reached 100%.
The median progression-free survival (PFS) was 8.5 months, with a 6-month PFS rate of 84.4%.
Furthermore, the median overall survival (OS) was 16.8 months, with a 9-month OS rate of 81.8%. Notably, patients with gallbladder cancer exhibited a median OS of 16.8 months.
At the time of the analysis, the median follow-up time was 13.8 months. The study included patients with a median age of 65.3 years, of whom 81.8% had an ECOG performance status of 1. All enrolled patients are presented with unresectable tumors, and 40.9% were diagnosed with gallbladder cancer.

Biliary tract malignancies, originating from the bile ducts and gallbladder, represent a group of highly heterogeneous cancers associated with a poor prognosis. At the time of diagnosis, approximately 50% of biliary tract cancer patients are already in advanced stages, often with a survival period of less than one year. Although PD-1/L1 inhibitors in combination with chemotherapy have been approved as a first-line treatment for advanced biliary tract cancer, the overall survival benefit has been limited, particularly for patients with gallbladder cancer. The initial positive clinical data from the ivonescimab regimen indicates a possible advancement in the therapeutic landscape for these challenging malignancies.

About Ivonescimab (AK112/SMT112)

Ivonescimab is a novel global first-in-class PD-1/VEGF bi-specific immunotherapy drug independently developed by Akeso. Ivonescimab is known as SMT112 in Summit Therapeutics’s license territories, including the United States, Canada, Europe, Japan, Central America, South America, the Middle East and Africa. Ivonescimab was granted marketing approval by NMPA for the treatment of EGFR mutated locally advanced or metastatic non-squamous NSCLC patients who have progressed after EGFR TKI treatment. Currently, ivonescimab’s first indication has been approved in China, and Akeso is conducting 6 registrational trials versus anti-PD-1/L1 therapeutics. Akeso is also conducting multiple clinical trials of ivonescimab covering 17 indications including gastrointestinal cancer, hepatocellular carcinoma and colorectal cancer.

On October 31, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that the Company has completed its rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the investigational and potential first-in-class combination of avutometinib, an oral RAF/MEK clamp, and defactinib, an oral selective FAK inhibitor, for adults with recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC), who received at least one prior systemic therapy (Press release, Chugai, OCT 31, 2024, View Source;category= [SID1234647611]).

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There are currently no FDA-approved treatments specifically for LGSOC, a rare and distinct ovarian cancer that differs from high-grade serous ovarian cancer in both its biology and behavior. Verastem submitted the NDA under the FDA’s Accelerated Approval pathway and requested a Priority Review based on the combination’s potential to address significant unmet medical need among patients with recurrent LGSOC. If granted, the FDA review will be completed within six months following the 60-day filing period. If approved, Verastem expects that avutometinib plus defactinib will be the first-ever FDA-approved treatment specifically for adult patients in the United States with recurrent KRAS mutant LGSOC.

"We believe that avutometinib in combination with defactinib has the potential to change the treatment paradigm for patients with recurrent KRAS mutant low-grade serous ovarian cancer," said Dan Paterson, president and chief executive officer of Verastem Oncology. "Completing our NDA submission is a significant milestone not only for Verastem as we plan for potential FDA approval in mid-2025, but also for patients as there are no FDA-approved treatments specifically for this rare ovarian cancer."

The Company initiated the rolling NDA submission in May 2024 after reviewing preliminary data with the FDA. Updated results from the Phase 2 registration-directed RAMP 201 study were presented in a late-breaking oral plenary presentation at the International Gynecologic Cancer Society 2024 Annual Meeting and demonstrated in patients with KRAS mutant LGSOC, a confirmed overall response rate (ORR) of 44%, a median progression free survival (PFS) of 22 months, and a disease control rate at 6 months of 70%. The updated data continue to demonstrate avutometinib in combination with defactinib is generally well-tolerated, with a 10% discontinuation rate due to adverse events (AEs) across all patients (both KRAS mutant and KRAS wild-type). The NDA submission also includes supportive data from the FRAME Phase 1 trial, the first study conducted with the combination in recurrent LGSOC.

