On September 21, 2021 NanOlogy LLC, a clinical-stage interventional oncology drug company, reported that initial results from a Phase 1/2 clinical trial of intramural/intravesical (IMI/IVT) NanoDoce (large surface area microparticle [LSAM] docetaxel) suspension in high-risk nonmuscle invasive bladder cancer (hrNMIBC) were presented by Max Kates, MD (Johns Hopkins Medicine) at the American Urological Association annual meeting (AUA2021) via virtual platform on September 12, 2021 (Press release, NanOlogy, SEP 21, 2021, View Source;utm_medium=rss&utm_campaign=aus2021_presentation_highlights_pr [SID1234590065]).

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The oral presentation entitled Initial Results from a Phase 1/2 Trial of Large Surface Area Microparticle Docetaxel for High-Risk Non-Muscle Invasive Bladder highlighted safety and preliminary efficacy data from the multicenter dose-rising/confirmation clinical trial that enrolled 19 subjects. In addition to Dr. Kates, contributing clinical investigators were Ahmed Mansour, MD (UT Health San Antonio), Donald Lamm, MD (BCG Oncology), and Neal Shore, MD (Carolina Urologic Research Center).

Highlights from the presentation:

Overall, NanoDoce was well tolerated. Most treatment emergent adverse events were mild to moderate, and no severe adverse events were attributable to the study drug.
Systemic absorption of docetaxel was negligible and below the threshold for systemic toxicity in all subjects.
Across all doses and subjects (n=19), complete response (CR) at 3 months as 68% (13/19) and durability for responding subjects at 12 months was CR of 31% (4/13).
In the high-dose cohort (n=6), 6/6 maintained CR > 6 months with 4 subjects showing durability at 12 months, 1 subject showing recurrence, and 1 subject lost to follow up.
Tissue biopsies suitable for multiplexed immunofluorescence were obtained pre/post NanoDoce in 5 subjects. Analysis revealed directional increases in density of T Cells, macrophages (including PD-L1), and NK cells, and decreases in myeloid and MDSC cells.
NanoDoce (LSAM docetaxel) suspension is composed of large surface area microparticles of pure docetaxel designed for local administration and sustained drug release over time. In the dose-rising phase of the study (n=13), 3mg to 15mg of investigational drug were delivered IMI into and around the tumor resection bed post transurethral resection of bladder tumor (TURBT) followed by multiple periodic IVT of 50mg to 75mg. No dose limiting toxicities were encountered allowing target of 15mg IMI and 75mg IVT NanoDoce to continue into dose confirmation (n=6). Subjects were followed for up to one year. A separate study arm evaluated a post-TURBT single IMI/IVT administration of NanoDoce for safety over a 45-day period in 17 patients with muscle invasive bladder cancer. These data will be reported separately once final.

The American Cancer Society estimates 83,730 new cases of bladder cancer in the United States for 2021 with more than 20,000 presenting with hrNMIBC. For these patients, bladder removal often follows, which results in among the highest lifetime treatment costs and negative impact to quality of life of any cancer. NanOlogy is in planning of a later phase clinical trial in hrNMIBC.

In addition to this trial, NanOlogy clinical programs have advanced in lung, pancreatic, and other cancers. Data from preclinical and clinical studies in a variety of solid tumors have shown evidence of tumor kill, minimal local or systemic toxicity, and favorable antitumoral immune effects, which includes published preclinical research of NanoDoce synergy in combination with an immune checkpoint inhibitor.

The NanOlogy therapeutic platform is based on a proprietary supercritical precipitation technology that converts taxane API crystals into stable LSAMs of pure drug for tumor-directed therapy and sustained drug release. The taxane particles are covered by composition of matter patents issued in the US (US 9,814,685, US 10,507,195, & US 10,993,927), Canada, Europe, Japan, Russia, and Australia all valid through June 2036, plus applications pending globally. These composition of matter patents form the foundation of an extensive intellectual property portfolio protecting NanOlogy investigational drugs, methods, and technology.

On September 21, 2021 Roivant Sciences Ltd. ("Roivant" or the "Company"), a next-generation biopharmaceutical company dedicated to improving the delivery of healthcare to patients, reported its financial results for the fiscal quarter ended June 30, 2021 and provided an update on the Company’s operations (Press release, Roivant Sciences, SEP 21, 2021, View Source [SID1234590091]).

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"Over the past quarter we have made significant progress as a business, both at Roivant centrally and across our family of companies," said Matthew Gline, Chief Executive Officer of Roivant. "I look forward to providing an update on these developments and an overview of key milestones to come at our R&D Day next week."

On September 28, Roivant will host its annual R&D Day, at which the Company will provide updates on clinical development at the Vants and Roivant’s new small molecule discovery engine. The webcast for this virtual event will begin at 1 p.m. ET and can be accessed at View Source

Recent Developments

Datavant: In June 2021, Datavant and Ciox Health entered into a definitive agreement to merge the two companies. The combined entity, named Datavant, is the nation’s largest health data ecosystem, enabling patients, providers, payers, health data analytics companies, patient-facing applications, government agencies and life science companies to securely exchange their patient-level data. The merger closed on July 27, 2021. At closing, Roivant received approximately $320 million in cash and a minority equity stake in the combined company.
Aruvant: In June 2021, Aruvant announced data published on ARU-2801, an investigational gene therapy, that showed improved survival out to 18 months in hypophosphatasia mice.
Immunovant: In August 2021, Roivant made a $200 million investment in Immunovant. Following this transaction, Roivant owns 73,398,664 shares of Immunovant common stock, representing approximately a 63.8% ownership interest.
Dermavant: In August 2021, the FDA accepted for filing Dermavant’s NDA for tapinarof for the treatment of plaque psoriasis in adult patients. The FDA has assigned a PDUFA target action date in the second calendar quarter of 2022. In September 2021, Dermavant dosed the first patient in a Phase 3 trial of tapinarof for the treatment of atopic dermatitis.
Genevant: In August 2021, Genevant entered into a global collaboration and license agreement with Takeda for the development and commercialization of novel nonviral gene therapies for up to two rare liver diseases. Genevant will be eligible for up to $303 million in upfront and potential milestone payments, plus royalties on product sales. This is the second collaboration between Genevant and Takeda.
Major Upcoming Milestones

Roivant: We expect to close our business combination with MAAC, along with a concurrent PIPE financing, and commence trading on Nasdaq on October 1 under the symbol "ROIV." Assuming no redemptions by MAAC shareholders, the business combination and concurrent PIPE financing are expected to deliver approximately $575 million in net proceeds to Roivant.
Dermavant: We expect a decision from the FDA on the approval of tapinarof for the treatment of adults with plaque psoriasis in the second calendar quarter of 2022. We also expect to report topline data from Dermavant’s Phase 3 clinical trial of tapinarof for the treatment of atopic dermatitis in the first half of calendar year 2023.
Immunovant: Contingent upon FDA feedback, Immunovant plans to initiate a pivotal trial evaluating IMVT-1401 for the treatment of myasthenia gravis in the early part of calendar year 2022. Immunovant also plans to announce at least two new indications and submit INDs with their trial designs to the FDA over the next 12 months.
Aruvant: We expect Aruvant to report additional clinical data from the ongoing Phase 1/2 trial of ARU-1801 in sickle cell disease patients in the second half of calendar year 2021.
First Fiscal Quarter 2021 Financial Summary

Research and Development Expenses

Research and development expenses increased by $19.9 million to $78.6 million for the three months ended June 30, 2021 compared to $58.7 million for the three months ended June 30, 2020. The increase is primarily due to an increase in personnel-related expenses, which is partially driven by additional headcount to support drug discovery efforts using our computational discovery technology and targeted protein degradation platform, following the acquisition of Silicon Therapeutics in March 2021 and Oncopia Therapeutics, Inc. in November 2020.

General and Administrative Expenses

General and administrative expenses increased by $25.6 million to $82.8 million for the three months ended June 30, 2021 compared to $57.1 million for the three months ended June 30, 2020. The increase was primarily due to increases in professional and transaction fees, personnel-related expenses and share-based compensation expense.

Capital Resources

As of June 30, 2021, we had cash and cash equivalents of approximately $2.0 billion.

On September 21, 2021 Novartis reported that it has acquired Arctos Medical, adding a pre-clinical optogenetics-based AAV gene therapy program and Arctos’ proprietary technology to its ophthalmology portfolio (Press release, Novartis, SEP 21, 2021, View Source [SID1234588089]). The acquisition underscores the Novartis commitment to finding treatments for patients with vision loss and the potential of optogenetics as the basis of successful therapeutics.

