On February 15, 2024 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, and ReCode Therapeutics, a clinical-stage genetic medicines company using tissue-specific delivery to power the next wave of mRNA and gene correction therapeutics, reported a strategic collaboration to develop novel genomic medicines for the treatment of cystic fibrosis (CF) (Press release, ReCode Therapeutics, FEB 15, 2024, View Source;utm_medium=rss&utm_campaign=intellia-therapeutics-and-recode-therapeutics-announce-strategic-collaboration-to-develop-novel-gene-editing-therapies-for-cystic-fibrosis [SID1234640149]). CF is a genetic disease caused by mutations in the CFTR gene, leading to the accumulation of thick mucus in the lungs, digestive systems and other organs. CF can result in life-threatening infections, respiratory failure and other serious complications.

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The collaboration will leverage Intellia’s proprietary CRISPR-based gene editing platform, including its DNA writing technology, and ReCode’s proprietary Selective Organ Targeting (SORT) lipid nanoparticle (LNP) delivery platform to precisely correct one or more CF disease-causing gene mutations. As part of the agreement, the companies will focus initial research efforts on therapeutic approaches that address CF for patients who have limited or no treatment options available, with the opportunity to expand the scope of the collaboration in later phases. Intellia will be responsible for the design of the editing strategy and research-grade components for the investigational therapies. ReCode will lead the subsequent preclinical and clinical development. ReCode will also lead worldwide commercialization for certain programs arising from the collaboration. Intellia will be eligible to receive pre-specified development and commercial milestone payments, as well as royalties on potential sales. Intellia may also exercise an option to lead commercialization in the U.S. for certain programs.

"Intellia’s vision to realize the full promise of gene editing includes extending the reach of our industry-leading CRISPR-based platform to targets outside the liver. This collaboration with ReCode is aimed at achieving that goal as we work together to accelerate the development of potentially life-changing therapies for people with cystic fibrosis," said Intellia President and Chief Executive Officer John Leonard, M.D. "Building on our CRISPR/Cas9 capabilities, we have made important progress advancing our proprietary DNA writing technology to enable a range of precise editing strategies. We are excited to combine our gene editing expertise and platform with ReCode’s novel lung-directed LNP delivery platform."

"We are excited to partner with Intellia, a clear leader in the gene editing space, with the ultimate goal of bringing life-altering therapies to CF patients," said ReCode Chief Executive Officer Shehnaaz Suliman, M.D. (MB ChB), M.B.A., M.Phil. "This collaboration provides further validation of ReCode’s SORT LNP platform to deliver diverse gene editing modalities to specific cells and tissues. By combining our highly synergistic technologies and capabilities, we are excited about the potential to enable a faster path for next-generation gene editing therapeutics to CF patients."

On February 15, 2024 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, reported financial results for the fourth quarter and full year 2023 (Press release, Prothena, FEB 15, 2024, View Source [SID1234640148]). In addition, the Company provided 2024 financial guidance and business highlights.

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"2023 was a year of strong progress for Prothena as we advanced our protein dysregulation portfolio and moved closer to becoming a fully integrated commercial company. The next 12 to 18 months have the potential to transform Prothena with multiple upcoming clinical readouts across our robust portfolio," said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. "We continue to advance our confirmatory Phase 3 AFFIRM-AL clinical trial for birtamimab and for PRX012 are evaluating multiple dose level cohorts in our ongoing Phase 1 clinical trial. In addition, we ended the year with IND clearances by the FDA for both PRX123 and PRX019, including Fast Track designation for PRX123. As we continue to grow our leadership at Prothena, we also appointed the founding, former Director of the FDA CDER Office of Neuroscience, Dr. Billy Dunn, to our board of directors. Dr. Dunn brings immeasurable regulatory and clinical development expertise, combined with a passion for helping patients, which will greatly benefit the millions of people affected by diseases caused by protein

dysregulation. Lastly, Prothena remains well financed with sufficient capital to ensure funding of activities beyond the completion of ongoing clinical trials."

2023 Business Highlights and Upcoming Milestones

Neurodegenerative Diseases Portfolio

Alzheimer’s Disease

PRX012, a wholly-owned potential best-in-class, next-generation subcutaneous antibody for the treatment of Alzheimer’s disease that targets a key epitope at the N-terminus of amyloid beta (Aβ) with high binding potency. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PRX012 for the treatment of Alzheimer’s disease.
•Presented two preclinical studies at AD/PD in March 2023 and AAIC in July 2023 showing superior binding characteristics of PRX012
•Partnered with Walgreens in April 2023 to accelerate patient identification and recruitment for ongoing ASCENT-2 clinical trial
•Initial Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) data supports once-monthly subcutaneous administration and ongoing evaluation in MAD cohorts
•Ongoing Phase 1 clinical trial continues as planned and expect to update in 2024

BMS-986446 (formerly PRX005), a potential best-in-class antibody for the treatment of Alzheimer’s disease that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, a protein implicated in the causal pathophysiology of Alzheimer’s disease. BMS-986446 is part of a Global Neuroscience Research and Development Collaboration with Bristol Myers Squibb.
•Presented Phase 1 clinical trial SAD results in a poster presentation at AAIC in July 2023 showing that all three tested dose levels (low, medium, high) of PRX005 were considered generally safe and well tolerated, meeting the primary objective of this part of the clinical trial and supporting evaluation of doses in the ongoing MAD portion of this two-part clinical trial
•Bristol Myers Squibb paid $55 million for exclusive worldwide rights for PRX005 in July 2023 under the Global Neuroscience Research and Development Collaboration
•Bristol Myers Squibb will be responsible for future development, manufacturing, and commercialization of BMS-986446
•Bristol Myers Squibb reported that Phase 1 data supports moving BMS-986446 into a Phase 2 clinical trial in 1H 2024

PRX123, a wholly-owned potential first-in-class dual Aβ/tau vaccine designed for the treatment and prevention of Alzheimer’s disease, is a dual-target vaccine targeting key epitopes within the N-terminus of Aβ and MTBR-tau designed to promote amyloid clearance and block the transmission of pathogenic tau
•Presented preclinical results in a late breaker poster presentation at AAIC in July 2023 showing a PRX123 vaccine surrogate elicited robust antibody responses that bound with high avidity to Aβ plaques in Alzheimer’s disease brain tissue ex vivo and significantly reduced Aβ brain plaques
•Investigational new drug (IND) application cleared by FDA
•Fast Track designation granted by FDA
•Phase 1 timeline update expected in 2024

Parkinson’s Disease

Prasinezumab, a potential first-in-class antibody for the treatment of Parkinson’s disease that is designed to target key epitopes within the C-terminus of alpha-synuclein, and is the focus of a worldwide collaboration with Roche
•Roche completed enrollment for the Phase 2b PADOVA clinical trial in patients with early Parkinson’s disease in the first quarter of 2023
•Poster and oral presentations at AD/PD in March/April 2023 highlighted aspects of the Phase 2 PASADENA clinical trial of prasinezumab for the treatment of Parkinson’s disease
•Roche presented data at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) from the open-label extension of the PASADENA clinical trial which shows that prasinezumab slowed the progression of motor deficits (MDS-UPDRS Part III OFF state score) in early-stage Parkinson’s disease
•Topline results from Phase 2b PADOVA clinical trial expected in 2024 (NCT04777331)

Neurodegenerative Diseases

PRX019, a potential treatment of neurodegenerative diseases with an undisclosed target, is part of a Global Neuroscience Research and Development Collaboration with Bristol Myers Squibb.
•IND application cleared by FDA in December 2023
•Phase 1 clinical trial timeline update expected in 2024

Rare Peripheral Amyloid Diseases Portfolio

AL Amyloidosis

Birtamimab, a wholly-owned potential best-in-class amyloid depleter antibody for the treatment of AL amyloidosis designed to directly neutralize soluble toxic light chain aggregates and promote clearance of amyloid that causes organ dysfunction and failure. Among patients with AL amyloidosis, a rare, progressive, and fatal disease, newly diagnosed individuals with advanced disease (e.g., Mayo Stage IV) are at the highest risk for early death. Birtamimab has been granted Fast Track designation by the FDA for the treatment of patients with Mayo Stage IV AL amyloidosis to reduce the risk of mortality and has been granted Orphan Drug Designation by both the FDA and European Medicines Agency. A significant survival benefit was observed in the post hoc analysis of birtamimab-treated patients categorized as Mayo Stage IV at baseline in the previous Phase 3 VITAL clinical trial (Blood 2023).
•Published Phase 3 VITAL clinical trial data in June 2023 in Blood, the peer-reviewed journal of American Society of Hematology (ASH) (Free ASH Whitepaper)
•The ongoing confirmatory Phase 3 AFFIRM-AL clinical trial in patients with Mayo Stage IV AL amyloidosis is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA with a primary endpoint of all-cause mortality (time-to-event) at a significance level of 0.10
•Topline results from confirmatory AFFIRM-AL Phase 3 clinical trial expected between 4Q 2024 and 2Q 2025 (NCT04973137)

