On November 8, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial stage, oncology-focused biopharmaceutical company, reported financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, AVEO, NOV 8, 2021, View Source [SID1234594705]).

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

                  Schedule Your 30 min Free Demo!

"During the third quarter, we continued to see strong commercial uptake for FOTIVDA, further underscoring the significant unmet medical need that exists in the indicated treatment population. FOTIVDA has been well received by oncologists treating relapsed or refractory (R/R) renal cell carcinoma (RCC), noting both the durable responses and tolerability profile as attractive for their third-line patients. We believe FOTIVDA has the potential to serve as a standard of care for these later line patients," said Michael Bailey, president and chief executive officer of AVEO. "Opening enrollment for our pivotal Phase 3 TiNivo-2 trial of tivozanib and nivolumab marks an important milestone in our efforts to assess tivozanib’s potential as an earlier line of therapy and in the immunotherapy combination setting."

Mr. Bailey continued: "Following the recent receipt of Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA) for ficlatuzumab and cetuximab in relapsed or recurrent head and neck squamous cell carcinoma (R/R HNSCC), we believe the clinical development of ficlatuzumab is well positioned to advance in this important potential new treatment option. We expect to commence manufacturing of ficlatuzumab clinical supply in the second quarter of 2022, with the initiation of a potential registrational clinical trial in the human papillomavirus negative (HPV-) HNSCC patient population anticipated in the first half of 2023."

Third Quarter 2021 and Recent Highlights

Strong Third Quarter Sales Growth for U.S. Commercial Launch of FOTIVDA for the Treatment of Adult Patients with R/R Advanced RCC Following Two or More Prior Systemic Therapies.
U.S. net product revenue for the third quarter of 2021 was $14.3 million, which reflects inventory shipped to distributors and a gross-to-net estimate of 16% during the quarter. As of September 30, 2021, year-to-date U.S. net product revenue since FOTIVDA’s commercial launch on March 22, 2021 was $22.1 million.
$14.3 million of U.S. net product revenue for the third quarter of 2021, representing a 113% increase from $6.7 million in the second quarter of 2021.
619 commercial prescriptions filled in the third quarter of 2021, representing a 119% increase from 283 commercial prescriptions filled in the second quarter of 2021.
Approximately 260 accounts have ordered as of September 30, 2021, representing a 90% increase compared to 137 accounts having ordered as of June 30, 2021.
Quarter-end inventory of approximately two weeks for the third quarter of 2021 suggests that the Company’s quarterly sales revenue are currently primarily driven by end user demand.
As planned, the Company’s early launch sampling program has decreased to 75 samples delivered in the third quarter of 2021 compared to 180 samples in the second quarter of 2021.
Enrollment Open for Pivotal Phase 3 TiNivo-2 Trial in IO Advanced Refractory RCC. Patient enrollment opened this quarter for the Phase 3 TiNivo-2 trial evaluating tivozanib in combination with nivolumab, Bristol Myers Squibb’s (NYSE: BMS) antibody directed against programmed death-1, in patients with advanced refractory RCC following one or two lines of therapy, one of which is immunotherapy. Per the previously announced March 2021 clinical trial collaboration and supply agreement, BMS will provide nivolumab clinical drug supply for the trial.
Ficlatuzumab Well-Positioned to Advance in Clinical Development for Treating R/R HNSCC Following FTD Being Granted by the FDA. In September 2021, AVEO announced that the FDA granted FTD for the investigation of ficlatuzumab and cetuximab for the treatment of patients with R/R HNSCC. Ficlatuzumab is AVEO’s investigational potent humanized immunoglobulin G1 monoclonal antibody that targets hepatocyte growth factor.

The Company expects to commence manufacturing of ficlatuzumab clinical supply in the second quarter of 2022, subject to availability of key raw materials and manufacturing supplies also used in COVID-19 vaccine manufacturing, with the initiation of a potential registrational clinical trial in HPV- HNSCC now anticipated in the first half of 2023. The Company expects to continue to discuss potential ficlatuzumab pivotal clinical trial designs with the FDA and to continue to seek a strategic partner.
Third Quarter 2021 Financial Highlights

