On February 27, 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 fourth quarter and full year ended December 31, 2023, and provided a corporate update (Press release, Arvinas, FEB 27, 2024, View Source [SID1234640506]).

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"Our focused execution in 2023 enabled us to progress multiple trials across our entire portfolio and we are well-positioned for a catalyst rich year ahead, including completing our first Phase 3 trial," said John Houston, Ph.D., president and chief executive officer at Arvinas. "Our collaboration with Pfizer remains strong and we are on track to report topline data from our first Phase 3 clinical trial with vepdegestrant, the only PROTAC ER degrader in clinical development for patients with ER+/HER2- breast cancer. If successful, assuming regulatory approval, we have the opportunity to address an area of high unmet need and offer patients a new oral treatment option in the second-line metastatic breast cancer setting. And with the recent Phase 1 initiation with our LRRK2 PROTAC degrader – our first neuroscience program – we continue making significant progress with our novel PROTAC technology."

Recent Developments and Fourth Quarter Business Highlights

Vepdegestrant (ARV-471)

Received U.S. Food and Drug Administration Fast Track designation for the investigation of vepdegestrant for monotherapy in the treatment of adults with estrogen receptor (ER) positive/human growth epidermal growth factor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.
Presented interim results (data cutoff: June 6, 2023) from the Phase 1b vepdegestrant and palbociclib (IBRANCE) combination cohort at the 2023 San Antonio Breast Cancer Symposium (SABCS), which demonstrated encouraging clinical activity in heavily pre-treated patients with locally advanced or metastatic ER+/HER2- breast cancer with a median of four lines of therapy across disease settings.
A clinical benefit rate (CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥ 24 weeks) of 63% (95% CI: 47.5–76.8), or 29/46 patients; at the recommended Phase 3 dose of 200 mg (n=21), the CBR was 67% (95% CI: 43.0 – 85.4), or 14/21 patients.
An objective response rate (ORR) in evaluable patients with measurable disease at baseline (n=31) of 42% (95% CI: 24.5–60.9), or 13/31 patients; at the RP3D of 200 mg (n=15), the ORR was 53% (95% CI: 26.6 – 78.7); the median duration of response was 10.2 months.
Median progression free survival (PFS) of 11.1 months (95% CI: 8.2 – NE); 22 of 46 patients across all doses had progression events by time of data cutoff.
Median PFS of 11.1 and 11.0 months in patients with ESR1 wild-type and ESR1 mutant tumors, respectively.
The safety profile of vepdegestrant plus palbociclib was manageable. The primary toxicity was neutropenia, which was managed with palbociclib dose modifications (reductions and/or interruptions) per protocol. There was no febrile neutropenia and 3 of 46 patients discontinued due to neutropenia.
Initiated Phase 1b/2 with vepdegestrant plus Pfizer’s novel CDK4 inhibitor (PF-07220060) (TACTIVE-K: ClinicalTrials.gov Identifier: NCT06206837).
Initiated an additional arm of the Phase 1b/2 combination umbrella trial with the CDK7 inhibitor samuraciclib (TACTIVE-U: ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).
Completed enrollment in the TACTIVE-N Phase 2 trial of vepdegestrant as a monotherapy in the neoadjuvant setting in patients with ER+/HER2- localized breast cancer (ClinicalTrials.gov Identifier: NCT05549505).
Completed enrollment in the TACTIVE-E Phase 1 trial of vepdegestrant in combination with everolimus for the treatment of advanced or metastatic ER+/HER2- breast cancer (ClinicalTrials.gov Identifier: NCT05501769).
Androgen Receptor PROTAC degraders

Presented data from the Phase 1/2 clinical trial with bavdegalutamide (ARV-110) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress showing a median radiographic progression free survival (rPFS) of 11.1 months in patients with AR 878/875 tumor mutations, demonstrating the strong potential for a PROTAC AR degrader in prostate cancer.
Manageable tolerability profile with no grade >4 treatment-related adverse events (TRAEs).
Selected our second generation PROTAC AR degrader, ARV-766, as the lead program in prostate cancer and prioritized the initiation of a Phase 3 trial with ARV-766 in metastatic castrate resistant prostate cancer (mCRPC).
New interim data from Phase 1/2 trial with ARV-766 showed a broader efficacy profile and superior tolerability versus bavdegalutamide in the clinical setting, with a potentially differentiated profile against other AR-directed therapies.
Completed enrollment in the bavdegalutamide Phase 1b combination trial with abiraterone.
Pipeline

