On August 5, 2021 Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported financial results for its fiscal third quarter ended June 30, 2021 (Press release, Arrowhead Research Corporation, AUG 5, 2021, View Source [SID1234585865]). The company is hosting a conference call today, August 5, 2021, at 4:30 p.m. ET to discuss the results.

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Conference Call and Webcast Details

Investors may access a live audio webcast on the Company’s website at View Source For analysts that wish to participate in the conference call, please dial 855-215-6159 or 315-625-6887 and provide Conference ID 7398304.

A replay of the webcast will be available on the company’s website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 855-859-2056 or 404-537-3406 and provide Conference ID 7398304.

Selected Recent Events

Received Breakthrough Therapy designation from the U.S. Food and Drug Administration for ARO-AAT, also known as TAK-999, the company’s second-generation investigational RNA interference (RNAi) therapeutic being co-developed with Takeda Pharmaceutical Company Limited as a treatment for the rare genetic liver disease associated with alpha-1 antitrypsin deficiency.
Presented additional positive interim 48-week liver biopsy results from the ongoing AROAAT2002 study, an open-label Phase 2 clinical study of ARO-AAT, at The International Liver Congress – The Annual Meeting of the European Association for the Study of the Liver (EASL). The results demonstrate that investigational ARO-AAT treatment led to improvements in multiple measures of liver health, including fibrosis, with substantial and sustained reductions in the level of mutant AAT protein. In addition, ARO-AAT treatment was generally well tolerated after up to 1 year of treatment.
Presented positive interim results from AROHSD1001, an ongoing Phase 1/2 clinical study of ARO-HSD, the company’s investigational RNAi therapeutic being developed as a treatment for patients with alcohol-related and nonalcohol related liver diseases, such as nonalcoholic steatohepatitis (NASH), at EASL. The data demonstrate that ARO-HSD is the first investigational therapeutic to achieve robust reductions in messenger RNA and protein levels of hepatic HSD17B13, leading to reductions in alanine aminotransferase (ALT), a liver enzyme typically elevated in liver diseases including NASH.
Announced positive interim results from the first two cohorts of AROHIF21001, a Phase 1b dose-finding clinical study of ARO-HIF2, the company’s investigational RNAi therapeutic being developed as a treatment for patients with clear cell renal cell carcinoma. The data show clear signs of meaningful target engagement and some potentially early signs of efficacy in at least one patient.
Initiated and began dosing patients in AROANG3-2001, a Phase 2b clinical study of ARO-ANG3, the company’s investigational RNAi therapeutic being developed as a treatment for patients with mixed dyslipidemia.
Initiated and began dosing patients in AROAPOC3-2001, a Phase 2b clinical study of ARO-APOC3, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with severe hypertriglyceridemia (SHTG). Arrowhead also intends to initiate a Phase 2b study and a Phase 3 study of ARO-APOC3 in two additional patient populations in 2021.
Announced a global collaboration and license agreement with Horizon Therapeutics for ARO-XDH, a previously undisclosed discovery-stage RNAi therapeutic being developed by Arrowhead as a potential treatment for people with uncontrolled gout. Arrowhead received $40 million as an upfront payment from Horizon and is eligible to receive up to $660 million in potential development, regulatory and commercial milestones, and is further eligible to receive royalties in the low- to mid-teens range on net product sales.
Earned a $10 million option exercise fee from Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, for ARO-JNJ1.
Presented promising preclinical data on ARO-DUX4, Arrowhead’s first muscle-targeted program being developed as a treatment for patients with facioscapulohumeral muscular dystrophy (FSHD) at the 28th Annual FSHD Society International Research Congress. The data show that the TRiMTM muscle delivery platform achieved functional delivery to various types of skeletal muscle and achieved deep, durable, and dose-dependent knockdown of target genes. In addition, ARO-DUX4 improved multiple measures of FSHD-like muscle phenotype in relevant preclinical animal models.
Nominated ARO-C3, which is designed to reduce production of complement component 3 (C3) as a potential treatment for various complement mediated diseases, as a clinical candidate and initiated IND-enabling toxicology studies.

On August 5, 2021 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the second quarter of 2021 and provided an update on progress toward achieving key corporate objectives, as well as commercial, clinical and pipeline development milestones (Press release, Exelixis, AUG 5, 2021, View Source [SID1234585880]).

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"In the second quarter of 2021, Exelixis delivered a 59 percent year over year increase in CABOMETYX net product revenue growth and record total revenues, based on the broad adoption of the CABOMETYX and OPDIVO combination regimen as a preferred treatment in first-line renal cell carcinoma"

"In the second quarter of 2021, Exelixis delivered a 59 percent year over year increase in CABOMETYX net product revenue growth and record total revenues, based on the broad adoption of the CABOMETYX and OPDIVO combination regimen as a preferred treatment in first-line renal cell carcinoma," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "Following this strong commercial performance, we are raising our net product and total revenue guidance for 2021. In parallel, we also made significant progress across our development activities, with the filing of a supplemental New Drug Application for cabozantinib in differentiated thyroid cancer based on the COSMIC-311 study, and announcements of top-line results from both the COSMIC-312 trial in first-line advanced hepatocellular carcinoma and the expanded Cohort 6 of the COSMIC-021 trial in patients with advanced prostate cancer. In addition, on the pipeline front, we broadened the development program of XL092 with a new clinical collaboration with Bristol Myers Squibb and initiated the Phase 1 trial for XB002, our first antibody-drug conjugate. I’d like to thank the entire Exelixis team for a very strong first half of 2021 and look forward to providing further updates on our progress in the second half of the year."

