Arvinas Reports Second Quarter 2024 Financial Results and Provides Corporate Update

On July 30, 2024 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported financial results for the second quarter ended June 30, 2024, and provided a corporate update (Press release, Arvinas, JUL 30, 2024, View Source [SID1234645147]).

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"During the second quarter, we continued making meaningful progress across our entire portfolio, with upcoming milestones that will further support our mission to improve patient lives with pioneering therapies from our revolutionary PROTAC protein degradation platform," said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. "The readout of VERITAC-2, our first Phase 3 clinical trial, will be a landmark event for Arvinas. We are on-track to complete enrollment in the fourth quarter of the year, with topline data anticipated in either the fourth quarter of 2024 or first quarter of 2025. If positive, we believe these results will support our first new drug application filing and our transition to a commercial-stage company, assuming regulatory approval."

"We are well on our way to becoming a multi-product, commercial-stage organization with strong leadership and a robust pipeline across several indications," continued Dr. Houston. "Our first PROTAC degrader with the potential to treat neurodegenerative diseases, ARV-102, was recently cleared to initiate the multiple ascending dose portion of our Phase 1 clinical trial. In addition, we initiated the first-in-human Phase 1 clinical trial in patients with B-cell lymphomas with our PROTAC BCL6 degrader ARV-393. I’m excited by the progress we have made and the ongoing confidence we have in our PROTAC platform, which was further validated by our recent strategic transaction with Novartis. We believe Novartis will accelerate and broaden the development of ARV-766 as a potential best-in-class treatment for patients with prostate cancer."

Recent Developments and 2Q Business Highlights

Vepdegestrant

Evaluated enrollment and blinded event rates in the ongoing VERITAC-2 Phase 3 monotherapy clinical trial (NCT05654623) in patients with metastatic breast cancer.
The trial is on track to complete enrollment in 4Q24.
Based on current trial status, the primary completion date has been reprojected to November 2024, with topline data now anticipated in 4Q24/1Q25.
Completed enrollment of the study lead-in for the VERITAC-3 Phase 3 clinical trial of vepdegestrant in combination with palbociclib as a first-line treatment in patients with estrogen receptor (ER) positive/human growth epidermal growth factor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer.
Continued enrollment globally in multiple clinical studies of vepdegestrant in ER+/HER2- metastatic breast cancer.
Presented updated clinical data from a Phase 1b clinical trial combination cohort evaluating vepdegestrant in combination with palbociclib in heavily pre-treated patients with locally advanced or metastatic ER+/HER2- breast cancer at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer Annual Congress.
After six months of additional follow-up, updated data from the trial continued to demonstrate an encouraging clinical benefit rate, objective response rate and progression-free survival, and a consistent safety profile as previously reported at the San Antonio Breast Cancer Symposium (SABCS) in December 2023.
The clinical benefit rate across all dose levels (n=46) was 63%; the objective response rate in evaluable patients with measurable disease at baseline (n=31) was 42%; median progression-free survival based on 27 (59%) events across all dose levels was 11.2 months (95% CI: 8.2 – 16.5) and the safety profile of vepdegestrant in combination with palbociclib were consistent with data previously reported at SABCS in December 2023.
Patients receiving the recommended Phase 3 dose of vepdegestrant (200mg) in combination with palbociclib 125mg (n=21), achieved a median progression-free survival of 13.9 months (95% CI: 8.1-NR).
Strategic Transaction with Novartis

Entered into a license agreement and asset purchase agreement with Novartis (NYSE: NVS) for the exclusive, worldwide development, manufacture and commercialization of ARV-766, Arvinas’ second generation PROTAC androgen receptor (AR) degrader for patients with prostate cancer, and the sale of Arvinas’ preclinical AR-V7 program, which closed on May 28, 2024.
Arvinas received a one-time, upfront payment in the aggregate amount of $150.0 million in accordance with the terms of the license agreement and the asset purchase agreement. Under the terms of the license agreement, Arvinas is also eligible to receive up to an additional $1.01 billion as contingent payments based on specified development, regulatory, and commercial milestones for ARV-766 being met, as well as tiered royalties based upon worldwide net sales of ARV-766.
Pipeline