Received authorization from the European Medicines Agency to initiate clinical trials with the Company’s new PROTAC degrader, ARV-102, designed to target the LRRK2 protein.
Initiated first-in-human Phase 1 clinical trial in healthy volunteers with LRRK2 targeting PROTAC ARV-102.
Received clearance from the U.S. Food and Drug Administration to initiate clinical trials with the Company’s PROTAC degrader, ARV-393, designed to target the BCL6 protein.
Corporate

Completed oversubscribed $350 million private placement co-led by EcoR1 Capital and RTW Investments LP, with participation by new and existing investors.
Announced the resignation of Chief Financial Officer and Treasurer, Sean Cassidy, effective February 29, 2024.
Announced the appointment of Randy Teel, Ph.D., Arvinas’ current senior vice president of corporate and business development, to the role of interim chief financial officer and treasurer.
The Arvinas Board of Directors has launched a formal search process to identify Mr. Cassidy’s permanent replacement.
Appointed Jared Freedberg, J.D., as general counsel.
Entered into a new collaboration with Pfizer to identify novel chemical matter for E3 ligases leveraging Pfizer’s proprietary compound libraries and Arvinas’ ligase ligand expertise.
Anticipated Upcoming Milestones and Expectations
Vepdegestrant (ARV-471)
As part of Arvinas’ global collaboration with Pfizer, the companies plan to:

Complete enrollment of the VERITAC-2 Phase 3 monotherapy trial (ClinicalTrials.gov Identifier: NCT05654623) in patients with metastatic breast cancer (2H 2024).
Continue enrollment in the study lead-in for the VERITAC-3 Phase 3 trial of vepdegestrant and palbociclib as a first-line treatment in patients with ER+/HER2- locally advanced or metastatic breast cancer.
Continue enrollment of the ongoing Phase 1b/2 clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor (PF-07220060) (TACTIVE-K: ClinicalTrials.gov Identifier: NCT06206837).
Continue enrollment of the ongoing Phase 1b combination umbrella trial evaluating combinations of vepdegestrant with abemaciclib, ribociclib, or samuraciclib (TACTIVE-U: ClinicalTrials.gov Identifiers: NCTC05548127, NCTC05573555, and NCT06125522).
Initiate discussion with regulatory authorities on a second-line Phase 3 trial of vepdegestrant in combination with palbociclib and potentially other CDK4/6 inhibitors, and a new first-line Phase 3 trial of vepdegestrant plus Pfizer’s novel CDK4 inhibitor (PF-07220060).
ARV-766

Continue enrollment of Phase 2 dose expansion study with ARV-766, with progression free survival data anticipated in mid-2024.
Continue enrollment of Phase 1b/2 dose escalation trial with ARV-766 in combination with abiraterone in patients who have not previously received novel hormonal agents.
Initiate discussions with regulatory authorities for a planned Phase 3 clinical trial with ARV-766 in mCRPC (2Q 2024).
Pipeline

Continue enrollment in Phase 1 clinical trial in healthy volunteers with LRRK2 targeting PROTAC ARV-102 (2024)
Initiate first-in-human Phase 1 clinical trial in B-cell lymphomas with BCL6 targeting PROTAC ARV-393 (1H 2024)
Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, restricted cash and marketable securities as of December 31, 2023, is sufficient to fund planned operating expenses and capital expenditure requirements into 2027.

Full Year and Fourth Quarter Financial Results

Cash, Cash Equivalents and Marketable Securities Position: As of December 31, 2023, cash, cash equivalents, restricted cash and marketable securities were $1,266.5 million, as compared with $1,210.8 million as of December 31, 2022. The increase in cash, cash equivalents, restricted cash and marketable securities of $55.7 million for the year was primarily related to net proceeds from our private placement and ATM offerings of $370.2 million, unrealized gains on marketable securities of $16.1 million and proceeds from the exercise of stock options and issuance of ESPP shares of $4.5 million, offset by cash used in operations of $331.3 million (net of $2.5 million received from two collaborators), purchases of lab equipment and leasehold improvements of $2.9 million and losses on the sale of securities of $0.9 million.

