On May 6, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the European Medicines Agency (EMA) has validated its Type II variation application for Opdivo (nivolumab) plus Yervoy (ipilimumab) for the first-line treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) (Press release, Bristol-Myers Squibb, MAY 6, 2024, View Source [SID1234642671]). The EMA’s validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

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"Colorectal cancer is the third most commonly diagnosed cancer in the world, and more options are needed specifically for patients with MSI-H/dMMR mCRC, who are less likely to benefit from treatment with chemotherapy," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "We look forward to working with the European Medicines Agency to discuss bringing the dual immunotherapy combination of Opdivo and Yervoy to patients with MSI-H/dMMR mCRC across Europe."

The submission is based on results from the CheckMate -8HW study, in which Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy as assessed by Blinded Independent Clinical Review (BICR) for the first-line treatment of patients with MSI-H/dMMR mCRC. These data from CheckMate -8HW were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium. The study is ongoing to assess the other dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone, as well as secondary endpoints. The safety profile for the dual immunotherapy combination remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.

About CheckMate -8HW

CheckMate -8HW (NCT04008030) is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or investigator’s choice chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).

Approximately 830 patients were randomized to receive either Opdivo monotherapy (Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. The trial also includes several secondary safety and efficacy endpoints, including overall survival (OS).

The study is ongoing to assess the second dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy, as well as secondary endpoints.

About dMMR or MSI-H Colorectal Cancer

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined.

Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors; they are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.

On May 6, 2024 bluebird bio, Inc. (Nasdaq: BLUE) reported that it will host a conference call to discuss first quarter 2024 results and business updates on May 9, at 8:00 a.m. ET (Press release, bluebird bio, MAY 6, 2024, View Source [SID1234642670]).

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To participate in the conference call, please dial +1 (800) 715-9871 (U.S. and Canada) and ask to be joined into the bluebird call or provide the Conference ID 9768329.

In addition, members of the management team will participate in the following upcoming investor conferences:

BofA Securities 2024 Health Care Conference, Thursday, May 16, at 10:00 a.m. PT (1:00 p.m. ET) in Las Vegas, NV
Goldman Sachs 45th Annual Global Healthcare Conference, Wednesday, June 12, at 11:20 a.m. ET in Miami Beach, FL
To access the live webcasts of bluebird bio’s first quarter results conference call and fireside chats, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source Replays of the webcasts will be available on the bluebird bio website for 90 days following the events.

On May 6, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported financial results for the three months ended March 31, 2024, and provided an update on its corporate progress (Press release, BioNTech, MAY 6, 2024, View Source [SID1234642669]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"In the past weeks, we have reported positive preliminary data for both our individualized and off-the-shelf mRNA-based candidates which further underline the potential of our iNeST and FixVac platforms. We look forward to providing more updates this year across our oncology portfolio, including our bispecific antibody and ADC programs," said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "In the remainder of the year, we plan to develop and commercialize a variant-adapted COVID-19 vaccine and accelerate our clinical development activities towards realizing the full potential of our oncology pipeline with a view to becoming a commercial company with marketed medicines for cancer and infectious diseases."

Financial Review for the First Quarter 2024

in millions €, except per share data First Quarter 2024 First Quarter 2023
Total Revenues 187.6 1,277.0
Net (Loss) / Profit (315.1) 502.2
(Loss) / Diluted Earnings per Share (1.31) 2.05
Total revenues reported were €187.6 million for the three months ended March 31, 2024, compared to €1,277.0 million for the comparative prior year period. The year-over-year change was mainly due to lower commercial revenues from the sales of BioNTech’s COVID-19 vaccine worldwide resulting from endemic-level demand for COVID-19 vaccines.

Cost of sales were €59.1 million for the three months ended March 31, 2024, compared to €96.0 million for the comparative prior year period. The change was mainly due to recognizing lower cost of sales from BioNTech’s decreased COVID-19 vaccine sales, which included the share of gross profit that BioNTech owes its collaboration partner Pfizer Inc. ("Pfizer") and royalty expenses based on BioNTech’s sales. In addition, cost of sales was impacted by expenses arising from inventory write-offs and destruction of inventory.

Research and development ("R&D") expenses were €507.5 million for the three months ended March 31, 2024, compared to €334.0 million for the comparative prior year period. R&D expenses were mainly influenced by progressing clinical studies for pipeline candidates. The increase was further driven by an increase in wages, benefits and social security expenses resulting from an increase in headcount.

