On February 26, 2024 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported a business update and announced financial results for the fourth quarter and full year of 2023 (Press release, Cogent Biosciences, FEB 26, 2024, View Source [SID1234640445]).

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"We have entered 2024 in a very strong position," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "We are now actively enrolling three registration-directed clinical trials of bezuclastinib across NonAdvSM, AdvSM and 2nd-line GIST patients, all of which are on track to deliver top-line results in 2025. With our recent fundraising, we are funded into 2027, and based on the clinical data we have presented across these programs to date, believe strongly that bezuclastinib has the opportunity to become the best-in-class KIT mutant inhibitor for these three indications."

Q4 2023 and Recent Business Highlights

In February 2024, reported positive Part 1b data from the Company’s ongoing Phase 2 SUMMIT trial at the 2024 American Academy of Allergy Asthma & Immunology Annual Meeting (AAAAI) meeting. SUMMIT is a registration-directed, randomized, double-blind, placebo-controlled, global, multicenter, clinical trial of bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM). Key highlights include:

Announced the 100 mg Recommended Phase 2 Dose (RP2D)
Demonstrated a well-tolerated safety profile, generally consistent with placebo
Introduced Cogent’s MS2D2, a novel, refined patient reported outcomes measure (PROM) designed to assess symptomatic severity and improvement
Reported a 51% week 12 mean improvement in total symptom score (TSS) for bezuclastinib, including 70% of patients achieving ≥50% improvement in symptom severity
Reported a 49% week 12 mean improvement in quality of life (MC-QoL) for bezuclastinib

In February 2024, closed a $225 million oversubscribed private investment in public equity (PIPE) financing. Cogent sold approximately 17 million shares of its common stock at a price of $7.50 per share, representing a premium of approximately 37% to its closing price on February 13, 2024. The financing also included Series B non-voting convertible Preferred Stock convertible into approximately 13 million shares of its common stock.

In December 2023, reported positive clinical data from the Phase 2 SUMMIT and APEX trials at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting. Highlights from APEX, a registration-directed trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM), include:

Reported an encouraging safety and tolerability profile with no related cognitive impairment or bleeding events
Achieved impressive effects in key biomarkers of disease burden
Achieved 56% Overall Response Rate (ORR) in TKI-naïve patients, including 86% ORR by Pure Pathological Response (PPR) criteria

In December 2023, presented new preclinical data highlighting the potential best-in-class potency and selectivity of Cogent’s ErbB2 inhibitor and announced a third Cogent discovery stage PI3Kα inhibitor program at the San Antonio Breast Cancer Symposium (SABCS).

The novel EGFR-sparing, brain-penetrant ErbB2 inhibitor demonstrated a superior efficacy profile, reaching 80% brain penetrance with potent coverage of key mutations
The novel, H1047R mutant-selective PI3Kα inhibitor demonstrated high clinical target engagement without metabolic dysfunction commonly associated with molecules in the class

In November 2023, reported updated clinical data from the lead-in portion of the ongoing PEAK Phase 3 trial evaluating bezuclastinib in combination with sunitinib in patients with GIST at the Connective Tissue Oncology Society (CTOS) annual meeting. Positive lead-in data was first presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in June.

Safety and tolerability data from 42 patients enrolled in Part 1a and Part 1b were consistent with results shared at the 2023 ASCO (Free ASCO Whitepaper) annual meeting, demonstrating the combination of bezuclastinib and sunitinib was well tolerated with an adverse event profile similar to sunitinib monotherapy
Updated clinical activity from a subset of 2nd-line GIST patients demonstrated a 33% confirmed overall response rate (ORR) with ongoing median duration of therapy greater than 14 months. Together with clinical data previously reported from a Phase 1/2 trial, 4 of 10 evaluable 2nd-line GIST patients treated with the combination have reached confirmed partial response status

In October 2023, presented updated preclinical data from the Company’s next-generation selective fibroblast growth factor receptor 2 (FGFR2) program in a poster presentation at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).

