On August 1, 2024 ARCA biopharma, Inc. (Nasdaq: ABIO), (the "Company") a biopharmaceutical company applying a precision medicine approach to developing genetically targeted therapies for cardiovascular diseases, reported second quarter 2024 financial results and provided a corporate update (Press release, Arca biopharma, AUG 1, 2024, View Source [SID1234646051]).

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In April 2022, ARCA established a Special Committee of the board of directors (the "Board") of ARCA to conduct a comprehensive review of strategic alternatives. As part of the strategic review process, the Company explored potential strategic alternatives that included, without limitation, an acquisition, merger, business combination or other transactions. The Company has and is continuing to explore strategic alternatives related to its product candidates and related assets, including, without limitation, licensing transactions and asset sales.

On April 3, 2024, following a comprehensive review of strategic alternatives, the Company, Atlas Merger Sub Corp., a Delaware corporation and a wholly-owned subsidiary of ARCA ("Merger Sub I"), Atlas Merger Sub II LLC, a Delaware limited liability company and a wholly-owned subsidiary of ARCA ("Merger Sub II") and Oruka Therapeutics, Inc., a Delaware corporation ("Oruka"), entered into an Agreement and Plan of Merger and Reorganization (the "Merger Agreement"), pursuant to which, among other matters, and subject to the satisfaction or waiver of the conditions set forth in the Merger Agreement, Merger Sub I will merge with and into Oruka, with Oruka continuing as a wholly owned subsidiary of ARCA and the surviving corporation of such merger (the "First Merger") and as part of the same overall transaction, the surviving corporation in the First Merger will merge with and into Merger Sub II with Merger Sub II continuing as a wholly owned subsidiary of ARCA and the surviving entity of such merger (the "Second Merger" and together with the First Merger, the "Merger"). The Merger is intended to qualify for federal income tax purposes as a tax-free reorganization under the provisions of Section 368(a) of the Internal Revenue Code of 1986, as amended.

Additional descriptions about the Merger Agreement and related agreements were previously disclosed on a Current Report on Form 8-K filed with the U.S. Securities and Exchange Commission (the "SEC") on April 3, 2024. In connection with the proposed Merger, the Company has filed relevant materials with the SEC, including a registration statement on Form S-4 that contains a definitive proxy statement and prospectus of the Company.

In connection with the Merger, the Company will dispose of (or is in the process of disposing of) its legacy technology and intellectual property, including those related to Gencaro (bucindolol hydrochloride) and Recombinant Nematode Anticoagulant Protein c2 ("rNAPc2"). Any such disposal of legacy technology and intellectual property will be contingent upon obtaining stockholder approval for the Merger and is expected to occur immediately prior to or concurrently with the closing of the Merger. In the event that the Company shall enter into an agreement for any such sale or other disposition of its legacy assets at or prior to the closing of the Merger, the net proceeds received at or prior to the closing of the Merger will be included in the calculation of the net cash of the Company as of the closing.

The Company’s future operations are highly dependent on the success of the Merger and there can be no assurances that the Merger will be successfully consummated. In the event that the Company does not complete the Merger, the Company may explore strategic alternatives, including, without limitation, another strategic transaction and/or pursue a dissolution and liquidation of the Company.

Second Quarter 2024 Summary Financial Results

Cash and cash equivalents were $33.3 million as of June 30, 2024, compared to $37.4 million as of December 31, 2023. ARCA believes that its current cash and cash equivalents, consisting primarily of money market funds, will be sufficient to fund its operations through the end of 2025. Our future viability beyond that point is dependent on the results of the strategic review process and our ability to raise additional capital to fund our operations. We expect to continue to incur costs and expenditures in connection with the process of evaluating strategic alternatives. There can be no assurance, however, that we will be able to successfully consummate any particular strategic transaction, including the Merger. The process of continuing to evaluate these strategic options may be very costly, time-consuming and complex and we have incurred, and may in the future incur, significant costs related to this continued evaluation, such as legal, accounting and advisory fees and expenses and other related charges.

