On April 28, 2021 Alkermes plc (Nasdaq: ALKS) reported financial results for the first quarter of 2021 (Press release, Alkermes, APR 28, 2021, View Source [SID1234578653]).

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"Our first quarter results reflect solid execution against our strategy to grow revenues and actively manage our cost structure. As the country begins to see signs of recovery from the pandemic, we believe we are well-positioned to efficiently manage our business and to achieve our long-term profitability targets," commented Iain Brown, Chief Financial Officer of Alkermes. "Today, we are reiterating our financial expectations for 2021, as we continue to position VIVITROL and ARISTADA for long-term growth, prepare for the anticipated launch of LYBALVI, advance the clinical development program for nemvaleukin and invest in our neuroscience and oncology development pipeline."

Quarter Ended March 31, 2021 Financial Results

Revenues

Total revenues for the quarter were $251.4 million. This compared to $246.2 million for the same period in the prior year.
Net sales of proprietary products for the quarter were $130.0 million, compared to $129.7 million for the same period in the prior year.
Net sales of VIVITROL were $74.5 million, compared to $78.8 million for the same period in the prior year, representing a decrease of approximately 5%, primarily due to COVID-19-related disruptions.
Net sales of ARISTADAi were $55.4 million, compared to $51.0 million for the same period in the prior year, representing an increase of approximately 9%.
Manufacturing and royalty revenues for the quarter were $119.8 million, compared to $116.3 million for the same period in the prior year.
Manufacturing and royalty revenues from RISPERDAL CONSTA, INVEGA SUSTENNA/XEPLION and INVEGA TRINZA/TREVICTA were $75.7 million, compared to $82.2 million for the same period in the prior year.
Manufacturing and royalty revenues from VUMERITY were $13.4 million, compared to $1.7 million for the same period in the prior year.
Costs and Expenses

Total operating expenses for the quarter were $267.9 million, compared to $283.6 million for the same period in the prior year.
Cost of Goods Manufactured and Sold were $41.0 million, compared to $47.2 million for the same period in the prior year.
Research and Development (R&D) expenses were $92.3 million, compared to $93.3 million for the same period in the prior year.
Selling, General and Administrative (SG&A) expenses were $125.2 million, compared to $133.4 million for the same period in the prior year.
Profitability

Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $22.4 million for the quarter, or a basic and diluted GAAP loss per share of $0.14. This compared to GAAP net loss of $38.7 million, or a basic and diluted GAAP loss per share of $0.24, for the same period in the prior year.
Non-GAAP net income was $17.8 million for the quarter, or a non-GAAP basic and diluted earnings per share of $0.11. This compared to non-GAAP net income of $1.7 million, or a non-GAAP basic and diluted earnings per share of $0.01 for the same period in the prior year.
Balance Sheet

At March 31, 2021, the company recorded cash, cash equivalents and total investments of $627.4 million, compared to $659.8 million at Dec. 31, 2020, driven primarily by the company’s operating results and changes in working capital. The company’s total debt outstanding as of March 31, 2021 was $297.7 million, following the March 2021 refinancing of the company’s term loan, which extended its maturity date to March 2026.
Financial Expectations for 2021

Alkermes reiterates its financial expectations for 2021, and the assumptions underlying such expectations, as set forth in its press release dated Feb. 11, 2021.

"We are intensely focused on increasing Alkermes’ value through the combination of scientific and business excellence. The first few months of 2021 were highlighted by important advancements in our nemvaleukin immuno-oncology program, including receipt of orphan drug designation for mucosal melanoma, initiation of ARTISTRY-6, a phase 2 trial to further evaluate nemvaleukin’s monotherapy utility in melanoma, entry into a clinical trial and supply agreement with MSD (a tradename of Merck & Co., Inc. Kenilworth, NJ, USA) in platinum-resistant ovarian cancer, and achievement of the first partial response in platinum-resistant ovarian cancer in the ARTISTRY-2 subcutaneous dosing study. At our recent Investor Day, we also introduced new assets from our pipeline, including our CoREST-selective HDAC inhibitor program, our orexin 2 receptor agonist program and our platform of engineered cytokines, including our tumor-targeted, split IL-12 fusion protein," said Richard Pops, Chief Executive Officer of Alkermes. "Coupled with expected growth of our commercial portfolio, including the potential launch of LYBALVI and growth of VUMERITY, and a focus on efficiency, cost management and strong governance, we have the potential to drive significant growth and value creation in 2021 and beyond."

Recent Events:

Nemvaleukin alfa ("nemvaleukin", formerly referred to as ALKS 4230)

In March 2021, nemvaleukin, the company’s investigational engineered interleukin-2 (IL-2) variant immunotherapy, was granted orphan drug designation for the treatment of mucosal melanoma by the U.S. Food and Drug Administration (FDA).
In April 2021, the company entered into a clinical trial collaboration and supply agreement with MSD (a tradename of Merck & Co., Inc. Kenilworth, NJ, USA) for a planned phase 3 study to evaluate nemvaleukin in combination with KEYTRUDA (pembrolizumab), in comparison to investigator choice chemotherapy in patients with platinum-resistant ovarian cancer. The study is planned to initiate in the second half of 2021.
In April 2021, the company initiated ARTISTRY-6, a global phase 2 study evaluating the anti-tumor activity, safety and tolerability of intravenous nemvaleukin monotherapy in patients with mucosal melanoma. The study also includes a cohort of patients with advanced cutaneous melanoma who will receive subcutaneous (SC) nemvaleukin with intent to establish monotherapy proof-of-concept with SC dosing.
Psychiatry

In April 2021, the company presented new research from its psychiatry portfolio at the 2021 Congress of the Schizophrenia International Research Society (SIRS), which took place virtually April 17-21, 2021. The company’s presentations included new exploratory analyses from its phase 3 ENLIGHTEN-2 study of LYBALVI.
Corporate

In March 2021, Alkermes held a virtual Investor Day to discuss the company’s research and development strategy and portfolio, including updates from its nemvaleukin development program and introduction of new preclinical neuroscience and immuno-oncology programs. The company also provided an update on the implementation of its Value Enhancement Plan announced in December 2020.
Conference Call

Alkermes will host a conference call and webcast presentation with accompanying slides at 8:00 a.m. ET (1:00 p.m. BST) on Wednesday, April 28, 2021, to discuss these financial results and provide an update on the company. The webcast may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. The conference call may be accessed by dialing +1 877 407 2988 for U.S. callers and +1 201 389 0923 for international callers. In addition, a replay of the conference call will be available from 11:00 a.m. ET (4:00 p.m. BST) on Wednesday, April 28, 2021, through Wednesday, May 5, 2021, and may be accessed by visiting Alkermes’ website or by dialing +1 877 660 6853 for U.S. callers and +1 201 612 7415 for international callers. The replay conference ID is 13718854.

On April 28, 2021 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported Phase 1b/2 program priorities across seven hematologic and solid tumor indications, and governance changes with its Board of Directors (Press release, Trillium Therapeutics, APR 28, 2021, View Source [SID1234578652]).

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"We have reached a critical milestone in Trillium’s evolution," said Jan Skvarka, Trillium’s President and CEO. "We have built a robust foundation for advancing into a Phase 1b/2 program – a foundation of two highly differentiated CD47 assets with monotherapy proof-of-concept across several lymphoma indications. Our new data further solidify our position in the CD47 field as having potentially class-leading single agent activity with both TTI-622 and 621, as well as potentially best-in-class tolerability with TTI-622. Furthermore, we are particularly excited to observe substantial anti-tumor activity in the skin of our CTCL patients, which suggests that TTI-622 and 621 have the ability to exit blood circulation and penetrate skin tumors, thus underscoring the potential of both drug candidates to treat solid tumors. Finally, new translational data suggest that natural killer cell engagement plays a key role in what we believe is TTI-621’s mechanism of action, thus further differentiating TTI-621 in the CD47 field."

"We are now rapidly advancing into a Phase 1b/2 program, with multiple shots on goal – two drug candidates, seven target indications, multiple drug combinations – in patients with hematologic malignancies and solid tumors," added Ingmar Bruns, Chief Medical Officer. "Over the next twelve months, we expect to initiate studies across nine patient settings. The pipeline represents a portfolio of different risk-reward opportunities, multiple potentially accelerated regulatory paths to market, and a total addressable US patient population of over 30,000 patients in our entry settings. In parallel, we are continuing to evaluate less frequent dosing regimens than our current weekly dosing. This is supported by pharmacokinetic data, and, in the case of TTI-622, clinical experience with two CR patients who are on every three- and four-week dosing schedules."

"On a more personal note, as we are announcing governance changes, we would like to thank Bob Kirkman for his invaluable contributions over his eight-year tenure with Trillium as a Board member, including periods when he held Chair and Executive Chair roles," said Dr. Skvarka. "Bob has played a pivotal role in transitioning the CEO leadership in 2019, and positioning the company for our subsequent transformation program in 2020. Trillium would not be where it is today without Bob’s leadership, hands-on contributions and personal sacrifices. We will sorely miss Bob, and wish him all the best as he scales down his professional commitments."

TTI-622 Study Update

As of the data cutoff date of April 12, 2021, a total of 42 patients have been enrolled in the ongoing open-label Phase 1 dose escalation study of TTI-622 in patients with R/R lymphoma (NCT03530683). Patients received weekly intravenous doses between 0.05 and 18 mg/kg. All dose levels were very well-tolerated and an MTD was not reached. Adverse events (AEs) were predominantly Grade 1-2; related AEs ≥Grade 3 were neutropenia (9%), thrombocytopenia (5%) and anemia (2%). Pharmacokinetic data demonstrated dose-proportional increases in drug exposure between 8 and 18 mg/kg, and support evaluating less frequent dosing. Objective responses were achieved in 9 of 27 (33%) heavily pre-treated response-evaluable patients at dose levels ≥0.8 mg/kg, and included 2 CRs and 7 PRs. Three responses (1 CR and 2 PRs) at 12 and 18 mg/kg were obtained since the last data disclosure at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting. All responses occurred within the first eight weeks of treatment across multiple lymphoma indications. One CR patient (0.8 mg/kg dose level) has been on study for more than 22 months and was transitioned to monthly dosing. The second CR patient (18 mg/kg) achieved a response after receiving only two doses with a 4-week dosing interval and is being maintained on every three weeks (Q3W) dosing. The study is continuing, with 3 more patients at 18 mg/kg pending response assessments as of the April 12, 2021 cutoff date.

