On April 25, 2025 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company, reported that its BTK inhibitor orelabrutinib received approval from the China National Medical Products Administration (NMPA) for the first-line treatment of patients with chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) (Press release, InnoCare Pharma, APR 25, 2025, View Source [SID1234652178]). The approval of the first-line CLL/SLL treatment will enable orelabrutinib to benefit an even broader population of lymphoma patients.

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Orelabrutinib has been approved for the treatment of three indications in China, including relapsed and refractory (R/R) CLL/SLL, r/r mantle cell lymphoma (R/R MCL) and r/r marginal zone lymphoma (R/R MZL), all of which have been covered in the National Reimbursement Drug List.

Jianyong Li, the principal investigator of the clinical trial and a professor at the Jiangsu Province Hospital, said: "Orelabrutinib has demonstrated excellent efficacy and safety in the treatment of B-cell malignancies such as R/R CLL/SLL since its launch in 2020, showing a higher complete response rate. The first-line approval means more lymphoma patients will benefit from this highly effective treatment regimen. The study showed a complete response rate as high as 12.1%, which will bring new hope to the treatment of hematological tumors in China."

Lugui Qiu, the principal investigator of the clinical trial and a professor at the Blood Diseases Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, said, "Despite the challenges posed by the COVID-19 pandemic in initiating the study, enrolling patients and patient management, orelabrutinib demonstrated significant efficacy and good safety in first-line treatment of CLL/SLL. It also provides an effective treatment option for high-risk patients and those with comorbidities, both in clinical research and real-world settings."

Jun Ma, professor at the Harbin Blood Disease and Oncology Research Institute, said, "With the approval of orelabrutinib for first-line CLL/SLL treatment and the accumulation of additional real-world data, more lymphoma patients will benefit. Furthermore, orelabrutinib has been listed as a Class I recommendation for first-line treatment of CLL/SLL in the CSCO lymphoma guidelines. We look forward to more extensive and longer follow-up data on orelabrutinib to guide clinical practice and offer better treatment options for more lymphoma patients."

Jun Zhu, professor at Beijing Cancer Hospital said, "The prospect of orelabrutinib in the treatment of hematological tumors is remarkable. Its high selectivity and low off-target effects give it advantages in both efficacy and safety. We believe that with the extensive use of orelabrutinib in first-line treatment, more patients will benefit from this novel therapy."

Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare, said: "We are delighted to see the approval of orelabrutinib for the first-line treatment of CLL/SLL. This marks another important milestone for our company in hematological malignancies. We sincerely thank all the physicians, patients and employees who have worked tirelessly on this study. We look forward to bringing new hope and treatment options to more lymphoma patients."

Orelabrutinib is a novel BTK inhibitor developed by InnoCare. With high target selectivity, it can avoid adverse events related to off-target effects and improve safety and efficacy.

CLL/SLL, one of the most prevalent forms of leukemia, is an indolent malignancy of B lymphocytes. Globally, there are 191,000 newly diagnosed CLL cases each year, with 61,000 related deaths1. The incidence rate of CLL/SLL is on the rise in China.

On April 25, 2025 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, reported that its Phase 1/2 clinical trial of NDI-219216, the company’s investigational non-covalent Werner syndrome helicase (WRN) inhibitor, is actively enrolling and dosing patients with advanced solid tumors (Press release, Nimbus Therapeutics, APR 25, 2025, View Source [SID1234652146]).

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"The initiation of this clinical trial marks an important milestone in advancing our novel WRN inhibitor program," said Anita Scheuber, M.D., Ph.D., Senior Vice President, Therapeutic Head, Oncology at Nimbus. "We are excited to be evaluating NDI-219216 in patients with advanced disease, who currently have limited treatment options when they experience disease progression on standard of care therapies. The trial is actively enrolling across multiple clinical sites, and we look forward to generating important additional safety and efficacy data as we advance this promising candidate through clinical development."

The Phase 1/2 clinical trial (NCT06898450) is an open-label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced cancer. The study will be conducted in three parts: Part A (dose escalation), Part B (dose optimization), and Part C (dose expansion).

Nimbus presented promising preclinical data on NDI-219216 (previously NTX-452) at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in October 2024. The data demonstrate that NDI-219216 is a potent and selective WRN inhibitor with significant tumor regression and sustained complete responses observed at low doses in MSI-H tumor models refractory to immunotherapy and chemotherapy.