ARV-102: Oral PROTAC LRRK2 degrader

Presented preclinical data at the Biennial International LRRK2 Meeting further supporting the potential of PROTAC-induced leucine-rich repeat kinase 2 (LRRK2) degradation as a potential treatment for neurodegenerative diseases. Key findings included:
With Arvinas’ PROTAC LRRK2 degrader, near-complete LRRK2 target engagement, as well as LRRK2 degradation, in mouse and non-human primate lung and brain.
Differing effects of the LRRK2 PROTAC degraders in the lungs compared to kinase inhibitors, suggesting reduced pulmonary function risk.
Substantially less Type II pneumocyte enlargement compared to MLi-2, an experimental LRRK2 kinase inhibitor.
Surfactant protein accumulation in mouse lung observed after treatment with the LRRK2 kinase inhibitor MLi-2, but not after treatment with the PROTAC LRRK2 degrader.
No evidence of collagen deposition in lung to date with PROTAC LRRK2 degraders in non-human primates.
Received health authority approval to initiate the multiple ascending dose portion of the ongoing Phase 1 clinical trial in healthy volunteers with the PROTAC LRRK2 degrader ARV-102.
ARV-393: Oral PROTAC BCL6 degrader

Presented preclinical data for ARV-393 at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Annual Congress that showed ARV-393:
Potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines.
Showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma.
Initiated the first-in-human Phase 1 clinical trial in patients with B-cell lymphomas with PROTAC BCL6 degrader ARV-393.
Corporate

Announced the appointment of Andrew Saik, MBA, to the role of Chief Financial Officer.
Announced the promotion of Ian Taylor, Ph.D., to President of Research and Development.
Announced the promotion of Angela Cacace, Ph.D., to Chief Scientific Officer.
Announced the promotion of Randy Teel, Ph.D., to Chief Business Officer.
Anticipated Upcoming Milestones and Expectations

Vepdegestrant (ARV-471)
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.
Evaluate data from the study lead-in of the VERITAC-3 Phase 3 trial to support dose selection for vepdegestrant plus palbociclib in planned Phase 3 combination trials in patients with ER+/HER2- locally advanced or metastatic breast cancer (2H24).
Present initial safety and pharmacokinetic data from the abemaciclib arm of the ongoing TACTIVE-U trial (2H24).
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).
Continue enrollment and evaluate preliminary data from the ongoing clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor atirmociclib (TACTIVE-K; ClinicalTrials.gov Identifier: NCT06206837) to inform the study design for the planned Phase 3 first line combination trial with either atirmociclib or palbociclib, with planned initiation in 2025.
Pipeline

Continue enrollment in the single ascending dose portion of the Phase 1 clinical trial in healthy volunteers with the PROTAC LRRK2 degrader ARV-102 and begin enrolling the multiple ascending dose portion by the end of 2024.
Continue enrollment in the first-in-human Phase 1 clinical trial in patients with B-cell lymphomas with PROTAC BCL6 degrader ARV-393.
Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, restricted cash and marketable securities as of June 30, 2024, is sufficient to fund planned operating expenses and capital expenditure requirements into 2027.

Second Quarter Financial Results
Cash, Cash Equivalents, Restricted Cash and Marketable Securities Position: As of June 30, 2024, cash, cash equivalents, restricted cash and marketable securities were $1,234.2 million as compared with $1,266.5 million as of December 31, 2023. The decrease in cash, cash equivalents, restricted cash and marketable securities of $32.3 million for the six months ended June 30, 2024 was primarily related to cash used in operations of $36.0 million (net of $150.0 million received from the Novartis agreements), unrealized losses on marketable securities of $0.7 million and the purchase of lab equipment and leasehold improvements of $0.8 million, partially offset by proceeds from the exercise of stock options of $5.3 million.

Research and Development Expenses: Research and development expenses were $93.7 million for the quarter ended June 30, 2024, as compared with $103.4 million for the quarter ended June 30, 2023. The decrease in research and development expenses of $9.7 million for the quarter was primarily due to decreases in expenses related to our ER program (which includes the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer) of $6.6 million and our platform and exploratory programs of $5.7 million, partially offset by an increase in our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $2.6 million.

