Abemaciclib

INDIANAPOLIS, Nov. 1, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that data from the Phase 3 trial (EMBER-3) for imlunestrant, an oral selective estrogen receptor degrader (SERD), will be reported for the first time in a late-breaking oral presentation at the San Antonio Breast Cancer Symposium (SABCS) taking place December 10-13 in San Antonio, TX. EMBER-3 is a study in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. The trial is evaluating imlunestrant alone or in combination with Verzenio (abemaciclib; CDK4/6 inhibitor), in patients who were pretreated with endocrine therapy, with or without a CDK4/6 inhibitor. Lilly will also share results of a real-world analysis of risk of recurrence by nodal status and high-risk features in patients with hormone receptor positive (HR+), HER2- early breast cancer. Additional presentations from investigational mutant selective PI3Ka inhibitor assets include preclinical characterization data for LY4045004, which is expected to enter the clinic in the first half of 2025, and Phase 1a/b clinical data for a predecessor molecule, LOXO-783, which informed the development of LY4045004. A full list of abstract titles and viewing details are listed below: Imlunestrant (investigational oral SERD) Presentation Title: Imlunestrant, an Oral Selective Estrogen Receptor Degrader (SERD), as Monotherapy and Combined with Abemaciclib, for Patients with ER+, HER2- Advanced Breast Cancer (ABC), Pretreated with Endocrine Therapy (ET): Results of the Phase 3 EMBER-3 trial. Presentation Number: GS1-01 Presentation Date & Time: Wednesday, Dec.11, 2024, 9:15-9:30 a.m. CST Location: Hall 1 Presenter: Komal Jhaveri Presentation Title: Patient and health care provider perspectives on oral versus intramuscular endocrine therapy for locally advanced or metastatic breast cancer Presentation Number: P4-03-11 Presentation Date & Time: Thursday, Dec.12, 2024, 5:30-7 p.m. CST Location: Halls 2-3 Presenter: Rebecca Speck Presentation Title: Evaluation of pharmacokinetics and safety of imlunestrant in participants with hepatic impairment Presentation Number: P4-10-07 Presentation Date & Time: Thursday, Dec.12, 2024, 5:30-7 p.m. CST Location: Halls 2-3 Presenter: Xuejing Aimee Wong Real World Evidence Presentation Title: Risk of Recurrence by Nodal Status and High-Risk Features in Patients with HR+, HER2-, Early Breast Cancer: An Analysis of Real-world Data Presentation Number: P1-11-02 Presentation Date & Time: Wednesday, Dec.11, 2024, 12-2 p.m. CST Location: Halls 2-3 Presenter: Sara Tolaney Verzenio® (abemaciclib) Presentation Title: Genomic profiling of ctDNA and association with efficacy in patients from the postMONARCH trial of abemaciclib + fulvestrant vs placebo + fulvestrant for HR+, HER2-, advanced breast cancer following progression on a prior CDK4/6i plus endocrine therapy Presentation Number: P1-01-26 Presentation Date &Time: Wednesday, Dec.11, 2024, 12-2 p.m. CST Location: Halls 2-3 Presenter: Seth Wander Presentation Title: Clinical Characteristics and Treatment Persistence in US Patients with HR+/HER2-, Node Positive Early Breast Cancer Treated with Abemaciclib: Real-World Study from First Year After Approval Presentation Number: P1-11-29 Presentation Date & Time: Wednesday, Dec.11, 2024, 12-2 p.m. CST Location: Halls 2-3 Presenter: Hatem Soliman Presentation Title: Unveiling the Antitumor Mechanism of abemaciclib in Human Breast Cancer Through Circulating Tumor Chromatin Analysis Presentation Number: P5-02-23 Presentation Date & Time: Friday, Dec.13, 2024, 12-2 p.m. CST Location: Halls 2-3 Presenter: Mamoru Takada PI3Ka Inhibitor (LOXO-783) Presentation Title: A first-in-human phase 1a/b trial of LOXO-783, a potent, highly mutant-selective, brain-penetrant, allosteric PI3Kα H1047R inhibitor advanced breast cancer and other solid tumors: Results from the PIKASSO-01 study Presentation Number: PS7-03 Presentation Date & Time: Wednesday, Dec.11, 2024, 7-8:30 a.m. CST Location: TBD Presenter: Komal Jhaveri Next-Gen PI3Ka Inhibitor (LY4045004) Presentation Title: Preclinical characterization of LY4045004, a next-generation, mutant-selective PI3Kα inhibitor Presentation Number: P4-12-24 Presentation Date & Time: Thursday, Dec.12, 2024, 5:30-7 p.m. CST Location: Halls 2-3 Presenter: Raymond Gilmour (Lilly) About Verzenio® (abemaciclib) Verzenio® (abemaciclib) is approved to treat people with certain HR+, HER2- breast cancers in the adjuvant and advanced or metastatic setting. Verzenio is the first CDK4/6 inhibitor approved