On October 25, 2024 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported that on Oct. 23, 2024, the company approved non-statutory stock options to purchase an aggregate of 13,690 shares of its common stock and 20,250 restricted stock units ("RSUs"), each representing the right to receive one share of its common stock upon vesting, to nineteen new employees (Press release, PTC Therapeutics, OCT 25, 2024, View Source [SID1234647420]). The awards were made pursuant to the Nasdaq inducement grant exception as a component of the new hires’ employment compensation.

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The inducement grants were approved by PTC’s Compensation Committee on Oct. 23, 2024, and are being made as an inducement material to each employee’s acceptance of employment with the company in accordance with Nasdaq Listing Rule 5635(c)(4).

All stock option awards have an exercise price of $42.48 per share, the closing price of PTC’s common stock on Oct. 23, 2024, the immediately preceding trading day. The stock options each have a 10-year term and vest over four years, with 25% of the original number of shares vesting on the first anniversary of the applicable employee’s new hire date and 6.25% of the original number of shares vesting at the end of each subsequent three-month period thereafter until fully vested, subject to the employee’s continued service with the company through the applicable vesting dates. The RSUs each will vest over four years with 25% of the original number of shares vesting on each annual anniversary of the applicable employee’s new hire date until fully vested, subject to the employee’s continued service with the company through the applicable vesting dates.

On October 25, 2024 IDEAYA Biosciences, Inc. (the "Company") reported clinical data from the Company’s Phase 1 expansion dose of IDE397 in patients with methylthioadenosine phosphorylase ("MTAP")-deletion urothelial cancer and non-small cell lung cancer ("NSCLC") in a late breaker abstract oral presentation at the 36th edition of the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium ("ENA 2024") in Barcelona, Spain (Press release, Ideaya Biosciences, OCT 25, 2024, View Source [SID1234647418]). The Company had additional poster presentations at ENA 2024 that highlighted preclinical data for the methionine adenosyltransferase 2 alpha ("MAT2A") and poly (ADP-ribose) glycohydrolase programs. IDE397 is the Company’s potent and selective potential first-in-class MAT2A inhibitor in Phase 2 clinical trials for the treatment of MTAP-deletion solid tumors.

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The interim Phase 1 expansion data for IDE397 in MTAP-deletion urothelial cancer and NSCLC demonstrated preliminary clinical efficacy and a favorable safety profile. The reported Phase 1 clinical data are based on 27 evaluable patients at the expansion dose of 30 mg once-a-day ("QD") of IDE397. The heavily pre-treated MTAP-deletion urothelial cancer and NSCLC patients, including ten urothelial cancer patients, nine adenocarcinoma NSCLC patients and eight squamous NSCLC patients, had a median of two to three prior lines of therapy, ranging from one to seven prior lines of treatment. Reported clinical efficacy and tolerability data are preliminary and based on investigator review from an unlocked database as of the data analysis cutoff date of August 22, 2024.

The Company reported an overall response rate of approximately 33% (one complete response and eight partial responses by RECIST 1.1 evaluation). Nine out of the nine responses have been confirmed, including four urothelial cancer patients (of which one was a complete response), three squamous NSCLC patients and two adenocarcinoma NSCLC patients. Two patients were confirmed after the data cutoff date. The Company also reported overall response rate by RECIST 1.1 evaluation by solid tumor type. For MTAP-deletion urothelial cancer patients, the confirmed overall response rate was 40%, or 4 out of 10 patients, for MTAP-deletion squamous NSCLC patients, the confirmed overall response rate was approximately 38%, or 3 out of 8 patients, and for MTAP-deletion adenocarcinoma NSCLC patients, the confirmed overall response rate was approximately 22%, or 2 out of 9 patients. As the Company previously disclosed in its Current Report on Form 8-K filed with the Securities and Exchange Commission on July 8, 2024, five confirmed responses were reported out of the 18 evaluable patients enrolled in the IDE397 Phase 2 monotherapy study. Further, there were zero non-evaluable patients reported as of the data analysis.

Additionally, multiple confirmed partial responses by RECIST 1.1 evaluation harbored genetic co-alterations, including MTAP-deletion and FGFR-TACC3 fusion in urothelial cancer patients and MTAP-deletion and KRAS G12D mutation in NSCLC patients.