General and administrative (G&A) expenses were $3.0 million for the quarter ended June 30, 2024, compared to $1.7 million for the corresponding period in 2023, an increase of approximately $1.3 million. During the three months ended June 30, 2024, we recorded $370,000 for one-time termination benefits related to the separation of Dr. Michael Bristow, the former Chief Executive Officer of ARCA, effective April 3, 2024. The increase for the three month period was primarily the result of a $0.9 million increase in professional fees primarily related to the Merger Agreement discussed above and $0.4 million higher one-time termination benefits from the termination discussed above in 2024. G&A expenses in 2024 are expected to be higher than those in 2023 as we incur professional fees related to the Merger Agreement discussed above and maintain administrative activities to support our ongoing operations. We expect to incur significant costs related to our exploration of strategic alternatives and the Merger, including legal, accounting and advisory expenses and other related charges.

Research and development (R&D) expenses were $0.1 million for the quarter ended June 30, 2024, compared to $0.3 million for the corresponding period in 2023. Of the $0.2 million decrease in R&D expenses in the second quarter of 2024 as compared to the second quarter of 2023, $0.1 million was primarily related to decreased headcount and $0.1 million was primarily related to the unrestricted research grants with ARCA’s former President and Chief Executive Officer’s academic research laboratory at the University of Colorado. There was no expense under these arrangements for the three months ended June 30, 2024. Total expense under these arrangements for the three months ended June 30, 2023 was $0.1 million. In December 2023, the Company made a payment of $125,000 for the grant period July 2022 through December 2023 under these arrangements. As discussed above, the former President and Chief Executive Officer resigned in April 2024. R&D expense in 2024 is expected to be lower than 2023 while we explore strategic alternatives. Should we resume clinical trials of product candidates, we expect research and development costs to increase significantly for the foreseeable future as our product candidate development programs progress.

Total operating expenses for the quarter ended June 30, 2024 were $3.1 million compared to $2.0 million for the second quarter of 2023.

Net loss for the quarter ended June 30, 2024 was $2.7 million, or $0.18 per basic and diluted share, compared to $1.5 million, or $0.10 per basic and diluted share in the second quarter of 2023.

On August 1, 2024 Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, gene insertion, and gene excision, reported financial results for the second quarter ended June 30, 2024 and provided a business update (Press release, Precision Biosciences, AUG 1, 2024, View Source [SID1234645240]).

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"During the first half of 2024 we have made excellent progress against our key priorities. We rapidly advanced PBGENE-HBV toward planned investigational new drug (IND) submission and/or clinical trial application (CTA) in 2024. We believe we are in a strong position to advance our first wholly owned in vivo gene editing program into the clinic. PBGENE-HBV is expected to be the first and only potentially curative gene editing program to enter the clinic that is specifically designed to provide a functional cure for chronic Hepatitis B by eliminating the root source of viral replication. I’m proud of our team’s operational progress this year, including nearing completion of final toxicology studies, production of final clinical trial material, onboarding global clinical study sites in multiple countries to conduct the Phase 1 trial, and adding world-class clinicians to our Hepatitis Scientific Advisory Board," said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences.

"While advancing PBGENE-HBV as our first operational priority in 2024, we have also made steady progress on our second wholly owned program PBGENE-PMM for 3243 mutated (m.3243) mitochondrial disease, which is targeted for IND and/or CTA filing in 2025."

"As we enter the second half of the year, we are sufficiently capitalized based on our expected cash runway as a result of multiple business development deals combined with a $40 million equity raise to propel our two wholly owned programs to Phase 1 data readouts in 2025 and 2026," emphasized Mr. Amoroso.

Wholly Owned Portfolio

PBGENE-HBV (Viral Elimination Program): Precision is developing PBGENE-HBV for the treatment of patients with chronic Hepatitis B. Currently, it is estimated that approximately 300 million people worldwide are afflicted with chronic Hepatitis B. PBGENE-HBV is expected to be the first and only potentially curative gene editing program to enter the clinic that is specifically designed to eliminate cccDNA and inactivate integrated HBV DNA.