The poster showed Cogent’s internally-developed FGFR2 inhibitor exhibits low nM potency on WT FGFR2 and FGFR2 mutations and is selective against the kinome and a panel of channels and receptors.
Exploratory pharmacokinetics (PK) studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in an AN3 CA model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at 5 mg/kg PO and was well-tolerated
Projected Near-Term Milestones

Bezuclastinib – Systemic Mastocytosis (SM)

Complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and deliver top-line results by the end of 2025

Provide additional safety, tolerability and patient-reported outcomes data from the open label extension portion of SUMMIT Part 1 during 2024

Complete enrollment in the registration-directed APEX Phase 2 trial in patients with Advanced Systemic Mastocytosis (AdvSM) by the end of 2024
Bezuclastinib – Gastrointestinal Stromal Tumors (GIST)

Complete enrollment in the global, randomized Phase 3 PEAK trial in 2nd-line GIST patients by the end of 2024

Provide additional clinical results from the PEAK lead-in trial, including longer duration safety and tolerability results along with updated efficacy measures, including objective response rate (ORR) and progression free survival (PFS) during 2024
CGT4859 (FGFR2 inhibitor)

Initiate a Phase 1 trial of the first Cogent-discovered pipeline program, designed as a potent, selective, reversible FGFR2 inhibitor with best-in-class potential in the second half of 2024
Preclinical Pipeline

Initiate IND-enabling studies for lead candidate from potent, selective ErbB2 program, highlighted by potential best-in-class brain penetrant properties

Select lead candidate and initiate IND-enabling studies from ongoing PI3Ka program, designed to potently and selectively target the H1047R driver mutation, which affects >30,000 cancer patients each year
Upcoming Investor Conference

Leerink Healthcare Conference on Tuesday, March 12 at 2:20 p.m. ET.

A live webcast can be accessed on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days.
Fourth Quarter and Full Year 2023 Financial Results

Cash and Cash Equivalents: As of December 31, 2023, Cogent had cash, cash equivalents and marketable securities of $273.2 million. Cogent believes this year-end balance, together with the gross proceeds from the $225.0 million oversubscribed private placement, which closed February 16, 2024, will be sufficient to fund its operating expenses and capital expenditure requirements into 2027, including through clinical readouts from the ongoing SUMMIT, PEAK and APEX registration-directed trials.

R&D Expenses: Research and development expenses were $48.7 million for the fourth quarter of 2023 and $173.8 million for the year ended December 31, 2023, as compared to $36.7 million for the fourth quarter of 2022 and $121.6 million for the year ended December 31, 2022. The increase is driven by progress on the APEX, SUMMIT and PEAK trials and the continued development of the research pipeline. During the quarter Cogent also completed and paid for bulk manufacturing campaigns of bezuclastinib to continue supporting the company’s clinical trials. R&D expenses include non-cash stock compensation expense of $4.1 million for the fourth quarter of 2023 and $14.6 million for the year ended December 31, 2023, as compared to $2.4 million for the fourth quarter of 2022 and $8.5 million for the year ended December 31, 2022.

G&A Expenses: General and administrative expenses were $9.5 million for the fourth quarter of 2023 and $34.4 million for the year ended December 31, 2023, as compared to $7.0 million for the fourth quarter of 2022 and $26.2 million for the year ended December 31, 2022. G&A expenses include non-cash stock compensation expense of $4.8 million for the fourth quarter of 2023 and $16.0 million for the year ended December 31, 2023, as compared to $2.6 million for the fourth quarter of 2022 and $9.9 million for the year ended December 31, 2022.

Net Loss: Net loss was $54.4 million for the fourth quarter of 2023 and $192.4 million for the year ended December 31, 2023, as compared to a net loss of $39.6 million for the fourth quarter of 2022 and $140.2 million for the year ended December 31, 2022.

On February 26, 2024 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the fourth quarter and year ended December 31, 2023 and provided a corporate update (Press release, Celldex Therapeutics, FEB 26, 2024, View Source [SID1234640444]).

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"In 2023, Celldex made transformational progress across the barzolvolimab development program, reporting multiple positive data sets across mast cell mediated diseases where patients desperately need better treatment options," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "We carried this momentum into 2024, presenting positive 12 week data from our ongoing Phase 2 CSU study that directly support the planned initiation of registrational studies in CSU this summer, a major milestone for barzolvolimab and Celldex."

"This year we will continue to build on our leadership position in mast cell biology—reporting data from multiple barzolvolimab studies, expanding barzolvolimab into additional mast cell mediated diseases and introducing our first bispecific for inflammatory diseases. We look forward to an exciting year."

Recent Program Highlights

Barzolvolimab – KIT Inhibitor Program

Barzolvolimab is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells.

