On August 4, 2021 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) reported its financial results for the second quarter of 2021 and recent business achievements (Press release, Ionis Pharmaceuticals, AUG 4, 2021, View Source [SID1234585703]).

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"Since our last quarterly update, we continued to execute on our strategic objectives to prepare for multiple Ionis commercial launches, expand our drug delivery capabilities and advance new products towards the market. Biogen completed dosing in the tofersen Phase 3 VALOR study and began offering tofersen to SOD1-ALS patients on an individual compassionate use basis. We achieved full enrollment in the eplontersen Phase 3 NEURO-TTRansform study and 50 percent enrollment in the pelacarsen Phase 3 Lp(a) HORIZON study. Additionally, we licensed Bicycle Therapeutics’ technology to expand the capabilities of our LICA technology," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "Looking ahead, we expect data from multiple pipeline programs, including additional data supporting the potential for our IONIS-PKK-LRx program to change the standard of care for patients with hereditary angioedema. And by this fall, we expect 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 recent achievements and upcoming catalysts keep us on track for a regular cadence of Phase 3 data and new drug applications, leading to 12 or more products on the market in 2026."

Second Quarter 2021 and Recent Summary Financial Results

Second quarter results reflect focus on Ionis’ strategic objectives
$126 million in total revenues
$154 million of operating expenses on a non-GAAP basis(1) and $199 million on a GAAP basis
Net loss of $36 million on a non-GAAP basis(1) and $81 million on a GAAP basis
Well capitalized with cash and investments of $2.1 billion at the end of the second quarter
"In addition to advancing our pipeline and expanding our drug discovery capabilities, we have taken multiple steps to streamline our operations in support of our wholly owned medicines. We have completed the integration of Akcea, entered distribution arrangements with Sobi and restructured our commercial operations. These steps enabled us to unlock significant resources that we are redirecting towards our highest priority programs," said Elizabeth L. Hougen, chief financial officer of Ionis. "We remain on track to achieve our 2021 revenue guidance of more than $600 million. We continue to expect increased R&D revenue in the second half of this year. Already in the third quarter, we earned $25 million from Novartis for the pelacarsen enrollment milestone. We are revising our 2021 operating expense and net loss guidance because of our license of Bicycle’s technology. Importantly, we remain well-capitalized with the resources we need to achieve our strategic objectives."

Revised 2021 Financial Guidance

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 commercial operations and the related tax effects. Please refer to the section below titled "Financial Impacts of Akcea Acquisition and Restructured Commercial 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.

Second Quarter 2021 Marketed Products Highlights

SPINRAZA: The global market leader for the treatment of spinal muscular atrophy (SMA) patients of all ages
$500 million in worldwide sales in the second quarter
More than 11,000 patients worldwide on therapy at the end of the second quarter across commercial, expanded access and clinical trial settings
New data presented at CureSMA reinforce the potential for higher-dose SPINRAZA to improve SMA patient outcomes and further support SPINRAZA’s potential long-term benefit for SMA patients of all ages
TEGSEDI and WAYLIVRA: important medicines approved for the treatment of patients with severe rare diseases
Successfully completed the transition of North American TEGSEDI operations to Swedish Orphan Biovitrum AB (Sobi)
Second Quarter 2021 and Recent Events

Phase 3 Pipeline: Six Phase 3 studies on track for a regular cadence of data readouts beginning this year
Completed dosing in the Phase 3 VALOR study of tofersen in patients with SOD1-ALS, with data expected by this fall
Opened individual compassionate use access for SOD1-ALS patients with the most rapidly progressive disease
Achieved full enrollment in the Phase 3 NEURO-TTRansform study of eplontersen in patients with TTR polyneuropathy, with data expected by mid-2022
Achieved 50 percent enrollment in the Phase 3 Lp(a) HORIZON study of pelacarsen for patients at risk for Lp(a)-driven cardiovascular disease, resulting in a $25 million payment from Novartis
Advanced ION363 into a Phase 3 study in patients with FUS-ALS

