On October 23, 2023 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported that positive initial data from the first-in-human study evaluating JK08 in adults with solid tumors were presented in a poster session during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2023 (Press release, Salubris Biotherapeutics, OCT 23, 2023, View Source [SID1234636283]).

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The presentation included safety data from 32 patients with relapsed or refractory solid tumors who received subcutaneous JK08 monotherapy once weekly in this Phase 1b/2 dose escalation study. At the dose levels evaluated to date, JK08 has been well tolerated, demonstrating preliminary disease stability and anticipated modulation of target immune cell populations in heavily pre-treated patients. Marked induction of NK and CD8+ T cells has been observed, and corresponding activation of these cell populations has been demonstrated through increased HLA-DR expression within these populations. More than 20% of heavily, pre-treated advanced metastatic cancer patients have remained on treatment for 3 months or longer demonstrating preliminary clinical benefit with monotherapy JK08, with the longest continuing therapy for 29 weeks. The most common adverse events have been mild to moderate (Grade 1 & 2) and consist of injection site reactions (ISRs), fatigue, pyrexia, anemia and nausea. No dose limiting toxicities or drug related adverse events leading to treatment discontinuations have been observed to date.

"JK08 combines CTLA-4 targeting with the effects of IL-15, with the aim of enhancing anti-tumor immune responses while managing potential side effects," said Sam Murphy, Chief Executive Officer of SalubrisBio. "We are pleased to see promising, dose-dependent pharmacodynamic activity and a favorable safety and tolerability profile in this heavily pre-treated patient population. While early, the data are very encouraging and we look forward to further evaluating JK08’s potential for solid tumor patients."

The ongoing Phase 1b/2, open label, dose escalation and cohort expansion study (NCT05620134) is designed to evaluate the safety and preliminary anti-tumor activity of JK08 in patients with unresectable locally, advanced or metastatic cancer. After dose escalation, monotherapy and combination dose expansion cohorts are planned. SalubrisBio plans to report additional data from this study at future medical meetings.

About JK08

JK08 is a recombinant fusion protein consisting of a CTLA-4-specific antibody and an IL-15 fusion domain. The JK08 design builds upon a breadth of clinical studies with CTLA-4 antibodies and recombinant IL-15 molecules, which together portend synergistic effects in an antibody fusion construct. The CTLA-4-specific antibody ipilimumab validated CTLA-4 as a target for cancer therapy, but response rates are limited. Analysis of clinical samples demonstrated that NK cell activity signatures and ADCC biomarkers correlate with ipilimumab responses. Recombinant IL-15 has exhibited potent stimulation of NK cell expansion and enhancement of ADCC in pre-clinical and clinical studies. Through the incorporation of a CTLA-4 antibody and IL-15 into a single molecule, JK08 can channel the potent immune stimulation of IL-15 through the CTLA-4 antibody domain towards depletion of T-regulatory cells and targeted reversal of immunosuppression which may contribute to cancer progression.

On October 23, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that the full results of its Phase 2 BGBC008 study of bemcentinib and pembrolizumab in second line Non-Small Cell Lung Cancer (NSCLC) were presented during the European Society of Clinical Oncologists (ESMO) (Free ESMO Whitepaper) Annual Meeting 2023 (Press release, BerGenBio, OCT 23, 2023, View Source [SID1234636282]).

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The poster presentation is now available on BerGenBio’s website under →Pipeline→Scientific Publications.

In addition, on October 21st, Dr. Oddbjorn Straume, M.D., Ph.D., Assistant Professor, Clinical Science at the Haukeland University Hospital in Bergen, Norway presented results of the Investigator Led Study LBA52 of bemcentinib in addition to pembrolizumab or the targeted therapies dabrafenib/trametinib in 1L and 2L metastatic melanoma patients.

Cristina Oliva, Chief Medical Officer of BerGenBio, commented: "The full data analysis of the BGBC008 second line NSCLC study of bemcentinib in combination with the immune checkpoint inhibitor pembrolizumab showed promising long-term clinical benefits in patients regardless of their prior therapies, or PD-L1 status. In addition, the combination of bemcentinib with pembrolizumab was well tolerated with no new safety signals identified. These data provide a strong foundation for further clinical investigations of bemcentinib in NSCLC patients with high unmet needs, including those with STK11 mutations."

