On June 2, 2025 Sanofi and Blueprint Medicines Corporation (Blueprint), a US-based, publicly traded biopharmaceutical company specializing in systemic mastocytosis (SM), a rare immunological disease, and other KIT-driven diseases, reported to have entered into an agreement under which Sanofi will acquire Blueprint (Press release, Blueprint Medicines, JUN 2, 2025, View Source [SID1234653560]).

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The acquisition includes a rare immunology disease medicine, Ayvakit/Ayvakyt (avapritinib), approved in the US and the EU, and a promising advanced and early-stage immunology pipeline. Furthermore, Blueprint’s established presence among allergists, dermatologists, and immunologists is expected to enhance Sanofi’s growing immunology pipeline.

Ayvakit/Ayvakyt is the only approved medicine for advanced and indolent systemic mastocytosis (ASM & ISM), a rare immunology disease, which is characterized by the accumulation and activation of aberrant mast cells in bone marrow, skin, the gastrointestinal tract, and other organs. The acquisition will also bring elenestinib, a next-generation medicine for SM, as well as BLU-808, a highly selective and potent oral wild-type KIT inhibitor that has the potential to treat a broad range of diseases in immunology.

Under the terms of the acquisition, Sanofi will pay $129.00 per share in cash at closing, representing an equity value of approximately $9.1 billion. Blueprint shareholders also will receive one non-tradeable contingent value right (CVR) which will entitle the holder to receive two potential milestone payments of $2 and $4 per CVR for the achievement, respectively, of future development and regulatory milestones for BLU-808. The total equity value of the transaction, including potential CVR payments, represents approximately $9.5 billion on a fully diluted basis.

Paul Hudson
CEO, Sanofi
"The proposed acquisition of Blueprint Medicines represents a strategic step forward in our rare and immunology portfolios. It enhances our pipeline and accelerates our transformation into the world’s leading immunology company. This acquisition is fully aligned with our strategic intent to strengthen our existing therapeutic areas, to bring relevant and differentiated medicines to patients and to secure attractive returns to our shareholders. It complements recent acquisitions of early-stage medicines that remain our main field of interest. Sanofi still retains a sizeable capacity for further acquisitions. We are excited to welcome Blueprint’s talented people and we look forward to chasing the miracles of science together. This makes sense for science, for both companies, for healthcare professionals, and – most of all – for patients."

Kate Haviland
CEO, Blueprint Medicines
"Since our founding, Blueprint Medicines has worked at the intersection of scientific innovation and operational excellence. I’m incredibly proud of the medical innovations our people have created and delivered to patients. We have translated our unique scientific understanding of mast cell biology into a portfolio of important therapies including Ayvakit – the first and only medicine approved to treat the root cause of systemic mastocytosis – and worked collaboratively with communities to improve standards of care and patient outcomes. With this agreement, we begin our next chapter with Sanofi, whose exceptional leadership in rare disease and immunology and proven ability to solve medical challenges at scale stand to accelerate our joint mission to bring life-changing medicines to many more patients around the world."

Mast cells play an important role in immune responses and are typically found in tissues that encounter the external environment, such as the skin, lungs, and gastrointestinal tract. Upon activation, mast cells release pro-inflammatory molecules such as histamines and proteases. Systemic mastocytosis is a rare immunologic disorder that can lead to a range of debilitating symptoms across multiple organ systems and a significant impact on patients’ quality of life. The symptoms that patients with SM experience can include anaphylaxis, bone disease, gastrointestinal distress and skin lesions. ISM represents the majority of SM cases.

Ayvakit achieved net revenues of $479 million in 2024 and nearly $150 million in Q1 2025, representing year-on-year growth of more than 60 percent over Q1 2024. The oral medicine is a potent and selective inhibitor of activated KIT and PDGFRA mutant kinases. In certain diseases, mutations in KIT and PDGFRA force protein kinases into an increasingly active state and Ayvakit/Ayvakyt is designed to bind and inhibit these proteins.