Second Quarter 2021 Financial Results

Total revenues for the quarter ended June 30, 2021 were $385.2 million, compared to $259.5 million for the comparable period in 2020.

Total revenues for the quarter ended June 30, 2021 included net product revenues of $284.2 million, compared to $178.7 million for the comparable period in 2020. The increase in net product revenues was primarily related to an increase in sales volume that was driven by strong uptake for the combination therapy of CABOMETYX (cabozantinib) and OPDIVO (nivolumab) following approval by the U.S. Food and Drug Administration (FDA) in January 2021.

Collaboration revenues, composed of license revenues and collaboration services revenues, were $100.9 million for the quarter ended June 30, 2021, compared to $80.7 million for the comparable period in 2020. The increase in collaboration revenues was primarily related to increases in development cost reimbursements earned, and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited (Takeda), which was partially offset by a decrease in the recognition of milestone-related revenues.

Research and development expenses for the quarter ended June 30, 2021 were $148.8 million, compared to $114.9 million for the comparable period in 2020. The increase in research and development expenses was primarily related to increases in license and other collaboration costs, personnel expenses and stock-based compensation expense, which was partially offset by decreases in clinical trial costs.

Selling, general and administrative expenses for the quarter ended June 30, 2021 were $98.5 million, compared to $59.8 million for the comparable period in 2020. The increase in selling, general and administrative expenses was primarily related to increases in personnel expenses, marketing costs, corporate giving and stock-based compensation expense.

Provision for income taxes for the quarter ended June 30, 2021 was $28.8 million, compared to $13.9 million for the comparable period in 2020, primarily due to an increase in pre-tax income.

GAAP net income for the quarter ended June 30, 2021 was $96.1 million, or $0.31 per share, basic and $0.30 per share, diluted, compared to GAAP net income of $66.8 million, or $0.22 per share, basic and $0.21 per share, diluted, for the comparable period in 2020.

Non-GAAP net income for the quarter ended June 30, 2021 was $117.9 million, or $0.38 per share, basic and $0.37 per share, diluted, compared to non-GAAP net income of $79.4 million, or $0.26 per share, basic and $0.25 per share, diluted, for the comparable period in 2020. Non-GAAP net income excludes stock-based compensation, adjusted for the related income tax effect.

Cash, cash equivalents, restricted cash equivalents and investments were $1.7 billion at June 30, 2021, compared to $1.5 billion at December 31, 2020.

Non-GAAP Financial Measures

To supplement Exelixis’ financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented.

Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

2021 Financial Guidance

Exelixis is providing the following updated financial guidance for fiscal year 2021:

Total revenues (1)

$1,300 million – $1,400 million

Net product revenues (1)

$1,050 million – $1,150 million

Cost of goods sold

Approximately 5% – 6% of net product revenue

Research and development expenses (1)(2)

$650 million – $700 million

Selling, general and administrative expenses (1)(3)

$375 million – $425 million

Effective tax rate

20% – 22%

Cash and investments (4)(5)

$1.7 billion – $1.8 billion

(1)

Guidance updated on August 5, 2021 from previously provided guidance on May 6, 2021.

(2)

Includes $45 million of non-cash stock-based compensation expense.

(3)

Includes $60 million of non-cash stock-based compensation expense.

(4)

This cash and investments guidance does not include any potential new business development activity.

(5)

Cash and investments is composed of cash, cash equivalents, restricted cash equivalents and investments.

Cabozantinib Highlights

Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $284.2 million during the second quarter of 2021, up 25 percent over the prior quarter, with net product revenues of $275.6 million from CABOMETYX and $8.6 million from COMETRIQ (cabozantinib). Exelixis earned $24.9 million in royalty revenues during the quarter ended June 30, 2021, pursuant to collaboration agreements with our partners, Ipsen and Takeda.

Announcement of Phase 1b Results from Cohort 6 of COSMIC-021 Trial in Patients with Metastatic Castration-Resistant Prostate Cancer (CRPC). In May, Exelixis announced results from the metastatic CRPC cohort 6 of COSMIC-021, the phase 1b trial of cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic solid tumors. The analysis included 132 patients, 101 of whom had high-risk disease, defined as measurable visceral and/or extra-pelvic lymph node metastases. Based on these promising results, Exelixis intends to discuss the data with the FDA to determine next steps toward a potential regulatory submission for the combination regimen for patients with high-risk metastatic CRPC and plans to present detailed results at a medical meeting in the second half of 2021.