The company will present new findings comparing covalent versus non-covalent WRN inhibition mechanisms and demonstrating NDI-219216’s superior efficacy across multiple preclinical MSI-H tumor models compared with other clinical-stage WRN inhibitors in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 25-30, 2025 in Chicago. The poster entitled "NDI-219216: a non-covalent, potent, selective and highly efficacious WRN inhibitor with best-in-class potential for the treatment of MSI-H tumors" highlights key preclinical findings related to NDI-219216, including:

Demonstration of activity against a potential resistance mutation at Cysteine 727 that could significantly reduce the efficacy of covalent WRN inhibitors
Robust tumor regression across multiple MSI-H tumor models, including those that are refractory to existing standard of care agents
Superior efficacy at lower doses and in less responsive MSI-H tumor models compared to other clinical-stage WRN inhibitors
"The data we are presenting at AACR (Free AACR Whitepaper) 2025 highlight several important features of our non-covalent WRN inhibitor," said Peter J. Tummino, Ph.D., President of Research and Development at Nimbus. "NDI-219216 has the potential for more durable target engagement than covalent inhibitors and maintains potency against potential resistance mutations. Its superior efficacy across multiple MSI-H tumor models, including those less sensitive to other WRN inhibitors and those refractory to current therapies, reinforces our belief that NDI-219216 represents a best-in-class opportunity with broad potential across multiple MSI-H tumor types with significant unmet need."

About NDI-219216

NDI-219216 is a highly potent and selective non-covalent investigational inhibitor of Werner syndrome helicase (WRN) activity being developed for the treatment of MSI-H tumors. WRN is a DNA helicase required for DNA replication and DNA repair and is a validated synthetic lethal target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of deficient mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric, and endometrial cancers. In preclinical studies, treatment with NDI-219216 exhibited robust antitumor activity across multiple cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) MSI-H tumor models, including models for colorectal, gastric, and endometrial cancers.

On April 25, 2025 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the conditional marketing authorization of zanidatamab, an investigational dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, as monotherapy for the treatment of adults with unresectable locally advanced or metastatic HER2-positive (IHC 3+)† biliary tract cancer (BTC) previously treated with at least one prior line of systemic therapy (Press release, Jazz Pharmaceuticals, APR 25, 2025, View Source [SID1234652162]).

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"This positive CHMP opinion is a welcome step for physicians and patients in Europe who face a critical unmet need in HER2-positive biliary tract cancers, a rare and aggressive group of cancers with poor prognosis and limited treatment options," said Robert Iannone, MD., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "If approved, zanidatamab would be the first HER2-targeted therapy licensed for this difficult-to-treat cancer in the EU, marking an important milestone in addressing this unmet need. We look forward to the European Commission’s decision and the opportunity to provide a new treatment option for patients."

The CHMP recommendation is based on data from the Phase 2b HERIZON-BTC-01 trial, which evaluated zanidatamab in previously treated, inoperable, and advanced or metastatic HER2-positive BTC.2,3

While biliary tract cancers (BTCs), which include gallbladder cancer (GBC) and cholangiocarcinoma (CCA),4 account for less than 1% of all human cancers,5 CCA is the second most common primary liver cancer after hepatocellular carcinoma (HCC).5 It comprises approximately 10–15% of all primary liver cancers,4,5 and its global mortality rate has risen in recent decades.5

Most BTC cases are diagnosed at an advanced stage due to the vague or nonspecific nature of early disease symptoms,6 making curative surgery an option for only a minority of patients.5,7,8 Although chemotherapy and, more recently, immunotherapy-based combinations are used in the first-line setting, disease progression is common, and second-line treatment options are, in the absence of molecular analysis, largely limited to chemotherapy.5,7,9 HER2 overexpression or amplification has been identified as a distinct molecular subtype of BTC10,11 and is associated with a worse prognosis compared to HER2-negative BTC.12 Yet, no HER2-targeted therapies are currently approved for this indication in the European Union (EU).

The CHMP’s recommendation will now be reviewed by the European Commission which has the authority to approve medicines in all EU Member States, Iceland, Norway, and Liechtenstein, and is expected to make a final decision.

About Zanidatamab
Zanidatamab is a dual HER2-targeted bispecific antibody that simultaneously binds extracellular domains 2 and 4 on separate HER2 monomers (binding in trans). Binding of zanidatamab with HER2 results in internalization leading to a reduction of the receptor on the cell surface. Zanidatamab induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and tumor cell death.13

On November 20, 2024, in the United States, the U.S. Food and Drug Administration (FDA) granted accelerated approval of zanidatamab-hrii (Ziihera) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.14 This accelerated approval was granted based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the ongoing Phase 3 HERIZON-BTC-302 confirmatory trial.14

Zanidatamab is also being investigated in multiple other clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule. Jazz has rights to commercialize zanidatamab in the U.S., Europe, Japan and all other territories except for those Asia/Pacific territories that Zymeworks previously licensed to BeiGene, Ltd. [which are Asia (excluding Japan), Australia and New Zealand].

The FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer.

About Biliary Tract Cancer
Biliary tract cancers (BTC), including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers worldwide and are often associated with a poor prognosis.5,7 Approximately 26% of patients with BTC are HER2-positive.10 The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers.7,15 Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.16 Most patients (>65%) are diagnosed with tumors that cannot be removed surgically.