to treat node-positive, high risk early breast cancer (EBC) patients. The National Comprehensive Cancer Network® (NCCN®) recommends consideration of two years of abemaciclib (Verzenio) added to endocrine therapy as a Category 1 treatment option in the adjuvant setting.1 NCCN® also includes Verzenio plus endocrine therapy as a preferred treatment option for metastatic breast cancer.1 The collective results of Lilly's clinical development program continue to differentiate Verzenio as a CDK4/6 inhibitor. In high risk EBC, Verzenio has shown a persistent and deepening benefit beyond the two-year treatment period in the monarchE trial, an adjuvant study designed specifically to investigate a CDK4/6 inhibitor in a high-risk population.2 In metastatic breast cancer, Verzenio has demonstrated statistically significant OS in the Phase 3 MONARCH 2 study.3 Verzenio has shown a consistent and generally manageable safety profile across clinical trials. Verzenio is an oral tablet taken twice daily and available in strengths of 50 mg, 100 mg, 150 mg, and 200 mg. Discovered and developed by Lilly researchers, Verzenio was first approved in 2017 and is currently authorized for use in more than 90 counties around the world. For full details on indicated uses of Verzenio in HR+, HER2- breast cancer, please see full Prescribing Information, available at . INDICATIONS FOR VERZENIO® VERZENIO® is a kinase inhibitor indicated: in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. IMPORTANT SAFETY INFORMATION FOR VERZENIO (abemaciclib) Severe diarrhea associated with dehydration and infection occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, diarrhea occurred in 81 to 90% of patients who received Verzenio. Grade 3 diarrhea occurred in 8 to 20% of patients receiving Verzenio. Most patients experienced diarrhea during the first month of Verzenio treatment. The median time to onset of diarrhea ranged from 6 to 8 days; and the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to 11 days and 5 to 8 days, respectively. Across trials, 19 to 26% of patients with diarrhea required a Verzenio dose interruption and 13 to 23% required a dose reduction. Instruct patients to start antidiarrheal therapy, such as loperamide, at the first sign of loose stools, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose. Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, neutropenia occurred in 37 to 46% of patients receiving Verzenio. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 19 to 32% of patients receiving Verzenio. Across trials, the median time to first episode of Grade ≥3 neutropenia ranged from 29 to 33 days, and the median duration of Grade ≥3 neutropenia ranged from 11 to 16 days. Febrile neutropenia has been reported in <1% of patients exposed to Verzenio across trials. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider. Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia. Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis can occur in patients treated with Verzenio and other CDK4/6 inhibitors. In Verzenio-treated patients in EBC (monarchE), 3% of patients experienced ILD or pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality (0.1%). In Verzenio-treated patients in MBC (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD or pneumonitis have been observed in the postmarketing setting, with fatalities reported. Monitor patients for pulmonary symptoms indicative of ILD or pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations. Dose interruption or dose reduction is recommended in patients who develop persistent or recurrent Grade 2 ILD or pneumonitis. Permanently discontinue Verzenio in all patients with Grade 3 or 4 ILD or pneumonitis. Grade ≥ 3 increases in alanine aminotransferase (ALT) (2 to 6%) and aspartate aminotransferase (AST) (2 to 3%) were reported in patients receiving Verzenio. Across three clinical trials in 3559 patients (monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade ≥3 ALT increases ranged from 57 to 87 days and the median time to resolution to Grade <3 was 13 to 14 days. The median time to onset of Grade ≥3 AST increases ranged from 71 to 185 days and the median time to resolution to Grade <3 ranged from 11 to 15 days. Monitor liver function tests (LFTs) prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or any Grade 3 or 4 hepatic transaminase elevation. Venous thromboembolic events (VTE) were reported in 2 to 5% of patients across three clinical trials in 3559 patients treated with Verzenio (monarchE, MONARCH 2, MONARCH 3). VTE included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. In clinical trials, deaths due to VTE have been reported in patients treated with Verzenio. Verzenio has not been studied in patients with early breast cancer who had a history of VTE. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate. Dose interruption is recommended for EBC patients with any grade VTE and for MBC patients with a Grade 3 or 4 VTE. Verzenio can cause fetal harm when administered to a pregnant woman, based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for 3 weeks after the last dose. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants. The most common adverse reactions (all grades, ≥ 10%) observed in monarchE for Verzenio plus tamoxifen or an aromatase inhibitor vs tamoxifen or an aromatase inhibitor, with a difference between arms of ≥ 2%, were diarrhea (84% vs 9%), infections (51% vs 39%), neutropenia (46% vs 6%), fatigue (41% vs 18%), leukopenia (38% vs 7%), nausea (30% vs 9%), anemia (24% vs 4%), headache (20% vs 15%), vomiting (18% vs 4.6%), stomatitis (14% vs 5%), lymphopenia (14% vs 3%), thrombocytopenia (13% vs 2%), decreased appetite (12% vs 2.4%), ALT increased (12% vs 6%), AST increased (12% vs 5%), dizziness (11% vs 7%), rash (11% vs 4.5%), and alopecia (11% vs 2.7 %). The most frequently reported ≥ 5% Grade 3 or 4 adverse reaction that occurred in the Verzenio arm vs the tamoxifen or an aromatase inhibitor arm of monarchE were neutropenia (19.6% vs 1%), leukopenia (11% vs <1%), diarrhea (8% vs 0.2%), and lymphopenia (5% vs <1%). Lab abnormalities (all grades; Grade 3 or 4) for monarchE in ≥ 10% for Verzenio plus tamoxifen or an aromatase inhibitor with a difference between arms of ≥ 2% were increased serum creatinine (99% vs 91%; .5% vs <.1%), decreased white blood cells (89% vs 28%; 19.1% vs 1.1%), decreased neutrophil count (84% vs 23%; 18.7% vs 1.9%), anemia (68% vs 17%; 1% vs .1%), decreased lymphocyte count (59% vs 24%; 13.2 % vs 2.5%), decreased platelet count (37% vs 10%; .9% vs .2%), increased ALT (37% vs 24%; 2.6% vs 1.2%), increased AST (31% vs 18%; 1.6% vs .9%), and hypokalemia (11% vs 3.8%; 1.3% vs 0.2%). The most common adverse reactions (all grades, ≥ 10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole vs anastrozole or letrozole, with a difference between arms of ≥ 2%, were diarrhea (81% vs 30%), fatigue (40% vs 32%), neutropenia (41% vs 2%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3.1%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%). The most frequently reported ≥ 5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 1%), diarrhea (9% vs 1.2%), leukopenia (7% vs <1%)), increased ALT (6% vs 2%), and anemia (6% vs 1%). Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥ 10% for Verzenio plus anastrozole or letrozole with a difference between arms of ≥ 2% were increased serum creatinine (98% vs 84%; 2.2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs 0.6%), anemia (82% vs 28%; 1.6% vs 0%), decreased neutrophil count (80% vs 21%; 21.9% vs 2.6%), decreased lymphocyte count (53% vs 26%; 7.6% vs 1.9%), decreased platelet count (36% vs 12%; 1.9% vs 0.6%), increased ALT (48% vs 25%; 6.6% vs 1.9%), and increased AST (37% vs 23%; 3.8% vs 0.6%). The most common adverse reactions (all grades, ≥ 10%) observed in MONARCH 2 for Verzenio plus fulvestrant vs fulvestrant, with a difference between arms of ≥ 2%, were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 2.7%), thrombocytopenia (16% vs 3%), alopecia (16% vs 1.8%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs <1%), rash (11% vs 4.5%), pyrexia (11% vs 6%), and weight decreased (10% vs 2.2%). The most frequently reported ≥ 5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (25% vs 1%), diarrhea (13% vs 0.4%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (5.7% vs 3.5%). Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥ 10% for Verzenio plus fulvestrant with a difference between arms of ≥ 2% were increased serum creatinine (98% vs 74%; 1.2% vs 0%), decreased white blood cells (90% vs 33%; 23.7% vs .9%), decreased neutrophil count (87% vs 30%; 32.5% vs 4.2%), anemia (84% vs 34%; 2.6% vs .5%), decreased lymphocyte count (63% vs 32%; 12.2% vs 1.8%), decreased platelet count (53% vs 15%; 2.1% vs 0%), increased ALT (41% vs 32%; 4.6% vs 1.4%), and increased AST (37% vs 25%; 3.9% vs 4.2%). The most common adverse reactions (all grades, ≥ 10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), constipation (17%), leukopenia (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%). The most frequently reported ≥ 5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were diarrhea (20%), neutropenia (24%), fatigue (13%), and leukopenia (5%). Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (99%; .8%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 26.6%), anemia (69%; 0%), decreased lymphocyte count (42%; 13.8%), decreased platelet count (41%; 2.3%), increased ALT (31%; 3.1%), and increased AST (30%; 3.8%). Strong and moderate CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other than ketoconazole. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Verzenio dose in 50 mg decrements. Patients should avoid grapefruit products. Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents. Coadministration of strong or moderate CYP3A inducers decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity. With severe hepatic impairment (Child-Pugh C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr <30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min). Please see full Prescribing Information and Patient Information for Verzenio. AL HCP ISI 12OCT2021 About Imlunestrant Imlunestrant is an oral selective estrogen receptor (ER) degrader, that delivers continuous ER inhibition, including in ESR1-mutant cancers. The estrogen receptor (ER) is the key therapeutic target for patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Novel degraders of ER may overcome endocrine therapy resistance while providing consistent oral pharmacology and convenience of administration. Imlunestrant is currently being studied as a treatment for advanced breast cancer and as an adjuvant treatment in early breast cancer, including: NCT04975308, NCT05514054 , NCT04188548, NCT05307705. Verzenio® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. © Lilly USA, LLC 2024. ALL RIGHTS RESERVED. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram, and LinkedIn. P-LLY Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Verzenio® (abemaciclib), imlunestrant, LOXO-783 or LY4045004 as potential treatments for people with certain types of early breast cancer and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, or that Verzenio, imlunestrant, or LY4045004 will receive initial regulatory approvals or approvals for additional indications, as applicable, or that they will be commercially successful. For further discussion of risks and uncertainties relevant to Lilly's business that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. SOURCE Eli Lilly and Company WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– On track to report topline data from Phase 3 VERITAC-2 trial in 4Q24 or 1Q25 – – Initial clinical data from Phase 1/2 TACTIVE-U sub-study of abemaciclib in combination with vepdegestrant to be presented at San Antonio Breast Cancer Symposium in December 2024 – – Recently presented new preclinical data for the PROTAC LRRK2 degrader ARV-102 demonstrating that LRRK2 degradation affects biomarkers in the CSF – - $1.1 billion in cash, cash equivalents and marketable securities as of Sept. 30, 2024 - – Company to host conference call today at 8:00 a.m. ET – NEW HAVEN, Conn., Oct. 30, 2024 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, today reported financial results for the third quarter ended September 30, 2024, and provided a corporate update. “We maintained strong momentum across our portfolio in the third quarter and remain on track to report topline data from VERITAC-2, our Phase 3 clinical trial in metastatic breast cancer, in the fourth quarter of 2024 or the first quarter of 2025,” said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. “In partnership with our colleagues at Pfizer, we are excited by the possibility of changing the treatment paradigm for ER+/HER2- breast cancer and look forward to sharing results from VERITAC-2 in the coming months.” “Our path to reaching our goal of becoming a multi-product, commercial-stage organization with a robust pipeline across several indications is clearly defined, and our novel PROTAC platform technology has the potential to enable opportunities across multiple therapeutic areas,” continued Dr. Houston. “We look forward to completing the multiple ascending dose portion of our Phase 1 clinical trial with ARV-102, our first PROTAC degrader with the potential to treat neurodegenerative diseases, and sharing data in 2025. We are also encouraged by the preclinical profile of ARV-393, our BCL6 PROTAC degrader currently being evaluated in a first-in-human Phase 1 clinical trial in patients with B-cell lymphomas. We look forward to sharing more about these programs in the coming months.” 