On August 8, 2023 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported second quarter 2023 financial results and provided an update on its clinical and pipeline progress (Press release, Beam Therapeutics, AUG 8, 2023, View Source [SID1234633954]).

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"The first half of 2023 has been marked by focused execution across the business, with the singular goal of making an impact on the lives of people suffering from serious diseases," said John Evans, chief executive officer of Beam. "We are very pleased with the continued enrollment progress in the BEACON trial, having now consented enough patients projected to both fill the sentinel cohort and initiate the expansion cohort. In addition, the BEAM-201 trial is now open for enrollment at multiple clinical sites, with the first patient having been consented and dosing expected this quarter. We have also continued to accelerate development of BEAM-302, a potential best-in-class product candidate for patients with alpha-1 anti-trypsin deficiency, and are now prioritizing a BEAM-302 regulatory filing in the first quarter of 2024 as our first in vivo program, with a regulatory filing for BEAM-301 expected to follow shortly thereafter. Our critical manufacturing capability in North Carolina is anticipated to be cGMP ready for both cell manufacturing and LNP manufacturing this year. Finally, Beam is well capitalized to pursue the next wave of growth in its innovative research platform, from non-genotoxic conditioning with ESCAPE in hematology, to next-generation allogeneic cell therapies in cancer and immunology, to a growing number of wholly owned and partnered base editing programs targeting the liver. We believe we are well positioned to establish an industry-leading platform in precision genetic medicine."

Second Quarter 2023 Business Updates and Key 2023-2024 Anticipated Milestones

Hematology Portfolio

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Beam continues to advance its BEACON Phase 1/2 clinical trial, an open-label, single-arm, multicenter study evaluating the safety and efficacy of BEAM-101 in adult patients with severe sickle cell disease (SCD).
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Beam has continued to consent additional patients in the BEACON trial, all of whom are now moving in parallel through the screening, transfusion and mobilization activities required to enable treatment with BEAM-101.
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Beam now anticipates that currently consented patients are sufficient to both fill the sentinel cohort (n=3) and to initiate the expansion cohort. Beam will continue adding additional patients to the BEACON trial through the end of year and beyond, with a total target of 45 treated patients.
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Treatment with BEAM-101, in which the edited cell product is delivered in an autologous bone marrow transplant, will occur on a sequential basis for the first three patients treated in the trial, and then will be given in parallel for all subsequent patients.
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The company continues to anticipate reporting initial data on multiple patients from the BEACON trial in 2024.
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Beam continues to advance and invest in its Engineered Stem Cell Antibody Paired Evasion (ESCAPE) conditioning platform.

Immunology/Oncology Portfolio

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Beam continues to advance BEAM-201, a multiplex-edited allogeneic CAR-T product candidate, for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL). Multiple sites for the Phase 1/2 clinical trial of BEAM-201 are now open for enrollment.
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The first patient has consented and is expected to be dosed in the third quarter of 2023.
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Beam also continues to invest in and advance its next-generation allogeneic strategies designed to improve cell persistence and expand the utility and accessibility of cell therapies in cancer and other diseases. The company plans to share updates on these efforts by year-end 2023.
Genetic Disease (in vivo) Portfolio

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Beam continues to advance its two in vivo base editing product candidates, BEAM-301 for the treatment of glycogen storage disease 1a (GSD1a) and BEAM-302 for the treatment of alpha-1 antitrypsin deficiency (AATD), leveraging lipid nanoparticles (LNPs) for delivery to the liver.
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To promote speed to the clinic of a top priority program, the company has leveraged the learnings and capability build from BEAM-301 to accelerate development of BEAM-302, which is now expected to be its first in vivo liver regulatory filing, followed by BEAM-301.
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The company expects to:
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Submit a regulatory application for authorization to initiate clinical trials for BEAM-302 in the first quarter of 2024; and
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Submit a regulatory application for authorization to initiate clinical trials for BEAM-301 in the first half of 2024.
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Beam continues to advance multiple additional in vivo editing programs targeting the liver, including both its wholly owned and collaboration programs, through lead optimization, and advance its LNP delivery technologies for delivery of base editing medicines to the liver and other tissues.
Manufacturing Updates