Cabozantinib Presentations at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO 2021) Demonstrate Consistent Results in Renal Cell Carcinoma (RCC). In June, cabozantinib was the subject of multiple RCC data presentations at ASCO (Free ASCO Whitepaper) 2021, which included: a post-hoc exploratory analysis demonstrating consistent efficacy benefits across subgroups in the phase 3 CheckMate -9ER pivotal trial with CABOMETYX in combination with OPDIVO compared with sunitinib as a first-line treatment for advanced RCC; results from another post-hoc analysis of the CheckMate -9ER trial demonstrating that CABOMETYX in combination with OPDIVO resulted in a statistically significant and clinically meaningful increase in quality-adjusted survival (Q-TWiST) compared with sunitinib; and positive phase 2 results from an investigator-sponsored trial evaluating cabozantinib in combination with nivolumab in patients with advanced or metastatic non-clear cell RCC.

Detailed Results from Phase 3 COSMIC-311 Pivotal Trial of Cabozantinib in Patients with Previously Treated Radioactive Iodine (RAI)-Refractory Differentiated Thyroid Cancer (DTC) Also Presented at ASCO (Free ASCO Whitepaper) 2021. In June, Exelixis and Ipsen announced detailed results from the phase 3 COSMIC-311 pivotal trial of cabozantinib in patients with previously treated RAI-refractory DTC, presented at ASCO (Free ASCO Whitepaper) 2021. Results from the trial, which met the primary endpoint of demonstrating significant improvement in progression-free survival (PFS) assessed by a blinded independent radiology committee, were recently published in The Lancet Oncology and served as the basis for the supplemental New Drug Application (sNDA) submitted to the FDA in June.

Announcement of Top-line Results of Phase 3 COSMIC-312 Pivotal Trial in Patients with Previously Untreated Advanced Hepatocellular Carcinoma (HCC). In June, Exelixis and Ipsen announced that COSMIC-312, the ongoing phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab versus sorafenib in patients with previously untreated advanced HCC, met one of the primary endpoints, demonstrating significant improvement in PFS at the planned primary analysis. A prespecified interim analysis for the second primary endpoint of overall survival (OS), conducted at the same time as the primary analysis for PFS, showed a trend favoring the combination of cabozantinib and atezolizumab but did not reach statistical significance. The trial will continue as planned to the final analysis of OS; results are anticipated in early 2022. Exelixis plans to present the trial results at a future medical meeting and intends to discuss the results with the FDA to determine next steps toward a potential regulatory submission for the combination regimen for patients with previously untreated advanced HCC.

FDA Accepts sNDA for CABOMETYX for Patients with Previously Treated RAI-Refractory DTC. In August, Exelixis announced that the FDA accepted the company’s sNDA for CABOMETYX as a treatment for patients 12 years and older with DTC who have progressed following prior therapy and are RAI-refractory (if RAI is appropriate). The FDA granted Priority Review designation and assigned a Prescription Drug User Fee Act goal date, or target action date, of December 4, 2021.

Pipeline Highlights

FDA Accepts Investigational New Drug Application (IND) and Phase 1 Trial Initiated for Tissue Factor-Targeting Antibody-Drug Conjugate (ADC) XB002 in Patients with Advanced Solid Tumors. In April, Exelixis announced that the FDA accepted its IND to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of XB002 in patients with advanced solid tumors, and in June, a phase 1 trial was initiated. As a next-generation tissue factor-targeting ADC, XB002 has the potential for an improved therapeutic index and may provide a favorable safety profile compared with earlier-generation tissue factor-targeting ADCs. Exelixis in-licensed XB002 from Iconic Therapeutics, Inc. in December 2020 under the companies’ May 2019 collaboration agreement.

Exelixis and Bristol Myers Squibb (BMS) Enter Clinical Trial Collaboration and Supply Agreement to Evaluate XL092 in Combination with Immuno-oncology Therapies in Advanced Solid Tumors. In June, Exelixis announced a clinical trial collaboration and supply agreement with BMS for STELLAR-002, a new phase 1b trial evaluating XL092 in combination with immuno-oncology therapies in advanced solid tumors. The objective of the study is to evaluate the safety, tolerability and efficacy of XL092, Exelixis’ novel next-generation tyrosine kinase inhibitor, in combination with: nivolumab; nivolumab and ipilimumab (YERVOY); and nivolumab and bempegaldesleukin, an investigational CD122-preferential IL-2–pathway agonist developed by Nektar Therapeutics (Nektar). The trial is anticipated to begin enrolling patients in the second half of 2021. Nektar will supply bempegaldesleukin to BMS through their existing global development and commercialization collaboration, which is evaluating nivolumab in combination with bempegaldesleukin.

Corporate Updates

Exelixis Expands its Biotherapeutics Portfolio with Acquisition of Anti-Müllerian Hormone Receptor 2 (AMHR2) Program from GamaMabs Pharma SA (GamaMabs). In May, Exelixis entered into an asset purchase agreement with GamaMabs under which Exelixis will, upon the closing of the asset purchase and subject to certain conditions, acquire all rights, title and interest in GamaMabs’ antibody program directed at AMHR2, a novel oncology target with relevance in multiple forms of cancer. Exelixis believes applying its ADC capabilities to GamaMabs’ panel of antibodies against AMHR2 could yield potential additions to the company’s biotherapeutics portfolio.

Exelixis Files Lawsuit to Enforce Its Intellectual Property Rights for CABOMETYX against Abbreviated New Drug Application (ANDA) Filers. In June, Exelixis filed a patent lawsuit against Teva Pharmaceuticals Development, Inc. and Teva Pharmaceuticals USA, Inc. (individually and collectively referred to as Teva), along with Teva Pharmaceutical Industries Limited, following receipt of two Paragraph IV certification notice letters from Teva informing Exelixis that it had filed an ANDA with the FDA requesting approval to market a generic version of CABOMETYX tablets. Teva’s notice letters included a Paragraph IV certification with respect to three of Exelixis’ Orange Book-listed patents: U.S. Patent Nos. 9,724,342 (formulations), 10,034,873 (methods of treatment) and 10,039,757 (methods of treatment), which expire in 2033, 2031 and 2031, respectively. Teva’s notice letter did not provide a Paragraph IV certification against any additional CABOMETYX patents. Exelixis is seeking, among other relief, an order that the effective date of any FDA approval of the ANDA would be a date no later than the expiration of all of U.S. Patent Nos. 9,724,342, 10,034,873 and 10,039,757, the latest of which expires on July 9, 2033, and equitable relief enjoining Teva and Teva Pharmaceutical Industries Limited from infringing these patents.

Basis of Presentation

Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31st. For convenience, references in this press release as of and for the fiscal periods ended July 2, 2021, January 1, 2021 and July 3, 2020 are indicated as being as of and for the periods ended June 30, 2021, December 31, 2020, and June 30, 2020, respectively.

Conference Call and Webcast

Exelixis management will discuss the company’s financial results for the second quarter of 2021 and provide a general business update during a conference call beginning at 5:00 p.m. EDT / 2:00 p.m. PDT today, Thursday, August 5, 2021.

To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 855-793-2457 (domestic) or 631-485-4921 (international) and provide the conference call passcode 7296685 to join by phone.

A telephone replay will be available until 8:00 p.m. EDT on August 7, 2021. Access numbers for the telephone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 7296685. A webcast replay will also be archived on www.exelixis.com for one year.

On August 5, 2021 Sanofi and Regeneron reported that it’s PD-1 inhibitor Libtayo in combination with platinum-doublet chemotherapy was stopped early after meeting its overall survival (OS) primary endpoint in patients with advanced non-small cell lung cancer (NSCLC) (Press release, Sanofi, AUG 5, 2021, View Source [SID1234585896]). Adding Libtayo to chemotherapy significantly improved OS, compared to chemotherapy alone, in the trial that enrolled patients with metastatic or locally advanced disease and tumors with either squamous or non-squamous histology and across all PD-L1 expression levels . These data are planned to form the basis of regulatory submissions in the U.S. and European Union.

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"Libtayo in combination with chemotherapy increased median overall survival to 22 months in patients with advanced non-small cell lung cancer, compared to 13 months with chemotherapy alone," said Miranda Gogishvili, M.D., an oncologist at the High Technology Medical Center, University Clinic, in Tbilisi, Georgia and a trial investigator. "Notably, the Phase 3 trial enrolled patients with a variety of challenging-to-treat disease characteristics, as well as those with locally advanced disease. These data add to the growing body of evidence supporting Libtayo in advanced non-small cell lung cancer, which also include the pivotal results for Libtayo monotherapy in cases of high PD-L1 expression."

The decision to stop the trial early was based on a recommendation by the Independent Data Monitoring Committee (IDMC) during a protocol-specified interim analysis. In this top-line initial analysis of 466 patients, combining Libtayo with chemotherapy reduced the risk of death by 29% compared to chemotherapy alone (hazard ratio: 0.71; 95% confidence interval [CI]: 0.53-0.93; p=0.014). Median OS was 22 months (95% CI: 16 months to not evaluable) for Libtayo and chemotherapy, and 13 months (95% CI: 12 to 16 months) for chemotherapy alone. No new Libtayo safety signals were identified in the IDMC analysis, and additional detailed efficacy and safety data will be presented at an upcoming medical meeting.

Lung cancer is the leading cause of cancer death worldwide. In 2020, an estimated 2.2 million and 225,000 new cases were diagnosed globally and in the U.S., respectively. Approximately 84% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages. While PD-1 inhibitor monotherapy has primarily advanced the treatment of NSCLC with ≥50% PD-L1 expression, approximately 70% of all NSCLC cases will have <50% PD-L1 expression, making it the most common treatment setting.

The use of Libtayo in combination with chemotherapy for advanced NSCLC is currently under clinical investigation, and its safety and efficacy have not been fully evaluated by any regulatory authority.