The FDA previously granted Breakthrough Therapy Designation for avutometinib plus defactinib for the treatment of patients with recurrent LGSOC 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.

The Company is currently enrolling patients with recurrent LGSOC regardless of KRAS mutation status for RAMP 301, an international Phase 3 trial, which will serve as a confirmatory study for the initial indication and has potential to support an expanded indication regardless of KRAS mutation status.

About RAMP 201

RAMP 201 (ENGOTov60/GOG3052) is an adaptive, two-part multicenter, parallel cohort, randomized, open-label trial to evaluate the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer. The first part of the study (Part A) determined the selection of the go forward regimen, which was the combination of avutometinib and defactinib versus avutometinib alone, based on overall response rates. The expansion phases of the trial (Parts B and C) are evaluating the safety and efficacy of the go forward regimen of avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily. The Part D portion of the trial is evaluating a low dose of avutometinib in combination with defactinib to inform individualized dose reduction.

About Low-Grade Serous Ovarian Cancer (LGSOC)

LGSOC is a rare ovarian cancer that is insidious, persistent and ultimately fatal. LGSOC is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and 80,000 worldwide are living with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival of approximately ten years. The majority of patients report a negative impact of LGSOC on their mental and physical health, fertility, and long-term quality of life. The current standard of care for this disease includes hormone therapy and chemotherapy, but there are no treatments specifically approved by the U.S. Food and Drug Administration to treat LGSOC.

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.

Verastem Oncology is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. Verastem is currently enrolling patients and activating sites for RAMP 301 (NCT06072781) an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib, a selective FAK inhibitor, versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (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 for the RAMP 201 trial.

Verastem completed its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for the investigational combination of avutometinib and defactinib in adults with recurrent KRAS mutant LGSOC who received at least one prior systemic therapy in October 2024, with a potential FDA decision mid-2025. The FDA granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib for the treatment of patients with recurrent LGSOC 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 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. FDA granted Orphan Drug Designation to avutometinib and defactinib combination for the treatment of pancreatic cancer.

On October 31, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported financial results for the third quarter and provided a business update (Press release, Merus, OCT 31, 2024, View Source [SID1234647610]).

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"I’m encouraged by our continued operational effectiveness, with phase 3 trials accelerating for petosemtamab in both 1L and 2/3L recurrent/metastatic head and neck cancer. I believe petosemtamab has the potential to offer both a first and best in class chemo-free option for these patients," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "We look forward to providing an update on petosemtamab’s monotherapy efficacy, duration and safety in 2L+ HNSCC this December at ESMO (Free ESMO Whitepaper) Asia and, in the near future, providing more information on a number of important potential near term catalysts in 2025."

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors
LiGeR-HN1 phase 3 trial in 1L head and neck squamous cell carcinoma (HNSCC) and LiGeR-HN2 phase 3 trial in 2/3L HNSCC enrolling; phase 2 trial in 2L metastatic colorectal cancer (mCRC) enrolling; clinical data update on 2L+ HNSCC planned for ESMO (Free ESMO Whitepaper) Asia in December 2024

In the third quarter, Merus announced the first patient was dosed in LiGeR-HN1, a phase 3 trial evaluating the efficacy and safety of petosemtamab in combination with pembrolizumab in 1L HNSCC expressing PD-L1 (CPS≥1) compared to pembrolizumab. In this trial, patients will be randomized to petosemtamab plus pembrolizumab or pembrolizumab monotherapy. This was detailed in our press release, Merus Announces First Patient Dosed in LiGeR-HN1, a Phase 3 Trial Evaluating Petosemtamab in Combination with Pembrolizumab in 1L r/m HNSCC (September 30, 2024).

Merus provided an interim clinical update on petosemtamab with pembrolizumab in 1L r/m HNSCC at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024, demonstrating a 67% response rate among 24 evaluable patients. The oral presentation was detailed in our press release, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC (May 28, 2024).