The Company also observed a disease control rate of 93%, including one complete response, eight partial responses and 16 stable disease by RECIST 1.1 evaluation, reflecting 25 of 27 evaluable patients with stable disease or better. Of the 27 evaluable patients, 15 are still on treatment and seven of the nine responses by RECIST 1.1 evaluation responses remain on treatment. The median duration of treatment has not been reached and is greater than 6.2 months. The median time to response is approximately 2.7 months. The median duration of response and median progression free survival data is still immature. Three urothelial cancer patients have been on treatment greater than 250 days, four squamous NSCLC patients on treatment greater than 200 days, and three adenocarcinoma NSCLC patients on treatment greater than 200 days.

The Company also reported a ctDNA molecular response ("MR") rate of approximately 81%, representing 17 of 21 reportable patients with 50% or greater ctDNA reduction and approximately 33%, representing 7 of 21 reportable patients, with a deep 90% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis). All 17 MRs were rapid occurring at the first ctDNA sample analysis.

The interim Phase 1 expansion data for IDE397 in MTAP-deletion urothelial cancer and NSCLC demonstrated a favorable adverse event ("AE") profile at the 30 mg QD expansion dose. Approximately 18% of patients experienced a Grade 3 or higher drug-related AE at the 30 mg QD expansion dose and no drug-related serious adverse events were observed. The Company observed no drug-related AEs leading to discontinuations. The Company anticipates that the favorable AE profile and dosing convenience of a 30 mg QD tablet has the potential to enable long-term dosing and combination development, including with MTA-cooperative PRMT5 inhibitors and topoisomerase payload antibody drug conjugates.

Additionally, the Company reported the first preliminary clinical case study of the IDE397 and Trodelvy (sacituzumab govitecan-hziy), Gilead’s Trop-2 directed antibody-drug conjugate, combination in MTAP-deletion urothelial cancer patients. The Company reported a partial response by RECIST 1.1 evaluation in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation molecular responses with ctDNA reduction of greater than 95% observed, that will be presented at ENA 2024. The Company is targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion urothelial cancer in Q4 2024.

There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumors, highlighting the unmet medical need. The priority MTAP-deletion solid tumor types for the IDE397 Phase 1/2 monotherapy program are urothelial cancer and NSCLC. MTAP-deletion prevalence has been reported at over 15% in NSCLC and over 25% in urothelial cancer, based on The Cancer Genome Atlas ("TCGA") database. The Company estimates that the MTAP-deletion annual incidence in the U.S. in NSCLC and urothelial cancer is approximately 48,000 patients, based on the 2024 Surveillance, Epidemiology, and End Results database. In addition, there are several potential expansion MTAP-deletion solid tumor types that are also being considered for monotherapy and combination development, including pancreatic, head and neck, gastric, and squamous esophageal cancer, among others. Based on the TCGA database, MTAP-deletion prevalence in pancreatic, head and neck, gastric, and squamous esophageal cancer represents an aggregate U.S. annual incidence of approximately 27,000 patients.

The Company has activated over 35 clinical trial sites globally in the U.S., Canada, Europe, and Asia Pacific to enable potential rapid enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer in its ongoing trial (NCT04794699). There is also an ongoing Amgen-sponsored Phase 1/2 trial of IDE397 and AMG 193 combination in MTAP-Deletion NSCLC (NCT05975073). The Company published at ENA 2024 preclinical combination efficacy data and the combination mechanistic rationale for IDE397 with clinical stage PRMT5 inhibitors, including BMS-986504 and AMG 193.

Next, the Company is enrolling a Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy in MTAP-deletion urothelial cancer patients (NCT04794699). Pursuant to the Clinical Trial Collaboration and Supply Agreement dated November 29, 2023, the Company and Gilead retain the commercial rights to their respective compounds, including with respect to use as a monotherapy or combination agent. The Company is the study sponsor and Gilead will provide the supply of Trodelvy. IDE397 monotherapy or in combination with Trodelvy has not been approved by any regulatory agency, and the efficacy and safety of this combination has not been established.

On October 25, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported its financial results for the third quarter of fiscal year 2024 (Press release, Chugai, OCT 25, 2024, View Source [SID1234647417]).