3Q 2024 Business Highlights and Recent Developments Vepdegestrant Continued enrollment globally in multiple clinical studies of vepdegestrant in ER+/HER2- metastatic breast cancer. VERITAC-2: Phase 3 monotherapy clinical trial in patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT05654623)TACTIVE-U: Phase 1b/2 combination umbrella trial evaluating combinations of vepdegestrant with abemaciclib, ribociclib, or samuraciclib (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).TACTIVE-K: Phase 1/2 clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor atirmociclib (ClinicalTrials.gov Identifier: NCT06206837) ARV-102: Oral PROTAC LRRK2 degrader In October, presented preclinical data at the 2024 Michael J. Fox Foundation Parkinson’s Disease Conference further supporting the potential of PROTAC-induced leucine-rich repeat kinase 2 (LRRK2) degradation as a potential treatment for patients with neurodegenerative diseases. New findings presented included data demonstrating: Orally delivered ARV-102 crosses the blood-brain barriers and degrades LRRK2 in the cerebrospinal fluid (CSF) of non-human primates (NHPs).Degradation of LRRK2 by ARV-102 induces changes in pathway (lysosomal and inflammation) biomarkers in the CSF of NHPs, which has not previously been demonstrated by kinase inhibitors of LRRK2.In murine tauopathy models, oral PROTAC LRRK2 degrader treatment led to ~50% pathologic tau reduction. Initiated the multiple ascending dose portion of the ongoing Phase 1 clinical trial in healthy volunteers. ARV-393: Oral PROTAC BCL6 degrader Continued recruiting patients in the first-in-human Phase 1 clinical trial in patients with B-cell lymphomas. Anticipated Upcoming Milestones and Expectations Vepdegestrant As part of Arvinas global collaboration with Pfizer, the companies plan to: Complete enrollment (4Q24) and announce topline data (4Q24/1Q25) for the VERITAC-2 Phase 3 monotherapy clinical trial in patients with metastatic breast cancer.Present initial safety and pharmacokinetic data from the TACTIVE-U sub-study (NCT05548127) of abemaciclib in combination with vepdegestrant at the San Antonio Breast Cancer Symposium (SABCS) in December 2024.Present data from the Phase 1 healthy volunteer pharmacokinetic trial of vepdegestrant in combination with midazolam to assess potential for drug-drug interaction at SABCS in December 2024 (NCT06256510).Continue enrollment of the ongoing Phase 1b/2 combination umbrella trial evaluating combinations of vepdegestrant with abemaciclib, ribociclib, or samuraciclib (TACTIVE-U; ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).Evaluate data from the study lead-in of the VERITAC-3 Phase 3 trial (NCT05909397) in patients with ER+/HER2- locally advanced or metastatic breast cancer (2H24).Continue enrollment and evaluate preliminary data from the ongoing clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor atirmociclib (TACTIVE-K).Start Phase 3 combination trials in the first- and second-line settings (anticipated in 2025; pending emerging data and regulatory feedback). First-line setting with vepdegestrant plus atirmociclib or palbociclib.Second-line setting with vepdegestrant plus palbociclib and/or another CDK4/6 inhibitor. ARV-102: Oral PROTAC LRRK2 degrader Complete enrollment in the ongoing multiple ascending dose portion of a Phase 1 trial evaluating ARV-102 in healthy volunteersPresent data from the Phase 1 trial in 2025. ARV-393: Oral PROTAC BCL6 degrader Continue recruiting patients in the first-in-human Phase 1 clinical trial evaluating ARV-393 in patients with B-cell lymphomas. Novel PROTAC KRAS G12D degrader File an Investigational New Drug (IND) application in 2025. Financial GuidanceBased on its current operating plan, Arvinas believes its cash, cash equivalents, and marketable securities as of September 30, 2024, is sufficient to fund planned operating expenses and capital expenditure requirements into 2027. Third Quarter Financial Results Cash, Cash Equivalents, and Marketable Securities Position: As of September 30, 2024, cash, cash equivalents and marketable securities were $1,121.6 million as compared with cash, cash equivalents, restricted cash and marketable securities of $1,266.5 million as of December 31, 2023. The decrease in cash, cash equivalents and marketable securities of $144.9 million for the nine months ended September 30, 2024 was