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Beam continues to expect initiation of current good manufacturing practice compliant operations at its North Carolina manufacturing facility in late 2023.
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Beam is now planning to enable cGMP manufacturing of both autologous cell products in support of its sickle cell programs as well as LNP products in support of its liver programs BEAM-302 and BEAM-301 in its North Carolina facility.
Recent Nature Genetics Preclinical Publication Suggests Base Editing Enables More Uniform HbF Upregulation than Nuclease Editing

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In July, Beam co-founder David Liu, Ph.D., and St. Jude Children’s Research Hospital collaborators Jonathan Yen, Ph.D., and Mitchell Weiss, M.D., Ph.D., published preclinical research comparing five gene editing strategies in CD34+ hematopoietic stem and progenitor cells using either Cas9 nuclease or adenine base editors to induce fetal hemoglobin (HbF) red blood cells. Notably, the data suggest that base editing can provide a strategy for potent, uniform induction of HbF, yielding a consistent, predictable, and precise editing outcome. Conversely, nuclease editing of either the fetal hemoglobin gene or the BCL11A enhancer created a complex, uncontrolled distribution of alleles with a wide range of outcomes for induction of fetal hemoglobin, including numerous cells with minimal or no induction detected. These data illustrate the potential advantages of base editing’s mechanism of action, including the creation of predictable and consistent gene modifications with well-characterized, uniform biological effects across edited cells, as compared to the uncontrolled mixture of allele outcomes that result from nuclease-based knockout through double-stranded breaks.

Second Quarter 2023 Financial Results

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Cash Position: Cash, cash equivalents and marketable securities were $1.1 billion as of June 30, 2023, as compared to $1.1 billion as of December 31, 2022.
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Research & Development (R&D) Expenses: R&D expenses were $97.6 million for the second quarter of 2023, compared to $74.6 million for the second quarter of 2022.
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General & Administrative (G&A) Expenses: G&A expenses were $24.7 million for the second quarter of 2023, compared to $24.1 million for the second quarter of 2022.
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Net Loss: Net loss was $82.8 million for the second quarter of 2023, or $1.08 per share, compared to $72.0 million for the second quarter of 2022, or $1.02 per share.
Cash Runway

Beam expects that its cash, cash equivalents and marketable securities as of June 30, 2023, will enable the company to fund its anticipated operating expenses and capital expenditure requirements at least into 2025. This expectation includes funding directed toward reaching each of the key anticipated milestones for BEAM-101, BEAM-201, BEAM-301 and BEAM-302 described above, as well as continued investments in platform advancements and manufacturing capabilities.

On August 8, 2023 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported financial results for the second quarter 2023, recent business highlights and key upcoming catalysts (Press release, Atara Biotherapeutics, AUG 8, 2023, View Source [SID1234633953]).

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"We are pleased to announce IND clearance for ATA3219, our first allogeneic CAR-T cell product candidate expected to enter the clinic in the coming months as a potential best-in-class treatment for patients with certain B-cell malignancies," said Pascal Touchon, President and Chief Executive Officer of Atara. "Building on this momentum, our discussions with FDA and potential commercial partners for tab-cel in the U.S. are progressing well and we are excited to soon conduct the primary analysis of the EMBOLD Phase 2 study in progressive MS, with clinical and biomarker data from more than 90 patients."

Tabelecleucel (tab-cel or EBVALLO) for Post-Transplant Lymphoproliferative Disease (PTLD)

Continued productive discussions between Atara and FDA have addressed outstanding chemistry, manufacturing, and controls (CMC) questions. A meeting is scheduled to resolve the remaining topic of comparability between clinical and intended commercial process versions which should provide clarity on timing for a potential BLA submission
Following significant levels of engagement, discussions with potential U.S. commercialization partners are advancing
Patients in Europe are now receiving treatment with EBVALLO in the commercial setting, as Pierre Fabre is progressively launching on a country-by-country basis
Atara is investigating label expansion opportunities with its ongoing Phase 2 multi-cohort study with initial data expected in Q4 2023
ATA188 for Progressive Multiple Sclerosis (MS)

Atara plans to communicate data from the primary analysis of the double-blind placebo-controlled Phase 2 EMBOLD study in progressive MS in early November
This communication will include data from more than 90 patients, covering the primary endpoint of confirmed disability improvement (CDI) based on expanded disability status scale (EDSS) at 12 months, other clinical endpoints, and additional biomarkers
In addition, the Company anticipates sharing longer-term results for patients that have completed study visits beyond the 12-month primary endpoint
Atara will present new biomarker analyses from its ongoing Phase 1 trial of ATA188 at the International Society of Neuroimmunology (ISNI) congress taking place August 20-24. The data show ATA188-treated patients who achieved CDI by EDSS exhibited reduced accumulation of plasma Glial Fibrillary Acidic Protein (GFAP), a potential biomarker of disease progression in MS. Additionally, a novel application of TCRβ-sequencing allowed for detection of ATA188-derived EBV-specific TCRβ clonotypes in patients
ATA3219: Allogeneic CD19 CAR T for Various Indications

A Phase 1 study in relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL) is expected to start in the coming months following Atara’s receipt of a Safe to Proceed letter from FDA in response to an Investigational New Drug Application (IND) submitted for ATA3219. ATA3219 is an allogeneic CD19-1XX CAR+ EBV T cell immunotherapy that incorporates multiple clinically validated technologies designed for T-cell memory, robust expansion and persistence, and potent anti-tumor efficacy
A large unmet medical need remains for CD19-directed CAR T products that can be reliably manufactured at scale, are available in advance of patient need, and are enabling more complete and durable responses with favorable safety
Second Quarter 2023 Financial Results

Cash, cash equivalents and short-term investments as of June 30, 2023, totaled $153.6 million, as compared to $205.4 million as of March 31, 2023
Net cash used in operating activities was $52.8 million for the second quarter 2023, as compared to $64.0 million in the same period in 2022
Atara believes that its cash and investments as of June 30, 2023, will be sufficient to fund the Company’s planned operations into second quarter 2024
Atara reported a net loss of $71.1 million, or $0.68 per share for the second quarter 2023, as compared to net income of $18.5 million, or $0.18 per share for the same period in 2022. Second quarter 2022 net income included $50.9 million of deferred revenue recognized due to the termination of the Bayer Collaboration Agreements and a gain on the sale of the ATOM facility of $50.2 million.
Total costs and operating expenses include non-cash stock-based compensation, depreciation and amortization expenses of $13.8 million for the second quarter 2023, as compared to $15.6 million for the same period in 2022
Research and development expenses were $56.1 million for the second quarter 2023, as compared to $64.9 million for the same period in 2022
Research and development expenses include $7.2 million of non-cash stock-based compensation expenses for the second quarter 2023 as compared to $7.9 million for the same period in 2022
General and administrative expenses were $13.3 million for the second quarter 2023, as compared to $18.8 million for the same period in 2022
General and administrative expenses include $5.4 million of non-cash stock-based compensation expenses for the second quarter 2023, as compared to $6.2 million for the same period in 2022

On August 8, 2023 Astex Pharmaceuticals (UK) ("Astex"), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, reported an exclusive worldwide research collaboration and license agreement with MSD (Merck & Co., Inc., Rahway, N.J., USA) (Press release, Astex Pharmaceuticals, AUG 8, 2023, View Source [SID1234633952]). The goal of the collaboration is to identify small molecule candidates with activity towards a tumour suppressor protein for the treatment of cancer.

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"Astex is applying its fragment-based drug discovery capability to design and generate small molecule modulators tailored to a wide range of potentially important therapeutic targets," said Harren Jhoti, president and CEO of Astex. "This new alliance builds on our existing productive collaboration and allows us to combine our expertise and assets with MSD’s wide-ranging oncology capabilities."

