On July 7, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing both first- and best-in-class therapies for hematological malignancies, reported that its novel BCR-ABL1 tyrosine kinase inhibitor (TKI), olverembatinib, has been approved by the Pharmaceutical Administration Bureau (ISAF) of the Macau Special Administrative Region (SAR) of the People’s Republic of China for the treatment of adult patients with tyrosine kinase inhibitors (TKI)-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first-and second-generation TKIs (Press release, Ascentage Pharma, JUL 7, 2024, View Source [SID1234644697]). This approval marks another major milestone for olverembatinib following initial approvals granted to the drug in the Chinese mainland for the above indications.

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Olverembatinib, a novel drug developed by Ascentage Pharma with support from the National Major New Drug Development program, is the first third-generation BCR-ABL1 inhibitor approved by China’s National Medical Products Administration (NMPA). As a potential global best-in-class drug that can effectively target BCR-ABL1 and a spectrum of BCR-ABL1 mutants, including the T315I mutation, clinical trial results of olverembatinib have already been included in the National Comprehensive Cancer Network (NCCN) guidelines for the management of CML.[1] Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics. All lead drug candidates are being studied as they are an investigational drug and not approved in the US.

"Olverembatinib has the potential to be a global best-in-class drug. We are glad that the drug is set to benefit patients with CML in Macau, China, with the approval marking another major milestone in the clinical development of olverembatinib," said Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma. "Since its inception, Ascentage Pharma has steadfastly committed to its mission of addressing unmet clinical needs in China and around the world. We are confident that over time, olverembatinib and our other investigational drugs will bring greater benefits to more patients globally."

On July 5, 2024 Zhiyi Biotech, a clinical-stage biotech leading in discovery and development of LBPs (live biotherapeutic products), reported positive results from a Phase 1 clinical trial in U.S. of SK10 (Press release, Guangzhou Zhiyi Biotech, JUL 5, 2024, View Source [SID1234644693]). SK10 is an innovative heat-killed Bacteroides fragilis product for Chemotherapy-induced Diarrhea (CID).

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This was a randomized, double-blind, placebo-controlled, sequential dose-escalation clinical study to evaluate the safety and tolerability of SK10 in healthy adult subjects. A total of 24 healthy subjects were enrolled in the study. All dose groups of SK10 were generally safe and well tolerated. All the TEAEs (treatment-emergent adverse event) were mild in severity without dose-dependent increase.

This promising result lays the foundation for SK10 as a potential novel drug for CID patients.

About SK10:

SK10, the first Bacteroides fragilis-based LBP obtained FDA IND approval, is also the first LBP of Next-generation probiotics developed by Chinese biotech company that approved for clinical trials by FDA. Studies have shown that SK10 can ameliorate 5-FU induced injury via mitochondrial apoptotic BCL2/BAX pathway, reduce inflammatory cytokines, and enhance mucosal barrier function, thereby effectively inhibiting the inflammatory response of intestinal epithelial cells induced by chemotherapy and the associated diarrhea symptoms.

Meanwhile, heat-killed Bacteroides fragilis has better safety in cancer patients and better commercialization performance.

About CID:

Cytotoxic drugs or targeted therapy can cause drug-associated diarrhea. However, available drugs for CID are limited. For example, loperamide, as a short-term symptomatic treatment, and octreotide, an intravenous/subcutaneous injection, serious adverse effects have been reported for both drugs. Hence the need for effective drugs is urgent.

On July 5, 2024 Hinova Pharmaceuticals Inc. (688302.SH), a leading biopharmaceutical company dedicated to developing innovative cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for HP518, an investigational drug for the treatment of Androgen-receptor positive (AR+) triple-negative breast cancer (TNBC) (Press release, Hinova Pharmaceuticals, JUL 5, 2024, View Source [SID1234644692]). This designation is intended to expedite the development and review process for drugs that address serious conditions and fill an unmet medical need.

