On May 9, 2022 Nykode Therapeutics AS (Euronext Growth (Oslo): NYKD), a clinicalstage biopharmaceutical company dedicated to the discovery and development of vaccines and novel immunotherapies, reported positive interim results from its Phase 2 VB C-02 trial of VB10.16, its wholly-owned therapeutic cancer vaccine, in combination with the PD-L1 inhibitor atezolizumab in patients with HPV16-positive advanced cervical cancer (Press release, Nykode Therapeutics, MAY 9, 2022, View Source [SID1234613862]). Interim results from 39 patients with a median follow up of 6 months show an ORR of 21%—including two patients who achieved a complete response and six who achieved a partial response—and a very high disease control rate of 64%. The trial enrolled a heavily pre-treated patient population with more than two thirds of the patients having received at least two previous systemic lines of treatment.

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Interestingly, anti-tumor activity was observed in both PD-L1 positive (ORR of 27% and DCR of 77%) and PD-L1 negative patients (ORR of 17% and DCR of 58%) indicating a potential clinical benefit also in the PD-L1 negative population. In addition, a DCR of 71% was observed in patients with noninflamed tumors, including both immune desert and T cell excluded tumors. Together these findings suggest a differentiated anti-tumor response pattern of the combination treatment compared to checkpoint inhibitor monotherapy.

"We are thrilled to report these positive interim safety and efficacy results from our Phase 2 trial with VB10.16, which showed evidence of durable anti-tumor activity in a heavily pre-treated population of patients with late-stage cervical cancer," said Michael Engsig, Chief Executive Officer of Nykode Therapeutics. "These interim results support Nykode’s unique approach of targeting AntigenPresenting Cells (APCs), designed to produce a robust and long-lasting CD8 killer T cell response against cancer cells. We look forward to reporting updated efficacy data readouts from the Phase 2 trial during the first half of 2023 as we continue to advance our cervical cancer program."

Immunological analyses of the peripheral T cell responses demonstrated an increased HPV16-specific IFN T cell immune response post-vaccination in the majority of subjects and were associated with clinical efficacy indicating the induction of clinically relevant T cell responses. Clearance of circulating HPV16 DNA was significantly correlated with clinical response and progression free survival suggesting ctDNA may be an early marker of response to treatment in cervical cancer. VB10.16 is potentially a first-in-class therapeutic vaccine against HPV16-positive cervical cancer.

"The patients who were treated with VB10.16 in combination with atezolizumab in the C-02 trial were heavily pre-treated and are prone to progress quickly," said Professor Peter Hillemanns, Director of the Departments of Gynecology, Obstetrics and Breast Cancer at Hannover University Hospital, Germany and principal investigator of the C-02 trial. "It is very encouraging to see that a majority of patients experienced a clinical benefit and that many patients had durable responses. The combination of VB10.16 and atezolizumab was also well tolerated by patients."

"Treatment advances within the area of advanced cervical cancer have been limited though checkpoint inhibitors have demonstrated clinical efficacy in some patients. The unmet need is still high, and we are very pleased to see a high disease control rate and durable responses in these heavily pre-treated HPV16+ cervical cancer patients. The anti-tumor activity seen in both noninflamed and PD-L1 negative populations may potentially open up a new subset of patients for treatment. These findings indicate that VB10.16 may give a meaningful added clinical benefit compared to the existing standard of care treatment in this setting. We would like to thank all the investigators, patients and their relatives for participating in this trial. Without all of you the advances of VB10.16 would not have been possible," added Siri Torhaug, Chief Medical Officer of Nykode Therapeutics.

VB10.16 was generally safe and well tolerated, with 10% of patients experiencing Grade 3 or more treatment-related adverse events, indicating no increased toxicity compared with atezolizumab monotherapy and a favorable safety profile that is consistent with previously published data for the Nykode DNA vaccine technology platform. Nykode expects to report updated efficacy data read-outs from VB C-02 during the first half of 2023. Webcast Investors and analysts are invited to join a webcast presentation of the interim results conducted by CEO Michael . The slide presentation will be available in the Investors section of the Company’s website at View Source following the event. The live and archived webcast of the presentation can be accessed in the Investors section of the Company’s website at View Source/financial-reports-and-presentations.

