On June 14, 2021 Asieris Pharmaceuticals (Asieris) reported that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application of oral APL-1202 in combination with BeiGene’s tislelizumab as neoadjuvant therapy in patients with muscle invasive bladder cancer (MIBC) (Press release, Asieris Pharmaceuticals, JUN 14, 2021, View Source [SID1234583974]). Asieris will accelerate the initiation of the clinical trial enrollment in the U.S. and also file a Clinical Trial Application (CTA) to the National Medical Products Administration (NMPA) of China in the near future.

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This is an open-label, multi-center Phase I/II clinical study with the following objectives: to evaluate the safety in MIBC patients; to determine the RP2D (recommended Phase 2 dose), and to assess efficacy as neoadjuvant therapy for MIBC.

APL-1202 is an orally available reversible MetAP2 Inhibitor with anti-angiogenic, anti-tumor activities and can also modulate tumor immune microenvironment. It is currently in Phase III/pivotal clinical trials in China, either as single agent as first-line treatment for patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC), or in combination with a chemotherapy as second-line treatment in patients with intermediate and high-risk chemo-refractory NMIBC. Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. The China National Medical Products Administration (NMPA) has granted tislelizumab approval in three indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies and for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

According to the 2020 Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Urothelial Carcinoma, the Level I recommendation for MIBC is that patients who tolerate cisplatin undergo radical cystectomy (RC) after neoadjuvant chemotherapy. The commonly used chemotherapy regimen is gemcitabine plus cisplatin (GC). However, cisplatin can cause serious side effects such as renal dysfunction, peripheral neuropathy, and bone marrow suppression, and some patients are intolerant. Patients with intolerance to cisplatin don’t have any preoperative/neoadjuvant therapy that can bring survival benefits.

"We are very pleased that FDA approved the IND application for oral APL-1202 in combination with tislelizumab as a neoadjuvant therapy in MIBC patients," said Dr. Xue Yong, MD, PhD, Chief Medical Officer at Asieris. "The approval is expected to accelerate the clinical development, and Asieris will conitnue to explore cutting-edge technologies and therapeutics in our focused areas to meet the urgent medical needs and establish an outstanding portfolio that covers diagnosis and treatment to benefit more patients. "

On June 14, 2021 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, reported that it has commenced an underwritten public offering of $125 million of its common stock (Press release, RAPT Therapeutics, JUN 14, 2021, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-announces-proposed-public-offering-common [SID1234585134]). In addition, RAPT expects the underwriters to be granted a 30-day option to purchase up to an additional $18.75 million of its common stock on the same terms and conditions. All of the shares of common stock are being offered by RAPT. The proposed offering is subject to market conditions, and there can be no assurance as to whether or when the proposed offering may be completed or as to the actual size or terms of the proposed offering.

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J.P. Morgan, SVB Leerink and Piper Sandler are acting as joint lead book-running managers for the proposed offering. Cantor is acting as book-running manager for the proposed offering.

The offering is being made pursuant to a shelf registration statement, including a base prospectus, filed by RAPT with the Securities and Exchange Commission (SEC), which was declared effective by the SEC on November 16, 2020. The offering may be made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. When available, electronic copies of the preliminary prospectus supplement and the accompanying prospectus may also be obtained from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected] or by telephone at (866) 803-9204; SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by email at [email protected] or by telephone at (800) 808-7525, ext. 6105; or Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, Attention: Prospectus Department, by email at [email protected] or by telephone at (800) 747-3924.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On June 14, 2021 CEBINA GmbH, Central European Biotech Incubator and Accelerator, reported the launch of Danube Labs, a partnership with Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) to fast-track early-stage academic research to drug discovery and development (Press release, Evotec, JUN 14, 2021, View Source;announcements/press-releases/p/evotec-partners-with-cebina-to-launch-danube-labs-a-partnership-to-develop-cutting-edge-biotechnology-projects-sourced-from-central-and-eastern-european-universities-and-research-institutions-6070 [SID1234583941]). The joint project, financed by a dedicated group of private investors, will identify, and develop academic projects into mature therapeutic product development opportunities, primed for biotech company formation or partnering. Danube Labs aims to create up to 8 new biotech companies over 4 years, and is supported by CEBINA Bridge Capital Limited, a private fund established in Gibraltar and committed to providing a minimum investment of € 10 m.