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About HP518

HP518 is a potent PROTAC AR degrader showing efficacy in AR+ TNBC. In preclinical IND-enabling studies, HP518 has demonstrated promising antitumor activity in AR+ TNBC animal models, showcasing significant tumor reduction and a favorable safety profile. The molecular subforms of TNBC are particularly aggressive forms of breast cancer that lack targeted treatment options, accounting for approximately 15-20% of all breast cancer cases, and are characterized by the absence of estrogen and progesterone receptors and HER2 expression. Notably, a significant proportion of TNBC cases (up to 50%) express the androgen receptor, highlighting the potential impact of AR-targeted therapies like HP518.

HP518 is an oral AR PROTAC protein degrader that degrades both wild-type AR and clinically relevant AR ligand-binding domain (LBD) mutants including L702H. Phase 1 clinical trial in Australia achieved several long term PSA50 and partial responses (PR), demonstrated HP518’s promising efficacy and acceptable safety profile in mCRPC patients. The clinical Phase 1/2 trial of HP518 for patients with mCRPC in China is ongoing.

FDA Fast Track Designation

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need. Fast Track designation enables more frequent communication with the FDA to discuss the drug’s development plan and ensures eligibility for Accelerated Approval and Priority Review if relevant criteria are met.

"We are thrilled to receive Fast Track designation from the FDA for HP518," said Dr. Yuanwei Chen, Chief Executive Officer of Hinova. "This designation underscores the significant need for new treatment options for patients with TNBC and highlights the potential of our investigational therapy to make a meaningful impact on this devastating disease. The discovery of HP518’s novel mechanism of action provides new hope for effective treatment. We look forward to working closely with the FDA to advance HP518 through the clinical development process as efficiently as possible."

Next Steps

Hinova plans to update in near future the existing IND (IND 164902) for TNBC development. The company is committed to accelerating the development of HP518 and bringing this promising therapy to patients in need.

On July 5, 2024 Biostar Pharma, Inc., the U.S. subsidiary of Beijing Biostar Pharmaceuticals Co., Ltd. (Biostar), which is a synthetic biology-driven biopharma company focusing on the development and commercialization of innovative oncology drugs, reported that their core pipeline product Utidelone Injection (UTD1) had been granted to conduct a phase 2 study (BG01-2402) for HER2- breast cancer brain metastasis (BCBM) by the US FDA (Press release, Beijing Biostar Technologies, JUL 5, 2024, View Source;breast-cancer-brain-metastasis-302189908.html [SID1234644691]).

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Depending on the molecular classification of breast cancer, approximately 20~50% of metastatic breast cancer patients develop brain metastases.[1] The current standard of care for BCBM is primarily local treatment with surgery and radiation therapy, supplemented by drug therapy. Due to blood-brain barrier (BBB) and blood-tumor barrier (BTB), many drugs that are effective for extracranial metastasis of breast cancer have very limited intracranial permeability, leading to poor prognosis for BCBM patients, especially with HER2- BCBM.[2-3] The mPFS for HR+/HER2- BCBM is about 4-6 months,[4-8] while the mFPS for TNBC brain metastasis is only 2.8 months.[9]

In recent years, multiple small-molecule TKIs and ADC drugs have brought survival benefits to HER2+ BCBM patients. However, there is still a lack of drug treatment regimens with proven efficacy for HER2- BCBM, and no drug has been approved for HER2- BCBM worldwide, suggesting a significant unmet medical need.

Utidelone can penetrate BBB due to its unique physicochemical characteristics and insusceptibility to P-glycoprotein-mediated efflux, which has been confirmed by preclinical drug tissue distribution studies and several clinical trials. A phase 2 study of utidelone in combination with bevacizumab for the treatment of HER2- BCBM presented at the ASCO (Free ASCO Whitepaper) 2024 demonstrated efficacy outcomes of 42.6% of CNS-ORR, 7.7 months of mPFS, and 74.4% of 12-month OS rate with total 47 eligible patients being enrolled. The efficacy was even better in HR-/HER2- subgroup, showing 55% of CNS-ORR and 8.4 months of mPFS. The safety was manageable with majority of the AEs being Grade 1~2, suggesting a promising efficacy and manageable safety profile of utidelone for HER2- BCBM, and the potential of utidelone to become a new treatment option in the space.