Merus also provided an interim clinical update on petosemtamab monotherapy in 2L+ HNSCC at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, demonstrating a 37% response rate among 43 evaluable patients. The oral presentation was detailed in our press release (April 17, 2023). Merus plans to provide updated efficacy, durability and safety data of this cohort along with clinical data from the dose optimization cohort evaluating petosemtamab monotherapy 1500 or 1100 mg dose levels in 2L+HNSCC. This was detailed in our press release, Merus Announces Abstract Accepted for Presentation at the ESMO (Free ESMO Whitepaper) Asia Congress 2024 (September 17, 2024).

Merus believes a randomized registration trial in HNSCC with an overall response rate endpoint could potentially support accelerated approval and the overall survival results from the same study could potentially verify its clinical benefit to support regular approval.

In the third quarter, Merus announced the first patient was dosed in a phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 2L mCRC. This was detailed in our press release, Merus Announces First Patient Dosed in Phase 2 Trial of Petosemtamab in 2L CRC (July 8, 2024).

Zenocutuzumab (Zeno or MCLA-128: HER2 x HER3 Biclonics): NRG1 fusion-positive (NRG1+) lung, pancreatic and other solid tumors
Zeno BLA for treatment of NRG1+ non-small cell lung cancer (NSCLC) and pancreatic cancer (PDAC) accepted for priority review by the FDA

The FDA has accepted for priority review a Biologics License Application (BLA) for the bispecific antibody Zeno in patients with NRG1+ NSCLC and PDAC cancer. This acceptance was detailed in our press release Merus Announces U.S. FDA Acceptance and Priority Review of Biologics License Application for Zeno for the Treatment of NRG1+ NSCLC and PDAC (May 6, 2024).

Merus believes that obtaining a commercialization partnership agreement is an important step in bringing Zeno to patients with NRG1+ cancer, if approved.

MCLA-129 (EGFR x c-MET Biclonics): Solid Tumors
Investigation of MCLA-129 is ongoing in METex14 NSCLC; phase 2 trial in combination with chemotherapy in 2L+ EGFR mutant (EGFRm) NSCLC enrolling

In the third quarter, Merus announced the first patients were dosed in the phase 2 trial evaluating MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC, with a cohort receiving MCLA-129 and paclitaxel and carboplatin, and another cohort receiving MCLA-129 and docetaxel. We also remain interested in partnering MCLA-129 to sufficiently resource the development of MCLA-129 and the potential benefit it may have for patients.

MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains global rights outside of China.

MCLA-145 (CD137 x PD-L1 Biclonics): Solid Tumors

Investigation continues of the phase 1 trial of MCLA-145 in combination with pembrolizumab

Collaborations

Incyte Corporation
Since 2017, Merus has been working with Incyte Corporation (Incyte) under a global collaboration and license agreement focused on the research, discovery and development of bispecific antibodies utilizing Merus’ proprietary Biclonics technology platform. For each program under the collaboration, Merus receives reimbursement for research activities and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved.

Eli Lilly and Company
In January 2021, Merus and Eli Lilly and Company (Lilly) announced a research collaboration and exclusive license agreement to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies utilizing Merus’ Biclonics platform and proprietary CD3 panel along with the scientific and rational drug design expertise of Lilly. The collaboration is progressing well with three programs ongoing at various stages of preclinical development.

Gilead Sciences
In March 2024, Merus and Gilead Sciences announced a collaboration to discover novel antibody based trispecific T-cell engagers using Merus’ patented Triclonics platform. Under the terms of the agreement, Merus will lead early-stage research activities for two programs, with an option to pursue a third. Gilead will have the right to exclusively license programs developed under the collaboration after the completion of select research activities. If Gilead exercises its option to license any such program from the collaboration, Gilead will be responsible for additional research, development and commercialization activities for such program. Merus received an equity investment by Gilead of $25 million in Merus common shares and an upfront payment of $56 million.