Celldex is conducting Phase 2 clinical studies of barzolvolimab for the treatment of chronic spontaneous urticaria (CSU) and the two most common forms of chronic inducible urticaria (CIndU) – cold urticaria (ColdU) and symptomatic dermographism (SD). These randomized, double-blind, placebo-controlled Phase 2 studies are evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategies.

Celldex is currently planning two Phase 3 studies of barzolvolimab in CSU, which are expected to initiate this summer.

In November 2023, Celldex reported positive topline data from the Phase 2 CSU study and in February 2024, 12 week treatment results were reported at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in a late breaking oral presentation. Barzolvolimab achieved the primary efficacy endpoint of the study, with a statistically significant mean change from baseline to week 12 of UAS7 (weekly urticaria activity score) compared to placebo across multiple dosing groups and was well tolerated. Secondary and exploratory endpoints in the study, including ISS7 (weekly itch severity score) and HSS7 (weekly hives severity score) and responder analyses strongly support the primary endpoint results. Importantly, barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action. Patients on study will continue to receive barzolvolimab for 52 weeks and the Company plans to report 52 week data in the second half of 2024.

In October 2023, data on quality of life outcomes from the Phase 1b CSU study were presented at the European Academy of Dermatology & Venereology (EADV) Congress. The Dermatology Life Quality Index (DLQI) assesses patients’ perceptions of the impact of their disease across different aspects of their health-related quality of life and includes questions on symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. A rapid improvement in the DLQI was noted within 4 weeks in all barzolvolimab treated patients. DLQI improvement was sustained at doses ≥1.5mg/kg. Physician Global Assessment (PhysGA) for the treated cohorts also improved by week 1 and was sustained through week 24.

Enrollment to the Phase 2 CIndU study is nearing completion and 12 week primary endpoint data from this study is expected to be reported in the second half of 2024. The study is designed to enroll approximately 180 patients with ColdU or SD.

Celldex is currently planning for the initiation of a Phase 2 subcutaneous study in prurigo nodularis (PN) in early 2024. This randomized, double-blind, placebo-controlled, parallel group study will evaluate the efficacy and safety profile of barzolvolimab in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable. Patients will receive barzolvolimab injections of 150 mg Q4W after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo during a 24‑week Treatment Phase.

Data from the Phase 1b randomized, double-blind, placebo-controlled study in patients with prurigo nodularis were reported in an oral presentation at the 12th World Congress on Itch (WCI) in November 2023. A single IV dose of 3.0 mg/kg barzolvolimab resulted in rapid and durable reductions in itch and healing of skin lesions in patients with moderate to severe PN and barzolvolimab was generally well tolerated.
In July 2023, the first patient was dosed in the Phase 2 randomized, double-blind, placebo-controlled study in eosinophilic esophagitis (EoE); enrollment is ongoing. To optimize potential efficacy signal in this difficult to treat indication, we have recently amended the protocol to dose 300 mg every 4 weeks rather than 8 weeks. Approximately 75 patients will be enrolled in total.

Bispecific Antibody Platform

CDX-585 – Bispecific ILT4 & PD-1

CDX-585 combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. ILT4 is emerging as an important immune checkpoint on myeloid cells.

In May 2023, the first patient was dosed in the Phase 1 study of CDX-585. This open-label, multi-center study of CDX-585 is evaluating patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. Enrollment is ongoing in the dose-escalation portion of the study.

Fourth Quarter and Twelve Months 2023 Financial Highlights and 2024 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2023 were $423.6 million compared to $235.3 million as of September 30, 2023. The increase was primarily driven by net proceeds of $216.2 million from our November 2023 underwritten public offering, partially offset by cash used in operating activities of $32.5 million, which includes the $12.5 million payment to Shareholder Representative Services (SRS), the representative of the former stockholders of Kolltan Pharmaceuticals, Inc., pursuant to our settlement agreement. At December 31, 2023, Celldex had 55.9 million shares outstanding.

Revenues: Total revenue was $4.1 million in the fourth quarter of 2023 and $6.9 million for the year ended December 31, 2023, compared to $1.6 million and $2.4 million for the comparable periods in 2022. The increase in revenue was primarily due to an increase in services performed under our manufacturing and research and development agreements with Rockefeller University.

R&D Expenses: Research and development (R&D) expenses were $30.4 million in the fourth quarter of 2023 and $118.0 million for the year ended December 31, 2023, compared to $22.9 million and $82.3 million for the comparable periods in 2022. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial, barzolvolimab contract manufacturing, and personnel expenses.