TTI-621 Study Update

We have provided a further update on the safety data and anti-tumor activity observed in the ongoing open-label Phase 1 dose escalation study of intravenous TTI-621 in patients with R/R hematologic malignancies (NCT02663518). The study consists of four parts: (a) "Parts 1-3" in hematologic malignancies, with dosing up to 0.5 mg/kg weekly, now complete; and (b) "Part 4" in CTCL, with dosing at 0.5 mg/kg weekly and higher, currently ongoing. As of the data cutoff date of April 12, 2021, TTI-621 was well-tolerated and an MTD in Part 4 was not reached. Across Parts 1-4, the most common treatment-related AEs ≥Grade 3 were thrombocytopenia (22%), which was transient and not dose-limiting, anemia (8%), neutropenia (6%), and infusion-related reactions (4%), which occurred mostly at the first dose and were effectively managed by prophylactic treatment. Monotherapy activity was observed in CTCL (19% ORR, n=62), peripheral T-cell lymphoma (18% ORR, n=22) and diffuse large B-cell lymphoma (DLBCL) (29% ORR, n=7). Three responses (1 CR and 2 PRs) in CTCL patients treated at 1.4 and 2.0 mg/kg were obtained since the last data disclosure at ASH (Free ASH Whitepaper) 2020. Emerging translational data from patient samples suggest that NK cell activation plays a key role in the anti-tumor activity of TTI-621, in addition to inhibition of the "don’t eat me" signal and delivery of a pro-phagocytic signal. This highly differentiated proposed mode of action, together with encouraging monotherapy activity and good tolerability, prompt continued and focused further investigation of TTI-621. The study is continuing, with 3 more patients at 2.0 mg/kg pending response assessments as of the April 12, 2021 cutoff date.

Phase 1b/2 Program

Based on the strong and differentiated foundation that Trillium has built, including potentially class-leading monotherapy activity, the Company is initiating Phase 1b/2 programs with both TTI-622 and TTI-621. These programs will initially cover seven indications (four hematological cancers, three solid tumors), and study TTI-622 and TTI-621 primarily in combination with other anti-cancer agents.

Specifically, TTI-622 will be evaluated in the following settings and combination regimens:

R/R multiple myeloma, in a combination with carfilzomib + dexamethasone;
First line p53 mutant acute myeloid leukemia (AML), in a combination with azacitidine;
First line elderly or unfit p53 wild type AML patients, in a combination with azacitidine and venetoclax;
R/R DLBCL, in a combination with anti-PD-1, in an investigator-sponsored trial at Mayo Clinic;
Platinum-resistant ovarian cancer, in a combination with chemotherapy; and
A second solid tumor combination study to be announced later this year.
These studies will be initiated with 8 mg/kg weekly dosing, or potentially less frequent dosing regimens at higher doses.

The Phase 1b/2 program for TTI-622 has now been initiated with the dosing of a first multiple myeloma patient with TTI-622 in a combination with carfilzomib + dexamethasone. Both AML cohorts are open for enrollment, and we expect the first patients to be dosed this quarter.

TTI-621 will be evaluated in the following settings and combination regimens:

Second line peripheral T-cell lymphoma (PTCL), as a TTI-621 monotherapy;
R/R DLBCL, in a combination with anti-PD-1, in an investigator-sponsored trial at Mayo Clinic; and
First line leiomyosarcoma, a subtype of soft tissue sarcoma, in a combination with doxorubicin.
Initial Phase 1b/2 studies will be initiated at two dose levels (0.2 mg/kg and up to 2.0 mg/kg weekly); different levels may be chosen based on overlapping toxicities with combination agents.

In addition, bi-weekly (Q2W) and Q3W dosing schedules will be evaluated for each molecule in the ongoing monotherapy dose escalation studies.

Governance Update

Effective April 28, 2021, Scott Myers is joining the Board of Directors. Scott is an accomplished executive who brings to the Board nearly three decades of pharmaceutical and medical device industry experience. Previously, he served as CEO of AMAG Pharmaceuticals, Rainier Therapeutics, Cascadian Therapeutics, and Aerocrine AB. He currently serves on the Boards of Directors of Selecta Biosciences and Harpoon Therapeutics. We are very excited that Scott has agreed to join the Board, and look forward to benefitting from his extensive executive experience and track record of building successful biotechnology companies.

Robert Kirkman elected to retire from the Board of Directors, effective April 28, 2021. Robert has served as a director since December 2013, the Chair of the Board since March 2019, and acted as the Executive Chair from April 2019 to March 2020.

As previously announced, Tom Reynolds joined our scientific advisory board (SAB) in November 2020. Due to the resulting loss of his independent status as a Board member, Tom is now (effective April 28, 2021) retiring from the Board to focus on the SAB role, as well as to serve as a senior advisor to assist with initiation of our extensive Phase 1b/2 program and a scale-up of the clinical development organization.

Upcoming Milestones and Guidance

In 2021, Trillium expects two data updates:

TTI-622 data update from the ongoing dose escalation study in R/R lymphomas at a medical conference in 4Q 2021; and
TTI-621 data update from the ongoing dose escalation study in R/R CTCL at a medical conference in 4Q 2021.
Over approximately the next twelve months, the Company plans to initiate studies in the following indications and patient settings:

TTI-622 + azacitidine combination in p53 mutant AML patients in 2Q 2021 (enrollment open);
TTI-622 + azacitidine + venetoclax combination in elderly or unfit p53 wild type AML patients in 2Q 2021 (enrollment open);
TTI-622 + chemotherapy combination in platinum-resistant ovarian cancer patients in 2H 2021;
TTI-622 combination study in a to-be-announced solid tumor indication in 1H 2022;
TTI-622 + anti-PD-1 and TTI-621 + anti-PD-1 in DLBCL patients in 4Q 2021 to 1H 2022 (investigator-sponsored trial);
TTI-621 monotherapy study in PTCL in 3Q 2021; and
TTI-621 + doxorubicin combination in leiomyosarcoma in 3Q 2021.
As all of the above studies are open-label trials, the Company expects a robust flow of new data updates and multiple catalysts in 2022, in addition to the above mentioned updates from the continuing dose escalation studies in the fourth quarter of 2021.

As of March 31, 2021, Trillium had $276 million in cash, cash equivalents, and marketable securities, sufficient to fund operations and the above outlined clinical development priorities into 2023.

R&D Day Presentation and Webcast

The archived webcast from Trilium’s R&D Day can be found at View Source and will be available on Trillium’s website for 30 days. The R&D Day presentation can be found on our website at www.trilliumtherapeutics.com.