General and administrative ("G&A") expenses reached €117.0 million for the three months ended March 31, 2024, compared to €111.8 million for the comparative prior year period. G&A expenses were primarily driven by increased expenses for IT environment and wages, benefits, and social security expenses resulting from an increase in headcount.

Income taxes were realized with an amount of €16.7 million of tax income for the three months ended March 31, 2024, compared to €205.5 of tax expenses accrued for the comparative prior year period. The effective income tax rate for the three months ended March 31, 2024, was approximately 5.0% applicable on the negative income.

Net loss was €315.1 million for the three months ended March 31, 2024, compared to a net profit of €502.2 million for the comparative prior year period.

Cash and cash equivalents as well as security investments as of March 31, 2024, reached €16,939.3 million, comprising €8,976.6 million cash and cash equivalents and €7,962.7 million security investments, respectively.

Loss per share was €1.31 for the three months ended March 31, 2024, compared to diluted earnings per share of €2.05 for the comparative prior year period.

Shares outstanding as of March 31, 2024, were 237,725,735, excluding 10,826,465 shares held in treasury.

"We started the year making good progress across our oncology pipeline. We dosed the first patient in our second pivotal Phase 3 trial and aim to have ten or more potentially registrational trials by the end of 2024. Revenues in the first quarter reflect the seasonal demand for COVID-19 vaccines, and we expect to recognize approximately 90% of our full year revenues in the last months of 2024, mostly in Q4 of 2024. With a strong cash position of €16.9 billion, we are well positioned to invest in our innovative R&D pipeline and scale the business for commercial readiness in oncology," said Jens Holstein, CFO of BioNTech. "We remain committed to seizing the opportunity to transform the way cancer and infectious diseases are treated, especially with our tremendous experience in using our mRNA platforms. We will focus the remainder of the year on executing and delivering on this vision with the aim to drive sustainable long-term growth and to create future value for patients, society and our shareholders."

Outlook for the 2024 Financial Year

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 group revenues for the full 2024 financial year to be in the range of €2.5 to €3.1 billion. The range reflects certain assumptions, including, but not limited to, expectations regarding: 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 the Company’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 Capex2:

R&D expenses3 €2.4 billion – €2.6 billion
SG&A expenses4 €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 March 31, 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 three months ended March 31, 2024, as published by the German Central Bank (Deutsche Bundesbank).
2 Numbers reflect current base case projections and are calculated based on constant currency rates, and exclude external risks that are not yet known and/or quantifiable, including, but not limited to, the effects of ongoing and/or future legal disputes or related activity.
3 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.
4Anticipated expenses related to external legal advice in connection with certain legal litigations are not reflected in SG&A but in other operating expenses. Guidance does not include and may be impacted by potential payments resulting from the outcomes of ongoing or future contractual and legal disputes or related activity, such as judgments or settlements.

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

Omicron XBB.1.5-adapted Monovalent COVID-19 Vaccine (COMIRNATY)

BioNTech and Pfizer developed, manufactured and delivered their Omicron XBB.1.5-adapted monovalent COVID-19 vaccine, which has received multiple regulatory approvals, including full approvals, authorizations for emergency or temporary use, or marketing authorizations, in more than 40 countries and regions. BioNTech is now focused on preparing for variant strain vaccine adaptation to be ready for commercial launch ahead of the upcoming 2024/2025 vaccination season, pending approvals.

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 ongoing.

Select Oncology Pipeline Highlights

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"). The program has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration ("FDA") for the treatment of advanced endometrial cancer in patients who progressed on or after treatment with immune checkpoint inhibitors.

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 is enrolling HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) patients with advanced/recurrent endometrial carcinoma and aims to recruit 140 patients. A confirmatory Phase 3 trial (NCT06340568) in this patient population is planned to start in 2024.

In January, the first patient was dosed in a pivotal Phase 3 trial (NCT06018337) evaluating BNT323/DB-1303 in patients with Hormone Receptor-positive ("HR+") and HER2-low metastatic breast cancer that have progressed on hormone therapy and/or cyclin-dependent kinase 4/6 ("CDK4/6") inhibition.

BNT325/DB-1305 is an ADC candidate targeting TROP2 that is being developed in collaboration with DualityBio. In January, BioNTech and DualityBio received Fast Track designation for BNT325/DB-1305 from the U.S. FDA for the treatment of patients with platinum-resistant ovarian epithelial, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens. A Phase 1/2 clinical trial (NCT05438329) is ongoing.

