On November 6, 2024 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the third quarter of 2024 and provided a corporate update (Press release, Aclaris Therapeutics, NOV 6, 2024, View Source [SID1234647796]).

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"The third quarter of 2024 marked an important milestone for Aclaris with the dosing of our first patient in the Phase 2a trial of ATI-2138 for moderate to severe atopic dermatitis," said Dr. Neal Walker, Interim President & CEO and Chair of the Board of Directors of Aclaris. "This milestone, combined with our robust financial position, underscores our commitment to executing a capital-efficient development strategy."

Research and Development Highlights:

● ITK Inhibitor Programs
● ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor
o Atopic Dermatitis (ATI-2138-AD-201): This Phase 2a open-label trial to investigate the safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of ATI-2138 in patients with moderate to severe atopic dermatitis (AD) is ongoing. Aclaris continues to expect top-line data in the first half of 2025.
● ITK Selective Compound
o Aclaris is progressing a second generation ITK selective inhibitor to development candidate selection for autoimmune indications.
● Lepzacitinib (ATI-1777), an investigational topical "soft" JAK 1/3 inhibitor
o In January 2024, Aclaris reported positive top-line results from its Phase 2b trial of lepzacitinib in AD.
o Aclaris is currently seeking a global development and commercialization partner for this program (excluding Greater China). As previously announced, in 2022 Aclaris granted Pediatrix Therapeutics exclusive rights to develop and commercialize lepzacitinib in Greater China.
● Zunsemetinib (ATI-450), an investigational oral small molecule MK2 inhibitor
o Aclaris plans to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib as a potential treatment for pancreatic cancer and metastatic breast cancer. Aclaris expects these trials to be primarily funded by grants awarded to Washington University.

Financial Highlights:

Liquidity and Capital Resources

As of September 30, 2024, Aclaris had aggregate cash, cash equivalents and marketable securities of $173.4 million compared to $181.9 million as of December 31, 2023.

Aclaris anticipates that its cash, cash equivalents and marketable securities as of September 30, 2024 will be sufficient to fund its operations into 2028, without giving effect to any potential business development transactions, financing activities or the outcome of its strategic review.

Financial Results

Third Quarter 2024

● Net loss was $7.6 million for the third quarter of 2024 compared to $29.3 million for the third quarter of 2023.
● Total revenue was $4.3 million for the third quarter of 2024 compared to $9.3 million for the third quarter of 2023. The decrease was primarily driven by higher milestones earned during the prior year period compared to the current year period.
● Research and development (R&D) expenses were $6.0 million for the quarter ended September 30, 2024 compared to $23.9 million for the prior year period.
o The $17.9 million decrease was primarily the result of:
◾ Zunsemetinib development expenses associated with clinical trials in 2023, and drug candidate manufacturing costs;
◾ Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;
◾ ATI-2138 development expenses, including costs associated with a Phase 1 multiple ascending dose (MAD) trial which was completed in September 2023 and other preclinical activities, which were partially offset by clinical development expenses associated with a Phase 2a clinical trial which commenced in August 2024; and
◾ Lower compensation-related expenses due to a decrease in headcount and higher forfeiture credits.
● General and administrative (G&A) expenses were $5.7 million for the quarter ended September 30, 2024 compared to $7.1 million for the corresponding prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits.
● Licensing expenses were $1.8 million for the quarter ended September 30, 2024 compared to $7.3 million for the corresponding prior year period. The decrease was primarily due to higher milestones earned during the prior year period compared to the current year period.
● Revaluation of contingent consideration resulted in a $0.8 million loss for the quarter ended September 30, 2024 compared to a loss of $1.7 million for the prior year period.
Year-to-date 2024