Elenestinib is a next-generation, potent and highly selective KIT D816V inhibitor with limited central nervous system penetration. The oral investigational ISM medication is the subject of HARBOR, a phase 2/3 study (clinical study identifier: NCT04910685). The ongoing, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of elenestinib plus symptom-directed therapy in patients with ISM and smoldering SM.

BLU-808 is an investigational oral, highly potent and selective wild-type KIT inhibitor that was developed leveraging Blueprint’s expertise in mast cell biology. Wild-type KIT plays a central role in mast cell activation, which is implicated in a broad range of inflammatory diseases.

Transaction terms and financial considerations
Under the terms of the merger agreement, Sanofi will commence a cash tender offer to acquire all outstanding shares of Blueprint for $129.00 per share in cash, reflecting a total equity value of approximately $9.1 billion. In addition, Blueprint’s shareholders will receive one non-tradeable CVR per Blueprint share with two potential milestone payments as follows:

$2 per share, conditioned upon the achievement of a clinical development milestone for BLU-808, and
$4 per share, conditioned upon the achievement of a regulatory milestone for BLU-808.
The upfront offer price represents a premium of approximately 27% over the closing price of Blueprint on May 30, 2025 and a premium of approximately 34% over the 30 trading days volume weighted average price (VWAP) of Blueprint as of May 30, 2025. Together with the CVR, the premium is approximately 33% over the closing price on May 30, 2025 and approximately 40% over the 30 trading days VWAP.

The consummation of the tender offer is subject to customary closing conditions, including the tender of a number of shares of Blueprint common stock representing at least a majority of the outstanding shares of Blueprint common stock, the receipt of required regulatory approvals, and other customary conditions.

If the tender offer is successfully completed, a wholly owned subsidiary of Sanofi will merge with and into Blueprint and all of the outstanding Blueprint shares that are not tendered in the tender offer will be converted into the right to receive the same $129.00 per share in cash and one CVR per share offered to Blueprint shareholders in the tender offer. Sanofi plans to finance the transaction with a combination of cash on hand and proceeds from new debt. The tender offer is not subject to any financing condition. Subject to the satisfaction or waiver of customary closing conditions, Sanofi currently expects to complete the acquisition in the third quarter of 2025. The acquisition will not have a significant impact on Sanofi’s financial guidance for 2025. It is immediately accretive to gross margin and accretive to business operating income and EPS after 2026.

Conference call for investors and analysts
Sanofi will host a conference call for investors and analysts at 08:30 CEST today. A presentation will be available for download from the Investor Relations section of sanofi.com before the conference call starts.

The call will be held on Zoom with the following access details:
View Source
Webinar ID: 979 9146 5119
Passcode: 801394

About Ayvakit
Ayvakit (avapritinib) is the first and only medicine approved by the US Food and Drug Administration (FDA) to treat the root cause of SM. It was FDA approved for the treatment of advanced SM in June 2021 and indolent SM in May 2023. It now is indicated in adults with ISM, adults with advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. The medicine is approved in the EU as Ayvakyt for the treatment of adults with ISM with moderate to severe symptoms inadequately controlled on symptomatic treatment, adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. Globally, the medicine is approved for one or more indications in 16 countries, including China where it is marketed by CStone Pharmaceuticals, paying tiered percentage royalties on sales.

On June 2, 2025 Novartis reported topline results from a pre-specified interim analysis of the Phase III PSMAddition trial. The trial met its primary endpoint with a statistically significant and clinically meaningful benefit in radiographic progression-free survival (rPFS) with a positive trend in overall survival (OS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic hormone-sensitive prostate cancer (mHSPC) treated with radioligand therapy (RLT), Pluvicto (lutetium (177Lu) vipivotide tetraxetan), in combination with standard of care (SoC) versus SoC alone (Press release, Novartis, JUN 2, 2025, View Source [SID1234653556]). In PSMAddition, the SoC is a combination of androgen receptor pathway inhibitor (ARPI) therapy and androgen deprivation therapy (ADT)3.

