On August 1, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported the positive discussion in and outcome of its End of Phase 1B/2 (EOP1B/2) meeting with the US Food and Drug Administration (FDA) supporting the advancement of Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") to a Phase 3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML) (Press release, Moleculin, AUG 1, 2024, View Source [SID1234645265]). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) will be a global trial, including sites in the US.

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"We thank the FDA’s Divisions of Hematologic Malignancies I and Cardiology and Nephrology, as well as related divisions, for a very constructive EOP1B/2 meeting and for their valuable feedback. Armed with this, we are now able to finalize plans for a pivotal approval pathway in AML," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "Importantly, consistent with the FDA’s recommendations, the adaptive Phase 3 trial will rely solely on CR (complete remission) at day 30 as the primary endpoint versus placebo, a standard we are confident Annamycin will meet and that provides an opportunity for accelerated approval."

Mr. Klemp continued: "We now also have additional confidence that our planned pivotal trial should be able to generate data supportive of a true value inflection point for shareholders in a timely manner. We plan to utilize a double-blind, placebo-controlled design, where the control arm is high dose cytarabine (HiDAC) plus placebo. There is considerable historical data on the use of HiDAC. You can see in this graphic that, compared to this historical data, AnnAraC has already demonstrated more than double the CR rate. The MIRACLE trial will initially focus on 2nd line treatment for R/R AML subjects and then follow-up with treatment for 3rd line R/R AML."

"This approach should also allow us to use this trial for approval in Europe. Based on our discussions with the FDA, we intend to amend our current investigational new drug application or IND to allow dosing above the lifetime maximum allowable dose (LTMAD) for currently prescribed anthracyclines in this trial in the US."

The Company obtained valuable input from the FDA and having resolved a number of key issues, believes that it has significantly de-risked the pathway to approval. The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, is expected to initially utilize an adaptive design whereby the first 75 patients will be randomized to receive HiDAC combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin. At that point, the trial will be unblinded to select the Optimum Dose for Annamycin. For the second half of the trial, approximately 120 additional patients will be randomized to receive either HiDAC plus placebo or HiDAC plus the Optimum Dose of Annamycin. The selection of the Optimum Dose will be based not only on the absence of dose limiting toxicities but also on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative.

Mr. Klemp concluded: "The FDA also wants to see the durability of response (DoR) and overall survival (OS) as secondary endpoints, as well as data for patients beyond 2nd line, which is why our plan includes a follow-on MIRACLE2 trial in 3rd line patients starting once the optimum dose is established in the MIRACLE trial. From a Company perspective, we believe this approach is the best of all worlds. We are not only making the leap into being a Phase 3 company, but our planned approval is also based on a primary endpoint comparing to a control that we are optimistic we can beat with the ability to report unblinded progress after just 75 patients. We are truly excited to launch the MIRACLE trial."

Moleculin Planned Significant Milestones

The Company has established plans for the following milestones:

2H 2024 – Begin contracting with MIRACLE trial sites
Q1 2025 – First subject treated in MIRACLE trial
Mid 2026 – Interim data (n=75) unblinded and Optimum Dose set for MIRACLE trial
2026 – Begin enrollment of 3rd line subjects in MIRACLE2
2027 – Enrollment ends in 2nd line subjects
2028 – Final Data for 2nd line subjects in MIRACLE
2H 2028 – Begin submission of a new drug application (NDA) the treatment of R/R AML for accelerated approval on primary endpoint of CR from MIRACLE
Annamycin currently has Fast Track Status and Orphan Drug Designation from the US Food and Drug Administration for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA). For more information about the ongoing MB-106 Phase 1B/2 trial, visit clinicaltrialsregister.eu and reference EudraCT 2020-005493-10 or clinicaltrials.gov and reference NCT05319587.

On August 1, 2024 Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, reported results for the second quarter ended June 30, 2024 and updated full-year guidance (Press release, LabCorp, AUG 1, 2024, View Source [SID1234645264]).

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"Labcorp delivered strong revenue and EPS growth in the second quarter and has significant momentum as we enter the second half of the year," said Adam Schechter, chairman and CEO of Labcorp. "We expanded our leadership in key therapeutic areas, including oncology, women’s health and neurology, and strengthened our position with customers through acquisitions and innovative digital and data solutions. We will continue driving long-term value by expanding our laboratory and testing solutions, forging new partnerships with health systems, and leveraging science and technology to improve health and improve lives around the world."

Labcorp continued to progress against its growth initiatives:

Received approval for the acquisition of select assets from Invitae, a leading medical genetics company. Through this acquisition, the company will utilize genetic insights to develop new treatments and deliver personalized care in oncology and select rare diseases. The transaction is expected to close in early August.
Subsequent to quarter end, entered into a comprehensive strategic collaboration with Naples Comprehensive Healthcare (NCH) in Southwest Florida to manage the daily operations of NCH’s inpatient lab operations. Separately, Labcorp will begin to serve as the primary lab for NCH’s physician network later this summer.
The company continues to make strides in science, technology, and innovation:

Received FDA approval as a Humanitarian Use Device for its companion diagnostic (CDx) to determine patient eligibility for treatment with BEQVEZ (fidanacogene elaparvovec-dzkt), Pfizer’s recently FDA-approved hemophilia B gene therapy.
Introduced first trimester preeclampsia screening test to determine the risk of developing preeclampsia before 34 weeks of pregnancy. It is the only test of its kind available in the United States and is relevant for all pregnant individuals. With the addition of this test, Labcorp is the only lab that can detect preeclampsia risk across all trimesters.
Launched new strategic service offerings within its precision oncology portfolio to strengthen the company’s leadership as a premier, single-source partner for biopharmaceutical companies. This includes the expanded availability of Labcorp Tissue Complete to Geneva and Shanghai and the addition of OmniSeq INSIGHT circulating tumor DNA into the portfolio of genomic profiling services.
Introduced Labcorp Global Trial Connect, a suite of central laboratory solutions aimed at increasing the speed of clinical trials.
Expanded Labcorp OnDemand with several new tests, including a standard drug, complete drug, comprehensive testosterone, HIV and complete Heart Health.
On July 25, 2024, the company announced a quarterly cash dividend of $0.72 per share of common stock, payable on September 13, 2024, to stockholders of record at the close of business on August 29, 2024. In addition, the Board of Directors approved an increase in share repurchase authorization by $1.0 billion to a total of $1.4 billion.

Consolidated Results

Second Quarter Results

Revenue for the quarter was $3.22 billion, an increase of 6.2% from $3.03 billion in the second quarter of 2023. The increase was due to organic revenue of 3.8%, acquisitions, net of divestitures, of 2.5%, partially offset by foreign currency translation of (0.1%). The 3.8% increase in organic revenue was driven by a 4.5% increase in the company’s organic Base Business, partially offset by a (0.7%) decrease in COVID-19 PCR testing (COVID-19 Testing). Compared to the Base Business last year, Base Business revenue grew 6.9%. Base Business includes Labcorp’s operations except for COVID-19 Testing.

Operating income for the quarter was $294.8 million, or 9.2% of revenue, compared to $266.3 million, or 8.8%, in the second quarter of 2023. The company recorded amortization, restructuring charges, and special items, which together totaled $185.1 million in the quarter, compared to $182.0 million during the same period in 2023. Adjusted operating income (excluding amortization, restructuring charges, and special items) for the quarter was $479.9 million, or 14.9% of revenue, compared to $448.3 million, or 14.8%, in the second quarter of 2023. The increase in operating income and margin was driven by demand and LaunchPad savings, partially offset by personnel costs.

Net earnings from continuing operations for the quarter were $205.6 million compared to $155.2 million in the second quarter of 2023. Diluted EPS from continuing operations were $2.43 in the quarter compared to $1.74 during the same period in 2023. Adjusted EPS (excluding amortization, restructuring charges, and special items) were $3.94 in the quarter compared to $3.42 in the second quarter of 2023.

Operating cash flow from continuing operations for the quarter was $561.1 million compared to $161.5 million in the second quarter of 2023. The increase in operating cash flow was due to cash earnings and working capital. Capital expenditures totaled $128.2 million compared to $103.3 million a year ago. As a result, free cash flow from continuing operations (operating cash flow from continuing operations less capital expenditures) was $432.9 million compared to $58.2 million in the second quarter of 2023.

At the end of the quarter, the company’s cash balance was $265.1 million and total debt was $5.07 billion. During the quarter, the company invested $33.9 million in acquisitions, paid out $60.4 million in dividends, and used $100.0 million for share repurchases.

