On November 7, 2023 Ascendis Pharma A/S (Nasdaq: ASND) reported financial results for the third quarter ended September 30, 2023 and provided business updates (Press release, Ascendis Pharma, NOV 7, 2023, View Source [SID1234637119]).

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"This quarter marks an important milestone for Ascendis on our path to become a leading, sustainable biopharma company, where we began our journey to extend our SKYTROFA U.S. market value leadership globally with our first EU product launch in Germany," said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer. "Expected approval in the EU for our second product, TransCon PTH, this month demonstrates the value of following our algorithm for product innovation."

Corporate Highlights

TransCon hGH (marketed in the U.S. and EU as SKYTROFA):
Third quarter 2023 SKYTROFA revenue totaled €47.0 million, a 31% sequential increase. Increased full year 2023 SKYTROFA revenue expectations from €165 – €170 million to €170 – €175 million.

Q3-2022 Q4-2022 Q1-2023 Q2-2023 Q3-2023
SKYTROFA revenue (millions) €12.3 €17.1 €31.6 €35.9 €47.0

Announced results from enliGHten, the Company’s open-label extension trial evaluating the long-term safety and efficacy of TransCon hGH for children and adolescents with growth hormone deficiency (GHD), demonstrating the long-term safety and efficacy of TransCon hGH in patients treated up to six years, with the majority of children meeting or exceeding average parental height SDS at time of treatment completion or last visit.
Topline results from Phase 3 foresiGHt Trial in adult growth hormone deficiency expected in the fourth quarter of 2023, potentially opening a new label expansion opportunity.
TransCon PTH:
On September 14, 2023, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the approval of TransCon PTH (palopegteriparatide) as a parathyroid hormone replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. Final European Commission decision is expected this month. If approved, the first launch is planned in Germany, leveraging the Company’s existing SKYTROFA commercial infrastructure, in January 2024.
In the U.S., expect to resubmit NDA for TransCon PTH for adults with hypoparathyroidism to the FDA before mid-November.
Presented 52-week data from Phase 3 PaTHway Trial demonstrating that skeletal dynamics of patients with chronic hypoparathyroidism trended toward a new steady state closer to age-appropriate norms with continued use of TransCon PTH. Results confirm trends previously reported in the Phase 2 PaTH Forward Trial.
As of September 30, 2023, 145 out of 154 participants continue in the open-label extension (OLE) portions of the Phase 2 PaTH Forward, Phase 3 PaTHway, and PaTHway Japan trials.
TransCon CNP:
Completed enrollment in ApproaCH, a Phase 3, global randomized, double-blind, placebo-controlled trial in children ages 2–11 years with achondroplasia. Topline results are expected in the second half of 2024.
Filed an Investigational New Drug (IND) amendment with the FDA to initiate reACHin, a Phase 2, multicenter, double-blind, randomized, placebo-controlled trial, designed to evaluate the safety, tolerability, and efficacy of 100 μg/kg of TransCon CNP once-weekly for 52 weeks in infants aged 0 to < 2 years with achondroplasia.
One-year follow-up data from AComplisH OLE expected in the fourth quarter of 2023.
During the fourth quarter of 2023, the Company expects to file an IND amendment or similar for COACH, a combination trial evaluating TransCon CNP and TransCon hGH in children with achondroplasia. The Company believes that this combination therapy may provide greater annualized height velocity than CNP alone, and at the same time, address the comorbidities of achondroplasia.
TransCon IL-2 β/γ:
Reported new data from ongoing Phase 1/2 IL-Believe Trial demonstrating clinical activity of TransCon IL-2 β/γ as monotherapy or in combination with a checkpoint inhibitor. Of three small-cell lung cancer patients treated in the combination portion of the trial who had previously progressed on checkpoint inhibitors, a partial response (confirmed) and a complete response (unconfirmed, treatment ongoing) were observed to date.
Enrollment continues in the Phase 2 portion in indication-specific cohorts; first patient dosed with TransCon IL-2 β/γ and TransCon TLR7/8 Agonist in combination. Initial data from indication-specific cohorts expected in the second half of 2024.
TransCon TLR7/8 Agonist:
Enrollment continues in Phase 2 portion of transcendIT-101, a Phase 1/2 trial to evaluate TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab in dose escalation and dose expansion. Initial data expected in the second half of 2024.
Ended the third quarter of 2023 with cash, cash equivalents, and marketable securities totaling €455.4 million.
Third Quarter 2023 Financial Results
Total revenue for the third quarter of 2023 was €48.0 million compared to €15.3 million during the same period in 2022. The increase was primarily attributable to higher SKYTROFA revenue of €47.0 million compared to €12.3 million in the same period last year.

