On August 5, 2024 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the second quarter ended June 30, 2024 (Press release, CRISPR Therapeutics, AUG 5, 2024, View Source [SID1234645336]).

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"In addition to the continued momentum of CASGEVY’s launch, we are making significant progress across the rest of our pipeline," said Samarth Kulkarni, Ph.D., Chief Executive Officer and Chairman of CRISPR Therapeutics. "We continue to advance our next generation CD19-directed CAR T cell program, CTX112, which has the potential to be best-in-class in both oncology and autoimmune indications. We have opened the clinical trial for CTX131 in hematologic malignancies, and continue to dose-escalate with our in vivo directed programs, CTX310 and CTX320. We are making outstanding progress across our early stage discovery efforts and are well-positioned to realize our mission of bringing multiple transformative medicines to patients in need."

Recent Highlights and Outlook

Hemoglobinopathies and CASGEVY (exagamglogene autotemcel [exa-cel])

CRISPR Therapeutics has two next generation approaches with the potential to significantly expand the addressable population with SCD and TDT. The Company continues to advance its internally developed targeted conditioning program, an anti-CD117 (c-Kit) antibody-drug conjugate (ADC), through preclinical studies. Additionally, the Company has ongoing research efforts to enable in vivo editing of hematopoietic stem cells. This work could obviate the need for conditioning altogether, expand geographic reach, and enable the treatment of multiple additional other diseases beyond SCD and TDT.
Enrollment has been completed in two global Phase 3 studies of CASGEVY in people 5 to 11 years of age with SCD or TDT and the trials are ongoing.
In June, positive long-term data from CLIMB-111, CLIMB-121 and the long-term follow-up study of CASGEVY were presented at the 2024 Annual European Hematology Association (EHA) (Free EHA Whitepaper) Congress. These long-term data from more than 100 patients dosed with CASGEVY, with the longest follow-up of more than five years, confirm the transformative, consistent, and durable clinical benefits of CASGEVY over time.
The French National Authority for Health (HAS) approved Vertex’s request for the implementation of an early access program (EAP) for the use of CASGEVY in indicated patients with SCD. HAS previously approved the implementation of an EAP for CASGEVY in indicated patients with TDT in the first quarter of 2024.
As of mid-July, more than 35 authorized treatment centers (ATCs) have been activated globally, including centers in all regions where CASGEVY is approved, and approximately 20 patients have had cells collected across all regions.
CASGEVY is approved in the U.S., Great Britain, the European Union (EU), the Kingdom of Saudi Arabia (KSA), and the Kingdom of Bahrain (Bahrain) for the treatment of both sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), and launches are ongoing. Regulatory submissions for CASGEVY have been completed in both SCD and TDT in Switzerland and Canada where it received Priority Review. CASGEVY is the first therapy to emerge from a strategic partnership between CRISPR Therapeutics and Vertex Pharmaceuticals established in 2015. As part of an amendment to the collaboration agreement in 2021, Vertex now leads global development, manufacturing, regulatory and commercialization of CASGEVY with support from CRISPR Therapeutics.
Immuno-Oncology and Autoimmune Diseases

CTX131 is currently in an ongoing clinical trial in solid tumors. In addition, the Company has opened a clinical trial for CTX131 in hematologic malignancies including T cell lymphomas (TCL). Allogeneic CAR T approaches for TCL may have greater potential to meet the unmet need in this patient population given the patients’ own T cells are not suitable for autologous manufacturing.
CRISPR Therapeutics opened a clinical trial for CTX112 in systemic lupus erythematosus (SLE), with the potential to expand into additional autoimmune indications in the future. Early clinical studies conducted by third parties have shown that CD19-directed autologous CAR T therapy can produce long-lasting remissions in multiple autoimmune indications by deeply depleting B cells. The Company’s first generation allogeneic CD19-directed CAR T program has demonstrated effective depletion of B cells in oncology settings, which supports the potential for CTX112 in autoimmune diseases.
CTX112 is being developed for both oncology and autoimmune indications. In oncology settings, CTX112 is in a Phase 1/2 trial for CD19 positive relapsed or refractory B-cell malignancies, and the Company expects to report preliminary clinical data this year.
CRISPR Therapeutics’ next generation allogeneic CAR T candidates reflect the Company’s mission of innovating continuously to bring potentially transformative medicines to patients as quickly as possible. Clinical trials are ongoing for the Company’s next generation CAR T product candidates, CTX112 and CTX131, targeting CD19 and CD70, respectively, across multiple indications. CTX112 and CTX131 both contain novel potency edits which can lead to significantly higher CAR T cell expansion and cytotoxicity, potentially representing best-in-class allogeneic CAR T products for these targets.
In Vivo

CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) platform for the delivery of CRISPR/Cas9 to the liver. The first two in vivo programs utilizing this proprietary platform, CTX310 and CTX320, are directed towards validated therapeutic targets associated with cardiovascular disease.
CTX310 is currently in an ongoing Phase 1 trial targeting ANGPTL3 in patients with homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (SHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias. Natural loss-of-function mutations in ANGPTL3 are associated with reduced low-density lipoprotein (LDL-C), triglycerides (TG) and atherosclerotic cardiovascular disease (ASCVD) risk without any negative impact on overall health.
CTX320 is currently in an ongoing Phase 1 trial targeting LPA in patients with elevated lipoprotein(a) [Lp(a)], which has shown to have an independent association with major adverse cardiovascular events (MACE). Up to 20% of the global population has elevated Lp(a) levels.
The Company continues to advance two additional preclinical programs, CTX340 targeting angiotensinogen (AGT) for the treatment of refractory hypertension and CTX450 targeting 5’ aminolevulinic acid synthase (ALAS1) for the treatment of acute hepatic porphyrias (AHP). CRISPR Therapeutics has initiated IND/CTA-enabling studies for CTX340, targeting hepatic AGT for hypertension, and expects to initiate both clinical trials in the second half of 2025.
Regenerative Medicine

CTX211, an allogeneic, gene-edited, stem cell-derived beta islet cell precursor, is currently in an ongoing Phase 1 clinical trial for the treatment of Type 1 Diabetes (T1D). CRISPR Therapeutics remains committed to its goal of developing a beta-cell replacement product that does not require chronic immunosuppression.
Vertex has non-exclusive rights to certain CRISPR Therapeutics’ CRISPR/Cas9 technology to accelerate development of potentially curative cell therapies for T1D. CRISPR Therapeutics remains eligible for development milestones and would receive royalties on any future products resulting from this agreement.
Other Corporate Matters

In May, CRISPR Therapeutics announced the appointment of Naimish Patel, M.D., as Chief Medical Officer. Dr. Patel brings in-depth experience in successfully accelerating innovation and advancing drug candidates across a breadth of modalities and disease areas. Dr. Patel is an experienced drug developer who has worked across a wide range of disease areas, including his most recent leadership role as the Global Development Therapeutic Area Head of Immunology and Inflammation at Sanofi. In addition, the Company announced the promotions of (i) Julianne Bruno, M.B.A., to Chief Operating Officer; Ms. Bruno previously served as the Company’s Senior Vice President and Head of Programs & Portfolio Management; and (ii) Susan Kim to Senior Vice President, Investor Relations and Corporate Communications; Ms. Kim previously served as the Company’s Vice President of Investor Relations and Corporate Communications.
Second Quarter 2024 Financial Results

Cash Position: Cash, cash equivalents, and marketable securities were $2,012.8 million as of June 30, 2024, compared to $1,695.7 million as of December 31, 2023. The increase in cash was primarily driven by proceeds from the $280.0 million February 2024 registered direct offering, a $200.0 million milestone payment received from Vertex in connection with the approval of CASGEVY, proceeds from employee option exercises as well as interest income, offset by operating expenses.
Revenue: Total collaboration revenue for the second quarter of 2024 was not material. Collaboration revenue for the second quarter of 2023 was $70.0 million. Collaboration revenue recognized in the second quarter of 2023 was primarily attributable to a research milestone achieved during the current quarter in connection with a non-exclusive license agreement with Vertex.
R&D Expenses: R&D expenses were $80.2 million for the second quarter of 2024, compared to $101.6 million for the second quarter of 2023. The decrease in R&D expense was primarily driven by reduced variable external research and manufacturing costs.
G&A Expenses: General and administrative expenses were $19.5 million for the second quarter of 2024, compared to $19.0 million for the second quarter of 2023.
Collaboration Expense: Collaboration expense, net, was $52.1 million for the second quarter of 2024, compared to $44.6 million for the second quarter of 2023. The increase in collaboration expense, net, was primarily attributable to manufacturing and commercial costs under the CASGEVY collaboration with Vertex.
Net Loss: Net loss was $126.4 million for the second quarter of 2024, compared to a net loss of $77.7 million for the second quarter of 2023.
About CASGEVY (exagamglogene autotemcel [exa-cel])
CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.