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Almost all mHSPC patients ultimately progress to metastatic castration-resistant prostate cancer (mCRPC)4. There is a need for additional treatment options with novel mechanisms of action that further delay progression, prolong OS and improve disease control compared to the current SoC, while showing a favorable safety and tolerability profile.

"The progression from metastatic hormone-sensitive prostate cancer to castration-resistant disease remains a formidable challenge that can profoundly impact the survival of patients," said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer at Novartis. "These results further strengthen our confidence in Pluvicto as a PSMA-targeted radioligand therapy. Following the recent FDA approval based on the PSMAfore trial in metastatic castration-resistant prostate cancer, these data suggest using it in an earlier disease setting could advance care and address a significant unmet need for hormone-sensitive prostate cancer patients."

This is the third positive read-out for Pluvicto in a Phase III trial, following the VISION and PSMAfore studies5,6. Results from PSMAddition in mHSPC show potential for treatment in an earlier setting with Pluvicto, which was recently granted US Food and Drug Administration (FDA) approval for earlier use in mCRPC, based on results from PSMAfore1,2. Novartis is harnessing the innovation of world-class scientists, strategic partnerships and one of the industry’s most competitive pipelines to explore the potential of new, targeted therapies and precision medicine platforms to address the greatest unmet needs in prostate cancer.

Data will be presented at an upcoming medical meeting and, based on FDA feedback, will be submitted for regulatory review in the second half of the year.

About PSMAddition study
PSMAddition (NCT04720157) is a Phase III, open-label, prospective, 1:1 randomized study comparing the efficacy and safety of Pluvicto in combination with SoC (ARPI + ADT) vs. SoC alone in adult patients with PSMA-positive mHSPC3. Patients randomized to the SoC alone arm are allowed to crossover to receive Pluvicto, upon confirmation of radiographic progression by blinded independent review committee (BIRC) and per the discretion of the treating physician3. The primary endpoint is rPFS, defined as the time to radiographic progression by PCWG3-modified RECIST V1.1 (as assessed by BIRC) or death3. The key secondary endpoint of OS is defined as time to death due to any cause3.

About Pluvicto (INN: lutetium (177Lu) vipivotide tetraxetan)
Pluvicto is an intravenous RLT that combines a targeting compound (a ligand) with a therapeutic radionuclide (a radioactive particle, in this case lutetium-177)5,7. After administration into the bloodstream, Pluvicto binds to PSMA-expressing target cells, including prostate cancer cells that express PSMA, a transmembrane protein5,7. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells, disrupting their ability to replicate and/or triggering cell death7. Pluvicto is the only PSMA-targeted agent approved for PSMA-positive mCRPC and is the first targeted RLT to demonstrate a clinical benefit for patients with PSMA-positive mHSPC1. Novartis is investigating Pluvicto in earlier stages of disease, including oligometastatic prostate cancer (PSMA-DC, NCT05939414).

On June 1, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) and Novocure (NASDAQ: NVCR) reported that results from the Phase 3 PANOVA-3 trial of Tumor Treating Fields (TTFields) therapy for pancreatic cancer will be presented today at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago and simultaneously published in the Journal of Clinical Oncology (Press release, Zai Laboratory, JUN 1, 2025, View Source [SID1234653574]).

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"The data presented today from the PANOVA-3 trial of Tumor Treating Fields show a clinically meaningful and statistically significant improvement in overall survival for people with locally advanced pancreatic cancer," said Vincent Picozzi, MD, MMM, medical oncologist and investigator in the PANOVA-3 trial. "Importantly, we also saw an extension in the duration of time before pain progressed. Pain is a hallmark of this disease, and as a clinician, the potential of this therapy to address this aspect of pancreatic cancer is very encouraging. These results illustrate the potential of Tumor Treating Fields therapy concomitant with gemcitabine and nab-paclitaxel to become a standard of care for unresectable, locally advanced pancreatic cancer."

The Phase 3 PANOVA-3 trial evaluated the use of TTFields therapy concomitantly with gemcitabine and nab-paclitaxel as a first-line treatment for unresectable, locally advanced pancreatic adenocarcinoma compared to gemcitabine and nab-paclitaxel alone. The trial met its primary endpoint, demonstrating a statistically significant improvement in median overall survival (mOS) for patients treated with TTFields.