About the VB C-02 trial VB C-02 is a multi-center, single arm, open-label Phase 2 trial of patients with advanced or recurrent, non-resectable HPV16-positive cervical cancer. Patients received treatment with VB10.16 in combination with the PD-L1 inhibitor atezolizumab for up to one year. The main aim of the trial was to assess the efficacy, immunogenicity and safety of VB10.16 when given in combination with atezolizumab. The trial is now fully enrolled with 52 patients enrolled at sites in Europe, and the preplanned second interim analysis was performed at the cut-off date of 14 February 2022. Nykode has previously reported positive interim safety data from the trial. Additional information about the VB C-02 trial is available at clinicaltrials.gov (NCT04405349).

About VB10.16
VB10.16 is a potentially first-in-class off-the-shelf therapeutic cancer vaccine candidate in development for the treatment of human papillomavirus type 16 (HPV16)-positive cancers. The cancer vaccine is designed based on Nykode’s Vaccibody technology platform of targeting antigens to antigen presenting cells. The candidate has demonstrated favorable clinical data in a Phase I/IIa study in pre-cancerous HPV16-induced high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3) demonstrating a statistically significant correlation of immune responses and clinical responses. VB10.16 is currently being investigated in the VB C-02 trial in patients with advanced or recurrent, non-resectable HPV16-positive cervical cancer.

About cervical cancer
Cervical cancer is the fourth leading cause of cancer death in women worldwide and is most frequently diagnosed between the ages of 35 and 44. Each year around 600,000 women are diagnosed with cervical cancer worldwide. Almost all cases are caused by human papillomavirus (HPV) infection and HPV16 accounts for more than half of all cervical cancer cases. Approximately 80% of patients with cervical cancer have squamous cell carcinoma (arising from cells lining the bottom of the cervix) and most other patients have adenocarcinomas (arising from glandular cells in the upper cervix). Cervical cancer is often curable when detected early and effectively managed, but treatment options are more limited in advanced disease stages or when the cancer has spread.

On May 9, 2022 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care, reported financial results for the three months ended March 31, 2022 and highlighted recent corporate updates (Press release, Heron Therapeutics, MAY 9, 2022, View Source [SID1234613919]).

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Recent Corporate Updates

Acute Care Franchise

ZYNRELEF:

The ZYNRELEF (bupivacaine and meloxicam) extended-release solution New Drug Application (NDA) was approved by the U.S. Food and Drug Administration (FDA) in May 2021. In December 2021, the FDA approved our supplemental New Drug Application (sNDA) for ZYNRELEF, now covering approximately 7 million procedures annually. ZYNRELEF is currently indicated for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. The FDA also agreed to the contents of a second sNDA, planned for later this year, designed to further expand the indication statement.

ZYNRELEF net product sales for the three months ended March 31, 2022 were $1.1 million, which was net of $0.3 million in returns of short-dated ZYNRELEF and a continued reduction of initial distribution channel inventory. Short-dated product returns were due to delays in obtaining initial FDA approval of ZYNRELEF.

ZYNRELEF end-user (ambulatory surgical centers (ASC) and hospitals) demand units’ sales were 8,673 in the first quarter of 2022, representing an increase of 68% over the prior quarter.

During the first three quarters of commercial launch ended March 31, 2022, over 450 unique accounts purchased ZYNRELEF with 80% of those accounts reordering the product.

As of April 30, 2022, ZYNRELEF has received 319 formulary approvals, with over a 90% hospital approval rate, and an estimated 68% of formulary approvals have been for unrestricted use. Over 60 additional formulary review meetings are scheduled through June 30, 2022.

