On November 2, 2023 Eli Lilly and Company (NYSE: LLY) reported that data from studies of pirtobrutinib, a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, will be presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place December 9-12 in San Diego (Press release, Eli Lilly, NOV 2, 2023, View Source [SID1234636757]).

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The presentations will provide updated, longer follow-up clinical safety and efficacy data for approved and investigational uses of pirtobrutinib from the ongoing Phase 1/2 BRUIN study in multiple B-cell malignancies. In mantle cell lymphoma (MCL), an oral presentation will provide updated safety and efficacy results of pirtobrutinib in all patients, including those with biologically high-risk relapsed or refractory MCL. In chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), oral presentations include long-term follow-up data in patients with relapsed or refractory CLL/SLL in the post-cBTKi setting, including patients with or without BCL-2 inhibitor exposure, and an updated analysis of the genomic evolution of resistance mechanisms in pirtobrutinib-treated CLL patients. Additionally, poster presentations will provide data on the clinical impact of pirtobrutinib following cBTKi treatment across other B-cell malignancies.

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

Presentation Title: Pirtobrutinib in Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Patients with Prior cBTKi: Safety and Efficacy Including High-Risk Subgroup Analyses from the Phase 1/2 BRUIN Study
Abstract Number: 981
Oral Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Targeted Therapy
Presentation Date & Time: Monday, December 11, 5:00 PM PT
Location: Manchester Grand Hyatt San Diego, Grand Hall C
Presenter: Jonathon B. Cohen

Presentation Title: Pirtobrutinib in Post-cBTKi CLL/SLL: ~30 Months Follow-up and Subgroup Analysis With/Without Prior BCL2i from the Phase 1/2 BRUIN Study
Abstract Number: 325
Oral Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: New Inhibitors and Cellular Therapies for Treatment of Relapsed CLL
Presentation Date & Time: Saturday, December 9, 4:00 PM PT
Location: Manchester Grand Hyatt San Diego, Grand Hall D
Presenter: Jennifer A. Woyach

Presentation Title: Genomic Evolution and Resistance during Pirtobrutinib Therapy in Covalent BTK-Inhibitor (cBTKi) Pre-Treated Chronic Lymphocytic Leukemia Patients: Updated Analysis from the BRUIN Study
Abstract Number: 326
Oral Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: New Inhibitors and Cellular Therapies for Treatment of Relapsed CLL
Presentation Date & Time: Saturday, December 9, 4:15 PM PT
Location: Manchester Grand Hyatt San Diego, Grand Hall D
Presenter: Jennifer R. Brown

Presentation Title: Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Relapsed/Refractory Follicular Lymphoma: Results from the Phase 1/2 BRUIN Study
Abstract Number: 3026
Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Presentation Date & Time: Sunday, December 10, 6:00 – 8:00 PM PT
Location: San Diego Convention Center, Halls G-H
Presenter: Nirav N. Shah

Presentation Title: Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Relapsed/Refractory Marginal Zone Lymphoma: Results from Phase 1/2 BRUIN Study
Abstract Number: 1660
Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Presentation Date & Time: Saturday, December 9, 5:30 – 7:30 PM PT
Location: San Diego Convention Center, Halls G-H
Presenter: Krish Patel

Presentation Title: Pirtobrutinib in Richter Transformation: Updated Efficacy and Safety Results with 18-Month Median Survival Follow-up from the Phase 1/2 BRUIN Study
Abstract Number: 1737
Poster Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I
Presentation Date & Time: Saturday, December 9, 5:30 – 7:30 PM PT
Location: San Diego Convention Center, Halls G-H
Presenter: William G. Wierda

Presentation Title: Fixed-Duration Pirtobrutinib Combined with Venetoclax ± Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia: Updated Results, Including MRD Data, from the BRUIN Phase 1b Study
Abstract Number: 3269
Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II
Presentation Date & Time: Sunday, December 10, 6:00 – 8:00 PM PT
Location: San Diego Convention Center, Halls G-H
Presenter: Lindsey E. Roeker