Under the terms of the agreement, Astex will apply its fragment-based drug discovery platform to develop compounds targeting multiple forms of the p53 tumour suppressor protein and provide MSD with lead compounds for further optimization and preclinical development. MSD is granted an exclusive global license to research, develop, and commercialise candidates arising under the collaboration. Astex will receive an upfront payment of $35 million and is eligible for milestone payments associated with the achievement of preclinical, clinical, regulatory and sales milestones, totalling approximately $500 million per program, as well as tiered royalties on sales of any products arising from the collaboration. MSD will assume responsibility for funding all future research and development of lead candidates as well as commercialisation of products globally.

"At MSD we are committed to driving innovation with the goal of improving outcomes for patients with cancer," said George Addona, senior vice president discovery and translational medicine, MSD. "We look forward to building on our collaboration with the Astex team to advance this potentially impactful area of oncology research."

On August 8, 2023 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, 2023 and provided a corporate update (Press release, Arvinas, AUG 8, 2023, View Source [SID1234633951]).

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"We continue to make meaningful advances across our entire portfolio and have a data and milestone rich balance to the year," said John Houston, Ph.D., president and chief executive officer at Arvinas. "In addition to sharing promising interim data from our ongoing Phase 1/2 trial with ARV-766, and together with Pfizer, we initiated enrollment for the study lead-in for the first-line Phase 3 trial with vepdegestrant in combination with palbociclib in metastatic breast cancer. We now have two ongoing Phase 3 trials with vepdegestrant with the potential for our first Phase 3 data read-out in the second half of 2024. We are also on track to initiate a Phase 3 trial with bavdegalutamide in the second half of the year. These accomplishments are particularly meaningful as we celebrate our 10-year anniversary this year and reflect our commitment to bringing an entirely new class of transformative medicines to patients."

Recent Developments and Second Quarter Business Highlights

Initiated the study lead-in of the VERITAC-3 Phase 3 trial of vepdegestrant plus palbociclib as a first-line treatment in patients with ER+/HER2- locally advanced or metastatic breast cancer.
Shared data from the Phase 1/2 dose escalation and expansion trial showing that ARV-766 was well-tolerated and demonstrated promising activity in a heavily pre-treated, post-NHA, all-comers patient population:
42% of patients with AR ligand binding domain (LBD) mutations achieved PSA50.
In all patients with L702H mutations, 3 of 5 achieved PSA50; in patients with co-occurring T878/H875/L702 mutations, 3 of 3 achieved PSA50.
RECIST (Response Evaluation Criteria in Solid Tumors) partial responses were observed.
Of four RECIST-evaluable patients with AR LBD mutations, one achieved a confirmed partial response, and one achieved an unconfirmed partial response.
ARV-766 was well tolerated and the majority of treatment-related adverse events (TRAEs) have been Grade 1 or 2, with no Grade ≥4 TRAEs and no dose limiting toxicities.
Low rates of discontinuation (1 of 47) and dose reductions (2 of 47) were observed.
Evaluated and announced preliminary data from Part C of the ongoing Phase 1b/2 ARV-471-mBC-101 study (ClinicalTrials.gov Identifier: NCT04072952).
Continued enrollment in the VERITAC-2 Phase 3 2L+ clinical trial of vepdegestrant as a monotherapy for the treatment of patients with ER+/HER2- metastatic breast cancer (ClinicalTrials.gov Identifier: NCT05654623).
Continued enrollment in the TACTIVE-U study (vepdegestrant in combination with abemaciclib or ribociclib, [ClinicalTrials.gov Identifiers: NCT05548127 and NCT05573555]) and, with Pfizer, entered a collaboration and supply agreement with Carrick Therapeutics to evaluate samuraciclib in combination with vepdegestrant in the TACTIVE-U study.
Continued enrollment in the TACTIVE-E study (vepdegestrant in combination with everolimus; ClinicalTrials.gov Identifier: NCT05501769), and the TACTIVE-N study (vepdegestrant as a monotherapy in the neoadjuvant setting; ClinicalTrials.gov Identifier: NCT05549505).
Announced the inclusion of vepdegestrant in the I-SPY-2 (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis 2) trial sponsored by Quantum Leap. The I-SPY-2 Endocrine Optimization Platform (EOP) study (ClinicalTrials.gov Identifier: NCT01042379) includes a vepdegestrant monotherapy arm and a vepdegestrant plus letrozole arm.
Awarded Innovation Passport Designation for vepdegestrant by the U.K. Innovative Licensing and Access Pathway Steering Group.
Announced that John Houston, Ph.D., was named Chairperson replacing Timothy Shannon, M.D., who stepped down from the role. Additionally, Sunil Agarwal, M.D., was appointed to join the company’s Board of Directors and Briggs Morrison, M.D., was appointed Lead Independent Director of the Board.
Anticipated Upcoming Milestones and Expectations