Ono Pharmaceutical
In 2018, the Company granted Ono Pharmaceutical Co., Ltd. (Ono) an exclusive, worldwide, royalty-bearing license, with the right to sublicense, research, test, make, use and market a limited number of bispecific antibody candidates based on Merus’ Biclonics technology platform directed to an undisclosed target combination. During the third quarter of 2024, Merus achieved and received a milestone payment based on the filing of an Investigational New Drug (IND) application in Japan.

Cash Runway, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2028

As of September 30, 2024, Merus had $782.9 million cash, cash equivalents and marketable securities. Based on the Company’s current operating plan, the existing cash, cash equivalents and marketable securities are expected to fund Merus’ operations into 2028.

Third Quarter 2024 Financial Results

Collaboration revenue for the three months ended September 30, 2024 increased by $0.8 million as compared to the three months ended September 30, 2023, primarily as a result of increases in amortization of upfront deferred revenue. The change in exchange rates did not significantly impact collaboration revenue.

Research and development expense for the three months ended September 30, 2024 increased by $26.5 million as compared to the three months ended September 30, 2023, primarily as a result of increases in external clinical services and drug manufacturing expenses.

General and administrative expense for the three months ended September 30, 2024 increased by $8.2 million as compared to the three months ended September 30, 2023, primarily as a result of increases in personnel related expenses, facilities, depreciation expense and consulting expenses.

Collaboration revenue for the nine months ended September 30, 2024 decreased by $8.0 million as compared to the nine months ended September 30, 2023, primarily as a result of decreases in milestone revenue and amortization of deferred revenue.

Research and development expense for the nine months ended September 30, 2024 increased by $51.0 million as compared to the nine months ended September 30, 2023, primarily as a result of increases in external clinical services and drug manufacturing expenses.

General and administrative expense for the nine months ended September 30, 2024 increased by $15.5 million as compared to the nine months ended September 30, 2023, primarily as a result of increases in personnel related expenses and consulting expenses.

Other income (loss), net consists of interest earned and fees paid on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange (losses) gains on our foreign denominated cash, cash equivalents and marketable securities. Other gains or losses relate to the issuance and settlement of financial instruments.

On October 31, 2024 HOOKIPA Pharma Inc. (NASDAQ: HOOK) ("HOOKIPA" or the "Company"), a clinical-stage biopharmaceutical company developing next generation immunotherapeutics for the treatment of cancer and serious infectious diseases, reported that updated Phase 2 data for eseba-vec (HB200) plus pembrolizumab in first-line recurrent/metastatic HPV16-positive head and neck cancer will be presented as a late-breaking poster presentation at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2024), taking place in Houston, Texas from November 8-10, 2024 (Press release, Hookipa Pharma, OCT 31, 2024, View Source [SID1234647609]).

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The poster will be presented by Alan Ho, MD, PhD, Chief of the Head and Neck Oncology Service at Memorial Sloan Cancer Center (MSKCC), a clinical collaborator of HOOKIPA.

Details of the poster presentation are:

Abstract Title: Eseba-vec (HB-200) plus pembrolizumab as first-line treatment of recurrent/metastatic HPV16-positive head and neck cancer: updated results in PD-L1 CPS ≥20 patients
Presenter: Dr. Alan Ho, MSKCC
Session Date: Saturday, November 9, 2024
Session Time: 9:00 AM – 8:00 PM CDT
Late Breaking Abstract Number: 1480

The poster will be available on November 9, 2024 on the HOOKIPA website on the "Scientific Publications" tab of the "Our Science" page.

About Eseba-vec
Eseba-vec (also known as HB-200) is an investigational immunotherapeutic agent being evaluated for HPV16 positive cancers. The first indication for eseba-vec is for the potential treatment of patients with HPV16+ recurrent/metastatic oropharyngeal squamous cell carcinoma (R/M OPSCC) with a PDL1 CPS of 20 or higher, in combination with pembrolizumab, in the first line (1L) setting. Eseba-vec has received Fast Track Designation from the U.S. Food and Drug Administration and PRIME designation from the European Medicines Agency for the treatment of 1L HPV16+ OPSCC. Eseba-vec was developed using HOOKIPA’s proprietary arenavirus platform.