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"In the third quarter of 2024, we achieved increased revenue and profit, primarily driven by strong overseas exports. While the domestic sales continued to be affected by the completion of government supply of Ronapreve in the previous year, as well as the impact of biosimilars and NHI drug price revisions, our overseas revenue growth was led by a significant increase in exports of our in-house developed product Hemlibra to Roche. In consideration of the good progress as of the third quarter, we raised our full year forecasts for FY2024. In research and development, PiaSky received approval in Europe for paroxysmal nocturnal hemoglobinuria (PNH), while NEMLUVIO(nemolizumab), out-licensed to Galderma, was approved in the United States for prurigo nodularis. Furthermore, Alecensa obtained approval for additional indication in Japan for adjuvant therapy for ALK-positive non-small cell lung cancer. We are very pleased that these in-house developed products can contribute to the treatment of more patients. In early-stage development, our in-house project RAY121 initiated a phase Ib basket trial targeting six autoimmune diseases, aiming for early value maximization. This basket trial approach outside the oncology field is a novel challenge with few precedents worldwide. We will continue to pursue innovation to deliver innovative new drugs to patients around the world," said Dr. Osamu Okuda, Chugai’s President and CEO.

Chugai reported increased revenue by 3.7% and operating profit by 25.3% year-on-year for the third quarter (nine months, Core-basis), mainly driven by strong overseas exports, and increase in other revenue.

Regarding revenue, domestic sales decreased by 22.7%. In the oncology field, although the growth of new product Phesgo was favorable, the overall decrease was 5.8% due to Avastin biosimilars and other impacts. In the specialty field, sales decreased by 36.4%, mainly due to continued impact of the completion of Ronapreve supply to the government in the previous year, while our new product Vabysmo grew and PiaSky was launched positively, and our mainstay product Actemra performed well. Overseas, Hemlibra’s exports to Roche increased greatly by 47.9%, leading to the increase by 33.8% in total overseas sales. Our mainstay product Alecensa also performed well, and Enspryng almost doubled its sales compared to the previous year. Other revenue increased by 23.8%, driven by the increase in Hemlibra related income including royalties, and one-time income.

Cost to sales ratio improved by 10.6 percentage points year-on-year to 32.5%, mainly due to a change in the product mix. Research and development expenses increased by 5.1% mainly due to investments into drug discovery and early development, and increases associated with the progress of development projects. Selling, general and administration expenses increased by 1.5% mainly due to foreign exchange rate fluctuations and an increase in the enterprise tax (pro forma standard taxation). Other operating income (expense) was ¥2.4 billion in income, including the recognition of income from disposal of product rights. As a result, Core operating profit totaled ¥426.6 billion (+25.3%).

Chugai also made good progress in research and development, in both early and late stages of developments.

For in-house products, Alecensa has been granted additional indication in Japan and Taiwan for adjuvant treatment of ALK-positive non-small cell lung cancer (NSCLC). Additionally, PiaSky, an anti-complement (C5) recycling antibody, has been approved in Europe for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). It is the first monthly (every four weeks) subcutaneous treatment for PNH in Europe. Furthermore, NEMLUVIO, developed by Galderma outside of Japan, has been approved under priority review in the U.S. as the treatment of adults with prurigo nodularis. In early development, RAY121, an anti-complement C1s recycling antibody, has initiated a phase Ib clinical study as a basket study in six autoimmune diseases. Moreover, BRY10 has initiated a phase I clinical study for chronic diseases and has been added to the pipeline.

For the products in-licensed from Roche, delandistrogene moxeparvovec, a gene therapy product (development code: SRP-9001, overseas product name: Elevidys) has been filed for Duchenne muscular dystrophy. Additionally, Vabysmo has been filed for an additional indication for angioid streaks associated with neovascularization. Evrysdi has been approved for an additional indication for pre-symptomatic spinal muscular atrophy (SMA) and an additional dosage for SMA infants under 2 months of age. Furthermore, divarasib, the KRAS G12C inhibitor, has initiated a phase III clinical study for second-line treatment of NSCLC. In addition, Chugai has in-licensed the PI3K inhibitor inavolisib for PIK3CA-mutated breast cancer and the anti-TL1A therapy RG6631 for refractory diseases such as ulcerative colitis and Crohn’s disease.

Chugai raised forecasts (Core-basis) for FY2024 following the strong nine-month results. Regarding domestic sales, the forecasted sales amount reflects the progress and revised assumptions for products including Phesgo, Polivy, Vabysmo, and Perjeta. For overseas sales, mainly Hemlibra and Actemra exports to Roche have been forecasted to be higher than the original forecast. For other revenue, the forecasts for items including one-time income and royalties have also been updated. As a result, revenue has been raised to ¥1,150.0 billion, an increase of ¥80.0 billion from the initial forecast. Operating profit forecast has been revised to ¥540.0 billion, up ¥80.0 billion from the initial forecast, taking into account a lower cost to sales ratio due to a change in the product mix from the initial assumption, and increase in some expenses.

