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Thursday, February 11, 2021

Ayala starts Phase 2 of triple-negative breast cancer trial

 Ayala Pharmaceuticals, Inc. (NASDAQ: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, today announced the first patient dosed in the Phase 2 TENACITY clinical trial of its potent, selective small molecule AL101, for the treatment of patients with Notch-activated recurrent or metastatic (R/M) triple negative breast cancer (TNBC).

“The dosing of the first patient in our Phase 2 TENACITY trial is an important step for Ayala as we now have two ongoing Phase 2 clinical trials for AL101 monotherapy in heavily pre-treated patient populations, further building its safety and efficacy profile across these difficult to treat, Notch-activated cancers,” said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. “We believe the need for a novel therapeutic option is critical as Notch-activated TNBC correlates with a poorer prognosis and higher rates of potential relapse. We are confident that TNBC is a logical second indication for AL101 based on extensive preclinical work and we look forward to further advancing the TENACITY trial.”

The Phase 2 study is designed to evaluate the efficacy and safety of AL101 monotherapy in patients with Notch-activated R/M TNBC. It is an open-label, multicenter, single arm study which is expected to initially enroll up to 26 patients with Notch-activated R/M TNBC whose disease has recurred or progressed after three or fewer lines of prior therapy. Notch activation will be determined using a Next Generation Sequencing (NGS) based assay screen. Ayala expects to report preliminary data by the end of 2021.

https://finance.yahoo.com/news/ayala-pharmaceuticals-announces-first-patient-141500903.html

ESSA: Favorable Initial Phase 1 Data on EPI-7386 for Advanced Prostate Cancer

 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, today will present preclinical and clinical pharmacology data from ESSA's Phase 1 clinical trial of EPI-7386 for the treatment of patients with metastatic castration-resistant prostate cancer ("mCRPC") at the 2021 American Society of Clinical Oncology Genitourinary ("ASCO GU") Cancers Symposium. EPI-7386, ESSA's lead product candidate, is an investigational, highly-selective, oral, small molecule inhibitor of the androgen receptor's N-terminal domain. ASCO GU is being held virtually from Thursday, February 11 to Saturday, February 13, 2021.

The oral poster presentation titled, "Preclinical and clinical pharmacology of EPI-7386, an androgen receptor N-terminal domain inhibitor for castration-resistant prostate cancer," will be presented and available for viewing starting February 11 at 8:00am ET.

Data highlights compare preclinical projections of EPI-7386's clinical pharmacokinetic parameters to the pharmacokinetic, safety and preliminary clinical data from the initial 200 mg cohort of patients enrolled in ESSA's multi-center, open-label, ascending multiple-dose Phase 1 study of EPI-7386 to treat patients with mCRPC who have become resistant to standard of care treatments. Patients participating in this trial have progressed on two or more approved systemic therapies for mCRPC, including at least one second generation antiandrogen therapy not necessarily in the metastatic disease setting. In this initial cohort of patients receiving the 200 mg once-daily dose, EPI-7386 was well-tolerated with no SAEs observed. The results from this cohort support ESSA's preclinical projections regarding the pharmacologic properties of EPI-7386 in patients. EPI-7386 was well-absorbed, demonstrated high exposure levels and was confirmed to have a long half life of at least 24 hours. The predicted exposures of EPI-7386 in patients were similar to our modeled projections and were still below optimal target exposures of EPI-7386 associated with anti-tumor activity in animal models. Despite the suboptimal 200 mg dose, one out of three patients who completed 12 weeks of therapy experienced a prostate specific antigen ("PSA") decline of more than 50 percent after three cycles of EPI-7386 therapy (12 weeks) with ongoing continued PSA declines continuing through six cycles of therapy, despite previously having failed enzalutamide and abiraterone acetate. ESSA recently completed the 28-Day safety evaluation period for the 400mg dose cohort and is currently dosing patients in the 600 mg cohort.

Public option for health insurance could be disaster, especially in times of crisis

 In a step to help more Americans get health insurance, President Biden signed an executive order creating an additional opportunity for Americans to sign up for subsidized coverage on the health insurance marketplaces created by the Affordable Care Act.

But Biden has his eyes set on something bigger to fulfill his goals of expanding health coverage: creating a public option to compete with private insurance.

Under a public option, the federal government would administer an insurance plan that competes with private insurance. It would collect premiums from enrollees and directly reimburse doctors, nurses, and other clinicians for the care they provide.

Supporters of such a government-run plan argue that it will expand health insurance coverage while delivering lower premiums and reducing federal deficits.

But there is a problem: The public option would actually increase long-term federal deficits, especially during times of economic strain, much like the one being caused by the Covid-19 pandemic.

Basic assumptions about the long-term costs of a public option are flawed. Research we have done shows that a public option will mean soaring deficits and debts because politicians in Washington will eventually succumb to political pressure both to subsidize enrollee premiums and to pay doctors and hospitals closer to what they are paid by private insurance rather than by existing government programs like Medicare and Medicaid. According to our calculations, the public option would add $800 billion to deficits in the first 10 years and increase the federal debt by more than 30% of the gross domestic product by 2050 — the equivalent of $6 trillion in today’s economy.

The effects on the budget are even worse when the economy suffers or if health costs unexpectedly rise. How much worse? With support from the Partnership for America’s Health Care Future — a coalition of leading health care providers, insurers, biopharmaceutical companies and employers that oppose one-size-fits-all health care — we looked at a few ways policymakers might adjust the public option to respond to future economic shocks and the impact these changes would have on long-term deficits and debt.

First, if a public option was open to all Americans, its promise of cheap premiums would make it the largest government program in terms of enrollment. We estimate that more than 100 million Americans would enroll. Under current public option proposals, the government would be required to raise premiums annually on all enrollees. Congress is unlikely to allow premium hikes to occur during recessions or times of economic strain. We estimated that if Congress chose to suspend premium increases during subsequent recessions, the long-term federal debt would grow by more than $1.4 trillion adjusted for inflation by 2050 — and that is before accounting for other potential program liberalizations.

Second, unlike federal transfer programs such as Social Security, public option enrollees or their employers would generally have to write checks to the federal government, not the other way around. The federal government would be required to kick enrollees who lost their jobs off their insurance — unless Congress decided to give unemployed enrollees a reprieve.

There would be precedent for such action. During the 2007 recession, the federal government subsidized unemployed workers’ health premiums for COBRA continuation coverage so they could stay on their prior employers’ plans. Last year, during the Covid-19 crisis, some lawmakers proposed paying 100% of COBRA premiums for individuals who lost their jobs during the pandemic.

If Congress follows these precedents and allows unemployed individuals to stay on the public option for the first six months after they are laid off, that would add an extra $132 billion to 10-year deficits and increase the 2050 debt by an inflation-adjusted $800 billion.

And that’s nothing compared to how expensive a public option would be if health care costs grow unexpectedly, as they have in the past. In such an event, the government would have few good options. It might allow premiums to rise or cut provider reimbursement rates. But the more politically realistic outcome is obvious: Congress would forget about the promises made by today’s public option proponents and move to subsidize the program, ultimately adding trillions of dollars in federal debt.

If Congress limited premium growth to inflation and health care costs grew at their historical average, the long-term federal debt would grow by an inflation-adjusted $17.5 trillion dollars with more than half of all Americans enrolling in the heavily subsidized program. Or politicians could bite the bullet and pay for the higher costs with a broad-based payroll tax that would cost the typical American family an extra $4,150 per year in inflation-adjusted dollars.

Biden may be tempted to use the budget reconciliation process — a legislative maneuver that allows certain revenue and spending proposals to pass the Senate with a simple majority vote — to pass a public option. In fact, advocates called for doing just that during the debate over the ACA in 2010. These efforts were ultimately rebuffed by the Obama administration, which saw the public option as too controversial.

Democrats aren’t the only ones who have looked to reconciliation to pass their health policy priorities with a narrow, partisan majority. In 2017, Republicans considered using reconciliation to repeal and replace the Affordable Care Act. These efforts failed as moderates in both parties concluded that reconciliation was a poor legislative vehicle for dramatic changes to the nation’s health care system.

The reconciliation process requires that any permanent spending increase be matched with permanently higher taxes or other deficit-reducing policies. With a razor-thin majority, Democrats are poised to use the public option, which government scorekeepers have traditionally seen as deficit-reducing, to help offset their long-term spending proposals. But our research makes clear that the public option only increases deficits over time.

