Summary of Arvinas FY Conference Call (November 11, 2025) Company Overview - **Company**: Arvinas (NasdaqGS:ARVN) - **Industry**: Biotechnology, specifically focused on protein degrader technology Key Points and Arguments Protein Degrader Technology - Arvinas is recognized as a pioneer in protein degrader technology, with a focus on developing degraders for specific targets such as androgen and estrogen receptors [4][3] - The company is on the verge of potentially having the first PROTAC (Proteolysis Targeting Chimera) approved, with a PDUFA date set for June 6 for vepdegestrant, targeting estrogen receptor-positive second-line breast cancer [4][5] Pipeline Development - Arvinas has three drugs currently in clinical trials and plans to introduce two more drugs into the clinic next year [5] - The company has partnered with Novartis for an androgen receptor degrader, which is currently in three Phase 2 studies [4] Vepdegestrant Commercialization - The process for finding a third party to commercialize vepdegestrant is ongoing, with multiple interested parties [7] - The company views vepdegestrant as a financial asset and is open to the best bid, regardless of whether the buyer intends to further develop the drug [7][8] LRRK2 Target Validation - LRRK2 is considered a well-validated target for neurodegenerative diseases, particularly Parkinson's disease, with genetic variants linked to the disease [9][10] - The company aims to achieve a 50% reduction in LRRK2 levels in the cerebrospinal fluid (CSF) to restore physiological levels, with current results showing a 75% knockdown in healthy volunteers [17][14] Clinical Trials and Future Studies - Ongoing studies in Parkinson's disease aim to confirm the 75% reduction in LRRK2 levels in patients, with results expected in the first quarter of next year [19][20] - A Phase 1b study in progressive supranuclear palsy (PSP) is planned, with the potential to start a registration-quality Phase 2 study based on the results of the Phase 1b [24][26] ARV-102 and Differentiation - ARV-102 is positioned as a differentiated approach compared to classical inhibitors, demonstrating higher target engagement and pathway engagement in preclinical models [12][13] - The drug has shown significant brain penetration and effective degradation of LRRK2 in preclinical studies [14][15] ARV-393 and Hematological Cancers - ARV-393 targets BCL6, a promising but previously undruggable target in hematological cancers, with plans to combine it with bispecific antibodies for enhanced efficacy [28][29] - The company is observing responses in B cell malignancies and is also enrolling patients with T cell malignancies [28] KRAS G12D Degrader - The KRAS G12D degrader is in Phase 1 trials, with Arvinas claiming it is 25-40 times more potent than competitors' inhibitors [36][37] - The degrader is expected to overcome resistance mechanisms that inhibit traditional therapies [37] New Programs - Arvinas announced two new programs targeting SBMA (spinal and bulbar muscular atrophy) and HPK1, with plans to start clinical studies next year [42][43] - The SBMA program focuses on degrading the androgen receptor, while the HPK1 program aims to enhance immune response against solid tumors [43][44] Additional Insights - The company is closely monitoring competitor studies, particularly Biogen's LUMA study, to inform its development strategies [27] - Arvinas emphasizes a biotech-friendly development path, aiming for rapid advancement in clinical trials and potential accelerated approvals [24][26] This summary encapsulates the key insights and developments discussed during the Arvinas FY Conference Call, highlighting the company's innovative approaches and strategic plans in the biotechnology sector.

Clinical Development - The company is progressing multiple product candidates through clinical development, including ARV-102 for neurodegenerative disorders and ARV-393 for non-Hodgkin lymphoma [120]. - The ongoing Phase 1 clinical trial of ARV-102 in patients with Parkinson's disease has completed the single ascending dose cohort and is progressing to multiple ascending doses [124]. - The company plans to present initial data from the multiple dose cohort of the Phase 1 clinical trial of ARV-102 in patients with Parkinson's disease in 2026 [133]. - The Phase 1 clinical trial of ARV-102 included a randomized, double-blind, placebo-controlled design to assess safety and pharmacodynamics [125]. - The company has received Clinical Trial Application approval in the Netherlands for the Phase 1 clinical trial of ARV-102 in patients with Parkinson's disease [124]. - The Phase 1 clinical trial of ARV-102 was well tolerated, with no serious adverse events reported among 15 patients treated [136]. - The Phase 1 clinical trial of ARV-393 in patients with relapsed/refractory NHL is ongoing, with multiple responses observed in early cohorts [140]. - The company intends to share updated clinical data from the ongoing Phase 1 trial of ARV-393 at a medical congress in 2026 [140]. - The company plans to initiate a Phase 1 clinical trial of ARV-393 in combination with glofitamab in patients with DLBCL in 2026 [139]. - The company plans to initiate a first-in-human Phase 1 clinical trial for ARV-027 in healthy volunteers in 2026, pending regulatory feedback [166]. Product Efficacy - ARV-102 demonstrated over 90% reduction of LRRK2 in peripheral blood mononuclear cells at single doses of 60 mg or greater [131]. - In the Phase 1 clinical trial of ARV-102, treatment resulted in median LRRK2 protein reductions of 86% with a 50 mg dose and 97% with a 200 mg dose in patients with Parkinson's disease [136]. - ARV-393 showed strong synergistic antitumor activity in preclinical models of aggressive diffuse large B-cell lymphoma when combined with standard of care chemotherapy [135]. - ARV-393 in combination with R-CHOP chemotherapy achieved complete tumor regressions in all treated mice, indicating significant tumor growth inhibition (TGI) compared to other treatments [137]. - In preclinical studies, ARV-393 demonstrated robust tumor growth inhibition (≥95%) in two patient-derived xenograft (PDX) models of transformed follicular lymphoma (tFL) and showed enhanced antitumor activity in combination with small molecule inhibitors [141]. - ARV-806, a novel PROTAC KRAS G12D degrader, exhibited in vitro potency approximately 25 times greater than existing KRAS inhibitors and 40 times greater than the leading clinical-stage degrader [143]. - ARV-806 achieved over 90% degradation of KRAS G12D for seven days in a colorectal tumor xenograft model, indicating sustained pharmacodynamic activity [146]. - Vepdegestrant demonstrated near-complete ER degradation in tumor cells and superior anti-tumor activity compared to fulvestrant in preclinical studies [149]. Financial Performance - The company has raised approximately $1.7 billion in gross proceeds since inception through September 30, 2025, and received $913.1 million from collaboration partners and licensing arrangements [170]. - Revenue for Q3 2025 was $41.9 million, a decrease of $60.5 million from $102.4 million in Q3 2024, primarily due to reduced revenue from Novartis agreements [224]. - For the nine months ended September 30, 2025, revenue totaled $253.1 million, an increase of $48.9 million compared to $204.2 million in the same period of 2024, driven by a $157.9 million increase from the Vepdegestrant collaboration with Pfizer [225]. - The company recognized $20.0 million in revenue during the three months ended September 30, 2025, upon achieving a development milestone under the Novartis License Agreement [192]. - The company has not generated any revenue from product sales and does not expect to do so in the near future, relying instead on research collaborations and licensing arrangements [179]. Expenses and Cost Management - Research and development expenses for the three months ended September 30, 2025, totaled $64.7 million, a decrease of 25.5% compared to $86.9 million for the same period in 2024 [205]. - Total program-specific external expenses for the nine months ended September 30, 2025, were $89.2 million, down from $101.7 million in 2024, reflecting a decrease of 12.4% [205]. - The total unallocated internal expense for research and development was $24.4 million for the three months ended September 30, 2025, compared to $39.2 million in 2024, a decrease of 37.5% [205]. - General and administrative expenses for Q3 2025 totaled $21.0 million, a decrease of $54.8 million from $75.8 million in Q3 2024, mainly due to a loss on lease termination [230]. - The company expects to achieve annual operating cost savings of $100 million on a run-rate basis following workforce reductions [175]. - The company announced a workforce reduction of approximately 33% in April 2025 and an additional 15% in September 2025 to streamline operations [172][174]. Collaborations and Agreements - The collaboration agreement with Pfizer includes an upfront payment of $650 million and potential contingent payments of up to $1.4 billion based on regulatory and sales milestones [181]. - The Vepdegestrant (ARV-471) Collaboration Agreement allows for shared research and development expenses with Pfizer, which have been equal since July 22, 2021 [206]. - The Novartis Transaction resulted in a one-time upfront payment of $150.0 million and potential contingent payments of up to $1.01 billion based on specified milestones for luxdegalutamide (ARV-766) [192]. - The Bayer Collaboration Agreement was terminated effective August 12, 2024, after receiving a total of $29.5 million in upfront and additional payments [197][196]. - The company is eligible to receive up to $225.0 million in development milestone payments and up to $550.0 million in sales-based milestone payments under the Pfizer Research Collaboration Agreement [188]. Tax and Cash Management - As of December 31, 2024, the company had $111.0 million in federal net operating loss carryforwards, which can be carried forward indefinitely, subject to an 80% limit on taxable income [213]. - The company has provided a valuation allowance against deferred tax assets, indicating that it is more likely than not that the benefits will not be realized based on its earnings history [214]. - Cash, cash equivalents, and marketable securities amounted to $787.6 million as of September 30, 2025, compared to $1.0 billion as of December 31, 2024 [243]. - Net cash used in operating activities for the nine months ended September 30, 2025, increased by $68.2 million to $(243.4) million, primarily due to a $187.6 million decrease in deferred revenue [246]. - The company anticipates that its cash, cash equivalents, and marketable securities will fund its planned operating expenses into the second half of 2028 [252].

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Financial Data and Key Metrics Changes - As of the end of Q3 2025, the company had approximately $787.6 million in cash, cash equivalents, and marketable securities, down from $1.04 billion as of December 31, 2024 [31] - Revenue for Q3 2025 totaled $41.9 million, a decrease of $60.5 million compared to $102.4 million for Q3 2024, primarily due to the Novartis License agreement [31][32] - General and Administrative expenses were $21 million in Q3 2025, down from $75.8 million in the same period of 2024, mainly due to lease termination and reduced personnel costs [32] - Research and Development expenses were $64.7 million in Q3 2025, compared to $86.9 million in Q3 2024, driven by decreases in various programs [33] Business Line Data and Key Metrics Changes - The company reported significant progress in its clinical pipeline, including updates on ARV-102, ARV-393, and ARV-806, with multiple ongoing and planned clinical trials [12][14][27] - ARV-102 showed promising results in both healthy volunteers and Parkinson's disease patients, with significant reductions in LRRK2 protein levels [19][20][21] - ARV-393 demonstrated early responses in both B and T cell lymphomas, with ongoing dose escalation trials [25][26] Market Data and Key Metrics Changes - The company is focused on addressing significant unmet needs in oncology and neurology, with a deep pipeline of assets [13][14] - The FDA has issued a PDUFA action date of June 5, 2026, for the new drug application of vepdegestrant, with plans to have a commercialization partner in place before this date [15] Company Strategy and Development Direction - The company aims to deliver innovative and differentiated assets in areas of high unmet need, with a focus on progressing its early pipeline [37] - The strategic partnership with Pfizer for the commercialization of vepdegestrant is expected to enhance the company's market position [15] - The company is committed to maintaining a quarterly run rate spend below $75 million to manage expenses effectively [34] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential for ARV-102 and its ability to address neurodegenerative diseases, with plans for a phase 1b trial in PSP [12][37] - The company anticipates a data-rich period with multiple readouts from early-stage clinical programs, reinforcing its belief in the promise of its pipeline [13][14] - Management highlighted the importance of cost reduction programs and strategic flexibility to navigate the evolving market landscape [34] Other Important Information - The company has authorized the repurchase of up to $100 million of its outstanding common stock, reflecting confidence in its long-term strategy [34] - The company expects to maintain its cash runway into the second half of 2028, allowing for continued investment in high-value assets [36] Q&A Session Summary Question: Updates on the BCL6 degrader program - Management expressed excitement about the BCL6 program and its differentiation from competitors, highlighting ongoing studies and expected data at the upcoming ASH meeting [45][48] Question: Signals to look for in the Parkinson's disease MAD phase one - Management indicated that the ongoing phase one study aims to generate biomarker-related data, with expectations for clinical efficacy data to follow [54][56] Question: Plans for ARV806 in KRAS amplified populations - The company is studying ARV806 in resistance settings and has seen promising early data in models of KRAS amplification [61][63] Question: Dosing cohorts for ARV393 - Management confirmed that they are not yet in the predicted efficacious range for ARV393 but are seeing significant responses at lower dose levels [129][139] Question: Evaluating combination strategies for ARV806 - The company has preclinically evaluated combinations with anti-EGFR inhibitors and believes this selective approach will provide advantages [89][91]

Financial Performance - Revenue for Q3 2025 was $41.9 million, a decrease of $60.5 million compared to $102.4 million in Q3 2024, primarily due to reduced revenue from the Novartis License Agreement[18] - Revenue for Q3 2025 was $41.9 million, a decrease from $102.4 million in Q3 2024, representing a decline of 59%[39] - For the nine months ended September 30, 2025, revenue was $253.1 million, up from $204.2 million in the same period of 2024, an increase of 24%[39] - Net loss for Q3 2025 was $35.1 million, an improvement from a net loss of $49.2 million in Q3 2024, reflecting a 29% reduction in losses[39] - Loss per common share for Q3 2025 was $0.48, compared to $0.68 in Q3 2024, indicating a 29% improvement[39] - Interest and other income for Q3 2025 was $9.0 million, compared to $11.7 million in Q3 2024, a decrease of 23%[39] Expenses - GAAP Research and Development (R&D) expenses for Q3 2025 were $64.7 million, down from $86.9 million in Q3 2024, a decrease of $22.2 million[14] - GAAP General and Administrative (G&A) expenses for Q3 2025 were $21.0 million, significantly reduced from $75.8 million in Q3 2024, a decrease of $54.8 million[16] - Total operating expenses for Q3 2025 were $85.7 million, down from $162.7 million in Q3 2024, a reduction of 47%[39] - Research and development expenses for Q3 2025 were $64.7 million, compared to $86.9 million in Q3 2024, a decrease of 25%[39] - Non-GAAP research and development expenses for Q3 2025 were $56.9 million, down from $73.2 million in Q3 2024, a decrease of 22%[41] - Non-GAAP general and administrative expenses for Q3 2025 were $14.6 million, compared to $64.8 million in Q3 2024, a significant reduction of 77%[41] Cash and Assets - As of September 30, 2025, cash, cash equivalents, and marketable securities were $787.6 million, down from $1,039.4 million as of December 31, 2024, reflecting a decrease of $251.8 million[12] - As of September 30, 2025, Arvinas reported total current assets of $826.3 million, down from $1,067.3 million as of December 31, 2024[37] - Total liabilities decreased to $279.9 million from $529.7 million over the same period[37] - The accumulated deficit increased to $(1,545.0) million as of September 30, 2025, compared to $(1,531.6) million at the end of 2024[37] Clinical Trials and Drug Development - ARV-102 showed greater than 90% reductions of LRRK2 protein in peripheral blood mononuclear cells and over 50% reductions in cerebrospinal fluid with repeated daily doses[4] - ARV-806 demonstrated in vitro potency approximately 25 times greater than KRAS inhibitors and 40 times greater than the leading clinical-stage degrader[7] - The FDA accepted the New Drug Application for vepdegestrant, with a PDUFA action date set for June 5, 2026[7] - The company plans to initiate a Phase 1b clinical trial for ARV-102 in patients with progressive supranuclear palsy in the first half of 2026[12] - ARV-393 is currently in a Phase 1 clinical trial for relapsed/refractory non-Hodgkin lymphoma, targeting BCL6, a major driver of B-cell lymphomas[23] - ARV-806, designed to degrade KRAS G12D, is also in a Phase 1 clinical trial for advanced solid tumors, addressing high unmet needs in cancers like pancreatic and colorectal[24] - ARV-027, targeting polyQ-AR for spinal and bulbar muscular atrophy, plans to initiate a Phase 1 clinical trial in healthy volunteers in 2026[26] - ARV-6723, aimed at degrading HPK1 in immuno-oncology, is set to begin a Phase 1 clinical trial in 2026[27] - Vepdegestrant showed significant improvement in progression-free survival in the VERITAC-2 Phase 3 study for ER+/HER2- ESR1-mutated breast cancer, with an NDA filed with the FDA[28] - Arvinas and Pfizer announced a global collaboration for the co-development and commercialization of vepdegestrant, sharing development costs and profits[29] Research and Development Strategy - The company aims to drive innovation across its PROTAC degrader portfolio and deliver transformative therapies to patients[3] - Arvinas plans to present initial data from multiple clinical trials and share preclinical data at upcoming medical congresses, indicating ongoing research and development efforts[32]

Core Insights - Arvinas, Inc. reported significant progress in its clinical pipeline, including positive Phase 1 trial data for ARV-102 in Parkinson's disease and promising preclinical results for ARV-806 and ARV-027 [1][3][6][11] - The company announced a collaboration with Pfizer for the commercialization and further development of vepdegestrant, an investigational drug for breast cancer [1][10][30] - Financial results for Q3 2025 showed a decrease in revenue and operating expenses, with cash reserves sufficient to fund operations into the second half of 2028 [14][15][21] Clinical Developments - ARV-102 demonstrated well-tolerated results in healthy volunteers and Parkinson's patients, with significant reductions in LRRK2 protein levels [6][24] - ARV-806 showed robust anti-tumor activity in preclinical models of KRAS G12D-mutant cancers, with a Phase 1 trial initiated [11][26] - ARV-027 exhibited effective degradation of polyQ-AR in muscle, supporting its potential as a disease-modifying therapy for spinal bulbar muscular atrophy [1][9][27] Financial Performance - Revenue for Q3 2025 was $41.9 million, down from $102.4 million in Q3 2024, primarily due to decreased revenue from previous collaborations [21] - Research and development expenses decreased to $64.7 million from $86.9 million year-over-year, reflecting reduced external costs [16] - The company reported a net loss of $35.1 million for Q3 2025, compared to a loss of $49.2 million in the same quarter of the previous year [39] Strategic Collaborations - The agreement with Pfizer aims to enhance the commercialization potential of vepdegestrant, with plans to select a third-party partner for further development [10][30] - The collaboration underscores the strategic focus on bringing innovative therapies to market, particularly in oncology and neurodegenerative diseases [1][23] Future Outlook - Arvinas plans to initiate multiple clinical trials in 2026, including a Phase 1b trial for ARV-102 in progressive supranuclear palsy and a trial for ARV-027 [1][12][29] - The company is positioned for a data-rich period with several upcoming readouts from its clinical programs, aiming to drive innovation in its PROTAC degrader portfolio [3][10]

Core Viewpoint - Arvinas, Inc. is advancing its investigational drug ARV-393, a PROTAC designed to degrade the BCL6 protein, which is a significant driver of B-cell lymphomas, and will present preclinical data in December 2025 at the ASH Annual Meeting [1][3]. Group 1: About ARV-393 - ARV-393 targets the BCL6 protein, which plays a crucial role in B-cell lymphoma by repressing cell cycle checkpoints and apoptosis, making it a challenging target for traditional therapies [3]. - The drug is currently in a Phase 1 clinical trial for patients with non-Hodgkin lymphoma, indicating its potential therapeutic application in this area [3]. Group 2: About Arvinas - Arvinas is a clinical-stage biotechnology company focused on developing therapies that utilize its PROTAC platform to selectively degrade disease-causing proteins [4]. - The company is also developing other investigational drugs, including ARV-102 for neurodegenerative disorders, ARV-806 for mutated cancers, and vepdegestrant for ER+/HER2-breast cancer [4].