"The encouraging data from the Phase 3 PANOVA-3 study demonstrate a meaningful improvement in outcomes for patients with unresectable, locally advanced pancreatic cancer—including pain reduction and a statistically significant improvement in overall survival," said Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. "Pancreatic cancer remains one of the most challenging cancers to treat globally, with approximately 134,000 new cases diagnosed annually in China alone. Zai Lab participated in this trial and looks forward to continuing our collaboration with Novocure to bring this innovative therapy to patients in China as quickly as possible."

"Most people with pancreatic cancer are diagnosed with advanced disease, which is very difficult to treat and only about 1 in 10 people are alive five years after diagnosis," said Nicolas Leupin, MD, PhD, Chief Medical Officer, Novocure. "The results shared today at ASCO (Free ASCO Whitepaper) and in the Journal of Clinical Oncology demonstrate that Tumor Treating Fields therapy improved overall survival and pain-free survival in unresectable, locally advanced pancreatic cancer. We plan to submit these data to the FDA in the second half of 2025 to support a premarket approval for Tumor Treating Fields therapy."

Results from PANOVA-3

In the intent-to-treat population, patients treated with TTFields therapy concomitantly with gemcitabine and nab-paclitaxel had an mOS of 16.2 months compared to 14.2 months for patients treated with gemcitabine and nab-paclitaxel alone, a statistically significant 2.0-month improvement [hazard ratio (HR) 0.82; p=0.039 (N=571)].

TTFields therapy concomitant with gemcitabine and nab-paclitaxel demonstrated improvement in several secondary endpoints including the one-year survival rate and pain-free survival. Pancreatic cancer can cause significant pain as the disease progresses and managing pain is a key clinical challenge.

The one-year survival rate showed a statistically significant improvement in the TTFields concomitant with gemcitabine and nab-paclitaxel treated group with 68.1% [95% CI: 62.0–73.5] compared to those who received gemcitabine and nab-paclitaxel alone, 60.2% [95% CI: 54.2–65.7], p=0.029.
Patients treated with TTFields concomitant with gemcitabine and nab-paclitaxel had a median pain-free survival of 15.2 months [95% CI: 10.3–22.8] compared to a median 9.1 months in the group treated with gemcitabine and nab-paclitaxel alone [95% CI: 7.4–12.7]; HR 0.74 [95% CI: 0.56–0.97], p=0.027. This is a statistically significant 6.1-month extension in pain-free survival. Pain-free survival was defined as the time from baseline until an increase of 20 or more points was reported by patients on a visual scale for pain or until death.
Quality of life was also measured as a secondary endpoint. Analyses were performed for all patients using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) with the pancreatic cancer specific PAN26 addendum. Deterioration-free survival in global health status, pain and digestive problems were significantly improved in patients receiving TTFields therapy concomitant with gemcitabine and nab-paclitaxel compared to the gemcitabine and nab-paclitaxel alone group. Full analysis of the quality of life results in PANOVA-3 will be shared at a future scientific conference.

There was no statistically significant difference in additional secondary outcome measures of progression-free survival, local progression-free survival, objective response rate, puncture-free survival or tumor resectability rate between the TTFields with gemcitabine and nab-paclitaxel and the gemcitabine and nab-paclitaxel arms.

TTFields therapy was well-tolerated, no new safety signals were observed, and safety was consistent with prior clinical studies. Mild to moderate skin adverse events (AEs) were the most common device-related AEs.

Data Presentation & Publication Details

The PANOVA-3 data, (LBA 3500) Phase 3 study of Tumor Treating Fields (TTFields) with gemcitabine and nab-paclitaxel for locally advanced pancreatic ductal adenocarcinoma (LA-PAC), will be presented today by Dr. Picozzi in Hall D1 during the 3:00 – 6:00 p.m. Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary oral session.