About the Phase 3 Trial

The randomized, multicenter Phase 3 trial, called EMPOWER-Lung 3, investigated a first-line combination treatment of Libtayo and platinum-doublet chemotherapy, compared to platinum-doublet chemotherapy alone, in squamous or non-squamous advanced NSCLC irrespective of PD-L1 expression. Specifically, the trial included 466 patients who tested negative for ALK, EGFR and ROS1 mutations and had either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) and were not candidates for definitive chemoradiation.

Patients were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) administered intravenously every three weeks for 108 weeks, plus platinum-doublet chemotherapy administered every three weeks for four cycles. The co-primary endpoints were OS and progression-free survival, and key secondary endpoints included objective response rate and best overall response.

Among trial patients, 30% (n=139) had tumors with <1% PD-L1 expression, 38% (n=175) had tumors with 1% to 49% PD-L1 expression, and 33% (n=152) had tumors with ≥50% PD-L1 expression.

About Libtayo

Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

The generic name for Libtayo in its approved U.S. indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA. Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in advanced cervical cancer, as well as in trials combining Libtayo with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

On August 5, 2021 Radius Health, Inc. ("Radius" or the "Company") (Nasdaq: RDUS), reported its financial results for the second quarter ended June 30, 2021 and year-to-date (Press release, Radius, AUG 5, 2021, View Source [SID1234585911]). In addition, the Company provided an update on components of the business.

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"Over the past 12 months we have focused on repositioning the business in a comprehensive manner," said Kelly Martin, Radius’ President and CEO. Martin continued, "within this effort three specific goals warrant being highlighted. They are, to become a cash flow positive company, to complete enrollment and execute our three ongoing pivotal trials in a high-quality manner, and opportunistically add assets that have the potential to enhance the Company’s value proposition. While there is still more to do, significant progress on all three of these objectives has been made to date."

Q2 and YTD FINANCIAL HIGHLIGHTS:

Total Net Revenue vs. prior year:
$52 million in Q2, 2021 vs. $50 million in Q2, 2020, +3% year-over-year
$108 million 1H, 2021 vs. $98 million 1H, 2020, +10% year-over-year
TYMLOS Net Revenue:
$52 million in Q2, 2021 vs. $50 million in Q2, 2020, +3% year-over-year
$97 million 1H, 2021 vs. $98 million 1H, 2020, -1% year-over-year
Total Company Adjusted EBITDA:
($6) million in Q2, 2021 vs. ($29) million in Q2, 2020
($11) million 1H, 2021 vs. ($55) million 1H, 2020
FY 2021 guidance: reiterate Adj. EBITDA of $10 million; while reducing TYMLOS revenue from $250 to $240 million
Liquidity position: $100 million of cash, cash equivalents and marketable securities as of 6/30/2021
ABALOPARATIDE COMMERCIAL UPDATE:

Patient growth continues in both quarter-over-quarter and year-over-year periods. Progress on business and market segment includes:

TYMLOS year-over-year new patient growth of 40+% in Q2, 2021 and 18% in 1H, 2021
Top 500 prescribers accounted for ~50% of new patients in Q2, 2021 vs. ~32% in Q1, 2021
In Q2, 2021, ~50% of our top 125 prescribers were orthopedic or spine-focused practices
New patient growth attributable to ortho/spine and bone health prescribers accelerated vs. prior quarter
As a reflection of the timing of new patient adds, we are reducing our FY 2021 TYMLOS net revenue guidance by $10 million. Given new patient growth during Q4, 2020 and 1H, 2021, we anticipate that the net revenue for TYMLOS in 2H, 2021 will be stronger than 1H, 2021.

The Company remains focused on making further progress in the commercial market space by concentrating resources, time, and effort on postmenopausal women with osteoporosis at high risk of fracture, including those with recent fractures.

ELACESTRANT UPDATE:

In partnership with the Menarini Group, progress continues to be made on the elacestrant asset and pivotal trial. The topline readout is still expected to occur in 2H, 2021 as previously communicated.

Importantly, there was a successful outcome in the completion of the bioequivalency study (BE study). This critical path item establishes equivalency between the clinical trial product and commercial product and is an important step forward on the progression of the asset.

Life cycle discussions and planning have been held with Menarini, and will continue to take place, regarding the possible therapeutic applications of elacestrant within the selective estrogen degrader (SERD) space.

RAD011 UPDATE:

As announced in a press release on July 23, Radius plans to initiate a seamless Phase 2/3 pivotal trial for patients with Prader-Willi Syndrome (PWS) in Q4, 2021 or early Q1, 2022. This trial will be global and incorporates feedback from the FDA, the KOL community as well as input from patient advocacy organizations.

Second Quarter 2021 Financial Results

Three Months Ended June 30, 2021

Net Loss
For the three months ended June 30, 2021, Radius reported a net loss of $16.8 million, or $0.35 per share, compared to a net loss of $43.9 million, or $0.95 per share, for the three months ended June 30, 2020.

