On October 30, 2024 Akeso Biopharma (9926.HK) reported the enrollment of the first patient in its randomized, controlled, multicenter Phase III clinical study (AK117-302) for head and neck squamous cell carcinoma (Press release, Akeso Biopharma, OCT 30, 2024, View Source [SID1234647549]). This trial evaluates the innovative PD-1/VEGF bispecific antibody ivonescimab in combination with Akeso’s next-generation CD47 monoclonal antibody ligufalimab (AK117) against pembrolizumab for the first-line treatment of PD-L1 positive (CPS≥1) recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The AK117-302 study represents a significant milestone as the first Phase III clinical trial globally to investigate a CD47 monoclonal antibody therapy for solid tumors. This trial is the fifth Phase III study for ivonescimab, utilizing PD-1/L1 monoclonal antibody therapy as a positive control, and the third Phase III study comparing ivonescimab with pembrolizumab. The AK117-302 trial underscores Akeso’s commitment to advancing the field of cancer immunotherapy and establishing a global standard of care for cancer treatment. Furthermore, it highlights our capability to maximize the number of cancer patients globally that can benefit from our product portfolio through a strategic approach to clinical development.

In 2022, there were 770,000 new cases of head and neck cancer globally, with 84,000 cases reported in China. Squamous cell carcinoma of the head and neck (HNSCC) accounts for over 90% of these cancers. Unfortunately, the five-year survival rate for patients with recurrent/metastatic HNSCC (R/M HNSCC) is just 3.6%. While targeted therapies and immunotherapies have improved treatment options, the median overall survival (OS) remains below one year.

Pembrolizumab has emerged as the first-line standard treatment for R/M HNSCC and is recommended in both CSCO and NCCN guidelines. There is a critical unmet need for more effective therapies to help HNSCC patients achieve long-term survival.

At the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, Akeso reported initial positive data on its combination therapy of ivonescimab and ligufalimab. This combination demonstrated significant tumor reduction and survival benefits, particularly for HNSCC patients, who require rapid tumor shrinkage. The preliminary efficacy data from this therapy surpassed that of previously disclosed PD-1 studies, positioning it as a potentially new immunotherapy option for HNSCC patients.

About Ligufalimab (AK117)

AK117, independently developed by Akeso, is a next-generation humanized lgG4 anti-CD47 antibody without hemagglutination effect. AK117 can bind to CD47 expressed on tumor cells and block the interaction between CD47 and SIRPα, in order to enhance the phagocytic activity of phagocytes on tumor cells, thereby inhibiting the growth of tumors.

Currently, several phase II clinical trials are underway to investigate the potential of AK117 in combination with azacitidine for hematological tumors, as well as AK117 alone or in combination with ivonescimab and cadonilimab for various solid tumors. Preliminary studies have shown promising efficacy and safety profiles, with no observed dose-limiting toxicity events. Additionally, the Chinese Phase II clinical study of the first-line treatment for unfit AML using AK117 in combination with venetoclax and zzacitidine, as well as the international multicenter Phase II clinical study of AK117 for treating MDS, are both ongoing with patient enrollment.

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 30, 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 researchers at Memorial Sloan Kettering Cancer Center (MSKCC) have dosed the first patients in an investigator initiated trial (IIT) of eseba-vec, HOOKIPA’s human papillomavirus type 16 (HPV16+)-targeted investigational immunotherapeutic agent, in patients with minimal residual disease positive (MRD+) HPV-driven head and neck cancer (Press release, Hookipa Pharma, OCT 30, 2024, View Source [SID1234647548]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Based on the positive Phase 2 data generated to date in recurrent/metastatic (R/M) HNSCC, we believe eseba-vec has broad potential across HPV16+ cancers. We are enthusiastic to explore the potential of eseba-vec as an adjuvant treatment for patients with locally advanced HNSCC and continue our collaboration with Drs. Wong and Ho and the team at MSKCC," said Mark Winderlich, PhD, Chief Research and Development Officer at HOOKIPA. "We believe eseba-vec can help address unmet needs within the adjuvant setting and pave the way for us to help more patients with HNSCC."

Malte Peters, Chief Executive Officer of HOOKIPA added, "Eseba-vec was well tolerated and has demonstrated compelling efficacy in combination with pembrolizumab in HPV+ (R/M) HNSCC. We look forward to building on these promising findings with the expansion into adjuvant care. Our eseba-vec clinical development program in HNSCC continues to advance and we are on track to initiate our pivotal AVALON-1 Phase 2/3 study in the front-line setting for patients with HPV16+ oropharyngeal squamous cell carcinoma (OPSCC) in the fourth quarter of 2024. We expect initial safety and efficacy data from the IIT in 2026."

