On July 14, 2021 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and Ascentage Pharma (6855.HK), reported a multifaceted strategic collaboration (Press release, Innovent Biologics, JUL 14, 2021, https://www.prnewswire.com/news-releases/innovent-and-ascentage-pharma-reach-multifaceted-strategic-agreement-including-joint-commercialization-of-olverembatinib-in-china-joint-clinical-development-on-multiple-products-and-equity-investment-301333902.html [SID1234584858]). This collaboration includes: i) the joint commercialization of HQP1351 (olverembatinib) in China; ii) the collaborative clinical development of Bcl-2 inhibitor APG-2575 (lisaftoclax) with the anti-CD20 monoclonal antibody HALPRYZA (rituximab biosimilar injection) and the anti-CD47 monoclonal antibody letaplimab (IBI188); and iii) the equity investment in Ascentage Pharma.

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HQP1351, the core drug candidate of Ascentage Pharma, is the first China-developed third-generation BCR-ABL TKI targeting drug-resistant chronic myeloid leukemia (CML). At present, an NDA for HQP1351 has been submitted and subsequently granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) in China. According to the agreement, Innovent and Ascentage Pharma will be jointly responsible for the subsequent R&D of HQP1351 in China. Upon being granted a New Drug Application (NDA) approval, the two companies will jointly commercialize HQP1351 in China and equally split the profit generated by the joint commercialization. Innovent will leverage its advantage of broad commercial channel and experienced oncology commercial team to roll out HQP1351 to hospitals and pharmacies at various tiers, in aims to make this novel therapeutic available to the cancer patients in China.

After signing the agreement, Ascentage Pharma will receive an upfront payment of US$30 million from Innovent. Upon achieving certain pre-specified milestones in development, registration and annual sales performance of HQP-1351, Ascentage Pharma is eligible to receive up to US$115 million in milestone payments.

In addition, the two companies agree to jointly explore the possibility of developing the Bcl-2 TKI APG-2575 with the anti-CD20 monoclonal antibody HALPRYZA (rituximab biosimilar injection) and the anti-CD47 monoclonal antibody letaplimab (IBI188), in certain indications.

Furthermore, Innovent will subscribe to Ascentage Pharma’s common shares for a total consideration of US$50 million at HK$44.0 per share, and be granted stock warrants that will allow it to acquire additional Ascentage Pharma’s common shares for a total consideration of US$50 million at subscription price of HK$57.2 per share within the next two years.

Dr. Michael Yu, Founder, Chairman and CEO of Innovent Biologics, stated, "We are excited to form this strategic collaboration with Ascentage Pharma, a pioneer in the field of innovative R&D of apoptosis-targeted therapies. Innovent is deeply engaged in the oncology area having built up a robust oncology pipeline of nearly 20 clinical stage assets, an industry-leading medical operations and regulatory affairs team, a broad commercial channel and a professional commercial team of over 2000 people. The collaboration with Ascentage pharma adds another near-to-launch innovative medicine HQP1351 to our pipeline, and we will leverage our advantage in the joint commercialization after the drug is approved. In addition, this collaboration creates potential synergy with our oncology pipeline such as CD47 and CD20 antibodies. Meanwhile, we are impressed with Ascentage Pharma’s strong R&D capability and rich pipeline, and we hope to join in our partner’s growth potential realization through the strategic equity investment. We look forward to partnering with Ascentage Pharma and bringing the innovative therapies of both parties to patients as soon as possible.

The strategic collaboration represents a new model for China biopharmaceutical companies to work together to bring additional benefit to patients. Innovent has been exploring diversified and innovative strategic partnership models with outstanding pharmaceutical companies globally with the aim to make more innovative therapies available. This collaboration proves once again that Innovent is an ideal partner to help expand pipeline development and product commercialization."

Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, stated, "Innovent is a leading biopharmaceutical company with outstanding integrated capabilities in the R&D and commercialization of innovative therapies. It is our great pleasure to enter into this multifaceted and comprehensive landmark partnership with Innovent. HQP1351 is a novel therapeutic with practice-changing potentials. We hope that by leveraging the two companies’ expertise in clinical development, we will be able to quickly expand the indications of HQP1351. Another one of our assets, APG-2575, is the world’s second, and China’s first Bcl-2 inhibitor that has demonstrated compelling clinical activity with best-in-class potential. As a small-molecule drug, APG-2575’s potential utility in combination with Innovent’s anti-CD20 monoclonal antibody and anti-CD47 monoclonal antibody is very promising. The equity investment in Ascentage Pharma is a major strategic investment signifying Innovent’s strong recognition of our R&D capabilities and our growth potential, and generates powerful tailwind to our global clinical development programs. Moreover, this collaboration between two companies with shared company cultures and mission is groundbreaking for China’s biopharmaceutical industry. We hope this partnership between the two companies will accelerate the development of innovative therapeutics in China and benefit more patients around the world."