Core Insights - Arvinas, Inc. is set to review its third-quarter 2025 financial results and provide a corporate update on November 5, 2025 [1] - The company specializes in targeted protein degradation therapies through its PROTAC platform, aiming to treat various debilitating diseases [3] Company Overview - Arvinas is a clinical-stage biotechnology company focused on developing therapies for life-threatening diseases [3] - The company utilizes its PROTAC (PROteolysis TArgeting Chimera) platform to create drugs that selectively degrade disease-causing proteins [3] - Current investigational drugs include ARV-102 for neurodegenerative disorders, ARV-393 for non-Hodgkin Lymphoma, ARV-806 for mutated cancers, and vepdegestrant for ER+/HER2- breast cancer [3]

Core Insights - Arvinas, Inc. announced preclinical data for ARV-806, a PROTAC KRAS G12D degrader, demonstrating significant tumor growth inhibition in models of pancreatic, colorectal, and lung cancer, highlighting its best-in-class potential for KRAS G12D mutated cancers [1][2][5] Group 1: Drug Development and Efficacy - ARV-806 showed robust and durable KRAS G12D degradation, leading to significant tumor growth inhibition in various cancer models [1] - The drug targets both ON and OFF forms of KRAS G12D, which is the most common mutation of the KRAS protein, addressing high unmet needs in solid tumors [1][5] - In vitro studies indicated that ARV-806 degraded KRAS G12D with picomolar potency across multiple cancer cell lines without affecting wild-type and other mutant RAS isoforms [6] - Following a single intravenous dose, ARV-806 achieved over 90% degradation of KRAS G12D for seven days, with sustained effects on c-MYC suppression and BIM induction for at least five days [6] Group 2: Clinical Trials and Future Potential - Arvinas is currently evaluating ARV-806 in a Phase 1 clinical trial for patients with KRAS G12D–mutated advanced solid tumors [3] - The data suggest that ARV-806's sustained pharmacodynamic activity supports intermittent clinical dosing, indicating a potential for effective treatment regimens [3][8] - The drug demonstrated over 25-fold greater potency in reducing cancer cell proliferation and over 40-fold higher potency in degrading KRAS G12D protein compared to other clinical-stage G12D degraders [6] Group 3: Company Overview - Arvinas is a clinical-stage biotechnology company focused on developing protein degradation therapies through its PROTAC platform, targeting various diseases including cancers with KRAS mutations [7] - The company is advancing multiple investigational drugs, including ARV-806 for KRAS G12D, vepdegestrant for ER+/HER2- breast cancer, and ARV-393 for non-Hodgkin lymphoma [7]

Core Insights - Arvinas, Inc. announced the presentation of preclinical data for ARV-806, a PROTAC KRAS G12D degrader, at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics [1] - ARV-806 targets the KRAS G12D mutation, which is prevalent in various solid tumors, indicating a significant unmet medical need [2] - The company is advancing multiple investigational drugs, including ARV-806, through clinical development programs [3] Group 1: ARV-806 Presentation Details - Title of the presentation: Preclinical Activity of ARV-806, a PROTAC KRAS G12D Degrader [1] - Presentation type: Poster presentation, scheduled for October 24, 2025, from 12:30-4pm ET [1] - Poster number: B107, part of Poster Session B [1] Group 2: About ARV-806 - ARV-806 is designed to selectively target and degrade the KRAS G12D mutation, which is the most common mutation of the KRAS protein [2] - The drug is currently in a Phase 1 clinical trial for patients with advanced solid tumors harboring KRAS G12D mutations [2] Group 3: About Arvinas - Arvinas is a clinical-stage biotechnology company focused on developing therapies that utilize the body's natural protein disposal system [3] - The company is also developing other investigational drugs targeting various conditions, including breast cancer and neurodegenerative disorders [3] - Arvinas is headquartered in New Haven, Connecticut [3]