Research and Development Expenses: Research and development expenses were $379.7 million and $95.2 million for the year and quarter ended December 31, 2023, as compared with $315.0 million and $98.3 million for the year and quarter ended December 31, 2022. The increase in research and development expenses of $64.7 million for the year was primarily due to an increase in expenses associated with our platform and exploratory programs of $1.1 million, our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $22.0 million and our ER program of $41.6 million, which includes the cost sharing of vepdegestrant (ARV-471) under the Vepdegestrant (ARV-471) Collaboration Agreement. The decrease in research and development expenses of $3.1 million for the quarter was primarily due to a decrease in expenses associated with our platform and exploratory programs of $19.4 million, offset by increases in our AR program of $5.7 million and our ER program of $10.6 million.

General and Administrative Expenses: General and administrative expenses were $100.3 million and $27.0 million for the year and quarter ended December 31, 2023, as compared with $79.6 million and $15.1 million for the year and quarter ended December 31, 2022. The increase in general and administrative expenses of $20.7 million for the year was primarily due to an increase in personnel and infrastructure related costs of $11.5 million, an increase in professional fees of $6.3 million and increases related to establishing our commercial operations of $3.5 million, offset in part by reduced insurance costs of $1.0 million. The increase in general and administrative expenses of $11.9 million for the quarter was primarily due to an increase in personnel and infrastructure related costs of $8.4 million, an increase in professional fees of $1.8 million and increases related to establishing our commercial operations of $1.7 million.

Revenues: Revenue was $78.5 million and $(43.1) million for the year and quarter ended December 31, 2023 as compared with $131.4 million and $38.0 million for the year and quarter ended December 31, 2022. Revenue is related to the Vepdegestrant (ARV-471) Collaboration Agreement, the collaboration and license agreement with Bayer, the collaboration and license agreement with Pfizer, the amended and restated option, license and collaboration agreement with Genentech and revenue related to our Oerth Bio joint venture. The decrease of $52.9 million for the year was primarily due to adjustments to revenue from changes in contract estimates related to our Pfizer ARV-471 Collaboration Agreement, Pfizer Research Collaboration Agreement and Bayer Collaboration Agreement, net of current year revenues, totaling $39.7 million, a decrease of $8.1 million in previously constrained deferred revenue recognized in 2023 related to our Oerth Bio joint venture and a decrease in revenue recognized from our Genentech License Agreement of $5.1 million. The decrease of $81.1 million for the quarter was primarily due to an adjustment to revenue from a change in contract estimate related to our Pfizer ARV-471 Collaboration Agreement.

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 February 27, 2024 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported fourth quarter and full year 2023 financial results and recent portfolio and business updates (Press release, Alector, FEB 27, 2024, View Source [SID1234640505]). As of December 31, 2023, Alector’s cash, cash equivalents and investments totaled $548.9 million. Pro forma for Alector’s January 2024 equity offering, cash, cash equivalents and investments total $620.0 million, which the company anticipates will provide runway through 2026.

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"2023 was marked by continued progress on the execution of our late-stage clinical programs, highlighted by achieving target enrollment in both the INVOKE-2 Phase 2 trial of AL002 and the pivotal INFRONT-3 Phase 3 trial of latozinemab. Additionally, the FDA granted Breakthrough Therapy Designation to latozinemab for FTD-GRN, and we look forward to continued productive engagements with the FDA, recognizing the unmet need for people living with the condition. We are also pleased to report that the first patient has been dosed in the PROGRESS-AD Phase 2 trial of AL101/GSK4527226," said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. "Alector continues to be a pioneer in the field of immuno-neurology, and we are beginning the year with an advanced pipeline and an extended cash runway through 2026, approximately a full year beyond the expected FTD-GRN pivotal Phase 3 INFRONT-3 data readout. Our unwavering commitment to addressing neurodegeneration fuels progress across our clinical-stage programs, with an anticipated data readout from the INVOKE-2 Phase 2 trial of AL002 in the fourth quarter of this year."