About Olverembatinib (HQP1351)

Being developed by Ascentage Pharma, HQP1351 is a novel, orally active, potent third-generation BCR-ABL tyrosine kinase inhibitor (TKI) designed to effectively target a spectrum of BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL TKI targeting drug-resistant chronic myeloid leukemia (CML). Since 2018, the clinical results of HQP1351 have been selected for oral presentations at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting for three years in a row. At present, a New Drug Application (NDA) for HQP1351 has been submitted in China, and the application was subsequently granted the Priority Review status. Moreover, HQP1351 was cleared by the US Food and Drug Administration (FDA) to enter a Phase Ib clinical study, and was subsequently granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA.

About Lisaftoclax (APG-2575)

APG-2575 is a novel, orally administered small-molecule Bcl-2‒selective inhibitor being developed by Ascentage Pharma. APG-2575 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. APG-2575 is the first China-developed Bcl-2 inhibitor entering clinical development in China.

At present, APG-2575 has been cleared and approved to enter multiple Phase Ib/II studies in the US, China, Europe, and Australia, and is being developed globally for the treatment of multiple hematologic malignancies including chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and breast cancer. To date, APG-2575 has been granted five ODDs by the US FDA for the treatment of Waldenström macroglobulinemia (WM), CLL, multiple myeloma (MM), AML, and follicular lymphoma (FL).

About HALPRYZA (rituximab biosimilar injection)

HALPRYZA,a rituximab biosimilar injection, is a recombinant human/murine chimeric monoclonal antibody drug co-developed and co-commercialized by Innovent and Eli Lilly and Company. Rituximab binds to the CD20 antigen on the surface of B lymphocytes and mediates complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Normal and malignant B cells are targeted for destruction by the antibody, thereby achieving anti-tumor and immunosuppressive therapeutic effects. In China, HALPRYZA is approved by National Medical Products Administration (NMPA) for diffuse large b cell lymphoma (DLBCL), follicular lymphoma (FL), and CLL.

About letaplimab (IBI188)

IBI188 (letaplimab), developed by Innovent Biologics, is a recombinant fully humanized IgG4 monoclonal antibody targeting CD47. CD47 is a transmembrane protein that blocks phagocytosis of macrophage by binding to the signaling regulatory protein (SIRP) on the surface of macrophage, to send a "don’t eat me" signal. After blocking this myeloid checkpoint, IBI188 (letaplimab) enhanced phagocytosis of tumor cells and cross-activated T cells. Preclinical data showed that IBI188 (letaplimab) had clear target, clear mechanism of action and significant efficacy. Phase 1a clinical data showed that the escalation of all the preset doses has completed, with the highest exploratory dose of 30mg/kg QW. No dose-limiting toxicity occurred in each dose group, and IBI188 (letaplimab) was well tolerated generally.

On July 14, 2021 Ryvu Therapeutics (WSE: RVU), a clinical stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that the U.S. Food and Drug Administration, FDA, has lifted a partial clinical hold, previously announced on April 8, 2021, on the first-in-human (FIH) Phase Ib, dose escalation clinical trial of RVU120 (also known as SEL120) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (high-risk MDS), being conducted in the United States (Press release, Ryvu Therapeutics, JUL 14, 2021, View Source [SID1234584859]).

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"We are thankful to FDA for working with us in a swift and interactive manner to review the data from the trial and introduce modifications to the study protocol. We believe that the initially demonstrated benefit of treatment with RVU120 as a single agent for AML and MDS patients, coupled with the amended study protocol will lead to a safe, timely and successful completion of the clinical trial. We will be working closely with the investigators and the clinical sites to obtain IRBs’ approvals on the revised protocol and resume patient enrollment in Q3 2021" – said Pawel Przewiezlikowski, Chief Executive Officer of Ryvu.

