On May 5, 2021 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported its financial results for the first quarter of 2021 and recent business highlights (Press release, Ionis Pharmaceuticals, MAY 5, 2021, View Source [SID1234579178]).

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"In the first quarter, we took important steps to maximize the value of our wholly owned pipeline. We recently initiated pivotal studies with our wholly owned FUS-ALS and Alexander disease programs. We delivered positive results from our IONIS-PKK-LRx program, demonstrating its potential to change the standard of care for patients with hereditary angioedema. We also further strengthened the business and continued executing on our strategic priorities," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "This summer, we expect data from our IONIS-MAPTRx program in Alzheimer’s disease patients. And later this year, we look forward to data from the Phase 3 VALOR study of tofersen in patients with SOD1-ALS. If results from the VALOR study are positive, we expect tofersen to be our next commercial medicine. These key upcoming catalysts, together with our recent achievements, position us well to have 12 or more products on the market in 2026."

First Quarter 2021 and Recent Summary Financial Results

On track to achieve 2021 financial guidance reflecting investments in Ionis’ wholly owned pipeline, based on the following first quarter results
$112 million in total revenues
$159 million of operating expenses on a non-GAAP basis(1) and $204 million on a GAAP basis
Net loss of $45 million on a non-GAAP basis(1) and $90 million on a GAAP basis
Further strengthened the Company’s balance sheet with pro forma cash of $2.1 billion, after reflecting the convertible notes transaction
Enables expansion of manufacturing and R&D capacity
$632.5 million principal due in April 2026 with 0% interest and an effective conversion price of $76.39 after the purchase of a call spread
Will realize interest expense savings while keeping potential future dilution nearly flat
Repurchased approximately 80% of previously outstanding 1% convertible notes due in November 2021
"So far this year, we have taken important steps in support of developing and commercializing our wholly owned medicines. In addition to completing the restructuring of our European operations, we expanded our Sobi distribution agreement to include North America. These transactions unlocked significant resources that we are now redirecting towards our highest priority programs, including IONIS-TTR-LRx and IONIS-APOCIII-LRx," said Elizabeth L. Hougen, chief financial officer of Ionis. "We are on track to meet our 2021 financial guidance. In the second half of this year, we expect R&D revenue to increase as many of our partnered programs continue to advance. Importantly, we are well-capitalized with the resources we need to expand our manufacturing and R&D capacity to support the future needs of our wholly owned pipeline. This large capital project, which is now underway, is necessary to successfully execute on our goal to drive growth."

(1)

All non-GAAP amounts referred to in this press release exclude non-cash compensation expense related to equity awards and expenses related to the Akcea acquisition and restructured European operations and the related tax effects. Please refer to the section below titled "Financial Impacts of Akcea Acquisition and Restructured Operations" for a summary of the costs specific to these transactions. Additionally, please refer to the detailed reconciliation of non-GAAP and GAAP measures, which is provided later in this release.

First Quarter 2021 Marketed Products Highlights

SPINRAZA: a global foundation-of-care for the treatment of spinal muscular atrophy (SMA) patients of all ages
$521 million in worldwide sales in the first quarter
More than 11,000 patients worldwide were on therapy at the end of the first quarter across post-marketing, expanded access and clinical trial settings
Higher-dose SPINRAZA demonstrated safety and tolerability consistent with the currently approved dose in the open-label safety cohort of the DEVOTE study, enabling enrollment in the blinded, pivotal cohort to get underway
TEGSEDI and WAYLIVRA: important medicines approved for the treatment of patients with severe rare diseases
Completed the transition of European operations to Swedish Orphan Biovitrum AB (Sobi) and expanded the distribution agreement to include North American TEGSEDI operations
First Quarter 2021 and Recent Pipeline Events