On August 5, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported its financial results for the second quarter and six months ended June 30, 2024 (Press release, Castle Biosciences, AUG 5, 2024, View Source [SID1234645334]).

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"We achieved another quarter of exceptional performance, thanks to the hard work of our talented team and strength of our innovative test portfolio," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "We were especially pleased with the substantial top-line growth as well as growth in test report volumes across our therapeutic areas."

"Regarding our DecisionDx-SCC test, we were also pleased to see the publication of our first study evaluating the use of DecisionDx-SCC to guide adjuvant radiation therapy (ART) recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC). This study, which is the largest study to evaluate the effectiveness of ART in SCC, found that the DecisionDx-SCC test can identify patients who are considering ART under traditional clinicopathologic risk features and have a low likelihood of metastasis and a low likelihood of a receiving a clinical benefit from ART – thus enabling deferral of radiation therapy and avoidance of complications and associated impacts on the patient’s quality of life. This study was published in the American Society for Radiation Oncology’s flagship journal, International Journal of Radiation Oncology, Biology, Physics (also known as the Red Journal).

"Regarding our TissueCypher Barrett’s Esophagus test, the American Gastroenterological Association (AGA) recently recognized in its Clinical Practice Guideline that there is a high-risk subset of non-dysplastic Barrett’s esophagus patients who may benefit from early intervention with endoscopic eradication therapy (EET) and importantly, acknowledged that tissue-based biomarker testing, including the tissue systems pathology test (i.e., TissueCypher, also known as TSP-9) can help identify these patients.

"We believe we are well-positioned for near- and long-term success, supported by the potential for continued growth across our portfolio, as well as by our robust balance sheet and proven track record of strong execution. I am proud of what we have accomplished, and we will continue to work to operate with speed and agility to deliver value to patients, clinicians and stockholders alike."

Second Quarter Ended June 30, 2024, Financial and Operational Highlights
•Revenues were $87.0 million, a 74% increase compared to $50.1 million in the second quarter of 2023. Included in revenue for the period were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the quarter were $0.4 million of net positive revenue adjustments, compared to $0.1 million of net negative revenue adjustments for the same period in 2023.
•Adjusted Revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $86.6 million, a 72% increase compared to $50.2 million for the same period in 2023.
•Delivered 25,102 total test reports in the second quarter of 2024, an increase of 49% compared to 16,820 in the same period of 2023:
◦DecisionDx-Melanoma test reports delivered in the quarter were 9,585, compared to 8,597 in the second quarter of 2023, an increase of 11%.

◦DecisionDx-SCC test reports delivered in the quarter were 4,277, compared to 2,681 in the second quarter of 2023, an increase of 60%.
◦MyPath Melanoma test reports delivered in the quarter were 1,099, compared to 953 in the second quarter of 2023, an increase of 15%.
◦TissueCypher Barrett’s Esophagus test reports delivered in the quarter were 4,782, compared to 1,447 in the second quarter of 2023, an increase of 230%.
◦IDgenetix test reports delivered in the quarter were 4,903, compared to 2,681 in the second quarter of 2023, an increase of 83%.
◦DecisionDx-UM test reports delivered in the quarter were 456, compared to 461 in the second quarter of 2023, a decrease of 1%.
•Gross margin was 81%, and Adjusted Gross Margin was 83%, compared to 74% and 78%, respectively, for the same periods in 2023.
•Net cash provided by operations was $24.0 million, compared to $3.8 million net cash used in operations for the same period in 2023.
•Net income, which includes non-cash stock-based compensation expense of $13.2 million, was $8.9 million, compared to a net loss of $(18.8) million for the same period in 2023.
•Adjusted EBITDA was $21.5 million, compared to $(5.3) million for the same period in 2023.

Six Months Ended June 30, 2024, Financial and Operational Highlights
•Revenues were $160.0 million, a 74% increase compared to $92.2 million during the same period in 2023. Included in revenue for the period were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the six months ended June 30, 2024, were $1.0 million of net positive revenue adjustments, compared to $1.7 million of net negative revenue adjustments for the same period in 2023.
•Adjusted Revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $159.0 million, a 69% increase compared to $93.9 million for the same period in 2023.
•Delivered 45,990 total test reports in the six months ended June 30, 2024, an increase of 45% compared to 31,736 in the same period of 2023:
◦DecisionDx-Melanoma test reports delivered in the six months ended June 30, 2024, were 17,969, compared to 16,180 for the same period in 2023, an increase of 11%.
◦DecisionDx-SCC test reports delivered in the six months ended June 30, 2024, were 7,854, compared to 5,092 for the same period in 2023, an increase of 54%.
◦MyPath Melanoma test reports delivered in the six months ended June 30, 2024, were 2,097, compared to 1,933 for the same period in 2023, an increase of 8%.
◦TissueCypher Barrett’s Esophagus test reports delivered in the six months ended June 30, 2024, were 8,211, compared to 2,830 for the same period in 2023, an increase of 190%.
◦IDgenetix test reports delivered in the six months ended June 30, 2024, were 8,981, compared to 4,831 for the same period in 2023, an increase of 86%.
◦DecisionDx-UM test reports delivered in the six months ended June 30, 2024, were 878, compared to 870 for the same period in 2023, an increase of 1%.
•Gross margin for the six months ended June 30, 2024, was 79%, and Adjusted Gross Margin was 82%.
•Net cash provided by operations was $17.2 million, compared to $29.2 million net cash used in operations for the same period in 2023.
•Net income for the six months ended June 30, 2024, which includes non-cash stock-based compensation expense of $25.9 million, was $6.4 million, compared to a net loss of $(48.0) million for the same period in 2023.
•Adjusted EBITDA for the six months ended June 30, 2024, was $32.1 million, compared to $(20.4) million for the same period in 2023.
Cash, Cash Equivalents and Marketable Investment Securities
As of June 30, 2024, the Company’s cash, cash equivalents and marketable investment securities totaled $259.7 million.