Dr. Oliva continued, "During the meeting, our collaborator, Dr. Oddbjorn Straume, also presented data on the combination of bemcentinib with standard of care therapies in first line and second line melanoma patients. While this small study failed to show the benefit of adding a selective AXL inhibitor to the treatment for melanoma patients, the results are consistent with the current limited understanding of the function of AXL in melanoma. In totality, these new data substantiate BerGenBio’s focused strategy on the treatment of first line NSCLC patients with STK11m patients in our on-going BGBC016 study."

On October 23, 2023 Hummingbird Bioscience, a data-driven precision biotherapeutics company discovering and developing transformative biologic medicines for hard-to-treat diseases, reported presentation of positive clinical data for the dose escalation part of the HMBD-001 Phase I/IIa trial (NCT05057013) at the European Society for Medical Oncology Congress 2023 (ESMO 2023). The trial is evaluating HMBD-001 as a monotherapy across various tumor types in the UK (Press release, Hummingbird Bioscience, OCT 23, 2023, View Source [SID1234636281]).

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As of the data cut-off on 8 September 2023, the trial had enrolled 23 heavily pre-treated patients across various tumor types where HER3 may play an important role. The dose escalation trial cleared six monotherapy cohorts with no dose-limiting toxicities (DLTs) and there were no treatment discontinuations due to related adverse events. Of the enrolled patients, 21 were evaluable for efficacy. Disease control rate (DCR) was 43% (9/21), with one patient achieving partial response with a 51% tumor shrinkage after four cycles of HMBD-001 treatment. HMBD-001 as monotherapy had a maximal half-life of 12 days in this trial.

"The favorable safety and tolerability profile of HMBD-001 and its monotherapy activity in biomarker-unselected cohorts are very encouraging and shows that HMBD-001 is an active antibody that effectively inhibits HER3 signaling, which has been shown to be important for cancer growth and survival. HMBD-001 is designed to be a best-in-class HER3 antibody with a differentiated mechanism of action, leveraging knowledge around HER3 biology built up by Hummingbird Bio over the years. To optimize clinical development, we are executing a phased strategy to demonstrate benefit in patients with gene signatures most likely to benefit from HMBD-001. We look forward to evaluating HMBD-001 in patients with squamous non-small cell lung cancer (sqNSCLC) and patients with HER3 aberrations, including NRG1 fusions, in the precision Phase Ib clinical trials recently initiated in Australia," said Jerome Boyd-Kirkup, Ph.D., Chief Scientific Officer, Hummingbird Bioscience.

"I am convinced that HER3 remains an important target for treating many cancers including prostate cancer, where it is implicated in treatment resistance through an interaction between tumor cell HER3 and hijacked white blood cells generating the protein activating it called NRG1. This clinical trial of a novel antibody targeting HER3 has demonstrated good tolerability and early evidence of anti-tumor activity, with an impressive and ongoing response in a patient with advanced pancreatic cancer who has clearly had clinical benefit. We envision that biology-based trials targeting HER3 deserve to be prioritized to continue this important effort," said Johann De Bono, Chief Investigator of the trial, Professor in Experimental Cancer Medicine at The Institute of Cancer Research, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust.

Stephen Nabarro, Ph.D., Interim Director of Cancer Research UK’s Centre for Drug Development said: "We are proud to have played an integral part in the significant progress that HMBD-001 has made in the clinic since we presented at ESMO (Free ESMO Whitepaper) 2022. A year on, and following successful completion of the dose escalation phase, we are seeing promising results emerging from the trial. Having observed anti-tumor activity in one patient already, we are excited about the opening of the metastatic castration-resistant prostate cancer (mCRPC) expansion arm and hope to continue on this path to bring HMBD-001 to patients with HER3-driven cancers." The Phase I/IIa clinical trial in the UK is sponsored and managed by Cancer Research UK’s Centre for Drug Development. This trial began enrolling in October 2021 and is ongoing in the UK.

Based on the encouraging clinical data from the Phase I clinical trial in the UK, Hummingbird Bioscience has initiated two Phase Ib trials studying HMBD-001 in combination with various agents, in patients with sqNSCLC (NCT05910827) and in patients with NRG1 fusions and HER3 mutations (NCT05919537), in Australia in Q3 2023.