Year-To-Date Results

Revenue was $6.40 billion, an increase of 5.4% from $6.07 billion in the first six months of 2023. The increase was due to organic revenue of 3.0%, acquisitions, net of divestitures, of 2.1%, and foreign currency translation of 0.2%. The 3.0% increase in organic revenue was driven by a 4.3% increase in the company’s organic Base Business, partially offset by a (1.3)% decrease in COVID-19 Testing. Compared to the Base Business last year, Base Business revenue grew 6.8%.

Operating income was $616.1 million, or 9.6% of revenue, compared to $596.1 million, or 9.8%, in the first six months of 2023. The company recorded amortization, restructuring charges, special items, and impairments, which together totaled $316.6 million in the first six months of 2024 compared to $300.0 million during the same period in 2023. Adjusted operating income (excluding amortization, restructuring charges, special items, and impairments) was $932.7 million, or 14.6% of revenue, compared to $896.1 million, or 14.8%, in the first six months of 2023. The increase in adjusted operating income was driven by organic demand and LaunchPad savings, partially offset by personnel costs.

Net earnings from continuing operations were $433.9 million compared to $363.6 million in the first six months of 2023. Diluted EPS were $5.13 in the first six months of 2024 compared to $4.08 during the same period in 2023. Adjusted EPS (excluding amortization, restructuring charges, special items, and impairments) were $7.62 in the first six months of 2023 compared to $6.88 during the same period in 2023.

Operating cash flow from continuing operations was $531.3 million compared to $347.2 million in the first six months of 2023. The increase in operating cash flow was primarily due to higher cash earnings. Capital expenditures totaled $262.0 million compared to $181.5 million during the same period in 2023. As a result, free cash flow (operating cash flow less capital expenditures) from continuing operations was $269.3 million compared to $165.7 million in the first six months of 2023.

Second Quarter Segment Results

The company’s two segments include Diagnostics Laboratories and Biopharma Laboratory Services (comprised of Central Laboratories and Early Development Research Laboratories). The following segment results exclude amortization, restructuring charges, special items, and unallocated corporate expenses.

Diagnostics Laboratories

Revenue for the quarter was $2.52 billion, an increase of 7.9% from $2.34 billion in the second quarter of 2023. The increase was due to organic growth of 4.7% and acquisitions, net of divestitures, of 3.2%, partially offset by foreign currency translation of (0.1%). The 4.7% increase in organic revenue was due to a 5.6% increase in the Base Business, partially offset by a (0.9%) decrease in COVID-19 Testing. Total Base Business growth compared to the Base Business in the prior year was 8.9%.

Total volume (measured by requisitions) increased by 5.7% as organic volume increased by 2.9%, while acquisitions, net of divestitures increased 2.8%. Organic volume was up due to a 3.4% increase in the Base Business, partially offset by a (0.5%) decrease in COVID-19 Testing. Price/mix increased by 2.1% due to organic Base Business growth of 2.2% and acquisitions of 0.4%, partially offset by COVID-19 Testing of (0.4%). Base Business volume increased 6.3% compared to the Base Business last year. Price/mix was up 2.5% in the Base Business compared to the Base Business last year.

Adjusted operating income for the quarter was $441.5 million, or 17.5% of revenue, compared to $409.7 million, or 17.5%, in the second quarter of 2023. The increase in adjusted operating income was driven by organic demand, acquisitions, and Launchpad savings, partially offset by higher personnel costs.

Biopharma Laboratory Services

Revenue for the quarter was $707.0 million, an increase of 1.1% from $699.0 million in the second quarter of 2023. The increase was due to organic growth of 1.2%, partially offset by foreign currency translation of (0.1%).

Adjusted operating income for the quarter was $107.4 million, or 15.2% of revenue, compared to $104.6 million, or 15.0%, in the second quarter of 2023. Adjusted operating income and margin increased due to organic growth and LaunchPad savings, partially offset by higher personnel costs.

Net orders and net book-to-bill during the trailing twelve months were $2.82 billion and 1.00, respectively. Backlog at the end of the quarter was $7.92 billion, a decrease of (0.6)% compared to last year. The company expects approximately $2.50 billion of its backlog to convert into revenue in the next twelve months. The company expects net orders, net book-to-bill, and backlog to increase in the second half of the year.

Outlook for 2024

Labcorp is updating 2024 full year guidance to reflect its second quarter performance, the acquisition of Invitae, and full year outlook. The following guidance assumes foreign exchange rates effective as of June 30, 2024, for the remainder of the year. Enterprise level guidance includes the estimated impact from currently anticipated capital allocation, including acquisitions, share repurchases and dividends.