Vepdegestrant (ARV-471)
As part of Arvinas’ global collaboration with Pfizer, the companies plan to:

Present additional data from the Phase 1b combination trial with palbociclib (ClinicalTrials.gov Identifier: NCT04072952) at a medical congress (2H 2023).
Continue enrollment in the study lead-in (SLI) of the VERITAC-3 Phase 3 trial in first-line ER+/HER2- locally advanced or metastatic breast cancer. The SLI will identify the palbociclib dose (75 or 100 mg) to combine with vepdegestrant in the randomized portion of the study.
Initiate Phase 1b/2 trial with vepdegestrant plus Pfizer’s CDK4 (cyclin dependent kinase) inhibitor (2H 2023).
Initiate an additional arm of the Phase 1b/2 combination umbrella trial (TACTIVE-U: ClinicalTrials.gov Identifiers: NCT05548127 and NCT05573555) with Carrick Therapeutics’ CDK7 inhibitor (2H 2023).
Complete enrollment in VERITAC-2 Phase 3 monotherapy trial (ClinicalTrials.gov Identifier: NCT05654623) in patients with metastatic breast cancer (2H 2024).
Androgen Receptor (AR) Franchise (Bavdegalutamide/ARV-110, ARV-766)

Present updated data, including radiographic progression free survival, from the ongoing Phase 1/2 trial with bavdegalutamide at the European Society for Medical Oncology congress in Madrid (October 2023).
Initiate a global Phase 3 trial with bavdegalutamide in mCRPC (2H 2023).
Complete enrollment in the Phase 1b combination study with bavdegalutamide plus abiraterone (2H 2023).
Initiate a Phase 1b/2 dose escalation trial with ARV-766 in combination with abiraterone in patients who have not previously received novel hormonal agents (2H 2023).
Complete enrollment in the Phase 1b combination study with bavdegalutamide plus abiraterone (2H 2023).
Pipeline:

Submit two investigational new drug (IND)/clinical trial authorization (CTA) applications for the Company’s BCL6 (oncology) and LRRK2 (neuroscience) PROTAC protein degraders by year-end 2023.
Progress at least two additional PROTAC protein degrader programs into IND- or CTA-enabling studies by year-end 2023.
Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, restricted cash and marketable securities as of June 30, 2023, is sufficient to fund planned operating expenses and capital expenditure requirements into 2026.

Second Quarter Financial Results

Cash, Cash Equivalents and Marketable Securities Position: As of June 30, 2023, cash, cash equivalents, restricted cash and marketable securities were $1,044.3 million as compared with $1,210.8 million as of December 31, 2022. The decrease in cash, cash equivalents, restricted cash and marketable securities of $166.5 million for the six months ended June 30, 2023 was primarily related to cash used in operations of $172.9 million (net of $2.5 million received from two collaborators), leasehold improvements of $1.7 million and loss on the sale of marketable securities of $0.9 million, partially offset by unrealized gains on marketable securities of $7.0 million and proceeds from the exercise of stock options of $2.0 million.