On April 28, 2021 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV:TLT)(OTCQB:TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light activated PhotoDynamic Compounds ("PDC") and their associated drug formulations intended to safely and effectively destroy various cancer reported its audited annual consolidated 2020 financial statements (Press release, Theralase, APR 28, 2021, View Source [SID1234578651]).

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Financial Highlights:
For the years ended December 31st:

(1) Other represents (Gain) Loss on foreign exchange, interest accretion on lease liabilities and interest income

Total revenue remained predominantly flat, year over year, and is primarily attributed to the COVID-19 pandemic as most health care practitioners elected to temporarily close their practices and place any purchasing decisions on temporary or permanent hold.

Cost of sales for the year ended December 31, 2020 was $659,442, which included a one-time write-down of inventory of $131,983, resulting in an adjusted cost of sales of $527,459 or 57% of revenue with an adjusted gross margin of $401,663 or 43% of revenue. In comparison cost of sales for the same period in 2019 was $903,296, which included a one-time provision for inventory of $277,896, resulting in an adjusted cost of sales of $625,400 or 65% revenue with an adjusted gross margin of $338,651 or 35% of revenue. The gross margin increase, as a percentage of sales, year over year, is attributed to a decrease in labour and material costs and a one-time inventory provision of $277,896 in 2019.

The decrease in selling expenses is primarily due to the restructuring of the Canadian and US sales and marketing departments, as a result of the COVID-19 pandemic, resulting in the resignation and/or termination of certain non-essential sales and marketing personnel and significantly reduced travel expenditures.

The decrease in administrative expenses is primarily attributed to decreased spending on general and administrative expenses (40%), director and advisory fees (45%) and administrative salaries (59%) due to the COVID-19 pandemic, resulting in the termination of certain non-essential administrative personnel.

The decrease in research and development expenses for the year ended December 31, 2020 is attributed primarily to the delay in patient enrollment and treatment in the Phase II NMIBC clinical study ("Study II") due to the COVID-19 pandemic. Research and development expenses represented 59% of the Company’s operating expenses and represents investment into the research and development of the Company’s ACT technology

The net loss for the year ended December 31, 2020 was $5,598,540 which included $1,202,017 of net non-cash expenses (i.e.: amortization, stock-based compensation expense and foreign exchange gain/loss). This compared to a net loss in 2019 of $7,413,914 which included $677,224 of net non-cash expenses. The ACT division represented $4,282,813 of this loss (76%) for the year ended December 31, 2020.

The decrease in net loss is primarily attributed to the following:

Delay in patient enrollment and treatment due to the COVID-19 pandemic, resulting in decreased research and development expenses in Study II.
Decreased salaries due to the COVID-19 pandemic, resulting in the termination of certain non-essential administrative, research and production personnel.
Operational Highlights:

FDA Fast Track. On November 23, 2020, the FDA granted Theralase Fast Track Designation ("FTD") for Study II. As a Fast Track designee, Theralase will have access to early and frequent communications with the FDA to discuss Theralase’s development plans and ensure timely collection of the appropriate clinical data to support the approval process. The accelerated communication with the FDA potentially allows, TLD-1433, in combination with TLC-3200, to be the first intravesical patient-specific Ruthenium-based PDC for the treatment of patients with Bacillus Calmette-Guerin ("BCG") – Unresponsive Non- Muscle Invasive Bladder Cancer ("NMIBC") Carcinoma In-Situ ("CIS"), with or without papillary Ta or T1 tumors. FTD can lead to an Accelerated Approval ("AA"), Break Through Designation ("BTD") and/or Priority Review, if certain criteria are met, which the FDA has previously defined to the Company for BTD to represent approximately 20 to 25 patients enrolled and treated, who demonstrate significant safety and efficacy clinical outcomes.
COVID-19 Pandemic Update. In the ACT division, all Canadian Clinical Study Sites ("CSS") have re-commenced new patient enrollment and treatment in Study II as of September 24, 2020. The CSSs placed themselves on temporary hold due to the COVID-19 between March 20, 2020 to August 12, 2020 and September 24, 2020. In the CLT division, the Company continues to experience variations in sales and the timing of these sales due to the ongoing COVID-19 pandemic and has taken actions to reduce expenses by eliminating non-essential personnel and imposing a temporary hiring freeze, to be lifted, subject to the Canadian and United States economies demonstrating recovery from COVID-19.
Clinical study site status and update. The Company has successfully launched five CSSs in Canada and six CSSs in the US that are open for patient enrollment and treatment for a total of 11 CSSs.

To date, the phase II NMIBC clinical study has enrolled and provided the primary study treatment for 18 patients (including three patients from Phase Ib study treated at the Therapeutic Dose) for a total of 21 patients.
Additional cancer indications. The Company has demonstrated significant anti-cancer efficacy of Rutherrin, when activated by laser light or radiation treatment across numerous preclinical models; including: Glio Blastoma Multiforme ("GBM") and Non-Small Cell Lung Cancer ("NSCLC"). The Company has commenced Non – Good Laboratory Practices ("GLP") toxicology studies with Rutherrin in animals to help determine the maximum recommended human dose of the drug, when administered systemically into the human body, via intravenous injections. Theralase plans to commence GLP toxicology studies in animals in 2021.
COVID-19 Research Update. The Company’s PDC technology was proven to be effective in the destruction of Influenza H1N1 and Zika viruses at low nanomolar concentrations. These studies were expanded to include coronavirus Bio Safety Level ("BSL") 2. As a note, COVID-19 is caused by coronavirus (BSL-3), not coronavirus (BSL-2). A new assay was established to measure coronavirus destruction and using this new assay the Theralase PDC technology was able to destroy coronavirus (BSL-2) with drug doses 5 times lower than what was used to kill Influenza H1N1 and Zika viruses. These drug doses demonstrated a 99.995% destruction rate of the BSL-2 coronavirus and are significantly lower than those used by the Company to treat cancers; hence considered safe for human use. Coronaviruses are considered similar in their structure and these new results strongly suggest that Theralase’s PDC will be highly effective against the SARS-CoV-2 (BSL-3) virus responsible for COVID-19.