The Phase 3 PANOVA-3 publication in the Journal of Clinical Oncology, Tumor Treating Fields with gemcitabine and nab-paclitaxel for locally advanced pancreatic adenocarcinoma: randomized, open-label, pivotal phase 3 PANOVA-3 study, will be available online at View Source

On June 1, 2025 Protagonist Therapeutics, Inc. ("Protagonist") (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) reported detailed results from the Phase 3, randomized, placebo-controlled VERIFY study evaluating rusfertide in patients with polycythemia vera (PV), which met the primary and all key secondary endpoints (Press release, Takeda, JUN 1, 2025, View Source [SID1234653573]). The data will be presented as a late-breaking oral presentation at the 61st American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting Plenary Session (LBA3) at 2:09 pm CDT today.

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PV is characterized by overproduction of red blood cells (erythrocytosis), which may increase blood viscosity, or thickness, potentially resulting in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. People with PV can experience burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus, which may negatively impact their daily functioning and quality of life. Hematocrit is the ratio of red blood cells to total amount of blood in the body. Achieving and maintaining controlled hematocrit levels of <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate symptoms, but many patients still experience uncontrolled hematocrit levels with current standard of care treatments.

Rusfertide, an investigational, first-in-class hepcidin mimetic peptide therapeutic, is under evaluation in the Phase 3 VERIFY study for its potential to regulate iron homeostasis and red blood cell production to control hematocrit levels in patients with PV. In the study, patients dependent on frequent phlebotomy, with or without treatment with cytoreductive therapy, were randomized to receive once-weekly rusfertide or placebo, as an add-on to current standard of care treatment.

"PV poses significant challenges for patients, including debilitating symptoms and the risk of serious thrombotic events, and hematocrit control is crucial to improving patient outcomes. The VERIFY study demonstrated that treatment with rusfertide controls hematocrit levels in phlebotomy-dependent patients, including patients receiving cytoreductive therapies," said Dr. Andrew T. Kuykendall, M.D., VERIFY Lead Investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. "These results suggest rusfertide has the potential to become part of the standard of care treatment for patients with PV."

The study met its primary endpoint, which was the proportion of patients achieving a clinical response, defined as the absence of phlebotomy eligibility during study Weeks 20-32. Study results demonstrated 76.9% of patients treated with rusfertide plus current standard of care achieved a clinical response, compared to 32.9% in the placebo plus current standard of care group (p<0.0001).1 The response observed in the rusfertide arm was consistent across subgroups, regardless of risk status or type of concurrent cytoreductive therapy.1 In addition, all key secondary endpoints met statistical significance in favor of the rusfertide arm compared to the placebo arm in the VERIFY study, as follows:

The mean number of phlebotomies was 0.5 phlebotomies per patient for those treated with rusfertide plus current standard of care compared to 1.8 phlebotomies per patient for those treated with placebo plus current standard of care during Weeks 0-32 (p<0.0001).1
Only 27% of patients treated with rusfertide plus current standard of care required phlebotomy between Weeks 0-32, compared to 78% of patients who received placebo plus current standard of care.
The mean number of phlebotomies during Weeks 0-32 in the rusfertide arm was reduced across subgroups, including risk status and use of concurrent cytoreductive therapy, versus the placebo arm.
62.6% of patients treated with rusfertide plus current standard of care maintained hematocrit levels below 45% versus 14.4% treated with placebo plus current standard of care (p<0.0001).1
Rusfertide also showed statistically significant improvements in mean change from baseline to Week 32 in PROMIS Fatigue2 (p<0.03) and the MFSAF Total Symptom Score3 (p<0.03). Rusfertide is the first investigational therapy to prospectively demonstrate a statistically significant improvement in these patient-reported outcomes (PROs) of fatigue and symptom burden in patients with PV.1
Rusfertide was generally well tolerated. The majority of adverse events were low grade and non-serious and no serious adverse events considered related to rusfertide were reported. There was no evidence of increased risk of cancer in patients treated with rusfertide plus current standard of care compared to patients treated with placebo plus current standard of care at the time of the primary analysis. Cancer events were reported in one patient in the rusfertide arm (0.7%) and in seven patients in the placebo arm (4.8%). The most common treatment-emergent adverse events were localized injection site reactions (55.9%), anemia (15.9%) and fatigue (15.2%).1

