On May 16, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, reported ATG-101, a novel PD-L1/4-1BB bispecific antibody being developed by the company, has completed its quantitative and systems pharmacology (QSP) modeling that will provide data guiding the first-in-human study of ATG-101 (Press release, Antengene, MAY 16, 2021, View Source [SID1234580077]). Antengene plans to submit a clinical trial application for the first-in-human (FIH) study of ATG-101 in Australia starting in mid-2021, to be followed by submissions in US and China.

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QSP is a highly innovative methodology that has been used recently in drug discovery and development. QSP supports the pharmacological research of drugs through modeling and simulations, and quantitatively determines drug pharmacology and dynamical properties through integrated pharmacokinetics (PK), pharmacodynamics (PD), and statistical modeling, in providing evidential support to the design, decision-making, and dose selection in clinical trials1. In December 2020, Antengene entered into a strategic collaboration with Applied BioMath, LLC to initiate the pharmacology modeling of ATG-101 to determine the starting and efficacious doses for the first-in-human study of the drug candidate. Completing this QSP modeling will deepen our understanding of ATG-101’s antitumor mechanism and provide us with the quality data that will enhance the first-in-human study of ATG-101.

"We collaborated with Applied BioMath to best prepare our team for predicting accurate starting and efficacious doses for our first-in-human studies of ATG-101," said Dirk Hoenemann, M.D., VP, Head of Medical Affairs for Asia Pacific Region (APAC) and Early Clinical Development. "The Applied BioMath models provided us with a thorough understanding of ATG-101’s antitumor mechanism which enabled us to better design clinical trials moving forward, including our first-in-human trials."

"Systems pharmacology modeling is uniquely suited for the translation of antibody therapies from in vivo experiments to first-in-human studies," said Dr. John Burke, PhD, Co-Founder, President, and CEO of Applied BioMath. "Complicated mechanism of actions, as is common in modern antibody therapy designs, requires more sophisticated translational approaches than traditional methods and systems pharmacology has a proven track record of providing accurate translation for such therapies."

To date, Antengene has achieved multiple progress with the development of ATG-101, and is actively preparing to initiate clinical trials of ATG-101 in multiple countries and regions, including China, Australia, and the U.S. In China, Antengene has previously entered into a partnership with Wuxi Biologics for the chemistry, manufacturing, and control (CMC) manufacturing of ATG-101 to further optimize and accelerate the development of ATG-101.

About ATG-101

ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of cancer. ATG-101 can activate anti-tumor immune effectors by simultaneously blocking PD-L1/PD-1 binding and 4-1BB stimulation. In the presence of PD-L1 over-expressed cancer cells, ATG-101 showed a significant and PD-L1 crosslinking-dependent 4-1BB agonist activity, thus enhancing therapeutic efficacy, and mitigating hepatoxicity simultaneously. ATG-101 demonstrated potent activity in preclinical animal models, including strong tumor-suppressing effect in models of PD-1/PD-L1 inhibitor-resistant or -relapsed tumors. Meanwhile, the GLP toxicology study has produced results highlighting a favorable safety profile.

At present, Antengene has already completed the preclinical study of ATG-101, and is actively preparing to initiate clinical trials of ATG-101 in multiple countries and regions, including China, Australia, and the U.S. Antengene plans to submit a clinical trial application for the first-in-human (FIH) study of ATG-101 in Australia starting in mid-2021, to be followed by submissions in U.S. and China.

On May 16, 2021 Applied BioMath (www.appliedbiomath.com), the industry-leader in applying systems pharmacology and mechanistic modeling, simulation, and analysis to de-risk drug research and development, reported that was selected by Antengene Corporation to provide systems pharmacology modeling in immuno-oncology (Press release, Applied BioMath, MAY 16, 2021, View Source [SID1234580076]). Applied BioMath developed a systems pharmacology model for a PDL1/41BB bispecific antibody, ATG-101, in immuno-oncology indications. The model was used to understand the tumor killing mechanism of Antengene’s therapeutic and to inform clinical starting and efficacious doses for first-in-human studies. "We collaborated with Applied BioMath to best prepare our team for predicting accurate starting and efficacious doses for our first-in-human studies.," said Dirk Hoenemann, M.D., VP, Head of Medical Affairs for Asia Pacific Region (APAC) and Early Clinical Development. "The Applied BioMath models provided us with a thorough understanding of our tumor killing mechanism which enabled us to better design experiments moving forward, including our first-in-human trials."

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Applied BioMath employs a rigorous fit-for-purpose model development process which quantitatively integrates knowledge about therapeutics with an understanding of its mechanism of action in the context of human disease mechanisms. Their approach employs proprietary algorithms and software that were designed specifically for systems pharmacology model development, simulation, and analysis. "Systems pharmacology modeling is uniquely suited for the translation of antibody therapies from in vivo experiments to first-in-human studies," said Dr. John Burke, PhD, Co-Founder, President, and CEO of Applied BioMath. "Complicated mechanism of actions, as is common in modern antibody therapy designs, requires more sophisticated translational approaches than traditional methods and systems pharmacology has a proven track record of providing accurate translation for such therapies."