Mid-stage Pipeline: multiple medicines with potential to change the standard of care for patients with severe diseases
Continued to advance the Phase 2b RE-THINc ESRD study of IONIS-FXI-LRx, with data expected in the first half of 2022
Reported data from the Phase 1/2 study of IONIS-MAPTRx in patients with Alzheimer’s disease, demonstrating durable, time and dose-dependent reductions in CSF tau protein; IONIS-MAPTRx was generally well tolerated
Advanced the ongoing Phase 2 study of ION541 in patients with ALS regardless of family history, resulting in a $10 million payment from Biogen
Advanced ION224 into a Phase 2b study in patients with non-alcoholic steatohepatitis (NASH)
Advanced ION373 into the Phase 2 portion of a pivotal study in patients with Alexander disease
Strategic and Business Events
Entered a license agreement with Bicycle Therapeutics for exclusive rights to Bicycle’s peptide technology to expand the capabilities of Ionis’ LICA technology
Announced changes to the Ionis board of directors
Joseph Loscalzo, M.D., Ph.D., appointed as chairman and Allene M. Diaz as a member of the board
Joseph Wender appointed as lead independent director
Ionis founder and executive chairman, Stanley T. Crooke M.D., Ph.D. and Breaux B. Castleman retired from the board
Upcoming 2021 Pipeline Catalysts(2)

Second Quarter 2021 Financial Results

Revenue

Ionis’ revenue was comprised of the following (amounts in millions):

In the second quarter of 2021, the Company successfully completed the transition of its TEGSEDI operations in North America to Sobi. As a result, the Company’s commercial revenue from product sales shifted to distribution fees based on net sales generated by Sobi.

The Company’s R&D revenue decreased in the second quarter of 2021 compared to the same period last year primarily because the Company earned more milestone payments in the second 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 as its partnered programs advance. Already in the third quarter of 2021, the Company earned a $25 million milestone payment from Novartis when Novartis achieved 50 percent enrollment in the Phase 3 Lp(a) HORIZON study of pelacarsen.

Financial Impacts of Akcea Acquisition and Restructured Commercial Operations

In the second quarter of 2021, the Company incurred $15 million of costs in conjunction with the Akcea acquisition and restructuring of the Company’s commercial operations. The Company excluded these costs 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.

Operating Expenses

Ionis’ operating expenses for the second quarter of 2021 increased slightly compared to the same period last year driven by an increase in R&D expenses, partially offset by a decrease in SG&A expenses. Ionis’ increased R&D expenses were primarily driven by the Company’s investments in advancing its late-stage wholly owned pipeline. Ionis’ decreased SG&A expenses were primarily from operating efficiencies achieved from integrating Akcea and restructuring the Company’s commercial operations.

Net Loss Attributable to Ionis Common Stockholders

Ionis’ net loss attributable to Ionis’ common stockholders for the second quarter of 2021 increased compared to the same period in the prior year for the reasons discussed above. Additionally, the Company recognized an $8.6 million non-cash loss from the early retirement of a significant portion of its 1 percent senior convertible notes.

Balance Sheet

Ionis ended June 2021 with cash, cash equivalents and short-term investments of $2.1 billion, compared to $1.9 billion at December 31, 2020. In April 2021, Ionis issued $632.5 million of 0 percent senior convertible notes due in April 2026 and repurchased $247.9 million of its 1 percent senior convertible notes. The Company’s remaining $62 million of 1 percent senior convertible notes mature in November 2021.

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 August 4, 2021 vTv Therapeutics Inc. (Nasdaq:VTVT) reported financial results for the second quarter ended June 30, 2021, and provided an update on the progress of its clinical programs (Press release, vTv Therapeutics, AUG 4, 2021, View Source [SID1234585720]).

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"We held our first, highly-productive meeting with the FDA following the designation of Breakthrough Therapy for TTP399 as a potential adjunct treatment for type 1 diabetes," said Steve Holcombe, president and CEO, vTv Therapeutics. "Based upon the outcome of this meeting, we are planning to conduct two pivotal studies of TTP399 starting in the first half of 2022. We are appreciative of the ongoing dialogue that the Breakthrough Designation affords us and look forward to continuing to work closely with the agency as we refine the design of these studies in the coming weeks."

Recent Achievements and Outlook

Type 1 Diabetes

Breakthrough Therapy Designation Type B Meeting. As announced in April, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for TTP399 as an adjunctive therapy to insulin for the treatment of type 1 diabetes. The Company held its first Type B meeting with the FDA pursuant to the Breakthrough Therapy designation to discuss the development of TTP399.

Mechanistic Study of Ketoacidosis with TTP399. The Company completed enrollment in the mechanistic study of TTP399 in people with type 1 diabetes. This phase 1 study is designed to assess the impact of TTP399 on ketone body formation, and therefore the risk of diabetic ketoacidosis, during a period of acute insulin withdrawal. vTv expects to report topline results from this mechanistic study in late third quarter or early fourth quarter of 2021.

Pivotal Study Planning. The Company is planning two pivotal, placebo-controlled clinical trials of TTP399 in subjects with type 1 diabetes that are expected to begin in the first half of 2022.
Psoriasis

Multiple Ascending Dose Study with HPP737. The Company completed dosing healthy subjects in a phase 1 multiple ascending dose study to assess the safety, tolerability, and pharmacokinetic profile of HPP737, an oral PDE4 inhibitor. We expect to report the results from this study in the third quarter.

Phase 2 Study Planning. The Company is planning a phase 2 clinical trial of HPP737 in patients with psoriasis. We are discussing the proposed study design with the FDA during the third quarter and expect to begin the study late in the fourth quarter of 2021 or early in the first quarter of 2022.
License Partner Updates

vTv and Cantex Entered into a Strategic Licensing Agreement for Azeliragon. In June, the Company announced a new strategic collaboration with Cantex Pharmaceuticals under which Cantex will continue the development of azeliragon for the treatment of the complications associated with cancer, including cachexia and pain from bone metastasis. Cantex will be responsible for the development and commercialization of azeliragon and the companies will allocate profits under a tiered arrangement.

Reneo Dosed the First Patient in Phase 2b STRIDE Study. In July, Reneo Pharmaceuticals dosed the first patient in the phase 2b STRIDE Study, designed to assess the efficacy and safety of REN001 for the treatment of patients with primary mitochondrial myopathies.
Funding Updates

$50 Million ATM Program. The Company added an additional $50 million of capacity to its at-the-market equity program with Cantor Fitzgerald to fund the ongoing and planned development of TTP399 and HPP737.

Registration of Additional Shares to Support Equity Line. The Company registered an additional 9.4 million shares of Class A Common Stock to provide the continued flexibility to raise capital with share sales to Lincoln Park Capital under the Purchase Agreement entered into in November of 2020.
First Quarter 2021 Financial Results

Cash Position: The Company’s cash position as of June 30, 2021, was $10.8 million compared to $8.4 million as of March 31, 2021.

Revenue: Revenue for the second quarter of 2021 was an insignificant amount. For the first quarter of 2021 revenue was $1.0 million. The revenue for the first quarter was non-cash and related to the recognition of revenue pertaining to the Huadong license agreement.

R&D Expenses: Research and development expenses were $2.4 million and $3.1 million for the three months ended June 30, 2021 and March 31, 2021, respectively. This decrease of $0.7 million was driven primarily by the decreases in spending for the Elevage study as the analysis and close out of this study largely occurred in the first quarter as well as a decrease in spending for our study of HPP737 in psoriasis.

G&A Expenses: General and administrative expenses were consistent between periods at $2.2 million for each of the three months ended June 30, 2021 and March 31, 2021.

Other Income/(Expense): Other income for the three months ended June 30, 2021 was $3.8 million and was attributable to the changes in the fair value of our investment in Reneo Pharmaceuticals, Inc. which completed its initial public offering in the second quarter of 2021 as well as gains related to a reduction in fair value of the warrants to purchase shares of our own stock issued to a related party (the "Related Party Warrants"). Other expense for the three months ended March 31, 2021 was driven by losses related to an increase in the fair value of the Related Party Warrants.

Net Loss Before Non-Controlling Interest: Net loss before non-controlling interest was $0.8 million for the second quarter of 2021 compared to net loss of $5.9 million for the first quarter of 2021.

Net Loss Per Share: Diluted net loss per share was ($0.01) for the three months ended June 30, 2021 compared to diluted net loss per share of ($0.08) for the three months ended March 31, 2021, based on weighted-average diluted shares of 58.6 million and 56.5 million for the three-month periods ended June 30, 2021 and March 31, 2021, respectively.

On August 4, 2021 eFFECTOR Therapeutics, Inc. (eFFECTOR), a leader in the development of selective translation regulation inhibitors (STRIs) for the treatment of cancer, reported the initiation of dosing in the Phase 2a expansion portion of an ongoing Phase 1/2 trial of zotatifin (eFT226) in solid tumors (Press release, eFFECTOR Therapeutics, AUG 4, 2021, View Source [SID1234585736]). This followed conclusion of the Phase 1 dose escalation portion of the trial and selection of a recommended Phase 2 dose (RP2D). eFFECTOR expects to initiate multiple indication-specific expansion cohorts in ER+ breast cancer and KRAS-mutant non-small cell lung cancer (NSCLC). Zotatifin will be evaluated both as a single agent and in combination with targeted therapies in each indication.