AVEO ended Q3 2021 with $94.0 million in cash, cash equivalents and marketable securities, as compared with $102.9 million at the end of June 30, 2021 and $61.8 million at December 31, 2020.
Total revenue for Q3 2021 was approximately $15.2 million compared with $3.6 million of total revenue for Q3 2020.
FOTIVDA U.S. net product revenue for Q3 2021 was $14.3 million.
Research and development expense for Q3 2021 was $7.5 million compared with $5.9 million for Q3 2020.
Selling, general and administrative expense for Q3 2021 was $15.1 million compared with $5.8 million for Q3 2020.
The increase in selling, general and administrative expense for Q3 2021 is primarily due to costs associated with the commercial launch of FOTIVDA.
Net loss for Q3 2021 was $10.4 million, or net loss of $0.30 per basic and diluted share, compared with a net loss of $8.4 million for Q3 2020, or net loss of $0.33 per basic and diluted share.
Financial Guidance

AVEO believes that its $94.0 million in cash, cash equivalents and marketable securities as of September 30, 2021, along with expected net product revenues from the commercial launch of FOTIVDA in the United States, would enable AVEO to maintain its current operations for a period of at least 12 months following the filing of its Quarterly Report on Form 10-Q for the quarter ended September 30, 2021.

In 2021, AVEO expects commercial spend will be approximately $40 million, research and development expense will be approximately $30 million and general and administrative expense will be approximately $20 million. Gross margins are expected to be in the mid-to-high 80th percentile.

Conference Call and Webcast

In connection with this announcement, AVEO will host a conference call and audio webcast today, November 8, 2021, at 4:30 PM Eastern Time. The call can be accessed by dialing (844) 882-7841 (U.S. and Canada) or (574) 990-9828 (international). The passcode for the conference call is 1647457. To access the live webcast, or the subsequent archived recording, please visit the Calendar of Events sub-section within the Investors section of the AVEO website at www.aveooncology.com.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.1 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On November 8, 2021 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 that Pascal Touchon, President and Chief Executive Officer of Atara, will participate at three upcoming virtual conferences (Press release, Atara Biotherapeutics, NOV 8, 2021, View Source [SID1234594704]).

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

                  Schedule Your 30 min Free Demo!

Cowen 5th Annual IO Next Summit
Fireside chat on Monday, November 15, 2021 at 9:45 a.m. EST

Stifel 2021 Virtual Healthcare Conference
Fireside chat on Monday, November 15, 2021 at 4:40 p.m. EST

Evercore ISI 4th Annual HealthCONx Virtual Conference
Fireside chat on Tuesday, November 30, 2021 at 10:05 a.m. EST

Live video webcasts will be available by visiting the Investor Events and Presentations section of atarabio.com. Archived replays will be available on the Company’s website for 30 days following the live webcasts.

On November 8, 2021 Ascendis Pharma A/S (Nasdaq: ASND) reported that provided an update on the Company’s previously announced $25 million American Depositary Shares (ADS) Share Repurchase Program (Press release, Ascendis Pharma, NOV 8, 2021, View Source [SID1234594703]). Each ADS represents one ordinary share of Ascendis Pharma A/S. The program is executed under Rules 10b-18 and 10b5-1 of the U.S. securities regulations.

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

                  Schedule Your 30 min Free Demo!

In accordance with the program initiated on November 1, 2021, Ascendis Pharma A/S is authorized to repurchase up to $25 million of ADSs in the period starting November 1, 2021 and expected to end no later than December 31, 2021. A maximum of 300,000 ADS in total can be repurchased during the trading period. The maximum number of ADS that can be repurchased on a single trading day may not exceed 10% of the average daily trading volume of Ascendis Pharma A/S ADS, in the prior full four weeks of trading.

Since the initiation of the program, the following transactions have been executed.

Trade Date
Number of ADS Weighted Average
Purchase Price

Total Value*
November 1, 2021 24,540 $159.15 $3,906,181
November 2, 2021 24,631 $162.99 $4,015,444
November 3, 2021 24,631 $163.09 $4,017,730
November 4, 2021 24,631 $161.09 $3,968,488
November 5, 2021 23,989 $160.69 $3,855,409
Purchased under the program 122,422 $161.41 $19,763,252
*Total value includes fees and costs associated with the repurchase program.

Following these transactions, Ascendis Pharma A/S has repurchased a total of 122,422 ADSs under the Share Repurchase Program.

On November 8, 2021 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, 2021 and provided an update on the ARC-7 study of domvanalimab (Press release, Arcus Biosciences, NOV 8, 2021, View Source [SID1234594702]). Gilead Sciences has initiated its opt-in review process to potentially obtain rights to the Arcus anti-TIGIT program. If the option is exercised and closed, Gilead would obtain rights to both domvanalimab and AB308, a second and differentiated anti-TIGIT antibody in the Arcus portfolio. A decision is expected prior to the end of 2021.

