On June 30, 2023 Chime Biologics, a leading CDMO that enables its partners’ success in biologics, reported that it has established 3-way strategic cooperation with Leads Biolabs and BeiGene to accelerate LBL-007 mAb development and manufacturing for speedy clinical advancement (Press release, Nanjing Leads Biolabs, JUN 30, 2023, View Source [SID1234633014]).

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LBL-007 is a novel antibody targeting the LAG-3 pathway developed independently by Leads Biolabs. The phase I clinical trial data of LBL-007 in patients with later-stage solid tumors have been announced at the 2021 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).

Previously, Leads Biolabs and BeiGene reached an authorization and cooperation agreement. Leads Biolabs grants LBL-007 exclusive global development and production license to BeiGene, as well as a commercial manufacturing license outside China.

Leads Biolabs and Chime Biologics initiate strategic cooperation to accelerate IND application and provide clinical trial materials in China.

Leads Biolabs has entrusted Chime Biologics with the file supporting work related to the production of LBL-007 project and clinical trial materials in mainland China. Now, the project is progressing into clinical phase II stage. At 2023 ASCO (Free ASCO Whitepaper) conference in Chicago from June 2 to 6, Leads Biolabs presented a poster summarizing the latest clinical data research results on safety and efficacy of anti-LAG-3 (lymphocyte activating gene-3) antibody LBL-007 in the treatment of advanced or metastatic melanoma. This is an open-label, multicenter, dose-escalation or expansion Phase I clinical trial research conducted in China, focusing on safety, RP2D, pharmacokinetics and pharmacodynamics.

BeiGene and Chime Biologics establish strategic cooperation to facilitate IND applications overseas and clinical trial materials supply.

BeiGene is also entrusting Chime Biologics to provide support for clinical development and manufacturing of clinical trial materials in order to facilitate multiple clinical trials. The indications encompass colorectal cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, as well as other solid tumors. Clinical trials have been conducted in numerous countries worldwide, including Australia and the United States.

The three parties have established a comprehensive strategic partnership based on the principle of "Complementary Advantages, Resource Sharing, Strong Alliance, and Win-win Cooperation". Through 3-way cooperation, multiple clinical studies are advancing rapidly based on the global development distribution of LBL-007. We hope anti-LAG-3 antibodies can bring good news to cancer patients as soon as possible.

A Trusted Partner in Biologics Commercial Manufacturing

Chime Biologics serves as a long-term partner to biopharmaceutical clients with sound solutions for manufacturing and more recently moved into late stage and commercial manufacturing. We support various stages of new drug registration and application, provide production service for preclinical, clinical and listed drugs, including non-GMP standard production and the first modular biopharmaceutical factory in the world which meets the global cGMP standards.

Dr. Kang Xiaoqiang, Founder, Chairman and CEO of Leads Biolabs, stated: "We are so pleased to cooperate with BeiGene, a global leading enterprise in oncology field, and Chime Biologics with extensive antibody production experience. LBL-007 is the first innovative antibody drug with global intellectual property which we developed independently. I believe that the development and commercialization of LBL-007 can be expedited through our triangular cooperation, so we can address unmet medical needs and bring hope to cancer patients."

Dr. Wang Lai, Global R&D Director of BeiGene, said: "The clinical candidate drug developed by Leads Biolabs has a broad prospect, not only enriching our tumor immunotherapy drug pipeline but also supporting us for global clinical development strategic priorities and development opportunities. Chime Biologics has advanced drug commercial manufacturing experience, a sound quality system and efficient production management, providing assurance of LBL-007 for global development. Although the cooperation is not too long, LBL-007 has launched nearly ten Phase I and II clinical trials worldwide in the last year, with indications covering colorectal cancer, non-small cell lung cancer, head and neck squamous cell cancer, melanoma and other solid tumor cancers. I believe that this cooperation will bring new opportunities for the medical community to further conquer cancer."

Dr. Wei Jianzhong, President of Chime Biologics, stated:" We are glad to be the partner of these two leading Biopharma enterprises to provide the IND filing support of LBL-007 project and clinical trial materials production. The three parties will work together to deepen cooperation and promote the clinical trial process of LBL-007 project. Chime Biologics has always focused on quality management and technological innovation. This cooperation project is a remarkable milestone of company’s global development. We are very proud to be able to empower biopharma partners to bring more drugs to the market as soon as possible and benefit patients worldwide."

About LBL-007

LBL-007 is a fully humanized anti-LAG-3 (lymphocyte activating gene-3) monoclonal IgG4 antibody consisting of two IgG4 heavy chains and two κ light chains linked by disulfide bonds, with high affinity to human LAG-3, and exerts antitumor effects by blocking LAG-3 activation of immune function. In preclinical models, LBL-007 in combination with anti-programmed cell death protein 1 (PD-1) showed synergistic antitumor activity. Results from the phase I a study of LBL-007 monotherapy have been published in ASCO (Free ASCO Whitepaper) 2021 (Abstract 2523); preliminary safety and efficacy data for LBL-007 combined with toripalimab in patients with advanced melanoma (Part A) have been reported in ASCO (Free ASCO Whitepaper) 2022 (Abstract 9538/Poster 131), showing a favorable safety profile and better antitumor activity, particularly in anti PD-(L)1 naïve patients with acral melanoma. Several clinical studies of LBL-007 are currently in rapid progress based on global layout.

