On December 3, 2024 Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, and Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd. and fully integrated biopharmaceutical company dedicated to elevating treatment outcomes for patients who have limited or inadequate therapeutic options, reported an exclusive global licensing agreement for lirafugratinib (RLY-4008) (Press release, Elevar Therapeutics, DEC 3, 2024, View Source [SID1234648745]). Lirafugratinib is a selective oral small molecule inhibitor of fibroblast growth factor receptor 2 (FGFR2) that is being developed for patients with FGFR2-driven cholangiocarcinoma (CCA) and other FGFR2-altered solid tumors. The announcement of the partnership follows Relay’s recent positive FDA interaction and previously reported differentiated data in cholangiocarcinoma and data across other solid tumors.

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"Data to-date show that lirafugratinib has the potential to be an important novel medicine for patients with FGFR2-driven cholangiocarcinoma and other FGFR2-altered solid tumors. We are pleased that Elevar will continue its development and leverage their growing commercial capabilities to bring it to patients in need around the world," said Sanjiv Patel, M.D., President and Chief Executive Officer of Relay Therapeutics. "As a result of this agreement, we are able to remain fully focused on continuing to advance our PI3Kα programs, including initiating the RLY-2608 2L breast cancer pivotal trial and vascular malformations trial next year."

"Lirafugratinib is an NDA-ready therapy that has shown a potential best-in-class profile in both FGFR2-driven cholangiocarcinoma and in other FGFR2-altered solid tumors including in advanced stages where treatment options are limited," said Saeho Chong, Ph.D., chief executive officer of Elevar Therapeutics. "We are excited to diversify and expand our late-stage oncology pipeline with lirafugratinib, which is a strong strategic fit with our existing oncology portfolio and provides another opportunity to advance our mission of bringing life-changing medicines to cancer patients worldwide."

Lirafugratinib was granted breakthrough therapy designation and orphan drug designation by the FDA. Lirafugratinib is being investigated in the global ReFocus trial in patients with FGFR2-altered tumors. The study includes a pivotal cohort in patients with FGFR2-fusion CCA that was designed to support accelerated approval and is fully enrolled. Interim data from this cohort were presented at the European Society for Medical Oncology Congress in 2022. The study also includes cohorts in patients with other types of solid tumors, including gastric, pancreatic, and head and neck tumors. Interim data from these cohorts were presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in 2023 and 2024. Earlier in 2024, Relay Therapeutics met with the U.S. Food and Drug Administration (FDA) to discuss data from the ReFocus trial and potential regulatory pathways. The FDA recommended that the company first file an NDA for FGFR2-driven CCA, followed by a supplemental NDA for FGFR2-altered other solid tumors with data from an expanded cohort of patients.

Cholangiocarcinoma (CCA) or bile duct cancer is a rare disease in which malignant cells form in the bile ducts. Approximately 8,000 people in the United States are diagnosed with CCA each year.

Terms of the Agreement

Under the terms of the agreement, Elevar will be granted global development and commercialization rights for lirafugratinib. Elevar will assume full responsibility for all further development activities, including submission of the NDAs, all subsequent clinical development, and global commercialization for FGFR2-driven CCA and FGFR2-altered other solid tumors.

Relay Therapeutics is eligible to receive up to $75 million in upfront and regulatory milestones, plus up to $425 million in potential commercial milestone payments, as well as tiered royalties up to the low-teens percentage.

Moelis & Company LLC is serving as exclusive financial advisor to Relay Therapeutics in the transaction. Goodwin Procter LLP is serving as exclusive legal advisor to Relay Therapeutics in the transaction.

About Lirafugratinib

Lirafugratinib (RLY-4008) is a potent, selective and oral small molecule inhibitor of FGFR2, a receptor tyrosine kinase that is frequently altered in certain cancers. FGFR2 is one of four members of the FGFR family, a set of closely related proteins with highly similar protein sequences and properties. Preclinically, lirafugratinib demonstrated FGFR2-dependent killing in cancer cell lines and induced regression in in vivo models with minimal inhibition of other targets, including other members of the FGFR family. In addition, lirafugratinib demonstrated strong activity against known clinical on-target resistance mutations in cellular and in vivo preclinical models. Lirafugratinib is currently being evaluated in a clinical trial in patients with advanced or metastatic FGFR2-altered solid tumors with a single arm, potentially registration-enabling cohort for FGFRi-naïve FGFR2-fusion CCA.

On December 3, 2024 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity, reported encouraging early data from the ongoing dose escalation part of the Phase 1 CARDINAL study evaluating TERN-701 in patients with relapsed/refractory chronic myeloid leukemia (CML) (Press release, Terns Pharmaceuticals, DEC 3, 2024, View Source [SID1234648762]).