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"We are excited to join forces with Evotec to expand our mission to transform promising research and early-stage drug discovery projects from Central and Eastern Europe into mature projects attractive for forming new companies that will be embedded in the biotech ecosystem CEBINA has created. This partnership brings together great entrepreneurial expertise and experience in drug development that, we believe, will enable us to generate breakthrough therapeutics," commented Eszter Nagy, MD PhD, founder and CEO&CSO of CEBINA.

"Danube Labs represents the latest of Evotec’s BRIDGE partnerships, where we explore exciting academic science with the aim to accelerate the translation of early-stage drug discovery from academia to patients," commented Mark Slack, PhD, VP Academic Partnerships at Evotec. "Through our partnership with CEBINA, we see the opportunity to seek out and validate promising innovative research in Central and Eastern Europe".

On June 14, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company focused on novel immunotherapy platforms for the treatment of solid tumors, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to PVSRIPO for the improved survival in patients with advanced melanoma who have disease progression after anti-PD-1/anti-PD-L1 therapy (Press release, Istari Oncology, JUN 14, 2021, View Source [SID1234583959]). PVSRIPO is a novel viral immunotherapy with multiple clinical trials underway in combination with anti-PD-1/L1 therapies, aimed at further demonstrating safety and its ability to activate a patient’s immune system, which we believe will facilitate a systemic, durable anti-tumor response. In addition to Fast Track designation, FDA granted Orphan Drug Designation to PVSRIPO for the treatment of advanced melanoma earlier this year.

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Melanoma is the deadliest type of skin cancer with approximately 7,000 deaths in the U.S. each year1. Treatment-resistant, advanced melanoma patients have very poor survival rates, with less than 30% of metastatic melanoma patients surviving 5 years1. PVSRIPO aims to address the significant unmet need.

Fast Track is an FDA program designed to facilitate the expedited development of drugs to treat serious conditions and address an unmet medical need. This designation enables more frequent FDA interactions related to the drug development program, as well as rolling review, and potentially priority review, of the marketing application.

"We are thrilled with FDA’s decision to grant both Fast Track and Orphan Drug Designation to PVSRIPO for the treatment of advanced melanoma," said Matt Stober, President and Chief Executive Officer at Istari Oncology. "We strategically prioritized the clinical trials program for melanoma given the lack of effective options for patients whose cancer can’t be surgically resected and who failed other treatments. Together, these designations position us to expedite the development pathway and the necessary regulatory processes required to seek FDA marketing approval of PVSRIPO."

Istari is recruiting for LUMINOS-102, a Phase 2 open-label, randomized trial (clinicaltrials.gov NCT04577807) in patients with advanced, unresectable melanoma who previously failed anti-PD-1 therapy. The first patient dosed in LUMINOS-102 was announced on March 31, 2021. LUMINOS-102 follows a successful Phase 1 monotherapy study of PVSRIPO in anti-PD1 refractory advanced melanoma in which patients who received three PVSRIPO injections (6/12) had an overall response rate of 67% (4/6).

For more information about Istari Oncology and their ongoing clinical trials, visit www.istarioncology.com.

About PVSRIPO
PVSRIPO is an investigational immunotherapy based on the live attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO has a distinct target (the poliovirus receptor, CD155), which is expressed on virtually all solid tumors and antigen-presenting cells. Via CD155, PVSRIPO targets tumors with two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) engaging innate and adaptive anti-tumor immune responses via non-lethal infection of antigen-presenting cells in the tumor, which stimulates a specific signaling pathway resulting in a sustained, robust type-I/III interferon-dominant response, with minimal release of unwanted cytokines. Its effects are potentiated by prior vaccination against poliovirus. PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma. PVSRIPO has also been granted Orphan Status by the FDA for advanced melanoma.