In June 2024, Precision participated in a panel discussion on the application of gene editing to the treatment of chronic Hepatitis B during the HBV Forum and presented new preclinical safety data for PBGENE-HBV at the European Association for the Study of the Liver. This data further supported the ability of PBGENE-HBV to specifically target and cut HBV DNA, leading to the elimination of cccDNA and integrated HBV DNA. The data also demonstrated a lack of detectable off-target editing for PBGENE-HBV at therapeutically relevant doses, including no editing-associated translocations in HBV infected primary human hepatocytes. Importantly, new non-human primate data showed that PBGENE-HBV was well-tolerated across multiple dose administrations. PBGENE-HBV is advancing through final toxicology studies and drug for the planned Phase 1 clinical trial has been manufactured. Precision expects to submit an IND and/or CTA for this program in 2024 and plans to provide an additional program update later this year.

PBGENE-PMM (Mutant Mitochondrial DNA Elimination Program): PBGENE-PMM is a first of its kind potential treatment for m.3243-mitochondrial disease designed to target mutant mitochondrial DNA while having no adverse impact on wild type (normal) mitochondrial DNA. Mitochondrial diseases are the most common hereditary metabolic disorder in the world. The m.3243 mitochondrial disease population that the program intends to address is large, affecting approximately 20,000 people in the US alone. The highly specific ARCUS nuclease is designed to shift heteroplasmy by editing and eliminating mutant mitochondrial DNA while allowing wild type mitochondrial DNA to repopulate in the mitochondria, thus improving cellular function. Unlike CRISPR/Cas, base editors, and prime editors, ARCUS single-component nucleases do not require a guide RNA and are therefore differentiated amongst gene editing modalities due to their ability to penetrate mitochondrial membranes.

In June 2024, Precision presented additional data from the PBGENE-PMM program at the United Mitochondrial Disease Foundation Mitochondrial Medicine 2024 Conference. The presentation highlighted the ability of PBGENE-PMM to localize exclusively to mitochondria, avoiding any detectable off-target editing in the nuclear genome, while generating substantial shifts in heteroplasmy and improvements in mitochondrial function. The Company anticipates filing an IND and/or CTA for this program in 2025.

Wholly Owned Portfolio – Under Assessment

In July 2024, Precision regained control of three programs developed under its collaboration with Prevail Therapeutics Inc. The Company has received inbound interest from potential partners regarding these programs and is in the process of conducting a portfolio assessment for these returned programs for internal development and/or development through new partners and expects to provide an update as decisions are finalized. These programs include:

PBGENE-DMD – novel gene excision approach for treatment of Duchenne Muscular Dystrophy utilizing a pair of ARCUS nucleases, delivered by a single adeno-associated virus (AAV), that are designed to excise an approximately 500,000 base pair mutation "hot spot" region from the dystrophin gene to restore a functionally competent variant of the native dystrophin protein. We believe this approach is unique when compared with microdystrophin treatment and is the first in class gene editing application for Duchenne Muscular Dystrophy.
PBGENE-LIVER – liver target for gene insertion with data demonstrating that ARCUS achieved 40% to 45% high efficiency and durable gene insertion at 1- and 3-months in nondividing cells in adult nonhuman primates (NHPs), the most challenging context for gene insertion. To our knowledge, ARCUS is the only gene editor presented at a conference showing high efficiency gene insertion in non-dividing cells in NHPs. This opens therapeutic application for both pediatric patients whose cells divide quickly, as well as adult patients whose cells divide much less frequently than pediatric patients.
PBGENE-CNS – gene editing program targeting neurons to address a disease of the central nervous system. Precision is the first to demonstrate successful in vivo editing of neurons in both mice and NHPs. This remains a very attractive program for Precision or for partners focused on neurodegenerative diseases.
Partnered Programs:

iECURE-OTC (Gene Insertion Program for OTC deficiency): Led by iECURE, ECUR-506 is the first ARCUS-mediated in vivo gene editing program to advance into the clinic following regulatory approvals in the US, the United Kingdom, and Australia for initiation of the OTC-HOPE study. The OTC-HOPE study is a first-in-human Phase 1/2 trial evaluating ECUR-506 as a potential treatment for neonatal onset ornithine transcarbamylase (OTC) deficiency and has begun recruiting patients at two sites in the United Kingdom. In May 2024, iECURE announced that it had received Fast Track designation from the FDA for ECUR-506 and expects initial data from this trial to be available in late 2024 or in 2025.

PBGENE-NVS (Gene Insertion Program for Sickle Cell Anemia and Beta Thalassemia): Precision continues to advance its gene editing program with Novartis to develop a custom ARCUS nuclease for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia. The collaborative intent is to insert, in vivo, a therapeutic transgene as a potential one-time transformative treatment. We believe this is the only in vivo approach in development that can be administered directly to the patient to overcome disparities in patient treatment access with other therapeutic technologies, including those that are targeting an ex vivo gene editing approach.

Corporate Updates

Expansion of Hepatitis Scientific Advisory Board to include world-class clinical investigators: In June 2024, Precision announced the appointment of Mark Sulkowski, M.D. and Jordan Feld, M.D., M.P.H. to its Hepatitis Scientific Advisory Board. They join inaugural member Raymond Schinazi, Ph.D., DSc, to provide counsel and deepen the Company’s scientific and clinical expertise ahead of Precision’s anticipated IND and/or CTA submission for PBGENE-HBV.

Addition to the Russell Microcap Index: As of the close of U.S. markets on June 28, 2024, Precision BioSciences was added to the Russell Microcap Index as part of the index’s annual reconstitution.

Common Stock purchase by members of management for $300,000: In May 2024, Precision entered into a definitive subscription agreement, pursuant to which the Company issued and sold in a non-brokered private placement to members of its senior leadership team, including the Chief Executive Officer, 25,000 shares of its common stock at a price of $12.00 per share, representing a 13.5% premium to the closing price of its common stock immediately preceding the signing of the subscription agreement, for an aggregate amount of $300,000.

Banc of California Loan and Security Agreement: On July 31, 2024, the Company entered into an amended and restated loan and security agreement (the 2024 Loan and Security Agreement) with Banc of California (formerly known as Pacific Western Bank) pursuant to which Banc of California provided the Company with a term loan with a principal amount of $22.5 million. The proceeds from the term loan were used to repay the $22.5 million outstanding principal balance under the prior revolving line of credit with Banc of California, and pursuant to the terms of the 2024 Loan and Security Agreement, the revolving line of credit was terminated. The maturity date under the 2024 Loan and Security Agreement is June 30, 2027. The term loan bears interest at an annual rate equal to the greater of (i) 1.50% below the Prime Rate then in effect or (ii) 4.50%.

Quarter Ended June 30, 2024 Financial Results:

Cash and Cash Equivalents: As of June 30, 2024, Precision had approximately $123.6 million in cash and cash equivalents. Existing cash and cash equivalents, upfront and potential near-term cash from CAR T transactions, along with expected operational receipts, continued fiscal and operating discipline, availability of Precision’s at-the-market (ATM) facility, and available credit are expected to extend Precision’s cash runway into the second half of 2026.

Revenues: Total revenues for the quarter ended June 30, 2024 were $49.9 million, as compared to $19.8 million for the same period in 2023. The increase of $30.1 million in revenue during the quarter ended June 30, 2024 was primarily the result of recognizing deferred revenue related to the termination of the amended and restated development and license agreement with Prevail Therapeutics.

Research and Development Expenses: Research and development expenses were $17.2 million for the quarter ended June 30, 2024, as compared to $13.1 million for the same period in 2023. The increase of $4.1 million was primarily due to an increase in external development costs for the PBGENE-HBV and PBGENE-PMM programs as they continue to advance towards the clinic.