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TERN-701 is an investigational, oral, potent, small molecule allosteric BCR-ABL inhibitor being developed for patients with CML. CARDINAL is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, pharmacokinetics (PK), and efficacy of TERN-701 in patients with relapsed/refractory CML with or without BCR-ABL resistance mutations who were previously treated with at least one 2G tyrosine kinase inhibitor (TKI). Patients previously treated with asciminib are also eligible.

"These exciting early data from our Phase 1 dose escalation cohorts clearly show TERN-701 has compelling clinical activity with a highly encouraging cumulative MMR rate of 50% at 3 months. At the first two dose levels, we see clinically meaningful molecular and hematologic responses in patients with high baseline BCR-ABL transcript levels who had poor responses on prior 2G TKIs, 3G TKIs including ponatinib, as well as asciminib," said Emil Kuriakose MD, chief medical officer of Terns.

"The emerging safety data show a profile supporting best-in-class potential with no dose limiting toxicities across three completed dose levels, no clinically meaningful changes in liver or pancreatic enzymes, and no AE-related dose reductions or discontinuations at doses that achieve plasma exposures well above target efficacious concentrations. Taken together, the clinical activity and safety data across the dose range in these heavily pre-treated patients with refractory disease support a potential wide therapeutic index that allows for high levels of target coverage with favorable safety/tolerability."

"We are thrilled to share these impactful early data from the Phase 1 CARDINAL study of TERN-701, which support its potential to be a best-in-class allosteric inhibitor for the treatment of CML," said Amy Burroughs, chief executive officer of Terns. "In addition to the meaningful clinical data, the CARDINAL study highlights yet another example of excellent clinical and operational execution at Terns, with patients enrolled in all four dose escalation cohorts in less than a year. We are well-positioned to initiate dose expansion cohorts in the first half of 2025 and look forward to sharing additional safety and efficacy data, including longer term MMR data in late 2025."

As of the October 28, 2024 cutoff date, 15 patients were enrolled across three dose levels of 160mg (n=7), 320mg (n=5), and 400mg (n=3) of TERN-701 dosed once daily, with an overall median treatment duration of 3 months (range 0.79 – 7.5 months). Enrolled patients were heavily pretreated with a median of 4 prior TKIs (range: 1-6) and 80% having had 3 or more TKIs. 47% and 40% of patients, respectively, had previously received ponatinib and asciminib. 73% were not in MMR at baseline, with 60% having a baseline BCR-ABL transcript >1% international scale (IS). As of the data cutoff, 14 of 15 patients remain on treatment.

Twelve patients were efficacy evaluable, defined as having baseline BCR-ABL transcript and at least two post-baseline BCR-ABL transcript levels (centrally assessed). All efficacy evaluable patients were in the 160mg and 320mg dose levels. Key efficacy highlights include:

•
88% (7/8) of patients with baseline transcript > 1% had decreases in BCR-ABL on treatment, with 7 ongoing as of data cutoff
•
Cumulative MMR rate of 50% (5/10) in non-T315i mutation patients with 3 or more months of treatment and/or MMR or better at baseline
•
100% (4/4) of patients with MMR or better at baseline have maintained their response and remain on treatment
•
Additional notable responses include:
o
MR2 within 5 months in a 4L patient at 160mg QD with baseline transcript > 1% and suboptimal response and intolerance to asciminib
o
MR4 (deep molecular response) within 3 months in a 5L patient treated at 320mg with baseline transcript >10% and treatment failure on bosutinib at study entry

TERN-701 showed a highly encouraging safety profile across the 160mg to 400mg dose levels, with 500mg undergoing evaluation as of data cutoff. Key safety highlights:

•
No dose limiting toxicities (DLT) through 400mg dose level
•
No adverse event (AE)-related treatment discontinuations or dose reductions
•
No Grade 3 or higher treatment-related AEs
•
No treatment related serious AEs

The incidence of treatment emergent hematologic AEs was notably low in this heavily pre-treated population, with no Grade 3 or higher treatment-related cytopenias. There were no non-hematologic treatment-related AEs more than Grade 2 in severity. Finally, no clinically meaningful changes in liver and pancreatic enzymes, blood pressure and other vitals, or electrocardiogram were seen.

Steady state PK data, available for the 160mg and 320mg dose levels at data cutoff, showed linear PK with dose proportional increases in exposure. Plasma protein binding-corrected Caverage for TERN-701 exceeded the in vitro IC90 for multiple mutated and non-mutated BCR-ABL variants with once daily dosing. Importantly, at 160mg and 320mg QD, TERN-701 achieved average free drug concentrations approximately 4-fold and 8-fold higher, respectively, than in vivo exposures where potent inhibition of the BCR-ABL signaling pathway in was seen in CML mouse tumor models, indicating robust pharmacodynamic effects at these clinical doses.

As of December 3, 2024, the CARDINAL study has enrolled 19 patients inclusive of the 500mg cohort, with all dose escalation cohorts having enrolled at least 3 patients. The study is on track to initiate dose expansion in the first half of 2025 with additional efficacy data expected in the fourth quarter of 2025, including longer term MMR rates.

Company Webcast

Terns will host a company webcast at 8:00 am ET today. The discussion will cover TERN-701’s Phase 1 interim data, next steps for the CARDINAL program, and TERN-701’s potential role in the CML treatment landscape.

The event will be webcast live and can be accessed by visiting the investor relations section of the Company’s website at View Source An archived webcast will be available following the event.

About CARDINAL

The CARDINAL trial is an ongoing global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, PK, and efficacy of TERN-701 in patients with previously treated CML. Part 1 is the dose escalation portion of the trial evaluating once-daily TERN-701 monotherapy in up to five dose cohorts in up to 60 adults with chronic phase CML with confirmed BCR-ABL and a history of treatment failure or suboptimal response to at least one second generation TKI (nilotinib, dasatinib or bosutinib). Participants who are intolerant to prior TKI treatment (including asciminib) are also allowed. The primary endpoints for Part 1 are the incidence of DLTs during the first treatment cycle, and additional measures of safety and tolerability. Secondary endpoints include TERN-701 PK and efficacy assessments, such as hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels. The starting dose is 160 mg QD (once-daily) with dose escalations as high as 500 mg QD and the option to explore a lower dose of 80 mg QD. Part 2 is the dose expansion portion of the trial that will enroll approximately 40 patients, randomized to once-daily treatment with one of two doses of TERN-701 to be selected based on data from Part 1. The primary endpoint of the dose expansion portion of the trial is efficacy, measured by hematologic and molecular responses. Secondary endpoints include safety, tolerability and PK. The overall objective of the CARDINAL trial is to select the optimal dose(s) of TERN-701 to move forward to a potential pivotal trial in chronic phase CML.

On December 3, 2024 TRIO Pharmaceuticals, Inc., a biotechnology company pioneering bispecific antibodies for the treatment of cancer with unprecedented potency and selectivity, reported the successful completion of a $3.1 million financing round (Press release, Trio Pharmaceuticals, DEC 3, 2024, View Source [SID1234648780]). TRIO’s pre-Series A financing was led by San Diego based Friedman Bioventure Fund (FBVF). "The TRIO team has demonstrated impressive bioactivity for both their TRAILBody and TIE-ADC bispecific antibody architectures, and we believe these potential medicines warrant accelerated development," said Dr. Jeff Friedman of FBVF.

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Additional significant support came from the Multiple Myeloma Research Foundation (MMRF), through its venture philanthropy arm, the Myeloma Investment Fund (MIF), underscoring the potential of TRIO’s work to impact cancers with high unmet needs. Further investors included NuFund Venture Group, Life Science Angels and others.

Friedman Bioventure brings expertise in supporting innovative biotech startups, aiming to accelerate breakthrough therapies to market. The Myeloma Investment Fund focuses on advancing treatments for cancers affecting blood and bone marrow, notably multiple myeloma. The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. MMRF has raised over $600 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market.

"TRIO’s innovative approach aligns with our mission to drive breakthrough treatments for the myeloma community," said Dr. Stephanie Oestreich, Managing Director, Myeloma Investment Fund. "This investment underscores our commitment to accelerating therapeutic options for myeloma patients."

TRIO Pharmaceuticals’ proprietary platforms, TRAILBody and TIE-ADC, are advancing next-generation immunotherapies for cancers with high mortality rates, such as Multiple Myeloma, Acute Myeloid Leukemia, ovarian, endometrial, and triple-negative breast cancers. These therapies combine targeted tumor growth inhibition with immune system modulation to offer potent, less toxic options compared to conventional treatments.

"This financing round empowers us to expand our preclinical activities and advance our programs towards clinical development," said Dr. Reiner Laus, CEO of TRIO Pharmaceuticals. "The support from organizations like Friedman Bioventure and the Myeloma Investment Fund is invaluable as we work to bring our transformative therapies closer to patients in need."