Presentation Title: Pirtobrutinib, a Non-Covalent (reversible) BTK Inhibitor, in Mantle Cell Lymphoma Patients Previously Treated with a Covalent BTK Inhibitor: Results from a China Phase 2 Study
Abstract Number: 3626
Poster Session: 802. Chemical Biology and Experimental Therapeutics: Poster II
Presentation Date & Time: Sunday, December 10, 6:00 – 8:00 PM PT
Location: San Diego Convention Center, Halls G-H
Presenter: Jun Zhu

Presentation Title: Real-World Use and Outcomes of Therapies, Including Venetoclax-Based Treatments, after Discontinuation of a Covalent BTK Inhibitor in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Abstract Number: 5152
Poster Session: 905. Outcomes Research—Lymphoid Malignancies: Poster III
Presentation Date & Time: Monday, December 11, 6:00 – 8:00 PM PT
Location: San Diego Convention Center, Halls G-H
Presenter: Nitin Jain

About the BRUIN Phase 1/2 Trial
The BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of pirtobrutinib in patients with previously treated hematologic malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL).

The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by overall response rate (ORR) for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an independent review committee (IRC). Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and PK.

About Pirtobrutinib
Pirtobrutinib 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 plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation, and survival of normal white blood cells, known as B-cells, and malignant B-cells. 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 Pirtobrutinib was developed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, and preserve activity in the presence of the C481 acquired resistance mutations.

Pirtobrutinib was approved under the FDA’s Accelerated Approval pathway as Jaypirca (pirtobrutinib) on January 27, 2023. Jaypirca is indicated for the treatment of adult patients with relapsed or refractory MCL after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication 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, or fungal) and opportunistic infections have occurred in patients treated with Jaypirca. In the clinical trial, Grade ≥3 infections occurred in 17% of 583 patients with hematologic malignancies, most commonly pneumonia (9%); fatal infections occurred in 4.1% of patients. Sepsis (4.5%) and febrile neutropenia (2.9%) occurred. Opportunistic infections after Jaypirca treatment included, but are not limited to, 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 2.4% of 583 patients with hematologic malignancies treated with Jaypirca, including gastrointestinal hemorrhage; fatal hemorrhage occurred in 0.2% of patients. Bleeding of any grade, excluding bruising and petechiae, occurred in 14% of patients. Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (1.7%) 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: Grade 3 or 4 cytopenias, including neutropenia (24%), anemia (11%), and thrombocytopenia (11%), have developed in patients with hematologic malignancies treated with Jaypirca. In a clinical trial, Grade 4 neutropenia (13%) and Grade 4 thrombocytopenia (5%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Atrial Fibrillation and Atrial Flutter: Atrial fibrillation or flutter were reported in 2.7% of patients, with Grade 3 or 4 atrial fibrillation or flutter reported in 1% of 583 patients with hematologic malignancies treated with Jaypirca. 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 6% of 583 patients with hematologic malignancies treated with Jaypirca monotherapy. The most frequent malignancy was non-melanoma skin cancer (3.8%). 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.

Embryo-Fetal Toxicity: Based on animal findings, Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats during organogenesis 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 risk to a fetus and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients with Mantle Cell Lymphoma Who Received Jaypirca
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 dose of Jaypirca occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1%).

Dose Modifications and Discontinuations: ARs led to dosage 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 of Jaypirca in >1% of patients included pneumonia.

ARs (all Grades %; Grade 3-4 %) in ≥10% of Patients: fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -), peripheral neuropathy (14; 0.8), cough (14; -), rash (14; -), fever (13; -), constipation (13; -), arthritis/arthralgia (12; 0.8), hemorrhage (11; 3.1), abdominal pain (11; 0.8), nausea (11; -), upper respiratory tract infections (10; 0.8), dizziness (10; -).

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).

All grade ARs with higher frequencies in the total BRUIN population of patients with hematologic malignancies (n=583) were decreased neutrophil count (41%), bruising (20%), diarrhea (20%).