General and Administrative Expenses: General and administrative expenses were $31.3 million for the quarter ended June 30, 2024, as compared with $25.7 million for the quarter ended June 30, 2023. The increase in general and administrative expenses of $5.6 million for the quarter was primarily due to an increase in personnel and infrastructure related costs of $4.0 million and professional fees of $1.6 million.

Revenues: Revenues were $76.5 million for the quarter ended June 30, 2024, as compared with $54.5 million for the quarter ended June 30, 2023. Revenue for the quarter is related to the license agreement and the asset purchase agreement with Novartis, the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer, the collaboration and license agreement with Bayer, the collaboration and license agreement with Pfizer, and revenue related to our Oerth Bio joint venture. The increase in revenue of $22.0 million was primarily due to revenue from the Novartis agreements, which were entered into during the quarter, of $45.4 million, offset by a decrease in revenue from the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer of $22.2 million and a decrease of $1.3 million of previously constrained deferred revenue related to our Oerth Bio joint venture.

About Vepdegestrant
Vepdegestrant 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.

Aileron Therapeutics to Present at the Canaccord Genuity 44th Annual Growth Conference

On July 30, 2024 Aileron Therapeutics, Inc. ("Aileron") (NASDAQ: ALRN), a biopharmaceutical company advancing a novel pipeline of first-in-class medicines to address significant unmet medical needs in orphan pulmonary and fibrosis indications, reported that Brian Windsor, Ph.D., President and Chief Executive Officer, will present at the Canaccord Genuity 44th Annual Growth Conference on Tuesday, August 13, 2024 at 4:00 p.m. EDT in Boston, MA (Press release, Aileron Therapeutics, JUL 30, 2024, View Source [SID1234645146]).

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A live webcast of the event can be accessed at View Source A replay of the webcast will be available for 90 days following the presentation.

AngioDynamics to Participate in Upcoming Investor Conferences

On July 29, 2024 AngioDynamics, Inc. (NASDAQ: ANGO), a leading and transformative medical technology company focused on restoring healthy blood flow in the body’s vascular system, expanding cancer treatment options, and improving quality of life for patients, reported that its management is scheduled to participate in the following upcoming investor conferences (Press release, AngioDynamics, JUL 29, 2024, View Source [SID1234645142]):

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9th Annual Needham Virtual MedTech & Diagnostics 1×1 Conference
Date: August 12, 2024

Canaccord Genuity 44th Annual Growth Conference
Presentation: August 13, 2024 at 10:00am

A live webcast of the presentation will be accessible through the "Investors" section of the Company’s website at www.angiodynamics.com.

BerGenBio Announces Selection of 2nd Dose in Phase 2a First Line STK11m Non-Small Lung Cancer Trial

On July 29, 2024 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that the independent Data and Safety Monitoring Board (DSMB) for BerGenBio’s Phase 1b/2a BGBC016 study confirmed acceptable safety at the highest dose tested in the Phase 1b (Press release, BerGenBio, JUL 29, 2024, View Source [SID1234645141]). As a result, the DSMB also recommended that under the study protocol, no additional patients will be required for Phase 1b.

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The recommendation of the DSMB allows BerGenBio to proceed per study protocol and open the second dose level in the Phase 2a part of the study in NSCLC patients with STK11 mutations. This portion of the study is already open for enrollment and is designed to evaluate the efficacy of the combination of bemcentinib with pembrolizumab (Keytruda) and doublet chemotherapy.

Cristina Oliva, Chief Medical Officer of BerGenBio commented, "We continue to be reassured by the safety profile of bemcentinib when combined with the standard of care for 1L NSCLC patients. Opening the second dose level in the Phase 2a portion of the BGBC016 study will allow us to carefully evaluate the dose response to bemcentinib, an important goal to guide the dose optimization for future trials."

Martin Olin, Chief Executive Officer of BerGenBio added, "The BGBC016 clinical trial is our highest priority, and I am happy to see it continues to progress as planned. NSCLC STK11m patients are not currently eligible for targeted therapy and unfortunately face a very poor prognosis. The medical need is significant, and so are the commercial opportunities.

The Phase 2a is assessing the safety and efficacy of two different doses of bemcentinib in the same treatment combination. As previously communicated, the company expects to present an interim analysis in the second half of this year.

