On October 30, 2023 SparX Biopharmaceutical Corp. reported that its Investigational New Drug (IND) application for SPX-303, a First-in-Class anti-LILRB2/PD-L1 bispecific antibody drug candidate, has been greenlighted by the U.S. Food and Drug Administration (FDA) (Press release, Sparx Therapeutics, OCT 30, 2023, View Source [SID1234636465]). This approval propels SparX’s enduring commitment to deliver groundbreaking solutions to patients grappling with advanced or refractory solid tumors.

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Dr. Gui-Dong Zhu, Chief Executive Officer of SparX Biopharmaceutical, shared his exhilaration: "Receiving the FDA’s green light on our IND application is a seminal moment in our ongoing journey to redefine the paradigms of cancer treatment. The preclinical data for SPX-303 not only showcases promise but facilitate out confidence to harness its therapeutic prowess in a clinical setting, particularly for patients who previously had limited treatment options."

With this FDA endorsement, SparX Biopharmaceutical is primed to launch a Phase 1 clinical study, aiming to assess the safety, tolerability, and preliminary efficacy of SPX-303 in patients beleaguered by advanced or refractory solid tumors. This human trial is geared to evaluate the therapeutic potential of SPX-303, potentially heralding a new dawn of innovative and superior healthcare outcomes.

Developed by SparX, SPX-303 is a First-in-Its Class bispecific antibody therapy, ingeniously engineered to engage two cardinal immune checkpoint proteins, LILRB2 and PD-L1, simultaneously. Acting as pivotal fulcrums in sustaining the immune system’s equilibrium and vigor, these checkpoints help deter autoimmune anomalies. While LILRB2 majorly tempers overactive innate immune reactions, preserving the body’s natural defense harmony, PD-L1—often overexpressed in tumor cells—judiciously modulates T cell activation, curating a precise immune response. Yet, cancers often manipulate these immune-checkpoints, equipping themselves with a defense mechanism against immune retaliation. SPX-303 is meticulously designed to dismantle this barrier, empowering the immune system to discern and fervently annihilate malignant cells, thereby charting a transformative trajectory in cancer therapy.

On October 30, 2023 Applied BioMath (www.appliedbiomath.com), the industry-leader in providing model-informed drug discovery and development (MID3) support to help accelerate and de-risk therapeutic research and development (R&D), reported their participation at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) occurring November 1-5, 2023 in San Diego, CA (Press release, Applied BioMath, OCT 30, 2023, View Source [SID1234636464]).

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During the conference, Fei Hua, PhD, Vice President of Modeling and Simulation Services at Applied BioMath, will present the poster entitled, "Overcoming the dose-response prediction limitation from bench to clinic for T-cell engagers: Using Quantitative Systems Pharmacology (QSP) modeling in the development of CDR404 for solid tumors."

While T-cell Engagers (TCEs) offer a potentially very potent approach to treat cancer, they also have complex relationships between binding potency, exposure, and efficacy. These complex relationships bring challenges to drug discovery and development such as identifying optimal Kd for the drug candidate, predicting efficacious doses, and selecting dosing regimens for clinical study.

Applied BioMath’s poster describes a QSP model developed to support the first-in-human trial design for CDR404, a highly potent and highly specific antibody-based T-cell engager that binds bivalently to a MAGE-A4 peptide displayed on HLA-A*02:01 on cancer cells and monovalently to CD3 on T-cells. The QSP model will become an integrated part of the clinical development program and can be updated with emerging clinical data to facilitate discovery of a safe and therapeutic dose range for CDR404.

"For therapeutics with complex mechanisms of action (MoA), QSP modeling can be integral for progressing through the R&D pipeline," said John Burke, PhD, Co-founder, President and CEO. "Particularly for TCEs, we’ve had experience where QSP modeling has tested target feasibility, optimized molecule design, predicted therapeutic index, and guided clinical trial design."

To learn more about Applied BioMath, visit www.appliedbiomath.com.