BNT326/YL202 is an ADC candidate targeting HER3 that is being developed in collaboration with MediLink Therapeutics (Suzhou) Co., Ltd. ("MediLink"). A multicenter, open-label, first-in-human Phase 1 clinical trial (NCT05653752) evaluating BNT326/YL202 as a later-line treatment in patients with locally advanced or metastatic epidermal growth factor receptor ("EGFR")-mutated non-small cell lung cancer ("NSCLC") or HR+/HER2-negative breast cancer is ongoing in the United States and China. Preliminary data from this study are expected to be presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.

Next-Generation Immune Checkpoint Immunomodulator Programs

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 in collaboration with Genmab A/S ("Genmab"). Data from a Phase 2 trial (NCT05117242) evaluating BNT311/GEN1046 in combination with pembrolizumab in pretreated NSCLC patients are expected to be presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.

BNT327/PM8002 is an anti-VEGF-A antibody candidate fused to a humanized anti-PD-L1 VHH being developed in collaboration with Biotheus Inc. ("Biotheus"). BNT327/PM8002 is currently being evaluated in Phase 1 and Phase 2/3 clinical trials in China to assess the efficacy and safety of the candidate as monotherapy or in combination with chemotherapy in various indications. An Investigational New Drug application has been accepted by the U.S. FDA for further studies in the United States, and global trials are planned to start this year. Monotherapy data from the Phase 1/2 trials are planned to be presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.
Cancer Vaccine Programs

BNT116 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 six shared lung cancer associated antigens. A randomized, controlled Phase 2 clinical trial (NCT05557591) is ongoing to evaluate BNT116 in combination with cemiplimab versus cemiplimab alone as first-line treatment in patients with advanced NSCLC whose tumors express PD-L1 in ≥ 50% of tumor cells.

In April 2024, data from a Phase 1 trial cohort (NCT05142189) were presented at the AACR (Free AACR Whitepaper) Annual Meeting. Patients were treated with BNT116 in combination with docetaxel after progression on a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy. Preliminary data of BNT116 in combination with docetaxel show encouraging antitumor activity, consistent induction of immune responses, a manageable safety profile, and no signs of additive toxicity. Efficacy results suggest that combination therapy with BNT116 and docetaxel was active with an overall response rate ("ORR") of 30% and a disease control rate ("DCR") of 85%.

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., a member of the Roche Group ("Genentech"). Autogene cevumeran is being evaluated in ongoing Phase 2 trials in adjuvant resected PDAC (NCT05968326), first-line melanoma (NCT03815058) and adjuvant colorectal cancer ("CRC") (NCT04486378). Epidemiologic data including post-operative circulating tumor DNA ("ctDNA") prevalence and prognostic value from a non-interventional, observational study (NCT04813627) in patients with resected high-risk stage II/III CRC are expected to be presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting. A Phase 2 clinical trial in an additional indication is planned.

In April 2024, long-term follow-up data from an investigator-initiated Phase 1 trial in patients with resected PDAC were presented at the AACR (Free AACR Whitepaper) Annual Meeting. The data showed that the individualized mRNA cancer vaccine candidate autogene cevumeran continues to show polyspecific T cell responses up to three years after vaccination and that vaccine responses correlate with delayed tumor recurrence. The investigator-initiated, single center Phase 1 trial (NCT04161755) evaluated the safety of autogene cevumeran in sequential combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and standard-of-care chemotherapy in 16 patients with resected PDAC. Data from the 1.5-year median follow-up were previously published in Nature (Rojas, L.A et al. 2023).

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. After determination of the recommended Phase 2 dose, BioNTech plans to initiate a pivotal trial in patients with germ cell tumors. BioNTech plans to present 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.

Corporate Update for the First Quarter 2024 and Key Post Period-End Events

In February, BioNTech entered into a strategic collaboration with Autolus Therapeutics plc ("Autolus") aimed at advancing both companies’ autologous CAR-T programs towards commercialization, pending regulatory authorizations. The collaboration also grants BioNTech the option to access a suite of Autolus’s target binders and cell programming technologies.

In March, BioNTech announced that Annemarie Hanekamp will be joining the Company’s Management Board as Chief Commercial Officer on July 1, 2024. Sean Marett, current Chief Business and Commercial Officer, will retire as planned from the Management Board while remaining a specialist advisor. Sean Marett’s responsibilities as Chief Business Officer are being gradually transferred to James Ryan, Ph.D., Chief Legal Officer, who will also take on the role of Chief Business Officer at the end of the transition phase. BioNTech has also appointed a General Manager for the U.S. who has commenced building out commercial operations in the country and aims to establish further expertise in the Company’s global commercial group to drive its first global product launch.

