On August 11, 2020 Eisai Inc. reported the topline results from Study 211, a Phase 2 trial evaluating the efficacy and safety of LENVIMA, an orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, comparing two starting doses (18 mg versus 24 mg daily) in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) (Press release, Eisai, AUG 11, 2020, View Source [SID1234563462]). Results indicate that the lower starting dose (18 mg) of LENVIMA did not meet the non-inferiority requirement compared to the approved starting dose (24 mg) in patients with RAI-refractory DTC as measured by objective response rate (ORR) at week 24. The data from this study support the selection of 24 mg as an appropriate starting dose for patients with RAI-refractory DTC.

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Study 211 was conducted as a post-marketing commitment to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regions following priority review designation and approval of LENVIMA for the treatment of patients with locally recurrent or metastatic, progressive, RAI-refractory DTC.

The primary objective of the Phase 2, multicenter, randomized, double-blind study was to determine whether a starting dose of LENVIMA at 18 mg once daily would provide comparable efficacy based on ORR at 24 weeks with an improved safety profile compared to 24 mg starting dose based on treatment-emergent adverse events (TEAEs) of Grade 3 or higher. The 18 mg dose did not show non-inferiority in efficacy to the 24 mg dose as measured by ORR at week 24. The primary safety endpoint demonstrated that the incidences of Grade 3 or higher TEAEs through week 24 were similar between the 24 mg and 18 mg treatment arms.

"These findings help reinforce the efficacy and safety of LENVIMA for patients living with RAI-refractory differentiated thyroid cancer while supporting the appropriate starting dose for these patients," said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. "Studies like this post-marketing trial represent Eisai’s continued commitment to prioritizing patients’ needs and safety through the ongoing examination of our medicines. We would like to thank the patients, their families and clinical investigators for their participation in Study 211, and we look forward to presenting the full results of this study at an upcoming medical meeting."

Thyroid cancer is the most common endocrine malignancy and global figures show that its incidence is on the rise. In 2020, it is estimated that there will be 52,890 new cases of thyroid cancer in the U.S. and that women are three times more likely to develop thyroid cancer than men. The most common types of thyroid cancer, papillary and follicular (including Hürthle cell), are classified as DTC and account for approximately 90% of all cases. While most patients with DTC are curable with surgery and radioactive iodine treatment, the prognosis for those patients whose cancers persist or recur is poor.

About LENVIMA (lenvatinib)

LENVIMA (lenvatinib) is a kinase inhibitor that is indicated:

For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC)
In combination with everolimus, for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy, and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial
LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

Important Safety Information

Warnings and Precautions

Hypertension. In DTC, hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials. Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus– treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome. Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Impaired Wound Healing. Impaired wound healing has been reported in patients who received LENVIMA. Withhold LENVIMA for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LENVIMA after resolution of wound healing complications has not been established.

Embryo-fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus; and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose.

Adverse Reactions

In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

In EC, the most common adverse reactions (≥20%) observed in LENVIMA + pembrolizumab – treated patients were fatigue (65%), hypertension (65%), musculoskeletal pain (65%), diarrhea (64%), decreased appetite (52%), hypothyroidism (51%), nausea (48%), stomatitis (43%), vomiting (39%), decreased weight (36%), abdominal pain (33%), headache (33%), constipation (32%), urinary tract infection (31%), dysphonia (29%), hemorrhagic events (28%), hypomagnesemia (27%), palmar-plantar erythrodysesthesia (26%), dyspnea (24%), cough (21%) and rash (21%).

Adverse reactions led to dose reduction or interruption in 88% of patients receiving LENVIMA. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were fatigue (32%), hypertension (26%), diarrhea (18%), nausea (13%), palmar-plantar erythrodysesthesia (13%), vomiting (13%), decreased appetite (12%), musculoskeletal pain (11%), stomatitis (9%), abdominal pain (7%), hemorrhages (7%), renal impairment (6%), decreased weight (6%), rash (5%), headache (5%), increased lipase (5%) and proteinuria (5%).

Fatal adverse reactions occurred in 3% of patients receiving LENVIMA + pembrolizumab, including gastrointestinal perforation, RPLS with intraventricular hemorrhage, and intracranial hemorrhage.

Serious adverse reactions occurred in 52% of patients receiving LENVIMA + pembrolizumab. Serious adverse reactions in ≥3% of patients were hypertension (9%), abdominal pain (6%), musculoskeletal pain (5%), hemorrhage (4%), fatigue (4%), nausea (4%), confusional state (4%), pleural effusion (4%), adrenal insufficiency (3%), colitis (3%), dyspnea (3%), and pyrexia (3%).