(Dollars in billions, except per share data)

Previous

Updated

Invitae Impact

Results

2024 Guidance

2024 Guidance

In Guidance

2023

Low

High

Low

High

at Midpoint

Revenue

Labcorp Enterprise (1)(2)

$12.2

4.8 %

6.4 %

6.4 %

7.5 %

1.0 %

Diagnostics Laboratories

$9.4

4.8 %

6.0 %

6.9 %

7.9 %

1.3 %

Biopharma Laboratory Services (3)

$2.8

3.7 %

5.7 %

3.7 %

5.0 %

Adjusted EPS

$13.56

$14.45

$15.35

$14.30

$14.90

($0.40)

Free Cash Flow from Cont. Ops(4)

$0.89

$1.00

$1.15

$0.85

$1.00

($0.15)

(1) 2024 Guidance includes an impact from foreign currency translation of 0.1%.

(2) Enterprise level revenue is presented net of intersegment transaction eliminations.

(3) 2024 Guidance includes an impact from foreign currency translation of 0.4%.

(4) 2023 Free Cash Flow from continuing operations excluding spin-related items.

Use of Adjusted Measures

The company has provided in this press release and accompanying tables "adjusted" financial information that has not been prepared in accordance with GAAP, including adjusted net income, adjusted EPS (or adjusted net income per share), adjusted operating income, adjusted operating margin, free cash flow, and certain segment information. The company believes these adjusted measures are useful to investors as a supplement to, but not as a substitute for, GAAP measures, in evaluating the company’s operational performance. The company further believes that the use of these non-GAAP financial measures provides an additional tool for investors in evaluating operating results and trends, and growth and shareholder returns, as well as in comparing the company’s financial results with the financial results of other companies. However, the company notes that these adjusted measures may be different from and not directly comparable to the measures presented by other companies. Reconciliations of these non-GAAP measures to the most comparable GAAP measures and an identification of the components that comprise "special items" used for certain adjusted financial information are included in the tables accompanying this press release.

The company today is providing an investor relations presentation with additional information on its business and operations, which is available in the investor relations section of the company’s website at www.Labcorp.com. Analysts and investors are directed to the website to review this supplemental information.

A conference call discussing Labcorp’s quarterly results will be held today at 9:00 a.m. ET and is available by registering at this link, which will provide a dial-in number and unique PIN to access the call. It is recommended that participants join 10 minutes prior to the start of the call, although participants may register and join at any time during the call. A live webcast of Labcorp’s quarterly conference call on August 1, 2024, will be available at the Labcorp Investor Relations website beginning at 9:00 a.m. ET. This webcast will be archived and accessible through July 18, 2025.

On August 1, 2024 Kiromic BioPharma, Inc. (OTCQB: KRBP) ("Kiromic" or the "Company"), reported favorable eight-month follow-up results from the first patient enrolled in its Deltacel-01 Phase 1 clinical trial (Press release, Kiromic, AUG 1, 2024, View Source [SID1234645263]). This trial is evaluating Deltacel (KB-GDT-01), the Company’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with stage 4 metastatic non-small cell lung cancer (NSCLC) who have failed to respond to standard therapies.

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Scans taken eight months post-treatment showed the patient’s tumor size had decreased by 20% compared with the pre-treatment size and no new tumor lesions were detected, which indicate an eight-month progression-free survival. This follows a 13% reduction detected at six months post-treatment, showing a continued favorable progression. This patient is being treated at the Beverly Hills Cancer Center (BHCC).

"We are pleased to announce continued excellent clinical results from our Deltacel-01 trial, with the first patient enrolled demonstrating not only stable disease and continuing to do well, but also a 20% reduction in tumor size at the eight-month post-treatment evaluation. This result is a promising indication of the potential for our novel GDT therapy. We remain dedicated to advancing innovative cancer treatments and are encouraged by the progress we are making toward providing new options for patients," said Pietro Bersani, Chief Executive Officer of Kiromic BioPharma.

Kiromic expects to report additional follow-up results from the fourth and fifth patients in the study in August.