Research and development (R&D) costs for the third quarter were €111.4 million compared to €97.4 million during the same period in 2022. This increase was primarily due to higher development costs for the Oncology and Ophthalmology programs, increasing clinical trial activities for TransCon CNP, and higher employee-related costs, and was partly offset by lower development costs for TransCon hGH.

Selling, general, and administrative (SG&A) expenses for the third quarter were €63.6 million compared to €60.7 million during the same period in 2022. This increase was primarily due to higher employee related expenses and other expenses attributable to organizational growth.

Net finance expenses were €20.4 million in the third quarter compared to €20.9 million in the same period in 2022.

For the third quarter of 2023, Ascendis Pharma reported a net loss of €162.2 million, or €2.88 per share (basic and diluted) compared to a net loss of €169.0 million, or €3.03 per share (basic and diluted) for the same period in 2022.

As of September 30, 2023, Ascendis Pharma had cash, cash equivalents, and marketable securities totaling €455.4 million compared to €742.9 million as of December 31, 2022. As of September 30, 2023, Ascendis Pharma had 57,656,568 ordinary shares outstanding.

Conference Call and Webcast Information
Ascendis Pharma will host a conference call and webcast today at 4:30 pm Eastern Time (ET) to discuss its third quarter 2023 financial results.

To participate in the call, please dial (800) 445-7795 (domestic) or +1 (785) 424-1699 (international), and reference passcode ASNDQ323. The link to the live webcast will also be available on the Investors & News section of the Ascendis Pharma website at View Source A replay of the webcast will be available on this section of our website shortly after conclusion of the event for 30 days.

On November 7, 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 third quarter ended September 30, 2023 and provided a corporate update (Press release, Arvinas, NOV 7, 2023, View Source [SID1234637118]).

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"We continued making strong progress in the third quarter of 2023 as we executed across our entire portfolio of PROTAC protein degraders," said John Houston, Ph.D., chairperson, chief executive officer, and president at Arvinas. "We remain focused on developing best-in-class medicines and are very pleased with the progress of our ER and AR degraders, both of which have the potential to make meaningful differences for patients. In the second half of next year, we anticipate completion of our first Phase 3 trial with our novel PROTAC ER degrader, vepdegestrant, in a second-line metastatic breast cancer setting, which we are jointly developing with Pfizer. Additionally, the profile of our PROTAC AR degrader, ARV-766, gives us the confidence to initiate a Phase 3 trial in metastatic castration resistant prostate cancer as soon as possible. We are also preparing to move two new compounds – our LRRK2 and BCL6 PROTAC protein degraders – into the clinic in 2024, with two more PROTAC protein degraders in IND-enabling studies by the end of 2023. We have a lot of milestones to deliver on in 2024 and I look forward to Arvinas’ continued success, with the ultimate, and most important goal of improving the lives of patients with serious diseases."

Recent Developments and Third Quarter Business Highlights

Androgen Receptor Franchise

Presented data from the Phase 1/2 clinical trial with bavdegalutamide at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) 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).
Prioritized the initiation of a Phase 3 trial with ARV-766 in mCRPC instead of the previously planned Phase 3 trial for bavdegalutamide.
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.
Vepdegestrant (ARV-471)

Presented updated dose-escalation data from the Phase 1/2 trial with vepdegestrant at ESMO (Free ESMO Whitepaper) showing continued strong anti-tumor activity and highly differentiated tolerability.
Continued enrollment in 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 (ClinicalTrials.gov Identifier: NCT05909397).
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 trial evaluating vepdegestrant with targeted therapies [ClinicalTrials.gov Identifiers: NCT05548127 and NCT05573555]).
Continued enrollment in the TACTIVE-E trial of vepdegestrant in combination with everolimus (ClinicalTrials.gov Identifier: NCT05501769), and the TACTIVE-N trial of vepdegestrant as a monotherapy in the neoadjuvant setting (ClinicalTrials.gov Identifier: NCT05549505).
Received Study May Proceed letter from the U.S. FDA for the Phase 1b/2 clinical trial evaluating vepdegestrant in combination with Pfizer’s CDK4 inhibitor (PF-07220060).
Awarded Innovation Passport Designation for vepdegestrant by the U.K. Innovative Licensing and Access Pathway Steering Group.
Anticipated Upcoming Milestones and Expectations