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"Optogenetics is emerging as a promising therapeutic approach that might restore sight to patients who are legally blind," said Jay Bradner, President of the Novartis Institutes for BioMedical Research. "The Arctos technology builds on our conviction that optogenetic gene therapies may meaningfully help patients battling devastating eye diseases."

Arctos developed its technology as a potential method for treating inherited retinal dystrophies (IRDs) and other diseases that involve photoreceptor loss, such as age-related macular degeneration (AMD). Existing gene therapy treatments aim to correct a specific gene, so only a small subset of patients can benefit. The Arctos technology is not limited to a specific gene, and thus can potentially address many forms of IRDs regardless of the underlying mutation. Arctos’ proprietary, light-sensitive optogene is delivered to specific retinal cells using gene therapy, thus turning the targeted cells into replacement photoreceptor-like cells. If successful, a therapeutic based on such a technology could be used to treat any disease that causes blindness due to photoreceptor death.

"We’ve watched this technology develop and mature into a therapeutic program that complements our existing portfolio and gives us new optogenetics technology to wield in our efforts to bring desperately needed therapeutic options to patients for these blinding diseases," said Cynthia Grosskreutz, Global Head of Ophthalmology at the Novartis Institutes for BioMedical Research.

IRDs, which impact more than 2 million people globally and often result in complete blindness, can be caused by mutations in over 100 different genes.1 AMD is the leading cause of visual disability, affecting an estimated 170 million people globally.2 There are no curative therapies currently available for AMD.

The Arctos technology was based on discoveries by its scientific co-founders Drs. Sonja Kleinlogel and Michiel van Wyk of University of Bern, Switzerland. Arctos was originally incubated by +ND Capital and was later supported by Novartis Venture Fund through a Series A financing round led by +ND Capital.

On September 21, 2021 Galectin Therapeutics Inc. (NASDAQ:GALT), the leading developer of therapeutics that target galectin proteins, reported that it has entered into a $20 million convertible debt financing agreement with Richard E. Uihlein, the Company’s Chairman and largest individual stockholder (Press release, Galectin Therapeutics, SEP 21, 2021, View Source [SID1234590066]). This $20 million convertible debt is in addition to a $10 million convertible debt financing from Mr. Uihlein completed in April 2021.

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The loan agreement comprises two separate $10 million convertible notes, the first of which closed and funded on September 17, 2021 and the second which will close on or before December 17, 2021. The convertible notes are unsecured and bear interest at a rate of 2% compounded annually. Additional interest of 2.5% per quarter will accrue but will only be paid if the debt and interest are converted into shares of the Company’s common stock, at Mr. Uihlein’s option, on or prior to maturity, which is four years from the date of each loan closing. The conversion price of the debt and interest is fixed at 228% above the price per share of common stock on the day prior to each closing or $5.00 per share, whichever is greater.

Richard E. Uihlein, Chairman of Galectin Therapeutics, commented on his $20 million investment, "I remain deeply committed to the Company’s success and our goal of addressing large, unmet medical needs. We are the only Company addressing NASH cirrhosis using a clinically relevant endpoint to measure efficacy. Additionally, the results from a phase 1 trial using belapectin in combination with KEYTRUDA, a checkpoint inhibitor, were very encouraging, particularly in patients with metastatic melanoma. This financing demonstrates my confidence in our team and our science, and I look forward to advancing our programs."

"I want to thank Mr. Uihlein for his unwavering commitment to the Company. The impact of his financial backing and leadership as Chairman cannot be overstated," said Joel Lewis, president and Chief Executive Officer of Galectin Therapeutics. "We continue to make progress in our NAVIGATE trial for patients with NASH cirrhosis and we also are exploring how to best move forward in the treatment of metastatic melanoma, where we have seen promising early results of belapectin in combination with KEYTRUDA in the treatment of advanced melanoma. This financing, as well as the recent addition of several accomplished and experienced professionals to our management team, provide resources that will help us pursue our goals."