G&A Expenses: General and administrative (G&A) expenses were $8.8 million in the fourth quarter of 2023 and $30.9 million for the year ended December 31, 2023, compared to $6.6 million and $27.2 million for the comparable periods in 2022. The increase in G&A expenses was primarily due to higher stock-based compensation, recruiting and barzolvolimab commercial planning expenses, partially offset by a decrease in legal expenses.

Changes in Fair Value Remeasurement of Contingent Consideration: The Company recorded a $6.9 million gain on fair value remeasurement of contingent consideration for the year ended December 31, 2022, primarily due to the Company’s decision to deprioritize the CDX-1140 program in the second quarter of 2022.

Litigation Settlement Related Loss: The Company recorded a loss of $15.0 million in the second quarter of 2022 related to the $15.0 million initial payment made to SRS pursuant to our settlement agreement. During the fourth quarter of 2023, the Company announced positive topline results from our Phase 2 clinical trial of barzolvolimab in patients with moderate to severe CSU, satisfying the "Successful Completion" of a Phase 2 clinical trial of barzolvolimab milestone, thus triggering the payment of the $12.5 million milestone pursuant to the settlement agreement.

Net Loss: Net loss was $43.3 million, or ($0.83) per share, for the fourth quarter of 2023, and $141.4 million, or ($2.92) per share, for the year ended December 31, 2023, compared to a net loss of $26.5 million, or ($0.56) per share, for the fourth quarter of 2022 and $112.3 million, or ($2.40) per share, for the year ended December 31, 2022. The litigation settlement related loss had a ($0.26) impact on net loss per share for the twelve months ended December 31, 2023.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at December 31, 2023 are sufficient to meet estimated working capital requirements and fund current planned operations into 2026.

On February 26, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the company will participate in the TD Cowen 44th Annual Health Care Conference in Boston, Massachusetts, on Monday, March 4, 2024 (Press release, Bristol-Myers Squibb, FEB 26, 2024, View Source [SID1234640443]). Roland Chen, M.D., senior vice president, Immunology, Cardiovascular & Neuroscience development, will answer questions about the company during a fireside chat at 9:50 a.m. ET.

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Investors and the general public are invited to listen to a live webcast of the session here. An archived edition of the session will be available following its conclusion.

On February 26, 2024 Bristol Myers Squibb (NYSE: BMY) reported that it has successfully completed its acquisition of RayzeBio, Inc. (NASDAQ: RYZB) (Press release, Bristol-Myers Squibb, FEB 26, 2024, View Source [SID1234640442]). With the completion of the acquisition, RayzeBio shares have ceased trading on the NASDAQ Global Market and RayzeBio is now a wholly owned subsidiary of Bristol Myers Squibb.

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"We are excited to complete this transaction, which adds radiopharmaceutical therapeutics (RPTs), one of the fastest-growing new modalities for treating patients with solid tumors," said Chris Boerner, Ph.D., Chief Executive Officer, Bristol Myers Squibb. "By strengthening and further diversifying our oncology pipeline beyond I-O, we will unlock exciting opportunities that support BMS’s growth in the back half of the decade and beyond. RayzeBio is a pioneer in the application of this novel modality, and we look forward to working with their talented team to accelerate their preclinical and clinical programs for the benefit of patients around the world."

This transaction brings a promising pipeline of RPTs to Bristol Myers Squibb, including RayzeBio’s lead program RYZ101 (225Ac-DOTATATE), which targets somatostatin receptor 2 (SSTR2), over-expressed in GEP-NETs and extensive stage small cell lung cancer (ES-SCLC). A Phase 3 clinical trial is currently enrolling patients to evaluate RYZ101 in patients with SSTR-positive GEP-NETs who have previously been treated with lutetium-177 based somatostatin therapies. RayzeBio previously reported the interim results of the Phase 1b portion of the ACTION-1 clinical trial, suggesting encouraging efficacy and tolerability. A Phase 1b clinical trial is also currently enrolling patients to evaluate RYZ101 as a first-line treatment of ES-SCLC in combination with standard-of-care therapy. The platform has the potential to be a significant IND engine to generate a number of candidates and comes with a state-of-the-art RPT manufacturing facility, which is expected to begin operating in the first half of 2024.