TRIO Pharmaceuticals is dedicated to reimagining cancer care through the application of novel antibody therapeutics. This funding will accelerate TRIO’s journey towards clinical trials, offering new hope for patients facing cancers that resist standard therapies.

On December 3, 2024 Beyond Cancer, Ltd., a clinical-stage biotechnology company developing ultra-high concentration nitric oxide (UNO) as an immunotherapeutic for solid tumors, reported that the Israeli Ministry of Health (IMOH) has approved the use of Low Volume UNO (LV UNO) in a Phase 1b clinical trial of LV UNO in combination with anti-PD-1 therapy (Press release, Beyond Cancer, DEC 3, 2024, View Source [SID1234648763]). The trial will be conducted at four sites in Israel and patient screening will begin in the first quarter of 2025.

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The Phase 1b trial (NCT05351502) is a clinical proof-of-concept trial that will assess the intratumoral administration of LV UNO in patients with unresectable cutaneous or subcutaneous histologically confirmed primary or metastatic lesions, who have shown disease progression or prolonged stable disease ( 12 weeks) after receiving a single agent anti-PD-1 containing treatment. The trial, which is expected to enroll up to 20 subjects, is designed to assess the preliminary efficacy of LV UNO by objective response rate (ORR) and duration of response (DOR) per RECIST v1.1 and secondarily immune-related response via iRECIST. Safety and tolerability of LV UNO in combination with anti-PD-1 therapy, as well as its potential to enhance the type, density, and distribution of immune cells within the tumor microenvironment will also be observed. Topline data from the Phase 1b portion of the study are anticipated in the second half of 2025.

"We are excited to initiate the Phase 1b trial of LV UNO, a potentially groundbreaking solid tumor treatment approach, in combination with PD-1 inhibitors," said Dr. Jedidiah Monson, Chief Medical Officer of Beyond Cancer. "In preclinical studies, a single dose of UNO has been shown to increase PD-L1 expression and improve overall survival in animal models compared to anti-PD-1 alone. Further, Phase 1a human data that demonstrated immune system activation were presented at ASCO (Free ASCO Whitepaper)’s Key Opinion Leader Event held in June 2024. We look forward to the Phase 1b trial results to establish the basis of further investigation of UNO in combination with PD-1 inhibitors."

"The initiation of the Phase 1b trial represents a major step forward in our vision for personalized cancer treatment. We see UNO as a complementary therapy for future cancer treatment paradigms, particularly for patients with anti-PD-1 refractory or resistant disease, potentially offering more patients access to effective treatment," stated Dr. Selena Chaisson, Chief Executive Officer, and Director of Beyond Cancer.

About Nitric Oxide

Nitric Oxide (NO) is a potent molecule, naturally synthesized in the human body, proven to play a critical role in a broad array of biological functions. In the airways, NO targets the vascular smooth muscle cells that surround the small resistance arteries in the lungs. Currently, exogenous inhaled NO is used in adult respiratory distress syndrome, post certain cardiac surgeries and persistent pulmonary hypertension of the newborn to treat hypoxemia. Additionally, NO is believed to play a key role in the innate immune system and in vitro studies suggest that NO possesses anti-microbial activity not only against common bacteria, including both gram-positive and gram-negative, but also against other diverse pathogens.

About UNO Therapy for Solid Tumors

Cancer is the second leading cause of death globally, with tumor metastases responsible for approximately 90% of all cancer-related deaths. Current cancer treatment modalities generally include chemotherapy, immunotherapy, radiation, and/or surgery. Ultra-high concentration Nitric Oxide (UNO) therapy is a completely new approach to preventing relapse or metastatic disease. In vitro murine data show that local tumor ablation with UNO stimulates an anti-tumor immune response in solid tumor cancer models. Beyond Cancer, Ltd. believes that UNO has the potential to prevent relapse or metastatic disease with as little as a single 5-minute treatment and with limited toxicity or off-target effects.

On December 3, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) and Innovent Biologics, Inc. ("Innovent") (HKEX:1801) reported that the New Drug Application ("NDA") for the combination of ELUNATE (fruquintinib) and TYVYT (sintilimab injection) has been granted conditional approval in China for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient ("pMMR") tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation (Press release, Hutchison China MediTech, DEC 3, 2024, View Source [SID1234648747]). This approval follows the priority review status and breakthrough therapy designation by the National Medical Products Administration ("NMPA") of China and marks the first regulatory approval for the combination of fruquintinib with a leading immune checkpoint inhibitor.