In April 2021, Theralase executed a Collaborative Research Agreement ("CRA") with the National Microbiology Laboratory, Public Health Agency of Canada ("PHAC") for the research and development of a Canadian-based SARS-CoV-2 ("COVID-19") vaccine. Under the terms of the agreement, Theralase and PHAC are collaborating on the development and optimization of a COVID-19 vaccine by treating the SARS-CoV-2 virus grown on cell lines with Theralase’s patented PDC and then light activating it with Theralase’s proprietary TLC-3000A light technology to inactivate the virus and create the fundamental building blocks of a COVID-19 vaccine. This inactivated virus would then be purified and used to inoculate naive animals followed by challenge with the SARS-CoV-2 virus, to ascertain the efficacy of the vaccine. The project is entitled, "Photo Dynamic Compound Inactivation of SARS-CoV-2 Vaccine" and commenced in mid-April 2021.
* The Company does not claim or profess that they have the ability to treat, cure or prevent the contraction of the COVID-19 Coronavirus.

About Study II

Study II utilizes the Therapeutic Dose (0.70 mg/cm2) of TLD-1433 and is focused on the enrollment and treatment of approximately 100 BCG-Unresponsive NMIBC CIS patients in up to 20 clinical study sites located in Canada and the US.

Study II has a:

Primary endpoint of efficacy (defined by Complete Response ("CR") at any point in time
Secondary endpoint of duration of CR at 360 days post-initial CR (approximately 450 days post initial Study treatment, assuming CR is achieved at the 90 day assessment)
Tertiary endpoint of safety measured by incidence and severity of Adverse Events ("AEs") grade 4 or higher that do not resolve within 450 days post-initial treatment
The FDA, in its 2018 guidance to industry has stated that, "For single-arm trials of patients with BCG-unresponsive disease, the FDA defines a CR as at least one of the following:

Negative cystoscopy and negative (including atypical) urine cytology
Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology
For intravesical therapies without systemic toxicity, the FDA includes, in the definition of a CR, negative cystoscopy with malignant urine cytology, if cancer is found in the upper tract or prostatic urethra and random bladder biopsies are negative.
Intravesical instillation does not deliver the investigational drug to the upper tract or prostatic urethra; therefore, the development of disease in these areas cannot be attributed to a lack of activity of the investigational drug. Thus, sponsors can consider patients with new malignant lesions of the upper tract or prostatic urethra, who have received intravesical therapy to have achieved a CR in the primary analysis; however, sponsors should record these lesions and conduct sensitivity analyses in which these patients are not considered to have achieved a CR."1

On April 28, 2021 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported results for the quarter ended March 31, 2021 (Press release, Teva, APR 28, 2021, View Source [SID1234578650]).

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Mr. Kåre Schultz, Teva’s President and CEO, said, "As the COVID-19 pandemic continues to impact the world and our industry, our employees continue to work together to meet the needs of our customers and patients, all while we remain focused on our long-term goals and laying the foundation for future growth.

"We have improved our profitability and reduced our net debt to $23.2 billion. We have also seen solid performance from our key growth drivers: the biosimilar Truxima increased its market share to 26%, AUSTEDO continued its year-over-year growth, and AJOVY solidified its market share in the U.S. and continues to expand in Europe. Based on our results and expectations for the remainder of the year, we are reaffirming our guidance."

First Quarter 2021 Consolidated Results

Revenues in the first quarter of 2021 were $3,982 million, a decrease of 9% or 10% in local currency terms, compared to the first quarter of 2020. This decrease was mainly due to lower revenues from generic, OTC and respiratory products and from COPAXONE in our Europe segment, lower revenues from Anda, COPAXONE and BENDEKA/TREANDA in our North America segment, lower revenues from Japan resulting from the divestment of a majority of the generic and operational assets of our Japanese business venture, as well as regulatory price reductions and generic competition to off-patented products in Japan, partially offset by higher revenues from generic products and AUSTEDO in our North America segment. Revenues were also affected by changes in demand for certain products resulting from the impact of the COVID-19 pandemic.

Exchange rate movements during the first quarter of 2021, net of hedging effects, positively impacted our revenues by $74 million and negatively impacted our GAAP and non-GAAP operating income by $14 million and $10 million, respectively.

GAAP gross profit was $1,878 million in the first quarter of 2021, a decrease of 9% compared to the first quarter of 2020. GAAP gross profit margin was 47.2% in the first quarter of 2021, compared to 47.3% in the first quarter of 2020. The decrease in gross profit margin was mainly due to lower revenues from our Europe segment, partially offset by higher profitability in North America resulting from the change in mix of products. Non-GAAP gross profit was $2,144 million in the first quarter of 2021, a decrease of 7% compared to the first quarter of 2020. Non-GAAP gross profit margin was 53.8% in the first quarter of 2021, compared to 53.1% in the first quarter of 2020.

GAAP Research and Development (R&D) expenses in the first quarter of 2021 were $254 million, an increase of 15% compared to the first quarter of 2020. Non-GAAP R&D expenses were $244 million, or 6.1% of quarterly revenues, in the first quarter of 2021, compared to $221 million, or 5.1%, in the first quarter of 2020. In the first quarter of 2021, our R&D expenses related primarily to specialty product candidates in the respiratory and pain therapeutic areas, with additional activities in selected other areas and generic products including biosimilars. Our higher R&D expenses in the first quarter of 2021, compared to the first quarter of 2020, were mainly due to an increase in respiratory and biosimilar projects.