For the three months ended June 30, 2021, non-GAAP adjusted net loss, was $10.5 million, or $0.22 per share, compared to non-GAAP adjusted net loss of $31.1 million, or $0.67 per share, for the three months ended June 30, 2020.

Revenue
For the three months ended June 30, 2021, TYMLOS net product revenues were $51.8 million compared to $50.1 million for the three months ended June 30, 2020.

Costs and Expenses
For the three months ended June 30, 2021, research and development expense was $27.0 million compared to $44.9 million for the three months ended June 30, 2020, a decrease of $17.9 million, or 40%. This decrease was primarily driven by a decrease of $10.6 million in abaloparatide-TD program cost, a $0.4 million decrease in occupancy and depreciation costs, a $4.6 million decrease in compensation expense, which is comprised of a $1.7 million decrease in compensation expense related to headcount and $2.9 million of billed reimbursable expenses, and a $8.8 million decrease in elacestrant program costs, which is comprised of a $6.6 million increase in gross program expenses offset by $15.4 million of billed reimbursable expenses. These decreases were offset by a $0.8 million increase in abaloparatide-SC program costs, a $3.6 million increase in RAD011 program costs, and a $2.1 million increase in professional fees and other expenses.

For the three months ended June 30, 2021, selling, general and administrative expenses were $32.1 million compared to $38.2 million for the three months ended June 30, 2020, a decrease of $6.1 million, or 16%. This decrease was primarily the result of a $2.6 million decrease in compensation cost, a $3.9 million decrease in professional support costs, and a $0.2 million decrease in occupancy and depreciation costs. These decreases were partially offset by a $0.5 million increase in travel and entertainment costs, and a $0.1 million increase in other operating costs.

Six Months Ended June 30, 2021

Net Loss
For the six months ended June 30, 2021, Radius reported a net loss of $32.6 million, or $0.69 per share, compared to a net loss of $81.5 million, or $1.76 per share, for the six months ended June 30, 2020.

For the six months ended June 30, 2021, non-GAAP adjusted net loss, was $19.0 million, or $0.40 per share, compared to non-GAAP adjusted net loss of $58.6 million, or $1.26 per share, for the six months ended June 30, 2020.

Revenue
For the six months ended June 30, 2021, TYMLOS net product revenues were $97.1 million compared to $98.0 million for the six months ended June 30, 2020.

For the six months ended June 30, 2021, license revenue was $11.0 million. No license revenue was recognized for the six months ended June 30, 2020.

Costs and Expenses
For the six months ended June 30, 2021, research and development expense was $58.4 million compared to $83.9 million for the six months ended June 30, 2020, a decrease of $25.5 million, or 30%. This decrease was primarily driven by a decrease of $14.0 million in abaloparatide-TD program cost, a $0.2 million decrease in RAD140 program costs, a $0.8 million decrease in occupancy and depreciation costs, a $9.3 million decrease in compensation expense, which is comprised of a $2.8 million decrease in compensation expense related to headcount and $6.5 million of billed reimbursable expenses, and a $16.4 million decrease in elacestrant program costs, which is comprised of a $9.6 million increase in gross program expenses offset by $26.0 million of billed reimbursable expenses. These decreases were offset by a $6.1 million increase in abaloparatide-SC program costs, a $3.6 million increase in RAD011 program costs, and a $5.8 million increase in professional fees and other expenses.

For the six months ended June 30, 2021, selling, general and administrative expenses were $66.2 million compared to $74.7 million for the six months ended June 30, 2020, a decrease of $8.4 million, or 11%. This decrease was primarily the result of a $2.0 million decrease in professional support costs, a $6.1 million decrease in compensation cost, and a $0.3 million decrease in other operating costs.

Webcast and Conference Call

In connection with today’s reporting of Second Quarter 2021 Financial Results, Radius will host a conference call and live audio webcast at 8:30 a.m. ET today, August 5, 2021, to review the commercial, research and development, and financial highlights and provide a Company update.

A live audio webcast of the call can be accessed from the Investors section of the Company’s website, www.radiuspharm.com. The full text of the announcement and financial results will also be available on the Company’s website.

A replay of the conference call will be available on August 5 at 11:30 a.m. ET and the audio webcast of the call will be archived on the Company’s website for ninety days. To access the replay, dial (855) 859-2056 or (404) 537-3406 for International, using conference ID number 3659752. The live audio webcast of the call can be accessed from the Investors section of the Company’s website, View Source The full text of the announcement and financial results will also be available on the Company’s website.

On August 5, 2021 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) ("Aeterna" or the "Company"), a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products, reported its financial and operating results for the second quarter ended June 30, 2021 (Press release, AEterna Zentaris, AUG 5, 2021, View Source;id=209178&p=2201538&I=1206939-c7Z3G6f3m8 [SID1234585927]). The Company also provided an update on its pre-clinical and clinical development programs.