On June 30, 2023 Immuno-oncology leader, Agenus (Nasdaq: AGEN), reported promising data today from its Phase 1b trial on the botensilimab and balstilimab combination at a late-breaking session at the 2023 ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer (ESMO GI) (Press release, Agenus, JUN 30, 2023, View Source [SID1234633012]). The new data show substantial survival benefits and long-lasting responses for patients with non-MSI-H (microsatellite stable or non-microsatellite instability-high) metastatic colorectal cancer previously resistant to chemotherapy and/or immunotherapy.

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"The data from our expanded cohort demonstrate remarkable median overall survival and sustained responses in heavily pre-treated patients that historically haven’t responded to immunotherapy. These findings provide evidence of the benefit of botensilimab/balstilimab in metastatic colorectal cancer, the second leading cause of cancer death in the U.S.," said Dr. Steven O’Day, Chief Medical Officer at Agenus. "Our clinical research has shown confirmed responses in 8 other refractory tumor types, indicating the potential to transform clinical practice and patient outcomes for multiple challenging cancers."

Dr. Andrea Bullock, Assistant Professor of Medicine, Harvard Medical School, and study investigator, commented, "The new survival data underscore the potential of the botensilimab/balstilimab combination as an important treatment option for patients with non-MSI-H colorectal cancer. The patients in our study face one of the most challenging cancers to treat and represent the largest patient population with colorectal cancer where only a quarter of patients survive beyond one year with standard of care therapy. Botensilimab plus balstilimab continues to show deep and durable responses with 69% of objective responses still ongoing at the data cutoff."

Agenus is planning to submit its first Biologics License Application to the U.S. Food & Drug Administration (FDA) for patients with non-MSI-H metastatic colorectal cancer. The ongoing global randomized phase 2 trial for patients with non-active liver metastases has been granted Fast Track Designation from the FDA. Additionally, global randomized Phase 2 trials for the botensilimab/balstilimab combination in melanoma and botensilimab/chemotherapy in pancreatic cancer are underway, with plans to initiate Phase 3 studies in colorectal and non-small cell lung cancer (NSCLC).

Study Design:

The study enrolled 101 patients with refractory non-MSI-H metastatic colorectal cancer who were administered botensilimab (either 1 or 2 mg/kg every six weeks) and balstilimab (3 mg/kg every two weeks).

The patients had a median of four prior therapy lines, with 25% having failed previous immunotherapy.

Efficacy was evaluated in 87 patients who had undergone at least one six-week post-baseline imaging scan. Of these, 69 patients had no active liver metastases, defined as patients with no history of liver metastases or those with metastases that were treated or ablated without recurrence.

Half of the patients treated had poor-prognostic metastatic sites beyond the liver, such as bone and soft tissue.

Survival:

Patients without active liver metastases had a 12-month overall survival (OS) estimate of 74% and a median overall survival (mOS) of 20.9 months, surpassing the recently reported 12.9-month benchmark with standard of care.

Patients with active liver metastases had a 12-month OS estimate of 30% and a mOS of 8.7 months, surpassing the recently reported 5.9-month benchmark with standard of care. The botensilimab/balstilimab combination showed a survival benefit, regardless of RECIST 1.1 responses.

mOS estimates for patients, categorized by liver status, were comparable between the efficacy evaluable and the intent-to-treat populations.

Objective Responses:

Evaluable patients without active liver metastases showed a confirmed objective response rate of 23% and a disease control rate of 80%, significantly higher than the reported response rate of 3% with standard of care.

The responses were durable, with 69% of objective responses ongoing at data cutoff. Response durations ranged from 1.4+ months in recently treated patients to over 24.3+ months.

Tolerability:

The botensilimab/balstilimab combination demonstrated a manageable safety profile, with no new safety concerns emerging.