About Deltacel-01

In Kiromic’s open-label Phase 1 clinical trial, titled "Phase 1 Trial Evaluating the Safety and Tolerability of Gamma Delta T Cell Infusions in Combination With Low Dose Radiotherapy in Subjects With Stage 4 Metastatic Non-Small Cell Lung Cancer" (NCT06069570), patients with stage 4 NSCLC will receive two intravenous infusions of Deltacel with four courses of low-dose, localized radiation over a 10-day period. The primary objective of the Deltacel-01 trial is to evaluate safety, while secondary measurements include objective response, progression-free survival, overall survival, time to progression, time to treatment response and disease control rates.

About Deltacel

Deltacel (KB-GDT-01) is an investigational gamma delta T-cell (GDT) therapy currently in the Deltacel-01 Phase 1 trial for the treatment of stage 4 metastatic NSCLC. An allogeneic product consisting of unmodified, donor-derived gamma delta T cells, Deltacel is the leading candidate in Kiromic’s GDT platform. Deltacel is designed to exploit the natural potency of GDT cells to target solid cancers, with an initial clinical focus on NSCLC, which represents about 80% to 85% of all lung cancer cases. Data from two preclinical studies demonstrated Deltacel’s favorable safety and efficacy profile when it was combined with low-dose radiation.

On August 1, 2024 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company"), reported financial results for the second quarter of 2024 (Press release, Ionis Pharmaceuticals, AUG 1, 2024, View Source [SID1234645262]).

"Over the first half of this year, we continued to deliver on our goal to bring a steady cadence of medicines to people with serious diseases. The WAINUA launch for hereditary ATTR polyneuropathy (ATTRv-PN) continues to progress well with AstraZeneca. QALSODY is now approved in the EU, expanding the number of patients who can benefit from the first approved treatment for a genetic form of ALS. And we are well positioned for our first independent launch with olezarsen, which was accepted for Priority Review with a December FDA action date for people with familial chylomicronemia syndrome (FCS), a serious and rare disease with no approved treatments in the U.S. Additionally, we completed enrollment in our Phase 3 olezarsen program for the much larger severe hypertriglyceridemia (sHTG) patient population, keeping us on track for data in the second half of next year. And based on recent positive Phase 3 results, we believe donidalorsen, our second planned independent U.S. launch, is positioned to be a preferred choice for people with hereditary angioedema (HAE)," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We also advanced our next wave of potentially transformational medicines, including announcing plans to independently advance ION582 into a Phase 3 study next year, based on positive data in Angelman syndrome; this program is poised to become the cornerstone of our robust wholly owned neurology pipeline. Our recent achievements, together with multiple upcoming catalysts, position Ionis to deliver next-level value for all stakeholders."

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Second Quarter 2024 Summary Financial Results(1):

Three months ended
June 30,

Six months ended
June 30,

2024

2023

2024

2023

(amounts in millions)

Total revenue

$
225

$
188

$
345

$
319

Operating expenses

$
291

$
279

$
560

$
523

Operating expenses on a non-GAAP basis

$
260

$
252

$
498

$
469

Loss from operations

$
(66
)

$
(91
)

$
(215
)

$
(204
)
Loss from operations on a non-GAAP basis

$
(35
)

$
(64
)

$
(153
)

$
(150
)

(1)
Reconciliation of GAAP to non-GAAP basis contained later in this release.

1
Financial Highlights

•
Revenue increased for the second quarter and first half of 2024 by 20% and 8% compared to the same periods last year, respectively, primarily driven by an increase in R&D revenue reflecting the value Ionis’ pipeline and technology continues to generate

•
Operating expenses increased in the second quarter and first half of 2024 compared to the same periods last year, reflecting continued strategic investments in late-stage development, including WAINUA for ATTR cardiomyopathy and olezarsen for sHTG, and commercialization efforts for WAINUA, olezarsen and donidalorsen

•
Reaffirmed 2024 financial guidance

Recent Marketed Medicines Highlights

•
WAINUA for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated sales of $16 million and $21 million resulting in royalty revenue of $4 million and $5 million in the second quarter and first half of 2024, respectively

•
WAINUA for the treatment of adults with ATTRv-PN approved in Canada

•
SPINRAZA for the treatment of spinal muscular atrophy (SMA) generated global sales of $429 million and $770 million resulting in royalty revenue of $57 million and $95 million in the second quarter and first half of 2024, respectively