Phase 3 Pipeline: growing and positioned for 12 or more products on the market in 2026
Advanced ION363 into a Phase 3 study in patients with FUS-ALS
Advanced tofersen into the Phase 3 ATLAS study in presymptomatic SOD1-ALS patients
Roche reported tominersen data related to the dosing halt in the Phase 3 program
Mid-stage Pipeline: advancing multiple medicines with potential to change the standard of care for patients with severe diseases
Reported positive topline IONIS-PKK-LRx results in patients with hereditary angioedema
Advanced ION373 into the Phase 2 portion of a pivotal study in patients with Alexander disease
Advanced the IONIS-AGT-LRx development program:
Reported positive Phase 2 data in JACC: Basic to Translational Science
Advanced into a Phase 2b study in patients with hypertension uncontrolled with three or more antihypertensive medications
Advanced into a Phase 2 study in patients with chronic heart failure with reduced injection fraction
Advanced the ongoing Phase 2 study of ION541 in patients with ALS regardless of family history, resulting in a $10 million payment from Biogen
Upcoming 2021 Pipeline Catalysts(2)

(2) Timing of partnered program catalysts based on partners’ most recent publicly available disclosures

First Quarter 2021 Financial Results

TEGSEDI and WAYLIVRA revenue, net

Amortization from upfront payments

20The Company’s commercial revenue in the first quarter of 2021 was consistent with the same period last year. As the Company completes its transition of TEGSEDI operations in North America to Sobi, the Company’s commercial revenue from product sales will shift to distribution fees based on net sales generated by Sobi.

The Company’s R&D revenue decreased in the first quarter of 2021 compared to the same period last year primarily because the Company earned more milestone payments in the first quarter of 2020 than the same period this year. The Company expects its R&D revenue to increase in the second half of 2021 compared to the first half.

Financial Impacts of Akcea Acquisition and Restructured Operations

In conjunction with the Akcea acquisition and restructured European operations, in the first quarter of 2021, the Company incurred $7 million of costs, which it excluded from its non-GAAP amounts for the period. Refer to the detailed reconciliation of non-GAAP and GAAP measures that is provided later in this release. The Company expects to incur additional expenses in the range of $11 million to $14 million related to the restructuring of its North American TEGSEDI operations from the expanded distribution agreement with Sobi. The company will reflect the North American TEGSEDI restructuring costs primarily in the second quarter of 2021.

Operating Expenses

Ionis’ operating expenses for the first quarter of 2021 increased compared to the same period last year driven primarily by the Company’s investments in advancing its late-stage wholly owned pipeline.

Net Loss Attributable to Ionis Common Stockholders

Ionis’ net loss attributable to Ionis’ common stockholders for the first quarter of 2021 increased compared to the same period in the prior year for the reasons discussed above.

Balance Sheet

Ionis ended March 2021 with cash, cash equivalents and short-term investments of $1.8 billion, compared to $1.9 billion at December 31, 2020. In April 2021, Ionis issued $632.5 million of 0% senior convertible notes due in April 2026 and repurchased $247.9 million of its 1% senior convertible notes. After reflecting these transactions, Ionis’ pro forma cash, cash equivalents and short-term investments was $2.1 billion.

The Company revised its 2020 amounts to reflect the simplified convertible instruments guidance the Company adopted retrospectively on January 1, 2021.

Webcast

Today, at 11:30 a.m. Eastern Time, Ionis will conduct a live webcast to discuss this earnings release and related activities. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address.

On May 5, 2021 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported business updates and financial results for the first quarter ended March 31, 2021 (Press release, Alector, MAY 5, 2021, View Source [SID1234579189]).

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"Positive momentum continues to build throughout our early and late-stage product pipeline," said Arnon Rosenthal, Ph.D., co-founder and chief executive officer of Alector. "Our pivotal AL001 INFRONT-3 Phase 3 trial and AL002 INVOKE-2 placebo-controlled Phase 2 trial continue to enroll patients, and we look forward to sharing additional data from the AL001 Phase 2 clinical development program in people with FTD-GRN this summer at AAIC. In parallel, we continue to prepare for the initiation of a Phase 2 study evaluating AL001 in people with amyotrophic lateral sclerosis and advance our early-stage novel immuno-oncology candidates toward first-in-human studies. This is an exciting time for Alector and we look forward to continued execution on our clinical and corporate objectives."