2024 Outlook
Based upon revenue generated through June 30, 2024, the Company is increasing its guidance for anticipated total revenue in 2024 to between $275–300 million, compared to the previously provided guidance of between $255–265 million.
Second Quarter and Recent Accomplishments and Highlights
Dermatology
•DecisionDx-SCC: The Company announced the publication of a study in the International Journal of Radiation Oncology, Biology, Physics (Red Journal) demonstrating the ability of the DecisionDx-SCC test to identify high-risk SCC patients who are likely to benefit from ART to reduce metastatic disease progression, as well as high-risk patients who are unlikely to benefit from ART and who, therefore, may consider deferring treatment. This study is the single largest study ever conducted to evaluate the effectiveness of ART in patients diagnosed with SCC and demonstrates the impact of the test in guiding decision-making for recommending ART. See the Company’s news release from May 29, 2024, for more information.
•DecisionDx-SCC: The Company also shared new data that supported the utility of DecisionDx-SCC in patients with high-risk SCC tumors located on the head and neck at the 56th American College of Mohs Surgery (ACMS) Annual Meeting in Phoenix. Data presented demonstrated that testing with DecisionDx-SCC significantly increased the prediction accuracy of metastatic events, when used alone and when combined with National Comprehensive Cancer Network (NCCN) guidelines, Brigham and Women’s Hospital (BWH) staging or American Joint Committee on Cancer Staging Manual, 8th Edition (AJCC8) staging, to better guide risk-aligned patient care decisions regarding metastatic surveillance or the use of adjuvant treatments like radiation. See the Company’s news release from May 3, 2024, for more information.
•DecisionDx-Melanoma: The Company presented new data relating to its DecisionDx-Melanoma test at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, demonstrating the test’s ability to identify patients with localized cutaneous melanoma at the highest risk of metastasis to the central nervous system (CNS). Specifically, the study showed that DecisionDx-Melanoma can identify patients with earlier-stage melanoma who have a higher risk of CNS metastasis within the first three years post-diagnosis. These higher-risk patients may benefit from more frequent imaging surveillance to identify CNS metastases earlier to improve patient survival. See the Company’s news release from May 30, 2024, for more information.
Gastroenterology
•The Company announced that the AGA published new clinical practice guidelines for EET to treat Barrett’s esophagus (BE) and prevent its progression to esophageal adenocarcinoma. These guidelines recognized that there is a high-risk subset of patients with non-dysplastic BE (NDBE) who may benefit from early intervention with EET and acknowledged the role that tissue-based biomarkers, including TissueCypher, can play in identifying these patients. See the Company’s news release from June 24, 2024, for more information.
•The Company also shared three abstracts supporting the ability of its TissueCypher test to predict risk of progression to esophageal cancer in patients with BE at the Digestive Disease Week (DDW) 2024 Annual Meeting in Washington, D.C. The data that was shared further expanded the substantial clinical evidence supporting TissueCypher and its ability to improve the care that BE patients receive. See the Company’s news release from May 14, 2024, for more information.
Mental Health
•The Company was selected as the winner of the "Best Overall Mental Health Solution" award in the eighth annual MedTech Breakthrough Awards program for its IDgenetix pharmacogenomic (PGx) test. The MedTech Breakthrough Awards honor excellence and recognize innovation, hard work and success in a range of health and medical technology categories, attracting thousands of nominations from over 18 countries across the world. See the Company’s news release from May 10, 2024, for more information.
Uveal Melanoma
•The Company announced results from the largest prospective study to date of patients with uveal melanoma, titled "15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal

Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1)," confirming the prognostic accuracy of the DecisionDx-UM test and providing the first prospective validation of Preferentially Expressed Antigen in Melanoma (PRAME) status as a risk refinement tool when considered in the context of a Class 1 or Class 2 DecisionDx-UM result. The study data demonstrated that together, these two tests can guide more precise and risk-aligned decision-making for patients with UM, including referrals, intensity of imaging surveillance and eligibility for ongoing clinical trials. See the Company’s news release from May 8, 2024, and the published paper in the Journal of Clinical Oncology for more information.
Corporate
•The Company announced that its founder, president and chief executive officer, Derek Maetzold, was named by Ernst & Young LLP (EY) as an Entrepreneur Of The Year 2024 Gulf South Award winner. Now in its 38th year, Entrepreneur Of The Year is the preeminent competitive awards program that celebrates entrepreneurs and leaders of high-growth companies who disrupt markets, revolutionize sectors and have a transformational impact on lives. See the Company’s news release from June 14, 2024, for more information.

Conference Call and Webcast Details
Castle Biosciences will hold a conference call on Monday, August 5, 2024, at 4:30 p.m. Eastern time to discuss its second quarter 2024 results and provide a corporate update.

A live webcast of the conference call can be accessed here: View Source
or via the webcast link on the Investor Relations page of the Company’s website,
View Source Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until August 26, 2024.

To access the live conference call via phone, please dial 833 470 1428 from the United States, or +1 404 975 4839 internationally, at least 10 minutes prior to the start of the call, using the conference ID 802518.

There will be a brief Question & Answer session following management commentary.

On August 5, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported financial results for the three and six months ended June 30, 2024, and provided an update on its corporate progress (Press release, BioNTech, AUG 5, 2024, View Source [SID1234645332]).

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"The year to date has been marked by significant data updates across our oncology portfolio. These readouts reinforce the potential of our platform technologies including our individualized and off-the-shelf mRNA vaccine platforms, iNeST and FixVac. We have also advanced our strategy by initiating clinical trials evaluating novel combinations of synergistic drug candidates. Notably, we dosed the first patient in a trial evaluating the combination of the TROP2 antibody-drug conjugate BNT325/DB-1305 and the PD-L1-VEGF-A bispecific BNT327/PM8002, aiming to harness the potent anti-tumor activity of antibody drug conjugates along with the sustained benefit of immunomodulators," said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "In addition, we have started commercializing variant-adapted COVID-19 vaccines for the upcoming season, while accelerating our clinical development efforts to realize the full potential of our technologies. We are making progress towards our goal of becoming a company with marketed medicines for cancer and infectious diseases."

Financial Review for Second Quarter and First Half of 2024

in millions €, except per share data Second Quarter 2024 Second Quarter 2023 First Half
2024 First Half
2023
Revenues 128.7 167.7 316.3 1,444.7
Net Profit / (Loss) (807.8) (190.4) (1,122.9) 311.8
(Loss) / Diluted Earnings per Share (3.36) (0.79) (4.67) 1.28
Revenues reported were €128.7 million for the three months ended June 30, 2024, compared to €167.7 million for the comparative prior year period. For the six months ended June 30, 2024, revenues were €316.3 million, compared to €1,444.7 million for the comparative prior year period. The year-over-year change was mainly due to lower revenues from the sales of the Company’s COVID-19 vaccines worldwide resulting from the continued shift in demand from a pandemic to a seasonal endemic COVID-19 vaccine market.

Cost of sales were €59.8 million for the three months ended June 30, 2024, compared to €162.9 million for the comparative prior year period. For the six months ended June 30, 2024, cost of sales were €118.9 million, compared to €258.9 million for the comparative prior year period. The change was mainly due to COVID-19 vaccine production in line with demand.

Research and development ("R&D") expenses were €584.6 million for the three months ended June 30, 2024, compared to €373.4 million for the comparative prior year period. For the six months ended June 30, 2024, R&D expenses were €1,092.1 million, compared to €707.4 million for the comparative prior year period. R&D expenses were mainly influenced by progressing clinical studies for the Company’s late-stage oncology pipeline candidates. Further contributions to the increase came from wages, benefits and social security expenses resulting from an increase in headcount.

Sales, general and administrative ("SG&A") expenses2, in total, amounted to €183.8 million for the three months ended June 30, 2024, compared to €137.9 million for the comparative prior year period. For the six months ended June 30, 2024, SG&A expenses were €316.4 million, compared to €261.9 million for the comparative prior year period. SG&A expenses were primarily driven by increased expenses for IT environment and wages, benefits, and social security expenses resulting from an increase in headcount.

Other operating result amounted to €266.7 million negative operating result during the three months ended June 30, 2024, compared to €56.8 million negative operating result for the comparative prior year period. For the six months ended June 30, 2023, other operating result amounted to €262.3 million negative operating result compared with €125.4 million negative operating result for the prior year period. This change was primarily due to the recording of a provision related to a contractual dispute.

Income taxes were accrued with an amount of €2.0 million of tax expenses for the three months ended June 30, 2024, compared to €221.8 million of realized tax income for the comparative prior year period. For the six months ended June 30, 2024, income taxes were realized with an amount of €14.7 million of tax income for the six months ended June 30, 2024, compared to €16.3 million of realized tax income for the comparative prior year period. The effective income tax rate for the six months ended June 30, 2024, was approximately 1.3%.