Research and Development Expenses: Research and development expenses were $103.4 million for the quarter ended June 30, 2023, as compared with $75.3 million for the quarter ended June 30, 2022. The increase in research and development expenses of $28.1 million for the quarter was primarily due to increasing investment in our platform and exploratory programs of $5.4 million, as well as an increases our AR program of $7.4 million, which includes bavdegalutamide and ARV-766, and our ER program of $15.3 million, which is net of the cost sharing of vepdegestrant (ARV-471) under the global Pfizer collaboration agreement to develop and commercialize vepdegestrant that was initiated in July 2021 (Vepdegestrant (ARV-471) Collaboration Agreement).

General and Administrative Expenses: General and administrative expenses were $25.7 million for the quarter ended June 30, 2023, as compared with $24.3 million for the quarter ended June 30, 2022. The increase of $1.4 million was primarily due to an increase in professional fees of $2.0 million and increased investments in our commercial operations of $0.9 million, offset in part by reduced personnel and infrastructure related costs of $1.1 million and reduced insurance costs of $0.3 million.

Revenues: Revenues were $54.5 million for the quarter ended June 30, 2023 as compared with $33.8 million for the quarter ended June 30, 2022. Revenue is related to the Vepdegestrant (ARV-471) Collaboration Agreement, the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017 and revenue related to our Oerth Bio joint venture which was initiated in July 2019. The increase in revenues of $20.7 million was primarily due to an increase in revenue from the Vepdegestrant (ARV-471) Collaboration Agreement totaling $24.2 million, partially offset by a net decrease in revenue of $1.8 million as the performance period under the collaboration agreement with Genentech has concluded and a decrease of $1.2 million of previously constrained deferred revenue related to our Oerth Bio joint venture.

Income Tax Expense: Income tax benefit was $0.3 million for the quarter ended June 30, 2023, as compared with an income tax expense of $3.4 million for the quarter ended June 30, 2022. Current year tax benefit was driven by expected benefits from state net operating loss carryback claims. Prior year tax expense was driven by revenue recognized in 2022 for tax purposes from the Vepdegestrant (ARV-471) Collaboration Agreement.

Loss from Equity Method Investment: Loss from equity method investment was $1.3 million for the quarter ended June 30, 2023, as compared with $2.5 million for the quarter ended June 30, 2022 due to decreased operating losses incurred by Oerth Bio.

Net Loss: Net loss was $66.6 million for the quarter ended June 30, 2023, as compared with $70.0 million for the quarter ended June 30, 2022. The decrease in net loss for the quarter was primarily due to increased revenue and interest income from our marketable securities, as well as decreased income tax expense, partly offset by increased research and development expenses and general and administrative expenses.

About bavdegalutamide (ARV-110) and ARV-766
Bavdegalutamide (ARV-110) and ARV-766 are investigational orally bioavailable PROTAC protein degraders designed to selectively target and degrade the androgen receptor (AR). Bavdegalutamide and ARV-766 are being developed as potential treatments for men with prostate cancer. Preclinically, both investigational agents have demonstrated activity in models of wild type tumors in addition to tumors with AR mutation or amplification, both common mechanisms of resistance to currently available AR-targeted therapies.

About vepdegestrant (ARV-471)
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 early and locally advanced or metastatic ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Use of vepdegestrant in the ongoing and planned clinical trials will continue to monitor and evaluate patient safety and anti-tumor activity.

In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed increased anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

On August 8, 2023 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported results for the second quarter 2023 (Press release, Agenus, AUG 8, 2023, View Source [SID1234633950]).

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Key accomplishments and highlights include:

Botensilimab Update: Botensilimab/balstilimab combination data presented at ESMO (Free ESMO Whitepaper)-GI demonstrated median overall survival (mOS) of 20.9 months and a 23% overall response rate (ORR), both surpassing data reported for standard of care in 3L+ Non-MSI-H colorectal cancer (CRC) in patients without active liver metastases.
Regulatory: The U.S. FDA granted Fast Track designation for the botensilimab/balstilimab combination in 3L+ Non-MSI-H CRC in patients without active liver metastases. Agenus is exploring global accelerated approval strategies for CRC.
Clinical Trial Progress: Ongoing Phase 2 ACTIVATE trials in CRC and melanoma expected to fully enroll by end of year.
AGEN2373 Update: AGEN2373 Phase 1 dose escalation data presented at ASCO (Free ASCO Whitepaper) demonstrated promising monotherapy clinical responses in patients with advanced solid tumors.
"Botensilimab, alone or in combination with balstilimab, continues to display remarkable clinical activity in over 600 patients treated across nine late-stage, treatment resistant solid tumor cancers, demonstrating great potential to revolutionize the role of immunotherapy in cancer treatment," said Chief Executive Officer, Garo Armen, Ph.D. "Agenus is committed to advancing our diverse clinical pipeline with a focus on expediting our first regulatory submission for the botensilimab/balstilimab combination in colorectal cancer. Our data has demonstrated an unprecedented survival benefit over what has been reported for standard of care, underscoring this combination as an important potential treatment option for patients with non-MSI-high colorectal cancer, which represents 85% of the population of patients with colorectal cancer1."

Botensilimab/Balstilimab ("Bot/Bal") Combination in 3L+ Non-MSI-H Metastatic CRC Data Presented at the ESMO (Free ESMO Whitepaper)-GI World Congress on Gastrointestinal Cancer in June 2023:

In 69 evaluable patients with non-MSI-High CRC without active liver metastases, results demonstrated a meaningful improvement over standard of care in both overall response rate (ORR%) and median overall survival (mOS):
mOS of 20.9 months as compared to the recently reported 12.9-month benchmark with standard care.2
ORR of 23% as compared to the recently reported 2.8%1 benchmark with standard care.
In April 2023, the U.S. FDA granted Fast Track designation to the bot/bal combination for patients with non-MSI-H/dMMR metastatic CRC without active liver metastases.
The ACTIVATE Phase 2 trial in this patient population is on target to conclude enrollment by year-end. Planning is underway for a Phase 3 CRC study; with Fast Track designation from the FDA, study design and timing will be determined as we discuss our filing approach with the agency.
A Biologics License Application to the FDA is planned in 2024.
Botensilimab in Other Advanced Solid Tumor Cancers:

Lung: Enrollment continues for a Phase 1b trial targeting PD-(L)1 +/- chemotherapy relapsed/refractory non-small-cell lung cancer (NSCLC); data update planned by year-end.
Melanoma: Ongoing global enrollment in Phase 2 ACTIVATE trial with data update planned in 2024.
Ovarian: Phase 1b trial in patients with platinum-resistant ovarian cancer (PROC) demonstrated a 33% ORR and 67% disease control rate among primarily high-grade, heavily pretreated patients (presented at SGO in March 2023).
Sarcomas: Updated data for a Phase 1b cohort with advanced sarcomas to be presented at ESMO (Free ESMO Whitepaper) on October 21st 2023.
AGEN2373 Data Presented at the ASCO (Free ASCO Whitepaper) 2023 Annual Meeting:

Complete results from the first-in-human monotherapy dose escalation study of AGEN2373, a CD137 agonist, in patients with advanced solid tumors:
Reported responses in metastatic prostate cancer, ampullary carcinoma, and vulvar squamous cell carcinoma highlight the potential impact of AGEN2373.
AGEN2373 is the first CD137 agonist antibody to report single-agent responses with no major toxicities.
Clinical data are consistent with mechanistic design intent of AGEN2373 to avoid hepatic toxicity, a typical constraint of CD137-targeted agonists.
Leadership Appointments:

In alignment with Agenus’ next phase of growth and anticipated commercialization of the bot/bal combination, the company announced the following key executive appointments:

Robin Taylor, Ph.D., Chief Commercial Officer.
Homa Yeganegi, Chief Product Strategy and Global Medical Affairs Officer.
Stephanie Fagan, Chief Communications Officer.
Second Quarter 2023 Financial Results:

We ended our second quarter 2023 with a cash, cash equivalent and short-term investment balance of $157.6 million, compared to $193.4 million at December 31, 2022. In addition, we have raised $20.3 million through sales of our common stock under our at market issuance sales agreement since the end of Q2 2023.