Upcoming Investor and Analyst Events

Annual General Meeting: May 17, 2024
Second Quarter 2024 Financial Results and Corporate Update: August 5, 2024
Innovation Series (Digital & AI Day): October 1, 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, May 6, 2024, at 8:00 a.m. EDT (2:00 p.m. CEST) to report its financial results and provide a corporate update for three months ended March 31, 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.

Participants may also access the slides and the webcast of the conference call via the "Events & Presentations" page of the Investors’ section of the Company’s website at www.BioNTech.com. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

On May 6, 2024 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported that new economic model data will be presented on APHEXDA (motixafortide) for CD34+ hematopoietic stem cell (HSC) mobilization in patients with multiple myeloma at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) – The Professional Society for Health Economics and Outcomes Research – 2024 conference, taking place May 5-8, 2024, in Atlanta, Georgia (Press release, BioLineRx, MAY 6, 2024, View Source [SID1234642668]).

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Autologous stem cell transplantation (ASCT) is part of the standard of care treatment paradigm for multiple myeloma and prolongs survival for patients with this cancer type.1 Historically, depending on induction regimens and mobilization strategies, approximately 50% to 75% of patients required more than one apheresis session to collect a target number of cells.2,3 Uncertainty in stem cell mobilization and the possible need for multiple apheresis sessions may result in psychological and logistical burden on patients, in addition to financial and operational inefficiencies for apheresis centers.

The new economic model assessed the cost and healthcare resource utilization impacts of multiple apheresis attempts via a comparison between daily filgrastim (G-CSF) alone and in combination with APHEXDA, and an indirect comparison between daily filgrastim used with either plerixafor or APHEXDA, using drug costs from Micromedex, procedure costs from CMS.gov and data for apheresis days obtained from clinical trials and product labels. The data are expected to be published in Value in Health, Volume 27, Issue 6, S1 (June 2024.)

Poster Presentation at ISPOR 2024

Georgia World Congress Center, Atlanta, Georgia

Poster Session Details

Poster: Number EE148
Title: The Institutional Level Impact of Additional Apheresis Days for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation on Costs and Healthcare Resource Utilization
Presenter: Jeffrey R Skaar, PhD, Trinity Life Sciences, New York, NY and Jennifer L Lessor, MPH, BioLineRx USA, Inc., Waltham, MA
Poster Session: Economic Evaluation
Date: Monday, May 6, 2024
Time: 3:30 PM – 6:30 PM

The new economic model data to be presented at ISPOR 2024 builds on the evaluation of APHEXDA for CD34+ HSC mobilization in patients with multiple myeloma in apheresis center operations.

About the GENESIS Trial
GENESIS (NCT 03246529) is a 2-part, Phase-3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim (G-CSF), compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study. The primary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in one apheresis session.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow. According to the American Cancer Society, in 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the U.S.4 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.

About APHEXDA
APHEXDA (motixafortide) is a CXCR4 antagonist with long receptor occupancy (greater than 72 hours) that, in combination with filgrastim (G-CSF), enables mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplantation in patients with multiple myeloma.5

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION
APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide.

WARNINGS AND PRECAUTIONS

Anaphylactic Shock and Hypersensitivity Reactions: Anaphylactic shock and hypersensitivity reactions have occurred. Premedicate all patients with a triple drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor approximately 30-60 minutes prior to each dose of APHEXDA. Administer APHEXDA in a setting where personnel and therapies are immediately available for treatment of anaphylaxis and other systemic reactions. Monitor patients for 1 hour following APHEXDA administration and manage reactions promptly. Patients receiving negative chronotropic drugs (e.g., beta-blockers) may be more at risk for hypotension in the event of a hypersensitivity reaction and these drugs, when appropriate, should be replaced with non-chronotropic drugs.
Injection Site Reactions: Injection site reactions (73%) including pain (53%), erythema (27%), and pruritus (24%) have occurred. Severe reactions occurred in 9% of patients. Premedicate with an analgesic premedication (e.g., acetaminophen) prior to each APHEXDA dose. Use analgesic medication and local treatments post-dose, as needed.
Tumor Cell Mobilization in Patients with Leukemia: For the purpose of hematopoietic stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia.
Leukocytosis: Administering APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use.
Potential for Tumor Cell Mobilization: When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
Embryo-fetal Toxicity: Based on its mechanism of action, APHEXDA can cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating treatment with APHEXDA and advise use of effective contraception during treatment and for 8 days after the final dose.
ADVERSE REACTIONS
The most common adverse reactions (incidence >20%) in patients treated with APHEXDA were injection site reactions [73%, including pain (53%), erythema (27%), pruritus (24%)]; pruritus (38%); flushing (33%); back pain (21%).