Session Details
Date and time: 23rd October 2023, Monday, October 23, 2023, 12:00 – 13:00 CEST
Location: Hall 8

HMBD-001 Clinical Data Poster Details
Poster Title: A CRUK phase I/IIA, first in human dose-escalation and expansion trial of HMBD-001 (an anti-HER3 antibody) in patients with advanced HER3 positive solid tumours
Number: 687P
Presenter: Johann de Bono, Professor in Experimental Cancer Medicine at The Institute of Cancer Research, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust

HMBD-001 Pharmacokinetic Data Poster Details
Poster Title: Pharmacokinetics of HMBD-001, a human monoclonal antibody targeting HER3, a CRUK first-in-human phase I trial in patients with advanced solid tumours
Number: 688P
Presenter: Oladipo Idowu, Ph.D., Biomarker Research Associate, Cancer Pharmacology, Newcastle University Centre for Cancer

About HMBD-001

HMBD-001 is a clinical-stage IgG1 antibody designed to target HER3, discovered using Hummingbird Bioscience’s proprietary Rational Antibody Discovery (RAD) platform. We believe HMBD-001 is the only anti-HER3 antibody in development that has the potential to fully block both ligand-dependent and -independent HER3 activation and oncogenic signaling, by targeting a key epitope located at the interface where HER3 forms heterodimers with HER2 or EGFR. In preclinical models evaluating HMBD-001, superior affinity and more potent tumor growth inhibition compared to existing anti-HER3 antibodies were observed. HMBD-001 is currently in Phase Ib clinical trials for biomarker-selected indications with a strong scientific rationale, which includes squamous non-small cell lung cancer, NRG1 fusions, and HER3 mutations.

On October 23, 2023 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported the latest clinical progress of 2 novel drugs including Nectin-4 ADC 9MW2821, as well as the clinical study data to be reported on ESMO (Free ESMO Whitepaper) 2023 (Press release, Mabwell Biotech, OCT 23, 2023, View Source [SID1234636280]).

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Latest progress & phase I/II study data to report on ESMO (Free ESMO Whitepaper) 2023 of 9MW2821

Up to now, 195 patients with advanced solid tumor have been enrolled in the phase I/II study of Nectin-4 ADC 9MW2821. Among 115 patients with solid tumor treated with 9MW2821 at 1.25mg/kg or above and evaluable for tumor assessment, objective response rate (ORR) and disease control rate (DCR) was 43.5% and 81.7%, respectively. In 37 patients with UC who experienced platinum-based chemotherapy and immune checkpoint inhibitors, dosed at 1.25mg/kg and were evaluable for tumor assessment, ORR and DCR was 62.2% and 91.9%, respectively.

Core data reported on ESMO (Free ESMO Whitepaper) from phase I/II study of 9MW2821 showed that among 39 subjects with solid tumor who treated with 9MW2821 at 1.25mg/kg or above and evaluable for tumor assessment, ORR and DCR was 38.5% and 84.6%, respectively. In 18 patients with UC who dosed at 1.25mg/kg and evaluable for tumor assessment, ORR and DCR was 55.6% and 94.4%, respectively. All UC patients have been treated with platinum-based chemotherapy and immune checkpoint inhibitors before enrollment.

The results showed that 9MW2821 had manageable safety profile. Treatment related death was not observed. Objective responses were also observed in patients with breast cancer and cervical cancer. Enrollment continues to determine efficacy of 9MW2821 in certain solid tumors.

Proactive communication on pivotal trial of 9MW2821 is ongoing.

Latest progress & phase III study data to report on ESMO (Free ESMO Whitepaper) 2023 of 8MW0511

Up to now, Mabwell is in the preparation of New Drug Application submission of 8MW0511 within the year.

Core data from phase III study of recombinant (yeast-secreted) human granulocyte-colony stimulation factor fusion protein 8MW0511 for injection, reported at ESMO (Free ESMO Whitepaper), showed that 8MW0511 was clinically effective, non-inferior to the positive control. It is able to improve the incidence and duration of grade 4 neutropenia, with a significantly lower incidence and duration of grade 4 neutropenia observed at cycle 2-3 than in the positive control group. The overall safety profile is similar to that of the positive control group, which indicates manageable safety profile and good tolerance in humans.

About 9MW2821

Developed by Mabwell’s ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, 9MW2821 is the first clinical stage Nectin-4-targeting ADC developed by Chinese company. Multiple clinical studies of 9MW2821 is ongoing to evaluate safety, tolerability, pharmacokinetics, and preliminary antitumor activity in patients with different types of advanced solid tumors.

About 8MW0511

8MW0511 is a recombinant (yeast-secreted) human granulocyte-colony stimulation factor fusion protein, belonging to Category 1 Therapeutic Biological Products. It is indicated for use in adult patients with non-myeloid malignancies to reduce the incidence of infections manifested by febrile neutropenia when treated with myelosuppressive anticancer drugs that predispose to febrile neutropenia.

On October 23, 2023 Luoxin Pharmaceuticals Group Stock Co., Ltd. (Luoxin Pharmaceutical), reported that LX-039, an innovative anti-tumor drug was selected for poster presentation at the 2023 ESMO (Free ESMO Whitepaper) Annual Congress (Press release, Luoxin Pharmaceutical, OCT 23, 2023, View Source [SID1234636279]).

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ESMO is one of the most influential oncology conferences globally, attracting over 30,000 professionals every year from more than 150 countries and regions. The Congress covers basic research, translational research, and the latest advancements in clinical studies, providing an exchange platform in clinical diagnosis, treatment, and academic discussions.

LX-039 is an innovative selective estrogen receptor degrader (SERD) for oral administration. The aims of the dose escalation and expansion phase I study was to explore the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) profiles of LX-039 in postmenopausal patients with ER+ and HER2- advanced breast cancer who have failed endocrine therapy. The study was led by Professor Hu Xichun from Fudan University Shanghai Cancer Center.

In a 3+3 design, the trial evaluated the safety and tolerability from a daily dose of 50 mg to 1200 mg, with two dosage groups selected for expansion. [18F] Fluoroestradiol PET/CT imaging was used for PD study. All 44 enrolled subjects had previously undergone multiple lines of endocrine therapy. Specifically, 72.7% had received second-line therapy or higher. More than half had been treated with fulvestrant, a medication commonly used for hormone receptor-positive breast cancer. Also, over 50% had received advanced chemotherapy, and 40.9% had been treated with CDK4/6 inhibitors.

Maximum tolerated dose (MTD) was not reached in this study. Most adverse events are graded as mild to moderate (grade 1-2). The exposure of LX-039 increased along with the dose escalation, and no obvious accumulation after multiple doses. Inhibition of the ER pathway is observed in all subjects participating in the PD exploration. Four subjects achieved partial response, with an objective response rate of 10.8% and a clinical benefit rate at 24 weeks of 40%. LX-039 demonstrates good tolerability and PK/PD properties in ER+ and HER2- advanced breast cancer and shows preliminary anti-tumor activity. These encouraging results suggest that LX-039 holds great potential for further development. Consequently, a phase II study is under planning.

About 75% of breast cancer cases are classified as ER+. This subtype of breast cancer relies on the estrogen signaling pathway for its growth and progression. The primary therapeutic approach for ER+ breast cancer involves inhibiting the estrogen signaling pathway through various methods. Notably, drugs like tamoxifen and fulvestrant have been utilized in clinical settings to target the ER pathway. However, tamoxifen resistance and treatment non-compliance with fulvestrant have led to unmet clinical needs.

LX-039, an orally administered selective ER degrader (SERD) developed by Louxin Pharmaceutical, specifically focuses on modulating the estrogen signaling pathway. It antagonizes ER actions and promotes its ubiquitination and degradation within breast cancer cells, downregulating ER expression. LX-039 offers unique therapeutic benefits compared to selective ER modulators and aromatase inhibitors. Additionally, its oral formulation enhances patient convenience and compliance, as it eliminates the need for injections. There are currently no domestically available oral drugs with a similar mechanism of action to LX-039 in the market.

References:

Wang Y, Ayres K L, Goldman D A, et al. 18F-fluoroestradiol PET/CT measurement of estrogen receptor suppression during a phase I trial of the novel estrogen receptor-targeted therapeutic GDC-0810: using an imaging biomarker to guide drug dosage in subsequent trials[J]. Clinical Cancer Research, 2017, 23(12): 3053-3060.
Patel H K, Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment[J]. Pharmacology & therapeutics, 2018, 186: 1-24.