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

Present updated data for vepdegestrant at the San Antonio Breast Cancer Symposium, including new data from the Phase 1b trial assessing vepdegestrant in combination with palbociclib (December 2023).
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.
Initiate a Phase 1b/2 trial with vepdegestrant plus Pfizer’s CDK4 (cyclin dependent kinase) inhibitor (4Q 2023).
Continue enrollment of the Phase 1b combination umbrella trial evaluating combination of vepdegestrant with abemaciclib and with ribociclib (TACTIVE-U: ClinicalTrials.gov Identifiers: NCTC05548127 and NCTC05573555); initiate additional arm with Carrick Therapeutics’ CDK7 inhibitor.
Complete enrollment in the TACTIVE-N Phase 2 trial of vepdegestrant as a monotherapy in the neoadjuvant setting (ClinicalTrials.gov Identifier: NCT05549505) in patients with ER+/HER2- localized breast cancer (2024).
Complete enrollment of the VERITAC-2 Phase 3 monotherapy trial (ClinicalTrials.gov Identifier: NCT05654623) in patients with metastatic breast cancer (2H 2024).
Androgen Receptor (AR) Franchise (ARV-766/bavdegalutamide (ARV-110))

Continue enrollment of Phase 2 dose expansion study with ARV-766, with progression free survival data anticipated in 2024.
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 (4Q 2023).
Initiate discussions with regulatory authorities for a planned Phase 3 trial with ARV-766 in mCRPC (2Q 2024).
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 September 30, 2023, is sufficient to fund planned operating expenses and capital expenditure requirements into 2026.

Third Quarter Financial Results

Cash, Cash Equivalents and Marketable Securities Position: As of September 30, 2023, cash, cash equivalents, restricted cash and marketable securities were $1,004.0 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 $206.8 million for the nine months ended September 30, 2023 was primarily related to cash used in operations of $253.0 million (net of $2.5 million received from two collaborators), leasehold improvements of $2.8 million and loss on the sale of marketable securities of $0.9 million, partially offset by net proceeds from the issuance of common stock under our ATM offering of $36.0 million, unrealized gains on marketable securities of $10.0 million and proceeds from the exercise of stock options of $3.9 million.

Research and Development Expenses: Research and development expenses were $85.9 million for the quarter ended September 30, 2023, as compared with $77.5 million for the quarter ended September 30, 2022. The increase in research and development expenses of $8.4 million for the quarter was primarily due to increases our AR program of $5.2 million, which includes ARV-766 and bavdegalutamide, and our ER program of $6.2 million, which is net of the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement, offset by a decrease in our platform and exploratory programs of $3.0 million.

General and Administrative Expenses: General and administrative expenses were $22.6 million for the quarter ended September 30, 2023, as compared with $20.0 million for the quarter ended September 30, 2022. The increase of $2.6 million was primarily due to increased investments in our commercial operations of $1.0 million, an increase in personnel and infrastructure related costs of $1.1 million, and an increase in professional fees of $0.5 million.

Revenues: Revenues were $34.6 million for the quarter ended September 30, 2023, as compared with $33.2 million for the quarter ended September 30, 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 which was initiated in July 2019. The increase in revenues of $1.4 million was primarily due to an increase in revenue from the Vepdegestrant (ARV-471) Collaboration Agreement totaling $6.4 million, partially offset by a decrease in revenue of $2.8 million of previously constrained deferred revenue related to our Oerth Bio joint venture and a decrease of $1.8 million related to the conclusion of the performance period under the collaboration agreement with Genentech.

Income Tax Expense: Income tax was zero for the quarter ended September 30, 2023, as compared with an income tax expense of $2.2 million for the quarter ended September 30, 2022. Current year income tax expense was driven by valuation allowance recorded against the full amount of its net deferred tax assets. Prior year income 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 $0.1 million for the quarter ended September 30, 2023, as compared with $2.9 million for the quarter ended September 30, 2022, due to fully recognizing the remaining Oerth Bio related constrained revenue, which limited the amount of equity method losses recognized during the quarter.