● Net loss was $35.5 million for the nine months ended September 30, 2024 compared to $87.0 million for the nine months ended September 30, 2023.
● Total revenue was $9.5 million for the nine months ended September 30, 2024 compared to $13.7 million for the nine months ended September 30, 2023. The decrease was primarily driven by higher milestones earned during the prior year period compared to the current year period.
● R&D expenses were $24.6 million for the nine months ended September 30, 2024 compared to $71.7 million for the corresponding prior year period.
o The $47.1 million decrease was primarily the result of:
◾ Zunsemetinib development expenses associated with clinical trials in 2023, and drug candidate manufacturing costs;
◾ Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;
◾ ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial which was completed in September 2023 and other preclinical activities, which were partially offset by clinical development expenses associated with a Phase 2a clinical trial which commenced in August 2024; and
◾ Lower compensation-related expenses due to a decrease in headcount and higher forfeiture credits.
● G&A expenses were $17.2 million for the nine months ended September 30, 2024 compared to $24.2 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits and the recognition of bad debt expense recorded in the prior year period from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection.
● Licensing expenses were $4.1 million for the nine months ended September 30, 2024 compared to $9.0 million for the prior year period. The decrease was primarily due to higher milestones earned during the prior year period compared to the current year period.
● Revaluation of contingent consideration resulted in a $3.8 million loss for the nine months ended September 30, 2024 compared to a gain of $0.6 million for the corresponding prior year period.

On November 5, 2024 Avid Bioservices, Inc. (NASDAQ: CDMO) ("Avid" or the "Company"), a dedicated biologics contract development and manufacturing organization ("CDMO") working to improve patient lives by providing high quality development and manufacturing services to biotechnology and pharmaceutical companies, GHO Capital Partners LLP ("GHO") and Ampersand Capital Partners ("Ampersand") reported they have entered into a definitive merger agreement for Avid to be acquired by funds managed by GHO and Ampersand in an all-cash transaction valued at approximately $1.1 billion (Press release, Avid Bioservices, NOV 6, 2024, View Source [SID1234647786]).

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Under the terms of the merger agreement, GHO and Ampersand would acquire all the outstanding shares held by Avid’s stockholders for $12.50 per share in cash. The per share purchase price represents a 13.8% premium to Avid’s closing share price of $10.98 on November 6, 2024, the last full trading day prior to the transaction announcement, and a 21.9% premium to the Company’s 20-day volume-weighted average share price for the period ended November 6, 2024. This transaction equates to an enterprise value of approximately $1.1 billion, a 6.3x multiple to consensus FY2025E revenue.

"Since our founding, Avid Bioservices’ business has grown by evolving to meet our customers’ broad range of development and manufacturing needs. After years of investment and expansion, now is the right time to move forward as a private company with new owners that will support our next phase," stated Nick Green, president and CEO of Avid Bioservices. "In evaluating this transaction, our Board considered a range of alternatives and determined that it provides our stockholders significant, immediate and certain cash value for their shares. Partnering with GHO Capital and Ampersand Capital Partners allows us to build on our strong foundation by accessing their significant knowledge base, network and capital to position the business for the future with our customers."

"We are excited to announce this recommended cash acquisition of Avid," said Alan MacKay and Mike Mortimer, Managing Partners of GHO. "As experienced CDMO industry investors, GHO brings deep expertise and experience to support Avid’s management team going forward. Our mission at GHO is to make healthcare better, faster, and more accessible and at the heart of this is enabling efficient, high-quality manufacturing of innovative treatments. Avid exemplifies this perfectly – the Company operates in high-growth markets, producing complex biologics for leading pharmaceutical and biotech innovators at both the clinical and commercial stages. Avid’s recent investments, both in capacity and its exemplary team, position it strongly for future growth. We look forward to working with the Avid team to unlock the Company’s full potential through our established playbook of expanded offerings, talent investment and greater geographic reach."

"Avid has long been a trusted provider of biopharmaceutical development and manufacturing services, and we have tremendous respect for its team’s expertise, its broad spectrum of customized services and its strong regulatory track record. We look forward to leveraging our deep industry experience, focused strategy, and collaborative approach to drive growth," said, David Anderson, General Partner of Ampersand.

Transaction Details

The transaction, which was unanimously approved by the Avid Board of Directors, is currently expected to close in the first quarter of 2025, subject to customary closing conditions, including approval by Avid’s stockholders and receipt of required regulatory approvals. The transaction is not subject to a financing condition. The companies will continue to operate independently until the proposed transaction is finalized.