About STK11m NSCLC

Patients with STK11m NSCLC have a significantly poorer response to current therapies, including immune checkpoint inhibitors, when compared with patients with wild-type (non-mutated) STK11. AXL plays a significant role in the survival and spread of cancer and STK11m NSCLC patients have a high expression of AXL suggesting that AXL is an important target to prevent disease progression and resistance to existing therapies. Bemcentinib’s selective inhibition of AXL has been shown to improve the response to immune checkpoint inhibition in STK11m patient-derived preclinical models and in early clinical studies. There are currently no targeted therapies available for the STK11m NSCLC patient population, which represents up to 20% of 1L NSCLC patients.

Akeso’s sBLA for Ivonescimab in 1L Treatment of PD-L1 Positive NSCLC Accepted by NMPA

On July 29, 2024 Akeso (9926.HK) reported that the supplemental biologics license application (sBLA) for its independently developed, world’s first-in-class PD-1/VEGF bispecific antibody drug, 依达方 (generic name: ivonescimab Injection), as a monotherapy for first-line treatment of PD-L1 positive (PD-L1 TPS≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC), has been accepted by the China National Medical Products Administration (NMPA) (Press release, Akeso Biopharma, JUL 29, 2024, View Source [SID1234645140]).

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Ivonescimab is the world’s first bispecific antibody drug approved for the "tumor immunotherapy + anti-angiogenesis" mechanism. The first-line monotherapy treatment of PD-L1 positive (PD-L1 TPS ≥1%) locally advanced or metastatic NSCLC is ivonescimab’s second indication, following its approval for the treatment of EGFR-mutant non-squamous NSCLC that has progressed after EGFR-TKI therapy. Ivonescimab is also expected to become a new standard of care treatment option for both first-line and second-line lung cancer therapy.

This new indication application for ivonescimab is based on the HARMONi-2 (AK112-303) study. The Independent Data Monitoring Committee (IDMC) conducted a pre-specified interim analysis of the HARMONi-2 study, showing highly positive results. In the intent-to-treat (ITT) population, ivonescimab monotherapy significantly prolonged progression-free survival (PFS) compared to pembrolizumab monotherapy, with a hazard ratio (HR) significantly better than expected.

"As a researcher and clinician, we eagerly anticipate ivonescimab becoming the new standard treatment for first-line lung cancer, providing a superior ‘chemotherapy-free’ option for patients," said Professor Zhou Caicun, principal investigator of the HARMONi-2 study and director of the Oncology Department at East Hospital Affiliated To Tongji University. "The success of the HARMONi-2 study underscores the immense value of ivonescimab’s synergistic dual anti-tumor mechanism of ‘tumor immunotherapy + anti-angiogenesis.’"

Professor Zhou also emphasized that clinicians are looking forward to Akeso seizing the opportunity to establish ivonescimab as the new standard treatment for first-line lung cancer. He encouraged continuous exploration of combination therapies and ongoing global upgrades to standard treatment options, aiming to provide patients with better therapeutic choices.

Dr. Michelle Xia, Founder, Chairwoman, President, and CEO of Akeso, said: "We are thrilled that ivonescimab has achieved a significant milestone in first-line lung cancer therapy shortly after its approval for second-line treatment. We sincerely thank all our colleagues at Akeso for their decade-long dedication and craftsmanship, the experts for their meticulous contributions, and all the participants involved in the projects."

According to Dr. Xia, the approval of ivonescimab for second-line lung cancer therapy and its potential as a superior, chemotherapy-free new standard for first-line treatment fills a clinical unmet need in global lung cancer immunotherapy with bispecific antibodies, providing a more effective solution for patients and fulfilling Akeso’s commitment.

Dr. Xia also emphasized that the HARMONi-2 study showcases ivonescimab’s superior efficacy and safety, further solidifying its potential as a cornerstone product in tumor immunotherapy (IO). This includes its broad clinical development value and market prospects when used in combination with ADC drugs or other novel anti-cancer drugs. "We look forward to sharing ivonescimab’s robust clinical research data with global regulatory agencies to achieve worldwide approval and provide more effective solutions for patients around the globe."

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro.1 This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days,1 is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials, HARMONi and HARMONi-3.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.