GAAP Selling and Marketing (S&M) expenses in the first quarter of 2021 were $585 million, a decrease of 5% compared to the first quarter of 2020. Non-GAAP S&M expenses were $549 million, or 13.8% of quarterly revenues, in the first quarter of 2021, compared to $570 million, or 13.1%, in the first quarter of 2020.

GAAP General and Administrative (G&A) expenses in the first quarter of 2021 were $290 million, a decrease of 5% compared to the first quarter of 2020. Non-GAAP G&A expenses were $278 million, or 7.0% of quarterly revenues, in the first quarter of 2021, compared to $290 million, or 6.7%, in the first quarter of 2020.

GAAP operating income in the first quarter of 2021 was $434 million, compared to $191 million in the first quarter of 2020. The increase was mainly due to lower intangible asset impairment charges in the first quarter of 2021, partially offset by lower profit in our Europe segment along with higher legal settlements and loss contingencies.

Non-GAAP operating income in the first quarter of 2021 was $1,077 million, a decrease of 13%, compared to $1,244 million in the first quarter of 2020. The decrease was mainly due to lower profit in our Europe segment.

EBITDA (defined as operating income, excluding depreciation and amortization expenses) was $809 million in the first quarter of 2021, an increase of 37% compared to $590 million in the first quarter of 2020. Adjusted EBITDA (defined as operating income excluding depreciation and amortization expenses and certain other items) was $1,206 million in the first quarter of 2021, a decrease of 12% compared to $1,375 million in the first quarter of 2020.

GAAP financial expenses were $290 million in the first quarter of 2021, compared to $224 million in the first quarter of 2020. Non-GAAP financial expenses were $227 million in the first quarter of 2021, compared to $213 million in the first quarter of 2020. Financial expenses in the first quarter of 2021, were mainly comprise of interest expenses of $239 million and loss on revaluation of marketable securities of $64 million. Financial expense in the first quarter of 2020 were mainly comprised of interest expenses of $241 million.

In the first quarter of 2021, we recognized a GAAP tax expense of $62 million, on pre-tax income of $144 million. In the first quarter of 2020, we recognized a tax benefit of $59 million, on pre-tax loss of $33 million. Our tax rate for the first quarter of 2021 was mainly affected by legal settlements, impairments and amortization in jurisdictions in which tax rates are lower than Teva’s average tax rate on its ongoing business operations. Non-GAAP income taxes for the first quarter of 2021 were $146 million, or 17%, on pre-tax non-GAAP income of $851 million. Non-GAAP income taxes in the first quarter of 2020 were $175 million, or 17%, on pre-tax non-GAAP income of $1,030 million. Our non-GAAP tax rate for the first quarter of 2021 was mainly affected by the mix of products we sold and interest expense disallowance.

We expect our annual non-GAAP tax rate for 2021 to be 17%-18%, unchanged from our outlook provided in February 2021.

GAAP net income attributable to Teva and GAAP EPS were $77 million and $0.07 respectively, in the first quarter of 2021, compared to $69 million and $0.06 in the first quarter of 2020. This increase was mainly due to the increase in operating income, as discussed above. Non-GAAP net income attributable to Teva and non-GAAP diluted EPS in the first quarter of 2021 were $699 million and $0.63, respectively, compared to $835 million and $0.76 in the first quarter of 2020.

The weighted average diluted shares outstanding used for the fully diluted share calculation on a GAAP and non-GAAP basis for the three months ended March 31, 2021 and 2020 was 1,107 million and 1,096 million shares, respectively.

As of March 31, 2021 and 2020, the fully diluted share count for purposes of calculating our market capitalization was approximately 1,130 million and 1,118 million, respectively.

Non-GAAP information: Net non-GAAP adjustments in the first quarter of 2021 were $621 million. Non-GAAP net income and non-GAAP EPS for the first quarter of 2021 were adjusted to exclude the following items:

Amortization of purchased intangible assets of $242 million, of which $215 million is included in cost of sales and the remaining $27 million in S&M expenses;
Impairment of long-lived assets of $127 million, comprised mainly of impairment of intangible assets of IPR&D and product rights assets in connection with the Actavis Generics acquisition;
Legal settlements and loss contingencies of $104 million, mainly related to a provision for a potential patent setlement;
Restructuring expenses of $81 million;
Finance expense of $64 million, related to revaluation of marketable securities;
Equity compensation expenses of $31 million;
Other items of $57 million; and
Income tax of $85 million.
Teva believes that excluding such items facilitates investors’ understanding of its business. For further information, see the tables below for a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures and the information under "Non-GAAP Financial Measures." Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP.

Cash flow used in operating activities during the first quarter of 2021 was $405 million, compared to $305 million generated in the first quarter of 2020. The decrease in the first quarter of 2021 was mainly due to changes in working capital items resulting from a decrease in sales reserves and allowances (SR&A) and an increase in inventory, as well as lower profit in our Europe segment.

Free cash flow (cash flow from operating activities, cash used for capital investments, beneficial interest collected in exchange for securitized accounts receivables and proceeds from divestitures of businesses and other assets) was $59 million in the first quarter of 2021, compared to $551 million in the first quarter of 2020. The decrease in the first quarter of 2021 resulted mainly from lower cash flow from operating activities, partially offset by higher sales of assets.

As of March 31, 2021, our debt was $24,986 million, compared to $25,919 million as of December 31, 2020. This decrease was mainly due to redemption of $491 million of our convertible senior debentures and exchange rate fluctuations. The portion of total debt classified as short-term as of March 31, 2021 was 11%, compared to 12% as of December 31, 2020. Our average debt maturity was approximately 5.6 years as of March 31, 2021, compared to 5.8 years as of December 31, 2020. Our financial leverage was 69% as of March 31, 2021, compared to 70% as of December 31, 2020.