Effective April 1, 2022, ZYNRELEF became the only local anesthetic separately reimbursed for Medicare patients in the Hospital Outpatient Department (HOPD) setting of care under a 3-year transitional pass-through status. Multiple commercial and Medicaid payers covering over 120 million lives have agreed to reimburse ZYNRELEF outside of the surgical bundle payment for surgeries performed in ASCs, with many of these covered lives also having their hospital outpatient procedures reimbursed outside the surgical bundle payment. Commercial and Medicaid payers represent more than 80% of our target patients in the outpatient setting. On November 2, 2021, we were issued a specific C-code (C9088) for separate reimbursement in the ASC setting of care effective January 1, 2022.

In March 2022, Health Canada issued a Notice of Compliance to commercialize ZYNRELEF for instillation into the surgical wound for postoperative analgesia after bunionectomy, open inguinal herniorrhaphy, and total knee arthroplasty surgical procedures. Based on prior agreements with the FDA, Heron already has clinical studies underway, which we plan to submit to Health Canada to expand the indication statement. Heron is currently in partnering discussions related to Canada and other countries outside the U.S.
NDA Submission for HTX-019 for Prevention of PONV in Adults Under Review: A 505(b)(2) NDA for HTX-019 for the prevention of postoperative nausea and vomiting (PONV) in adults was submitted to the FDA in November 2021. The FDA accepted the NDA for filing and set a Prescription Drug User Fee Act (PDUFA) goal date of September 17, 2022.
Oncology Care Franchise

2022 Oncology Care Franchise Net Product Sales: For the three months ended March 31, 2022, oncology care franchise net product sales were $22.4 million, compared to $20.0 million for the same period in 2021. During the first quarter, Heron’s oncology care franchise net product sales grew by 13% over the prior quarter with continued moderate growth expected for the remainder of 2022.

CINVANTI Net Product Sales: Net product sales of CINVANTI (aprepitant) injectable emulsion for the three months ended March 31, 2022 were $20.3 million, compared to $18.5 million for the same period in 2021.

SUSTOL Net Product Sales: Net product sales of SUSTOL (granisetron) extended-release injection for the three months ended March 31, 2022 were $2.1 million, compared to $1.5 million for the same period in 2021.

2022 Oncology Care Franchise Net Product Sales Guidance: Heron currently expects the second quarter of 2022 net product sales for the oncology care franchise in the range of $22 million to $23 million, with full-year 2022 net product sales for the oncology care franchise in the range of $89 million to $93 million.
"Although the start of the first quarter was challenging due to the COVID-19 pandemic, in the last few months ZYNRELEF has gained momentum following the FDA approval of the expanded indications. We expect continued strong growth in the current quarter with the receipt of pass-through status from CMS for HOPD, as evidenced by an 85% increase in demand units in the first month of the second quarter versus the first month of the first quarter," said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. "In oncology care, our CINV portfolio continues to perform well and we look forward to achieving net product sales of $22 million to $23 million in the second quarter of 2022 and full year 2022 net product sales of $89 million to $93 million."

Financial Results

Net product sales for the three months ended March 31, 2022 were $23.5 million, compared to $20.0 million for the same period in 2021.

Heron’s net loss for the three months ended March 31, 2022 was $63.9 million, or $0.63 per share, compared to $52.6 million, or $0.58 per share, for the same period in 2021. Net loss for the three months ended March 31, 2022 included non-cash, stock-based compensation expense of $10.9 million, compared to $11.5 million for the same period in 2021.

As of March 31, 2022, Heron had cash, cash equivalents and short-term investments of $111.9 million, compared to $157.6 million as of December 31, 2021. Net cash used for operating activities for the three months ended March 31, 2022 was $43.9 million, compared to $41.9 million for the same period in 2021. The increase in our net cash used for operating activities was primarily due to changes in working capital related to the launch of ZYNRELEF, including manufacturing of commercial inventory, and an increase in net loss. We expect net cash used for operating activities of $37 million to $39 million in the second quarter of 2022.