Sara Kenkare-Mitra, Ph.D., President and Head of Research and Development at Alector added, "We also made meaningful strides in our Alector Brain Carrier platform, which is our proprietary blood brain barrier technology. We intend to leverage this platform technology selectively across our portfolio to increase exposure to the central nervous system by enhancing transport across the blood brain barrier. Moreover, we remain committed to the development of our early programs with additional targets in Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease, which could position us to further expand our portfolio of transformative investigational therapies and achieve our ambitious vision of making brain disorders history."

Cash Runway Extension Through 2026

With $620.0 million in cash, cash equivalents and investments pro forma for the January 2024 equity offering, Alector has extended its cash runway through 2026, approximately a full year beyond the expected data readout for the pivotal Phase 3 INFRONT-3 clinical trial of latozinemab in participants with frontotemporal dementia due to a mutation in the progranulin gene (FTD-GRN). The extended cash runway also allows the company to selectively accelerate investment in its novel, first-in-class proprietary portfolio.

Recent Clinical Updates

Immuno-Neurology Portfolio

Progranulin Programs (AL101/GSK4527226 and latozinemab (AL001)) Being Developed in Collaboration with GSK

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In February 2024, GSK dosed the first participant in the PROGRESS-AD global Phase 2 clinical trial of AL101/GSK4527226 in early Alzheimer’s disease (AD), including mild cognitive impairment and mild dementia due to AD. AL101 is an investigational human monoclonal antibody (mAb) designed to block and downregulate the sortilin receptor to elevate the level of progranulin (PGRN) in the brain in a manner that is similar to latozinemab but with different pharmacokinetic (PK) and pharmacodynamic (PD) properties. Alector and GSK are co-developing AL101 for the potential treatment of more prevalent neurodegenerative diseases, including AD and Parkinson’s disease.
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In August 2023, GSK received U.S. Food and Drug Administration (FDA) clearance of its Investigational New Drug (IND) application for AL101 in the treatment of early AD. Modest reduction in the levels of PGRN due to genetic mutations has been shown to be associated with an increased risk of developing AD. Conversely, an elevation of PGRN has been shown to be protective in animal models of AD.

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In February 2024, the FDA granted Breakthrough Therapy Designation to latozinemab for the treatment of FTD-GRN. The FDA’s Breakthrough Therapy Designation is granted to expedite the development and review of drugs in the United States that are intended to treat a serious condition when preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available therapy on clinically significant endpoint(s).1

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In October 2023, Alector achieved target enrollment of 103 symptomatic and 16 at-risk participants with FTD-GRN in the pivotal, randomized, double-blind, placebo-controlled INFRONT-3 Phase 3 clinical trial of latozinemab for a treatment duration of 96 weeks. Target enrollment was supported by feedback from the FDA and European Medicines Agency.

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In November 2023, Alector published a manuscript in the International Journal of Molecular Sciences titled, "Targeting Progranulin as an Immuno-Neurology Therapeutic Approach." The publication discusses immuno-neurology as an emerging therapeutic strategy for dementia and neurodegeneration designed to address immune surveillance failure in the brain. Immuno-neurology is a promising alternative and potentially complementary approach to current neurodegenerative therapies that focus on removing singular types of misfolded proteins from the central nervous system.

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In February 2024, Alector published a manuscript in Alzheimer’s & Dementia: Translational Research & Clinical Interventions (TRCI) titled, "Phase 1 study of latozinemab in progranulin-associated frontotemporal dementia." The publication outlines Phase 1b clinical trial results, demonstrating that latozinemab was well tolerated, and a favorable PK/PD profile was observed in eight symptomatic participants with FTD-GRN. Additionally, multiple-dose administration of latozinemab increased plasma and cerebrospinal fluid (CSF) PGRN levels in participants with FTD-GRN to levels approximating those seen in healthy volunteers.