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"Our team continues its solid execution to drive forward the development across our clinical and preclinical programs. During the second quarter, we achieved key milestones across multiple fronts including bolstering our management team and scientific expertise, commencing our pivotal Phase 3 DETECT-trial of macimorelin, and advancing our earlier-stage preclinical development pipeline," commented Dr. Klaus Paulini, Chief Executive Officer of Aeterna. "I believe we are well-positioned to propel the Company forward with the goal of creating meaningful shareholder value."

Recent Highlights:

Engaged neuro-immunologist, Michael Levy, MD, PhD, Research Director of the Division of Neuroimmunology & Neuroinfectious Disease at Massachusetts General Hospital as a scientific consultant to support the development of the Company’s targeted, highly specific immunosuppressive therapeutic proteins ("AIM Biologicals") for the potential treatment of neuromyelitis optica spectrum disorder ("NMOSD").
Advanced preclinical development planning for potential orally active COVID-19 (SARS-CoV-2) live-attenuated bacterial vaccine program.
Initiated the preclinical program to qualify macimorelin for clinical development as a potential treatment option for amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease).
Commenced its pivotal Phase 3 safety and efficacy study AEZS-130-P02 ("the DETECT-trial") evaluating macimorelin for the diagnosis of childhood-onset growth hormone deficiency ("CGHD") in collaboration with Novo Nordisk.
In consultation with The University of Sheffield, UK, selected AEZS-150 as the lead candidate in the Company’s delayed clearance parathyroid hormone fusion polypeptides ("DC-PTH") program.
Appointed Michael Teifel, Ph.D. as Senior Vice President, Non-Clinical Development and Chief Scientific Officer.
Fully settled the previously disclosed class-action lawsuit against it in the U.S. District Court for the District of New Jersey, as approved by the U.S. District Court for the District of New Jersey.
All amounts in this press release are in U.S. dollars unless otherwise noted.

Preclinical and Clinical Programs Update:

Diagnostics Development Pipeline

Macimorelin Diagnostic:Ghrelin agonistin development for diagnostic use in childhood-onset growth hormone deficiency ("CGHD")

Aeterna Zentaris is currently conducting its pivotal Phase 3 safety and efficacy study AEZS-130-P02 ("the DETECT-trial") evaluating macimorelin for the diagnosis of CGHD. Children and adolescents from two to less than 18 years of age with suspected GHD are to be included. The study is expected to include approximately 100 subjects worldwide, with at least 40 subjects in pre-pubertal and 40 subjects in pubertal status. Macimorelin growth hormone stimulation test ("GHST") will be performed twice for repeatability data and two standard GHSTs will be used as controls: arginine (i.v.) and clonidine (p.o.). On April 22, 2021, the U.S. FDA Investigational New Drug Application associated with this clinical trial became active. The first clinical site in the U.S. is now open for patient recruitment.

Next Steps

Conduct and completion of the DETECT-trial.
Therapeutics and Vaccine Development Pipeline

AIM Biologicals:Targeted, highly specific autoimmunity modifying therapeutics for the potential treatment of neuromyelitisoptica spectrum disorder ("NMOSD")

In January 2021, Aeterna Zentaris entered into an exclusive patent license and research agreement with Julius-Maximilians-University of Wuerzburg, Germany for worldwide rights to develop, manufacture and commercialize AIM Biologicals for the potential treatment of NMOSD. The Company is currently conducting in-vitro and in-vivo assessments to identify and characterize an AIM Biologicals-based development candidate for the treatment of NMOSD and to develop a manufacturing process for the selected candidate. Additionally, the Company recently engaged neuro-immunologist, Dr. Michael Levy, who will provide scientific support and advice in the field of inflammatory CNS disorders, autoimmune diseases of the nervous system, and NMOSD.

Next Steps

Conduct further preclinical research to identify and characterize an AIM Biologicals-based development candidate for the treatment of NMOSD.
Manufacturing process development for selected candidate.
Macimorelin Therapeutic:Ghrelin agonist in developmentfor the treatment of ALS (Lou Gehrig’s disease)

In January 2021, the Company entered into a material transfer agreement ("MTA") with Queensland University, Australia, to provide macimorelin for the conduct of preclinical and subsequent clinical studies evaluating macimorelin as a potential therapeutic for the treatment of ALS (Lou Gehrig’s disease). Queensland University researchers have filed for supportive grants and aim to conduct preclinical studies in multiple models to demonstrate the therapeutic reach of macimorelin on disease progression and disease-specific pathology. They also plan to conduct a subsequent investigator initiated clinical trial given positive pre-clinical results.

Macimorelin, a ghrelin agonist, is an orally active small molecule that stimulates the secretion of growth hormone from the pituitary gland. Acting via this mechanism, it is believed that macimorelin may slow the progression of certain neurodegenerative diseases like ALS.