On October 30, 2023 Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotech company developing novel drugs for cancer, fibrosis, and inflammation, reported that the company has initiated the Phase 1/2 clinical trial evaluating the safety, tolerability, and antitumor activity of BBT-207 in non-small cell lung cancer (NSCLC) patients with EGFR mutations (Press release, Bridge Biotherapeutics, OCT 30, 2023, View Source [SID1234636463]).

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BBT-207, a novel epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is designed to inhibit the signaling pathway of EGFR with C797S mutations, which arises due to osimertinib (Tagrisso)-resistant mutations in NSCLC. The mutation results in a cysteine to serine change on amino acid 797 within the kinase domain sequence of the EGFR. Preclinically BBT-207 has shown activity against treatment-emergent complex EGFR mutations containing T790M and/or C797S as well as drug- naïve mutants providing a possibility to overcome resistance to prior TKIs.

The Phase 1/2 study (NCT05920135), an open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of BBT-207 in patients with NSCLC who have progressed following the use of at least one third-generation EGFR TKI, consists of three parts: dose escalation (Part 1), recommended phase 2 dose selection (Part 2), and dose expansion (Part 3). The study is expected to enroll approximately 92 patient participants who have advanced stage and refractory NSCLC with an activating EGFR mutation, documented partial response, complete response, or durable stable disease after the treatment of an EGFR TKI, and previous treatment with all standard therapeutic options and at least one third-generation EGFR TKI, including Osimertinib and Lazertinib.

The Phase 1a dose escalation cohort will determine the Recommended Dose Range (RDR), based on the totality of the data including toxicity/tolerability, efficacy, pharmacokinetic (PK), and pharmacodynamic (PD). During the Phase 1b RP2D selection stage, the safety monitoring committee will determine the Recommended Phase 2 Dose (RP2D) based on the totality of the data including overall safety, PK, PD, and preliminary antitumor activity including the percentage of patients with partial response (PR) or complete response (CR) based on RECIST Version 1.1. and duration of response (DOR). Finally, the Phase 2 dose expansion cohort will include assessments of preliminary anti-tumor activity utilizing the objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. In addition, detailed mutation profiles collected through liquid and tumor biopsy procedures will be analyzed after the study.

"We are highly encouraged to be able to initiate the first-in-patient study of BBT-207, which is expected to address unmet medical needs of advanced NSCLC patients with C797S mutations across the globe," said James Lee, CEO of Bridge Biotherapeutics.

Additional information about the clinical trial may be found at clinicaltrials.gov/study/NCT05920135.

Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths. Lung cancer is classified into two main groups: non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC), where NSCLC accounts for approximately 85% of all lung cancer diagnoses. In 2019, there were a combined 0.79 million diagnosed cases of NSCLC in men and women, aged 18 years and older, across the US, France, Germany, Italy, Spain, the UK, Japan, and urban China. The incidence of NSCLC is expected to increase at an annual growth rate (AGR) of 3.01% from 2019 to 2029, reaching 1.03 million cases in 2029[1].

In September 2023, Bridge Biotherapeutics announced the discontinuation of the development of BBT-176, another fourth generation EGFR TKI at the Phase 1a stage, dose escalation part. The company will remain committed to the development of a fourth generation EGFR TKI, while seeking to concentrate its capacity and financial resources on BBT-207.

STUDY TITLE: First-in-Human Study of BBT-207 in Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutation After Treatment with EGFR TKI
STUDY DESIGN: An open-label, Phase 1/2 study evaluating safety, tolerability, PK, PD, and preliminary antitumor activity of BBT-207 in patients with advanced NSCLC harboring EGFR mutation after treatment with EGFR TKI. The study will consist of 3 parts; dose escalation, recommended phase 2 dose selection, and dose expansion phases
TEST PRODUCT: Oral administration of BBT-207 throughout a 21-day cycle for each phase
STUDY OBJECTIVES: To evaluate the safety, tolerability, PK, PD, and preliminary efficacy (antitumor activity) of BBT-207 in patients with advanced NSCLC harboring EGFR mutation after treatment with EGFR TKI

On October 30, 2023 Jiangsu Hengrui Pharmaceuticals Co., Ltd ("Hengrui Pharma"), a global pharmaceutical company focused on scientific and technological innovation, reported a licensing agreement with Merck KGaA, Darmstadt, Germany, a leading science and technology company, for its next-generation potent and selective PARP1 (poly (ADP-ribose) polymerase 1) inhibitor, HRS-1167 (Press release, Hengrui Pharmaceuticals, OCT 30, 2023, View Source [SID1234636462]). This is Hengrui’s first strategic collaboration with a global pharmaceutical company. The agreement includes an option to an exclusive license for its innovative Claudin-18.2 antibody drug conjugate (ADC) SHR-A1904.