Net loss was €807.8 million for the three months ended June 30, 2024, compared to €190.4 million loss for the comparative prior year period. For the six months ended June 30, 2024, loss was €1,122.9 million for the six months ended June 30, 2024, compared to a profit of €311.8 million for the comparative prior year period.

Cash and cash equivalents plus security investments as of June 30, 2024, reached €18,485.1 million, comprising €10,376.7 million cash and cash equivalents, €6,916.7 million current security investments and €1,191.7 million non-current security investments. This position increased during the second quarter of 2024 largely attributable to a cash payment received from BioNTech’s collaboration partner Pfizer Inc. ("Pfizer").

Loss per share was €3.36 for the three months ended June 30, 2024, compared to €0.79 for the comparative prior year period. For the six months ended June 30, 2024, loss per share was €4.67, compared to diluted earnings per share of €1.28 for the comparative prior year period.

Shares outstanding as of June 30, 2024 were 237,766,235, excluding 10,785,965 shares held in treasury.

"Our second quarter revenues correspond to the current demand of a seasonal endemic COVID-19 vaccine market," said Jens Holstein, CFO of BioNTech. "Supported by our strong financial position, we will continue to focus on our long-term growth strategy throughout the remainder of the year. This includes our clinical pipeline for individualized therapies, the build-out of our manufacturing capacities and capabilities to support additional late-stage trials as well as our commercialization activities. These investments build the foundation for the next stage of growth and the transformation of BioNTech into a multi-product company."

2024 Financial Year Guidance3 Reiterated

The Company reiterates its prior outlook for the financial year:

Total revenues for the 2024 financial year €2.5 billion – €3.1 billion
BioNTech expects revenues for the full 2024 financial year to be in the range of €2.5 to €3.1 billion. The range reflects certain assumptions and expectations, including, but not limited to: the timing and granting of regulatory approvals and recommendations; COVID-19 vaccine uptake and price levels; inventory write-downs by BioNTech’s collaboration partner Pfizer that would negatively influence BioNTech’s revenues; seasonal variations in SARS-CoV-2 circulation and vaccination uptake, which are expected to lead to demand peaks in the autumn and winter compared to other seasons; and revenues from a pandemic preparedness contract with the German government as well as revenues from the BioNTech Group service businesses, namely InstaDeep Ltd., JPT Peptide Technologies GmbH, and in Idar-Oberstein at BioNTech Innovative Manufacturing Services GmbH. Generally, the Company continues to remain largely dependent on revenues generated in its collaboration partner’s territories in 2024.

Planned 2024 Financial Year Expenses and Capex:

R&D expenses4 €2.4 billion – €2.6 billion
SG&A expenses €700 million – €800 million
Capital expenditures for operating activities €400 million – €500 million
The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Report on Form 6-K for the period ended June 30, 2024, filed today with the United States Securities and Exchange Commission ("SEC") and available at View Source

Endnotes

1 Calculated applying the average foreign exchange rate for the six months ended June 30, 2024, as published by the German Central Bank (Deutsche Bundesbank).

2 "SG&A expenses’’ includes sales and marketing expenses as well as general and administrative expenses.

3 Guidance excludes external risks that are not yet known and/or quantifiable. It does not include potential payments resulting from the outcomes of ongoing and/or future legal disputes or related activity, such as judgements or settlements, which may have a material effect on the Company’s results of operations and/or cash flows. BioNTech continues to expect to report a loss for the 2024 financial year and expects to recognize the vast majority of its full year revenues mostly in the fourth quarter.

4 Numbers include effects identified from additional collaborations or potential M&A transactions to the extent disclosed and are subject to update due to future developments.

Operational Review of the Second Quarter 2024, Key Post Period-End Events and Outlook

Variant-adapted Monovalent COVID-19 Vaccines (COMIRNATY)

In April 2024, the World Health Organization ("WHO"), the European Medicines Agency ("EMA") and, subsequently, other health authorities, provided guidance highlighting that updated vaccines targeting Omicron JN.1 or JN.1 sublineages may contribute to maintaining protection against COVID-19 during the upcoming fall and winter seasons.
On June 27, 2024, BioNTech and Pfizer announced that the Committee for Medicinal Products for Human Use ("CHMP") of the EMA recommended marketing authorization for the companies’ Omicron JN.1-adapted monovalent COVID-19 vaccine (COMIRNATY JN.1) for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals six months of age and older. On July 3, 2024, the European Commission ("EC") adopted a decision following the CHMP’s recommendation. Shortly following the EC decision, the updated vaccine was made available to ship to EU member states.
On June 6, 2024, the U.S. FDA’s Vaccines and Related Biological Products Advisory Committee ("VRBPAC") issued guidance recommending the manufacturing of a JN.1-adapted monovalent COVID-19 vaccine for the 2024/2025 fall and winter seasons. On June 13, 2024, the U.S. FDA announced the KP.2 strain as the preferred JN.1-lineage for COVID-19 vaccines (2024-2025 Formula). In June 2024, BioNTech and Pfizer submitted regulatory applications to the U.S. FDA for the companies’ Omicron JN.1-adapted monovalent vaccine, and initiated a rolling sBLA for an Omicron KP.2-adapted monovalent vaccine. The companies plan to prepare shipments in the United States of KP.2-adapted monovalent COVID-19 vaccines for fast delivery following potential regulatory approval, currently expected in September 2024.
On July 24, 2024, the United Kingdom’s Medicines and Healthcare products Regulatory Agency ("MHRA") approved the companies’ Omicron JN.1-adapted vaccine.
COVID-19 – Influenza Combination Vaccine Program

BNT162b2 + BNT161 is an mRNA-based combination vaccine program against COVID-19 and influenza being developed in collaboration with Pfizer.

Top-line data from the Phase 1/2 trial (NCT05596734) demonstrated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains and that the safety profile of the candidates was consistent with the profile of the companies’ COVID-19 vaccine.
A Phase 3 clinical trial (NCT06178991) is fully enrolled and data are expected later this year.
Select Oncology Pipeline Highlights

Cancer Vaccine Programs

BNT111 is based on BioNTech’s FixVac platform, and is a wholly owned, systemically administered, off-the-shelf uridine mRNA-lipoplex based cancer vaccine candidate encoding shared melanoma associated antigens.

A randomized Phase 2 clinical trial (NCT04526899) being conducted in collaboration with Regeneron Pharmaceuticals Inc. ("Regeneron") is ongoing to evaluate BNT111 in combination with cemiplimab, BNT111 alone, or cemiplimab alone in anti-PD-1-/anti-PD-L1 refractory/relapsed, unresectable stage III or IV melanoma.
In July 2024, BioNTech announced that the study met its primary efficacy outcome measure, demonstrating a statistically significant improvement in overall response rate ("ORR") in patients treated with BNT111 in combination with the anti-PD-1 checkpoint inhibitor, cemiplimab, as compared to a historical control in this indication and treatment setting. The ORR in the cemiplimab monotherapy arm was in line with the historical control of anti-PD-L1 or anti-CTLA-4 treatments in this patient group. The treatment was well tolerated and the safety profile of BNT111 in combination with cemiplimab in this trial was consistent with previous clinical trials assessing BNT111 in combination with anti-PD-L1-containing treatments. The Phase 2 trial will continue as planned to further assess the secondary endpoints which were not mature at the time of the primary analysis.
BioNTech plans to present data from this trial at an upcoming medical conference.
BNT113 is a cancer vaccine candidate based on FixVac’s platform encoding for shared antigens associated with Human Papilloma Virus ("HPV16+") head and neck cancer.