Next Steps

Work with Queensland University to conduct proof-of-concept studies with macimorelin in disease-specific animal models.
Assess alternative formulations.
Formalize preclinical development plan.
Delayed Clearance Parathyroid Hormone ("DC-PTH") Fusion Polypeptides:Potential treatment for primary hypoparathyroidism

In March 2021, Aeterna entered into an exclusive patent and know-how license agreement and research agreement with The University of Sheffield, United Kingdom, for the intellectual property relating to DC-PTH fusion polypeptides with delayed clearance covering the field of all human uses. In consultation with the University, Aeterna has selected AEZS-150 as the lead candidate in its delayed clearance parathyroid hormone fusion polypeptides ("DC-PTH") program. Aeterna will now start the formal preclinical development of AEZS-150 in preparation for a potential IND filing for conducting the first in-human clinical study of AEZS-150. AEZS-150 is being developed with the goal of providing a potential new treatment option of primary hypoparathyroidism in adults.

Next Steps

Work with The University of Sheffield to conduct in depth characterization of development candidate (in-vitro and in-vivo).
Develop manufacturing process.
Oral Coronavirus Vaccine Platform:Potential orally active COVID-19 (SARS-CoV-2) live-attenuated bacterial vaccine

In February 2021, Aeterna entered into an exclusive option agreement with Julius-Maximilians-University to evaluate a preclinical, potential COVID-19 vaccine developed at Julius-Maximilians-University. In March 2021, the Company exercised its option and entered into a license agreement where the Company was granted an exclusive, world-wide, license to certain patent applications and know-how owned by Julius-Maximilians-University to research and develop, manufacture, and sell a potential COVID-19 vaccine.

Julius-Maximilians-University also granted Aeterna an option for the exclusive use of certain patent applications and know-how in an additional, so-far undisclosed field. The Company has six months from the date of the license agreement to exercise that option. Additionally, Aeterna entered into a Research Agreement under which the Company has engaged Julius-Maximilians-University on a fee-for-service basis to conduct supplementary research work and preclinical development studies on the potential vaccine, the results of which will be included within the scope of the license agreement.

Next Steps

Conclude in-vivo immunology experiments with antigen variant vaccine candidates.
Perform challenge experiments in immunized transgenic animals as proof of concept.
Select a development candidate for initiation of the formal preclinical toxicology and safety studies.
Start manufacturing process assessment / development.
Financing and Warrant Exercises

During the period between January 1, 2021 and June 30, 2021, holders have exercised certain of the Company’s outstanding warrants to purchase 35,011,187 of the Company’s common shares for gross proceeds of approximately $20.0 million. The Company had $69.9 million cash and cash equivalents at June 30, 2021 (March 31, 2021 – 73.4 million).

Summary of Second Quarter 2021 Financial Results

Results of operations for the three-month period ended June 30, 2021

For the three-month period ended June 30, 2021, we reported a consolidated net loss of $2.0 million, or $0.02 loss per common share (basic), as compared with a consolidated net loss of $3.5 million, or $0.15 loss per common share (basic) for the three-month period ended June 30, 2020. The $1.5 million improvement in net loss is primarily from an increase in net finance income of $2.1 million and an increase of $0.5 million in total revenues, partially offset by an increase of $1.2 million in total operating expenses.

Revenues

Our total revenue for the three-month period ended June 30, 2021 was $0.60 million as compared with $0.07 million for the same period in 2020, representing an increase of $0.53 million. The 2021 revenue was comprised of $0.5 million in licensing revenue (2020 – $0.02 million), $0.04 million in supply chain revenue (2020 – $0.04 million) and $0.02 million in royalty income (2020 – $0.01 million). The licensing revenue was earned from the recognition of a portion of the deferred 5 million payment from Novo Nordisk received with the amendment to the Novo License agreement in the fourth quarter of 2020.
Operating expenses

Our total operating expenses for the three-month period ended June 30, 2021 was $2.7 million as compared with $1.5 million for the same period in 2020, representing an increase of $1.2 million. This increase arose primarily from a $0.5 million increase in research and development costs and $0.5 million increase in general and administrative expenses and an increase of $0.1 million in selling expenses. This increase in total operating expense is due to the initiation of research and development projects as announced in the first quarter of 2021, and higher public company costs incurred holding our annual shareholders meeting in May 2021, subsequent to our issuance of common shares in the February 2021 financing and the 2021 warrant exercises, in addition to higher auditor fees mostly related to F-3 warrant registration filings.
Net finance (costs) income

Our net finance income for the three-month period ended June 30, 2021 was $0.1 million as compared with net finance costs of ($2.0 million) for the same period in 2020, representing an increase in net finance income of $2.1 million. This is primarily due to the $2.1 million decrease in change in fair value of warrants. Unlike as at June 30, 2020, the Company did not account for its warrants as liabilities as at June 30, 2021. As at June 30, 2020, the fair value of such liabilities was classified as a finance cost in the consolidated statements of loss and comprehensive loss.
Consolidated Financial Statements and Management’s Discussion and Analysis

For reference, the Management’s Discussion and Analysis of Financial Condition and Results of Operations for the second quarter of 2021, as well as the Company’s unaudited consolidated interim financial statements as of June 30, 2021, will be available at www.zentaris.com in the Investors section or at the Company’s profile at www.sedar.com and www.sec.gov.