Permanent discontinuation due to adverse reaction (Grade 1-4) occurred in 21% of patients who received LENVIMA + pembrolizumab. The most common adverse reactions (>2%) resulting in discontinuation of LENVIMA were gastrointestinal perforation or fistula (2%), muscular weakness (2%), and pancreatitis (2%).

Use in Specific Populations

Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC or EC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or EC and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end stage renal disease. No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

No dose adjustment is recommended for patients with DTC, RCC, or EC and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or EC and severe hepatic impairment.

LENVIMA (lenvatinib) is available as 10 mg and 4 mg capsules.

Please see Prescribing Information for LENVIMA (lenvatinib) at View Source

About the Eisai and Merck Strategic Collaboration
In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck’s anti-PD-1 therapy pembrolizumab.

In addition to ongoing clinical studies evaluating the pembrolizumab plus LENVIMA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in 13 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer and triple-negative breast cancer) across 18 clinical trials.

Eisai’s Focus on Cancer
Eisai focuses on the development of anticancer drugs, targeting the tumor microenvironment (with experience and knowledge from Halaven and Lenvima) and the driver gene mutation and aberrant splicing (leveraging RNA Splicing Platform) as areas (Ricchi) where real patient needs are still unmet, and where Eisai can become a frontrunner in oncology. Eisai will discover innovative new drugs with new targets and mechanisms of action from these Ricchi, with the aim of contributing to the cure of cancers.

On August 11, 2020 Intabio, Inc., a developer of analytical solutions that provide profound efficiency gains across all stages of biopharmaceutical development and manufacturing, reported a co-marketing and equipment loan agreement with Agilent Technologies Inc. to support development of integrated iCIEF-MS assays by interfacing Intabio’s Blaze to the Agilent 6545XT AdvanceBio LC/Q-TOF mass spectrometer (Press release, Intabio, AUG 11, 2020, View Source [SID1234563461]). The combination of the Blaze system coupled to the Agilent 6545XT for the monitoring of Critical Quality Attributes (CQAs) on intact proteins will significantly increase productivity for biotherapeutic developers.

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Intabio’s Blaze System couples two gold-standard analytical techniques – imaged capillary isoelectric focusing (iCIEF) and high-resolution mass spectrometry (MS) – into a single 15-minute assay with 100 times the throughput of traditional workflows. Biotherapeutic developers can quickly monitor multiple CQAs directly on intact proteins – a powerful capability when faced with large numbers of samples and tight timelines.

"Our Biopharma customers have expressed the need for a Blaze integrated assay with the 6545XT and this agreement will enable Intabio to accelerate the launch of a coupled Blaze and Agilent 6545XT assay," said Lena Wu, Ph.D., Intabio CEO and co-founder. "As Intabio adds integrations with more leading MS platforms, access to our leading technology broadens and ultimately shortens the development of biotherapeutics."

The Agilent 6545XT AdvanceBio LC/Q-TOF system is designed to handle multiple workflows in biopharmaceutical characterization. It provides detailed information at the intact protein level, automatically confirming protein sequence at the peptide level and identifying post-translational modifications.

"The Blaze system and the 6545XT AdvanceBio LC/Q-TOF both excel at enabling researchers to see more information at the intact protein level," said David Edwards, Ph.D., Associate Vice President of Marketing for Agilent Technologies’ Mass Spectrometry Division. "The combination of these two technologies offers exciting opportunities from both a scientific and laboratory efficiency perspective."

The shipment release of the Blaze system is scheduled for December 2020 with anticipated shipments occurring before year end. Early access of mAb technical evaluations on the Blaze is currently available.

On August 11, 2020 Northwest Biotherapeutics (OTCQB: NWBO)("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that the Company has completed a financing on favorable terms for approximately $8 million (Press release, Northwest Biotherapeutics, AUG 11, 2020, View Source [SID1234563460]). The Company anticipates that this financing will help maintain the Company’s momentum, and will provide some prudent protection in the midst of the current global economic uncertainties. The financing also further broadens the lock-up of warrants that the Company has been building.