Supporters insist that the public option’s self-financing rules ensure that it won’t become a costly government program. But at the end of the day, its design makes liberalizations inevitable. When recessions or economic shocks occur, any limits that Congress may have placed on these programs are quickly abandoned. The public option would become yet another expensive line item on the federal budget — one that bears little resemblance to the proposal its supporters claim to want.

Lanhee J. Chen is a research fellow at the Hoover Institution, where Tom Church and Daniel L. Heil are policy fellows.

https://www.statnews.com/2021/02/11/public-health-insurance-disaster-times-of-crisis/

AstraZeneca Sees Profit Growth In 2021 Despite COVID-19 Vaccine Controversy

 

  • AstraZeneca plc (NASDAQ: AZN) expects profit growth to pick up this year after announcing better than expected quarterly drug sales, with demand for its cancer and other therapies cushioning the disruption caused by the pandemic.
  • Fourth-quarter net income rose to $1.01 billion from $313 million a year ago. Drug sales increased 11% to $7.41 billion, driven by a 24% increase in cancer treatments. Sales from AstraZeneca's best-selling drug Tagrisso soared 31%. AstraZeneca clocked $2 million in revenue from its COVID-19 vaccine, which it has pledged to supply on a non-profit basis during the pandemic, and said it would begin reporting sales of the vaccine separately starting in the next quarter.
  • This year, the company expects total revenue to rise by a low-teens percentage, accompanied by faster growth in core EPS to $4.75 to $5.00. The guidance does not incorporate any revenue or profit impact from sales of the COVID-19 vaccine.
  • The full-year dividend would remain unchanged at $2.80 per share.
  • $39 billion Alexion takeover is due to close in the third quarter. One deal motivator was profitability, and the company said when announcing the transaction. The company said that guidance for the year might be revised once the deal has been completed.
  • Recently, the COVID-19 vaccine jab was temporarily excluded from South Africa's immunization campaign over questions about its effectiveness against a new strain of the virus first identified in the country.
  • The company also said that it is working with the University of Oxford to adapt its COVID-19 vaccine to protect against new strains of the virus and hopes to cut the time needed to produce large amounts of any new vaccine to between six and nine months.
  • Yesterday, AstraZeneca said it plans to accelerate production of its COVID-19 in the second quarter to support EU needs, in a deal with Germany's IDT Biologika.
  • Have a look at the earnings presentation here.

Merck In Talks To Possibly Produce COVID-19 Shots

 

  • According to the Wall Street Journal, Merck & Co Inc (NYSE: MRK) is reportedly in talks with governments and companies to potentially help with the manufacturing of COVID-19 vaccines that have already been authorized.
  • The supply of COVID-19 shots remains limited, prompting the vaccine-makers such as Pfizer Inc PFE and BioNTech SE BNTX to team up with other companies to fill the gap. Teva Pharmaceutical Industries Ltd's TEVA 0.04% Chief Executive Kare Schultz said the company is in talks with companies to help manufacture shots.
  • Merck halted the development of its two COVID-19 vaccines in January after early trials showed both vaccines generated immune responses that were inferior to those seen in people who had recovered from COVID-19 as well as those reported for other COVID-19 vaccines. 
  • Though, Merck has built out its portfolio of COVID-19 medicines through a series of deals in recent months. It includes a $425 million OncoImmune Acquisition, from which the results of a late-stage study is expected by the end of March. Another therapy, oral antiviral dubbed as Ridgeback Biotherapeutics developed molnupiravir, is in Phase 2/3 trial for hospitalized and outpatient COVID-19 patients. Early data from a trial is expected as early as the first quarter.
  • Merck had acquired Themis, which is working on a COVID-19 vaccine candidate. It has also collaborated with IAVI, a nonprofit scientific research organization, to develop an investigational vaccine against SARS-CoV-2.

Piper Sandler Upgrades Pacific Biosciences (PACB) to Overweight

 Piper Sandler analyst William Quirk upgraded Pacific Biosciences of California (NASDAQ).

https://www.streetinsider.com/Analyst+Comments/UPDATE%3A+Piper+Sandler+Upgrades+Pacific+Biosciences+of+California+%28PACB%29+to+Overweight/17952073.html

Alkermes Financial Results for Q4, Year Ended Dec. 31, 2020, 2021 Guidance

 Alkermes plc (Nasdaq: ALKS) today reported financial results for the quarter and year ended Dec. 31, 2020 and provided financial expectations for 2021.