Key Business Updates

Progranulin Portfolio:

Alector plans to present updated data from the ongoing AL001 Phase 2 open-label study at the upcoming Alzheimer’s Association International Conference (AAIC), taking place July 26-30, 2021.

Enrollment is ongoing in INFRONT-3, a randomized, placebo-controlled, pivotal Phase 3 trial evaluating AL001 in people at risk for or with frontotemporal dementia due to a progranulin gene mutation (FTD-GRN). The ongoing pivotal trial is evaluating the efficacy and safety of AL001 in at-risk and symptomatic participants with FTD-GRN. Participants in the trial will be given the option to continue receiving treatment in an open-label extension study.

The Company is on track to initiate a Phase 2 study evaluating AL001 in people with amyotrophic lateral sclerosis (ALS) caused by C9orf72 repeats, which share TDP-43 pathology with FTD-GRN in the second half of 2021.
Alzheimer’s Disease Portfolio:

Alector continues patient enrollment in INVOKE-2, a Phase 2 trial evaluating AL002 in people with early Alzheimer’s disease. The randomized, double-blind, placebo-controlled, dose-ranging, multi-center Phase 2 study is expected to enroll approximately 265 participants with early Alzheimer’s disease (AD) at up to 90 sites globally. The AL002 clinical program is being developed in collaboration with AbbVie.

Alector plans to present two posters highlighting AL002 at AAIC, taking place July 26-30, 2021. The first poster will include the results of the AL002 Phase 1 study in healthy volunteers and the second poster will highlight the study design of the ongoing INVOKE-2 trial in people with early AD.

Data from the Phase 1b study evaluating AL003 in participants with AD is expected in 2021. Alector initiated the Phase 1b study in January 2020 and completed enrollment in 2020. The AL003 clinical development program is being developed in collaboration with AbbVie. Preliminary results from the study are expected to be presented at a scientific medical meeting in the second half of 2021.
Early-Stage Pipeline with Potential in Neurodegenerative Diseases and Oncology

The Company continues to progress AL044, a first-in-class antibody targeting the MS4A4A receptor. MS4A4A is a major risk gene for AD that encodes a transmembrane receptor protein that is expressed selectively in microglia in the brain and is associated with control of microglia functionality and potential viability.

Planning is underway to initiate first-in-human studies for AL008 and AL009, two oncology programs, in 2022. AL008 is a novel, investigational, antibody product candidate with a dual mechanism of action that combines inhibition of the CD47-SIRP-alpha (SIRPα) pathway with stimulation of activating Fc receptors and has the potential to yield a best-in-class product. AL009 is a first-in-class multi-Siglec inhibitor that works to enhance the innate and adaptive immune system response by blocking a critical glycan checkpoint pathway that drives immune inhibition.
First Quarter 2021 Financial Results

Revenue. Collaboration revenue for the quarter ended March 31, 2021, was $4.1 million, compared to $7.2 million for the same period in 2020. Revenue is recognized as the program costs are incurred by measuring actual costs incurred to date compared to the overall total expected costs to satisfy the performance obligation. Changes in estimates for revenue recognized over time are recognized on a cumulative basis.

R&D Expenses. Total research and development expenses for the quarter ended March 31, 2021, were $45.7 million, compared to $34.6 million for the same period in 2020. This increase was mainly driven by an increase in expenses to support the advancement of clinical and pre-clinical programs across several therapeutic initiatives as well as an increase in personnel-related expenses.

G&A Expenses. Total general and administrative expenses for the quarter ended March 31, 2021, were $11.1 million, compared to $14.6 million for the same period in 2020. This decrease was primarily due to a decrease in legal fees related to the conclusion of our arbitration proceedings for certain intellectual property matters.

Net Loss. For the quarter ended March 31, 2021, Alector reported a net loss of $52.2 million, compared to a net loss of $40.0 million for the same period in 2020.

Cash Position. Cash, cash equivalents, and marketable securities were $362.7 million as of March 31, 2021.

On May 5, 2021 Kintara Therapeutics, Inc. (Nasdaq: KTRA), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that its Chief Executive Officer Saiid Zarrabian will participate at the Benzinga Global Small Cap Conference on May 14, 2021 (Press release, Kintara Therapeutics, MAY 5, 2021, View Source [SID1234579214]).