Upon completion of the transaction, Avid common stock will no longer be listed on any public stock exchange. The Company will continue to operate under the Avid name and brand.

Advisors

Moelis & Company LLC is serving as exclusive financial advisor to Avid, and Cooley LLP is serving as legal counsel to Avid. William Blair & Company, LLC is serving as exclusive financial advisor and Ropes & Gray LLP is serving as legal counsel to GHO and Ampersand.

On November 5, 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 that data will be presented from its two Bruton’s tyrosine kinase (BTK) degrader programs, NX-5948 and NX-2127, in two oral presentations and one poster at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, CA (Press release, Nurix Therapeutics, NOV 5, 2024, View Source [SID1234649114]).

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Oral Presentation Details:

Title: Efficacy and Safety of the Bruton’s Tyrosine Kinase (BTK) Degrader NX-5948 in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Updated Results from an Ongoing Phase 1a/b Study
Authors: Nirav N. Shah, Zulfa Omer, Graham Collins, Francesco Forconi, Alexey Danilov, John Byrd, Dima El Sharkawi, Emma Searle, Alvaro Alencar, Shuo Ma, Sarah Injac, Talha Munir
Session Name: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Treating Refractory Disease-Novel Agents and Quality-of-Life
Session Date and Time: Monday, December 9, 2024, 2:45 p.m. – 4:15 p.m. PT
Presentation Time: 3:00 p.m. PT
Room: Marriott Marquis San Diego Marina, Marriott Grand Ballroom 5-6

Title: NX-2127 and NX-5948, Two Clinical Stage Cereblon-Recruiting BTK Degraders, Facilitate T Cell Functionality in Chronic Lymphocytic Leukemia
Authors: Tiana Huynh, Sonia Rodriguez-Rodriguez, Carly Roleder, Sarah Whelan, May Tan, Ernestine Lee, Paul Munson, and Alexey Danilov
Session Name: 641. Chronic Lymphocytic Leukemia: Basic and Translational: Therapeutic Vulnerabilities, Signaling, and Microenvironment
Session Date and Time: Saturday, December 7, 2024, 9:30 a.m. – 11:00 a.m. PT
Presentation Time: 10:30 a.m. PT
Room: Marriott Marquis San Diego Marina, Marriott Grand Ballroom 5-6

Poster Presentation Details

Title: BTK Degradation As a Novel Therapeutic Strategy in Relapsed CNS Lymphoma: Proof of Concept Studies in Intracranial Patient-Derived, Rodent Models

Authors: Jun Ma, Michael Randall, Ming Lu, Lingjing Chen, Huimin Geng, Aishwarya Kumar, Saloni Malla, Mark Noviski, Ryan Rountree, James L. Rubenstein
Session Name: 622. Lymphomas: Translational – Non-Genetic: Poster II
Session Date and Time: Sunday, December 8, 2024, 6:00 p.m. – 8:00 p.m. PT
Location: San Diego Convention Center, Halls G-H

About NX-5948: NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the Phase 1a/b clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022).

About NX-2127: NX-2127 is an investigational, orally bioavailable degrader of BTK and cereblon neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). NX-2127 is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the ongoing clinical trial can be accessed at www.clinicaltrials.gov (NCT04830137).

On November 5, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported that two abstracts from the ongoing Phase 1/2 trial of cemsidomide have been accepted for presentation at the ASH (Free ASH Whitepaper) Annual Meeting taking place from December 7 – 10, 2024 in San Diego, California (Press release, C4 Therapeutics, NOV 5, 2024, View Source [SID1234648575]). Non-Hodgkin’s lymphoma (NHL) data will be shared as an oral presentation and multiple myeloma (MM) data will be shared as a poster presentation. The abstracts are available online on the ASH (Free ASH Whitepaper) Annual Meeting website.

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The presentations on December 8th at the ASH (Free ASH Whitepaper) Annual Meeting will include updated data compared to the abstracts.