On June 14, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the Investigational New Drug (IND) application for the company’s novel Bcl-2 inhibitor, lisaftoclax (APG-2575), has been cleared by the US Food and Drug Administration (FDA) and the company is poised to initiate a clinical study of lisaftoclax as a single agent or in combination with other antitumor therapies for the treatment of patients with advanced estrogen receptor-positive (ER+) breast cancer or other solid tumors (Press release, Ascentage Pharma, JUN 14, 2021, View Source [SID1234583975]).

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This global multicenter, open-label Phase Ib/II clinical study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of lisaftoclax as a single agent in patients with advanced solid tumors, or in combination with palbociclib in patients with metastatic ER+ and human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer relapsed or refractory to prior treatment with cyclin–dependent kinase 4/6 (CDK4/6) inhibitors.

Breast cancer is one of the most common malignancies in women. About 75% of all breast cancer cases are hormone receptor positive (HR+)1, mainly estrogen receptor positive (ER+), and the antiapoptotic protein Bcl-2 is overexpressed in around 85% of this subset2. Endocrine therapy is the standard of care treatment for patients with early-stage or metastatic HR+/HER2- breast cancer. In the first-line treatment of metastatic ER+ breast cancer, an CDK4/6 inhibitor (palbociclib, ibociclib, or abemaciclib) in combination with endocrine therapy can offer longer progression-free survival (PFS) and overall survival (OS), as compared to endocrine therapy alone3,4. In the second-line setting, phosphoinositide 3-kinase (PI3K) inhibitor plus fulvestrant, and everolimus plus endocrine therapy can effectively target the PI3K-AKT-mTOR pathway, thus offering additional treatment options for patients who failed first-line treatments3. However, patients treated with endocrine therapies and targeted therapies commonly develop drug resistances, eventually necessitating chemotherapies. Therefore, there is an urgent clinical need for novel targeted therapies that can effectively blockade mutational pathways and delay chemotherapies.

Lisaftoclax is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. Lisaftoclax is designed to treat hematologic malignancies and solid tumors by selectively blocking antiapoptotic protein Bcl-2 to restore the normal apoptosis process in cancer cells. Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China. Previously, lisaftoclax had received clearances and approvals for multiple Phase Ib/II clinical studies in China, Australia, the US, and Europe, and is currently being developed in a range of hematologic malignancies globally. As a single agent, lisaftoclax has potent antitumor activity in Bcl-2-dependent tumor cell lines, and has shown broad antitumor effects when combined with other antitumor therapies.

Preclinical data of lisaftoclax in combination with palbociclib showed that palbociclib can induce cell cycle arrest and apoptosis, while lisaftoclax can bolster the expression of proapoptotic proteins such as BIM and downregulate ER levels, while lowering the levels of phosphorylated Rb protein, and the cyclin D1 and E. Therefore, Bcl-2 inhibitors combined with CDK4/6 inhibitors can synergistically enhance cell cycle arrest while inducing the cell death of ER+ tumors.

"Lisaftoclax is a core drug candidate in our apoptosis-targeted pipeline. This IND clearance by the US FDA for lisaftoclax in patients with solid tumors marks another major milestone for this drug candidate," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the first China-developed Bcl-2 inhibitor entering clinical development in China, lisaftoclax has enormous therapeutic potential, both as a single agent and in combinations. Lisaftoclax has shown promising clinical activity and favorable tolerability in hematologic malignancies, and we look forward to expanding and deepening our investigation of lisaftoclax in solid tumors. We are now advancing the clinical development of this drug candidate globally in the hope of soon benefiting patients in China and around the world."