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

                  Schedule Your 30 min Free Demo!

"The initiation of Gilead’s opt-in review process for our anti-TIGIT program is an important step towards our shared commitment to develop differentiated combination therapies for people with cancer," said Terry Rosen, Ph.D., Chief Executive Officer of Arcus. "We expect to continue our strong momentum of significant program advancement and milestone achievement starting with an update this fall from our Phase 1 study of quemliclustat, our first-in-class small molecule CD73 inhibitor, in development for pancreatic cancer, an area of enormous unmet need. Quemliclustat is a central component of our late-stage development strategy for 2022 and beyond."

Corporate & Partnership Updates

Gilead initiated the opt-in review process for our anti-TIGIT program. A decision is expected prior to the end of 2021. If Gilead exercises its option, and subject to receipt of applicable anti-trust approvals:
Arcus would receive a $275 million opt-in payment, and the parties would co-develop and share equally the global development costs related to the anti-TIGIT program.
Gilead would obtain rights to both domvanalimab, our Fc-silent anti-TIGIT antibody currently being evaluated in Phase 2 and Phase 3 studies, and AB308, our Fc-enabled anti-TIGIT antibody currently in a Phase 1 study in advanced malignancies.
If approved, Arcus and Gilead would co-commercialize and equally share profits and losses to both anti-TIGIT antibodies in the United States. Gilead would receive exclusive rights outside the U.S., subject to any rights of Arcus’s existing partners, and Gilead would pay to Arcus tiered royalties ranging from the high teens to low twenties.
Our collaboration partner Taiho initiated a Phase 1 platform study evaluating zimberelimab (our anti-PD1 antibody) with Taiho’s intra-portfolio combinations targeting oncology indications. The TARP (Taiho-Arcus Platform) study is currently enrolling. Further details can be found at View Source Trial Identifier: NCT04999761.
Zimberelimab was approved in China as a second-line treatment for recurrent/refractory classical Hodgkin lymphoma (CHL); Gloria Biosciences holds all rights to zimberelimab in China and conducts its development of zimberelimab independent of Arcus’s activities.
Anti-TIGIT program

Recent Highlights

Arcus conducted a second interim analysis (IA2) for ARC-7, our open-label randomized Phase 2 study evaluating the safety and efficacy of domvanalimab plus zimberelimab vs. zimberelimab alone vs. domvanalimab plus zimberelimab and etrumadenant (dual adenosine A2a/A2b receptor antagonist) as a first-line treatment for PD-L1 ≥ 50% and EGFR/ALK wild-type, metastatic NSCLC. The study has a target total enrollment of 150 patients who are being randomized 1:1:1 across three study arms and treated until disease progression or loss of clinical benefit. The timing of this interim analysis was pre-specified in the protocol to occur when a certain number of patients were randomized and had at least two disease evaluations.
Summary of Efficacy Observations from IA2:

Both domvanalimab-containing arms demonstrated differentiated clinical activity compared to that of zimberelimab alone.
Zimberelimab alone continued to demonstrate activity similar to that of other marketed anti-PD-1 antibodies in the setting.
As expected with immunotherapy treatments, continued deepening of response and greater tumor shrinkage were observed in patients with longer follow-up in both domvanalimab-containing arms.
Since the previous interim analysis, the doublet continued to show encouraging activity relative to the monotherapy, and the triplet continued to numerically outperform the doublet.
As of the data cut-off date for this interim analysis, data for progression-free survival (PFS) was immature but indicated that fewer events of progression or death had occurred in the domvanalimab-containing arms compared to zimberelimab alone.
Summary of Safety Observations from IA2:

No unexpected safety signals were observed; the current safety profile for each molecule in the study appeared to be consistent with known and published immune checkpoint inhibitors in this setting.
Early safety data from this interim analysis showed a lower incidence of infusion reactions relative to published numbers from other anti-TIGIT plus anti-PD-(L)1 clinical studies.
Arcus initiated enrollment of five expansion cohorts in the Phase 1b portion of the ARC-12 study evaluating AB308 plus zimberelimab in advanced malignancies. This study is designed to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB308 plus zimberelimab in tumor types believed to be potentially responsive to anti-TIGIT antibodies.
Upcoming anti-TIGIT Milestones:

ARC-7 is expected to be fully enrolled by mid-2022, and we anticipate a data presentation later in 2022, which will include progression-free survival data.
ARC-10, an ongoing registrational Phase 3 study in first-line, locally advanced or metastatic PD-L1≥50% NSCLC, continues to enroll and, if positive, is intended to support the potential approvals of both zimberelimab monotherapy and domvanalimab plus zimberelimab.
AstraZeneca and Arcus remain on track to initiate the PACIFIC-8 registrational Phase 3 study to evaluate domvanalimab plus durvalumab, an anti-PD-L1 antibody, in unresectable Stage 3 NSCLC with curative intent, where durvalumab is standard of care, by the end of 2021.
We are planning several additional clinical studies of domvanalimab-based combinations, including two additional Phase 3 studies anticipated to start in mid-2022.
Quemliclustat (small molecule anti-CD73 inhibitor)

Upcoming Milestones:

An update on ARC-8, our Phase I study of quemliclustat plus zimberelimab and gemcitabine/nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma (PDAC), is planned for this fall. This update includes data on approximately 30 patients treated at the 100mg and 125mg dose of quemliclustat.
We expect the randomized portion of ARC-8 to complete enrollment by the end of this month. This 90-patient cohort is evaluating quemliclustat plus zimberelimab and gemcitabine/nab-paclitaxel vs. quemliclustat plus gemcitabine/nab-paclitaxel to determine whether zimberelimab adds clinical benefit to the combination.
We anticipate landmark six-month PFS data from the randomized portion of ARC-8 in mid-2022. These results will inform the design of our planned Phase 3 study with the goal of starting this first registrational study for quemliclustat in 2022.
Etrumadenant (A2a/A2b adenosine receptor antagonist)

Upcoming Milestones:

ARC-4, our randomized Phase 1b study in EGFR+ NSCLC: we expect initial randomized data, including overall response rates and PFS, to be presented in 1H22. ARC-4 is evaluating etrumadenant plus zimberelimab and chemotherapy vs. zimberelimab plus chemotherapy in EGFRmut tyrosine kinase inhibitor (TKI)-relapsed and refractory NSCLC.
ARC-6, our Phase 1b/2 platform study in metastatic castration-resistant prostate cancer: we anticipate initial results in 2022 from the randomized cohort that is evaluating docetaxel versus docetaxel plus etrumadenant and zimberelimab.
Discovery Programs:

Upcoming Milestones:

AB308 (Fc-enabled anti-TIGIT antibody) poster presentation at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting, November 10-14, 2021.
Poster #258, Title: AB308 is an Anti-TIGIT Antibody That Enhances Immune Activation and Anti-tumor Immunity Alone and in Combination with Other I-O Therapeutic Agents.
AB521 (HIF-2α inhibitor): we expect to initiate Phase 1 clinical development in the fourth quarter of 2021. This first study is in healthy volunteers and is designed to expeditiously characterize the pharmacokinetic and safety profile of AB521 and to identify the starting dose for the planned Phase 1/1b study in oncology patients.
Financial Results for the Third Quarter 2021

Cash, cash equivalents and investments were $743.4 million as of September 30, 2021, compared to $735.1 million as of December 31, 2020. The increase was primarily due to gross proceeds of $220.4 million received upon the closing of the private placement of common stock under the Amended and Restated Stock Purchase Agreement with Gilead in February 2021, partially offset by cash utilized for our operations. We expect cash, cash equivalents and marketable securities on hand to be sufficient to fund operations at least through 2023.
Revenues: Collaboration and license revenues were $9.5 million for the three months ended September 30, 2021, compared to $64.5 million for the same period in 2020. In the three months ended September 30, 2021, we recognized $7.7 million in collaboration revenue related to Gilead’s ongoing rights to access our research and development pipeline in accordance with the Gilead collaboration agreement, as well as $1.8 million related to the Taiho collaboration agreement. In the three months ended September 30, 2020, we recognized $55.1 million in revenue related to Gilead’s license to zimberelimab and $7.7 million in collaboration revenue related to their access to our research and development pipeline, as well as $1.8 million related to the Taiho collaboration agreement. Collaboration and license revenues were $28.4 million for the nine months ended September 30, 2021, compared to $68.0 million for the same period in 2020.
R&D Expenses: Research and development expenses were $71.3 million for the three months ended September 30, 2021, compared to $51.8 million for the same period in 2020. The increase was primarily driven by costs incurred to support our expanded clinical and development activities including increased compensation costs related to a larger employee base, increased clinical trial costs, and increased early-stage research costs. Approximately $4.9 million of the increase in compensation costs is related to non-cash stock-based compensation. The overall increase in research and development expenses is partially offset by a decrease in milestone expenses incurred. Research and development expenses were $206.4 million for the nine months ended September 30, 2021, compared to $110.6 million for the same period in 2020.
G&A Expenses: General and administrative expenses were $16.3 million for the three months ended September 30, 2021, compared to $11.2 million for the same period in 2020. The increase was driven by the increased complexity of supporting our expanding clinical pipeline and collaboration obligations, as well as compliance costs associated with our growth. Our growing employee base and 2021 stock awards drove an increase in employee compensation costs, including approximately $3.7 million of increased non-cash stock-based compensation. The overall increase was partially offset by decreases in legal, accounting and consulting expenses due to costs related to the transaction with Gilead and other corporate development activities incurred in 2020. General and administrative expenses were $49.0 million for the nine months ended September 30, 2021, compared to $29.6 million for the same period in 2020.
Net Loss: Net loss was $78.0 million for the three months ended September 30, 2021, compared to net income of $1.8 million for the same period in the prior year. Net loss was $226.5 million for the nine months ended September 30, 2021, compared to $71.0 million for the same period in 2020.