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

Sensitive CYP2C8, CYP2C19, CYP3A, P-gP, 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: Inform pregnant women of 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 and effects on the breastfed child or on milk production 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, 392 (67%) were ≥65 years of age. 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 (eGFR 15-29 mL/min) increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to the approved labeling. No dosage adjustment is recommended in patients with mild or moderate renal impairment.

PT HCP ISI MCL APP

Please see Prescribing Information and Patient Information for Jaypirca.

On November 2, 2023 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported financial results for the third quarter ended September 30, 2023, and highlighted recent business achievements (Press release, Elevation Oncology, NOV 2, 2023, View Source;utm_medium=rss&utm_campaign=elevation-oncology-reports-third-quarter-2023-financial-results-and-highlights-recent-business-achievements [SID1234636756]).

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

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"In the third quarter, we achieved a key milestone in our efforts to establish EO-3021 as a potential best-in-class anti-Claudin 18.2 ADC therapy, initiating patient enrollment in our Phase 1 clinical trial," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "Claudin 18.2 is a validated target, expressed at varying levels in solid tumor types that affect millions of patients globally. As an ADC, EO-3021 is uniquely positioned to address a broad population by targeting tumors that express varying levels of Claudin 18.2, which may be inaccessible to other therapeutic approaches, while also potentially delivering improved efficacy and tolerability. As demonstrated by initial clinical data from our partner in China, we believe EO-3021 could deliver an important treatment option for patients."

Recent Business Achievements

In August 2023, Elevation Oncology began enrolling patients in its Phase 1 clinical trial of EO-3021 (NCT05980416). The Phase 1 clinical trial is an open-label, multi-center, dose escalation and expansion study designed to evaluate the safety, tolerability and preliminary anti-tumor activity of EO-3021 in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction, pancreatic or esophageal cancers. An additional objective of the study is to assess the association of Claudin 18.2 expression and objective response. Elevation Oncology expects to report preliminary safety and anti-tumor activity data during the first half of 2025.

Third Quarter 2023 Financial Results

As of September 30, 2023, Elevation Oncology had cash, cash equivalents and marketable securities totaling $94.8 million, compared to $90.3 million as of December 31, 2022. The increase in cash reflects net proceeds of approximately $46.5 million from Elevation Oncology’s underwritten public offering, which closed in June 2023, partially offset by cash used to fund operating activities.

Research and development (R&D) expenses for the third quarter 2023 were $7.4 million, compared to $34.3 million for the third quarter 2022. The decrease in R&D expenses in the third quarter of 2023 was primarily due to the cost related to the license agreement between Elevation Oncology and a subsidiary of CSPC Pharmaceutical Group Limited for rights to develop and commercialize EO-3021, which was recorded in the third quarter of 2022.

General and administrative (G&A) expenses for the third quarter 2023 were $3.5 million, compared to $4.2 million for the third quarter 2022. The decrease in G&A expenses in the third quarter of 2023 was primarily due to a decrease in administrative costs, including directors’ and officers’ insurance.

Net loss for the third quarter 2023 was $10.6 million, compared to $38.8 million for the third quarter 2022.

Financial Outlook

Elevation Oncology expects its existing cash, cash equivalents and marketable securities as of September 30, 2023, to be sufficient to fund its current operations into the second half of 2025.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2. EO-3021is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformations, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

On November 2, 2023 Electra Therapeutics, Inc., a clinical stage biotechnology company developing antibody therapies against novel targets, reported that the company will present the initial clinical data for its lead drug candidate, ELA026, in a poster at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting being held in San Diego, California, December 9-12, 2023 (Press release, Electra Therapeutics, NOV 2, 2023, View Source [SID1234636755]).

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ELA026 is a monoclonal antibody that targets signal regulatory protein-α/β1/γ (SIRP) to enable precise depletion of pathological immune cells. ELA026 is currently in a Phase 1b clinical study in patients with secondary hemophagocytic lymphohistiocytosis (sHLH), a life-threatening inflammatory disease.

Details of the poster presentations are as follows:

Title: A Phase 1b Study of ELA026, a Monoclonal Antibody Targeting Signal Regulatory Protein-α/β1/γ, in Patients with Newly Diagnosed and Previously Treated Secondary Hemophagocytic Lymphohistiocytosis
Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster I
Session Date and Time: Saturday, December 9, 2023, 5:30 – 7:30 p.m.
Location: San Diego Convention Center, Halls G-H
Publication Number: 1162

About Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory condition for which there is no approved treatment. sHLH can be triggered by cancer, immunotherapy, infection, or an autoimmune disease. Once triggered, sHLH requires immediate intervention. Without treatment, it can rapidly progress from symptoms such as persistent fever, hepatomegaly and/or splenomegaly, and cytopenias, to multi-organ failure and death. Even with the current use of off-label treatments that have toxicity challenges and limited efficacy, sHLH remains fatal in approximately 60% of adults within 3.5 years.

On November 2, 2023 Dynavax Technologies Corporation (Nasdaq: DVAX), a commercial-stage biopharmaceutical company developing and commercializing innovative vaccines, reported financial results and provided a business update for the quarter ended September 30, 2023 (Press release, Dynavax Technologies, NOV 2, 2023, View Source [SID1234636754]).

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

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"We’re pleased to report yet another record quarter of HEPLISAV-B revenue driven by continued market share growth and overall expansion of the adult hepatitis B market, demonstrating progress toward our goal of establishing HEPLISAV-B as the leading adult hepatitis B vaccine in the U.S., a market opportunity we believe will continue to expand to over $800 million by 2027," said Ryan Spencer, Chief Executive Officer of Dynavax. "In addition to HEPLISAV-B, we are focused on advancing our pipeline of innovative vaccine candidates, pursuing strategic opportunities to accelerate our growth, and continuing to drive strong financial performance, reflecting the solid foundation we’ve established for sustained success."

BUSINESS UPDATES

HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted]

HEPLISAV-B vaccine is the first and only adult hepatitis B vaccine approved in the U.S., the European Union and Great Britain that enables series completion with only two doses in one month. Hepatitis B vaccination is universally recommended for adults aged 19-59 in the U.S.

HEPLISAV-B achieved net product revenue of $62.3 million for the third quarter of 2023, an increase of 66% compared to $37.5 million for the third quarter of 2022.
HEPLISAV-B total market share in the U.S. increased to approximately 41%, compared to approximately 32% at the end of the third quarter of 2022.
HEPLISAV-B market share in the Integrated Delivery Networks (IDNs) and Large Clinics segment increased to approximately 54% at the end of the third quarter of 2023, compared to approximately 43% for the same quarter in 2022.
HEPLISAV-B market share in the retail pharmacy segment increased to approximately 53% at the end of the third quarter of 2023, compared to 43% for the same quarter in 2022.
A supplemental Biologic License Application (sBLA) for HEPLISAV-B vaccination of adults on hemodialysis is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) action date expected on May 13, 2024.
Clinical Pipeline
Dynavax is advancing a pipeline of differentiated product candidates that leverage its CpG 1018 adjuvant, which has demonstrated its ability to enhance the immune response with a favorable tolerability profile in a wide range of clinical trials and real-world commercial use.

Shingles vaccine program:
Z-1018 is an investigational vaccine candidate being developed for the prevention of shingles in adults aged 50 and older.

Dynavax recently received Type B meeting feedback from the FDA on the Z-1018 clinical development plan and expects to submit an Investigational New Drug Application (IND) to the FDA to support the initiation of a Phase 1/2 trial of Z-1018 in the first half of 2024.
Tdap vaccine program:
Tdap-1018 is an investigational vaccine candidate intended for active booster immunization against tetanus, diphtheria, and pertussis (Tdap).

Dynavax plans to submit an Investigational New Drug Application (IND) to the FDA to support the initiation of a Phase 2 human challenge study of Tdap-1018 in mid-2024.
Plague vaccine program:
Dynavax is developing a plague (rF1V) vaccine candidate adjuvanted with CpG 1018 currently in a Phase 2 clinical trial in collaboration with, and fully funded by, the U.S. Department of Defense.

Dynavax and the U.S. Department of Defense recently executed a contract modification to support advancement of the plague vaccine candidate into a nonhuman primate challenge study, which was initiated in August, with the agreement now totaling $33.7 million through 2025.
Dosing has been completed in a randomized, active-controlled Phase 2 clinical trial evaluating immunogenicity, safety, and tolerability, with top line data anticipated in 2024.
THIRD QUARTER 2023 FINANCIAL HIGHLIGHTS

Total Revenues and Net Product Revenue.

HEPLISAV-B vaccine net product revenue was $62.3 million for the third quarter of 2023, compared to $37.5 million for the third quarter of 2022, representing year-over-year growth of 66%. The increase was primarily due to higher sales volume driven by both continued improvement in market share and higher utilization of adult hepatitis B vaccines related to the ACIP universal recommendation.
Other revenue was $7.2 million for the third quarter of 2023, compared to $3.9 million in the same period of 2022. Other revenue primarily includes revenue from our plague vaccine agreement with the U.S. Department of Defense. The increase was primarily driven by the advancement into a nonhuman primate challenge study.
No CpG 1018 adjuvant product revenue was recorded in the third quarter of 2023, compared to $126.3 million in the third quarter of 2022, due to completion of all obligations and product delivery under the Company’s CpG 1018 adjuvant COVID-19 collaboration agreements as of December 31, 2022.
Total revenues for the third quarter of 2023 were $69.5 million, compared to $167.7 million for the third quarter of 2022.
Cost of Sales – Product. Cost of sales – product for HEPLISAV-B in the third quarter of 2023 increased to $13.2 million, compared to $11.5 million for the third quarter of 2022. The increase was primarily due to higher sales volume driven by continued improvement in HEPLISAV-B market share, offset by lower per-unit manufacturing costs as the result of previous process improvements. Total cost of sales – product for the third quarter of 2023 decreased to $13.2 million, compared to $61.3 million in the third quarter of 2022. The decrease is primarily due to no CpG 1018 adjuvant cost of sales – product for the third quarter of 2023 as a result of completing all obligations and product delivery under the prior CpG 1018 adjuvant collaboration agreements as of December 31, 2022.

Research and Development Expenses (R&D). R&D expenses for the third quarter of 2023 increased to $14.1 million, compared to $13.0 million for the third quarter of 2022. The increase was primarily driven by continued investments in advancing our clinical and preclinical development programs and collaborations.

Selling, General, and Administrative Expenses (SG&A). SG&A expenses for the third quarter of 2023 increased to $38.1 million, compared to $32.0 million for the third quarter of 2022. The increase was primarily driven by higher compensation and related personnel costs and an overall increase in targeted commercial and marketing efforts designed to increase HEPLISAV-B market share and maximize the opportunities presented by the ACIP’s universal recommendation.

Net income. GAAP net income was $14.3 million, or $0.11 per share (basic) and $0.10 per share (diluted) in the third quarter of 2023, compared to GAAP net income of $63.8 million, or $0.50 per share (basic) and $0.43 per share (diluted) in the third quarter of 2022.

Cash and Marketable Securities. Cash, cash equivalents and marketable securities were $720.4 million as of September 30, 2023.

2023 FINANCIAL GUIDANCE
Full year 2023 financial guidance has been revised to consist of the following expectations:

HEPLISAV-B net product revenue between approximately $210 – $220 million, compared to the prior range of approximately $200 – $215 million.
Research and development expenses between approximately $50 – $60 million, compared to the prior range of approximately $55 – $70 million.
Selling, general and administrative expenses between approximately $145 – $155 million, compared to the prior range of approximately $135 – $155 million.
Conference Call and Webcast Information
Dynavax will host a conference call and live audio webcast on Thursday, November 2, 2023, at 4:30 p.m. ET/1:30 p.m. PT. The live audio webcast may be accessed through the "Events & Presentations" page on the "Investors" section of the Company’s website at View Source A replay of the webcast will be available for 30 days following the live event.