On April 25, 2025 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported the publication of 3 abstracts for poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Obsidian Therapeutics, APR 25, 2025, View Source [SID1234652179]). In addition to a trial-in-progress study design update on the ongoing multicenter study Agni-01 (NCT06060613), Obsidian will share preclinical data from our cytoDRiVE platform demonstrating spatiotemporal regulation of membrane-bound IL12 in syngeneic solid tumor models and preclinical data on OBX-115 TIL phenotype starting from NSCLC tumor tissue.

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Obsidian is presenting new preclinical data from its cytoDRiVE regulation platform, further demonstrating the ability to unlock the therapeutic window of potent cytokines and broaden the reach of armored cell therapies. The poster for abstract LB025 demonstrates the application of Obsidian’s regulatable cytoDRiVE platform to enhance antigen-responsive ("spatial") promoter-induced activation by adding a critical pharmacologically regulatable ("temporal") signal to exert tight "spatiotemporal" control over IL12 expression1, resulting in a positive impact on safety and tumor control in syngeneic solid tumor models.

Obsidian will also present preclinical data from a multimodal phenotyping analysis comparing OBX-115 TIL generated with its proprietary manufacturing process to conventional, non-engineered TIL using NSCLC tumor samples. The poster for abstract LB359 provides evidence that, as observed with melanoma2, the OBX-115 process generates a minimally exhausted, CD8+ enriched and memory "stem-like" T-cell phenotype. Additionally, the tumor reactive gene signature analysis showed that the drug product is enriched for putative tumor-reactive T-cell clonotypes.

Obsidian Posters at AACR (Free AACR Whitepaper) 2025:

Spatiotemporally regulated expression of membrane-bound interleukin 12 (mbIL12) for armored adoptive cell therapy (ACT) shows strong antitumor activity in syngeneic solid tumor models without overt toxicity (Abstract LB025)
Presenting Author: Ross T, Obsidian Therapeutics
Poster: Sunday, April 27, 2:00-5:00pm CT
OBX -115 TIL from non-small cell lung cancer (NSCLC) are enriched for putative tumor-reactive, stem-like T cells with enhanced tumor cytotoxicity: Results from multimodal phenotyping analysis (Abstract LB359)
Presenting Authors: Schoenfeld AJ, Memorial Sloan Kettering Cancer Center
Poster: Tuesday, April 29, 2:00-5:00pm CT
Trial in progress: Phase 1/2 study of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced solid tumors (Abstract CT244)
Presenting Author: Shoushtari AN, Memorial Sloan Kettering Cancer Center
Poster: Tuesday, April 29, 2:00-5:00pm CT
1 Smith et al., SITC (Free SITC Whitepaper) 2024 (Abstract 463).
2 Bernatchez et al., ISCT 2024 (Abstract 909).

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. Obsidian is investigating OBX-115 in the phase 1/2 Agni-01 multicenter trial in patients with advanced solid tumors (NCT06060613).

On April 25, 2025, Bullfrog AI Holdings, Inc. (the "Company") entered into an At-The-Market Sales Agreement (the "Agreement") with BTIG, LLC ("BTIG"), pursuant to which the Company may offer and sell, from time to time in its sole discretion, shares of its common stock, par value $0.00001 per share (the "Common Stock"), having an aggregate offering price of up to $20,000,000 (the "Shares"), through BTIG as its sales agent (Filing, 8-K, Bullfrog AI, APR 25, 2025, View Source [SID1234652222]). The Shares will be offered and sold pursuant to the Company’s Registration Statement on Form S-3 (Registration No. 333-281341) filed by the Company on August 7, 2024, as amended by Amendment No. 1 thereto filed on August 15, 2024, and declared effective by the U.S. Securities and Exchange Commission on August 21, 2024 (the "Registration Statement") and the Company’s prospectus supplement filed on April 25, 2025 that forms a part of such Registration Statement. The issuance and sale, if any, of the Shares may be made by any method permitted by law deemed to be an "at-the-market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, including, without limitation, sales made directly on the Nasdaq Capital Market, or on any other existing trading market for the Common Stock.

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The Company is not obligated to make any sales of the Common Stock, and BTIG is not required to sell any specific number or dollar amount of shares of the Common Stock, under the Agreement. The Company and BTIG may suspend or terminate the offering of Shares upon notice to BTIG or the Company, as applicable, and subject to other conditions.

Subject to the Company’s request to sell Shares, BTIG will act as the Company’s sales agent and use commercially reasonable efforts, consistent with its normal trading and sales practices, to sell on the Company’s behalf, from time to time, such Shares based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions that the Company may impose). The Company will pay BTIG a commission fee of 3% of the gross sales price of any Shares sold through BTIG under the Agreement, and also has provided BTIG with customary representations and warranties and indemnification under the Agreement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and incorporated herein by reference. The opinion of Ballard Spahr regarding the validity of the Shares that will be issued pursuant to the Agreement is also filed herewith as Exhibit 5.1.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.