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The financing comprised:

Approximately $7 million from an offering at 32 cents per share of newly registered common stock of approximately 21.8 million shares with warrants averaging 21% (predominantly 20%, with a couple larger investors at 35%) exercisable at 34 cents per share for approximately 5.3 million shares, with an exercise period ranging from 18 to 30 months, and
$1 Million from a convertible note (the "Note") which is convertible at 34.5 cents. The Note contains no warrants unless it is converted. If, and only to the extent the Note is converted, it will carry 35% warrants exercisable at 34 cents per share.
The financing also broadened the warrant suspensions that the Company has been building and the Company plans to continue expanding:

An additional approximately 75.5 million existing warrants, outstanding prior to this financing and held by investors in this financing, have been suspended until December 15, 2020 as part of this financing. These warrant suspensions were compensated on a similar basis as the warrant suspensions previously reported. In addition, all new warrants in this financing are suspended until December 15, 2020.
As the Company approaches the read-out of its Phase III trial of DCVax-L for Glioblastoma brain cancer, the Company is working with a growing team of technical experts and regulatory advisers on various readiness preparations, including manufacturing related preparations. This financing will help the Company maintain its momentum in these very important activities.

"With this significant financing, we believe we are well positioned to execute on our near-term plans and to support the next critical phase of our business strategy," commented Linda Powers, Chairman and CEO of the Company. "We look forward to sharing more detail on these initiatives."

The majority of this financing involved no fees or placement expenses. On the remainder of the financing, the Company paid fees of 6% cash and 4% warrants.

On August 11, 2020 ThermoGenesis Holdings, Inc. (Nasdaq: THMO), a market leader in automated cell processing tools and services in the cell and gene therapy field, reported it will delay its second quarter earnings release and conference call for the quarter ended June 30, 2020, previously scheduled for Wednesday, August 12, 2020 (Press release, Thermogenesis, AUG 11, 2020, View Source [SID1234563459]). The Company now intends to report its second quarter 2020 results on Friday, August 14, 2020, after the close of trading. A conference call and webcast will follow at 1:30 p.m. PT/ 4:30 p.m. ET.

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To participate in the conference call, please dial 1-844-889-4331 (domestic), 1-412-380-7406 (international) or 1-866-605-3852 (Canada). To access a live webcast of the call, please visit: View Source

A webcast replay will be available on ThermoGenesis’ website for three months by visiting the Investor page of the Company’s website at www.thermogenesis.com.

On August 11, 2020 Aridis Pharmaceuticals, Inc. (Nasdaq: ARDS), a biopharmaceutical company focused on the discovery and development of novel anti-infective therapies to treat life-threatening infections, reported financial and corporate results for the second quarter ended June 30, 2020 (Press release, Aridis Pharmaceuticals, AUG 11, 2020, View Source [SID1234563458]).

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Second Quarter Highlights and Recent Developments

Reported positive safety data in the healthy subject (Phase 1) portion of AR-501’s Phase 1/2a clinical trial for treating chronic lung infections in patients with cystic fibrosis (CF). Safety and efficacy results from the Phase 2a portion in CF patients expected in 2H 2021
Continued enrolling Phase 3 global clinical trial of AR-301 in patients with ventilator associated pneumonia (VAP) including patients who presented with VAP secondary to ventilator placement for COVID-19. Interim data expected in 2H 2020; full data in 2H 2021
Directed ʎPEX platform’s discovery capabilities towards treatments for pulmonary infectious diseases given the on-going COVID-19 pandemic
Initiated mAb discovery and IND enabling studies for AR-701, a potential treatment or prophylaxis for COVID-19, ʎPEX’s first fully human mAb cocktail directed at multiple envelope proteins on SARS-CoV-2
Bolstered leadership team with appointment of Dr. Hasan Jafri as Chief Medical Officer
Enhanced corporate profile by participating in leading healthcare dedicated investor forums
"The second quarter proved to be a strong period of progress as we continue on our mission to become the leader in developing novel anti-infective treatments for lung infections," commented Vu Truong, Ph.D., Chief Executive Officer of Aridis Pharmaceuticals. "In addition to advancing multiple early and clinical stage programs while ramping-up our ʎPEXTM platform’s rapid discovery engine to identify targets for pulmonary infections, we were able to enhance our leadership team with the appointment of Dr. Hasan Jafri as Chief Medical Officer. Dr. Jafri solidifies our expertise in infectious disease immunotherapy utilizing mAbs given his specific experience developing similar programs during his tenure at AstraZeneca. As we head into the second half of the year, I firmly believe we are well positioned to advance our ongoing clinical studies of AR-301 for VAP and AR-501 for CF as well as potentially start a new trial for AR-701 for COVID-19."

ʎPEXTM Technology Platform and COVID-19 Program Update

During the quarter, and in response to the most pressing need of current times, Aridis was able to utilize its ʎPEX mAb discovery platform to generate AR-701, a fully human mAb cocktail derived from convalescent COVID-19 patients and directed at multiple envelope proteins on SARS-CoV-2 to enable broad coverage against SARS-CoV-2 variants and ensuring wide applicability across variants of the virus that may arise. During the quarter ended June 30, 2020, the Company went from collecting sera from convalescent COVID-19 patients at hospital centers in US and Europe to thousands of candidate mAbs, which highlights how ʎPEX can rapidly identify large number of drug candidates to SARS-CoV-2 and other potential emerging viral or bacterial pathogens.