•
QALSODY for the treatment of SOD1-ALS granted marketing approval in the EU

Recent Late-Stage Pipeline Highlights

•
Olezarsen achieved multiple clinical and regulatory milestones that support pursuit of two patient populations with urgent unmet need, familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG):

o
FDA accepted the NDA for patients with FCS for Priority Review with a PDUFA date of December 19, 2024

o
Presented positive Phase 3 Balance study data in patients with FCS with a simultaneous publication in the New England Journal of Medicine

o
Opened Expanded Access Program (EAP) for FCS in the U.S.

o
Completed enrollment for all Phase 3 sHTG studies: CORE pivotal study, CORE2 confirmatory pivotal study and ESSENCE supportive exposure study; on track for data across all three studies in H2:2025

o
Presented positive Phase 2b Bridge study data in patients with HTG and sHTG with a simultaneous publication in the New England Journal of Medicine

•
Donidalorsen achieved multiple clinical milestones positioning it to become the first RNA-targeted prophylactic treatment for people with hereditary angioedema (HAE):

o
Preparing to submit NDA

o
Otsuka preparing to submit MAA; expanded Otsuka EU commercial licensing agreement to include Asia Pacific

o
Presented positive Phase 3 OASIS-HAE study data in patients treated every four weeks or every eight weeks with a simultaneous publication in the New England Journal of Medicine

o
Presented positive Phase 3 OASISplus open-label extension study data in patients treated every four weeks or every eight weeks

o
Presented positive Phase 3 OASISplus switch study data in patients previously treated with other prophylactic therapies

•
Zilganersen (GFAP) Phase 3 study for the treatment of patients with Alexander disease fully enrolled; on track for data in 2025

2
•
Bepirovirsen Phase 3 studies for the treatment of patients with chronic hepatitis B (CHB) fully enrolled; on track for data in 2026

Recent Other Pipeline Updates

•
Presented positive Phase 2 data for ION582 (UBE3A), our wholly owned medicine, in patients with Angelman syndrome; preparing for meetings with global regulators ahead of planned Phase 3 study start in H1:2025

•
Presented positive Phase 2 data for ION224 (DGAT2) in patients with metabolic dysfunction-associated steatohepatitis (MASH)

•
Initiated the Phase 1/2 Orbit study of ION356 (PLP1) in patients with Pelizaeus-Merzbacher disease (PMD)

•
Discontinued development of IONIS-FB-LRx for geographic atrophy (GA) and ION541 for amyotrophic lateral sclerosis (ALS) following completion of Phase 2 studies showing favorable safety profiles and good target engagement, but insufficient efficacy to advance into Phase 3 development

Second Quarter 2024 Financial Results

"Ionis is at a critical inflection point. We have achieved important development and regulatory milestones for WAINUA, olezarsen and donidalorsen, all of which have significant potential to help patients in need. In parallel, we continue to advance our next wave of potentially transformational medicines," said Elizabeth L. Hougen, chief financial officer of Ionis. "To drive next-level of value creation for all stakeholders, we remain focused on strategically investing our capital to fully unlock the potential of our promising near-and longer-term portfolio. Our investments are focused on go-to-market preparations for our upcoming planned olezarsen and donidalorsen launches. And with our increased confidence in the potential of WAINUA and olezarsen to address broader patient populations, we are planning additional investments to scale our capabilities in line with the significant potential that these important medicines represent. Additionally, we are investing in our next wave of medicines, including pre-commercialization activities and Phase 3 development for ION582 for Angelman syndrome, which we plan to start in the first half of next year. We expect our investments today and in the years ahead will position Ionis for sustainable growth for years to come."

Revenue

Ionis’ revenue was comprised of the following:

Three months ended

Six months ended

June 30,

June 30,

2024

2023

2024

2023

Revenue:

(amounts in millions)

Commercial revenue:

SPINRAZA royalties

$
57

$
61

$
95

$
111

WAINUA royalties

4

–

5

–

Other commercial revenue:

TEGSEDI and WAYLIVRA revenue, net

8

11

17

17

Licensing and other royalty revenue

3

6

15

18

Total commercial revenue

72

78

132

146

Research and development revenue:

Amortization from upfront payments

35

15

77

29

Milestone payments

53

51

60

74

License fees

38

20

38

20

Other services

15

4

16

6

Collaborative agreement revenue

141

90

191

129

WAINUA joint development revenue

12

20

22

44

Total research and development revenue

153

110

213

173

Total revenue

$
225

$
188

$
345

$
319

3
Commercial revenue in the second quarter and first half of 2024 included a new source of royalty revenue with the launch of WAINUA in the U.S. in late January 2024. Ionis’ commercial revenue in the second quarter and first half of 2024 also included royalties from the net sales of QALSODY, which Biogen launched in the U.S. in the second quarter of 2023 and in the EU in the second quarter of 2024.