A global, randomized Phase 2 clinical trial (NCT04534205) evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma expressing PD-L1 is ongoing.
Data updates are expected to be presented at the 2024 Congress of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) ("ESMO") taking place from September 13-17, 2024 in Barcelona, Spain.
Abstract Title: Exploratory efficacy and translational results from the safety run in of AHEAD-MERIT, a phase II trial of first line pembrolizumab plus the fixed-antigen cancer vaccine BNT113 in advanced HPV16+ HNSCC
Poster Date: September 14, 2024
Presentation Number: 877P
Author: C. N. F. Saba

Abstract Title: HARE-40: A phase I/II trial of therapeutic HPV vaccine (BNT113) in patients with HPV16 driven carcinoma
Mini-oral Date & Time: September 16, 2024, 11:15 – 11:20 a.m. CEST
Presentation Number: 999MMO
Author: C. Ottensmeier

Autogene cevumeran (BNT122) is a uridine mRNA-lipoplex based cancer vaccine candidate for individualized neoantigen-specific immunotherapy ("iNeST") being developed in collaboration with Genentech, Inc. ("Genentech"), a member of the Roche Group ("Roche").

Autogene cevumeran is being evaluated in ongoing Phase 2 trials in adjuvant resected pancreatic ductal adenocarcinoma ("PDAC") (NCT05968326), first-line melanoma (NCT03815058) and adjuvant colorectal cancer ("CRC") (NCT04486378). A Phase 2 clinical trial in an additional indication is planned.
In June 2024, epidemiologic data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting, including data on post-operative circulating tumor DNA ("ctDNA") prevalence and prognostic value in disease-free survival, from an observational study (NCT04813627) in patients with resected high-risk stage II/III CRC. These epidemiological and prognostic data are supportive of the ongoing interventional Phase 2 clinical trial (NCT04486378).
Also in June 2024, at the 2024 European Society for Medical Oncology Gastrointestinal Cancers ("ESMO-GI") Congress, immunogenicity data were presented from the biomarker cohort of the ongoing Phase 2 (NCT04486378) that enrolled patients irrespective of post-surgical ctDNA status. The data indicate that autogene cevumeran is highly immunogenic and induces de novo polyepitopic, ex vivo detectable T-cell responses in all evaluable patients with resected​ stage II (high risk) or III CRC after completion of adjuvant chemotherapy.​ Among patients included in the immunogenicity analysis, all (12/12) were disease-free at data cut off.
Preliminary data from the ongoing Phase 2 clinical trial (NCT04486378) in stage II (high risk) and III ctDNA+ adjuvant CRC is expected in late 2025 or 2026.
Next-Generation Immune Checkpoint Immunomodulator Programs

BNT327/PM8002 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with VEGF-A neutralization and is being developed in collaboration with Biotheus Inc. ("Biotheus").

BNT327/PM8002 is currently being evaluated in multiple Phase 2 and Phase 3 clinical trials in China to assess the efficacy and safety of the candidate as monotherapy or in combination with chemotherapy in various indications.
In June 2024, at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, monotherapy data were presented from an ongoing Phase 1/2 clinical trial (NCT05918445) for cohorts of patients with advanced cervical cancer ("CC"), platinum-resistant recurrent ovarian cancer ("PROC"), and advanced non-small cell lung cancer ("NSCLC").
Data on 48 patients with advanced CC showed an ORR of 42.2% (52.4% in patients with PD-L1-positive tumors), a disease control rate ("DCR") of 93.3%, and a median progression-free survival ("mPFS") of 8.3 months. Data on 39 patients with PROC showed an ORR of 20.6%, a DCR of 67.7%, and a mPFS of 5.5 months. Treatment related adverse events ("TRAEs") occurred in 95.4% of patients (83/87) with ≥ Grade 3 TRAEs in 36.8% (32/87) and 14.9% (13/87) of patients discontinued BNT327/PM8002 treatment due to TRAEs. Median follow-up time in patients with CC and PROC was 13.8 months and 14.8 months, respectively.
Data on 61 patients with non-squamous NSCLC were also presented. Data on 17 evaluable patients with untreated NSCLC wild-type and PD-L1-positive showed an ORR of 47.1%, a DCR of 100% and a mPFS of 13.6 months at a median follow-up of 11.3 months. Data on 36 evaluable patients with epidermal growth factor receptor ("EGFR")-mutant NSCLC after progression on prior EGFR-tyrosine kinase inhibitor treatment showed an ORR of 19.4%, a DCR of 69.4% and a mPFS of 5.5 months at a median follow-up of 12.6 months. Data from 8 evaluable patients with EGFR/anaplastic lymphoma kinase ("ALK") wild-type NSCLC that progressed after anti-PD-1/L1 therapy and platinum-based chemotherapy showed an ORR of 12.5%, a DCR of 62.5%, and a mPFS of 5.8 months at a median follow-up of 5.8 months. TRAEs occurred in 85.2% of patients (52/61) with ≥Grade 3 TRAEs in 19.7% (12/61), serious adverse events were observed in 24.6% (15/61) of patients, 8.2% (5/61) of patients discontinued BNT327/PM8002 treatment due to TRAEs.
In June 2024, the first patient was dosed in the Phase 1/2 clinical trial (NCT05438329) evaluating the combination of BNT327/PM8002 with BNT325/DB-1305, an antibody-drug conjugate ("ADC") candidate targeting TROP-2. Additional trials with novel BNT327 and other ADC combinations are planned to begin this year.
Two Phase 2 dose optimization studies are expected to start soon.
A Phase 2 clinical trial (NCT06449222) to evaluate the safety, efficacy, and pharmacokinetics of BNT327/PM8002 at two dose levels in combination with chemotherapy in the first- and second-line treatment of patients with locally advanced/metastatic triple negative breast cancer ("TNBC").
A Phase 2 clinical trial (NCT06449209) to evaluate BNT327/PM8002 in combination with chemotherapy in patients with untreated extended-stage small-cell lung cancer ("ES-SCLC") or small-cell lung cancer ("SCLC") progressed on first- or second-line treatment.
Data from these studies are expected as early as 2025.
At the 2024 ESMO (Free ESMO Whitepaper) Congress the following datasets will be presented:
Abstract Title: A Phase II Safety and Efficacy Study of PM8002/BNT-327 in Combination with Chemotherapy in Patients with EGFR-mutated NSCLC
Mini-oral Presentation Date & Time: September 14, 2024, 10:25 – 10:30 a.m. CEST
Presentation Number: 1255MO
Author: Y-L. Wu

Abstract Title: A Phase Ib/II Study to Assess the Safety and Efficacy of PM8002/BNT327 in Combination with Nab-Paclitaxel for First Line Treatment of Locally Advanced or Metastatic Triple-Negative Breast Cancer
Mini-oral Presentation Date & Time: September 16, 2024, 08:35 – 08:40 a.m. CEST
Presentation Number: 348MO
Author: J. Wu

Abstract Title: A Phase Ib/IIa Trial to Evaluate the Safety and Efficacy of PM8002/ BNT327, a Bispecific Antibody Targeting PD-L1 and VEGF-A, as a Monotherapy in Patients with advanced renal cell carcinoma
Poster Date: September 15, 2024
Presentation Number: 1692P
Author: X. Sheng

BNT311/GEN1046 (acasunlimab) is a potential first-in-class bispecific antibody candidate combining PD-L1 checkpoint inhibition with 4-1BB costimulatory activation that is being developed for the treatment of solid tumors.