ATTR Amyloidosis

NNC6019 (formerly PRX004), a potential first-in-class amyloid depleter antibody for the treatment of ATTR cardiomyopathy designed to deplete the pathogenic, non-native forms of the transthyretin (TTR) protein and is being developed by Novo Nordisk as part of their up to $1.2 billion acquisition of Prothena’s ATTR amyloidosis business and pipeline

•Ongoing Phase 2 clinical trial in patients with ATTR cardiomyopathy is being conducted by Novo Nordisk;
•The Phase 2 clinical trial has fully recruited patients with topline data expected in 1H 2025 (NCT05442047)

2023 Organizational and Corporate Highlights

•Announced the appointment of Billy Dunn, M.D., founding, former Director of the FDA CDER Office of Neuroscience, to its Board of Directors

Fourth Quarter and Full Year of 2023 Financial Results
For the fourth quarter and full year of 2023, Prothena reported a net loss of $67.5 million and $147.0 million, respectively, as compared to a net income of $6.3 million and a net loss of $116.9 million for the fourth quarter and full year of 2022, respectively. Net loss per share was $1.26 and $2.76 for the fourth quarter of 2023 and for the full year of 2023, respectively, as compared to net income per share on a diluted basis of $0.12 and net loss per share of $2.47 for the fourth quarter and full year of 2022, respectively.
Prothena reported total revenue of $0.3 million and $91.4 million for the fourth quarter and full year of 2023, respectively, as compared to total revenue of $49.9 million and $53.9 million for the fourth quarter and full year of 2022, respectively. Total revenue for the fourth quarter and full year of 2023 included BMS collaboration revenue of $0.3 million and $91.3 million, respectively. The full year includes the $55 million option payment from BMS related to their exercise of their option to acquire the exclusive worldwide rights for BMS-986446, (formerly PRX005). This compares to total revenue for the fourth quarter of 2022 and the full year of 2022 that included BMS collaboration revenue of $9.9 million and $13.9 million, respectively and a $40.0 million milestone payment from Novo Nordisk related to the continued advancement of NNC6019 (formerly PRX004) in a Phase 2 clinical trial for the treatment of ATTR cardiomyopathy in the fourth quarter of 2022 and the full year of 2022.
Research and development (R&D) expenses totaled $61.9 million and $220.6 million for the fourth quarter and full year of 2023, respectively, as compared to $36.9 million and $135.6 million for the fourth quarter and full year of 2022, respectively. The increase in R&D expense for the fourth quarter and full year of 2023 compared to the same periods in the prior year was primarily due to higher clinical trial expenses, higher personnel related expenses, higher consulting and other R&D expenses. R&D expenses included non-cash share-based compensation expense of $5.0 million and $19.2 million for the fourth quarter and full year of 2023, respectively, as compared to $3.5 million and $14.8 million for the fourth quarter and full year of 2022, respectively.
General and administrative (G&A) expenses totaled $16.9 million and $61.8 million for the fourth quarter and full year of 2023, respectively, as compared to $13.1 million and $49.9 million for the fourth quarter and full year of 2022, respectively. The increase in G&A expenses for the fourth quarter and full year of 2023 compared to the same periods in the prior year was primarily related to higher personnel related and consulting expenses. G&A expenses included non-cash share-based compensation expense of $6.0 million and $21.7 million for the fourth quarter and full year of 2023, respectively, as compared to $3.9 million and $16.5 million for the fourth quarter and full year of 2022, respectively.
Total non-cash share-based compensation expense was $11.1 million and $40.9 million for the fourth quarter and full year of 2023, respectively, as compared to $7.4 million and $31.3 million for the fourth quarter and full year of 2022, respectively.

As of December 31, 2023, Prothena had $621.0 million in cash, cash equivalents and restricted cash, and no debt.
As of February 9, 2024, Prothena had approximately 53.7 million ordinary shares outstanding.

2024 Financial Guidance

The Company expects the full year 2024 net cash used in operating and investing activities to be $208 to $225 million and expects to end the year with approximately $405 million in cash, cash equivalents and restricted cash (midpoint). The estimated full year 2024 net cash used in operating and investing activities is primarily driven by an estimated net loss of $229 to $255 million, which includes an estimated $51 million of non-cash share-based compensation expense.

Conference Call Details

Prothena management will discuss these results and its 2024 financial guidance during a live audio conference call today, Thursday, February 15, 2024, at 4:30 PM ET. The conference call will be made available on the Company’s website at www.prothena.com under the Investors tab in the Events and Presentations section. Following the live audio webcast, a replay will be available on the Company’s website for at least 90 days.

To access the call via dial-in, please dial +1 (800) 715-9871 (U.S. and Canada toll free) or +1 (646) 307-1963 (international) five minutes prior to the start time and refer to conference ID number 1706941. A replay of the call will be available until February 22, 2024, via dial-in at +1 (800) 770-2030 (U.S. and Canada toll free) or +1 (609) 800-9909 (international), Conference ID Number 1706941.

On February 15, 2024 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported its financial results for the fiscal year ended December 31, 2023, and outlined key objectives for 2024 (Press release, Prelude Therapeutics, FEB 15, 2024, View Source [SID1234640147]).

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"In 2023, we prioritized and strengthened our pipeline to focus our resources on those programs that we believe have the highest likelihood of success and the greatest opportunity to deliver potentially safer and more effective therapies for patients that are currently underserved. We made significant progress with both our first-in-class IV SMARCA2 degrader compound, PRT3789, and our potentially best-in-class CDK9 inhibitor, PRT2527, which are on track to deliver meaningful initial proof-of-concept data in 2024," stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude.

Dr. Vaddi continued, "As evidence of our confidence in the potential therapeutic value of SMARCA2 to address a wide range of cancers with SMARCA4 mutations, we are also advancing our highly selective lead oral SMARCA2 degrader into Phase 1 clinical development in the second half of 2024. With both IV and oral molecules in the pipeline, we believe that we have the optionality to deliver the most appropriate treatment based on patient need and line of therapy and maintain our lead in this emerging new class of therapeutics.

"Our partnership with AbCellera represents a strategic step to expand our pipeline, based on our core competencies in medicinal chemistry, cancer biology and clinical development. The goal of the partnership is to create a portfolio of first-in-class precision ADCs that will utilize highly selective and potent small molecules and degrader payloads discovered by Prelude, coupled with highly differentiated antibodies from AbCellera. One of our first precision ADC programs utilizes a highly potent SMARCA degrader, which we expect will allow us to build on and extend the reach of our SMARCA programs."

Clinical Program Updates and Upcoming Milestones

SMARCA2 degrader PRT3789 on track to complete monotherapy dose escalation mid- year and initiate combination with docetaxel in first half of 2024; initial proof-of concept data expected in second half of 2024

PRT3789 is a potent and highly selective first-in-class SMARCA2 degrader, designed to be used in patients with a SMARCA4 mutation. Cancers with a SMARCA4 mutation represent a high unmet medical need. Patients with the SMARCA4 mutation have poor prognosis and, currently, no effective therapies.

PRT3789 is in Phase 1 clinical development in biomarker selected SMARCA4 mutant patients. To date, PRT3789 has completed the fifth dose escalation cohort and demonstrated selective, potent and dose dependent degradation of SMARCA2 with an acceptable safety profile. Based on PK/PD and safety data today, the Company expects to conclude monotherapy dose escalation mid-2024 and identify recommended Phase 2 dose(s). In addition, enrollment of patients into back-fill cohorts enriched for NSCLC and SMARCA4 loss-of-function mutations has been initiated. Objectives for this first Phase 1 clinical trial are to establish the safety and tolerability profile of PRT3789 as both monotherapy and in combination with docetaxel, evaluate efficacy, pharmacokinetics and pharmacodynamics and determine a dose and potential indications for advancement into a registrational clinical trial.

CDK9 inhibitor PRT2527 on track to complete monotherapy dose escalation mid-2024; initiate dosing in combination with zanubrutinib in first quarter of 2024; initial hematological proof-of-concept data expected in second half of 2024

PRT2527 is a potent and selective small molecule that has the potential to avoid off target toxicity and achieve greater clinical activity than other CDK9 programs currently in development. The Company is currently advancing PRT2527 as monotherapy in hematological indications such as B-cell malignancies and acute myeloid leukemia (AML) and has initiated the combination with zanubrutinib in B-cell malignancies.

PRT2527 is currently in Phase 1 clinical development and expected to complete monotherapy dose escalation in B-cell malignancies mid-year. A second cohort of patients with AML is expected to initiate in the first half of 2024.

Oral SMARCA2 degrader PRT7732 expected to enter Phase 1 clinical trial in the second half of 2024

Prelude’s discovery team has identified a series of highly selective and orally bioavailable SMARCA2 degraders. The lead oral molecule, PRT7732, is currently in investigational new drug (IND) enabling studies and on track to enter Phase 1 clinical development in the second half of 2024. PRT7732 is structurally distinct from PRT3789 and may provide clinically meaningful differences, more patient-friendly dosing and may be useful in earlier therapy lines.

Partnership with AbCellera expected to advance its first precision ADC

The AbCellera partnership, announced in November 2023, continues to progress towards the goal of delivering next-generation ADCs, combining AbCellera’s antibody discovery and development engine with Prelude’s expertise in medicinal chemistry and drug development. The partnership includes up to five precision ADC targets. Under the terms of the agreement, Prelude and AbCellera will jointly discover, develop, and commercialize products emerging from the collaboration. AbCellera will lead manufacturing activities and Prelude will lead clinical development and global commercialization, subject to AbCellera’s option to co-promote any resulting commercial products in the United States.

Full Year 2023 Financial Results

Cash and Cash Equivalents:

Cash and cash equivalents as of December 31, 2023 were $232.9 million. The Company anticipates that its existing cash, cash equivalents and marketable securities will fund Prelude’s operations into 2026.

Research and Development (R&D) Expenses:

R&D expenses for the year ended December 31, 2023 increased by $10.5 million to $103.4 million from $92.9 million for the year ended December 31, 2022. Included in research and development expenses for the year ended December 31, 2023 was $12.6 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $11.5 million for the year ended December 31, 2022. The increase in research and development expenses was due to the timing of our clinical development programs along with an increase in non-cash stock-based compensation expense.

General and Administrative (G&A) Expenses:

G&A expenses for the year ended December 31, 2023 decreased by $1.8 million to $28.9 million compared to $30.7 million for the year ended December 31, 2022. Included in the general and administrative expenses for the year ended December 31, 2023 was $13.0 million of non-cash expense related to stock-based compensation expense, including employee stock options, as compared to $13.6 million for the same period in 2022. The decrease in general and administrative expenses was primarily due to our continued management of general and administrative expenses.

Net Loss:

Net loss for the year ended December 31, 2023 was $121.8 million or $2.02 per share, compared with a net loss of $115.4 million, or $2.44 per share, for the year ended December 31, 2022.

On February 15, 2024 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, reported financial results for the fiscal quarter and fiscal year ended November 30, 2023, and provided a corporate update (Press release, Nurix Therapeutics, FEB 15, 2024, View Source [SID1234640146]).

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"Building on a very successful 2023, marked by impressive clinical data for both NX-5948 and NX-2127, Nurix has hit the ground running in 2024, with plans to accelerate enrollment in the NX-5948 leukemia and lymphoma program and enable development in inflammatory diseases," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "2023 was also a great year for our partnerships, generating significant non-dilutive funding and expanding our pipeline in both oncology and inflammation with our IRAK-4 degrader. We anticipate continued success with our partners Gilead, Sanofi, and Pfizer in the coming year."

Recent Business Highlights

•Nurix presented clinical data for Bruton’s tyrosine kinase (BTK) degrader NX-5948 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting: In December 2023, Nurix reported data from the dose escalation stage of the Phase 1 trial demonstrating dose-dependent pharmacokinetics (PK), resulting in rapid, robust, and sustained BTK degradation in all patients treated. NX-5948 was well-tolerated across all doses. Preliminary efficacy data demonstrated clinical benefit in six of seven patients with chronic lymphocytic leukemia (CLL). Durable responses were seen across indications in non-Hodgkin lymphoma (NHL) patients, with almost half the patients continuing to receive treatment as of the data cut-off date. Dose escalation in the NX-5948 trial continues across all indications and the study is actively enrolling patients in the United States, the United Kingdom, and the Netherlands.
•NX-5948 received U.S. FDA Fast Track designation: In January 2024, the FDA granted Fast Track designation for NX-5948 for the treatment of adult patients with relapsed or refractory CLL or small lymphocytic lymphoma after at least two lines of therapy, including a BTK inhibitor (BTKi) and a B-cell lymphoma 2 (BCL2) inhibitor. The FDA’s Fast Track designation is intended to facilitate and expedite the development and review of drug candidates to treat serious conditions and fulfill an unmet medical need. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review.
•Nurix presented clinical data for NX-2127, a dual BTK and IKZF1/3 degrader, at the ASH (Free ASH Whitepaper) Annual Meeting: In December 2023, Nurix reported data from its Phase 1a dose escalation and Phase 1b dose expansion cohorts in CLL, mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). NX-2127 exhibited dose-dependent PK, leading to robust and sustained degradation of BTK and biologically relevant degradation of IKZF1 (Ikaros). Treatment with NX-2127 resulted in encouraging rapid and durable responses in the heavily pre-treated patient population including patients with BTK inhibitor resistance mutations. Durable complete responses were reported in two patients with MCL and DLBCL which remained ongoing for over one year. NX-2127 had a manageable safety profile that was consistent with previous reports for BTK-targeted and immunomodulatory therapies.

•High profile publications provide scientific basis for BTK scaffold function and degrader mechanism: In February 2024, Nurix announced the publication of a manuscript in the journal Science titled: "Kinase Impaired BTK Mutations Are Susceptible to Clinical Stage BTK and IKZF1/3 Degrader NX-2127" that elucidates a previously unappreciated oncogenic scaffold function of BTK responsible for clinical resistance to enzymatic inhibitors and shows that NX-2127 can overcome this resistance across a broad range of acquired mutations. A second manuscript was published contemporaneously in The Journal of Medicinal Chemistry entitled "Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton’s Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies," which details the discovery and optimization of NX-2127.
Upcoming Program Highlights*
•NX-5948: NX-5948 is an investigational, orally bioavailable, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. In 2024, Nurix expects to define doses for Phase 1b cohort expansion in CLL and NHL and accelerate Phase 1 clinical trial enrollment to enable pivotal trials. Nurix plans to present additional clinical data with higher dose levels and longer treatment duration in mid-2024. In addition, Nurix expects to complete ongoing preclinical studies that can enable an investigational new drug (IND) application for NX-5948 in autoimmune indications. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022).

•NX-2127: NX-2127 is an orally bioavailable degrader of BTK with immunomodulatory activity for the treatment of patients with relapsed or refractory B-cell malignancies. Nurix is conducting a Phase 1a/b clinical trial of NX-2127, which includes three Phase 1b expansion cohorts in patients with DLBCL, MCL and CLL. Screening and enrollment of new study participants have been paused due to a partial clinical hold placed on the study by the FDA. Patients currently enrolled in the clinical study who are deriving clinical benefit may continue to receive treatment in accordance with the ongoing study protocol. In 2024, Nurix expects to resolve the partial clinical hold to enable the introduction of newly manufactured drug product into the ongoing Phase 1 clinical trial. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).

•NX-1607: Nurix’s lead drug candidate from its targeted protein elevation portfolio, NX-1607, is an orally bioavailable inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications including a range of solid tumor types and lymphoma. Nurix is evaluating NX-1607 in an ongoing, Phase 1 trial in monotherapy and in a combination cohort utilizing paclitaxel in adults in a range of oncology indications. In 2024, Nurix expects to present data from the Phase 1a dose-escalation portion of the trial of NX-1607 and to define dose(s) to enable Phase 1b cohort expansion. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).
•NX-0479/GS-6791: GS-6791 (previously NX-0479) is a potent, selective, oral IRAK4 degrader. Degradation of IRAK4 by GS-6791 has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. Nurix’s partner, Gilead, is responsible for conducting IND-enabling studies and advancing this program to clinical development.
•Selection of new drug candidate: Nurix expects to select a new targeted protein degrader development candidate in 2024.
•Continued pipeline advancement of strategic collaborations with Gilead, Sanofi and Pfizer: Nurix expects to continue to achieve substantial research collaboration milestones throughout the terms of its collaborations with Gilead, Sanofi and Pfizer.
*Expected timing of events throughout this press release is based on calendar year quarters.
Fiscal Fourth Quarter and Full Year 2023 Financial Results
Revenue for the three months and twelve months ended November 30, 2023, was $15.2 million and $77.0 million, respectively, compared with $6.8 million and $38.6 million for the three and twelve months ended November 30, 2022, respectively. The increase for the twelve-month period was primarily due to a higher percentage of completion of performance obligations and an increase in the value of milestones achieved in the current period. The increase was also due to the receipt of $20.0 million related to the license option exercise payment from Gilead. During the year ended November 30, 2023, Nurix achieved research milestones under its collaborations with Gilead and Sanofi totaling $12.5 million and $7.0 million, respectively.

Research and development expenses for the three months and twelve months ended November 30, 2023, were $49.7 million and $189.1 million, respectively, compared to $46.1 million and $184.5 million for the three and twelve months ended November 30, 2022, respectively. For the twelve-month period, there was an increase in compensation and related personnel costs and an increase in clinical costs as Nurix continued its clinical trial programs and ongoing patient enrollment, offset by a decrease in research related costs and in contract manufacturing.
General and administrative expenses for the three months and twelve months ended November 30, 2023, were $10.8 million and $42.9 million, respectively, compared to $9.4 million and $38.0 million for the three and twelve months ended November 30, 2022, respectively. The increase for the twelve-month period was primarily related to an increase in non-cash stock-based compensation expense and an increase in professional service costs related to the Pfizer collaboration agreement, offset by a decrease in outside consulting costs.
Net loss for the three months and twelve months ended November 30, 2023, was $42.0 million or ($0.77) per share and $143.9 million or ($2.65) per share, respectively, compared with $46.7 million or ($0.87) per share and $180.4 million or ($3.71) per share for the three and twelve months ended November 30, 2022, respectively.
Cash, cash equivalents and marketable securities was $295.3 million as of November 30, 2023, compared to $268.7 million as of August 31, 2023.

On February 15, 2024 Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, reported results for the fourth quarter and year ending Dec. 31, 2023, and full year 2024 guidance (Press release, LabCorp, FEB 15, 2024, View Source [SID1234640145]).

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Labcorp Logo (PRNewsfoto/Labcorp)

"We made significant progress on our strategy in 2023 and delivered strong results," said Adam Schechter, chairman and CEO. "Our teams developed and brought important diagnostic testing advancements to market and supported our biopharma clients as they advanced their new drug pipelines and treatments. With the successful integration of several hospital partnerships including Ascension, and the spin of Fortrea, we enter 2024 with a strong foundation and momentum. We remain focused on advancing science, technology and innovation to fuel our growth and fulfill our mission to improve health and improve lives."

In the fourth quarter and throughout the year, Labcorp executed on its enterprise strategy. The company closed its previously announced transaction with Legacy Health to acquire select assets of Legacy’s outreach laboratory business. Labcorp now manages Legacy’s inpatient hospital laboratories, serving patients throughout Oregon and Southwest Washington state.

In November, Ovia Health by Labcorp announced that it will offer a first-of-its-kind Fertility and Family Building Benefit, allowing employers and health plans to offer customizable solutions to employees and health plan members to support their family-building needs. Additionally, the company also became the first lab to launch a new, FDA-cleared blood test for risk assessment and clinical management of severe preeclampsia.

Last month, the company announced a strategic collaboration with Hawthorne Effect, Inc. to create new service offerings that support decentralized clinical trials and aim to improve the patient experience, accessibility, and efficiency.

On January 12, 2024, the company announced a quarterly cash dividend of $0.72 per share of common stock, payable on March 13, 2024, to stockholders of record at the close of business on February 27, 2024.

Consolidated Results

Fourth Quarter Results

Revenue for the quarter was $3.03 billion, an increase of 3.5% from $2.93 billion in the fourth quarter of 2022. The increase was due to organic revenue of 1.5%, acquisitions, net of divestitures of 1.4%, and foreign currency translation of 0.7%. The 1.5% increase in organic revenue was driven by a 5.0% increase in the company’s organic Base Business, partially offset by a (3.5%) decrease in COVID-19 PCR and antibody testing (COVID-19 Testing). Compared to the Base Business last year, Base Business revenue grew 7.4%. Base Business includes Labcorp’s operations except for COVID-19 Testing.

Operating loss for the quarter was ($122.8) million, or (4.0)% of revenue, compared to operating income of $28.5 million, or 1.0%, in the fourth quarter of 2022. The company recorded impairment charges, amortization, restructuring charges, and special items, which together totaled $517.6 million in the quarter, compared to $384.0 million during the same period in 2022. Included in these numbers are goodwill and other asset impairment charges of $333.8 million compared to $260.5 million in the fourth quarter 2022, which are primarily related to the Early Development business. Adjusted operating income (excluding impairment charges, amortization, restructuring charges, and special items) for the quarter was $394.9 million, or 13.0% of revenue, compared to $412.6 million, or 14.1%, in the fourth quarter of 2022. The decrease in adjusted operating income was due to a reduction in COVID-19 Testing.

Net losses from continuing operations for the quarter were $(166.8) million compared to net earnings of $37.1 million in the fourth quarter of 2022. Diluted EPS from continuing operations were $(1.95) in the quarter compared to $0.42 during the same period in 2022. Adjusted EPS (excluding impairment charges, amortization, restructuring charges, and special items) were $3.30 in the quarter compared to $3.05 in the fourth quarter of 2022.

Operating cash flow from continuing operations for the quarter was $579.6 million compared to $607.2 million in the fourth quarter of 2022. The decrease in operating cash flow was due to lower COVID-19 Testing. Capital expenditures totaled $165.4 million compared to $99.1 million a year ago. The increase in capital expenditures was primarily timing related. As a result, free cash flow from continuing operations (operating cash flow less capital expenditures) was $414.2 million compared to $508.1 million in the fourth quarter of 2022.