To dial into the call, participants will need to register for the call using the caller registration link. It is recommended that participants dial into the conference call or log into the webcast approximately 10 minutes prior to the call.

Important U.S. Product Information
HEPLISAV-B is indicated for the prevention of infection caused by all known subtypes of hepatitis B virus in adults aged 18 years and older.

For full U.S. Prescribing Information for HEPLISAV-B, click here.

Important U.S. Safety Information (ISI)
Do not administer HEPLISAV-B to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast.

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B.

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B.

Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration.

The most common patient-reported adverse reactions reported within 7 days of vaccination were injection site pain (23% to 39%), fatigue (11% to 17%), and headache (8% to 17%).

On November 2, 2023 Cytokinetics, Incorporated (Nasdaq: CYTK) reported financial results for the third quarter of 2023 (Press release, Cytokinetics, NOV 2, 2023, View Source [SID1234636753]). Net loss for the third quarter was $129.4 million, or $1.35 per share, compared to net loss for the third quarter of 2022 of $142.3 million, or $1.52 per share. Cash, cash equivalents and investments totaled $554.7 million on September 30, 2023.

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"During the third quarter we made considerable progress across our specialty cardiology franchise, with aficamten remaining our top priority. Of note, the baseline characteristics of patients enrolled in SEQUOIA-HCM met our objectives for the trial and align with our goal to assess aficamten as a potential next-in-class cardiac myosin inhibitor in a population with a substantial deficit in exercise capacity and significant symptom burden despite existing standard of care," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "In addition, we recently shared longer-term data from FOREST-HCM that demonstrate durable reductions in pressure gradients and cardiac biomarkers as well as improved symptoms in patients with obstructive HCM. During the quarter we also started ACACIA-HCM, a pivotal Phase 3 clinical trial of aficamten in patients with non-obstructive HCM. Alongside these increasing commitments to aficamten, we are approaching the end of 2023 in a strong position with the resources and pipeline to execute on our goals in service to both patients and shareholders."

Q3 and Recent Highlights

Cardiac Muscle Programs

aficamten (cardiac myosin inhibitor)

•
Presented baseline characteristics from SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), the first Phase 3 trial of aficamten in obstructive hypertrophic cardiomyopathy (HCM), at the HCM Society Scientific Sessions 2023.

•
Shared new long-term data from FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) the open-label extension clinical study of aficamten in patients with HCM, at the Company’s recent Investor and Analyst Day, demonstrating sustained reductions in left ventricular outflow tract (LVOT) gradients with no treatment interruptions for low left ventricular ejection fraction (LVEF) due to aficamten. Additionally, patients experienced sustained reductions in cardiac biomarkers and improved symptoms. Aficamten has been generally well-tolerated, with no treatment-related serious adverse events (SAEs) as assessed by investigators, and no patient deaths.

•
Announced the start of ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), a pivotal Phase 3 clinical trial of aficamten in patients with non-obstructive HCM.

•
Published a manuscript entitled "Aficamten in Patients with Drug-Refractory Obstructive Hypertrophic Cardiomyopathy Receiving Disopyramide: REDWOOD-HCM Cohort 3 Analysis" in the Journal of Cardiac Failure.

•
Published a manuscript entitled "Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of Aficamten in Healthy Chinese Participants: a Randomized, Double-blind, Placebo-controlled, Phase 1 Study" in the Frontiers of Pharmacology.

•
Published a manuscript entitled "Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design" in the Journal of the American College of Cardiology: Heart Failure.

omecamtiv mecarbil (cardiac myosin activator)

•
Submitted a Formal Dispute Resolution Request to the Office of New Drugs (OND) of the U.S. Food and Drug Administration (FDA) regarding the Complete Response Letter (CRL) for omecamtiv mecarbil with objective to appeal the FDA’s conclusion, as stated in the CRL, that
substantial evidence of effectiveness had not been established to support approval of omecamtiv mecarbil.