A Phase 2, multi-center, randomized, open-label clinical trial (NCT05117242) of BNT311/GEN1046 (acasunlimab) as monotherapy and in combination with pembrolizumab is ongoing in patients with relapsed/refractory metastatic NSCLC and a tumor PD-L1 expression of tumor proportion score, or TPS, of ≥1% after treatment with standard of care therapy with an immune checkpoint inhibitor. The primary endpoint is ORR according to Response Evaluation Criteria in Solid Tumors, or RECIST v1.1. Secondary endpoints include duration of response ("DOR"), time to response ("TTR"), progression-free survival ("PFS"), overall survival "OS" and safety.
Data from the ongoing Phase 2 trial (NCT05117242) evaluating BNT311/GEN1046 (acasunlimab) in combination with pembrolizumab in pretreated NSCLC patients were presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting. The results showed a 12-month OS rate of 69%, a median OS ("mOS") of 17.5 months, and a 30% ORR (confirmed ORR 17%) at the time of data cut-off in patients treated with the combination of BNT311/GEN1046 (acasunlimab) and pembrolizumab every 6 weeks. Anti-tumor activity was observed in patients with tumor proportion score ("TPS") of 1–49% and ≥50%, in patients with <6 months and ≥6 months of previous immune checkpoint inhibitor ("CPI") treatment, and in patients with squamous and non-squamous histology. Adverse events were consistent with the safety profiles of the individual drugs and TRAEs were primarily Grade 1 and 2.
Updated data from this ongoing trial is expected to be presented at the 2024 World Conference on Lung Cancer ("WCLC") taking place from September 7-10, 2024 in San Diego, California, U.S.
Abstract Title: Dosing Regimen for Acasunlimab (DuoBody-PD-L1x4-1BB) In Combination with Pembrolizumab
Poster Presentation Date & Time: September 9, 2024, 18:30-20:00 PDT
Presentation Number: 845
Author: G. Bajaj

Abstract Title: Acasunlimab Alone or in Combination with Pembrolizumab for Previously Treated Metastatic Non-Small Cell Lung Cancer
Mini-oral Presentation Date & Time: September 10, 2024, 15:07 – 15:12 PDT
Presentation Number: 1309
Author: L. Paz-Ares

While the emerging clinical profile of BNT311/GEN1046 (acasunlimab) is encouraging, for reasons relating to portfolio strategy, BioNTech opted not to participate in the further development of the program, including a planned Phase 3 trial. BioNTech and Genmab A/S ("Genmab") will continue their collaboration under the existing agreements which was expanded in 2022.
ADC Programs

BNT323/DB-1303 is an ADC candidate targeting Human Epidermal Growth Factor 2 ("HER2") that is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. ("DualityBio").

BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. A potentially registrational cohort with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) patients with advanced/recurrent endometrial carcinoma has completed enrollment. Data from this cohort are expected in 2025.
A confirmatory Phase 3 trial (NCT06340568) in patients with advanced endometrial cancer is planned to start in 2024.
A pivotal Phase 3 trial (NCT06018337) evaluating BNT323/DB-1303 in patients with Hormone Receptor-positive ("HR+") and HER2-low metastatic breast cancer ("BC") that have progressed on hormone therapy and/or cyclin-dependent kinase 4/6 ("CDK4/6") inhibition is ongoing.
Topline data from the ongoing Phase 3 trial in HR+ and HER2-low metastatic BC that have progressed on hormone therapy and/or CDK4/6 inhibition are expected as early as 2025.
BNT324/DB-1311 is an ADC candidate targeting B7H3 that is being developed in collaboration with DualityBio.

A first-in-human, open-label Phase 1/2a clinical trial (NCT05914116) evaluating BNT324/DB-1311 in patients with advanced solid tumors is ongoing.
In June 2024, BioNTech and DualityBio announced that BNT324/DB-1311 was granted Fast Track designation by the U.S. FDA for the treatment of patients with advanced/unresectable or metastatic castration-resistant prostate cancer who have progressed on or after standard systemic regimens.
In July 2024, the U.S. FDA granted Orphan Drug designation to BNT324/DB-1311 for the treatment of patients with advanced or metastatic esophageal squamous cell carcinoma.
BNT326/YL202 is an ADC candidate targeting HER3 that is being developed in collaboration with MediLink Therapeutics (Suzhou) Co., Ltd. ("MediLink").

A multicenter, international, open-label, first-in-human Phase 1 clinical trial (NCT05653752), sponsored by MediLink, evaluating BNT326/YL202 as a later-line treatment in patients with locally advanced or metastatic EGFR-mutated NSCLC or HR+ and HER2-negative BC is on partial clinical hold by the U.S. FDA, as announced on June 17, 2024. BioNTech and MediLink are working to address the U.S. FDA’s requirements and resolve the partial clinical hold.
Preliminary data from this study were presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting. BNT326/YL202 demonstrated encouraging activity in heavily pretreated locally advanced/metastatic NSCLC and BC with an ORR of 42.3% (22 out of 52 evaluable patients) and a DCR of 94.2% (49/52), with responses seen from the first dose level at 0.5 mg/kg. The safety profile of BNT326/YL202 was consistent with its mechanism of action and dose-dependent. The most common TRAEs were due to hematologic toxicity and gastrointestinal disorders. 7.3% (4/55) of patients discontinued treatment due to TRAEs, and there were 3 treatment-related Grade 5 events (deaths) at higher doses. Further clinical development is expected to focus on dose levels below 4.0 mg/kg, where the safety profile was manageable and encouraging clinical activity was observed.
Cell Therapy Programs

BNT211 consists of two investigational medicinal products: a CAR-T cell product candidate targeting Claudin-6 ("CLDN6")-positive solid tumors in combination with a CAR-T cell-amplifying RNA vaccine ("CARVac") encoding CLDN6.

A first-in-human, open-label, multi-center Phase 1 dose escalation and dose expansion basket trial (NCT04503278) evaluating CLDN6 CAR-T cells as monotherapy or in combination with CLDN6 CARVac in patients with CLDN6-positive relapsed or refractory solid tumors, including ovarian cancers and testicular germ cell tumors, is ongoing.
A data update is expected to be presented at the 2024 ESMO (Free ESMO Whitepaper) Congress.
Abstract Title: Updated results from BNT211-01 (NCT04503278), an ongoing, first-in-human, Phase 1 study evaluating safety and efficacy of CLDN6 CAR T cells and a CLDN6-encoding mRNA vaccine in patients with relapsed/refractory CLDN6+ solid tumors
Mini-oral Presentation Date & Time: September 15, 2024, 15:45 – 15:55 CEST
Presentation Number: 611O
Author: J. B. Haanen

A pivotal Phase 2 trial in patients with testicular germ cell tumors is expected to start in 2025 based on encouraging data in this patient group observed in the Phase 1 trial.
BioNTech presented an analysis of real-world evidence investigating overall survival and treatment patterns of patients with testicular germ cell tumors receiving palliative chemotherapy at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting. This analysis will inform the design of the Company’s planned pivotal clinical trial to evaluate BNT211 in patients with germ cell tumors.
Corporate Update for the Second Quarter 2024 and Key Post Period-End Events

In May 2024, BioNTech expanded its strategic partnership with the Coalition for Epidemic Preparedness Innovations ("CEPI") to contribute to building a sustainable and resilient end-to-end African vaccine ecosystem. CEPI is committing up to US $145 million to support BioNTech in broadening the scope of the manufacturing facility in Kigali, Rwanda. These capabilities will contribute to BioNTech and CEPI’s efforts to better prepare for potential future epidemic and pandemic threats in Africa.
On July 1, 2024, Annemarie Hanekamp joined the Company’s Management Board as Chief Commercial Officer and James Ryan, Ph.D., Chief Legal Officer, also assumed the role of Chief Business Officer.
Upcoming Investor and Analyst Events

Innovation Series (AI Day): October 1, 2024
Third Quarter 2024 Financial Results and Corporate Update: November 4, 2024
Innovation Series: November 14, 2024
Conference Call and Webcast Information

BioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, August 5, 2024, at 8:00 a.m. EDT (2:00 p.m. CEST) to report its financial results and provide a corporate update for the second quarter of 2024.

To access the live conference call via telephone, please register via this link. Once registered, dial-in numbers and a PIN number will be provided.