Conference Call and Webcast

Heron will host a conference call and webcast on May 9, 2022 at 4:30 p.m. ET. The conference call can be accessed by dialing 1-844-825-9789 for domestic callers and 1-412-317-5180 for international callers. Please provide the operator with the passcode 10166891 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron’s website at www.herontx.com. An archive of the teleconference and webcast will also be made available on Heron’s website for 60 days following the call.

About ZYNRELEF for Postoperative Pain

ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the FDA in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF’s indication. ZYNRELEF is now indicated in the U.S. in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. In September 2020, the European Commission granted a marketing authorization for ZYNRELEF for the treatment of somatic postoperative pain from small- to medium-sized surgical wounds in adults. As of January 1, 2021, ZYNRELEF is approved in 31 European countries including the countries of the European Union and European Economic Area and the United Kingdom. In March 2022, Health Canada issued a Notice of Compliance for ZYNRELEF for instillation into the surgical wound for postoperative analgesia after bunionectomy, open inguinal herniorrhaphy, and total knee arthroplasty surgical procedures.

Please see full prescribing information, including Boxed Warning, at www.ZYNRELEF.com.

About HTX-019 for PONV

HTX-019 is an IV injectable emulsion formulation designed to directly deliver aprepitant, the active ingredient in EMEND (aprepitant) capsules, which is the only substance P/neurokinin-1 (NK1) receptor antagonist (RA) to be approved in the U.S. for the prevention of PONV in adults. The FDA-approved dose of oral EMEND is 40 mg for PONV prevention, which is given within 3 hours prior to induction of anesthesia for surgery. In a Phase 1 clinical trial, 32 mg of HTX-019 as a 30-second IV injection was demonstrated to be bioequivalent to oral aprepitant 40 mg. The NDA for HTX-019 for PONV was submitted in November 2021 and the FDA set a PDUFA goal date of September 17, 2022.

About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection.

Please see full prescribing information at www.CINVANTI.com.

About SUSTOL for CINV Prevention

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

On May 9, 2022 Myovant Sciences (NYSE: MYOV) and Accord Healthcare, Ltd. (Accord) reported that they have entered into an exclusive license agreement for Accord to commercialize relugolix for the treatment of advanced hormone-sensitive prostate cancer under the trade name ORGOVYX (relugolix, 120 mg) in the European Economic Area, United Kingdom, Switzerland and Turkey, with the right of first negotiation if Myovant decides to enter into licensing arrangements in countries in the Middle East, Africa and India (Press release, Myovant Sciences, MAY 9, 2022, https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-and-accord-healthcare-ltd-enter-exclusive [SID1234613935]).

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Under the terms of the agreement, Myovant will receive an upfront payment of $50 million and is eligible to receive commercial launch, sales-based and other milestones totaling up to $90.5 million. In addition, Myovant is eligible to receive tiered royalties from the high-teens to mid-twenties on net sales. Myovant will continue to lead the global development of relugolix and provide initial product supply to Accord. Accord will be responsible for certain local clinical development, all commercialization for its territories, and has the option to manufacture relugolix in the future.

"We’re delighted to join forces with Accord to make available the first and only oral androgen deprivation therapy for men with advanced hormone-sensitive prostate cancer in Europe," said David Marek, Chief Executive Officer of Myovant. "Accord has a longstanding commitment to oncology with proven commercial capabilities that they will leverage to accelerate the launch to reach more patients with this meaningful therapy."

"We are proud to launch ORGOVYX in Europe, as an addition to our specialty brand offerings," said Binish Chudgar, Managing Director of Accord. "Accord currently supplies around 1 in 3 injectable oncology medicines in Europe and this agreement underpins our commitment to patients with cancer and our continued investment in novel therapies. With over 1.9 million men living with prostate cancer in Europe, our partnership with Myovant will provide men living with hormone-sensitive advanced prostate cancer a new oral treatment option."

On April 29, 2022, the European Commission approved the marketing authorization application for ORGOVYX (relugolix, 120 mg) for the treatment of adult patients with advanced hormone-sensitive prostate cancer. The decision applies to all 27 European Union member states plus Iceland, Norway, and Liechtenstein. The marketing authorization application for ORGOVYX is pending review by the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA). Accord expects to launch ORGOVYX in Europe in the second half of calendar year 2022.

Goldman Sachs & Co. LLC has acted as the exclusive financial advisor to Myovant and Sidley Austin LLP represented Myovant in the transaction.

About Prostate Cancer
In 2020, the total number of men in Europe with prostate cancer was approximately 1.9 million according to the World Health Organization’s Agency for Cancer Research WHO IntlAgencyCancerResearch PC.

Prostate cancer is considered advanced when it has spread beyond the prostate, is localized to the prostate and unlikely to be cured by surgery or radiation or has comeback after initial treatment and cannot be treated with salvage surgery. Front-line medical therapy for advanced prostate cancer typically involves androgen deprivation therapy, which reduces testosterone to very low levels, commonly referred to as castrate levels (< 50 ng/dL). Luteinizing hormone-releasing hormone (LHRH) receptor agonists, such as leuprolide acetate, are depot injections and the current standard of care for androgen deprivation therapy. LHRH agonists are associated with an initial surge in testosterone levels that may exacerbate clinical symptoms in some patients and delayed testosterone recovery after the drug is discontinued due to their depot injection formulation.

About ORGOVYX (relugolix)
ORGOVYX (relugolix, 120 mg) is indicated in Europe for the treatment of adult patients with advanced hormone-sensitive prostate cancer. As a gonadotropin-releasing hormone (GnRH) receptor antagonist ORGOVYX blocks the GnRH receptor and reduces production of testicular testosterone, a hormone known to stimulate the growth of prostate cancer.

On May 9, 2022 Ichnos Sciences Inc., a clinical-stage global biotechnology company developing innovative multispecific antibodies for oncology, reported the selection of ISB 2001, its first TREAT1 trispecific antibody, which engages BCMA x CD38 x CD3, as its next candidate to move into clinical development (Press release, Ichnos Sciences, MAY 9, 2022, View Source [SID1234613951]). The company has initiated IND-enabling studies for relapsed/refractory multiple myeloma and aims to advance ISB 2001 to a first-in-human study once clearance from the health authorities is received in 2023.

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ISB 2001 is the first T cell-engaging antibody that targets BCMA and CD38 on multiple myeloma cells. It is a trispecific antibody based on BEAT 2.0 technology2, a proprietary platform allowing maximal flexibility and manufacturability of full length multispecific antibodies. Additional ISB 2001 details include:

ISB 2001 combines three proprietary fragment antigen-binding arms, each targeting a different antigen, with one arm binding to the epsilon chain of CD3 on T cells, and the other two binding BCMA and CD38 on myeloma cells. Its fragment crystallizable (Fc) domain was fully silenced to suppress Fc effector functions.
In vitro studies showed that ISB 2001 exhibited increased killing potency of tumor cells compared to all tested antibodies that are either currently approved therapeutics for multiple myeloma or being tested in ongoing clinical studies. In vivo studies in the multiple myeloma models also demonstrated superior potency of ISB 2001 relative to approved antibody treatments of multiple myeloma.
ISB 2001 redirects CD3+ T lymphocytes to kill tumor cells expressing low to high levels of both BCMA and CD38.
With two different tumor-associated antigens instead of one, ISB 2001 has increased binding specificity to multiple myeloma cells due to enhanced avidity-based binding.
"This milestone represents another exciting step forward as Ichnos moves its first trispecific antibody targeting BCMA and CD38 into IND-enabling studies for relapsed/refractory multiple myeloma," said Cyril Konto, M.D., President and CEO of Ichnos. "We have made tremendous progress with our proprietary BEAT 2.0 platform and are excited about advancing our first TREAT trispecific antibody candidate to clinic in 2023."