Net Loss: Net loss was $64.0 million for the quarter ended September 30, 2023, as compared with $66.2 million for the quarter ended September 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 and loss from equity method investments, partly offset by increased research and development expenses and general and administrative expenses.

About ARV-766 and bavdegalutamide (ARV-110)
ARV-766 and bavdegalutamide (ARV-110) are investigational orally bioavailable PROTAC protein degraders designed to selectively target and degrade the androgen receptor (AR). ARV-766 and bavdegalutamide 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 ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.
In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced robust 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. Ongoing and planned clinical trials will continue to monitor and evaluate the safety and anti-tumor activity of vepdegestrant.

On November 7, 2023 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported financial results for the third quarter ended September 30, 2023, and provided a pipeline update on its clinical-stage investigational molecules – targeting TIGIT, the adenosine axis (CD73 and A2a/A2b receptors), HIF-2a and PD-1 – across multiple common cancers (Press release, Arcus Biosciences, NOV 7, 2023, View Source [SID1234637117]).

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"As we continue to execute on our Phase 3 trials for domvanalimab in lung and GI cancers, we have one of three important near-term data readouts now behind us. Today’s presentation of data from our Phase 2 EDGE-Gastric study provided important evidence to support domvanalimab’s potential as a differentiated and first-to-market anti-TIGIT antibody for the treatment of first-line upper GI adenocarcinomas. We are also looking forward to sharing more on our HIF-2a inhibitor, AB521, which continues to show a potentially improved clinical profile, with PK/PD results in patients consistent with those seen in healthy volunteers," said Terry Rosen, Ph.D., chief executive officer of Arcus. "Lastly, we will be presenting mature OS data from our Phase 1/1b study of quemliclustat in pancreatic cancer early next year; we are excited to share next steps in the coming months."

Pipeline Highlights:

Domvanalimab (Fc-silent anti-TIGIT monoclonal antibody)
•Preliminary data from Arm A1 of the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic upper gastrointestinal (GI) cancers, were presented during the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series on November 7, 2023. These data were from the cohort that includes a patient population and dosing regimen similar to the ongoing Phase 3 study, STAR-221.
◦Domvanalimab plus zimberelimab and chemotherapy showed encouraging objective response rates (ORR) of 80% (confirmed ORR (cORR) of 73%) in patients with PD-L1-high tumors (TAP ≥5%), 46% (all confirmed) in patients with PD-L1-low tumors (TAP <5%) and 59% (cORR of 56%) for patients overall.
◦Six-month landmark progression-free survival (PFS) was 93% for patients with PD-L1-high tumors (TAP ≥5%), 68% for patients with PD-L1-low tumors (TAP <5%) and 77% for patients overall.
◦Mature PFS has not been reached and data are expected in the second half of 2024.
◦Domvanalimab plus zimberelimab and chemotherapy was well tolerated, with a similar safety profile to what has been reported for anti-PD-1 plus chemotherapy in this setting.

◦Domvanalimab is the only Fc-silent anti-TIGIT antibody in Phase 3 for gastric, gastroesophageal junction and esophageal adenocarcinoma and has the potential to be first to market for these cancers. These tumor types represent a potential drug-treatable population of over 25,000 in the US and over 100,000 in G-7 countries.
AB521 (HIF-2a inhibitor)