NHL Oral Presentation Details:

Title: Initial Results of a Phase 1 First-in-Human Study of Cemsidomide (CFT7455), a Novel MonoDAC Degrader, in Patients with Non-Hodgkin’s Lymphoma
Format: Oral (10-minute presentation, followed by a 5-minute discussion)
Session: T Cell, NK Cell, or NK/T Cell Lymphomas: Clinical and Epidemiological: When Old Meets New in T Cell Lymphomas
Session Date: Sunday, December 8, 2024
Presentation Time: 10:30 AM PT (1:30 PM ET)
Location: San Diego Convention Center, Ballroom 20CD

MM Poster Presentation Details:

Title: Initial Results of a Phase 1 First-in-Human Study of Cemsidomide (CFT7455), a Novel MonoDAC Degrader, with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
Format: Poster presentation
Session: Multiple Myeloma: Pharmacologic Therapies: Poster II
Session Date: Sunday, December 8, 2024
Presentation Time: 6:00 PM – 8:00 PM PT (9 PM – 11 PM ET)
Location: San Diego Convention Center, Halls G-H
Publication Number: 3366

C4T Investor Webcast

C4T will host a webcast on Sunday, December 8, 2024 at 2 PM PT (5 PM ET). A live webcast of the event will be available using this link or under the "Events & Presentations" page of the Investors section on the company’s website at www.c4therapeutics.com. A replay of the webcast will be archived and available following the event.

On November 5, 2024 Eli Lilly and Company (NYSE: LLY) reported that data from studies of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, will be presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place Dec. 7-10 in San Diego (Press release, Eli Lilly, NOV 5, 2024, View Source [SID1234648267]).

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In an oral presentation, Lilly will report results from the Phase 3 BRUIN CLL-321 study, which is evaluating pirtobrutinib versus idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in BTK inhibitor pretreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). BRUIN CLL-321, which previously met its primary endpoint, is the first randomized Phase 3 study to evaluate an exclusively BTK inhibitor pretreated CLL population. The submitted abstract utilized a February 2024 data cut-off date, and the presentation will utilize an August 2024 data cut-off date.

Additionally, Lilly will have poster presentations that share analyses of real-world data, including looking at overall survival associated with treatment sequences in patients with CLL/SLL, and pre-clinical data for a first-in-class B-cell activating factor receptor (BAFF)-RxCD3 bispecific antibody for the treatment of certain B-cell malignancies.

A full list of abstract titles and viewing details are listed below:

Jaypirca (pirtobrutinib)
Presentation Title: BRUIN CLL-321: Randomized Phase 3 Trial of Pirtobrutinib Versus Idelalisib Plus Rituximab (IdelaR) or Bendamustine Plus Rituximab (BR) in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Abstract Number: 886
Presentation Date & Time: Monday, Dec. 9, 3:30 p.m. PST
Location: Marriot Marquis San Diego Marina, Marriott Grand Ballroom 5-6
Presenter: Jeff P. Sharman

Presentation Title: Overall Survival Associated with Real-World Treatment Sequences in Patients with CLL/SLL in the United States
Abstract Number: 5114
Presentation Date & Time: Monday, Dec. 9, 6-8 p.m. PST
Location: San Diego Convention Center, Halls G-H
Presenter: Joanna Rhodes

Presentation Title: Continuity of Care for Patients with Chronic Lymphocytic Leukemia: An Analysis of Real-World Data
Abstract Number: 5033
Presentation Date & Time: Monday, Dec. 9, 6-8 p.m. PST
Location: San Diego Convention Center, Halls G-H
Presenter: Sameh Gaballa

LY4152199 (investigational BAFF-RxCD3 bispecific antibody)
Presentation Title: LY4152199, a First-in-Class BAFF-RxCD3 Bispecific Antibody for the Treatment of B-Cell Malignancies
Abstract Number: 2785
Presentation Date & Time: Sunday, Dec. 8, 6-8 p.m. PST
Location: San Diego Convention Center, Halls G-H
Presenter: Wei Yang

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

INDICATIONS FOR JAYPIRCA
Jaypirca is a kinase inhibitor indicated for the treatment of

Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred (4.4%). Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (17%). Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%). Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. Upon confirmation of DILI, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Serious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%).

Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis.

Most common ARs (≥20%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Special Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.

PT HCP ISI MCL_CLL AA JUN2024

Please see Prescribing Information and Patient Information for Jaypirca.