Reflecting the significant changes in the business environment, year-end dividend forecast has been revised to undecided. The year-end dividends will be decided after the fiscal year end based on basic profit distribution principles*.
*Regarding income distribution, taking into account the strategic funding needs and earning prospects, Chugai aims for a consolidated dividend payout ratio of 45% on average in comparison with Core EPS to provide a stable allocation of profit to all shareholders.

[2024 third quarter results]

Billion JPY 2024
Jan – Sep 2023
Jan – Sep % change
Core results
　Revenue 868.5 837.6 +3.7%
　　Sales 750.3 742.1 +1.1%
　　Other revenue 118.2 95.5 +23.8%
　Operating profit 426.6 340.5 +25.3%
　Net income 301.3 250.3 +20.4%
IFRS results
　Revenue 868.5 837.6 +3.7%
　Operating profit 418.6 317.6 +31.8%
　Net income 295.8 234.3 +26.2%
[Sales breakdown]

Billion JPY 2024
Jan – Sep 2023
Jan – Sep % change
Sales 750.3 742.1 +1.1%
　Domestic sales 331.7 429.2 -22.7%
　　Oncology 180.3 191.4 -5.8%
　　Specialty 151.3 237.9 -36.4%
　Overseas sales 418.7 312.9 +33.8%
[Oncology field (Domestic) Top5-selling medicines]

Billion JPY 2024
Jan – Sep 2023
Jan – Sep % change
　Tecentriq 47.4 47.9 -1.0%
　Avastin 25.6 38.2 -33.0%
　Polivy 24.5 25.5 -3.9%
　Alecensa 22.4 22.0 +1.8%
　Perjeta 15.7 24.6 -36.2%
[Specialty field (Domestic) Top5-selling medicines plus Ronapreve]

Billion JPY 2024
Jan – Sep 2023
Jan – Sep % change
　Hemlibra 41.5 40.5 +2.5%
　Actemra 34.8 32.2 +8.1%
　Enspryng 17.8 16.9 +5.3%
　Vabysmo 14.7 10.8 +36.1%
　Evrysdi 11.3 10.3 +9.7%
　Ronapreve* - 81.2 -100.0%
*Ronapreve has not been listed in the National Health Insurance (NHI) price list.

[Forecasts for 2024 Jan-Dec]

Billion JPY Revised forecast
on Oct 25 Original forecast
on Feb 1 Growth vs
original forecast Growth vs
2023 actual
Core-basis
Revenue 1,150.0 1,070.0 +7.5% +38.6, +3.5%
　Sales 986.0 922.0 +6.9% +11.5, +1.2%
　Other revenue 164.0 148.0 +10.8% +27.1, +19.8%
Operating profit 540.0 460.0 +17.4% +89.3, +19.8%

About Core results

Chugai discloses its results on a Core basis from 2013 in conjunction with its decision to apply IFRS. Core results are the results after adjusting non-Core items to IFRS results. Chugai’s recognition of non-recurring items may differ from that of Roche due to the difference in the scale of operations, the scope of business and other factors. Core results are used by Chugai as an internal performance indicator, for explaining the underlying business performance both internally and externally, and as the basis for payment-by-results such as a return to shareholders.

Trademarks used or mentioned in this release are protected by law.

On October 24, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported data from the ongoing global Phase 1a/1b study of ZL-1310, a potential best-in-class next-generation antibody-drug conjugate (ADC), at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium 2024 in Barcelona, Spain, as an oral presentation during the plenary session (Press release, Zai Laboratory, OCT 24, 2024, View Source [SID1234647391]). ZL-1310 is being tested in patients with previously treated extensive-stage Small Cell Lung Cancer (ES-SCLC) after at least one prior platinum-based chemotherapy regimen.

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Data shared in the ENA presentation from the ongoing Part 1a monotherapy dose-escalation portion of the study included results from 25 patients across four dose cohorts (0.8 mg/kg, 1.6mg/kg, 2.0 mg/kg, and 2.4 mg/kg). Nineteen patients had evaluable tumor assessments.