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"Given the high unmet need in oncology, we are excited to work closely with Merck KGaA, Darmstadt, Germany, to bring Hengrui’s innovations to cancer patients worldwide," said Frank Jiang, board member and Chief Strategy Officer of Hengrui Pharma. "Partnering with Merck KGaA, Darmstadt, Germany, on our PARP franchise is an important milestone on Hengrui’s globalization journey. We look forward to advancing our molecules rapidly through development and reaching patients in need."

Under the terms of the agreement, Merck KGaA, Darmstadt, Germany, will provide Hengrui Pharma with an upfront payment of €160 million. Hengrui Pharma will receive payments for technology transfer as well as an option exercise for the Claudin-18.2 ADC for up to €90 million. Upon the achievement of certain development, regulatory and commercial milestones, Hengrui is eligible to receive royalty payments on net sales of such products by Merck KGaA, Darmstadt, Germany. Potential payments may total up to €1.4 billion with up to double-digit royalty payments.

"This partnership with Hengrui fully aligns with both our external innovation ambition and our oncology research and development strategy by diversifying our robust internal pipeline in our focus areas of DNA damage response inhibition and antibody-drug conjugates," said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business of Merck KGaA, Darmstadt, Germany. "The synergies of these assets with our portfolio offer broad potential for development and the opportunity to advance more therapeutic options for patients with difficult-to-treat cancers. We look forward to leveraging the significant expertise of Hengrui and our strong collaboration ahead."

Merck KGaA, Darmstadt, Germany, will receive exclusive rights to develop, manufacture and commercialize HRS-1167 worldwide, outside of mainland China, an exclusive option to develop, manufacture and commercialize SHR-A1904 worldwide, outside of mainland China, and an option to co-promote HRS-1167 and SHR-A1904 in mainland China.

About HRS-1167 and SHR-A1904

HRS-1167 is a selective, highly active and orally available PARP1 small molecule inhibitor internally developed by Hengrui with intellectual property rights, which belongs to the second generation of PARP inhibitors. Poly (ADP-ribose) polymerase (PARP) is key in DNA repair pathways. Compared to first-generation PARP inhibitors, HRS-1167 has higher selectivity and affinity for PARP1 and induces DNA trapping. HRS-1167 is currently in early clinical development (Phase 1) and has the potential to be used as a monotherapy and as part of a combination therapy for treating a wider range of patients.

SHR-A1904 is an antibody drug conjugate (ADC) targeting Claudin 18.2, internally developed by Hengrui with intellectual property rights. It binds to the target antigen on the surface of tumor cells, allowing the drug to be endocytosed by cells and releasing a small-molecule toxin to kill tumor cells. The product is currently in clinical Phase 1 trials in China, U.S. and Australia. Currently, no Claudin 18.2 targeting ADC product has received marketing authorization.

On October 30, 2023 ImmPACT Bio USA, Inc. ("ImmPACT BIO"), a clinical-stage company developing transformative logic-gate-based chimeric antigen receptor (CAR) T-cell therapies for treating cancer and autoimmune diseases, reported that it will participate in the 2023 Truist Securities BioPharma Symposium, to be held from November 8-9, 2023 in New York, NY (Press release, ImmPACT-Bio, OCT 30, 2023, View Source [SID1234636461]).

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Sumant Ramachandra, M.D., Ph.D., ImmPACT Bio’s chief executive officer, will participate in a panel discussion entitled "Considerations for an Oncology Company’s Autoimmune Side Hustle," on Thursday, November 9, 2023 at 11:40 AM ET. ImmPACT Bio management will also participate in one-on-one investor meetings.

To request a one-on-one meeting at the conference, please contact your Truist Securities representative.