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"Following successful conclusion of dose escalation and selection of the RP2D, we are expanding our zotatifin program with the initiation of several Phase 2a expansion cohorts in cancers with substantial unmet need, including ER+ breast cancer and KRAS-mutant NSCLC," said Steve Worland, Ph.D., president and CEO of eFFECTOR. "Zotatifin has been generally well-tolerated in our clinical trials to date and showed very compelling preclinical activity, including in combination with palbociclib for breast cancer and in combination with sotorasib for KRAS-mutant NSCLC, two indications that we plan to evaluate in expansion cohorts."

The Phase 2a expansion cohorts will evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of zotatifin in subjects with biomarker-positive solid tumor malignancies, including ER+ breast cancer and KRAS-mutant NSCLC. Each of the Phase 2a monotherapy and combination expansion cohorts will utilize a Simon’s Two Stage design, in which seven patients will be enrolled in the first stage of the trial and assessed for activity prior to advancing to the second stage of the trial. Zotatifin will be administered as a 1-hour intravenous (IV) infusion at the selected RP2D of 0.07 mg/kg on Day 1 and Day 8 of a 21-day cycle. eFFECTOR expects to present additional data from the Phase 1 dose escalation portion of the trial, as well as preliminary response data from Phase 2a expansion cohorts, at a medical conference in 2022.

The primary objective of this study is to assess the safety, tolerability and activity of zotatifin as a monotherapy treatment and in combination with targeted agents in biomarker-specific patient populations. If positive activity is observed in a Phase 2a expansion cohort, the company plans to evaluate zotatifin, potentially as a combination in a randomized trial against a relevant comparator control group, or potentially in a single-arm monotherapy trial following demonstration of an appropriate overall response rate (ORR) in the Phase 2a expansion cohort.

About Zotatifin (eFT226)

Zotatifin is a potent and sequence-selective inhibitor of eukaryotic translation initiation factor 4A (eIF4A) mediated translation. eIF4A is responsible for unwinding complex structures in the non-coding 5’ untranslated region of messenger RNA. Zotatifin is designed to block this process, thereby inhibiting the translation of mRNAs encoding several important oncogenes and survival factors, including receptor tyrosine kinases (RTKs), KRAS, Cyclin D, CDK4/6 and MYC. In vivo studies have shown potent tumor regression in multiple tumor models dependent on these factors, including non-small cell lung cancer (NSCLC) and breast cancer. Since zotatifin inhibits the translation of mRNA by acting in the non-coding region of mRNAs, it is not limited to specific KRAS activating mutation subtypes such as KRAS G12C or KRAS G12D. Zotatifin is currently being evaluated as an intravenous (IV) infusion in a Phase 2a clinical trial that will include patients with breast cancer and KRAS-mutant NSCLC and in a Phase 1b clinical trial in patients with mild to moderate COVID-19 infections pursuant to grant sponsorship by the Defense Advanced Research Projects Agency (DARPA).

United Therapeutics has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On August 4, 2021 Select Health of South Carolina and Quest Diagnostics reported that they have entered into an agreement that expands Select Health’s laboratory network for its Medicaid and Medicare-Medicaid dual eligible enrollees (Press release, Quest Diagnostics, AUG 4, 2021, View Source [SID1234585841]).

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Select Health, the state’s oldest and largest Medicaid managed care organization, and a member of the AmeriHealth Caritas Family of Companies, offers the First Choice Medicaid health plan statewide and the First Choice VIP Care Plus Medicare-Medicaid plan (MMP) in 42 counties. Members of both health plans are now able to obtain in-network laboratory services from Quest’s 20 locations throughout the state.

In addition, Select Health, the AmeriHealth Caritas Family of Companies, and Quest are working together to enhance access to diagnostics information services for members, increase efficiency in the delivery of laboratory services, and improve the quality of care.

"Select Health is pleased to welcome Quest Diagnostics to our network of laboratory providers," said Market President Courtnay Thompson. "We look forward to working together to improve access to the highest quality, most effective care and services for South Carolina citizens, with the shared goal of helping them achieve the best health outcomes and overall quality of life."

"We are excited about our relationship with Select Health of South Carolina and working together to drive improvements in health care, especially in underserved communities where we know health care disparities exist," said David Pivinski, executive director, Medicare & Medicaid for Quest Diagnostics. "Quest offers convenience and access to high-quality diagnostic information services, and we look forward to empowering better health for First Choice by Select Health and First Choice VIP Care Plus plan members."

First Choice Medicaid health plan members can access a full list of providers and other tools at View Source First Choice VIP Care Plus MMP members can do likewise at View Source Members of both plans may also obtain assistance by calling Member Services at the phone number on the back of their member identification card.