TREM2 Program (AL002) Being Developed in Collaboration with AbbVie

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In September 2023, Alector completed enrollment of 381 participants in the randomized, double-blind, placebo-controlled, dose-ranging, INVOKE-2 Phase 2 clinical trial. To date, more than 90 percent of eligible participants who completed the planned treatment period of INVOKE-2 have rolled over into the long-term extension portion of the trial. INVOKE-2 is designed to evaluate the efficacy and safety of AL002 in slowing disease progression in individuals with early AD. AL002 is a novel investigational humanized mAb that binds to TREM2 to increase TREM2 signaling and, thereby, is hypothesized to improve the functionality of microglia. It is the most advanced TREM2 activating product candidate in clinical development worldwide. Data from the trial is anticipated in the fourth quarter of 2024.

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INVOKE-2 utilizes a common close design with up to 96 weeks of randomized treatment, and all participants remain on their assigned regimen until the last participant completes 48 weeks of treatment. This design provides the opportunity to capture more observations for the primary analysis. The primary endpoint is disease progression as measured by the Clinical Dementia Rating Sum of Boxes (CDR-SB). The CDR-SB, which is used to assess (score) the severity of AD, is a validated instrument that assesses both cognitive and functional domains and is the FDA-accepted efficacy endpoint. The trial also employs multiple other clinical and functional outcome assessments, including CSF and plasma biomarkers, brain magnetic resonance imaging (MRI) and amyloid beta and tau positron emission tomography (PET) imaging to assess treatment effects on microglial signaling and Alzheimer’s pathophysiology.

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In July 2023, Alector presented an update on INVOKE-2 at the Alzheimer’s Association International Conference (AAIC). The presentation highlighted that treatment-emergent MRI findings resembling amyloid-related imaging abnormalities (ARIA) in INVOKE-2 are similar to the ARIA reported following treatment with anti-amyloid beta antibodies.
o
Alector previously presented results from a Phase 1 trial of AL002 in healthy volunteers, which demonstrated both dose-dependent target engagement and activation of microglia. In the trial, AL002 was also shown to be well tolerated.
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Microglial activation is hypothesized to not only enhance clearance of misfolded proteins that accumulate and form amyloid plaques but also perform other supportive microglia functions, including maintenance of neuronal and synaptic health.

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Alector received a $17.8 million milestone payment from AbbVie in March 2023 after enrolling and dosing the first participants in a long-term extension (LTE) of the INVOKE-2 Phase 2 clinical trial in participants with early AD. Additionally, in 2023, Alector received payments totaling $12.5 million from AbbVie to support enrollment in the INVOKE-2 trial.

Early Research Pipeline

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Alector continues to develop its Alector Brain Carrier (ABC), a proprietary, versatile blood-brain barrier technology, which is being applied to selectively enhance its next-generation product candidates.
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The company is strategically advancing its innovative research portfolio, including the development of ADP027-ABC. The ADP027-ABC program incorporates ABC technology to enhance brain penetrance and targets modulation of the glycoprotein GPNMB for the treatment of Parkinson’s disease.

Corporate

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In December 2023, Alector hosted two virtual research and development events discussing the company’s TREM2 and PGRN programs in detail. The events included presentations from leading scientific and clinical experts who provided their perspectives on the biological and genetic rationale for the TREM2 and PGRN targets, shared an overview of the current FTD and AD treatment landscapes, and discussed the significant unmet need that remains in the treatment of these neurodegenerative diseases.

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In the second quarter of 2023, the U.S. Patent and Trademark Office issued a patent covering methods of treatment using AL002. The European Patent Office also issued a patent in the second quarter of 2023 covering AL002 compositions and methods of use.

Fourth Quarter 2023 Financial Results

Revenue. Collaboration revenue for the quarter ended December 31, 2023, was $15.2 million, compared to $14.4 million for the same period in 2022. Collaboration revenue for the year ended December 31, 2023, was $97.1 million, compared to $133.6 million for the same period in 2022. The decrease in year-over-year collaborative revenue was primarily due to revenue recognized from the termination of the AL003 program in 2022, offset by higher revenue recognized for the AL101 programs, including a non-cash revenue adjustment due to contract modification to have GSK operationalize the AL101 Phase 2 study and higher revenue recognized for the AL002 program due to the addition of AL002 LTE and patient replacement revenue in 2023.