Carbo/pem: carboplatin/pemetrexed; dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab CRC: colorectal cancer; CRPC: castrate-resistant prostate cancer; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma

About domvanalimab and AB308

Domvanalimab, Arcus’s most advanced anti-TIGIT candidate, is an Fc-silent investigational monoclonal antibody that binds to TIGIT, a protein receptor on immune cells that acts as a brake on the immune response. Cancer cells can exploit TIGIT to avoid detection by the immune system. Domvanalimab binds to TIGIT to free up immune activating pathways and activate immune cells to attack and kill cancer cells.

Treatment with domvanalimab, an Fc-silent antibody, has not been associated with the depletion of peripheral regulatory T-cells. We believe this may result in fewer infusion reactions relative to what has been reported for other anti-TIGIT-containing regimens.

Arcus is developing a second anti-TIGIT candidate, AB308, an Fc-enabled investigational monoclonal antibody. AB308 is currently in a Phase I study for advanced malignancies.

About the Gilead Collaboration

In May 2020, Gilead and Arcus entered into a 10-year collaboration that provided Gilead immediate rights to zimberelimab and the right to opt in to all other Arcus programs arising during the collaboration term. For clinical programs in existence at the date of the agreement, Gilead’s opt-in payment ranges from $200 million to $275 million per program. For all other programs that enter clinical development thereafter, the opt-in payments are $150 million per program. Gilead’s option, on a program-by-program basis, expires after a prescribed period of time following the achievement of a development milestone for such program and Arcus’s delivery to Gilead of the requisite qualifying data package. Concurrent with the collaboration agreement, Gilead and Arcus entered into a stock purchase agreement under which Gilead made a $200 million equity investment in Arcus. That stock purchase agreement was amended and restated in February 2021 in connection with Gilead’s increased equity stake in Arcus from 13% to 19.5%, with an additional $220 million investment.

On November 8, 2021 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate the mutant tumor suppressor protein, p53, reported financial results for the three and nine months ended September 30, 2021 and provided a business update (Press release, Aprea, NOV 8, 2021, View Source [SID1234594701]).

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

                  Schedule Your 30 min Free Demo!

Third Quarter Financial Results

Cash and cash equivalents: As of September 30, 2021, the Company had $61.4 million of cash and cash equivalents compared to $89.0 million of cash and cash equivalents as of December 31, 2020. The Company expects cash burn for the full year 2021 to be between $30.0 million and $35.0 million. The Company believes its cash and cash equivalents as of September 30, 2021, will be sufficient to meet its current projected operating requirements into 2023.
Research and Development (R&D) expenses: R&D expenses were $6.0 million for the quarter ended September 30, 2021, compared to $8.8 million for the comparable period in 2020. The decrease in R&D expenses was primarily due to decreases in clinical trial costs for our pivotal Phase 3 clinical trial of eprenetapopt with azacitidine for the frontline treatment of TP53 mutant MDS which completed enrollment in Q2 2020 and our Phase 2 post-transplant MDS/AML clinical trial. These decreases were partially offset by increases in clinical trial costs for our other ongoing clinical trials.
General and Administrative (G&A) expenses: G&A expenses were $3.4 million for the quarter ended September 30, 2021, compared to $3.5 million for the comparable period in 2020. The decrease in G&A expenses was primarily due to a decrease in pre-commercialization development activities which was partially offset by increased non-cash stock-based compensation.
Net loss: Net loss was $9.5 million, or $0.45 per share for the quarter ended September 30, 2021, compared to a net loss of $12.3 million, or $0.58 per share for the quarter ended September 30, 2020. The Company had 21,360,140 shares of common stock outstanding as of September 30, 2021.
Business Operations Update:

Myeloid Malignancy Program

On August 4, 2021, the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on the clinical trials of eprenetapopt in combination with azacitidine in our Phase 3 frontline MDS clinical trial, our Phase 2 MDS/AML Post-Transplant clinical trial and our Phase 1/2 AML clinical trial. The FDA’s concerns referred to the safety and efficacy data from the Phase 3 frontline MDS clinical trial. In particular, the FDA requested more information related to a potential risk-reward imbalance between the combination of eprenetapopt and azacitidine versus azacitidine alone as it relates to increased serious adverse events in the Company’s Phase 3 frontline clinical trial in MDS. There are approximately 9 patients currently receiving eprenetapopt in combination with azacitidine in our myeloid malignancy programs, which includes the MDS, AML and post-transplant maintenance trials, all of which have completed enrollment. Patients who are benefiting from treatment can continue to receive study treatment. As part of the partial clinical hold, no additional patients should be enrolled to these clinical trials until the partial clinical hold is resolved, The Company intends to work with the FDA to analyze the data, address the specific questions raised, and seek to resolve the partial clinical hold as soon as possible.

APR-548 Phase 1 Trial — The Company’s second product candidate, APR-548, is a next-generation p53 reactivator that is being developed in an oral dosage form. The Company is currently enrolling a Phase 1 dose-escalation clinical trial evaluating the safety, tolerability, and preliminary efficacy of APR-548 with azacitidine in frontline and relapsed/refractory MDS patients. The trial is open and patients are enrolled in the first dosing cohort.

Lymphoid Malignancy Program

On August 11, 2021, the FDA placed a clinical on the Company’s clinical trial evaluating eprenetapopt with acalabrutinib or with venetoclax and rituximab in lymphoid malignancies. The FDA’s concerns referred to the safety and efficacy data from the Company’s Phase 3 frontline clinical trial in MDS. There are no patients currently receiving study treatment in this trial and no additional patients can be enrolled until the clinical hold is resolved. The Company intends to work with the FDA to address the specific questions raised and seek to resolve the clinical hold as soon as possible.

Solid Tumor Disease Program

Data from the Company’s Phase 1/2 clinical trial in relapsed/refractory gastric, bladder and non-small cell lung cancers assessing eprenetapopt with anti-PD-1 therapy was presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021. Results were presented from 31 patients who had initiated treatment, including three gastric/GEJ, three bladder/urothelial cancer and 19 non-small cell lung cancer (NSCLC) patients. In the bladder/urothelial cohort, one patient with localized TP53 mutant high-grade transitional cell bladder cancer had achieved complete remission (CR) by RECIST criteria at the first response assessment at 9 weeks. In the NSCLC cohort, two patients with TP53 mutant squamous NSCLC had reductions in target lesions of 26.7% and 8.2%, respectively, from baseline by RECIST criteria at the first response assessment at 9 weeks.

Upcoming Presentations

Investigators will present data from Aprea Therapeutics’ clinical trials evaluating eprenetapopt at the upcoming 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper).

Title: Long-Term Follow-up and Combined Phase 2 Results of Eprenetapopt (APR-246) and Azacitidine (AZA) in Patients with TP53 Mutant Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia (AML)

Date & Time: Saturday, December 11, 2021 at 3:15 pm ET
Oral Abstract Session: 637. Myelodysplastic Syndromes—Clinical and Epidemiological: Treatment of High Risk Myelodysplastic Syndrome
Title: Phase II Trial of Eprenetapopt (APR-246) in Combination with Azacitidine (AZA) As Maintenance Therapy for TP53 Mutated AML or MDS Following Allogeneic Stem Cell Transplantation (SCT)

Date & Time: Sunday, December 12, 2021 at 9:30 am ET
Oral Abstract Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence
Title: Phase I and Expansion Study of Eprenetapopt (APR-246) in Combination with Venetoclax (VEN) and Azacitidine (AZA) in TP53-Mutant Acute Myeloid Leukemia (AML)

Date & Time: Monday, December 13, 2021, 6:00 – 8:00 pm ET
Poster Abstract Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III