Based on the recommendations from the FDA, the study will resume enrollment at a 75mg dose (Every Other Day – EOD) in a standard 3+3 design, according to a revised protocol intended to increase patients’ safety. Protocol amendment covers modified exclusion criteria, scope of monitoring and frequency of laboratory testing. Following the completion of the 75mg cohort, the data generated will be reviewed by the agency and a further dose escalation strategy will be established. Additionally, Ryvu plans to use 75mg as the starting dose for the single-agent, open-label Phase I/II trial investigating the safety and efficacy of RVU120 in patients with relapsed/refractory metastatic or advanced solid tumors, which will commence patient enrollment in Q3.

The partial clinical hold was issued following Ryvu’s recent report to the FDA of a Serious Adverse Event (SAE) involving a patient death that may possibly be related to RVU120. Study enrollment was suspended but patients already on treatment could continue treatment. As of July 14, 2021 one patient still remains on RVU120 treatment.

The initial safety and efficacy data from the first four cohorts in the trial were presented at the Virtual EHA (Free EHA Whitepaper) Congress on June 11, 2021. RVU120 demonstrated acceptable safety profile and two clinically relevant responses were observed in the first five AML and high-risk MDS patients treated: one complete response (CR) and one erythroid response.

About RVU120

RVU120 (SEL120) is a selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in in vitro and in vivo models as well as in onco-hematological malignancies. The first-in-human phase I study with RVU120, in relapsed or refractory AML or high-risk MDS, will resume enrollment of patients at 5 investigational sites in USA (View Source). Additional sites are planned to be activated in Poland in Q3 2021.

The initial safety and efficacy data from the first four cohorts in the trial was presented at the Virtual EHA (Free EHA Whitepaper) Congress on June 11, 202. RVU120 demonstrated acceptable safety profile and two clinically relevant responses were observed in the first five AML and high-risk MDS patients treated: one complete response (CR) and one erythroid response.

Translational data suggest that RVU120 is particularly effective in undifferentiated AML STAT5-positive cancers. Administration of RVU120 in orthotopic AML patient derived xenograft models reduced tumor burden to the level undetectable in the peripheral blood, decreased splenomegaly and resulted in partial bone marrow recovery at well tolerated doses.

In addition, RVU120 has demonstrated single agent efficacy in multiple solid tumor models. On May 28, 2021, Ryvu’s Clinical Trial Application (CTA) to commence a single-agent, open-label Phase I/II trial, investigating the safety and efficacy of RVU120 in patients with relapsed/refractory metastatic or advanced solid tumors, was approved by the Polish Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, and the respective Central Ethics Committee.

On March 25, 2020, the U.S. Food and Drug Administration (FDA) granted an orphan drug designation (ODD) to RVU120, for the treatment of patients with AML.

RVU120 (SEL120) has been internally discovered by Ryvu and has received support from the Leukemia & Lymphoma Society Therapy Acceleration Program (TAP), a strategic initiative to partner directly with innovative biotechnology companies and leading research institutions to accelerate the development of promising new therapies for blood cancers.

On July 14, 2021 INmune Bio, Inc. (NASDAQ: INMB) (the "Company" or "INmune Bio"), a clinical-stage immunology company focused on developing treatments that harness a patient’s innate immune system to fight disease, reported that it has entered into a definitive agreement with one healthcare focused institutional investor and one family office for the purchase and sale of 1,818,182 shares of its common stock at a price of $22.00 per share for gross proceeds of approximately $40 million in a registered direct offering (Press release, INmune Bio, JUL 14, 2021, View Source [SID1234584841]). The closing of the offering is expected to occur on or about July 16, 2021, subject to the satisfaction of customary closing conditions.

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A.G.P./Alliance Global Partners is acting as the sole placement agent for the offering.

INmune Bio intends to use the net proceeds from this offering for working capital and general corporate purposes and to advance the development of its product candidates and expand its pipeline. This includes the completion and data readout from the Company’s planned Phase 2 clinical trial of its lead clinical candidate, XPro1595, in patients suffering from Alzheimer’s disease, which is expected to commence by the end of 2021. "With this investment, we expect the Company’s Phase II program in Alzheimer’s disease is completely funded" said RJ Tesi MD, CEO of Inmune Bio.