General and Administrative Expenses: General and administrative expenses were $8.5 million for the quarter ended June 30, 2024, as compared to $9.8 million for the same period in 2023. The decrease of $1.3 million was primarily due to decreased employee and share-based compensation expense from a decrease in headcount.

Net Income from Continuing Operations: Net income from continuing operations was $32.7 million for the quarter ended June 30, 2024, inclusive of a $7.8 million non-cash gain on the fair value of our warrant liability which does not impact our cash runway, as compared to a net loss from continuing operations of $11.9 million, for the same period in 2023. The improvement was primarily related to recognition of deferred revenue from termination of the Prevail Agreement as well as the non-cash gain related to the fair value adjustments of our warrant liability.

Net Income: Net income was $32.7 million, or $4.70 per share (basic) and $4.67 per share (diluted), for the quarter ended June 30, 2024, as compared to a net loss of $11.9 million, or $(3.13) per share (basic and diluted), for the same period in 2023.

Shares: Basic and diluted weighted-average common shares outstanding for the second quarter of 2024 were 6,966,680 and 7,011,630, respectively, compared to 3,803,083 (basic and diluted) for the same period in 2023.

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 Immunovia (Nasdaq Stockholm: IMMNOV), the pancreatic cancer diagnostics company, reported enhanced performance for its next-generation test for detecting stage 1 and 2 pancreatic ductal adenocarcinomas (PDAC) in high-risk individuals, which are potentially curable with surgery and modern treatments (Press release, Immunovia, AUG 1, 2024, View Source [SID1234645280]).

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On 22 April 2024, Immunovia announced positive results from the initial model-development study for its next-generation pancreatic cancer detection test. Subsequent efforts to increase test performance have now enhanced test accuracy, substantially improving the sensitivity of the next-generation test to 85% with a specificity of 98% in detecting stage 1 and 2 PDAC.

A sensitivity of 85% means the new test is capable of detecting pancreatic cancer in approximately 6 out of every 7 people with early-stage disease. Specificity of 98% means this new test should return a false positive result just once for every 50 people tested who do not have pancreatic cancer. Test performance was refined by leveraging additional samples with more complete and detailed clinical information and through more sophisticated statistical modeling. Test performance was independently confirmed by ACOMED, a statistical analysis firm with deep expertise in diagnostic studies.

In this study, Immunovia’s next-generation test outperformed the sensitivity of CA19-9, a commonly used pancreatic cancer biomarker, by 20 percentage points (85% vs 65%, respectively, p<0.001).

In 294 patients aged 65 years and older, the next-generation test achieved 91% sensitivity and 98% specificity. Results in this group are particularly important since the average age of PDAC diagnosis is near 70 years.

"Results from this study serve as a promising step that a simple blood test may detect pancreatic cancer early in at-risk patients who have limited early detection options," said Randall Brand, MD, gastroenterologist, professor of medicine at the University of Pittsburgh School of Medicine, and director of the UPMC GI Malignancy Early Detection, Diagnosis and Prevention Program. Dr. Brand was an advisor on the study.

"We have now completed research and development efforts for our next-generation test and are thrilled with the accuracy of the test," said Jeff Borcherding, CEO of Immunovia. "This is a critical milestone for the company. Our next-generation test shows tremendous promise for improving pancreatic cancer surveillance with a highly accurate, convenient and affordable test. We are very optimistic about the clinical impact of the test when we launch in the U.S. in 2025."

The model development study included 624 patient samples from 13 different clinical sites. 129 samples were from patients with stage 1 or 2 PDAC and 495 control samples came predominantly from people at high-risk for hereditary and/or familial pancreatic cancer, and also included people with pancreatic cysts, diabetics, and healthy individuals.