Aridis utilizes its ʎPEX technology platform for the unbiased discovery of new and highly potent antibodies against pathogens including COVID-19. The ʎPEX platform is comprised of a silicon wafer-based array of nanoliter sized tissue micro-culture wells that enable rapid screening of antibody secreting cells, enabling discovery of potent antibodies against targets such as SARS-CoV-2, the virus that causes COVID-19 disease within a few days of patient sample availability. It also features CRISPR enabled activation of endogenous genetic control elements that dramatically increase the yield of such therapeutic antibodies from manufacturing production cell lines. The technology also features a proprietary production cell line that is designed to rapidly manufacture multiple monoclonal antibody therapeutics at approximately half the manufacturing cycle time than currently available manufacturing technologies.

Clinical Program Update

AR-301: Aridis remains on track to report interim data in 2H 2020, and top line data in 2H 2021 of its ongoing Phase 3 clinical trial of AR-301. While this timeline may be further impacted by the on-going COVID-19 pandemic, the pace of the trial was not significantly impacted in the second quarter. In fact, during April, Aridis enrolled its first COVID-19 patient in the study. COVID-19 patients on prolonged mechanical ventilation in the intensive care unit (ICU) are prone to secondary infections (also called ‘superinfections’) by opportunistic pathogens such as bacteria. Superinfection is a reported complication in COVID-19 patients, which exacerbates morbidity and the rate of mortality. The AR-301 Phase 3 study allows for the enrollment of patients with baseline characteristics which are inclusive of certain COVID-19 patients. While AR-301 is not an agent to treat SARS-CoV-2 virus itself, it can potentially reduce the morbidity associated with secondary S. aureus pneumonia, which is a coronavirus complication and a contributing cause of death in such patients.

The trial, which was initiated in the first quarter of 2019, is expected to enroll 240 patients at approximately 160 clinical centers in 22 countries. Participating clinical centers that are activated continue to follow the same stringent clinical protocols and procedures for critically ill VAP patients, as is standard in the U.S. and Europe. The trial represents the first ever Phase 3 superiority clinical study evaluating immunotherapy with a fully human monoclonal antibody to treat acute pneumonia in the intensive care unit setting. Details of the study can be viewed on www.clinicaltrials.gov using identifier NCT03816956.

AR-301 is a fully human monoclonal IgG1 antibody specifically targeting gram-positive S. aureus alpha-toxin. It has been shown in vitro to protect against alpha-toxin mediated destruction of host cells, thereby potentially preserving the human immune response. AR-301’s mode of action is independent of the antibiotic resistance profile of S. aureus and it is active against infections caused by both MRSA (methicillin resistant S. aureus) and MSSA (methicillin sensitive S. aureus).

AR-501: On June 22, 2020 Aridis reported positive safety data from the healthy subjects portion of its Phase 1/2a clinical trial of an inhalable formulation of gallium citrate being evaluated for the treatment of chronic lung infections associated with cystic fibrosis. There were no reports of serious adverse events and the treatment was well tolerated. The study was designed to enroll 48 healthy adult volunteers (Phase 1) and 48 cystic fibrosis patients (Phase 2a) from approximately 18 sites in the U.S. In the now-completed Phase 1 arm, 48 healthy adults were randomized and treated in 6 cohorts (of 8 subjects each) to receive either a single ascending dose (SAD, Cohorts 1, 2, and 3 [N=24]) or weekly multiple ascending doses (MAD, Cohorts 4, 5, and 6 [N=24]) of active drug at 6.4 mg gallium (Ga+3), 20 mg Ga+3 and 40 mg Ga+3 or placebo. Phase 1 participants were randomized within each cohort in a 3:1 ratio of active drug to placebo. Subjects were followed for 28 days after study dose for safety and pharmacokinetics (PK) of inhaled AR-501 in HV subjects. AR-501 or placebo was delivered by a nebulizer device. Following the recommendations of the Data Safety Monitoring Board (DSMB) from the Cystic Fibrosis Foundation (CFF) and study’s Safety Monitoring Committee (SMC), the Company will proceed with the Phase 2a segment with cystic fibrosis subjects and expects to report data in 2H 2021. The achievement of this milestone triggered a $1.0 million milestone payment from the CFF, and the Company recognized $1.0 million in revenue during the second quarter of 2020.