"These findings underscore rusfertide’s potential as a first-in-class erythrocytosis-specific treatment for PV and validate more than a decade of scientific innovation originating from Protagonist’s peptide technology platform," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "We would like to thank all the patients, study staff and investigators for participating in the VERIFY study. We are pleased to partner with Takeda as we continue to advance rusfertide to potentially transform the standard of care in PV patients around the world."

"These promising pivotal data strongly support rusfertide’s potential benefit for a broad spectrum of patients with PV who may be receiving current standard of care therapies but not achieving adequate hematocrit control," said Phuong Khanh (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit (OTAU) at Takeda. "We look forward to receiving additional data from the VERIFY trial later this year, advancing rusfertide towards regulatory approval and continuing our collaboration with Protagonist to bring this innovative therapy to patients."

Rusfertide has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA).

Takeda Investor Conference Call and Webcast Details

Takeda will host an investor call regarding this update on Sunday, June 1, 6-6:45 pm CDT/ 7-7:45 pm EDT / Monday, June 2, 08:00-08:45 (JST).

The call will be held using the Zoom platform and Zoom simultaneous interpretation function. Kindly pre-register from the below link:
View Source

An on-demand replay will be made available on Takeda’s website after the conclusion of the event.

Protagonist Investor Conference Call and Webcast Details

The dial-in numbers for Protagonist’s investor update on Monday, June 2nd at 5:00-6:00 am PDT/ 8:00-9:00 am EDT are:

US-based Investors: 1-877-300-8521
International Investors: 1-412-317-6026
Conference Call ID: 10199589
The webcast link for the event can be found here: View Source;tp_key=360d3b714d

A replay of the presentation will be available on the Protagonist Investor Relations Events and Presentations webpage following the event.

About VERIFY

The Phase 3 VERIFY study (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment, which could include hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during Weeks 20-32, which was defined as the absence of "phlebotomy eligibility." To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%.

All patients have completed their participation in the randomized, placebo-controlled portion of the study evaluating the efficacy and safety of rusfertide plus current standard of care versus placebo plus current standard of care and are now in the open-label portions of the study.

On June 1, 2025 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported the first data for casdatifan plus cabozantinib in an oral presentation by Dr. Toni K. Choueiri, Dana-Farber Cancer Institute, at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Arcus Biosciences, JUN 1, 2025, View Source [SID1234653572]).

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"I was very encouraged to see that nearly half of patients had a confirmed response to the casdatifan plus cabozantinib combination despite short follow-up," 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. "Casdatifan plus cabozantinib was well tolerated, and the safety profile was consistent with that of either agent alone, supporting their potential as a combination therapy. I look forward to enrolling patients into the PEAK-1 trial as soon as it is open."

"The initial data for casdatifan plus cabozantinib in the ARC-20 study have already exceeded the historic benchmarks for either agent alone, as well as that of another HIF-2a inhibitor plus cabozantinib in the same second-line setting," said Terry Rosen, Ph.D., chief executive officer of Arcus. "These data serve as the proof of concept for PEAK-1, which will be initiated in the coming weeks and is designed to generate evidence to change the standard of care for people who have progressed on prior immunotherapy treatment."

ARC-20 is a Phase 1/1b dose-escalation and expansion study that includes a cohort evaluating once-daily 100mg of casdatifan plus 60mg of cabozantinib in patients with ccRCC who had progressed on prior immunotherapy. At the time of the data cutoff (DCO, March 14, 2025), 42 participants were evaluable for safety, and 24 reached at least 12 weeks of follow-up and were evaluable for efficacy. Among the safety-evaluable population (N=42), most participants (79%) had an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor of intermediate or poor. Nearly half (46%) of the efficacy-evaluable population (N=24) achieved a confirmed response per RECIST 1.1, and only one patient had primary progressive disease. The vast majority of the efficacy-evaluable population remains on treatment.