The Company will submit these results shortly for peer-reviewed publication as well as for presentation at medical conferences. A large, independent clinical validation study will be conducted in the fourth quarter of 2024 to confirm the accuracy of the Immunovia test in a larger set of patient samples. Immunovia remains on track to launch the new test in the United States in 2025.

On July 31, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported its financial results for the quarter ended June 30, 2024, and provided a business update (Press release, Syndax, AUG 1, 2024, View Source [SID1234645241]).

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"This is an exciting time for Syndax as we transition to a commercial stage company," said Michael A. Metzger, Chief Executive Officer. "We’ve made significant progress advancing our pipeline this quarter, including the presentation of updated revumenib combination data from the BEAT AML and AUGMENT-102 trials and additional axatilimab data from the AGAVE-201 trial at EHA (Free EHA Whitepaper). We are excited to continue building on this momentum as we look ahead to the approval of both first-in-class assets and sharing pivotal AUGMENT-101 data in mNPM1 AML this year."

Recent Pipeline Progress and Anticipated Milestones

Revumenib

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The New Drug Application (NDA) for revumenib, a highly selective menin inhibitor, for the treatment of adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia was granted Priority Review and is being reviewed under the U.S. FDA’s Real-Time Oncology Review (RTOR) Program. On July 29, 2024, the Company announced that the FDA extended the Prescription Drug User Fee Act (PDUFA) target action date for the revumenib NDA from September 26, 2024 to December 26, 2024 to provide FDA additional time to conduct a full review of supplemental information provided by the Company in response to the FDA’s requests.
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The Company expects to report topline data from the AUGMENT-101 pivotal trial cohort of patients with R/R mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML) in the fourth quarter of 2024. Positive data could support a supplemental NDA (sNDA) filing for revumenib in R/R mNPM1 AML in the first half of 2025.
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Multiple Phase 1 combination trials of revumenib in mNPM1 and KMT2Ar acute leukemias are ongoing across the treatment landscape. These trials include:

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BEAT AML: Evaluating the combination of revumenib with venetoclax and azacitidine in front-line AML patients. This trial is being conducted as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial. The Company presented updated positive data from the trial at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress, showing a 96% (23 of 24 pts) composite complete remission (CRc) rate in patients with newly diagnosed mNPM1 or KMT2Ar AML. The BEAT AML trial is expanding to validate the recommended Phase 2 dose of the combination of revumenib with venetoclax and azacitidine.
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SAVE: Evaluating the all-oral combination of revumenib with venetoclax and decitabine/cedazuridine in R/R AML or mixed phenotype acute leukemias. The trial is being conducted by investigators from MD Anderson Cancer Center. The trial is expanding to validate the recommended Phase 2 doses, with additional data expected in the second half of 2024.
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Intensive chemotherapy: Evaluating the combination of revumenib with intensive chemotherapy (7+3) followed by revumenib maintenance treatment in newly diagnosed patients with mNPM1 or KMT2Ar acute leukemias. The Phase 1 trial is designed to identify the recommended Phase 2 dose for this combination to support further development.

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The Company plans to initiate a pivotal trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed mNPM1 or KMT2Ar acute leukemia patients unfit to receive intensive chemotherapy by year-end 2024.
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The Company presented updated data from the AUGMENT-102 trial evaluating the combination of revumenib with fludarabine and cytarabine in patients with R/R acute leukemias at the EHA (Free EHA Whitepaper) 2024 Congress. Treatment with the combination in R/R mNPM1, NUP98-rearranged (NUP98r) or KMT2Ar acute leukemia patients resulted in a 52% (14 of 27 pts) CRc rate.
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The Company announced that it advanced into the Phase 1b portion of its Phase 1/2 proof-of-concept trial of revumenib in patients with R/R metastatic microsatellite stable (MSS) colorectal cancer (CRC) based on initial data from the Phase 1a portion of the trial.