primarily related to cash used in operations of $158.1 million (net of $150.0 million received from the Novartis agreements), inclusive of a one-time cash termination fee in the amount of $41.5 million related to the termination of our laboratory and office space lease with 101 College Street LLC in August 2024 and the purchase of lab equipment and leasehold improvements of $1.5 million, partially offset by proceeds from the exercise of stock options of $7.7 million and unrealized gains on marketable securities of $7.2 million. Research and Development Expenses: Research and development expenses were $86.9 million for the quarter ended September 30, 2024, as compared with $85.9 million for the quarter ended September 30, 2023. The increase in research and development expenses of $1.0 million for the quarter was primarily due to an increase in compensation and related personnel expenses of $2.8 million, which are not allocated by program, partially offset by a decrease in external expenses of $2.2 million. External expenses include program-specific expenses, which decreased by $1.1 million, primarily driven by decreases in our ARV-766 and ARV-110 programs of $3.8 million and $1.6 million, respectively, partially offset by increases in our ARV-102 and ARV-393 programs of $2.5 million and $1.4 million, respectively, and our non-program specific expenses, which decreased by $1.1 million. General and Administrative Expenses: General and administrative expenses were $75.8 million for the quarter ended September 30, 2024, as compared with $22.6 million for the quarter ended September 30, 2023. The increase in general and administrative expenses of $53.2 million for the quarter was primarily due to a loss on the termination of our laboratory and office space lease with 101 College Street LLC of $43.4 million as well as increases in personnel and infrastructure related costs of $5.0 million, professional fees of $3.4 million and in developing our commercial operations of $1.2 million. Revenue: Revenue was $102.4 million for the quarter ended September 30, 2024 as compared with $34.6 million for the quarter ended September 30, 2023. Revenue for the quarter is related to the license agreement with Novartis, the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer, the collaboration and license agreement with Bayer and the collaboration and license agreement with Pfizer. The increase in revenue of $67.8 million was primarily due to revenue from the Novartis license agreement of $76.7 million, offset by a decrease in revenue from the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer of $7.6 million related to timing differences in clinical trials and program expenses and a decrease in revenue from Bayer of $1.1 million related to the termination of the Bayer Collaboration Agreement in August 2024. Investor Call & Webcast Details Arvinas will host a conference call and webcast today, October 30, 2024, at 8:00 a.m. ET to review its third quarter 2024 financial results and discuss recent corporate updates. Participants are invited to listen by going to the Events and Presentation section under the Investors page on the Arvinas website at www.arvinas.com. A replay of the webcast will be available on the Arvinas website following the completion of the event and will be archived for up to 30 days. About VepdegestrantVepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits. The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy. About ArvinasArvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC® (PROteolysis Targeting Chimera) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; and ARV-102, targeting LRRK2 for neurodegenerative disorders. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the expected timing in connection with the completion of enrollment and reporting of topline data from the VERITAC-2 clinical trial; the potential to change the treatment paradigm for ER+/HER2- breast cancer; the goal of becoming a multi-product, commercial-stage organization with a robust pipeline across several indications; novel PROTAC platform technology having the potential to enable opportunities across multiple therapeutic areas; plans to present initial safety and pharmacokinetic data from the TACTIVE-U sub-study of abemaciclib in combination with vepdegestrant at SABCS; plans to present data from the Phase 1 healthy volunteer pharmacokinetic trial of vepdegestrant in combination with midazolam at SABCS; plans to continue enrollment in the TACTIVE-U study and evaluate data from the study lead-in of the VERITAC-3 Phase 3 clinical trial; plans to continue enrollment and evaluate preliminary data from the TACTIVE-K clinical trial; the expected timing of initiation of Phase 3 vepdegestrant combination trials in the first- and second-line settings, pending emerging data and regulatory feedback; expected timing of filing an investigational new drug application for a KRAS G12D degrader; plans to compete enrollment in the multiple ascending dose portion of the ARV-102 Phase 1 clinical trial, the timing of the presentation of data from such clinical trial, and the timing of sharing additional information about the program; plans to continue recruiting patients in the Phase 1 ARV-393 clinical trial and timing of sharing additional information about the program; and statements regarding Arvinas’ cash, cash equivalents and marketable securities. All statements, other than statements of historical fact, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “goal,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: Arvinas’ and Pfizer’s performance of the respective obligations with respect to Arvinas’ collaboration with Pfizer; whether Arvinas and Pfizer will be able to successfully conduct and complete clinical development for vepdegestrant; whether Arvinas will be able to successfully conduct and complete development for its other product candidates, including whether Arvinas initiates and completes clinical trials for its product candidates and receives results from its clinical trials and preclinical studies on its expected timelines or at all; whether Arvinas and Pfizer, as appropriate, will be able to obtain marketing approval for and commercialize vepdegestrant and other product candidates on current timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; whether Arvinas’ cash and cash equivalent resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements, and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent other reports on file with the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release. ContactsInvestors:Jeff Boyle+1 (347) 247-5089Jeff.Boyle@arvinas.com Media:Kirsten Owens+1 (203) 584-0307Kirsten.Owens@arvinas.com Arvinas, Inc.Condensed Consolidated Balance Sheets (Unaudited) (dollars and shares in millions, except per share amounts)September 30, 2024December 31,2023Assets Current assets: Cash and cash equivalents$85.2 $311.7 Restricted cash — 5.5 Marketable securities 1,036.4 949.3 Accounts receivable 7.3 — Other receivables 7.5 7.2 Prepaid expenses and other current assets 13.1 6.5 Total current assets 1,149.5 1,280.2 Property, equipment and leasehold improvements, net 6.8 11.5 Operating lease right of use assets 1.0 2.5 Collaboration contract asset and other assets 9.8 10.4 Total assets$1,167.1 $1,304.6 Liabilities and stockholders' equity Current liabilities: Accounts payable and accrued liabilities$75.9 $92.2 Deferred revenue 199.2 163.0 Current portion of operating lease liabilities 0.8 1.9 Total current liabilities 275.9 257.1 Deferred revenue 304.5 386.2 Long-term debt 0.6 0.8 Operating lease liabilities 0.1 0.5 Total liabilities 581.1 644.6 Stockholders’ equity: Preferred stock, $0.001 par value, zero shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively — — Common stock, $0.001 par value; 68.7 and 68.0 shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively 0.1 0.1 Accumulated deficit (1,486.5) (1,332.7)Additional paid-in capital 2,068.3 1,995.7 Accumulated other comprehensive income (loss) 4.1 (3.1)Total stockholders’ equity 586.0 660.0 Total liabilities and stockholders’ equity$1,167.1 $1,304.6 Arvinas, Inc.Condensed Consolidated Statements of Operations (Unaudited) Three Months Ended September 30,Nine Months Ended September 30,(dollars and shares in millions, except per share amounts) 2024 2023 2024 2023 Revenue$102.4 $34.6 $204.2 $121.6 Operating expenses: Research and development 86.9 85.9 264.9 284.5 General and administrative 75.8 22.6 131.3 73.3 Total operating expenses 162.7 108.5 396.2 357.8 Loss from operations (60.3) (73.9) (192.0) (236.2)Interest and other income, net 11.7 10.0 39.2 25.5 Net loss before income taxes and loss from equity method investment (48.6) (63.9) (152.8) (210.7)Income tax (expense) benefit (0.6) — (1.0) 0.7 Loss from equity method investment — (0.1) — (2.5)Net loss$(49.2)$(64.0)$(153.8)$(212.5)Net loss per common share, basic and diluted$(0.68)$(1.18)$(2.14)$(3.97)Weighted average common shares outstanding, basic and diluted 72.1 54.1 71.9 53.6