Big Picture – A Deep Dive Examination of Humanigen Inc
Humanigen Inc Snapshot
Derived from the company's Humaneered® platform, lenzilumab, ifabotuzumab and HGEN005 are monoclonal antibodies with first-in-class mechanisms. Our lead monoclonal antibody asset, lenzilumab, targets soluble GM-CSF and has been demonstrated to significantly reduce neurotoxicity and prevent cytokine release syndrome associated with CAR-T cell treatment in a proprietary human xenograft model while at the same time increasing CAR-T cell proliferation and effector functions. We are poised to begin clinical trials with lenzilumab for prophylaxis of neurotoxicity and cytokine release syndrome in combination with the leading CAR-T cell therapies. Ifabotuzumab, which targets Eph receptor A3 (EphA3), is being developed as a potential treatment for glioblastoma multiforme (GBM) and other deadly cancers, as well as a backbone for a novel CAR-T construct and as an antibody drug conjugate (ADC). HGEN005, which targets human epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1), has potential to treat eosinophilic diseases and is being developed as a novel CAR-T construct for eosinophilic leukemia.
Monoclonal Antibody to Improve CAR-T Safety and Efficacy
Lenzilumab is a Humaneered® recombinant monoclonal antibody that neutralizes soluble granulocyte-macrophage colony-stimulating factor (GM-CSF) a critical inflammatory cytokine. GM-CSF is an upstream driver in the paths of multiple inflammatory diseases. Specifically, new science demonstrates that GM-CSF is the key initiator of inflammatory side-effects, neurotoxicity and cytokine release syndrome, associated with chimeric antigen receptor T-cell (CAR-T) cancer therapy.
Monoclonal Antibody/CAR-T Construct for the Treatment of Cancers
Ifabotuzumab is a first-in-class, Non-Fucosylated Humaneered® monoclonal antibody targeting the EphA3 receptor tyrosine kinase.
TARGETING CANCER VASCULATURE
Ifabotuzumab is unique in its potential to attack tumors at their source by killing tumor stromal cells that protect them and the vasculature that feeds them without killing normal cells. This unique combination of activities may provide the potential to generate durable responses.
Eph and ephrin proteins are critical to fetal development and vasculogenesis. EphA3 is not expressed in normal adult tissue but is thought to be important for the creation of the cancer stem cell compartment including stromal cells that surround and protect cancers and the tumor vasculature that feeds cancers. EphA3 is highly expressed in the tumor vasculature in cancers of the brain, kidney, and bladder in addition to melanoma. Glioblastoma multiforme (GBM) is the most common form of brain cancer and the most deadly. Targeting other antigens expressed by GBM such as IL-13Ra2 and EGFRvIII is associated with the development of antigen loss variants and there are safety concerns targeting HER2 given is expression in normal adult tissue. EphA3 is increasingly being recognized as therapeutic target given its lack of expression in normal adult tissues and its expression on bone marrow derived stromal cells that support the cancer’s growth and metastatic potential.
The first patients have been dosed in an ifabotuzumab clinical trial of patients with glioblastoma multiforme (GBM) at the Olivia Newton-John Cancer Research Institute in Australia. The trial is an Investigator-Sponsored Phase 1 trial with a radiolabeled imaging component in GBM. According to the investigators, the trial will seek to confirm the safety of ifabotuzumab and potentially determine the best dose to effectively penetrate brain tumors. The investigators expect about 12 patients to participate in the trial, for which eligibility criteria are recurrent GBM and receipt of only one type of chemotherapy for disease recurrence.
Humanigen is also developing ifabotuzumab as an antibody-drug conjugate (ADC) and as a CAR-T construct with a leading medical center in the U.S.
Monoclonal Antibody/CAR-T Construct for the Treatment of Eosinophilic Diseases
HGEN005 is a first-in-class Humaneered® monoclonal antibody targeting human epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1).
ELIMINATING EOSINOPHILS IN TISSUE
HGEN005 has the cutting-edge potential to demonstrate superior efficacy to treat eosinophilic diseases due to its selectivity to hit the right target and its penetration to deplete eosinophils in tissue. A major limitation of current eosinophil-targeted therapies is incomplete depletion of tissue eosinophils and/or lack of cell selectivity.
Eosinophils are a type of white blood cell. If too many are produced in the body, chronic inflammation and tissue and organ damage may result. The origin and development of eosinophilic disorders is mostly due to eosinophils infiltrating tissue.
EMR1 is expressed exclusively on eosinophils, making it an ideal potential target for the treatment of eosinophilic disorders. Regardless of the eosinophilic disorder, mature eosinophils express EMR1 in tissue, blood and bone marrow in patients with eosinophilia.