•
Submitted responses to the Day 120 questions to the European Medicines Agency (EMA) in connection with its review of the marketing application for omecamtiv mecarbil for the treatment of advanced or worsening heart failure with reduced ejection fraction (HFrEF).

•
Ji Xing Pharmaceuticals submitted a request for voluntary withdrawal of the NDA for omecamtiv mecarbil to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of the People’s Republic of China, subject to potential re-submission upon receipt of favorable feedback from EMA or FDA with regard to potential drug approval for omecamtiv mecarbil in the EU or U.S., respectively.

CK-3828136 (CK-136, cardiac troponin activator)

•
Completed the single ascending dose (SAD) cohorts of the Phase 1 study of CK-136 in healthy participants. Initiated analyses of the SAD data to inform potentially proceeding to the multiple ascending dose (MAD) cohorts of the Phase 1 study.

CK-4021586 (CK-586, cardiac myosin inhibitor)

•
Completed the SAD cohorts of the Phase 1 study of CK-586 in healthy participants. Completed analyses of the SAD data which are supportive of proceeding to the MAD cohorts of the Phase 1 study in Q4 2023.

Pre-Clinical Development and Ongoing Research

•
Continued research activities directed to our other muscle biology research programs.

Corporate

•
Announced a call for proposals for the sixth annual Cytokinetics Communications Grant Program. The program awards five grants worth $20,000 each to patient advocacy organizations serving the HCM, heart failure or ALS communities, and is intended to support increased capacity in communications and outreach.

Upcoming Corporate Milestones

Cardiac Muscle Programs

aficamten (cardiac myosin inhibitor)

•
Expect topline results from SEQUOIA-HCM in late December.

•
Continue enrollment of MAPLE-HCM.

•
Continue enrollment of ACACIA-HCM.

•
Continue advancing go-to-market strategy for aficamten.

omecamtiv mecarbil (cardiac myosin activator)

•
Continue to pursue potential approval for omecamtiv mecarbil in Europe.

CK-3828136 (CK-136, cardiac troponin activator)

•
Analyze SAD data from the Phase 1 study of CK-136 to inform potentially proceeding with the MAD cohorts in the Phase 1 study.

CK-4021586 (CK-586, cardiac myosin inhibitor)

•
Proceed to the MAD cohorts in the Phase 1 study of CK-586.

Financials

Revenues for the three and nine months ended September 30, 2023 were $0.4 million and $5.9 million (inclusive of $2.5 million milestone, in the nine months ended, from Ji Xing Pharmaceuticals upon the start of ACACIA-HCM), respectively, compared to $2.5 million and $92.6 million (inclusive of $87 million from the sale of our royalty on mavacamten) for the corresponding periods in 2022.

Research and development expenses for the three and nine months ended September 30, 2023 increased to $82.5 million and $245.2 million, respectively, compared to $62.7 million and $165.8 million for the same periods in 2022, respectively, due primarily to increased spending for our cardiac myosin inhibitor programs.

General and administrative expenses for the three months ended September 30, 2023 decreased to $40.1 million from $48.2 million from the three months ended September 20, 2022, primarily due to lower outside services spend. General and administrative expenses for the nine months ended September 30, 2023 increased to $129.5 million from $124.0 million from the nine months ended September 20, 2022,

primarily due to higher personnel related cost including stock-based compensation offset by lower outside service spend.

During the quarter we also received a $50 million cash milestone payment from Royalty Pharma plc upon the start of ACACIA-HCM, treated as a liability on our balance sheet in accordance with GAAP.

Conference Call and Webcast Information

Members of Cytokinetics’ senior management team will review the company’s third quarter 2023 results on a conference call today at 4:30 PM Eastern Time. The conference call will be simultaneously webcast and can be accessed from the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by registering in advance at the following link: Cytokinetics Q3 2023 Earnings Conference Call. Upon registration, participants will receive a dial-in number and a unique passcode to access the call. An archived replay of the webcast will be available via Cytokinetics’ website for twelve months.