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Mr. Zarrabian will deliver his corporate presentation at 12:25 pm ET on May 14, 2021.

Investors can also request a one-on-one meeting with Mr. Zarrabian to be arranged following the conclusion of the conference.

On May 5, 2021 Everest Medicines (HKEX 1952.HK), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products in Greater China and other parts of Asia, reported that the Ministry of Food and Drug Safety (MFDS) in South Korea has granted Orphan Drug Designation (ODD) for sacituzumab govitecan-hziy (SG), an investigational treatment for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease (Press release, Everest Medicines, MAY 5, 2021, View Source [SID1234579231]).

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"We are very pleased that the Ministry of Food and Drug Safety in South Korea has granted Orphan Drug Designation for SG, which we believe has the potential to become a transformative treatment for patients around the world living with metastatic triple-negative breast cancer – a highly aggressive disease with limited treatment options," said Kerry Blanchard, MD, PhD, CEO of Everest Medicines. "Breast cancer is the leading cause of cancer death in women in South Korea, and the incidence for this disease continues to climb rapidly in the region. As we work closely with local regulatory bodies to bring this innovative treatment to patients in South Korea as quickly as possible, we look forward to continuing to expand our international footprint outside of China and adding to our recent New Drug Application submission for SG in Singapore earlier this year."

Orphan Drug Designation is granted by the MFDS to pharmaceuticals used to treat diseases with a prevalence of 20,000 patients or less in the Korean population, pharmaceuticals used to treat diseases for which appropriate therapy and pharmaceuticals have not been developed, or pharmaceuticals that have been significantly improved in terms of safety and/or efficacy, compared to existing alternative therapies.

About Triple-Negative Breast Cancer

Triple-Negative Breast Cancer (TNBC) is a highly aggressive disease and accounts for approximately 15% of all breast cancer types worldwide. The median age of breast cancer diagnoses tends to be younger in Asian than western countries, and the percentage of the TNBC molecular subtype has been increasing in the past 10 years. TNBC cells lack sufficient estrogen, progesterone or HER2 receptor expression to benefit from the use of hormonal or HER2-directed therapy. Overall survival among patients with this form of breast cancer has not changed in the past 20 years, which highlights the need for advances in therapeutic options for these patients.

In South Korea, the growth in breast cancer incidence in recent decades has been one of the fastest in the world.[1] It is the leading cause of cancer death in South Korean women. Statistics from the International Agency for Cancer Research indicate that breast cancer was the leading cause of cancer diagnoses in South Korea in 2020, accounting for 23.7% of total cases.[2]

About Sacituzumab Govitecan-Hziy

Sacituzumab govitecan-hziy (SG) is a first-in-class, antibody-drug conjugate (ADC) directed at TROP-2, a membrane antigen that is over-expressed in many common epithelial cancers. SG is approved in the United States under the trade name Trodelvy.

Under a licensing agreement with Gilead Sciences, Inc., Everest Medicines has exclusive rights to develop, register, and commercialize SG for all cancer indications in Greater China, South Korea, and certain Southeast Asian countries. In October 2020, SG was included in the updated 2020 China Guidelines for the Standardized Diagnosis and Treatment of Advanced Breast Cancer, compiled by the Breast Cancer Expert Committee of the National Cancer Control Center, the Breast Cancer Professional Committee of the Chinese Anti-Cancer Association, and the Cancer Drug Clinical Research Professional Committee of the Chinese Anti-Cancer Association.

On May 5, 2021 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported that the company will present at the Bank of America 2021 Healthcare Conference on Wednesday, May 12, 2021 at 12:30 p.m. ET and the 2021 RBC Capital Markets Global Healthcare Conference on Wednesday, May 19, 2021 at 1:20 p.m. ET (Press release, BioCryst Pharmaceuticals, MAY 5, 2021, View Source [SID1234579146]). Both are being conducted as virtual conferences.

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Links to a live audio webcast and replay of these presentations may be accessed in the Investors section of BioCryst’s website at http://www.biocryst.com.