R&D revenue in the second quarter and first half of 2024 increased compared to the same periods last year primarily due to the amortization of upfront payments from the new collaborations with Roche and Novartis that Ionis entered into during the second half of last year. In addition, license fees increased year over year as a result of new collaborations Ionis entered into during the second quarter of 2024, including the expanded donidalorsen licensing agreement with Otsuka, which now includes the Asia-Pacific region in addition to Europe. These increases were partially offset by the decrease in WAINUA joint development revenue, which decreased as development activities relating to ATTRv-PN wound down with the launch of WAINUA for this indication.

Operating Expenses

Ionis’ operating expenses increased in the second quarter and first half of 2024 compared to the same periods in 2023, consistent with expectations. SG&A expenses increased year over year primarily due to the launch of WAINUA in the U.S. and launch preparation activities for olezarsen and donidalorsen, including establishing the field team for olezarsen. R&D expenses decreased in the second quarter and were essentially flat in the first half of 2024 compared to the same periods last year as several late-stage studies have ended.

Balance Sheet

As of June 30, 2024, Ionis’ cash, cash equivalents and short-term investments decreased to $2.1 billion compared to $2.3 billion at December 31, 2023. The Company plans to continue deploying its capital resources toward growth opportunities, and as previously guided, projects to end 2024 with $1.7 billion in cash, cash equivalents and short-term investments. Ionis’ working capital also decreased over the same period primarily due to the Company’s lower cash and short-term investments balance. We expect to make increased strategic investments in the years ahead, with a focus on late-stage programs, wholly owned assets, and our next wave of innovative medicines.

Webcast

Management will host a conference call and webcast to discuss Ionis’ second quarter 2024 results at 11:30 a.m. Eastern time on Thursday, August 1, 2024. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company’s second quarter 2024 earnings slides click here.

For more information about SPINRAZA and QALSODY, visit View Source and View Source, respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s).

INDICATION for WAINUA (eplontersen)
WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

On August 1, 2024 Instil Bio, Inc. (Nasdaq: TIL, "Instil") and ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (HKEX Code: 1541.HK, "ImmuneOnco"), reported a definitive agreement pursuant to which Instil is in-licensing ex-China development and commercial rights to ImmueOnco’s proprietary PD-L1xVEGF bispecific antibody, IMM2510, as well as its next-generation anti-CTLA-4 antibody, IMM27M (Press release, Instil Bio, AUG 1, 2024, View Source [SID1234645261]).

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IMM2510 is a novel, potentially best-in-class bispecific antibody consisting of an anti-PD-L1 antibody fused to a vascular endothelial growth factor (VEGF) receptor "trap" which binds VEGF. IMM2510 is differentiated from other PD(L)1xVEGF antibodies by its ability to bind multiple VEGF receptor ligands beyond VEGF-A, a smaller molecular weight allowing for potentially better tumor penetration, and enhanced antibody-dependent cellular cytotoxicity (ADCC) designed to improve tumor killing. IMM2510 has completed a dose-escalation clinical trial for advanced solid tumors and demonstrated multiple responses including patients with squamous non-small cell lung cancer (NSCLC) who previously failed PD-1 inhibitors.

IMM27M is a next-generation anti-CTLA-4 antibody with enhanced ADCC activity, which has been designed to promote intratumoral regulatory T cell depletion to enhance the efficacy and reduce the toxicity associated with first-generation anti-CTLA-4 antibodies. IMM27M has completed a dose-escalation clinical trial demonstrating anti-tumor activity in patients with advanced solid tumors and has entered combination studies with IMM2510 in China in July 2024.

Terms of License and Collaboration Agreement
Under the terms of the agreement, a wholly owned subsidiary of Instil will receive global development and commercialization rights for IMM2510 and IMM27M outside of Greater China, while ImmuneOnco will retain development and commercialization rights in Greater China including Taiwan, Macau, and Hong Kong. ImmuneOnco will receive an upfront payment and potential near-term payments of up to $50 million as well as potential additional development, regulatory, and commercial milestones exceeding $2 billion plus single digit to low double-digit percentage royalties on global ex-China sales.