"2020 was a demonstration of the resiliency of our organization, as we adapted our business to endure a pandemic that has proved to be one of the most disruptive events in our recent history. Despite the challenges posed by COVID-19, we achieved significant growth of net sales from our portfolio of proprietary commercial products, advanced our pipeline of neuroscience and oncology candidates, and announced a Value Enhancement Plan designed to drive growth and improve operational and financial performance," said Richard Pops, Chief Executive Officer of Alkermes. "We are focused on value creation in 2021 as we seek to grow and diversify our commercial portfolio, demonstrate the value of our R&D investments, and manage the company for growth and long-term profitability, all while striving to make a meaningful difference in the lives of people living with serious mental illness, addiction and cancer."

Quarter Ended Dec. 31, 2020 Financial Highlights

  • Total revenues for the quarter were $280.0 million. This compared to $412.7 million for the same period in the prior year, which included a $150.0 million milestone payment from Biogen related to the U.S. Food and Drug Administration's (FDA) approval of VUMERITY® in 2019.
  • Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $42.6 million for the quarter, or a basic and diluted GAAP loss per share of $0.27. This compared to GAAP net loss of $5.4 million, or a basic and diluted GAAP loss per share of $0.03, for the same period in the prior year.
  • Non-GAAP net income was $16.5 million for the quarter, or a non-GAAP basic and diluted earnings per share of $0.10. This compared to non-GAAP net income of $131.4 million, or a non-GAAP basic and diluted earnings per share of $0.83 for the same period in the prior year.

Year Ended Dec. 31, 2020 Financial Results

Revenues

  • Total revenues for the year were $1.04 billion. This compared to $1.17 billion in the prior year. Total revenues in 2019 included a $150.0 million milestone payment from Biogen related to the FDA's approval of VUMERITY, of which $144.8 million was recorded as license revenue and $5.2 million was recorded as research and development (R&D) revenue.
  • Net sales of proprietary products for the year were $551.8 million, compared to $524.5 million in the prior year.
    • Net sales of VIVITROL® were $310.7 million, compared to $335.4 million in the prior year, representing a decrease of approximately 7%, primarily due to COVID-19-pandemic-related disruptions.
    • Net sales of ARISTADA®i were $241.0 million, compared to $189.1 million in the prior year, representing an increase of approximately 27%.
  • Manufacturing and royalty revenues for the year were $484.0 million, compared to $447.9 million in the prior year.
    • Manufacturing and royalty revenues from RISPERDAL CONSTA®, INVEGA SUSTENNA®/XEPLION® and INVEGA TRINZA®/TREVICTA® were $345.6 million, compared to $323.3 million in the prior year.

Costs and Expenses

  • Total operating expenses for the year were $1.15 billion, compared to $1.35 billion in the prior year.
    • R&D expenses were $394.6 million, compared to $512.8 million in the prior year, which included the $86.6 million charge related to the acquisition of Rodin Therapeutics, Inc. (Rodin) in 2019.
    • Selling, General and Administrative (SG&A) expenses were $538.8 million, compared to $599.4 million in the prior year, primarily reflecting the impact of the restructuring implemented in 2019 and additional expense management measures in 2020.

Net Loss/Net Income

  • GAAP net loss for the year was $110.9 million, or a basic and diluted GAAP loss per share of $0.70. This compared to GAAP net loss of $196.6 million, or a basic and diluted GAAP loss per share of $1.25, in the prior year.
  • Non-GAAP net income for the year was $68.6 million, or a non-GAAP basic and diluted earnings per share of $0.43. This compared to non-GAAP net income of $112.2 million, or a non-GAAP basic and diluted earnings per share of $0.71, in the prior year, which included the $150 million of revenue from Biogen following approval of VUMERITY.

Balance Sheet

  • At Dec. 31, 2020, Alkermes recorded cash, cash equivalents and total investments of $659.8 million, compared to $597.2 million at Sept. 30, 2020, and $614.4 million at Dec. 31, 2019, driven primarily by the company's operating results and changes in working capital. The company's total debt outstanding as of Dec. 31, 2020 was $275.0 million, consisting of a term loan that matures in March 2023.