At the end of the quarter, the company’s cash balance and total debt were $0.54 billion and $5.05 billion, respectively. During the quarter, the company invested $154.8 million on acquisitions, paid out $61.1 million in dividends, and settled its accelerated share repurchase program, receiving approximately 1.1 million additional shares. At the end of the quarter, the company had $530.4 million of share repurchase authorization remaining.

Full Year Results

Revenue was $12.16 billion, an increase of 2.5% from $11.86 billion in 2022. The increase was due to acquisitions, net of divestitures of 1.7%, organic revenue of 0.6%, and favorable foreign currency translation of 0.2%. The 0.6% increase in organic revenue was due to an 8.7% increase in the Company’s organic Base Business, partially offset by an (8.1%) decrease in COVID-19 Testing.

Operating income was $725.6 million, or 6.0% of revenue, compared to $1,436.5 million, or 12.1%, in 2022. The company recorded impairment charges, amortization, restructuring charges, and special items, which together totaled $989.3 million compared to $736.0 million during 2022. Adjusted operating income (excluding impairment charges, amortization, restructuring charges, and special items) was $1.71 billion, or 14.1% of revenue, compared to $2.17 billion, or 18.3%, in 2022. The decrease in adjusted operating income was due to lower COVID-19 Testing.

Net earnings from continuing operations were $380.4 million compared to $1,003.5 million in 2022. Diluted EPS were $4.33 compared to $10.94 in 2022. Adjusted EPS (excluding impairment charges, amortization, restructuring charges, and special items) were $13.56 compared to $16.66 in 2022.

Operating cash flow from continuing operations was $1.20 billion compared to $1.76 billion in 2022. The decrease in operating cash flow was primarily due to lower COVID-19 Testing and items related to the Fortrea spin-off. Capital expenditures totaled $453.6 million compared to $429.3 million in 2022. As a result, free cash flow from continuing operations (operating cash flow less capital expenditures) was $748.7 million compared to $1,335.5 million in 2022.

During the year the company repurchased $1.00 billion of stock representing approximately 4.8 million shares and invested $0.67 billion on acquisitions.

Fourth Quarter Segment Results

The following segment results exclude impairment charges, amortization, restructuring charges, special items, and unallocated corporate expenses.

Diagnostics Laboratories

Revenue for the quarter was $2.35 billion, an increase of 2.6% from $2.29 billion in the fourth quarter of 2022. The increase was primarily due to acquisitions of 1.8% and organic revenue of 0.8%. The 0.8% increase in organic revenue was due to a 5.3% increase in the Base Business, partially offset by a (4.5%) decrease in COVID-19 Testing. Total Base Business growth compared to the Base Business in the prior year was 7.6%.

Total volume (measured by requisitions) increased by 2.4% as organic volume increased by 0.3% and acquisition volume contributed 2.1%. Organic volume was impacted by a (2.6%) decrease in COVID-19 Testing, partially offset by a 3.0% increase in Base Business. Price/mix increased by 0.2% due to organic base business growth of 2.4%, partially offset by COVID-19 Testing of (1.9%), and acquisitions of (0.3%). Base Business volume increased 5.2% compared to the Base Business last year. Price/mix was up 2.4% in the Base Business compared to the Base Business last year.

Adjusted operating income for the quarter was $353.7 million, or 15.1% of revenue, compared to $387.0 million, or 16.9%, in the fourth quarter of 2022. The decrease in adjusted operating income was due to a reduction in COVID-19 Testing. The benefit of higher organic demand, acquisitions, and launchpad savings was partially offset by higher personnel costs. The decrease in adjusted operating income margin was due to the reduction in COVID-19 Testing and the mix impact from recently closed hospital partnerships.

Biopharma Laboratory Services

Revenue for the quarter was $694.8 million, an increase of 7.1% from $648.8 million in the fourth quarter of 2022. The increase was primarily due to organic revenue of 4.0%, and foreign currency translation of 3.1%.

Adjusted operating income for the quarter was $109.0 million, or 15.7% of revenue, compared to $95.2 million, or 14.7%, in the fourth quarter of 2022. Adjusted operating income and margin increased due to organic growth and LaunchPad savings, partially offset by higher personnel and stranded costs.

Net orders and net book-to-bill during the trailing twelve months were $2.89 billion and 1.04, respectively. Backlog at the end of the quarter was $8.25 billion, an increase of 4.9% compared to last year. The company expects approximately $2.47 billion of its backlog to convert into revenue in the next twelve months.

2024 Guidance

The following guidance assumes foreign exchange rates effective as of Dec. 31, 2023, for the full year. Enterprise level guidance includes the estimated impact from currently anticipated capital allocation, including acquisitions, share repurchases and dividends.