AR-501 is being developed in collaboration with the CF Foundation and has been granted Orphan Drug Designation (ODD), Fast Track and Qualified Infectious Disease Product (QIDP) designations by the U.S. Food and Drug Administration (FDA). In addition, the European Medicines Agency (EMA) granted ODD to AR-501. Details of the Phase 1/2a clinical trial, which is a randomized, double-blinded, placebo controlled single and multiple dose-ascending trial investigating the safety and PK of inhaled AR-501 in healthy volunteers and cystic fibrosis patients with chronic bacterial lung infections, can be viewed on www.clinicaltrials.gov using identifier NCT03669614.

Corporate Update

During the second quarter, the Company enhanced its leadership team by appointing Dr. Hasan Jafri as Chief Medical Officer. Dr. Jafri brings to Aridis over 25 years of experience in clinical practice and research, especially in the area of serious healthcare associated and community acquired infections, respiratory viral infections and invasive fungal infections. Immediately prior to joining Aridis, Dr. Jafri was at AstraZeneca, where he most recently served as Senior Medical Director, Clinical Research and Development, Microbial Sciences, Clinical Head of Antibacterial mAb Program, and Coordinator of the European Public-Private COMBACTE-NET & COMBACTE-MAGNET consortia focused on antibacterial drug development supported by the Innovative Medicines Initiative (IMI). During his tenure at AstraZeneca, he led the clinical development of the anti-bacterial monoclonal antibodies within the Serious Bacterial Infections Franchise, including its Phase 2 programs MEDI4893 (anti-S. aureus alphatoxin mAb) and MEDI3902 (anti-P. aeruginosa Psl/PcrV mAb).

Throughout the quarter, Aridis continued to increase its profile in the investment and business communities by participating in leading healthcare dedicated investor forums. The Company’s management team was hosted by Cantor Fitzgerald for a Fireside Chat on June 25th entitled "ʎPEXTM, a technology platform geared to rapidly discover new treatments for emerging pulmonary pathogens." On June 30th, Dr. Vu Truong, the Company’s CEO was also a featured speaker in another Cantor Fitzgerald symposium entitled "Winning Ways to Treat Infections and COVID-19." The event consisted of representatives from companies in various stages of development in the race to discover treatments for COVID-19.

Replays for both events can be found at View Source

Fiscal 2020 Second Quarter Results:

Cash: Total cash and cash equivalents as of June 30, 2020 was $11.8 million.
Paycheck Protection Program Loan: During the quarter ended June 30, 2020, the Company applied for and received a loan in the amount of approximately $715,000, pursuant to the Paycheck Protection Program.
Revenues: Grant revenue increased to $1.0 million for the quarter ended June 30, 2020 from zero for the quarter ended June 30, 2019, which was primarily due to the recognition of revenue related to a milestone under the grant award from the CFF during the second quarter of 2020 and none during the second quarter of 2019.
Research and Development Expenses: Research and development expenses incurred in the quarter ended June 30, 2020 were approximately $3.6 million, a decrease of approximately $3.0 million over the same period in 2019 due primarily to a decrease in spending on clinical trial activities and drug manufacturing expenses for the Phase 2 study of our AR-105 program, which terminated during 2019; a decrease in spending on our clinical trial activities and drug manufacturing expenses for the Phase 3 study of our AR-301 program during the second quarter of 2020 as compared to the second quarter of 2019, which included increased study start-up costs; and a decrease in personnel, consulting and other related costs. These decreases were partially offset by an increase in spending on clinical trial activities for the Phase 1/2a study of our AR-501 program.
General and Administrative Expenses: There was no material difference in general and administrative expenses for the quarter ended June 30, 2020 when compared to the same period in 2019.
Interest Income, net: Interest income, net was approximately $10,000 for the quarter ended June 30, 2020, a decrease of approximately $59,000 over the same period in 2019. This decrease was primarily due to lower interest rates.
Share of Loss from Equity Method Investment: Loss from equity method investment decreased by $186,000 for the quarter ended June 30, 2020 when compared to the same period in 2019 due to there being no share of losses from our equity method investment recorded in the second quarter of 2020 as the net book value of the investment was zero at March 31, 2020.
Net Loss: The net loss for the quarter ended June 30, 2020 was approximately $4.2 million, or $0.47 net loss per share, compared to a net loss of approximately $8.4 million, or $1.03 net loss per share, for the quarter ended June 30, 2019. The weighted average common shares outstanding was approximately 8.9 million and approximately 8.1 million for the second quarter of 2020 and 2019, respectively.