Ichnos’ pipeline continues to expand, and the selection of ISB 2001 as Ichnos’ next clinical candidate follows the decision to advance ISB 1442, a CD38 x CD47 biparatopic bispecific antibody for hematologic malignancies, in August 2021. A first-in-human study with ISB 1442 is planned to start in mid-2022. Ichnos’ lead clinical candidate, ISB 1342, a CD38 x CD3 bispecific antibody, continues to enroll patients with relapsed/refractory multiple myeloma in an ongoing Phase 1, dose escalation and expansion study.

On May 9, 2022 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 first quarter ended March 31, 2022 and provided a pipeline update on its six clinical-stage molecules targeting TIGIT, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a and PD-1 across multiple common cancers (Press release, Arcus Biosciences, MAY 9, 2022, View Source [SID1234613968]). In addition, today Arcus announced encouraging results from the third interim analysis of the ongoing Phase 2 ARC-7 study. In this interim analysis, both domvanalimab-containing arms continued to show meaningful differentiation compared to zimberelimab alone across multiple efficacy measures, including overall response rate (ORR) and duration of response (DoR). The clinical activity of zimberelimab alone was in line with established anti-PD-1 therapies in this patient population. At the time of data cut off, no unexpected safety signals were observed.

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"We are optimistic about the potential for and committed to the goal of domvanalimab becoming a best-in-class anti-TIGIT antibody," said Terry Rosen, Ph.D., chief executive officer of Arcus. "The results from our most recent interim analysis further support the significant investment we and Gilead are making in the domvanalimab program, which is on track to increase from two ongoing to four Phase 3 studies by year-end and include expansion into new areas of unmet need with broader populations in lung and upper gastrointestinal cancers. Moreover, with a strong cash balance and six clinical-stage molecules across multiple cancer types, we are well-positioned to develop potentially practice-changing therapies for cancer patients in need of better treatment options."

Anti-TIGIT program (domvanalimab and AB308)

Update on ARC-7:

Arcus conducted a third interim analysis (IA3) for ARC-7, a randomized Phase 2 study evaluating the safety and efficacy of zimberelimab alone vs. domvanalimab plus zimberelimab (doublet) vs. domvanalimab plus zimberelimab and etrumadenant (triplet) as a first-line treatment for metastatic NSCLC PD-L1 TPS≥50% with no actionable mutations. 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.
ARC-7 is an ongoing study and the data continues to mature as more patients are enrolled and patients are followed for longer durations.
Gilead and Arcus are co-developing and equally share co-development costs for the three investigational molecules: domvanalimab, an Fc-silent anti-TIGIT antibody, etrumadenant, a dual adenosine A2a/A2b receptor antagonist, and zimberelimab, an anti-PD1 antibody.
Summary of Efficacy and Safety Observations from IA3:

With more patients and longer follow up, both domvanalimab-containing arms continued to show meaningful differentiation compared to zimberelimab alone across multiple efficacy measures, including ORR and DoR.
Since the last interim analysis, ORR for the doublet continued to increase and further separate from zimberelimab alone.
Although early, the depth of response for the triplet remains encouraging; Arcus and Gilead will continue to monitor the triplet for potential differentiation in duration and depth of response vs. the doublet.
At this interim analysis, Arcus performed its first assessment of DoR. While the data are still immature, at the time of IA3, Arcus observed a substantial improvement for the domvanalimab-containing arms compared to zimberelimab alone.
Zimberelimab alone continued to demonstrate activity consistent with that of marketed anti-PD-1 antibodies in the setting.
No unexpected safety signals were observed; 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.
Other Anti-TIGIT Updates:

In May 2022, Arcus presented Phase 1 and preclinical data at the Annual Meeting of the American Association of Immunologists; the data demonstrated the potential of domvanalimab, as an Fc-silent antibody, to achieve anti-tumor effects and the incidence of pruritis, rash, maculopapular rash and infusion-related adverse events appear to be lower than Fc-enabled anti-TIGIT monoclonal antibodies. The poster can be found in the publications section of the Arcus website.
2022 Anti-TIGIT Milestones:

Enrollment for ARC-7 remains on track to complete mid-2022; we expect to provide a data update in the second half of 2022.
Arcus and Gilead plan to initiate STAR-121, in 4Q 2022, a Phase 3 registrational trial to evaluate the combination of domvanalimab plus zimberelimab and chemotherapy versus standard of care pembrolizumab with chemotherapy in first-line NSCLC PD-L1 all-comers.
STAR-221, a pivotal Phase 3 study of a domvanalimab-based combination in upper gastrointestinal cancers, is currently in advanced stages of planning.
Arcus and Gilead expect to initiate two signal-finding Phase 2 studies to further evaluate multiple domvanalimab-combinations, including triplet combinations with etrumadenant and quemliclustat, by year-end.
Etrumadenant (A2a/A2b adenosine receptor antagonist)

Recent Etrumadenant Updates:

Gilead announced the addition of etrumadenant plus Trodelvy (sacituzumab govitecan-hziy) cohorts in the ongoing Phase 2 ARC-6 trial in castration-resistant prostate cancer.
2022 Etrumadenant Milestones:

As discussed above, Arcus and Gilead expect to initiate a Phase 2 platform study to evaluate domvanalimab-based combinations, including with etrumadenant, this year.
Data analysis from the randomized cohort of ARC-6 evaluating etrumadenant plus zimberelimab and docetaxel versus docetaxel in second-line metastatic castrate-resistant prostate cancer (CRPC) is anticipated in the second half of 2022 with a presentation of results expected in 2023.
Quemliclustat (small molecule CD73 inhibitor)

2022 Quemliclustat Milestones:

Results from ARC-8, including an assessment of progression-free survival, are expected in the second half of 2022 with detailed results to be presented at a future medical congress.
Additional clinical studies for quemliclustat are being planned with Gilead.
AB521 (HIF-2a inhibitor)

Recent AB521 Updates:

Initial PK/PD data from the evaluation of AB521 in healthy human volunteers as well as preclinical data for AB521, alone and in combination with cabozantinib, were presented at the ESMO (Free ESMO Whitepaper) Targeted Anticancer Therapies Congress in March 2022. The early clinical data suggest that AB521 potentially has an improved clinical profile compared to that of the approved HIF-2a inhibitor.
2022 AB521 Milestones:

A Phase 1/1b study to explore AB521 in clear-cell renal cell carcinoma, alone and in combination with other molecules, including those targeting the CD73-adenosine axis, is anticipated to be initiated in mid-2022. Data from the healthy volunteer study should enable Arcus to start dose escalation in patients at a biologically relevant dose level.
Discovery Programs:

AB598 (Arcus’ anti-CD39 antibody) continues to progress through preclinical development, and we expect to file an IND in the first half of 2023. Recent clinical data at AACR (Free AACR Whitepaper) from a competitor antibody is supportive of Arcus’ development plans for this molecule, in combination with other agents in our portfolio.
Arcus anticipates selection of a development candidate for at least one other discovery program to occur this year, with potential for IND filing in 2023.
Financial Results for the First Quarter 2022