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The conditional approval by the NMPA was supported by registration stage data from FRUSICA-1, the endometrial cancer registration cohort of a multi-center, open-label Phase II study investigating fruquintinib in combination with sintilimab in endometrial cancer patients who have experienced disease recurrence, disease progression or intolerable toxicity with treatment on platinum-based doublet chemotherapy. Results from FRUSICA-1 were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in June 2024.1 The study results showed that IRC-assessed objective response rate (ORR) and disease control rate (DCR) was 35.6% and 88.5% respectively. The combination treatment showed rapid on-set efficacy, with a median time to response (TTR) of only 1.6 months. The median progression free survival (PFS) and overall survival (OS) reached 9.5 months and 21.3 months respectively. Adverse events are consistent with those reported for similar immunotherapy and antiangiogenic agents combination treatments. Additional details can be found at clinicaltrials.gov, using identifier NCT03903705.

"This approval of fruquintinib plus sintilimab could represent a paradigm shift in managing this challenging disease. This innovative combination not only leverages the synergistic effects of targeted therapy and immunotherapy, but also addresses a critical gap in treatments available for patients with limited responses to traditional therapies," said Prof. Xiaohua Wu, Director of the Department of Gynecologic Oncology at Fudan University Affiliated Cancer Hospital and Principal Investigator of the FRUSICA-1 study. "With the promising efficacy and manageable safety profile observed in clinical trials, we are eager to have this treatment option available to patients. It brings us closer to our goal of improving survival and enhancing quality of life for patients living with advanced endometrial cancer."

"This NMPA approval of fruquintinib in combination with sintilimab represents a significant advancement for patients with advanced endometrial cancer who have long await more effective treatments. It underscores the potential of fruquintinib to be used with other therapeutic agents to improve patient outcomes," said Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED. "It is also a testament to our ongoing efforts to extend the clinical benefit of fruquintinib to a broader patient population. We are eager to make this innovative treatment available to advanced endometrial cancer patients as soon as we can and will continue to explore further opportunities to bring hope to more patients battling cancer."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "This approval of sintilimab and fruquintinib combination therapy marks a meaningful advancement in the treatment landscape for advanced endometrial cancer. Together with HUTCHMED, we aim to provide a novel treatment option that improves survival rates and quality of life for patients facing limited treatment options against this aggressive cancer. TYVYT (sintilimab injection), as a cornerstone in immuno-therapy, continues to be evaluated in clinical trials in combination with novel modalities. We remain steadfast in our commitment to reinforcing the leadership position of TYVYT (sintilimab injection) in immuno-therapy and driving forward treatment solutions through innovation and cooperation."

In July 2023, the NMPA granted Breakthrough Therapy Designation to the combination of fruquintinib and sintilimab for this potential indication. This designation recognizes the potential of a therapy to address a severe condition with no effective treatment options, and where clinical evidence demonstrates substantial advantages over existing therapies.

A Phase III confirmatory study of the fruquintinib and sintilimab combination in this setting has been planned (NCT06584032).

About Endometrial Cancer

Endometrial cancer originates in the uterus and remains a significant global health challenge. In 2020, approximately 417,000 people were diagnosed with endometrial cancer, resulting in around 97,000 deaths.2 Іn China alone, an estimated 82,000 new cases and 17,000 were reported in 2020.3 While early-stage endometrial cancer can often be surgically resected, recurrent and/or metastatic endometrial cancer remains an area of high unmet need with poor outcomes and limited treatment options.

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor ("VEGF") receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.

About Fruquintinib Approvals

Fruquintinib is approved for marketing for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, and those who have previously received or are not suitable for receiving anti-VEGF therapy or anti-epidermal growth factor receptor ("EGFR") therapy (RAS wild-type) in China, where it is co-developed and co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE. It was included in the China National Reimbursement Drug List ("NRDL") in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau, and markets under the FRUZAQLA brand name. Fruquintinib received approval in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024, in Canada, Japan and the United Kingdom in September 2024 and in Argentina, Australia and Singapore in October 2024. Regulatory applications are progressing in many other jurisdictions.

The global regulatory submissions are based on data from two large, randomized, controlled Phase III trials, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023,7 while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.

In China, sintilimab has been approved and included in the updated NRDL for seven indications. The updated NRDL reimbursement scope for TYVYT (sintilimab injection) includes:

● For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
● For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
● For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
● For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
● For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
● For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
● For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

Furthermore, sintilimab’s eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, has been approved by the NMPA in December 2024.

In addition, two clinical studies of sintilimab have met their primary endpoints:

● Phase II study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
● Phase III study of sintilimab monotherapy as second-line treatment for squamous non-small cell lung cancer with disease progression following platinum-based chemotherapy.