Axatilimab

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The Biologics License Application (BLA) for axatilimab, an anti-CSF-1R antibody, for patients with chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy, is under FDA Priority Review with a PDUFA action date of August 28, 2024.
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Enrollment is ongoing in a 26-week randomized, double-blinded, placebo-controlled Phase 2 trial of axatilimab on top of standard of care in patients with idiopathic pulmonary fibrosis (IPF).

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The Company’s partner, Incyte, plans to initiate two combination trials with axatilimab in earlier lines of treatment for chronic GVHD in the second half of 2024, including a Phase 2 combination trial with ruxolitinib and a Phase 3 combination trial with steroids.
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The Company presented additional positive data from the AGAVE-201 pivotal trial evaluating axatilimab monotherapy in patients with refractory chronic GVHD at the EHA (Free EHA Whitepaper) 2024 Congress. Responses were noted in all fibrosis-dominant organs and the clinical activity was supported by clinician-reported and patient-reported changes in organ-specific symptoms, such as improvements in swallowing, shortness of breath, skin and joints, and sclerotic skin

Corporate Updates

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In May 2024, the Companyannounced the appointment of Aleksandra Rizo, M.D., Ph.D to its Board of Directors. Dr. Rizo has extensive clinical development experience and a track record of successfully leading the development of several oncology drugs from discovery through commercialization.

Second Quarter 2024 Financial Results

As of June 30, 2024, Syndax had cash, cash equivalents, and short and long-term investments of $454.6 million and 85.3 million common shares and prefunded warrants outstanding.

Second quarter 2024 research and development expenses increased to $48.7 million from $34.8 million for the comparable prior year period. The increase was primarily due to greater clinical development expenses, higher pre-commercial manufacturing costs, and increased employee-related expenses and professional fees.

Second quarter 2024 selling, general and administrative expenses increased to $29.1 million from $14.9 million for the comparable prior year period. The increase was driven by a greater level of pre-commercialization activities for revumenib and axatilimab as well as higher employee-related expenses and professional fees.

For the three months ended June 30, 2024, Syndax reported a net loss attributable to common stockholders of $68.1 million, or $0.80 per share, compared to a net loss attributable to common stockholders of $44.6 million, or $0.64 per share, for the comparable prior year period.

Financial Guidance

For the third quarter of 2024, the Company expects research and development expenses to be $70 to $75 million and total operating expenses to be $105 to $110 million. For the full year of 2024, the Company continues to expect research and development expenses to be $240 to $260 million and total operating expenses to be $355 to $375 million, which includes milestone payments that the Company expects to become due as well as an estimated $43 million in non-cash stock compensation expense.

The Company continues to believe it has sufficient capital to fund its research, clinical development and commercial operations through 2026.

Conference Call and Webcast

In connection with the earnings release, Syndax’s management team will host a conference call and live audio webcast at 4:30 p.m. ET today, Thursday, August 1, 2024.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website. Alternatively, the conference call may be accessed through the following:

Conference ID: Syndax2Q24
Domestic Dial-in Number: 800-590-8290
International Dial-in Number: 240-690-8800
Live webcast: https://www.veracast.com/webcasts/syndax/events/SNDX2Q24.cfm

For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2Ar, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including acute lymphoid leukemia (ALL) and AML, and mNPM1 AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation for the treatment of AML and ALL by the FDA and for the treatment of AML by the European Commission, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

About Axatilimab

Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In pre-clinical models, inhibition of signaling through the CSF-1 receptor has been shown to reduce the number of disease-mediating macrophages along with their monocyte precursors, which has been shown to play a key role in the fibrotic disease process underlying diseases such as chronic GVHD and IPF. Positive topline results from the Phase 2 AGAVE-201 trial showing the trial met its primary endpoint were recently presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and Phase 1/2 data of axatilimab in chronic GVHD were published in the Journal of Clinical Oncology. Axatilimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with chronic GVHD and IPF. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab. Syndax has exercised its option under the collaboration agreement to co-commercialize axatilimab in the U.S. and will provide 30% of the commercial effort. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.

About the Real-Time Oncology Review Program (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source