Cash, cash equivalents and investments were $1,342.4 million as of March 31, 2022, compared to $681.3 million as of December 31, 2021. The increase was primarily due to the receipt of $725 million from Gilead in January 2022. Arcus expects cash, cash equivalents and marketable securities on-hand to be sufficient to fund operations into 2026.
Revenues: Collaboration and license revenues were $18.0 million for the three months ended March 31, 2022, compared to $9.5 million for the same period in 2021. In the three months ended March 31, 2022, Arcus recognized $8.3 million in collaboration revenue related to Gilead’s ongoing rights to access Arcus’ research and development pipeline in accordance with the Gilead collaboration agreement, $7.9 million in license and development service revenues for all programs optioned by Gilead, based on estimates of progress made toward satisfying the related performance obligations, as well as $1.8 million related to the collaboration agreement with Taiho. In the three months ended March 31, 2021, Arcus recognized $7.7 million in other collaboration revenue related to Gilead’s access to Arcus’ research and development pipeline, as well as $1.8 million related to the Taiho collaboration agreement.
R&D Expenses: Research and development expenses were $61.2 million for the three months ended March 31, 2022, compared to $66.4 million for the same period in 2021. The decrease was due to increased cost-sharing reimbursements from Gilead for its optioned programs and decreases in milestone expenses due to the timing of development milestones and the related payments, largely offset by an increase in costs incurred to support Arcus’ expanded clinical and development activities. There was a $2.3 million increase in compensation costs related to non-cash stock-based compensation to approximately $8.5 million for the three months ended March 31, 2022 compared to the prior year period.
G&A Expenses: General and administrative expenses were $24.0 million for the three months ended March 31, 2022, compared to $15.8 million for the same period in 2021. The increase was driven by the increased size and complexity of Arcus’s clinical development organization associated with Arcus’s expanding clinical pipeline and collaboration obligations. Arcus’s growing employee base and 2022 stock awards drove increases in office facilities expense and employee compensation costs, including a $1.4 million increase in non-cash stock-based compensation to approximately $8.0 million for the three months ended March 31, 2022 compared to the prior year period.
Net Loss: Net loss was $68.0 million for the three months ended March 31, 2022, compared to a net loss of $72.6 million for the same period in the prior year.
Arcus Ongoing and Announced Clinical Studies

Trial Name

Arms

Setting

Status

NCT No.

Lung Cancer

ARC-7

zim vs. dom + zim vs. dom + etruma + zim

1L NSCLC (PD-L1 ≥ 50%)

Ongoing Randomized Phase 2

NCT04262856

PACIFIC-8

dom + durva vs. durva

Curative-Intent Stage 3 NSCLC

Ongoing Registrational Phase 3

NCT05211895

ARC-10

dom + zim vs. zim vs. chemo

1L NSCLC (PD-L1 ≥ 50%)

Ongoing Registrational Phase 3

NCT04736173

STAR-121

dom + zim + chemo vs pembro + chemo

1L NSCLC (PD-L1 all-comers)

Planned Registrational Phase 3

TBD

EDGE-Lung

dom + zim + (quemli or etruma)

1L/2L NSCLC (lung cancer platform study)

In Planning Phase 2

TBD

Gastrointestinal Cancers

ARC-9

etruma + zim + mFOLFOX vs. SOC

2L/3L/3L+ CRC

Ongoing

Randomized Phase 2

NCT04660812

ARC-21

dom + zim ± chemo

1L/2L Upper GI Malignancies

Ongoing

Phase 2

NCT05329766

STAR-221

dom + zim + chemo vs. SOC

GI Malignancies

Planned Registrational Phase 3

TBD

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 (Adding sacituzumab govitecan (Trodelvy) combination cohorts)

2L/3L CRPC

Ongoing Randomized Phase 2

NCT04381832

Various

ARC-12

AB308 + zim

Advanced Malignancies

Ongoing

Phase 1/1b

NCT04772989

ARC-14

AB521

Healthy Volunteer

Ongoing

NCT05117554

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

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 into all other Arcus programs arising during the collaboration term. In November 2021, Gilead and Arcus amended the collaboration in connection with Gilead’s option exercise for three of Arcus’s then-clinical stage programs. For all other programs that are in clinical development or new 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 specified 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 May 2020 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 19.7%, with an additional $220 million investment.

Gilead and Arcus are co-developing and equally share global development costs for five clinical candidates, including domvanalimab, an Fc-silent anti-TIGIT antibody, etrumadenant, a dual adenosine A2a/A2b receptor antagonist, and zimberelimab, an anti-PD1 antibody.