On May 16, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, reported that multiple clinical data in relation to TYVYT (sintilimab injection), pemigatinib (IBI375, FGFT1/2/3 inhibitor) and IBI110 (anti-LAG-3 monoclonal antibody) will be published at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, Innovent Biologics, MAY 16, 2021, View Source [SID1234580075]). A brief summary of the studies is as follows:

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Cancer Type: Lung Cancer
Topic: Two-year Follow up of Single PD-1 Blockade in Neoadjuvant Resectable NSCLC.
Presentation Type: Poster
Abstract Number: 8522
Researcher: Professor Shugeng GAO, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Cancer Type: Colorectal Cancer
Topic: Preliminary results of a phase 1b study of fruquintinib plus sintilimab in advanced colorectal cancer
Presentation Type: Poster Discussion
Abstract Number: 2514
Researcher: Professor Ye Guo, Professor Jin Li, Shanghai East Hospital of Tongji University, Shanghai, China

* The study is jointly cooperated by Innovent and HUTCHMED (China) Limited.

Cancer Type: Advanced Malignancy
Topic: A phase 1 study evaluating preliminary safety, pharmacokinetic and pharmacodynamic of pemigatinib in Chinese patients with advanced malignancy.
Presentation Type: Abstract
Abstract Number: e15051
Researcher: Professor Yi Ba, Tianjin Medical University Cancer Hospital, Tianjin, China

Cancer Type: Solid Tumors
Topic: Phase Ia/Ib dose-escalation study of IBI110 (anti-LAG-3 mAb) as a single agent and in combination with sintilimab (anti-PD-1 mAb) in patients (pts) with advanced solid tumors
Presentation Type: Poster
Abstract Number: 334761
Researcher: Professor Caicun Zhou, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China; Professor Nong Xu, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China

Multiple independent investigators’ studies in relation to sintilimab aras the following:

Cancer Type: Cervical Cancer
Topic: Anlotinib plus sintilimab in patients with recurrent advanced cervical cancer: A prospective, multicenter, single-arm, phase II clinical trial.
Presentation Type: Poster Discussion
Abstract Number: 5524
Researcher: Professor Qin Xu, Fujian Cancer Hospital, Fujian, China

Cancer Type: Gastric Cancer
Topic: SHARED: efficacy and safety of sintilimab in combination with concurrent chemoradiotherapy (cCRT) in patients with locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma.
Presentation Type: Poster
Abstract Number: 4040
Researcher: Professor Baorui Liu, Professor Jia Wei, Nanjing Drum Tower Hospital, Jiangsu, China

Cancer Type: Endometrial Cancer
Topic: Anlotinib plus Sintilimab in patients with recurrent advanced endometrial cancer：A prospective open-label, single-arm, phase II clinical trial
Presentation Type: Poster
Abstract Number: 5583
Researcher: Professor Jundong Li, Sun Yat-Sen University Cancer Center, Guangdong, China

Cancer Type: Non-small-cell Lung Carcinoma
Topic: A Single-arm phase Ib study of autologous cytokine-induced killer (CIK) cell immunotherapy in combination with sintilimab plus chemotherapy in patients with advanced non-small-cell lung cancer(NSCLC)-CCICC-002
Presentation Type: Poster
Abstract Number: 2531
Researcher: Professor Xiubao Ren, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China

Cancer Type: NK/T Lymphoma
Topic: Combination of sintilimab, anlotinib and pegaspargase "Sandwich" with radiotherapy in localized natural killer/T cell Lymphoma: A multicenter, phase 2 study
Presentation Type: Poster
Abstract Number: 7537
Researcher: Professor Zhiming Li, Sun Yat-Sen University Cancer Center, Guangdong, China

Cancer Type: Hepatocellular Carcinoma
Topic: Sintilimab plus anlotinib as first-line therapy in patients(pts)with advanced hepatocellular carcinoma(aHCC)
Presentation Type: Abstract
Abstract Number: e16146
Researcher: Professor Xiaofeng Chen, Jiangsu Province Hospital, Jiangsu, China

Cancer Type: Gastric Cancer
Topic: CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with Nab-PTX, S-1 and apatinib for the first-line treatment of stage IV gastric cancer (GC)
Presentation Type: Abstract
Abstract Number: e16041
Researcher: Professor Han Liang, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China

On May 15, 2021 Arbella Therapeutics, a U.S. early stage biotechnology company focused on the discovery and development of innovative small molecule therapies, and Hangzhou Polymed Biopharmaceuticals ("Polymed"), a leading biopharmaceutical company in China, reported a collaboration to develop and commercialize ARB-085 – a preclinical development candidate targeting dual EGFR and HER2 Exon 20 mutations – in Greater China and South Korea (Press release, Polymed Biopharmaceuticals, MAY 15, 2021, View Source [SID1234630620]).