Utidelone has been granted an "orphan drug designation" by the US FDA for the treatment of BCBM in Mar 2024. Biostar then filed an IND application for this phase 2 study for HER2- BCBM. The US FDA clearance of the application marks an important milestone of Biostar’s globalization development strategy.

About BG01-2402 Study

BG01-2402 study refers to "A Pivotal Phase II Clinical Trial of Utidelone Injection (UTD1) Plus Capecitabine (CAP) in HER2-negative Breast Cancer Patients with Brain Metastases". The purpose of the study is to evaluate the intracranial and systemic efficacy of Utidelone Injection in combination with capecitabine in HER2- BCBM patients. This study follows a Simon’s 2-stage design, and is planned to be conducted at 10-15 sites in the US with enrollment target of 120 patients. The primary endpoint is CNS-ORR; the secondary endpoints include PFS, DOR and OS, etc.

On July 5, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, and IASO Biotechnology ("IASO Bio"), a biopharmaceutical company engaged in discovering, developing, manufacturing, and marketing innovative cell therapies and antibody products, reported the agreement on a series of cooperation, including IASO Bio’s purchase from Innovent regarding its relevant right of FUCASO (Equecabtagene Autoleucel) and obtaining license from Innovent regarding the intellectual property related to FUCASO, as well as Innovent’s equity investment in IASO Bio (Press release, Innovent Biologics, JUL 5, 2024, View Source [SID1234644690]).

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According to the agreement, IASO Bio will purchase Innovent’s relevant rights of FUCASO under the original "BCMA CAR-T Cell Therapy Cooperation Agreement" at the agreed price and Innovent will use the proceeds to acquire an 18% stake in IASO Bio. Under the new strategic cooperation framework, the parties will achieve high-level integration in the field of cellular immunotherapy. IASO Bio obtains global commercial rights and the intellectual property license for FUCASO and will be fully responsible for development, manufacturing and commercialization of the product, while Innovent becomes a strategic shareholder of IASO Bio.

FUCASO was jointly developed by Innovent and IASO Bio and was approved by the National Medical Products Administration (NMPA) on June 30, 2023 to treat relapsed and/or refractory multiple myeloma (RRMM) patients who have undergone at least 3 lines of prior treatment and progressed. FUCASO is the world’s first approved fully human CAR-T product, as well as the first approved BCMA CAR-T product in China. On March 28, 2024, FUCASO received the investigational new drug (IND) application for treating RRMM patients who have undergone 1-2 lines of prior therapies and are refractory to lenalidomide. In 2024, its IND application for the treatment of autoimmune diseases such as refractory generalized myasthenia gravis (gMG) has also been approved in both China and the United States.

Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated: "We appreciate IASO Bio for their expertise, innovation, and strong execution capability in the field of cell therapy. We believe that the new collaboration model will better leverage our mutual strengths and resources. The new model will endow more integrated resources and dedicated team in the full chain of manufacturing, development and commercial operation of CAR-T cell therapy as a special novel modality. Also, we will continue to support IASO Bio as a strategic shareholder. We look forward to working with IASO Bio to improve the accessibility of medications and bring hope to patients worldwide."

Ms. Zhang Jinhua, Founder, Chairwoman and CEO of IASO Bio, stated: "We extend our gratitude to Innovent for their recognition and trust in our research and development capabilities as well as our commercialization strength. Over the past six years, we have built a solid partnership with Innovent and witnessed each other’s innovation and growth in the biopharmaceutical field. We firmly believe that this new strategic alliance will bring significant synergistic effects to both parties. We can fully leverage our strengths and work together to advance innovative therapeutic solutions. We will remain committed to our original mission of bringing more innovative treatments to patients and look forward to achieving mutual success in our future strategic partnership with Innovent."