In pre-clinical work, eosinophil killing was enhanced in the presence of HGEN005 and immune effector cells. Evidence shows HGEN005’s anti-EMR1 activity could selectively target and safely eliminate eosinophils in vivo in a primate model.
Thus, HGEN005 offers promise in a range of eosinophil-driven diseases, such as:
- eosinophilic leukemia
- eosinophilic asthma
- eosinophilic esophagitis
- eosinophilic granulomatosis with polyangiitis.
HGEN005 is another plank in our growing platform of CAR-T therapies. Because of its high selectivity, HGEN005 has significant potential incorporated into a CAR-T construct. Discussions are underway with a leading center in the U.S. to develop a series of CAR constructs based on HGEN005 and to explore further pre-clinical testing in eosinophilic leukemia, an orphan condition with significant unmet need.
CAMERON DURRANT, MD, MBA
CHAIRMAN & CEO
- Senior pharmaceutical and biotech exec, turnaround specialist
- Senior exec roles at Pharmacia/Pfizer, J+J in US, Merck, GSK in Europe; experience as Exec Chairman, CEO and CFO; CEO roles at three specialty pharma groups
- Expertise in anti-infectives, pediatrics, oncology
TAREK SAHMOUD, MD, PHD
CHIEF MEDICAL OFFICER
- 25+ years oncology drug development, medical, regulatory affairs experience
- Novartis CAR-T clinical development consultant; former Novartis VP, Senior Global Clinical Program Head (oncology); senior development roles at Celgene, Bristol-Myers Squibb and Boehringer-Ingelheim
- Registered Arimidex, Afinitor; responsibility for Kymriah, Yervoy, Abraxane, marizomib, dasatinib
CHIEF FINANCIAL OFFICER
- Decades of financial, operational and entrepreneurial experience in life sciences
- Vice president, finance, for privately held Tris Pharma, Inc
- CFO roles at private and publicly owned pharmaceutical companies, including Alvogen and Innovive
BOARD OF DIRECTORS
RAINER BOEHM, MD, MBA
Boehm brings more than three decades of biopharmaceutical leadership experience to Humanigen’s board. At Novartis for 29 years, he held roles of increasing responsibility culminating with his position as Chief Commercial and Medical Affairs Officer and as ad interim CEO of Novartis’ pharmaceuticals division. His background spans senior leadership, marketing, sales and medical affairs positions in both oncology and pharmaceuticals and he has led regions around the world, including North America, Asia and all emerging markets. Boehm has overseen the launch and commercialization of many new drugs in his career, including blockbuster breakthroughs Cosentyx and Entresto, and major oncology brands including Afinitor, Exjade, Tasigna, Femara, Zometa and Glivec. Among his many interests are developing healthcare leaders and new business models in the industry.
Boehm also currently serves on the board of directors for Cellectis, a clinical-stage biopharmaceutical company focused on immunotherapies based on gene-edited CAR-T cells; as an advisor in leadership development for senior executives at the GLG Institute in New York City; and as a consultant to healthcare companies. He graduated from the medical school at the University of Ulm in Germany and received his MBA from Schiller University at the Strasbourg campus in France.
ROBERT SAVAGE, MBA
Mr. Savage is a seasoned executive with more than 40 years of experience in marketing, sales, drug development, operations and business development in the pharmaceutical and biotechnological industries. Moreover, Mr. Savage has served on 12 boards over two decades helping to guide companies and organizations, both public and private. He most recently served on the board of directors for Depomed and The Medicines Company. He has led multinational groups to successfully execute on corporate strategies to develop, launch and market multiple pharmaceutical brands with sales exceeding $4 billion. Currently, Mr. Savage is the president, chief executive officer and chairman of Strategic Imagery, LLC. He served as group vice president and president, worldwide general therapeutics & inflammation business, at Pharmacia Corporation from 2002 until its acquisition by Pfizer. Prior to his work with Pharmacia, Mr. Savage held leadership positions at Johnson & Johnson, where he was the worldwide chairman of the pharmaceuticals group, with prior senior roles at Ortho-McNeil Pharmaceuticals and Hoffman La-Roche.
CAMERON DURRANT MD, MBA
Dr. Cameron Durrant is the Chairman and Chief Executive Officer of Humanigen, since March 1, 2016. He was elevated to that position after serving on the board of directors starting January 7, 2016.
Dr. Durrant’s expertise and business career has revolved around transformations, whether for brands, business units, or small companies. He has particular therapeutic experience in infectious diseases, pediatrics and oncology – coupled with experience as a practicing physician.
He has served as board chairman, lead independent director and as CEO for several specialty pharma or biotech companies in both the private and public sector. He has been involved in several exits and has raised significant funding from a variety of sources.