•Pharmacokinetic (PK) and pharmacodynamic (PD) data from the dose-escalation phase of ARC-20, a Phase 1/1b study of AB521 in cancer patients, are consistent with the results seen in healthy volunteers to date.
◦No dose-limiting toxicities have been observed to date in ARC-20.
◦Detailed PK, PD and safety data along with preliminary anti-tumor activity from this stage of ARC-20 will be shared in early 2024.
•Enrollment for the dose-expansion stage of ARC-20 in clear cell renal cell carcinoma (ccRCC) patients is near completion. Efficacy data from this stage of the ARC-20 study are expected later in 2024. The dose-expansion stage will include 30 patients on a 100-mg daily dose, which Arcus believes has the potential to achieve substantially greaterHIF-2a inhibition than the approved dose of the marketed competitor.
•A Phase 2 study evaluating AB521 in combination with a tyrosine kinase inhibitor (TKI) is anticipated to begin in the fourth quarter of 2023.
Quemliclustat (small-molecule CD73 inhibitor)
•Arcus conducted an analysis of mature OS data (minimum follow-up of 18 months) from the ongoing Phase 1/1b ARC-8 trial evaluating quemliclustat plus chemotherapy with or without zimberelimab in first-line pancreatic cancer.
◦At this analysis, 122 patients in the study had received the go-forward dose of 100 mg of quemliclustat; median follow-up time was 21 months.
◦These data will be presented in early 2024.
Etrumadenant (A2a/A2b adenosine receptor antagonist)
•Data from ARC-9, a Phase 1b/2 study evaluating etrumadenant plus zimberelimab plus chemotherapy in second-line and third-line metastatic colorectal cancer (mCRC), which is fully enrolled, are expected in the first half of 2024.
Early Clinical and Preclinical Programs
•ARC-25, a Phase 1 trial in cancer patients for AB598, an anti-CD39 antibody, is currently enrolling.
•Arcus initiated a Phase 1 study in healthy volunteers of AB801, its potent and highly selective AXL inhibitor, and expects to initiate a Phase 1 study in advanced cancer patients in the first quarter of 2024.
•Arcus expects to select a new development candidate against KIT, a target involved in multiple allergic and immune-mediated diseases, by year end.
Financial Results for Third Quarter 2023:
•Cash, Cash Equivalents and Marketable Securities were $950 million as of September 30, 2023, compared to $1.1 billion as of December 31, 2022. The decrease during the period is primarily due to the use of cash in research and development activities, partially offset by receipts of $35 million in upfront payments from Gilead to initiate Arcus-led discovery and early development activities on two jointly selected inflammation targets and $25 million in proceeds from the issuance of 1.2 million shares of our common stock. Arcus now expects cash utilization between $265 million and $290 million for the year ended December 31, 2023. Arcus continues to expect cash, cash equivalents and marketable securities on-hand to be sufficient to fund operations into 2026.
•Revenues were $32 million for the third quarter 2023, compared to $33 million for the same period in 2022. In the third quarter 2023, Arcus recognized $22 million in license and development service revenues related to the advancement of programs, primarily the Gilead collaboration, as well as $10 million in other collaboration revenue primarily related to Gilead’s ongoing rights to access Arcus’s research and development pipeline in accordance with the Gilead collaboration agreement. Revenues were $86 million for the nine months ended September 30, 2023, compared to $78 million for the same period in 2022.
•Research and Development (R&D) Expenses were $82 million for the third quarter 2023, compared to $77 million for the same period in 2022. The net increase of $5 million was primarily driven by: $7 million of higher spend for Arcus programs not under a cost-sharing collaboration due to our expanding clinical and development activities; partially offset by a net decrease of $2 million in shared costs for programs optioned by our collaboration partners, primarily from the Gilead collaboration. The net decrease of $2 million was due to a decrease in shared collaboration costs of $10 million primarily from the timing of clinical manufacturing; with a corresponding decrease in reimbursements for shared expenses of $8 million. Non-cash stock-based compensation expense was $8 million for each of the third quarter 2023 and 2022. R&D expenses were $247 million for the nine months ended September 30, 2023, compared to $208 million for the same period in 2022. For third quarter 2023 and 2022, Arcus recognized reimbursements of $33 million and $41 million, respectively, for shared expenses from its collaborations, primarily the Gilead collaboration. Reimbursements were $119 million for the nine months ended September 30, 2023, compared to $111 million for the same period in 2022. R&D expense by quarter may fluctuate due to the timing of clinical manufacturing and standard-of-care therapeutic purchases with a corresponding impact on reimbursements.
•General and Administrative (G&A) Expenses were $30 million for the third quarter 2023, compared to $26 million for the same period in 2022. The increase was primarily driven by the increased complexity of supporting Arcus’s expanding clinical pipeline and partnership obligations. Non-cash stock-based compensation expense was $10 million for the third quarter 2023, compared to $8 million for the same period in 2022. G&A expenses were $88 million for the nine months ended September 30, 2023, compared to $76 million for the same period in 2022.
•Net Loss was $71 million for the third quarter 2023, compared to $65 million for the same period in 2022. The increase in net loss included an increase of $2 million in income tax expense primarily due to an increase in taxable income compared to the prior year. Net loss was $226 million for the nine months ended September 30, 2023, compared to $200 million for the same period in 2022.

