On September 23, 2020 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that recent new contracting with partners and investments in manufacturing capacity have contributed to its Captisol business operating at the highest levels in the history of the technology and position Captisol for major growth (Press release, Ligand, SEP 23, 2020, View Source [SID1234565518]). Significant new clinical and regulatory developments with Evomela and Kyprolis, among other drugs, are reinforcing the role the proprietary technology serves in enabling important medicines. During 2020, Ligand has facilitated the successful installation of equipment to allow production at significantly higher levels to support anticipated demand. In addition to manufacturing at partner Hovione’s facilities in Ireland and Portugal, Ligand has now added final step processing capacity for Captisol in both the United States and England. Ligand also introduces guidance for 2021 Captisol material sales of approximately $200 million.

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"The global medical need for Captisol-enabled drugs has never been higher," said John Higgins, Chief Executive Officer of Ligand. "Our recently expanded operating team has successfully positioned our Captisol technology for the substantial growth we now expect in 2021 and beyond. There is significant ongoing investment by our partners for over 30 Captisol-enabled medicines in clinical development. We have entered into more contracts this year than any other year and are proud to be working closely with Gilead under our recently extended 10-year supply contract. We continue to be pleased with the momentum relating to Captisol, as it is a critical component in multiple life-saving medicines."

Recent Captisol technology business highlights include the following:

To date in 2020 Ligand has entered into more than 120 Captisol research use agreements and eight clinical and/or commercial license agreements. This is the highest number of use agreements to be signed in a single year since the invention of Captisol.
Captisol is utilized in the formulation of Gilead Sciences’ Veklury (remdesivir), which has received emergency use authorizations or regulatory approvals for the treatment of moderate or severe COVID-19 in over 50 countries and is included in more than 30 ongoing clinical trials. Ligand is supplying Captisol to Gilead and the company’s voluntary licensing partners who are supplying generic remdesivir to 127 low- and middle-income countries. Ligand expects Captisol orders into 2021 and beyond to Gilead and its partners to help countries around the world manage the pandemic.
Ligand recently extended its Captisol supply agreement with Gilead until September 2030. The contract defines terms and conditions for forecasting, supply, order commitments and price.
Ligand’s manufacturing partner Hovione announced today that to meet Captisol demand associated with Veklury, Hovione will soon be producing more Captisol per month than it usually produces per year. "This spike in demand has required unique mobilization efforts across the Hovione network to secure additional raw material supply, execute major capital expenditure projects at oursites, maximize operational efficiency, hire additional talent and identify external partners to expand our overall capacity. The pharmaceutical supply chain is working together in an unprecedented fashion to treat patients and save lives. Hovione is privileged to be part of this truly global rapid response," said Jean-Luc Herbeaux, Chief Operating Officer of Hovione.
Recent clinical data have been announced including publication of a study from the Medical College of Wisconsin that compared safety parameters for Captisol-enabled Evomela versus Alkeran in patients undergoing autologous stem cell transplantation for the treatment of multiple myeloma. The study of 294 patients demonstrated a statistically significant reduction in 30-day re-hospitalization rates for patients treated with Evomela (6.8% for Evomela vs. 17.9% for Alkeran, p=0.04)a with a similar safety profile to Alkeran. Evomela is marketed by Acrotech Biopharma in the U.S. and by CASI Pharmaceuticals in China.
Partner Marinus was recently awarded a BARDA contract by the U.S. government to develop Captisol-enabled IV ganaxolone for the treatment of refractory status epilepticus caused by nerve agent exposure.
Ligand’s pivotal trial for Captisol-enabled Iohexol (CE-Iohexol) is planned to initiate in December 2020. CE-Iohexol is an iodine-based contrast agent for hospital-based imaging procedures. The market for iodinated contrast agents is substantial with approximately 20 million imaging procedures per year in the U.S., representing an estimated $1.5 billion in sales. The objective of the clinical trial will be to demonstrate a reduction in the incidence of contrast-induced acute kidney injury and an equivalent image quality compared to GE’s Omnipaque. The trial is expected to enroll approximately 500 patients and results are expected within two years.
Ligand’s forecast for 2021 Captisol material sales of approximately $200 million is based on information it has on anticipated demand from its major partners given growth in existing and new markets, clinical requirements for Captisol-enabled development programs and binding orders from certain commercial or pre-commercial partners. The 2021 Captisol outlook compares with the Company’s guidance for 2020 Captisol material sales of approximately $90 million.

About Captisol

Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella, University Distinguished Professor at the University of Kansas’ Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled several FDA-approved products, including Gilead’s VEKLURY, Amgen’s KYPROLIS, Baxter International’s NEXTERONE, Acrotech Biopharma L.L.C.’s and CASI Pharmaceuticals’ EVOMELA, Melinta Therapeutics’ BAXDELA and Sage Therapeutics’ ZULRESSO. There are many Captisol-enabled products currently in various stages of development. Ligand maintains a broad global patent portfolio for Captisol with more than 400 issued patents worldwide relating to the technology (including 37 in the U.S.) and with the latest expiration date in 2033. Other patent applications covering methods of making Captisol, if issued, extend to 2040.

On September 23, 2020 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) reported that it has entered into separate, privately-negotiated exchange agreements with certain holders of its 5.25% Convertible Senior Notes due 2021 under which such holders have agreed to exchange an aggregate principal amount of $62.55 million of Notes in exchange for aggregate consideration consisting of $41.03 million in cash (including $1.07 million of accrued interest) and 8,746,117 shares of Lexicon’s common stock, par value $0.001 per share (Press release, Lexicon Pharmaceuticals, SEP 23, 2020, View Source [SID1234565517]).

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The transactions are expected to close by September 28, 2020, subject to customary closing conditions. Immediately following the closings, $24.95 million in aggregate principal amount of the Notes will remain outstanding.

The completion of the transactions will reduce Lexicon’s remaining interest expense through 2021 on the exchanged Notes by approximately $3.9 million. Once completed, and together with other debt reductions, including the repayment of Lexicon’s secured loan concurrent with the closing of its sale of XERMELO (telotristat ethyl) and related assets to TerSera Therapeutics, LLC, Lexicon will have reduced the principal amount of its outstanding debt by approximately 90% since June 30, 2020, better aligning with its strategic focus on its LX9211 neuropathic pain program and other research and development assets.

This press release does not constitute an offer to sell or the solicitation of an offer to buy any securities of the Company. The issuance of common stock has not been registered under the Securities Act of 1933 (the "Securities Act") or the securities laws of any other jurisdiction, and these securities may not be offered or sold in the United States absent registration or an applicable exemption from the Securities Act and applicable state laws.

About LX9211
LX9211 is a potent, orally delivered, selective small molecule inhibitor of AAK1, a target with a pain phenotype discovered and extensively characterized in an alliance with Bristol Myers Squibb. Preclinical studies of LX9211 demonstrated central nervous system penetration and reduction in pain behavior in models of neuropathic pain without affecting opiate pathways. Lexicon holds exclusive research, development and commercialization rights to LX9211 and additional compounds acting through AAK1 under the alliance.

On September 23, 2020 Immunomic Therapeutics, Inc. reported that it will be participating in Precision Medicine’s webinar on utilizing liquid biopsy to promote oncolytic therapeutic development. On Thursday, September 24, Vice President of Clinical Development at Immunomic, Dr. Andrew Eisen, will be discussing methods and tools to utilize liquid biopsy to promote oncology therapeutic development alongside Akoya Biosciences’ CMO, Dr. Gerald Messerschmidt and Sr. Vice President, Dr. Darren Davis (Press release, Immunomic Therapeutics, SEP 23, 2020, View Source [SID1234565516]).

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This webinar will examine:

– Clinical utility of liquid biopsy and specifically of circulating tumor cells (CTC) biomarkers
– Methods to capture and concentrate CTCs to enable effective analysis
– Tools to image CTCs and analyze CTC biomarkers
– Case study exploring CTCs as a tool to understand drug pharmacodynamics in melanoma patients

Webinar details are as follows:

Title: Utilizing Liquid Biopsy to Promote Oncolytic Therapeutic Development

Date and Time: Thursday, September 24, 2020 12:00 PM ET

Register here: View Source

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein 1, an endogenous protein in humans, for immune processing. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach puts UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in a Phase II clinical trial as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.

On September 23, 2020 Silverback Therapeutics, Inc. ("Silverback") ("the Company"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered and tissue-targeted therapeutics for the treatment of cancer and other serious diseases, reported the close of an $85 million Series C financing round. EcoR1 Capital led the round, with participation from new investors including Boxer Capital of Tavistock Group, Fidelity Management & Research Company LLC, Nantahala Capital Management, and RA Capital (Press release, Silverback Therapeutics, SEP 23, 2020, View Source [SID1234565515]). Existing investors also participating in the financing included OrbiMed Advisors, U.S. Venture Partners, Nextech Invest Ltd., Hunt Technology Ventures, and Pontifax Venture Capital. Silverback intends to use the proceeds to support its clinical development of SBT6050, a TLR8 agonist conjugated to a HER2-directed antibody currently in a Phase 1 clinical study for the treatment of HER2-expressing solid tumors, and to advance its robust pipeline of other ImmunoTAC therapeutics.

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"Silverback has made impressive progress developing a differentiated approach to immuno-oncology," said Scott Platshon, principal, EcoR1 Capital. "Broad activation of innate immune cells has been difficult to achieve due to systemic toxicities. Silverback has persisted in understanding how to deliver TLR8 agonists with a good preclinical safety and tolerability profile, and we are excited to lead an investment round that will help Silverback investigate the translatability of these findings to patients with HER2-expressing solid tumors."

The Company also announced two key executive promotions. Valerie Odegard, Ph.D., has been named president and chief scientific officer, and Naomi Hunder, M.D., has been named chief medical officer. "Drs. Odegard and Hunder bring comprehensive drug development expertise to Silverback, as well as a fierce drive for scientific excellence and improving patient outcomes," said Laura Shawver, Ph.D., chief executive officer of Silverback Therapeutics. "We are at an important growth phase for the company and their ongoing leadership will be critical as we progress SBT6050 through clinical development, as well as advance our robust preclinical pipeline. It is awesome to work with them and the entire Silverback team as we create a new generation of much-needed therapies."

Valerie Odegard, Ph.D., joined Silverback in 2016 and has served as chief scientific officer since 2018. She brings over 15 years of research and drug development experience to the Company. Prior to Silverback, Dr. Odegard served as vice president of research at Juno Therapeutics, where she was responsible for discovery, preclinical development, and translational research efforts to advance novel cancer immunotherapies into clinical development. Previously, she held research leadership positions at Novo Nordisk and Trubion Pharmaceuticals, where she oversaw the discovery and preclinical development of therapeutics for oncology and inflammatory conditions. Dr. Odegard received her Ph.D. in immunobiology from Yale University.

Naomi Hunder, M.D., joined Silverback in 2019, bringing both late-stage and early clinical development experience to the Company. Prior to Silverback, Dr. Hunder was vice president, head of clinical development and medical affairs at Acerta Pharma, responsible for the acalabrutinib clinical program and lifecycle strategy. Before joining Acerta, Dr. Hunder was vice president of clinical development at Seattle Genetics, where she led the brentuximab vedotin clinical program and early phase programs in lymphoma and myeloma. Dr. Hunder previously served as medical director at ZymoGenetics, developing therapeutics for oncology and viral hepatitis. A board-certified medical oncologist, Dr. Hunder received her M.D. from Jefferson Medical College and her internal medicine training at the University of Pennsylvania. She completed her oncology fellowship training at Fred Hutchinson Cancer Research Center/University of Washington.

On September 23, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported the publication of a manuscript in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), highlighting the development of MGC018, the Company’s investigational antibody-drug conjugate (ADC) targeting B7-H3 for the treatment of solid tumors (Press release, MacroGenics, SEP 23, 2020, View Source [SID1234565512]).

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B7-H3 has been identified as a cell surface protein with limited expression on normal tissues but over-expressed on the epithelium and tumor-associated vasculature in solid tumors. Overexpression of this molecule has been shown to be associated with cancer disease severity, risk of recurrence and reduced survival. The Company’s early studies showed that ligation of B7-H3 by select monoclonal antibodies (mAbs) led to mAb internalization and antitumor activity toward B7-H3-expressing tumor cells when conjugated to a toxic payload. Based on these results, MacroGenics selected a lead candidate mAb and developed MGC018, an ADC targeting B7-H3 for the treatment of cancer.

As described in the paper "Preclinical Development of MGC018, a Duocarmycin-based Antibody-drug Conjugate Targeting B7-H3 for Solid Cancer," the authors report on preclinical studies that showed that MGC018 mediated specific in vitro killing across a range of B7-H3-expressing solid tumor cell types. Furthermore, the preclinical studies showed that MGC018 mediated bystander in vitro killing of B7-H3-negative tumor cells in the presence of B7-H3-positive tumor cells.

MGC018 displayed potent antitumor activity in preclinical tumor xenograft models of breast, ovarian and lung cancer, as well as melanoma. Additionally, antitumor activity was observed toward patient-derived tumor xenograft models of breast, prostate and head and neck cancer displaying heterogeneous expression of B7-H3. Importantly, MGC018 exhibited an acceptable pharmacokinetic and safety profile in cynomolgus monkeys following repeat-dose administration.

"With its overexpression on a wide range of solid cancers but limited presence on normal tissues, B7-H3 is an attractive candidate for an ADC-targeting approach," said Deryk Loo, Ph.D., Senior Director of Research at MacroGenics and the lead author of the paper. "The published preclinical antitumor activity data and safety profile provided evidence of a potentially favorable therapeutic index to support the development of MGC018 for the treatment of solid tumors."

Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics, further commented: "Encouraged by the MGC018 interim clinical dose escalation data presented at ASCO (Free ASCO Whitepaper) in May, we have recently initiated recruitment of patients with metastatic castration-resistant prostate, triple negative breast and non-small cell lung cancers in the dose expansion portion of the Phase 1 clinical study. We expect to provide an update on this study next year."

About MGC018

MGC018 is comprised of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody conjugated via a cleavable linker to the prodrug seco-DUocarmycin hydroxyBenzamide Azaindole (DUBA; licensed from Byondis, B.V.), with an average drug-to-antibody ratio (DAR) of ~2.7. DUBA is an alkylating agent that can damage DNA in both dividing and non-dividing cells, causing cell death. MGC018 is being evaluated in a Phase 1 study (NCT03729596). Preliminary clinical results from the dose escalation portion of this study were presented at the 2020 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Scientific Program. MacroGenics retains full worldwide rights to MGC018.