He is currently a founding director of a private nanotech oncology company, Bexion Pharmaceuticals, a board member of Immune Pharmaceuticals, a publicly traded immune-oncology biotech, and on the board of two private medical device companies. Dr. Durrant is also founder of the start-up Taran Pharma Limited, a private, semi-virtual specialty pharma company developing and registering treatments in Europe for orphan conditions
Previously, Dr. Durrant was president and CEO of ECR Pharmaceuticals and a corporate officer of Hi-Tech Pharmacal; and the founder, Chairman, CEO and CFO of PediatRx, Inc., which marketed therapies for pediatric care, orphan conditions and oncology supportive care.
His career has been built on extensive experience – including commercial, P&L, US and global responsibilities – as an operating executive at blue-chip pharmaceutical companies. Dr. Durrant has been President and CEO of PediaMed Pharmaceuticals, a company focused on bring important medicines to children in the US; and held senior executive positions at Johnson & Johnson and Pharmacia. He also had earlier roles at GlaxoSmithKline and Merck.
He is a prior regional winner of the Ernst and Young ‘Entrepreneur of the Year’ award.
Dr. Durrant earned his MD from the Welsh National School of Medicine, Cardiff, UK, his DRCOG from the Royal College of Obstetricians and Gynecologists, London, UK, and his MRCGP from the Royal College of General Practitioners, London, UK. He practiced medicine for eight years in the UK and Australia. He also earned his MBA from Henley Management College, Oxford, UK.
TIMOTHY MORRIS, CPA
Timothy Morris currently serves as the chief financial officer of Iovance Biotherapeutics, Inc. He brings over 30 years of professional finance and accounting experience, of which 19 have been as a chief financial officer. He has raised over $980 million in equity and convertible securities for six companies. He has extensive deal experience with over 65 transactions with a combined value of more than $2 billion. Mr. Morris previously served as the CFO of AcelRx Pharmaceuticals, a publicly traded specialty pharmaceutical company with two late-stage products for acute pain, starting in 2014. He added the responsibilities of head of business development in 2015.
Prior to that, Mr. Morris served as a CFO, SVP finance and global corporate development of VIVUS, Inc. from November 2004 to December 2013. At VIVUS Mr. Morris oversaw finance, corporate development, IT, human resources, legal, and investor relations functions.
From September 2001 to November 2004, Mr. Morris was CFO, SVP finance, manufacturing and administration for Questcor Pharmaceuticals, Inc., a specialty pharmaceutical company. He was a member of the Office of the President from August 2004 to November 2004.
Mr. Morris serves as a non-executive director of PAION Inc., the US subsidiary of PAION AG, a publicly traded company based in Germany. He graduated cum laude with a BS in business with emphasis in accounting from California State University, Chico, and is a Certified Public Accountant.
RONALD BARLIANT, JD
Ronald Barliant is of counsel with the Chicago law firm Goldberg Kohn, where he had been a principal in the Bankruptcy & Creditors’ Rights Group after joining in September 2002. He has represented debtors and creditors in complex bankruptcy cases, and counseled major financial institutions, business firms and boards of directors in connection with workouts.
He served as a United States bankruptcy judge for the Northern District of Illinois from 1988 to 2002, and as a visiting judge in the District of Delaware in 2002.
He is a member of the board of directors of a closely held information technology company and the board of the estate representative supervising the liquidation of assets in the Global Crossing case. And he was previously a director of a Delaware debtor in the automotive industry. He has also counseled boards of directors and individual directors in connection with their fiduciary duties in distressed situations.
Mr. Barliant has taught debtor-creditor relations at John Marshall Law School and has frequently lectured and participated in panel discussions on bankruptcy-related topics at the invitation of many organizations, including the Federal Judicial Center, the National Conference of Bankruptcy Judges (NCBJ), the American Bankruptcy Institute, the American Bar Association, the American College of Bankruptcy, the Commercial Finance Association, the Turnaround Management Association, the Chicago Bar Association and LexisNexis Mealey’s.
His published writings include articles on Chapter 11 plans, executory contracts, preferences, the anti-trust litigation in the United Airlines case (in which he represented an indenture trustee/defendant), and asbestos bankruptcies. He was a member of the board of governors of the NCBJ from 1998 to 2000 and of the NCBJ’s Endowment for Education from 1997 to 1998. In addition, he served on national judicial committees and on working groups considering technology issues and the treatment of mass torts in bankruptcy cases.
Mr. Barliant has been recognized annually by the Leading Lawyers Network, Super Lawyers, and Best Lawyers. He was named by Chambers USA 2014 as a leading lawyer in the United States in Bankruptcy/Restructuring. He is currently a member of the ABI (Business Reorganization Committee), ABA (Business Law Section), and NCBJ (Former Judges Section) and is a former Chair of the Bankruptcy and Reorganizations Committee of the CBA. He is a Fellow in the American College of Bankruptcy and served as the College’s Regent for the Seventh Circuit.