R&D Expenses. Total research and development expenses for the quarter ended December 31, 2023, were $47.7 million, compared to $54.5 million for the quarter ended December 31, 2022. Total research and development expenses for the year ended December 31, 2023, were $192.1 million compared to $210.4 million for the same period in 2022. The decrease in year-over-year R&D expenses was mainly driven by the Company’s strategy to prioritize late-stage programs.

G&A Expenses. Total general and administrative expenses for the quarter ended December 31, 2023, were $14.9 million, compared to $15.4 million for the quarter ended December 31, 2022. Total general and administrative expenses for the year ended December 31, 2023, were $56.7 million compared to $61.0 million for the year ended December 31, 2022. The decrease in year-over-year G&A expenses is primarily due to the decrease in consulting expenses related to accounting, recruiting, IT, and other general expenses, plus a decrease in insurance costs.

Net Loss. For the quarter ended December 31, 2023, Alector reported a net loss of $41.4 million, or $0.49 per share, compared to a net loss of $52.4 million, or $0.63 net loss per share, for the same period in 2022. For the year ended December 31, 2023, Alector reported a net loss of $130.4 million or $1.56 net loss per share, compared to a net loss of $133.3 million or $1.62 net loss per share, for the same period in 2022.

Cash Position. Cash, cash equivalents, and investments were $548.9 million as of December 31, 2023. In January 2024, Alector further strengthened its balance sheet with the completion of a follow-on financing issuing 10,869,566 shares of its common stock for total gross proceeds of $75 million before deducting underwriting discounts and commissions and estimated offering expenses. Management expects that this will be sufficient to fund current operations through 2026.

2024 Guidance. Management anticipates, for the year ending 2024, collaboration revenue to be between $60 million and $70 million, total research and development expenses to be between $210 million and $230 million, and total general and administrative expenses to be between $60 million and $70 million.

Fourth Quarter and Full Year 2023 Conference Call

Alector’s management team will host a conference call discussing Alector’s results for the fourth quarter and full year 2023 and provide a business update. The conference call will be webcast and accessible via the investor relations section of Alector’s website at www.alector.com.

To access the call, please use the following information:

Date: Tuesday, February 27, 2024

Time: 4:30 p.m. ET, 1:30 p.m. PT

The event will be webcast live under the investor relations section of Alector’s website at View Source and following the event a replay will be archived there for 30 days. Interested parties participating by phone will need to register using this online form. After registering for dial-in details, all phone participants will receive an auto-generated e-mail containing a link to the dial-in number along with a personal PIN number to use to access the event by phone.

On February 27, 2024 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company redefining the treatment of solid tumor cancers with cell therapy, reported the reappointment of Cintia Piccina as Chief Commercial Officer effective March 18, 2024 (Press release, Adaptimmune, FEB 27, 2024, View Source [SID1234640504]). Cintia served in this role from January 2022 to March 2023. Cintia will lead a rapidly expanding commercial team as it prepares for the launch of afami-cel for the treatment of advanced synovial sarcoma which, on approval, will be the first engineered TCR T-cell therapy on the market targeting solid tumors.

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Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer: "It is my pleasure and the Company’s great fortune to welcome back Cintia and her wealth of cell therapy commercial expertise. With a priority review and an August 4, 2024 PDUFA date set for afami-cel, we have the opportunity to leverage Cintia’s established track record and her familiarity with Adaptimmune, our products, and the company culture. Cintia was instrumental in designing and steering our commercial model design and her leadership will be critical as we continue launch planning and execution for the late-stage products in our sarcoma franchise."

Cintia Piccina, Adaptimmune’s incoming Chief Commercial Officer: "I am thrilled to have the opportunity to return to Adaptimmune as we prepare for the launch and commercialization of afami-cel. I look forward to joining this incredible team again as we aim to deliver important and much-needed new treatment options for people diagnosed with advanced cancers."