The slide presentation and audio of the webcast will be available via this link.

On August 5, 2024 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported financial results for the quarter and six months ended June 30, 2024 (Press release, BioMarin, AUG 5, 2024, View Source [SID1234645331]).

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"Strong execution across our business resulted in record double-digit revenue growth in the second quarter and first half of 2024. These top-line results, along with a focus on operational efficiency, resulted in a 78% year-over-year improvement in quarterly non-GAAP earnings per share," said Alexander Hardy, President and Chief Executive Officer of BioMarin. "Strong global demand for VOXZOGO led to nearly 900 new patient starts in the first half of 2024, the highest in VOXZOGO’s history. Record VOXZOGO contributions in the quarter, driven by patient growth in all geographies, combined with double-digit growth from our enzyme therapies drove today’s increased 2024 full-year guidance."
Mr. Hardy added, "During the quarter, global demand for VOXZOGO continued to increase as more families sought treatment with the only approved and genetically-targeted medicine for achondroplasia. Approximately 3,500 children were receiving VOXZOGO by the end of the second quarter, with more than half of new treatment starts in the United States for children under the age of 5. We are seeing strong interest from families in the United States seeking VOXZOGO treatment for their children and we expect this market to continue to drive significant expansion over the coming quarters." Mr. Hardy continued, "With VOXZOGO’s safety and efficacy well-established, based on nearly 6,000 patient years of demonstrated and durable evidence, we are confident in our rapidly expanding leadership. Enrollment in our pivotal study with VOXZOGO for the treatment of hypochondroplasia is proceeding well, and enrollment in our separate studies for idiopathic short stature, Noonan Syndrome, Turner Syndrome and SHOX deficiency are advancing this year as planned, following alignment with health authorities."

Financial Highlights:

•Total Revenues for the second quarter of 2024 were $712.0 million, an increase of 20%, compared to the same period in 2023, driven by strong VOXZOGO contributions from new patient starts, high compliance rates, and customer stock levels normalizing facilitated by ample supply. In the quarter, demand across BioMarin’s enzyme therapies (VIMIZIM, NAGLAZYME, ALDURAZYME, BRINEURA and PALYNZIQ) drove 15% growth compared to the second quarter of 2023. This increase was partially driven by NAGLAZYME product revenues due to the timing of large government orders in certain regions outside the United States and higher PALYNZIQ revenues in the United States driven by new patient starts. Partially offsetting the increase were lower KUVAN product revenues attributed to continued generic competition as a result of the loss of market exclusivity.
•GAAP Net Income increased by $51.2 million to $107.2 million in the second quarter of 2024 compared to the same period in 2023. The increase was primarily due to higher gross profit driven by the factors noted above. The increase was partially offset by higher spend in Selling, General and Administrative (SG&A), primarily due to severance and other restructuring costs associated with the Company’s portfolio strategy review and the associated organizational redesign efforts announced in the second quarter of 2024.

•Non-GAAP Income increased by $83.7 million to $188.9 million in the second quarter of 2024 compared to the same period in 2023. The increase in Non-GAAP Income was primarily due to higher gross profit, partially offset by higher SG&A expenses primarily related to sales and marketing activities for VOXZOGO, higher partner distribution fees, incremental administrative expenses, as well as higher Research and Development (R&D) expenses related to expansion into new VOXZOGO indications and our prioritized pipeline products.

2Q Update on 2024 Strategic Priorities

In the second quarter, BioMarin continued to deliver on its four strategic priorities, first outlined in January, and focused on value creation through accelerating growth, optimizing efficiencies and driving operational excellence.

Accelerate and maximize the VOXZOGO opportunity
•During the second quarter, the number of children with achondroplasia benefiting from VOXZOGO treatment increased to approximately 3,500 across 44 countries. Global access to VOXZOGO from infancy had a significant impact on uptake as families pursued maximum therapeutic benefit by starting treatment early.
•In the U.S., the largest potential market, the majority of new patient starts in the quarter were for children under the age of 5 years. VOXZOGO’s extensive safety and efficacy profile led more families to begin therapeutic intervention early to potentially impact greater improvements in craniofacial growth, foramen magnum compression, body proportionality and quality of life, in addition to durable increases in growth velocity.
•During the quarter, new, multi-year data demonstrating that treating achondroplasia with VOXZOGO improved health related quality of life and proportionality, which are important benefits, beyond height, for affected children and their families. These results were presented at the Pediatric Endocrine Society (PES) annual meeting (press release), and the 2024 International Conference on Children’s Bone Health (ICCBH) (press release). In addition, positive results with VOXZOGO from Phase 2 in children with Noonan Syndrome, idiopathic short stature and other growth-related conditions were presented.
◦At PES on May 4, results from a Phase 3 extension study in children with achondroplasia who began VOXZOGO treatment at 10 years of age or older, demonstrated that meaningful height gains were observed despite the age of participants at treatment initiation. Results from a Phase 2 extension study showed that VOXZOGO maintained positive effects on linear growth over 4 years in children who began treatment under age five. Results from an investigator-sponsored Phase 2 in children 3-11 years old with several genetic growth-related conditions demonstrated marked improvement in annualized growth velocity and height standard deviation across all conditions studied.
◦At ICCBH on June 17, a new investigator-led study showed VOXZOGO significantly increased bone length while maintaining bone strength through 5 years of observation in children with achondroplasia, an essential functional outcome for children receiving multi-year treatment. Phase 2 and Phase 3 data on VOXZOGO demonstrated durable safety and efficacy, and improvements on proportionality and health-related quality of life in children with achondroplasia.
•Building on its leadership in achondroplasia, BioMarin’s clinical programs across multiple new growth-related conditions are underway. The pivotal study with VOXZOGO for hypochondroplasia is actively enrolling. Clinical programs in idiopathic short stature, Noonan Syndrome, Turner Syndrome and SHOX deficiency are all on track for enrollment later this year.

•During the second quarter, through extensive supply chain efforts, BioMarin secured ample VOXZOGO supply to support patient demand worldwide. As of the end of the quarter, the company was able to provide VOXZOGO supply to new patients immediately, as identified. Additionally, the company has ample supply capacity to support all ongoing VOXZOGO clinical programs in hypochondroplasia, idiopathic short stature, Noonan Syndrome, Turner Syndrome and SHOX deficiency, as well as expected commercial demand.

Establish ROCTAVIAN opportunity

•Today, the company announced its updated strategy for ROCTAVIAN. The strategy will enable ROCTAVIAN to contribute to BioMarin’s long-term profitability. By focusing commercial, research and manufacturing programs in three prioritized countries, including the United States, Germany and Italy, BioMarin anticipates reducing annual direct ROCTAVIAN expenses to approximately $60 million, beginning in 2025. The company has already begun to operationalize the reduction of ROCTAVIAN expenses this year to achieve $60 million in expenses beginning in full-year 2025. As a result of these changes, the company expects ROCTAVIAN to be profitable by the end of 2025.
•During the quarter, BioMarin treated 3 patients in the U.S. and 2 in Italy, generating $7 million in revenue. BioMarin’s global commercial team will continue to focus on key elements critical to supporting ROCTAVIAN uptake in with the U.S., Germany and Italy.

Focus R&D on the most promising assets

•During the quarter, BioMarin progressed development of its prioritized pipeline products: BMN 351, BMN 349, and BMN 333. BMN 351, BioMarin’s next generation oligonucleotide for Duchenne Muscular Dystrophy, has completed enrollment of the first dose cohort, with data expected by year-end. With BMN 349, a potential best-in-class, oral therapeutic for Alpha-1 antitrypsin deficiency (AATD)-associated liver disease, the company will begin enrolling its first-in-human study with healthy volunteers later this year. BMN 333, a long-acting C-type natriuretic peptide (CNP) for multiple growth disorders, is completing IND-enabling activities and is expected to enter the clinic in early 2025.
•During the quarter, the company chose to discontinue development of BMN 293, a gene therapy for hypertrophic cardiomyopathy. Applying its focused approach to investing in only those assets that have the highest potential impact for patients, the time and resources anticipated to bring BMN 293 through development and to market no longer met BioMarin’s high bar for advancement.