In the safety-evaluable population, no unexpected safety risks were identified at the time of DCO, and casdatifan plus cabozantinib had an acceptable safety profile with no meaningful overlapping toxicity for the two drugs. Only two patients discontinued any drug, and no patients discontinued treatment with both drugs. The incidence of treatment-emergent adverse events (TEAEs) with casdatifan, particularly anemia and hypoxia, was similar to TEAEs observed with casdatifan monotherapy, and there were no casdatifan-related Grade 4 or 5 adverse events. The incidence of TEAEs associated with each drug was consistent with what is expected for each drug alone.

A summary of the efficacy and safety results is below.

Efficacy-Evaluablea

casdatifan 100mg QD + cabozantinib 60mg QD

(n=24)

Median Follow-Up

5.3 months

Confirmed ORR (cORR) per RECIST v1.1 [95% CI]

46% (11)b

[26,67]

Best Overall Response:

Complete Response

4% (1)

Partial Response

42% (10)b

Stable Disease

50% (12)

Progressive Disease

4% (1)

CI: confidence interval; QD: daily

a All eligible patients who received any study treatment and reached a minimum of 12 weeks follow-up or discontinued due to progression or death.

b Inclusive of one patient who had partial response confirmation after March 14, 2025.

Safetya

casdatifan 100mg QD + cabozantinib 60mg QD

(n=42)

casdatifan

cabozantinib

Patients with any Treatment-Related Grade ≥3 AEb

Anemia

24% (10)

14% (6)

Hyponatremia

0

7% (3)

Hypoxia

7% (3)

0

Hypertension

0

5% (2)

Neutrophil count decrease

2% (1)

5% (2)

Patients with any AE leading to dose reductionb

Fatigue

2% (1)

12% (5)

Anemia

10% (4)

2% (1)

Hypoxia

10% (4)

0

Palmar-plantar erythrodysesthesia

0

5% (2)

Stomatitis

0

5% (2)

AE: adverse event

a Safety population included patients who received any amount of study drug and had at least one month of safety follow-up at the data cutoff date.

b Treatment-emergent adverse events (grade 3 or higher) related to casdatifan, cabozantinib, or any study drug reported in ≥3% of patients in any treatment arm.

Arcus is pursuing a broad development program in both the immuno-oncology (IO)-naive and post-IO settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. These studies include:

Arcus’s planned Phase 3 study, PEAK-1, which will evaluate casdatifan plus cabozantinib versus cabozantinib monotherapy as a first- or second-line treatment in patients with metastatic ccRCC who have previously received anti-PD-1/PD-L1 therapy. The primary endpoint will be PFS with a key secondary endpoint of overall survival.
eVOLVE-RCC02, a Phase 1b/3 study sponsored by AstraZeneca, which will evaluate casdatifan plus volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody, as first-line treatment for participants with ccRCC.
ARC-20, which includes three cohorts evaluating casdatifan in earlier-line settings, including casdatifan plus zimberelimab in first-line ccRCC, casdatifan monotherapy in favorable risk ccRCC, and casdatifan monotherapy in immunotherapy-experienced, TKI-naive settings.
Investors may dial in to the conference call at +1 404 975 4839 (local) or +1 833 470 1428 (toll-free) using Conference ID: 446724 on Monday, June 2, 2025, at 5:00 AM PT / 7:00 AM CT. Participants may also register for the call online using the following link: View Source 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 transcription factor responsible for activating multiple tumor growth pathways in hypoxic and pseudo-hypoxic tumor environments. By selectively binding HIF-2a, casdatifan is designed to shut down hypoxic oncogenesis and key oncogenic pathways, which leads to cancer cell death. Clear cell renal cell carcinoma is almost universally associated with HIF-2a dysregulation. Casdatifan is currently being evaluated in ARC-20, a Phase 1/1b study in renal cell carcinoma.

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 80,980 Americans will be diagnosed with kidney cancer in 2025. 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 18%. 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.