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Under the terms of the collaboration, Arbella is eligible to receive an upfront collaboration fee and additional payments contingent on certain development and regulatory milestones, plus royalties on net product sales. Polymed will lead the development and commercialization of ARB-085 in Greater China.

"We are glad to have begun this partnership with Polymed to progress ARB-085 in China, where there is a significant unmet medical need for the treatment of non-small cell lung cancer caused by genetic mutations. We look forward to working in close collaboration with Polymed to continue the development of ARB-085 as we progress toward the clinical stage," said Fred Martin, Ph.D., Founder and Manager of Arbella.

"We look forward to a successful collaboration with Arbella for developing ARB-085," said Dr. Jason Shaoyun Xiang, the founder and CEO of Polymed. "In addition to pushing forward highly innovative internal PROTAC projects, Polymed is leveraging its capabilities for collaboration with leading world-class institutions to bring urgently-needed therapeutics into clinical development", said Dr. Xiang.

Discovered through research conducted in collaboration with the Dana-Farber Cancer Institute ("DFCI") of Harvard University, ARB-085 is a potent and selective dual EGFR/HER2 Exon 20 insertion inhibitor for non-small cell lung cancers, currently in preclinical stage.

On May 14, 2021 IntelGenx Technologies Corp. (the "Corporation") reported that issued (i) 37,300,000 shares of common stock of the Corporation (the "Shares"), (ii) 22,380,000 warrants (the "Warrants") and (iii) a unit purchase warrant (the "Additional Unit Warrant") to purchase up to 130,000,000 additional units ("Additional Units"), to ATAI Life Sciences AG ("atai") for aggregate gross proceeds of US$12,346,300 (the "Investment"), pursuant to an amended and restated securities purchase agreement (the "Securities Purchase Agreement") entered into by the Corporation and atai on the Initial Closing Date (Filing, 8-K, IntelGenx, MAY 14, 2021, View Source [SID1234580127]). The Securities Purchase Agreement amended and restated in its entirety the securities purchase agreement previously entered into between the parties on March 15, 2021 and includes certain mechanical amendments involving the settlement of securities.

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Each Warrant will entitle atai to purchase one Share at a price of US$0.35 for a period of three years from the Initial Closing Date. The Additional Unit Warrant will entitle atai to purchase the Additional Units for a period of three years from the Initial Closing Date. Each Additional Unit will be comprised of (i) one share of common stock (an "Additional Share") and (ii) one half of one warrant (each whole warrant, an "Additional Warrant"). The price for the Additional Units will be (i) until the date which is 12 months following May 11, 2021, the date on which the Investment was approved by the shareholders of the Corporation (the "Shareholder Approval Date"), US$0.331 (subject to certain exceptions), and (ii) following the date which is 12 months following the Shareholder Approval Date, the lower of (A) a 20% premium to the market price on the date of purchase, and (B) US$0.50 if purchased in the second year following the Shareholder Approval Date and US$0.75 if purchased in third year following the Shareholder Approval Date. Each Additional Warrant will entitle atai, for a period of three years from the date of issuance, to purchase one Share at the lesser of either (i) a 20% premium to the price of the corresponding Additional Share, or (ii) the price per share under which shares of the Corporation are issued under convertible instruments that were outstanding on February 16, 2021, the date on which the parties entered into a non-binding letter of intent to enter into a definitive Securities Purchase Agreement ("Outstanding Convertibles"), provided that atai may not exercise Additional Warrants to purchase more than the lesser of (x) 44,000,000 common shares of the Corporation, and (y) the number of common shares issued by the Corporation under Outstanding Convertibles.

Under the Securities Purchase Agreement, the Corporation also granted atai a pro-rata equity participation right for any issuances of new securities, subject to certain exceptions.

Amendment to Term Loan

On March 9, 2021 atai funded a secured loan in the amount of US$2,000,000 pursuant to a loan agreement entered into between IntelGenx Corp. (the "IntelGenx"), a wholly owned subsidiary of the Corporation, and atai. On May 14, 2021, IntelGenx and atai entered into a first amendment to loan agreement (the "Amendment") providing that the loan is repayable on the business day after the closing of the first subscription for Additional Units under the Securities Purchase Agreement if the additional subscription proceeds at such closing amount to at least US$3,000,000 in the aggregate and such proceeds are paid in cash.

The foregoing is a summary of certain material terms and conditions of the Securities Purchase Agreement and Amendment and are not a complete discussion of such agreements. Accordingly, the foregoing is qualified in its entirety by reference to the full text of the Securities Purchase Agreement and Amendment attached to this Current Report on Form 8-K as Exhibit 10.1 and Exhibit 10.2 respectively and incorporated herein by reference