Bristol Myers Squibb’s previously announced tender offer to acquire all of the outstanding shares of RayzeBio common stock for a purchase price of $62.50 per share in cash, or approximately $4.1 billion, expired at one minute after 11:59 p.m., Eastern Time on February 22, 2024. Approximately 53,052,499 shares of RayzeBio common stock were validly tendered, and not validly withdrawn from the tender offer, representing approximately 86% of RayzeBio’s issued and outstanding shares of common stock. In accordance with the terms of the tender offer, all shares that were validly tendered and not validly withdrawn have been accepted for payment and Bristol Myers Squibb expects to promptly pay for all such shares.

Following completion of the tender offer, Bristol Myers Squibb completed the acquisition of RayzeBio through the merger of its wholly owned subsidiary Rudolph Merger Sub Inc. with and into RayzeBio, without a vote of RayzeBio’s stockholders pursuant to Section 251(h) of the General Corporation Law of the State of Delaware. As a result of the merger, each share of common stock of RayzeBio issued and outstanding and not tendered in the tender offer was converted into the right to receive an amount in cash equal to $62.50, without interest and less any required withholding taxes, the same price offered in the tender offer.

RayzeBio stockholders can direct questions regarding the tender offer to Georgeson LLC, the information agent for the tender offer, toll free at 1-888-815-8542 or by email at [email protected].

Advisors

BofA Securities, Inc., is serving as financial advisor to Bristol Myers Squibb, and Covington & Burling LLP is serving as legal counsel. Centerview Partners LLC is serving as financial advisor to RayzeBio, and Cooley LLP is serving as legal counsel.

On February 26, 2024 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update (Press release, BioCryst Pharmaceuticals, FEB 26, 2024, View Source [SID1234640441]).

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"The impressive growth we are seeing with ORLADEYO has put us in a position to accelerate our path to profitability while continuing to invest in our diverse pipeline of first-in-class or best-in-class molecules that we believe will deliver our next marketed product," said Jon Stonehouse, president and chief executive officer of BioCryst.

Program Updates and Key Milestones

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

ORLADEYO net revenue in the fourth quarter of 2023 was $90.9 million.

The total number of U.S. patients on paid or long-term free product reached 1,104 at the end of the fourth quarter (+30 percent y-o-y) with 71.5 percent of those patients on paid product.

Net U.S. patient growth totaled 321 in 2023, including new patients still on short-term quick start product at the end of the quarter.

The number of new ORLADEYO prescribers in the fourth quarter of 2023 (Q4 2023) was the largest number of new prescribers of any quarter in 2023.

Real-world data presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting reinforced prior data showing patients switching to ORLADEYO experience sustained attack reduction regardless of baseline attack rate or prior HAE prophylaxis treatment.

Access to ORLADEYO continues to expand to more HAE patients around the world. In Q4 2023, ORLADEYO was approved in Argentina, launched in Spain, and granted final pricing approval in Austria. In the first quarter of 2024, ORLADEYO secured final reimbursement in Italy.
"As the real-world evidence with ORLADEYO consistently underscores, patients are switching to ORLADEYO because they can achieve outstanding HAE attack control and tolerability with an oral, once-daily therapy, leading to life-changing results," said Charlie Gayer, chief commercial officer of BioCryst.

Fourth Quarter 2023 Financial Results

For the three months ended December 31, 2023, total revenues were $93.4 million, compared to $79.5 million in the fourth quarter of 2022. The increase was primarily due to $90.9 million in ORLADEYO net revenue in the fourth quarter of 2023, compared to $70.7 million in the fourth quarter of 2022. Revenue in the fourth quarter of 2023 also included $2.3 million of net revenue from RAPIVAB related sales, compared to $8.7 million in the fourth quarter of 2022.

Research and development (R&D) expenses for the fourth quarter of 2023 decreased to $70.1 million from $73.2 million in the fourth quarter of 2022 (-4 percent year-over-year), primarily due to the discontinuation of the BCX9930 and BCX9250 programs announced in December 2022 and November 2022, respectively. These reductions were partially offset by increased investment in BCX17725 and our other early-stage programs, including the $5 million upfront payment to Clearside Biomedical related to avoralstat, and ORLADEYO label expansion and life cycle investments, such as our ongoing ORLADEYO pediatric trial.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2023 increased to $64.4 million, compared to $50.2 million in the fourth quarter of 2022 (+28 percent year-over-year). The increase was primarily due to increased investment to expand and enhance the U.S. commercial team and international operations.