Most recently, Cintia served as Chief Commercial Officer at AlloVir (NASDAQ: ALVR) helping to build the company’s commercialization capabilities and team to support the launch of the first allogeneic multi-Viral Specific T-cell (VST) therapy, AlloVir’s anticipated first commercial product. Prior to her time at Adaptimmune, Cintia served as SVP Commercial Oncology and US General Manager at Bluebird Bio (NASDAQ: BLBD)/2seventy Bio (NASDAQ: TSVT), leading the launch of the first cell therapy product in multiple myeloma, Abecma (idecabtagene vicleucel). Before that, she spent more than 20 years at Novartis (SIX:NOVN; NYSE:NVS) from 1997 to April 2020, first in Brazil then in the United States, where she held a series of commercial, marketing, and sales roles across multiple therapeutic areas including oncology. In her final role at Novartis, Cintia was VP, Global Oncology Cell and Gene Strategy & Program Management Office, for Kymriah and the CAR-T pipeline, leading the cross-functional leadership teams for business (marketing, medical affairs, market access), manufacturing, and pipeline. Cintia holds a Doctorate in Pharmacy and Biochemistry from the University of Sao Paulo, Brazil, and an MBA from the Escola Superior de Propaganda e Marketing, Sao Paulo.

On January 31, 2024, Adaptimmune announced that the U.S. Food and Drug Administration (FDA) had accepted for priority review its Biologics License Application (BLA) for afami-cel, an investigational engineered T-cell therapy for advanced synovial sarcoma. The application has a PDUFA target action date of August 4, 2024.

About Afami-cel

Afami-cel is an engineered T-cell receptor (TCR) T-cell therapy, targeted to the MAGE A4 cancer target, and designed as a single-dose treatment for advanced synovial sarcoma. The last FDA approved therapy for treatment in this setting was for Votrient in 2012. The BLA submission for afami-cel was supported by clinical data from the SPEARHEAD-1 pivotal trial, which has met its primary endpoint for efficacy. ~39% of patients who received afami-cel had clinical responses with a median duration of response of ~12 months (CTOS 2022). Median overall survival (mOS) was ~17 months in SPEARHEAD-1 compared to historical mOS of <12 months for people with synovial sarcoma who received two or more prior lines of therapy. Seventy percent of people with advanced synovial sarcoma who respond to afami-cel are alive two years post-treatment.

On February 27, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported its participation in the Leerink Partners Global Biopharma Conference 2024, taking place March 11-13 in Miami, Florida (Press release, Adagene, FEB 27, 2024, View Source [SID1234640503]).

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Adagene’s Chairman, Chief Executive Officer and President of R&D, Peter Luo, Ph.D., will provide an update on its masked, anti-CTLA-4 SAFEbody ADG126, including key milestones for 2024. Company management will also host investor meetings.

Leerink Partners Global Biopharma Conference 2024

Date:
Tuesday, March 12
Presentation Time:
1:40 PM (Eastern Time)
Location:
The Fontainebleau Miami
A live webcast of the presentation will also be accessible in the Investors section of the company’s website at View Source A webcast replay will be available for at least 30 days.

On February 27, 2024 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the fourth quarter and full year of 2023 and provided a corporate update (Press release, Aclaris Therapeutics, FEB 27, 2024, View Source [SID1234640502]).

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"As we enter 2024, we are financially strong, focused and motivated," stated Dr. Neal Walker, co-founder and Interim Chief Executive Officer & President of Aclaris. "Returning to the CEO role, I look forward to building on our strong foundation and deep expertise in kinase discovery and development as we look to shape the future of Aclaris."

Research and Development Highlights:

ATI-1777, an investigational topical "soft" JAK 1/3 inhibitor
In January 2024, Aclaris reported positive top-line results from its Phase 2b trial in atopic dermatitis, and is currently seeking a development and commercialization partner for this program.
ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor
Aclaris is assessing the most effective development pathway, including the lead indication, for ATI-2138. Aclaris reported positive results from its Phase 1 MAD trial of ATI-2138 in September 2023.
Zunsemetinib (ATI-450), an investigational oral small molecule MK2 inhibitor
Aclaris plans to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib as a potential treatment for pancreatic cancer and metastatic breast cancer. Aclaris expects these trials to be primarily funded by grants awarded to Washington University.
ATI-2231, Aclaris’ second MK2 inhibitor, was previously being developed for oncology and Aclaris was supporting Washington University in an investigator-initiated Phase 1a trial of ATI-2231 in patients with advanced solid tumor malignancies. However, Aclaris and Washington University agreed to instead study zunsemetinib in oncology in order to expedite the development timeline by eliminating the need to conduct the Phase 1a trial due to zunsemetinib’s more advanced clinical package.