Arcus Ongoing and Announced Clinical Studies:
Trial Name Arms Setting Status NCT No.
Lung Cancer
ARC-7 zim vs. dom + zim vs. etruma + dom + zim 1L NSCLC (PD-L1 ≥ 50%) Ongoing Randomized Phase 2 NCT04262856
PACIFIC-8
(Operationalized by AZ)
dom + durva vs. durva Curative-Intent Stage 3 NSCLC Ongoing Registrational Phase 3 NCT05211895
ARC-10 dom + zim vs. pembro 1L NSCLC (PD-L1 ≥ 50%) Ongoing Registrational Phase 3 NCT04736173
STAR-121
(Operationalized by Gilead)
dom + zim + chemo vs. pembro + chemo 1L NSCLC (PD-L1 all-comers) Ongoing Registrational Phase 3 NCT05502237
EDGE-Lung dom +/- zim +/- quemli +/- chemo 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2 NCT05676931
VELOCITY-Lung
(Operationalized by Gilead)
dom +/- zim +/- etruma +/- sacituzumab govitecan-hziy or other combos 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2 NCT05633667
Gastrointestinal Cancers
ARC-9 etruma + zim + mFOLFOX vs. SOC 2L/3L/3L+ CRC
Ongoing
Randomized Phase 2
NCT04660812
EDGE-Gastric (ARC-21) dom +/- zim +/- quemli +/- chemo 1L/2L Upper GI Malignancies
Ongoing
Randomized Phase 2
NCT05329766
STAR-221 dom + zim + chemo vs. nivo + chemo 1L Gastric, Gastroesophageal Junction (GEJ) and Esophageal Adenocarcinoma (EAC) Ongoing Registrational Phase 3 NCT05568095
Pancreatic Cancer
ARC-8 quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac 1L, 2L PDAC Ongoing Randomized Phase 1/1b NCT04104672
Prostate Cancer
ARC-6 etruma + zim + SOC vs. SOC 2L/3L CRPC Ongoing Randomized Phase 2 NCT04381832
Renal Cancer
ARC-20 AB521 Cancer Patients / ccRCC Ongoing Phase 1/1b NCT05536141
Other
ARC-25 AB598 Advanced Malignancies Ongoing NCT05891171
ARC-26 AB801 Healthy Volunteers Ongoing NCT06004921
ARC-27 AB801 Advanced Malignancies Planned NCT06120075

dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; nivo: nivolumab; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab;
ccRCC: clear-cell renal cell carcinoma; CRC: colorectal cancer; CRPC: castrate-resistant prostate cancer; GI: gastrointestinal; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma.

On November 7, 2023 Arbutus Biopharma Corporation (Nasdaq: ABUS) ("Arbutus" or the "Company"), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a cure for people with chronic hepatitis B virus (cHBV) infection, reported third quarter 2023 financial results and provided a corporate update (Press release, Arbutus Biopharma, NOV 7, 2023, View Source [SID1234637116]).

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"We are looking forward to our upcoming data presentations at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting 2023, specifically the preliminary data from the Phase 2a clinical trial, AB-729-202, evaluating imdusiran, our RNAi therapeutic, in combination with VTP-300 and a nucleos(t)ide analogue in patients with chronic hepatitis B virus," said William Collier, President and Chief Executive Officer of Arbutus Biopharma. "These data have the potential to support our hypothesis that a functional cure for cHBV can be achieved by reducing surface antigen, suppressing HBV DNA and boosting the immune system. We continue to explore imdusiran as a cornerstone therapy as we dose patients in the additional treatment arm of the AB-729-202 trial that adds a low dose of nivolumab (Opdivo), an anti-PD-1 monoclonal antibody, to the triple combination, as well as continuing to dose and follow patients in the on-going AB-729-201 clinical trial combining imdusiran with short durations of Peg-IFNα-2a and ongoing NA therapy. In addition, we have dosed our first group of healthy subjects in our Phase 1a/1b clinical trial with AB-101 and are on-track to report data from the first part of this trial in the first half of 2024. We look forward to sharing additional updates on our progress in the coming months."

Mr. Collier, continued, "Following our recent pipeline optimization, we made the difficult decision to reduce our workforce as we continue to manage our operating expenses. I’d like to thank our departing employees for their dedication and valuable contributions towards our mission. The Company remains committed to continuing discovery research in chronic HBV."