USE IN SPECIFIC POPULATIONS

Pregnancy: Please see the important information in Warnings and Precautions under Embryo-fetal Toxicity.

Lactation: There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Advise females that breastfeeding is not recommended during treatment with APHEXDA and for 8 days after the final dose.

Pediatric Use: The safety and effectiveness of APHEXDA have not been established in pediatric patients.

Please see the accompanying full Prescribing Information.

On May 6, 2024 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the first quarter ended March 31, 2024, and provided a corporate update (Press release, BioCryst Pharmaceuticals, MAY 6, 2024, View Source [SID1234642667]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"We are off to a fantastic start to the year with outstanding ORLADEYO revenue growth and our prioritized pipeline programs advancing on schedule. We are focused on continuing this momentum as we see strong patient demand for ORLADEYO and more pipeline programs advancing into the clinic, starting later this year," 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 first quarter of 2024 was $88.9 million (+30 percent year-over-year (y-o-y)).

In the first quarter, the U.S. commercial team accelerated patients going through annual reimbursement reauthorization from free drug to paid drug faster than in previous years, generating higher than expected ORLADEYO revenue.

New patient growth remained strong, with the past two quarters having the most new prescriptions in the United States since the first two quarters of the launch.

Sales from outside the U.S. contributed 10 percent of global ORLADEYO net revenues in the first quarter, as the number of patients treated with ORLADEYO continued to grow strongly and consistently in new and existing markets.

New real-world evidence showing significant reductions in healthcare resource utilization among patients with HAE following ORLADEYO initiation to be presented in a poster on May 8 at the 2024 International Society for Pharmacoeconomics and Outcomes Research conference (ISPOR).
"Our team made exceptional efficiency improvements in the U.S. prescription reauthorization process, and new prescriptions remained very strong as physicians and patients increasingly understand that ORLADEYO provides excellent efficacy and convenience. These two successes helped us exceed our revenue projections for the quarter and, as a result, we are increasing our revenue guidance for 2024," said Charlie Gayer, chief commercial officer of BioCryst.

Rare Disease Pipeline

The goal with our pipeline is to continue bringing selected, highly differentiated rare disease products to the market, and to reproduce the commercial success we have delivered with ORLADEYO. Milestones in the next 18 months include:

The ongoing proof-of-concept trial with BCX10013, an oral Factor D inhibitor, remains on track. The company expects to partner or discontinue the program later this year.

Enrollment is complete in the APeX-P pediatric trial. Data from the trial will support a regulatory filing in 2025 to expand the ORLADEYO label to enable children as young as two years of age to receive ORLADEYO. ORLADEYO would be the first oral prophylactic therapy for children with HAE.

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 rare, lifelong genetic disorder that often presents in neonates or infancy with red, scaly and inflamed skin and susceptibility to recurrent skin infections. 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 the most common cause of vision loss in individuals with diabetes and at least one-third of patients have persistent DME despite anti-VEGF therapies, which are administered via monthly injection. By delivering avoralstat with Clearside’s SCS microinjector directly into the suprachoroidal space of the eye in the clinical trial, avoralstat could inhibit plasma kallikrein at the sites of edema formation in DME disease, the retinal and choroidal vascular endothelium. With its low solubility, the drug could persist in the eye at the site of disease for a long duration, resulting in less frequent injections.
"It is very exciting to be advancing our pipeline of first-in-class/best-in-class molecules into the clinic to generate proof-of-concept data across multiple programs and diseases, and to be so close to delivering the first oral prophylactic option to children with HAE," said Dr. Helen Thackray, chief research and development officer of BioCryst.

First Quarter 2024 Financial Results

For the three months ended March 31, 2024, total revenues were $92.8 million, compared to $68.8 million in the first quarter of 2023 (+34.9 percent y-o-y). The increase was primarily due to $88.9 million in ORLADEYO net revenue in the first quarter of 2024, compared to $68.4 million in ORLADEYO net revenue in the first quarter of 2023 (+30 percent y-o-y).