Winston Wong, MD, commented, "Targeted immunotherapeutic agents can play an important role in the care of patients with HPV16+ HSNCC. I am encouraged by the potential for eseba-vec in this setting based on promising Phase 2 combination data with pembrolizumab in the first line setting presented at this year’s American Society for Clinical Oncology annual meeting showing rapid and durable activation of antigen-specific CD8+ T cells and promising clinical response rates, especially in the CPS 20 or higher subgroup. Patients who are HPV16+ after receiving standard of care treatment for curative intent may also benefit from an immunotherapy treatment and we are currently testing whether eseba-vec may be a new, effective adjuvant treatment option."

The Phase 2, randomized, double-blind, placebo-controlled study (NCT06373380) will evaluate the use of eseba-vec in patients with minimal residual disease positive (MRD+) HPV-driven head and neck cancer. The primary endpoint of the study is disease-free survival. Secondary endpoints include an assessment of safety and tolerability. The study is expected to enroll approximately 50 patients.

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.

On October 30, 2024 Numab Therapeutics AG ("Numab") reported the start of a Phase 1 clinical trial evaluating NM32, a next generation tri-specific immuno-oncology therapeutic targeting the receptor tyrosine kinase-like orphan receptor 1 (ROR1) and the T-cell receptor associated antigen CD3 (Press release, Numab, OCT 30, 2024, View Source [SID1234647547]). The third binding moiety of NM32 targets serum albumin to provide half-life extension allowing for convenient bi-weekly dosing and to keep the lower molecular weight than immunoglobulin enabling efficient tumor penetration.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Generated from our proprietary Lambda-capTM and MATCHTM technology platform, NM32 represents a T-cell engager designed to help the patient’s immune system recognize and attack tumor cells. ROR1 is overexpressed on a wide spectrum of highly prevalent solid tumor indications but has very limited expression on normal tissue, making it an optimal antigen for a CD3 engager," said David Urech, Ph.D., Founder and Chief Executive Officer of Numab Therapeutics.

"We are pleased to start NM32’s clinical development path enabling us to potentially bring this novel therapy to patients with advanced solid tumors who are in need of treatment options that provide durable anti-tumor activity with a tolerable safety profile. Enrollment is progressing nicely, with patients completing the first treatment cycle of the initial dose level", commented Martin Stern, Senior Vice President Clinical Science at Numab Therapeutics. "Despite the introduction of checkpoint inhibitors and several commercially available CD3 engagers for the treatment of hematological malignancies, there has been limited success in solid tumors mainly due to the lack of highly tumor-specific antigens allowing selective T-cell activation against tumor cells."

This multi-center Phase 1 study of NM32 is a dose-escalation trial to characterize the pharmacokinetic properties, pharmacodynamic effects and safety profile of NM32 and to select an optimal dosing regimen for further clinical development. It is planned to enroll up to 60 patients with solid tumors overexpressing ROR1 from major clinical sites across the United States. Generated preclinical data in non-human primates indicate a high potency and an excellent safety profile.

About NM32 (NM32-2668)
NM32 is a next generation tri-specific immuno-oncology drug targeting the receptor tyrosine kinase-like orphan receptor 1 (ROR1) and the T-cell receptor associated antigen CD3. The third domain targets serum albumin to provide half-life extension to allow convenient bi-weekly dosing. T-cell redirection using CD3 engagers is an established treatment modality showing high response rates and durable activity in hematological malignancies and has more recently also shown promising results for selected targets overexpressed in solid tumors. ROR1 is a clinically validated tumor associated antigen with overexpression in several indications with high unmet need including lung, breast, ovarian, endometrial, renal and gastric cancer and limited expression on healthy tissue.

On October 30, 2024 SynOx Therapeutics Limited ("SynOx"), a late clinical-stage biopharmaceutical company developing a novel treatment for CSF-1 related and macrophage-driven disorders, reported that it has raised additional funding in a final close of its Series B financing (Press release, SynOx Therapeutics, OCT 30, 2024, View Source [SID1234647546]). The Series B extension was led by new investor Gilde Healthcare and brings the total capital raised by SynOx in the round to $92 million including earlier investments from Forbion, HealthCap and Bioqube Ventures. Proceeds from the financing are supporting a registrational Phase 3 clinical trial of emactuzumab, a potentially best-in-class CSF-1 receptor (CSF-1R) inhibiting monoclonal antibody for the treatment of Tenosynovial Giant Cell Tumour (TGCT).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In conjunction with the closing of the Series B extension, SynOx reported that the first patients have been dosed in its Phase 3 registrational study of emactuzumab. The study, named TANGENT, is a global, multi-centre, randomized, double-blind, placebo-controlled Phase 3 trial designed to evaluate the efficacy and safety of emactuzumab in patients with TGCT. The study’s primary outcome measure is overall response rate (ORR). Investigators will also assess several secondary outcomes including functional and quality of life measurements, impact on tumour volume, and duration of response. Investigators expect to enrol approximately 130 patients in the trial. Additional study details can be found on ClinicalTrials.gov (Identifier: NCT05417789).