Segment Results for the First Quarter of 2021

North America Segment

Our North America segment includes the United States and Canada.

Revenues from our North America segment in the first quarter of 2021 were $1,989 million, a decrease of $94 million, or 5%, compared to the first quarter of 2020, mainly due to a decrease in revenues from Anda, COPAXONE and BENDEKA/TREANDA, partially offset by higher revenues from generic products and AUSTEDO. Our North America segment has experienced some reductions in volume due to less physician and hospital activity during the COVID-19 pandemic, but has also experienced increase in demand for certain products related to the treatment of COVID-19 and its symptoms. In addition, the ability to promote certain specialty products, primarily AJOVY and AUSTEDO, has been impacted by less physician visits by patients and less physician interactions by our sales personnel.

Revenues in the United States, our largest market, were $1,854 million in the first quarter of 2021, a decrease of $87 million, or 4%, compared to the first quarter of 2020.

Revenues by Major Products and Activities

The following table presents revenues for our North America segment by major products and activities for the three months ended March 31, 2021 and 2020:

Generic products revenues in our North America segment (including biosimilars) in the first quarter of 2021 were $1,053 million, an increase of 11% compared to the first quarter of 2020. This increase was mainly due to higher revenues from emtricitabine and tenofovir disoproxil fumarate tablets (the generic equivalent of Truvada), Truxima (the biosimilar to Rituxan) and ProAir authorized generic, partially offset by lower volume and pricing of other generic products.

In January 2021, we launched etonogestrel and ethinyl estradiol vaginal ring, 0.120 mg/0.015 mg per day (the generic equivalent of NuvaRing) in the U.S., which is an estrogen/progestin combination hormonal contraceptive (CHC) indicated for use by women to prevent pregnancy.

In the first quarter of 2021, our total prescriptions were approximately 322 million (based on trailing twelve months), representing 9.2% of total U.S. generic prescriptions according to IQVIA data.

AJOVY revenues in our North America segment in the first quarter of 2021 were $31 million, an increase of $2 million, or 8% compared to the first quarter of 2020, mainly due to growth in volume. AJOVY is the only anti-CGRP product indicated for quarterly treatment and in January 2021 we launched a new triple pack product offering, providing quarterly dosing.

AUSTEDO revenues in our North America segment in the first quarter of 2021 increased by 20% to $146 million, compared to $122 million in the first quarter of 2020. This increase was mainly due to growth in volume.

BENDEKA and TREANDA combined revenues in our North America segment in the first quarter of 2021 decreased by 14% to $91 million, compared to the first quarter of 2020, mainly due to availability of alternative therapies and continued competition.

COPAXONE revenues in our North America segment in the first quarter of 2021 decreased by 17% to $164 million, compared to the first quarter of 2020, mainly due to generic competition in the United States.

ProAir (HFA and RespiClick) revenues in our North America segment in the first quarter of 2021 decreased by 9% to $54 million, compared to the first quarter of 2020. In January 2019, we launched our own ProAir authorized generic in the United States, following the launch of a generic version of Ventolin HFA, another albuterol inhaler. Revenues from our ProAir authorized generic are included in "generic products" above.

Anda revenues in our North America segment in the first quarter of 2021 decreased by 32% to $289 million, compared to $426 million in the first quarter of 2020, mainly due to lower demand. In addition, revenues were higher in first quarter of 2020 as a result of significant customer stocking due to the COVID-19 pandemic.

North America Gross Profit

Gross profit from our North America segment in the first quarter of 2021 was $1,074 million, an increase of 1%, compared to $1,062 million in the first quarter of 2020.

Gross profit margin for our North America segment in the first quarter of 2021 increased to 54.0%, compared to 51.0% in the first quarter of 2020. This increase was mainly due to the change in mix of products.

North America Profit

Profit from our North America segment consists of gross profit less R&D expenses, S&M expenses, G&A expenses and any other income related to this segment. Segment profit does not include amortization and certain other items.

Profit from our North America segment in the first quarter of 2021 was $577 million, an increase of 5% compared to $550 million in the first quarter of 2020, mainly due to higher gross profit, as discussed above, as well as lower S&M expenses.

Europe Segment

Our Europe segment includes the European Union and certain other European countries.

The following table presents revenues, expenses and profit for our Europe segment for the three months ended March 31, 2021 and 2020:

Revenues from our Europe segment in the first quarter of 2021 were $1,214 million, a decrease of 13%, or $188 million, compared to the first quarter of 2020. In local currency terms, revenues decreased by 20%, mainly due to higher revenues in first quarter of 2020 as a result of significant customer stocking due to the COVID-19 pandemic. In addition, revenues were impacted by lower demand of generic, OTC and respiratory products resulting from a decline in doctor and hospital visits by patients resulting in fewer prescriptions as well as lower sales of cough and cold products, both due to the COVID-19 pandemic. The decrease in revenues is also attributed to a decline in COPAXONE revenues due to competing glatiramer acetate products and price declines in oncology products as a result of generic competition.

Revenues by Major Products and Activities

The following table presents revenues for our Europe segment by major products and activities for the three months ended March 31, 2021 and 2020:

Generic products revenues in our Europe segment in the first quarter of 2021, including OTC products, decreased by 16% to $865 million, compared to the first quarter of 2020. In local currency terms, revenues decreased by 23% compared to the first quarter of 2020, mainly due to higher revenues in first quarter of 2020 as a result of significant customer stocking due to the COVID-19 pandemic. In addition, revenues were impacted by lower demand of generic and OTC products resulting from a decline in doctor and hospital visits by patients resulting in fewer prescriptions as well as lower sales of cough and cold products, both due to the COVID-19 pandemic.