Discovery

Aclaris plans to continue to advance discovery programs through KINect, its proprietary drug discovery platform.
Financial Highlights:

Liquidity and Capital Resources

As of December 31, 2023, Aclaris had aggregate cash, cash equivalents and marketable securities of $181.9 million compared to $229.8 million as of December 31, 2022.

Financial Results

Fourth Quarter 2023

Net loss was $1.5 million for the fourth quarter of 2023 compared to $27.6 million for the fourth quarter of 2022.

Total revenue was $17.6 million for the fourth quarter of 2023 compared to $7.8 million for the fourth quarter of 2022. The increase was primarily driven by a one-time upfront payment under the license agreement with Sun Pharmaceutical Industries, Inc. (Sun Pharma) received in the fourth quarter of 2023.

Research and development (R&D) expenses were $26.6 million for the quarter ended December 31, 2023 compared to $21.1 million for the prior year period. The $5.5 million increase was primarily the result of an increase in expenses associated with drug candidate manufacturing for zunsemetinib.

General and administrative (G&A) expenses were $8.2 million for the quarter ended December 31, 2023 compared to $7.1 million for the corresponding prior year period. The increase was primarily due to an increase in personnel and stock-based compensation expenses.

Licensing expenses were $5.7 million for the quarter ended December 31, 2023 compared to $0.6 million for the prior year period. The increase was primarily attributable to amounts payable to third parties in connection with amounts earned under the Sun Pharma license agreement.

Revaluation of contingent consideration resulted in a $26.3 million gain for the quarter ended December 31, 2023 compared to a charge of $7.1 million for the prior year period.

Intangible asset impairment charges were $6.6 million for the quarter ended December 31, 2023, representing the full balance of the in-process research and development (IPR&D) intangible asset. The impairment charge resulted from Aclaris’ decision to discontinue further development of the drug candidate for immuno-inflammatory diseases.
Full Year 2023

Net loss was $88.5 million for the year ended December 31, 2023 compared to $86.9 million for the year ended December 31, 2022.

Total revenue was $31.2 million for the year ended December 31, 2023 compared to $29.8 million for the year ended December 31, 2022. The increase was primarily driven by a one-time upfront payment under the license agreement with Sun Pharma received in the year ended December 31, 2023. The increase was partially offset by both a one-time upfront payment received under a license agreement with Eli Lilly and Company and a one-time upfront payment received under a license agreement with Pediatrix Therapeutics, Inc. in the year ended December 31, 2022.

R&D expenses were $98.4 million for the year ended December 31, 2023 compared to $77.8 million for the prior year period.

The $20.6 million increase was primarily the result of higher:
Zunsemetinib development expenses, including costs associated with clinical activities for the Phase 2b trial for rheumatoid arthritis and drug candidate manufacturing costs;
ATI-2138 development expenses, including costs associated with the Phase 1 MAD trial and other preclinical activities; and
Compensation-related expenses due to an increase in headcount.

G&A expenses were $32.4 million for the year ended December 31, 2023 compared to $25.1 million for the prior year period.

The $7.3 million increase was primarily the result of higher compensation-related costs due to increased headcount and the impact of equity awards granted during the year ended December 31, 2023.
Bad debt expense recorded from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection also contributed to the increase.

Revaluation of contingent consideration resulted in a $26.9 million gain for the year ended December 31, 2023 compared to a charge of $4.7 million for the corresponding prior year period.

Intangible asset impairment charges were $6.6 million for the year ended December 31, 2023, representing the full balance of the IPR&D intangible asset. The impairment charge resulted from Aclaris’ decision to discontinue further development of the drug candidate for immuno-inflammatory diseases.