TGCT is a rare, non-malignant but aggressively growing tumour of the synovium, primarily located in knee, hip, and ankle joints and caused by excessive production of CSF-1. It is a chronically debilitating disease for patients causing loss of function of the affected joints, pain, stiffness and limited range of motion. Emactuzumab specifically inhibits CSF-1R and earlier clinical work in TGCT1 showed it to be a highly effective, next-generation therapy with a short treatment cycle, rapid onset of action and long duration of response.

"We are pleased to add Gilde Healthcare to our impressive investor syndicate and are appreciative for their support of our team and our vision for the potential of emactuzumab to address the unmet needs, and improve the quality of life, of TGCT patients around the world," said Ray Barlow, Ph.D., Chief Executive Officer of SynOx. "The dosing of patients in the TANGENT trial marks an important milestone for SynOx and is a testament to the dedication and hard work of our team. We look forward to efficiently conducting this study and continuing to pursue our goal of advancing emactuzumab toward market for TGCT patients in desperate need of new treatment options."

As part of the Series B extension, Arthur Franken, general partner at Gilde Healthcare, will join the SynOx Board of Directors. Mr. Franken brings more than two decades of venture and growth capital investment expertise, including several public listings and trade sales.

"We are pleased to join SynOx as an investor and help support the late-stage development of emactuzumab, which we believe has a best-in-class profile as a CSF-1R targeted antibody. Importantly, we also believe that the SynOx team is well positioned to successfully complete clinical development of emactuzumab and deliver this important treatment option to TGCT patients," said Mr. Franken.

On October 30, 2024 SynOx Therapeutics Limited ("SynOx" or the "Company"), the late-stage clinical biopharmaceutical company developing emactuzumab for the treatment of Tenosynovial Giant Cell Tumour (TGCT) and other diseases, reported it has entered into a $35m loan facility with Hercules Capital, Inc. (NYSE:HTGC) ("Hercules") (Press release, SynOx Therapeutics, OCT 30, 2024, View Source [SID1234647545]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The transaction strengthens the Company’s balance sheet as it executes TANGENT, a registrational Phase 3 study of emactuzumab, SynOx’s potentially best-in-class CSF-1(R) inhibiting monoclonal antibody (mAb) for the treatment of TGCT.

This loan facility provides SynOx with flexibility to fund additional clinical work in TGCT to augment TANGENT, activities to support the successful registration and commercialisation of emactuzumab in TGCT, and potentially to explore the use of emactuzumab in other CSF-1 driven and macrophage-mediated diseases.

The term loan facility provides up to $35m, in total, in four tranches. The initial tranche was drawn on signing, with subsequent tranches available over the medium term and upon achievement of certain clinical milestones.

Ray Barlow, Chief Executive Officer of SynOx Therapeutics, said: "This funding will provide SynOx with additional capital to fulfil its mission of establishing emactuzumab as a best-in-class drug, to address significant unmet medical needs and greatly improve the quality of life for as many patients as possible. We are grateful for the support from Hercules, which together with the $75m we raised recently in our Series B round, puts SynOx on a strong financial footing."

R. Bryan Jadot, Senior Managing Director and Group Head – Life Sciences, Hercules, said: "We have been impressed by the quality of data SynOx has already generated on emactuzumab, which demonstrate it to be highly differentiated from other CSF-1 inhibiting drugs in development. Emactuzumab is showing great promise in treating TGCT, and we believe it has the potential to treat other related conditions as well."

TGCT is a type of tumour that affects the soft tissue lining of joints and tendons. It is a highly debilitating disease that often impacts large, important joints such as the knee, hip and ankle. It seriously impacts quality of life by causing significant pain and stiffness in affected joints and limiting range of motion. While most patients receive surgical intervention, more than 50% of patients with diffuse disease experience tumour recurrence within three years of surgery [1].

Emactuzumab, a novel next-generation CSF-1R mAb with a potentially best-in-class profile, has demonstrated substantial clinical activity in earlier clinical work in TGCT [2], with an objective response rate (ORR) of 71%, rapid and robust tumour reduction, a long duration of effect, significant improvements in functional ability, good tolerability and a manageable safety profile. The Phase 3 TANGENT trial will assess its safety and efficacy in patients with localized and diffuse TGCT.