Pipeline Updates and Key Milestones

Imdusiran (AB-729, RNAi Therapeutic)

Arbutus will be presenting preliminary data at AASLD from the first group of patients in its Phase 2a clinical trial (AB-729-202) that is evaluating imdusiran, nucleos(t)ide analogue (NA) therapy and Barinthus Bio’s (formerly Vaccitech plc) VTP-300, an HBV antigen-specific immunotherapy.

Enrollment is ongoing in the expanded cohort of the AB-729-202 clinical trial that is designed to enroll 20 patients who will receive imdusiran (60mg every 8 weeks) plus NA therapy for 24 weeks followed by VTP-300 plus up to two doses of low-dose nivolumab. Preliminary data from this additional treatment arm are expected in 2024.
Follow-up is continuing in the Company’s on-going Phase 2a clinical trial (AB-729-201), evaluating the safety, tolerability and antiviral activity of the combination of imdusiran and pegylated interferon alfa-2a (IFN) in patients with cHBV. Preliminary data presented at the EASL Congress in June 2023 suggest that the addition of IFN to imdusiran was generally well tolerated and appears to result in continued HBsAg declines in some patients. Arbutus plans to provide updates from this clinical trial in 2024.
AB-101 (Oral PD-L1 Inhibitor)

In September, the Company dosed the first subject in its Phase 1a/1b double-blind, randomized, placebo-controlled, clinical trial (AB-101-001) designed to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of AB-101 for up to 28 days in healthy subjects and patients with cHBV. The trial will be conducted in three parts starting with single ascending doses in healthy subjects, followed by multiple ascending doses in healthy subjects and culminating with multiple doses in patients with cHBV. Safety and PK/PD assessments will be performed prior to dose escalation in all trial parts. Initial data from part one of the trial are expected in the first half of 2024.
Corporate Updates

In connection with the Company’s decision in September to focus its pipeline on its HBV clinical stage compounds and discontinue its research programs, Arbutus has taken steps to streamline its organization and has reduced its workforce by 24%, effective November 6, 2023, primarily affecting its research function. As a result, Arbutus will incur a one-time restructuring charge of approximately $1.1 million that will be recorded in the fourth quarter of 2023.

With the organizational changes announced today and its ongoing cost management efforts, the Company now expects its current cash, cash equivalents and investments will be sufficient to fund its operations into the first quarter of 2026. The Company remains committed to continuing discovery research in chronic HBV.

In a separate press release issued today, Arbutus announced that William Collier will be retiring as President and CEO, as well as a member of the Company’s Board of Directors, at the end of 2023 and Michael J. McElhaugh, Arbutus Co-founder and COO, will serve as interim CEO and will join the Company’s Board of Directors.

The above corporate updates do not affect the Company’s pending litigations. Arbutus will continue to protect and defend its intellectual property, which is the subject of the on-going lawsuits against Moderna and Pfizer/BioNTech. The Company is seeking fair compensation for Moderna’s and Pfizer/BioNTech’s use of its patented LNP technology that was developed with great effort and at a great expense, without which Moderna and Pfizer/BioNTech’s COVID-19 vaccines would not have been successful. Document production is currently on-going in the lawsuit against Moderna with the claim construction hearing scheduled for February 7, 2024. Document and written discovery in the lawsuit against Pfizer/BioNTech is ongoing and a date for a claim construction hearing has not been set.

Financial Results

Cash, Cash Equivalents and Investments

As of September 30, 2023, we had cash, cash equivalents and investments in marketable securities of $144.7 million compared to $184.3 million as of December 31, 2022. During the nine months ended September 30, 2023, we used $68.6 million in operating activities, which was partially offset by $26.0 million of net proceeds from the issuance of common shares under our "at-the-market" offering program. We expect our 2023 net cash burn to range from between $90 to $95 million, excluding any proceeds received from our "at the market program". We believe our cash runway will be sufficient to fund our operations into the first quarter of 2026.

Revenue

Total revenue was $4.7 million for the three months ended September 30, 2023, compared to $6.0 million for the same period in 2022. The decrease of $1.3 million was due primarily to a decrease in royalty revenue because of a decrease in Alnylam’s sales of ONPATTRO.