Key efficacy results include (n=19):

The ORR in patients with at least one post-treatment evaluation was 74% (95%CI, 48.8, 90.9). ZL-1310 anti-tumor activity was demonstrated across all dose levels.
Responses were seen in patients with DLL3 H-scores from 5 (range: 5 to 260). No response was observed in a patient whose tumor did not express DLL3.
Across all cohorts, median length of follow up is 2.4 months making duration of response not estimable. Of the 14 responders, 13 remain on treatment with the longest patient ongoing at 6.5+ months.
Of the six response-evaluable patients with baseline brain metastases, all achieved a partial response (PR).
One patient who progressed after prior DLL3 bi-specific therapy achieved PR at the first tumor assessment.
Key safety findings include (n=25):

ZL-1310 was well tolerated across all dose levels with the majority of treatment emergent adverse events (TEAE) being Grade 1 or 2. One dose-limiting toxicity (DLT) was observed at 2.4mg/kg (Grade 4 transient neutropenia/thrombocytopenia). Grade ≥3 treatment-related adverse events occurred in five of the 25 patients (20%); neutropenia was the most common grade ≥3 event, occurring in three of the 25 patients (12%). Serious treatment-related adverse events occurred in two patients (8%); three patients (12%) required dose reductions, and no patients discontinued treatment due to TEAE.
All patients had progressed following standard platinum-based chemotherapy, and 92% of patients progressed after immune checkpoint inhibitors. Fifty-six percent had failed at least two prior lines of therapy. Twenty-eight percent of patients had brain metastases at baseline. At the time of the data cutoff, Oct. 10, 2024, 19 patients had at least one post-baseline tumor assessment per RECIST v1.1. DLL3 expression H-scores were assessed in 16 out of 19 patients.

"The preliminary results from the ongoing Phase 1 trial of ZL-1310 suggest that this next-generation ADC therapy has the potential to deliver anti-tumor responses in the majority of patients with ES-SCLC, with good tolerability," said Dr. Alex Spira, a medical oncologist at Virginia Cancer Specialists and NEXT Oncology. "This is particularly encouraging given the urgent need for improved treatment options for these patients. These promising data support continued evaluation of ZL-1310 as a monotherapy in the dose-expansion phase of the ongoing Phase 1 clinical trial and in combination."

"The ZL-1310 clinical program demonstrates Zai Lab’s commitment and ability to pursue novel modalities and validated cancer targets, and to advance innovative global oncology programs," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "Based on the encouraging preliminary findings from our Phase 1 trial, we look forward to continuing development of ZL-1310 and advancing this promising asset across lines of therapy as part of our global oncology pipeline."

Webcast and Conference Call

To access the webcast and conference call on October 24, 2024, at 8:30 a.m. ET, please register at https://register.vevent.com/register/BI6f8ba8dc42d04cd3afd7095cf7c83d40.

All participants must use the link provided above to complete the online registration process in advance of the conference call. Dial-in details will be in the confirmation email which the participant will receive upon registering.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website.

On October 24, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, reported the first clinical activity data for casdatifan, a HIF-2a inhibitor with best-in-class potential, in an oral plenary session by Dr. Toni K. Choueiri, Dana-Farber Cancer Institute at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain (Press release, Arcus Biosciences, OCT 24, 2024, View Source [SID1234647390]).

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"Based on our experience in the ARC-20 study, we have seen casdatifan’s ability to quickly bring tumor growth under control and its high response and disease control rates," said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber, the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School and lead investigator of ARC-20. "Based on these data, casdatifan has the potential to be a future treatment option for kidney cancer. I am particularly interested in planned research into novel combinations for casdatifan in both first- and second-line ccRCC."

"In the 100mg daily dose-expansion cohort of ARC-20, casdatifan showed encouraging results, particularly a low primary progressive disease rate and very durable responses. This was accomplished with a manageable safety profile," said Dimitry Nuyten, M.D., Ph.D., chief medical officer of Arcus. "These data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC. We look forward to initiating our first Phase 3 study for casdatifan, PEAK-1, in the first half of 2025, and expanding our development program into the first-line setting with a novel combination, as well as into other ccRCC subpopulations."

ARC-20 is a Phase 1/1b dose-escalation and -expansion study. In the dose escalation (20mg to 200mg) portion of the study, the safety profile was comparable across the doses; there were no dose-limiting toxicities, and the maximum tolerated dose was not reached at daily doses of up to 150 mg (200 mg portion of the study is currently ongoing). The 100 mg daily dose (50 mg BID [twice daily]) was selected for dose expansion, and casdatifan was evaluated in patients with metastatic ccRCC who had progressed on at least two prior lines of therapy, including both an anti-PD-1 and a tyrosine kinase inhibitor (TKI) therapy (n=33). The patient population was heavily pre-treated: 52% had received at least three prior lines of therapy; 26% had received at least four prior lines of therapy; and 61% had an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor of intermediate.