Interest expense was $24.6 million in the fourth quarter of 2023, compared to $26.5 million in the fourth quarter of 2022. 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 fourth quarter of 2023 was $61.7 million, or $0.31 per share, compared to a net loss of $71.5 million, or $0.38 per share, for the fourth quarter of 2022. Non-GAAP net loss for the fourth quarter of 2023 was $56.4 million, or $0.28 per share when excluding one-time costs associated with the R&D restructuring and the postponement of the expansion at our Discovery Center in Alabama, totaling $5.4 million. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Cash, cash equivalents, restricted cash and investments totaled $390.8 million as of December 31, 2023, compared to $443.9 million as of December 31, 2022. Net cash utilization for the fourth quarter of 2023 was $8.6 million.

Full Year 2023 Financial Results

For the full year ended December 31, 2023, total revenues were $331.4 million, compared to $270.8 million in the full year ended December 31, 2022. The increase was primarily due to $326.0 million of ORLADEYO net revenue in 2023, compared to $251.6 million in 2022. The increase in ORLADEYO net revenue was partially offset by a decrease in other net revenues of $13.8 million, primarily due to RAPIVAB stockpiling sales to complete the U.S. Department of Health and Human Services procurement contract during the year ended December 31, 2022.

R&D expenses in full year 2023 decreased to $216.6 million from $253.3 million in full year 2022 (-14 percent year-over-year), primarily due to the discontinuation of the BCX9930 and BCX9250 programs announced in December 2022 and November 2022, respectively. These reductions were partially offset by increased investment in BCX17725, increased investment in our other early-stage discovery programs, including the $5 million upfront payment to Clearside Biomedical related to avoralstat, ORLADEYO label expansion and life cycle investments, such as our ongoing ORLADEYO pediatric trial, and an increase in indirect costs to support our programs.

SG&A expenses in full year 2023 increased to $213.9 million, compared to $159.4 million in full year 2022 (+34 percent year-over-year). The increase was primarily due to increased investment in order to expand and enhance the U.S. commercial team and expanded international operations.

Interest expense was $108.2 million in full year 2023, compared to $99.1 million in full year 2022. The increase in interest expense was primarily associated with the interest accrued on the Tranche A Loan of $300.0 million under the Pharmakon Loan Agreement.

Other expense was comprised primarily of a loss on extinguishment of debt of $29.0 million on the repayment of the term loans under the Athyrium Credit Agreement and net foreign currency losses of $1.0 million, partially offset by interest income of $15.8 million for the year ended December 31, 2023. Other income was comprised of interest income of $5.1 million, partially offset by net foreign currency losses of $2.0 million for the year ended December 31, 2022.

Net loss for full year 2023 was $226.5 million, or $1.18 per share, compared to a net loss of $247.1 million, or $1.33 per share, for full year 2022. Non-GAAP net loss for full year 2023 was $192.2 million, or $1.00 per share when excluding the one-time loss on debt extinguishment of $29.0 million on the repayment of the term loans under the Athyrium Credit Agreement recognized in the second quarter of 2023, as well as the R&D restructuring and the postponement of previously planned capital expenditures at our Discovery Center in Alabama recognized in the fourth quarter of 2023, totaling $5.4 million. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

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 2023 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 fourth quarter 2023 and full year 2023 "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 loss on debt extinguishment on the repayment of the term loans under the Athyrium Credit Agreement, as well as the R&D restructuring and the postponement of previously planned capital expenditures at our Discovery Center in Alabama. A reconciliation between GAAP and non-GAAP net loss is provided in the table below.

Financial Outlook for 2024

The company expects full year 2024 global net ORLADEYO revenue to be between $380 million and $400 million. The general pattern of revenue throughout 2024 is expected to be similar to past years, with the seasonal impact of prescription reauthorizations and the potential impact of the Inflation Reduction Act in the first quarter driving a quarter-over-quarter revenue decline in the first quarter, followed by a strong return to growth in the second quarter.

The company expects full year 2024 operating expenses to be between $365 million and $375 million, flat to expected full year 2023 operating expenses. The company now expects that R&D expenses in 2024 will be reduced by between $20 million and $30 million versus 2023. SG&A expenses are expected to increase by $20 million in 2024, primarily to support the continued U.S. and global growth of ORLADEYO to $1 billion in peak sales.

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 revenue expected from ORLADEYO, the company expects to 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.