Operating Expenses

Research and development expenses were $20.2 million for the three months ended September 30, 2023 compared to $20.1 million for the same period in 2022. A decrease in expenses for drug supply manufacturing for our imdusiran Phase 2a clinical trials and expenses for our AB-836 Phase 1a/1b clinical trial, which was discontinued in the fourth quarter of 2022, were offset by an increase in expenses for our ongoing AB-101 clinical trial and our coronavirus program, which was discontinued in the third quarter of 2023. General and administrative expenses were $5.8 million for the three months ended September 30, 2023, compared to $3.5 million for the same period in 2022. This increase was due primarily to increases in employee-related costs, including non-cash stock-based compensation expense, and professional fees.

Net Loss

For the three months ended September 30, 2023, our net loss was $20.1 million, or a loss of $0.12 per basic and diluted common share, as compared to a net loss of $17.6 million, or a loss of $0.12 per basic and diluted common share, for the three months ended September 30, 2022.

Outstanding Shares

As of September 30, 2023, we had approximately 167.7 million common shares issued and outstanding, as well as approximately 21.0 million stock options and unvested restricted stock units outstanding. Roivant Sciences Ltd. owned approximately 23% of our outstanding common shares as of September 30, 2023.

Conference Call and Webcast Today

Arbutus will hold a conference call and webcast today, Tuesday, November 7, 2023, at 8:45 AM Eastern Time to provide a corporate update. To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus’ website at www.arbutusbio.com.

An archived webcast will be available on the Arbutus website after the event.

About imdusiran (AB-729)

Imdusiran is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single and multiple doses of imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Imdusiran is currently in multiple Phase 2a clinical trials.

About AB-101

AB-101 is our oral PD-L1 inhibitor candidate that we believe will allow for controlled checkpoint blockade while minimizing the systemic safety issues typically seen with checkpoint antibody therapies. Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. Preclinical data generated thus far indicates that AB-101 mediates re-activation of exhausted HBV-specific T-cells from cHBV patients. We believe AB-101, when used in combination with other approved and investigational agents, could potentially lead to a functional cure in patients chronically infected with HBV. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. We have identified compounds in our internal PD-L1 portfolio that could also be used in oncology indications.

About HBV

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 290 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2.4 million people in the United States suffer from chronic HBV infection. Approximately 820,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.

On November 7, 2023, Applied DNA Sciences, Inc. (the "Company") reported to have entered into an Equity Distribution Agreement (the "Agreement") with Maxim Group LLC, as sales agent (the "Agent"), pursuant to which the Company may, from time to time, issue and sell shares of its common stock, par value $0.001 per share, in an aggregate offering price of up to $6,397,939 (the "Shares") through the Agent (Filing, 8-K, Applied DNA Sciences, NOV 7, 2023, View Source [SID1234637115]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The offer and sales of the Shares made pursuant to the Agreement, if any, will be made under the Company’s effective "shelf" registration statement on Form S-3 (File No. 333-272267) dated May 30, 2023, the base prospectus contained therein, and a prospectus supplement related to the offering of the Shares dated November 7, 2023.

Under the terms of the Agreement, the Agent may sell the Shares at market prices by any method that is deemed to be an "at the market offering" as defined in Rule 415 under the Securities Act of 1933, as amended.

Subject to the terms and conditions of the Agreement, the Agent will use its commercially reasonable efforts to sell the Shares from time to time, based upon the Company’s instructions. The Company has no obligation to sell any of the Shares, and may at any time suspend sales under the Agreement or terminate the Agreement in accordance with its terms. The Company has provided the Agent with customary indemnification rights, and the Agent will be entitled to a fixed commission of 3.0% of the aggregate gross proceeds from the Shares sold. The Agreement contains customary representations and warranties, and the Company is required to deliver customary closing documents and certificates in connection with sales of the Shares. The Company has agreed to reimburse the Agent for the fees and disbursements of its counsel, payable upon execution of the Agreement, in an amount not to exceed $40,000 in connection with the establishment of this at-the-market offering program, in addition to certain ongoing fees of its legal counsel.

The legal opinion of McDermott Will & Emery LLP, counsel to the Company, relating to the Shares is filed as Exhibit 5.1 hereto.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of such agreement, a copy of which was filed as Exhibit 10.1 hereto and incorporated herein by reference.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of any offer to buy the Shares, nor shall there be an offer, solicitation or sale of the Shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state.