The securities described above will be offered by the Company pursuant to an effective "shelf" registration statement on Form S-3 (File No. 333-254221) previously filed with the Securities and Exchange Commission (the "SEC") on March 12, 2021 and declared effective by the SEC on May 5, 2021. The securities may be offered only by means of a prospectus. A preliminary prospectus supplement and the accompanying prospectus relating to and describing the offering will be filed with the SEC. Electronic copies of the prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, 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 July 14, 2021 BERG, a clinical-stage biotech that employs patient biology and artificial intelligence (AI) to research diseases and develop innovative treatments, reported that it will present two poster presentations at the Society for Neuro-Oncology: Basic and Translational Omics of Brain Tumors and Their Microenvironment Conference, on July 15th and 16th, 2021 (Press release, Berg, JUL 14, 2021, View Source [SID1234584860]).

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The first presentation, entitled "Interrogative Biology: Unraveling insights into causal disease drivers by use of a dynamic systems biology and Bayesian AI to identify the intersect of disease and healthy signatures", will emphasize the features of BERG’s proprietary Interrogative Biology Platform. Specifically, the presentation will focus on how BERG’s platform combines Bayesian AI analytics and patient-derived biological samples to generate an unbiased, data-informed network for identifying targets and biomarkers for disease interception, providing the opportunity to better understand and monitor human health in real-time.

The second presentation, entitled "Delivery of Ubidecarenone (BPM 31510) to mitochondria effectuates metabolic reprogramming and redox activated apoptosis in Glioblastoma" will further detail the platform’s utility in biological data-driven clinical development for GBM, including insights on anti-cancer effects of its BPM 31510. The presentation will highlight the use of BERG’s platform in generating comprehensive digital maps of a GBM model in response to BPM 31510 treatment and, in turn, the novel insights leading to potential mechanisms underlying BPM 31510 efficacy in GBM, including targeting mitochondrial function, influencing intermediary metabolism and activation of apoptosis.

"Brain cancers, such as GBM, are destroying patients and their families," said Dr. Niven R. Narain, CEO, President and Co-founder of BERG. "Using Interrogative Biology to guide the development of BERG’s BPM 31510 has allowed us to position the drug for this highly metabolic and aggressive cancer in an effort to potentially address a serious unmet need in medicine."

GBM is a destructive type of brain cancer often recognized for its steep morbidity and mortality rates. There are no effective treatment options for the vast majority of patients available in the marketplace, thus substantiating the urgent need for novel therapeutic approaches to improve outcomes for this disease. BPM 31510 is a unique therapeutic modality, that specifically targets cell metabolism and shifts the cancer’s glycolytic dependency toward mitochondrial oxidative phosphorylation. When applied, it induces oxidative stress and causes cell death, specifically of cancer cells.

"BERG’s pioneering research to deepen our understanding and treatment of GBM continues to be a game changer across the industry," said Dr. Eric J. Nestler, Director of Friedman Brain Institute at Icahn School of Medicine at Mount Sinai and Board director for BERG. "The Interrogative Biology Platform is leading the charge to digitize biology for the future of healthcare, and will empower patients to take back control of their personal care."

Details of BERG Abstracts:

Abstract #: CSAO-1: Interrogative Biology: Unraveling insights into causal disease drivers by use of a dynamic systems biology and Bayesian AI to identify the intersect of disease and healthy signatures – View Source
Abstract #: OMRT-13: Delivery of Ubidecarenone (BPM 31510) to mitochondria effectuates metabolic reprogramming and redox activated apoptosis in Glioblastoma – View Source
The Abstracts are available online and the Posters will be available to registered 2021 SNO Basic and Translational Omics of Brain Tumors and Their Microenvironment Conference attendees starting Thursday, July 15, 2021.

On July 14, 2021 Lipocine Inc. (NASDAQ: LPCN), a clinical-stage biopharmaceutical company focused on metabolic and endocrine disorders, reported that it has entered into a global settlement and license agreement with Clarus Therapeutics Inc. ("Clarus") to resolve all outstanding claims in the on-going intellectual property litigation between the two companies as well as the on-going interference proceeding between the two companies (Press release, Lipocine, JUL 14, 2021, View Source [SID1234584842]).

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Under the terms of the settlement announced today, Lipocine and Clarus have agreed to dismiss the Lipocine Inc. v Clarus Therapeutics, Inc., No 19-cv-622 (WCB) litigation presently pending in the U.S. District Court for the District of Delaware. Additionally, both parties have reached an agreement on the interference proceedings captioned Clarus Therapeutics, Inc. v. Lipocine Inc., Interference No. 106,128 presently pending in the U.S. Patent and Trademark. The terms of the settlement remain confidential.