Research and development (R&D) expenses for the first quarter of 2024 decreased to $46.5 million from $48.4 million in the first quarter of 2023 (-3.9 percent y-o-y), primarily due to decreased spending on BCX10013 due to our plan to either out-license or discontinue late-stage development and commercialization, which was announced in January 2024, as well as the discontinuation of the BCX9930 program, which was announced in December 2022. These reductions were partially offset by increased investment in BCX17725 and other discovery programs, and ORLADEYO label expansion and life cycle investments, such as our ongoing ORLADEYO pediatric trial.

Selling, general and administrative (SG&A) expenses for the first quarter of 2024 increased to $59.4 million, compared to $47.9 million in the first quarter of 2023 (+24.0 percent y-o-y). The increase was primarily due to increased investment to expand and enhance the U.S. commercial team and expand and support international operations.

Operating loss for the first quarter was $14.5 million, adjusted to $0.8 million excluding non-cash stock compensation.

Interest expense was $24.5 million in the first quarter of 2024, compared to $27.4 million in the first quarter of 2023 (-10.6 percent y-o-y). The decrease was primarily due to a decrease in the amortization of interest associated with our royalty financing obligations, partially offset by an increase in interest expense associated with the Pharmakon debt refinancing secured in April 2023.

Net loss for the first quarter of 2024 was $35.4 million, or $0.17 per share, compared to a net loss of $53.3 million, or $0.28 per share, for the first quarter of 2023. Non-GAAP net loss for the first quarter of 2024 was $34.1 million, or $0.17 per share when excluding one-time costs associated with the R&D restructuring, totaling $1.3 million. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Cash, cash equivalents, restricted cash and investments totaled $338.4 million at March 31, 2024, compared to $403.1 million at March 31, 2023. Net cash utilization for the first quarter of 2024 was $52.4 million, which was driven by debt service, royalty payments and one-time first quarter compensation expense. We expect, as in previous years, that the first quarter will be the highest quarter of operating cash use for the year, and that operating cash use for the remaining quarters of 2024 will normalize around $10-$12 million per quarter. We expect that total cash at the end of 2024 will be above $300 million.

Non-GAAP Pro forma Financial Measures

The information furnished in this release includes non-GAAP pro forma financial measures that differ from measures calculated in accordance with generally accepted accounting principles in the United States of America ("GAAP"), including financial measures labeled as "non-GAAP" or "adjusted."

We believe providing these non-GAAP measures, which show our pro forma results with these items adjusted, is valuable and useful since they allow the company and investors to better understand the company’s financial performance in the absence of these one-time events and allowed investors to more accurately understand our current period results and more easily compare them to future results. These non-GAAP pro forma measures also correspond with the way we expect investors and financial analysts to compare our results. Our non-GAAP pro forma measures should be considered only as supplements to, and not as substitutes for or in isolation from, our other measures of financial information prepared in accordance with GAAP, such as GAAP revenue, operating income, net income, and earnings per share.

Our references to our first quarter 2024 "non-GAAP pro forma" financial measures of adjusted net loss and adjusted earnings per share constitute non-GAAP financial measures. They refer to our GAAP results, adjusted to show the results without the one-time costs associated with the R&D restructuring. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Financial Outlook for 2024

Based on the team’s success in accelerating ORLADEYO patients through the U.S. reauthorization process faster than anticipated, the company is adjusting its outlook for full year 2024 global net ORLADEYO revenue to be between $390 million and $400 million, the top end of its prior guidance range.

The company expects full year 2024 operating expenses to be between $365 million and $375 million, flat to full year 2023 operating expenses.

This operating expense outlook does not reflect non-cash stock compensation expense, or one-time expenses related to the previously announced workforce reduction implemented in the first quarter of 2024.

Based on the company’s disciplined approach to capital allocation, and the adjusted revenue guidance for ORLADEYO, the company is even more confident that it will achieve a full-year operating profit in 2024 (not including non-cash stock compensation), be approaching quarterly positive earnings per share (EPS) and positive cash flow in the second half of 2025 (not including non-cash stock compensation), and be profitable on an EPS basis, with positive cash flow, for full year 2026. The company expects it can achieve these financial milestones without raising additional funds and does not intend to draw the additional $150 million of debt available to it from Pharmakon.

Conference Call and Webcast
BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 1-844-481-2942 for domestic callers and 1-412-317-1866 for international callers. A live webcast and replay of the call will be available online in the investors section of the company website at www.biocryst.com.