About Belapectin

Belapectin is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of NASH and fibrosis. Galectin-3 plays a major role in diseases that involve scarring of organs including fibrotic disorders of the liver, lung, kidney, heart and vascular system. Belapectin binds to galectin-3 and disrupts its function. Preclinical data in animals have shown that belapectin has robust treatment effects in reversing liver fibrosis and cirrhosis. A Phase 2 study showed belapectin may prevent the development of esophageal varices in NASH cirrhosis, and these results provide the basis for the conduct of the NAVIGATE trial. The NAVIGATE trial (NAVIGATEnash.com), entitled "A Seamless Adaptive Phase 2b/3, Double-Blind, Randomized, Placebo-controlled Multicenter, International Study Evaluating

the Efficacy and Safety of Belapectin (GR-MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis" began randomization of patients in August, 2020, and is posted on www.clinicaltrials.gov (NCT04365868). Galectin-3 has a significant role in cancer, and the Company has supported a Phase 1b study in combined immunotherapy of belapectin and KEYTRUDA in advanced melanoma and in head and neck cancer. This trial provided a strong rationale for moving forward into a Phase 2 development program which the company is considering.

About Fatty Liver Disease with Advanced Fibrosis and Cirrhosis

Non-alcoholic steatohepatitis (NASH) has become a common disease of the liver with the rise in obesity and other metabolic diseases. NASH is estimated to affect up to 28 million people in the U.S. It is characterized by the presence of excess fat in the liver along with inflammation and hepatocyte damage (ballooning) in people who consume little or no alcohol. Over time, patients with NASH can develop excessive fibrosis, or scarring of the liver, and ultimately liver cirrhosis. It is estimated that as many as 1 to 2 million individuals in the U.S. will develop cirrhosis as a result of NASH, for which liver transplantation is the only curative treatment available. Approximately 8,890 liver transplants are performed annually in the U.S. There are no drug therapies approved for the treatment of liver fibrosis or cirrhosis.

On September 21, 2021 HUYABIO International (HUYABIO), the leader in accelerating global development of China’s pharmaceutical innovations, reported the first patient treated in a pivotal trial designed to measure the safety and efficacy of HBI-8000 combined with Bristol Myers Squibb’s anti-PD-1, antibody Opdivo (nivolumab), in patients with unresectable or metastatic melanoma (Press release, HUYA Bioscience, SEP 21, 2021, View Source [SID1234590092]). The multicenter, randomized, double blinded, placebo-controlled Phase 3 trial entitled, "Study Comparing the Investigational Drug HBI-8000 Combined with Opdivo vs. Opdivo in Patients with Advanced Melanoma," will have a primary outcome of objective response rate and progression-free survival. Secondary outcomes include safety and overall survival. Opdivo is a trademark of Bristol-Myers Squibb Company.

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Dr. Mireille Gillings, CEO & Executive Chair of HUYABIO said, "The initiation of the Phase 3 trial represents another significant milestone for HBI-8000 following the recent approval for the drug as monotherapy for the treatment of ATLL in Japan. The Company has taken another important step in expanding the clinical indications for our lead oncology asset in solid tumors. The results from our Phase 2 trial of HBI-8000 combined with Opdivo in solid tumors pointed to the important immunomodulatory activity for our drug. We are pleased to begin this global study in collaboration with Bristol Myers Squibb."

The pivotal multi-national trial will enroll 480 patients from the United States, Europe, Australia, New Zealand and Japan. In the US Phase 2 trial, the combination of HBI-8000 with Opdivo was well tolerated with a favorable safety profile in checkpoint naïve melanoma patients who achieved a promising clinical response.

"Australia has one of the highest rates of melanoma in the world, especially relevant to the Sunshine Coast and Queensland", said Principal Investigator Dr. Hong Shue, who treated the first patient and is from Sunshine Coast Haematology and Oncology Clinic and University of the Sunshine Coast Clinical Trials Unit. "We are really excited to participate in this HUYABIO International sponsored Phase 3 registrational clinical trial. This trial potentially offers a practice-changing, effective combination treatment of HBI-8000 with Opdivo to our patients on the Sunshine Coast. This study, if positive, may provide an additional treatment option and significant change in the metastatic melanoma treatment paradigm."

About HBI-8000

HBI-8000 is an epigenetic immunomodulator approved for the treatment of lymphoma and metastatic breast cancer in China. This oral agent targets class I histone deacetylases causing cell cycle arrest and tumor cell death as the mechanism underlying its single agent activity against lymphoma. The drug also has immunomodulatory impact by increasing the efficacy of checkpoint inhibitors in preclinical animal models. The Company recently reported results from its ongoing Phase 2 study for the Opdivo combination demonstrating an overall objective response rate of approximately 70% with a disease control rate over 90% in a cohort of checkpoint naïve patients with melanoma.