Presentation Details:

Abstract Title: Results from an expanded phase 1 trial of botensilimab, a multifunctional anti-CTLA-4, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (NCT03860272)

Abstract Number: LBA-4

Presenting Author: Andrea J. Bullock, MD, MPH, Assistant Professor of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center

Session XVIII: Immune Mechanisms and Microbiome in GI Tumors

Session Time: 6/30/2023, 5:15pm – 6:30pm CEST

Presentation Date and Time: 6/30/2023, 6:00pm – 6:10pm CEST

The presentation can be accessed in the publications section of our website at View Source

References:

Grothey et. al. "Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial." Lancet 2013, 381(9863): 303-12

Mayer et. al. "Randomized trial of TAS-102 for refractory metastatic colorectal cancer." NEJM 2015, 372(20): 1909-19

Cohen et al. "Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis." ASCO (Free ASCO Whitepaper) Annual Meeting 2023, Abstract 3554

About Botensilimab

Botensilimab, an investigational multifunctional CTLA-4 antibody, is designed to extend immunotherapy benefits to "cold" tumors, which have not historically responded to standard of care or investigational therapies. Besides binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, and activates T cells, thereby enhancing immune responses. In a Phase 1b clinical study involving over 500 patients, botensilimab has shown clinical responses in 9 solid tumor cancers, either alone or in combination with Agenus’ PD-1 antibody, balstilimab. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT05608044, NCT05630183, and NCT05529316.

On June 30, 2023 Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, reported equity awards on June 30, 2023 that were previously approved by the Compensation Committee of its Board of Directors under Sarepta’s 2014 Employment Commencement Incentive Plan, as a material inducement to employment to 13 individuals hired by Sarepta in June 2023 (Press release, Sarepta Therapeutics, JUN 30, 2023, View Source [SID1234633011]). The equity awards were approved in accordance with Nasdaq Listing Rule 5635(c)(4).

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The employees received, in the aggregate, options to purchase 8,950 shares of Sarepta’s common stock, and in the aggregate 8,200 restricted stock units ("RSUs"). The options have an exercise price of $114.52 per share, which is equal to the closing price of Sarepta’s common stock on June 30, 2023 (the "Grant Date"). One-fourth of the shares underlying each employee’s option will vest on the one-year anniversary of the Grant Date and thereafter 1/48th of the shares underlying each employee’s option will vest monthly, such that the shares underlying the option granted to each employee will be fully vested on the fourth anniversary of the Grant Date, in each case, subject to each such employee’s continued employment with Sarepta on such vesting dates.

One-fourth of the RSUs will vest yearly on each anniversary of the Grant Date, such that the RSUs granted to each employee will be fully vested on the fourth anniversary of the Grant Date, in each case, subject to each such employee’s continued employment with Sarepta on such vesting date.

On June 30, 2023 Oxcia’s CEO Ulrika Warpman Berglund reported that it has been invited to present "OXC-101: A Novel Way to Treat Acute Myeloid Leukemia by Inducing Mitotic Arrest, ROS and Oxidative Damage" at the 18th Annual Congress of International Drug Discovery Science & Technology (IDDST) conference, Amsterdam, the Netherlands, July 12-14, 2023 (Press release, Oxcia, JUN 30, 2023, View Source [SID1234633010]).

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OXC-101 is a mitotic MTH1 inhibitor, with a unique synergistic dual mechanism of action. It arrests cancer cells in mitosis by disturbing microtubule polymerization, thereby accumulating ROS which in turn generates e.g. oxidized nucleotides. By inhibiting the enzyme MTH1, OXC-101 incorporates more oxidized nucleotides into DNA resulting in DNA damage and the cancer cell dies via apoptosis and mitotic catastrophe. Hematological cancers are highly responsive to OXC-101 treatment. Importantly, OXC-101 has been demonstrated to kill primary human AML blast cells as well as chemotherapy resistant leukemic stem cells. The latter are often responsible for AML progression. OXC-101 significantly improves survival in different AML disease models and is an excellent combination partner to the standard of care treatment of AML. The preclinical data supports that OXC-101 is a promising novel anticancer agent for AML, providing rationale for the on-going clinical phase 1 trial in advanced hematological cancers. Oxcia recently obtained a Swelife/MedTech4Health grant together with Karolinska University Hospital Örebro University Hospital and Karolinska institutet to further explore the clinical benefit and safety of OXC-101 in refractory/relapsed AML patients at the recommended phase 2 dose.

The IDSST congress focuses on drug discovery, practical pharmaceutical science, clinical studies, translational medicine and new drugs in the pipeline.

On June 30, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the approval of an inducement award to one new employee, Yisrael Katz, M.D. who is joining Oncternal as VP, Clinical Development (Press release, Oncternal Therapeutics, JUN 30, 2023, View Source [SID1234633009]).

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The award will be made on July 1, 2023 under Oncternal’s 2021 Employment Inducement Incentive Award Plan, which provides for the granting of equity awards to new employees of Oncternal as an inducement to join the Company. The award will consist of an option to purchase 125,000 shares of Oncternal common stock. The option will have a 10-year term and an exercise price equal to the closing price of Oncternal’s common stock on the date of grant. The option will vest over a four-year period, with 25% of the shares subject to the option vesting on the first anniversary of the employee’s start date, and the rest vesting in equal monthly installments over three years thereafter. The award was approved by Oncternal’s compensation committee, comprised entirely of independent directors, as required by Nasdaq Rule 5635(c)(4), and will be granted as an inducement material to the employee entering into employment with Oncternal in accordance with Nasdaq Rule 5635(c)(4).