Accelerate EPS growth and expand margins

•Sustained strong performance in the second quarter highlighted BioMarin’s ongoing execution of its financial strategy to drive year-over-year Non-GAAP Operating Margin expansion and Non-GAAP EPS growth faster than revenues.
•The company raised full-year 2024 guidance for Total Revenues, Non-GAAP Operating Margin, and Non-GAAP Diluted EPS. The improved guidance reflects the underlying strength of enzyme products and continued high demand for VOXZOGO, along with BioMarin’s commitment to accelerate profitability while continuing to invest in innovation. BioMarin’s updated full-year 2024 guidance does not reflect the impact of potential additional future business decisions that may result from its ongoing strategic business review.
Investor Day to be held Wednesday, September 4th. Event details will be available later in August.

On August 5, 2024 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the second quarter ended June 30, 2024, and provided a corporate update (Press release, BioCryst Pharmaceuticals, AUG 5, 2024, View Source [SID1234645330]).

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"The first half of 2024 has been outstanding for BioCryst due to the success we are having in the marketplace with ORLADEYO. As a result, we are increasing our full year guidance for ORLADEYO, advancing multiple programs toward the clinic in the next 18 months and moving the company closer to profitability," said Jon Stonehouse, president and chief executive officer of BioCryst.

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

ORLADEYO net revenue in the second quarter of 2024 was $108.3 million (+34 percent year-over-year (y-o-y)).

Operational improvements drove revenue above expectations for the second quarter. This included a three percent increase in the overall rate of paid patients relative to the end of 2023, which now stands at 74.4 percent.

New patient starts continued at the same high rate seen in the prior two quarters, matching the new patient demand seen in the first three quarters of the launch in 2021, and patient retention remained strong. We continue to see more than 60 percent of patients on paid therapy staying on for at least a year.

A recent market research study showed that 52 percent of allergist/immunologists are extremely likely to prescribe ORLADEYO to more patients, up from 29 percent in early 2023.

With additional recent approvals and reimbursement authorizations in Europe and Latin America, ORLADEYO is now commercially available to patients in more than 20 countries. Ex-U.S. ORLADEYO revenue in the second quarter increased 51 percent y-o-y and accounted for 11 percent of global ORLADEYO net revenues.
"Our second quarter revenue growth and increased full year guidance for ORLADEYO reflect strong underlying demand and favorable patient outcomes, combined with our continuing focus on improving patient services and market access operations. The real-world experience of patients who respond to ORLADEYO is consistent with the 91 percent reduction in attacks from baseline that we saw in long-term clinical trials. The potential for patients to have that high level of HAE attack control in a once-daily pill is a major differentiator in the marketplace that makes ORLADEYO’s trajectory toward $1 billion in peak sales increasingly clear," said Charlie Gayer, chief commercial officer of BioCryst.

Rare Disease Pipeline

The goal with our pipeline is to build on our success with ORLADEYO by bringing additional selected, highly differentiated rare disease products to patients.

The company remains on track to submit a regulatory filing in 2025 to expand the ORLADEYO label to enable children as young as two years of age to receive an oral granule formulation of ORLADEYO. ORLADEYO would be the first oral prophylactic therapy for children with HAE.

The company has completed its clinical evaluation of its oral Factor D inhibitor, BCX10013. The drug was safe and well tolerated at all doses studied, however the level of clinical activity observed was less than other therapies on the market and potential partners have declined to make the additional investment required to evaluate higher doses. BioCryst plans to discontinue development, consistent with its previously announced plans.

The company expects to advance BCX17725, its KLK-5 inhibitor for the treatment of Netherton syndrome, into the clinic by the end of 2024.

Netherton syndrome is a serious, rare, lifelong genetic disorder affecting the skin, hair and immune system. People with Netherton syndrome often have red, scaly, inflamed skin, fragile hair, and are more likely to develop skin infections, allergies, asthma and eczema. Netherton syndrome can be life threatening, especially during infancy when patients are vulnerable to dehydration and recurrent infections. Currently, there is no approved treatment for Netherton syndrome.

In 2025, the company plans to advance avoralstat, a plasma kallikrein inhibitor, into a clinical trial of patients with diabetic macular edema (DME).

DME is an important cause of vision loss in diabetes and is due to leakage from the blood vessels in the retina. While current treatments focus on VEGF inhibition, DME can develop from other mechanisms, such as the kallikrein-bradykinin pathway. This is supported by observations that many DME patients have an incomplete response to intravitreal anti-VEGF therapies that are administered every four to eight weeks. Avoralstat targets the kallikrein-bradykinin system on the retinal vascular endothelial cells and may result in less vascular leakage and less edema. Avoralstat, delivered to the suprachoroidal space as a depot formulation, is designed to provide high dose levels to the retinal vessels with long-lasting exposure, which could result in less frequent injections and a reduced burden on patients and the healthcare system.
Second Quarter 2024 Financial Results

For the three months ended June 30, 2024, total revenues were $109.3 million, compared to $82.5 million in the second quarter of 2023 (+32.5 percent year-over-year (y-o-y)). The increase was primarily due to $108.3 million in ORLADEYO net revenue in the second quarter of 2024, compared to $81.0 million in ORLADEYO net revenue in the second quarter of 2023 (+33.7 percent y-o-y).

R&D expenses for the second quarter of 2024 decreased to $37.6 million from $51.2 million in the second quarter of 2023 (-26.6 percent y-o-y), primarily due to decreased spending on BCX10013 and the discontinuation of the BCX9930 program. These reductions were partially offset by increased investment in BCX17725, avoralstat and other discovery programs, and our ongoing ORLADEYO pediatric trial.

Selling, general and administrative expenses for the second quarter of 2024 increased to $61.2 million, compared to $51.0 million in the second quarter of 2023 (+20.0 percent y-o-y), primarily due to an increase in commercial expenses to support growing revenue, newly launched regions and expanded international operations. In addition, there was an increase in general and administrative expenses, primarily related to an increase in resourcing to support our accounting and IT functions.

Total operating expenses were $100.6 million for the second quarter of 2024, compared to $103.2 million in the second quarter of 2023 (-2.5 percent y-o-y). Non-cash stock compensation was $13.2 million for the second quarter of 2024. Total operating expenses, not including non-cash stock compensation for the second quarter of 2024 were $87.4 million, compared to $90.4 million in the second quarter of 2023 (-3.3 percent y-o-y).

The company generated a GAAP operating profit of $8.8 million in the second quarter of 2024. This compares to a GAAP operating loss of $20.7 million in the second quarter of 2023. Adjusted for non-cash stock compensation, the non-GAAP operating profit was $21.9 million in the second quarter of 2024, compared to a non-GAAP operating loss of $7.9 million in the second quarter of 2023.

Interest expense was $24.7 million in the second quarter of 2024, compared to $28.9 million in the second quarter of 2023 (-14.5 percent y-o-y). The decrease was primarily due to a decrease in the amortization of interest associated with our royalty financing obligations.

Net loss for the second quarter of 2024 was $12.7 million, or $0.06 per share, compared to a net loss of $75.3 million, or $0.40 per share, for the second quarter of 2023. In the second quarter of 2023, there was a $29.0 million one-time debt extinguishment fee related to the close-out of the Athyrium debt facility. Excluding this one-time event, non-GAAP net loss for the second quarter of 2023 was $0.24 per share.

Cash, cash equivalents, restricted cash and investments totaled $338.1 million at June 30, 2024, compared to $415.7 million at June 30, 2023. Operating cash use for the second quarter of 2024 was $0.2 million.