AJOVY revenues in our Europe segment in the first quarter of 2021 were $16 million, compared to $4 million in the first quarter of 2020, mainly due to launches and reimbursements in additional European countries.

COPAXONE revenues in our Europe segment in the first quarter of 2021 decreased by 8% to $100 million, compared to the first quarter of 2020. In local currency terms, revenues decreased by 15%, due to price reductions and a decline in volume resulting from competing glatiramer acetate products.

Respiratory products revenues in our Europe segment in the first quarter of 2021 decreased by 12% to $93 million, compared to the first quarter of 2020. In local currency terms, revenues decreased by 19%, mainly due to significant customer stocking due to the COVID-19 pandemic in first quarter of 2020, as well as reduced demand resulting from COVID-19 restrictions in the first quarter of 2021.

Europe Gross Profit

Gross profit from our Europe segment in the first quarter of 2021 was $688 million, a decrease of 17% compared to $823 million in the first quarter of 2020.

Gross profit margin for our Europe segment in the first quarter of 2021 decreased to 56.6%, compared to 58.7% in the first quarter of 2020. This decrease was mainly due to lower revenues, as discussed above and increased write-offs and obsolescence provisions as a result of increased inventory levels.

Europe Profit

Profit from our Europe segment consists of gross profit less R&D expenses, S&M expenses, G&A expenses and any other income related to this segment. Segment profit does not include amortization and certain other items.

Profit from our Europe segment in the first quarter of 2021 was $338 million, a decrease of 33%, compared to $502 million in the first quarter of 2020. This decrease was mainly due to lower revenues, as discussed above.

International Markets Segment

Our International Markets segment includes all countries in which we operate other than those in our North America and Europe segments. The key markets in this segment are Japan, Russia and Israel.

On February 1, 2021, we completed the sale of the majority of the generic and operational assets of our business venture in Japan.

The following table presents revenues, expenses and profit for our International Markets segment for the three months ended March 31, 2021 and 2020:

Revenues from our International Markets segment in the first quarter of 2021 were $490 million, a decrease of $75 million, or 13%, compared to the first quarter of 2020. In local currency terms, revenues decreased by 7% compared to the first quarter of 2020, mainly due to lower revenues in Japan resulting from the divestment mentioned above, as well as regulatory price reductions and generic competition to off-patented products in Japan and lower positive impact from hedging activity.

Revenues by Major Products and Activities

The following table presents revenues for our International Markets segment by major products and activities for the three months ended March 31, 2021 and 2020:

Generic products revenues in our International Markets segment in the first quarter of 2021, which include OTC products, decreased by 13% to $392 million, compared to the first quarter of 2020. In local currency terms, revenues decreased by 11%, mainly due to lower sales in Japan resulting from the divestment mentioned above, as well as regulatory price reductions and generic competition to off-patented products in Japan.

COPAXONE revenues in our International Markets segment in the first quarter of 2021 were $12 million, flat compared to the first quarter of 2020. In local currency terms, revenues increased by 4%.

AJOVY was launched in certain International Markets countries and we are moving forward with plans to launch in other countries.

AUSTEDO launched in China for treatment of chorea associated with Huntington disease and for the treatment of tardive dyskinesia in early 2021. We continue with additional submissions in various other countries.

International Markets Gross Profit

Gross profit from our International Markets segment in the first quarter of 2021 was $260 million, a decrease of 15% compared to $305 million in the first quarter of 2020.

Gross profit margin for our International Markets segment in the first quarter of 2021 decreased to 53.0%, compared to 54.0% in the first quarter of 2020. This decrease was mainly due to lower positive impact from hedging activity and a change in mix of products.

International Markets Profit

Profit from our International Markets segment consists of gross profit less R&D expenses, S&M expenses, G&A expenses and any other income related to this segment. Segment profit does not include amortization and certain other items.

Profit from our International Markets segment in the first quarter of 2021 was $122 million, a decrease of 22%, compared to $156 million in the first quarter of 2020. This decrease was mainly due to lower positive impact from hedging activity, as well as lower sales in Japan resulting from regulatory price reductions and generic competition to off-patented products, partially offset by lower S&M expenses.

Other Activities

We have other sources of revenues, primarily the sale of active pharmaceutical ingredients ("APIs") to third parties, certain contract manufacturing services and an out-licensing platform offering a portfolio of products to other pharmaceutical companies through our affiliate Medis. Our other activities are not included in our North America, Europe or International Markets segments described above.

Our revenues from other activities in the first quarter of 2021 were $289 million, a decrease of 6% compared to the first quarter of 2020. In local currency terms, revenues decreased by 9%.

API sales to third parties in the first quarter of 2021 were $178 million, flat in both U.S. dollar and local currency terms, compared to the first quarter of 2020.

Conference Call

Teva will host a conference call and live webcast including a slide presentation on Wednesday, April 28, 2021 at 8:00 a.m. ET to discuss its first quarter of 2021 results and overall business environment. A question & answer session will follow.

In order to participate, please dial the following numbers:

A live webcast of the call will be available on Teva’s website at: ir.tevapharm.com.

Following the conclusion of the call, a replay of the webcast will be available within 24 hours on the Company’s website or by calling United States 1-866-331-1332; International +44 (0) 3333 009785; passcode: 8347148

On April 28, 2021 Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that it will report first quarter 2021 financial results on Monday, May 3, 2021 (Press release, Karyopharm, APR 28, 2021, View Source,-2021 [SID1234578649]). Karyopharm’s management team will host a conference call and audio webcast at 8:30 a.m. ET on Monday, May 3, 2021, to discuss the financial results and other company updates.

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To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.