"Our solid 2020 financial results demonstrate efficient management of our business from a financial and operational perspective in response to the significant disruptions caused by the pandemic. These efforts underscore our focus on execution and reflect our commitment to driving bottom line growth," commented Iain Brown, Chief Financial Officer of Alkermes. "We enter 2021 well positioned to execute on our strategic priorities and work toward the long-term profitability margin targets set forth in our Value Enhancement Plan. We plan to achieve these targets through commercial execution, focused investment in the company's future growth drivers and continued efforts to optimize our infrastructure and operating model. Our financial expectations for 2021 reflect anticipated growth of our commercial portfolio and focused investments to support the anticipated launch of LYBALVI™ and advance the clinical development program for nemvaleukin, as we position these programs to drive future value creation."

Financial Expectations for 2021

The following financial expectations for 2021 are based on recent trends and assume continuation of such trends into the first half of the year, and an anticipated improvement in patient access to treatment providers and to the company's commercial products in the second half of the year. If patient access does not improve as anticipated, or if new COVID-19-related disruptions emerge, the company's ability to meet these expectations could be negatively impacted. All line items are according to GAAP, except as otherwise noted.

In millions (except per share amounts)

 

2021 Expectation

(Provided 2/11/21)

   

Total Revenue

 

$1,100 – $1,170

VIVITROL Net Sales

 

$315 – $345

ARISTADA Net Sales

 

$260 – $290

LYBALVI Net Sales

 

<$10

Cost of Goods Sold

 

$190 – $200

R&D Expenses

 

$400 – $430*

SG&A Expenses

 

$570 – $600

Amortization of Intangible Assets

 

~$40

Income Tax Expense

 

$0 – $10

GAAP Net Loss

 

($85) – ($125)

GAAP Net Loss per Share

 

($0.53) – ($0.78)

Non-GAAP Net Income

 

$60 – $100

Non-GAAP Diluted EPS

 

$0.37 – $0.62

Capital Expenditures

 

~$40

*R&D expense expectations for 2021 include a potential $25 million milestone payment to the former shareholders of Rodin related to the anticipated submission of an investigational new drug application, or equivalent, for ALKS 1140, the first clinical candidate to emerge from the histone deacetylase (HDAC) inhibitor platform acquired by the company in late 2019.

Recent Events:

LYBALVI (formerly referred to as ALKS 3831)

  • In December 2020, the FDA acknowledged receipt of the company's New Drug Application (NDA) resubmission for LYBALVI and assigned the application a new Prescription Drug User Fee Act (PDUFA) target action date of June 1, 2021. Subsequent to Alkermes' resubmission of the NDA, the FDA issued a new request for records under Section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act to supplement the information previously provided by the company. The resubmission and records request followed the company's receipt of a Complete Response Letter (CRL) from the FDA in November 2020 following its remote review of records relating to the manufacture of LYBALVI at the company's Wilmington, OH facility. The CRL did not identify or raise any concerns about the clinical or non-clinical data in the NDA and the FDA has not asked the company to complete any new clinical trials to support approval of the application.

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

  • In November 2020, preliminary data from ARTISTRY-1 and ARTISTRY-2, phase 1/2 studies evaluating nemvaleukin administered intravenously and subcutaneously, respectively, as monotherapy and in combination with pembrolizumab in patients with refractory advanced solid tumors, were presented at the Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting.

HDAC-inhibitor platform

  • In December 2020, the company nominated ALKS 1140, a novel CoRESTii-selective HDAC inhibitor candidate with potential applications in neuropsychiatric indications. First-in-human studies for ALKS 1140 are planned to begin in 2021.

Other

  • In January 2021, results from a National Institute on Drug Abuse (NIDA)-funded study evaluating the efficacy and safety of naltrexone for extended-release injectable suspension (XR-NTX) administered once every three weeks plus oral extended-release bupropion administered daily as a combination treatment for adults with moderate or severe methamphetamine use disorder (MUD) were published by Dr. Madhukar H. Trivedi et al. in the New England Journal of Medicine (NEJM).iii

https://www.biospace.com/article/releases/alkermes-plc-reports-financial-results-for-the-fourth-quarter-and-year-ended-dec-31-2020-and-provides-financial-expectations-for-2021/