At the time of data cut off (DCO, Aug. 30, 2024), median follow-up was 11 months. Casdatifan showed a rapid time to response, and only 19% of patients had primary progressive disease (progressed at or before their first disease assessment). The majority of patients (81%) experienced disease control with either a partial response or stable disease. At the time of the DCO, the median progression-free survival had not been reached. 34% of patients experienced an objective response, meaning their tumor shrank by at least 30%. A summary of initial results is below.

Objective Response Rate (ORR) per RECIST v1.1

100mg Efficacy-Evaluable* Population (n=32)

ORR

[95% CI]

34% (11)**

[16,50]

Responses Pending Confirmation

2**

Confirmed ORR

[95% CI]

25% (8)

[12,43]

Progressive Disease

19% (6)

Disease Control Rate

[95% CI]

81%

[64,93]

Median Progression-Free Survival

Not Reached

CI=confidence interval

*100mg daily dose is 50mg BID (twice daily); efficacy-evaluable population for this expansion cohort is defined as all eligible participants who have measurable disease at baseline, receive at least one dose of casdatifan, and have at least one post-baseline efficacy assessment, or who discontinue study treatment due to progressive disease or death. One participant was enrolled but deemed not eligible for the study and was not evaluated for efficacy.

**One patient achieved a response after DCO and nearly a year on treatment, which increased the ORR from 31% (10) to 34%.

In the 100mg dose-expansion cohort, no unexpected safety signals were observed at the time of DCO, and casdatifan had an acceptable and manageable safety profile. Grade 3 treatment-emergent adverse events (TEAEs) related to casdatifan were 42%, including anemia (36%) and hypoxia (9%). No patients discontinued treatment from anemia. No TEAEs were life-threatening or led to death.

Arcus is pursuing a broad development program in both the first-line and post-anti-PD-1 settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. In addition to the monotherapy cohorts of ARC-20, the study is also enrolling a cohort to evaluate casdatifan in combination with cabozantinib, a VEGFR TKI which is intended to support the initiation of Arcus’s planned first Phase 3 study, PEAK-1, evaluating casdatifan in combination with cabozantinib versus cabozantinib monotherapy in patients with metastatic ccRCC who have previously received anti-PD-1 therapy. The primary endpoint will be progression-free survival with a key secondary endpoint of overall survival. Arcus also recently announced a clinical collaboration as part of its first-line strategy in advanced ccRCC to evaluate casdatifan in combination with volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody.

Investors may dial in to the conference call at +1 (404) 975- 4839 (local) or +1 (833) 470-1428 (toll-free), using Conference ID: 595409 on Thursday, October 24, 2024 at 5:00 AM PT / 8:00 AM ET. Participants may also register for the call online using the following link: View Source;confId=70796. In addition to the ARC-20 data, the conference call will address the development strategy and market potential for casdatifan. Arcus will also be joined by Dr. Rana McKay of the University of California San Diego. To access the live webcast and accompanying slide presentation, please visit the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay will be available following the live event.

About Casdatifan (AB521)

Casdatifan is a small-molecule inhibitor of HIF-2a, a tumorigenic transcription factor involved in oxygen sensing in multiple organs as well as in tumors. Clear cell RCC is almost universally associated with HIF-2a dysregulation as a result of genetic abnormalities in the VHL pathway. This creates a situation of pseudohypoxia and the abnormal increase in HIF-2a-mediated expression of a broad range of oncogenic proteins. By selectively inhibiting HIF-2a, casdatifan is designed to disable a wide array of pathways involved in tumor proliferation and survival, treatment resistance and angiogenesis, leading to cancer cell death. Casdatifan is being evaluated in ARC-20, a Phase 1/1b study in cancer patients, and STELLAR-009, a Phase 1b/2 study in combination with zanzalintinib in patients with advanced solid tumors, including ccRCC.

Under the Gilead and Arcus collaboration agreement, Gilead has the right to opt-in to development and commercialization for casdatifan after Arcus’s delivery of a qualifying data package.

Casdatifan is an investigational molecule. Approval from any regulatory authority for its use has not been received, and its safety and efficacy have not been established.

About RCC

According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 81,600 Americans will be diagnosed with kidney cancer in 2024. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 15%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment.