On March 20, 2025 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and reported financial results for the year ended December 31, 2024 (Press release, MacroGenics, MAR 20, 2025, View Source [SID1234651310]).

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"We concluded 2024 with the achievement of multiple clinical development milestones, including the completion of enrollment in the LORIKEET Phase 2 study evaluating lorigerlimab in combination with docetaxel in patients with mCRPC. We look forward to building upon this momentum in 2025 as we work to advance our novel pipeline of clinical product candidates, including lorigerlimab, MGC026 and MGC028," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Finally, we have determined that the results of the TAMARACK Phase 2 study of vobra duo in mCRPC do not support additional financial investment by MacroGenics. We believe the B7-H3 target continues to have potential and are pleased with the progress being made with our alternate anti-B7-H3 ADC, MGC026."

Updates on Proprietary Investigational Programs

Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART molecule designed to enhance CTLA-4 blockade on dual-expressing, tumor-infiltrating lymphocytes compared to a PD-1/CTLA-4 monoclonal antibody (mAb) combination therapy, while maintaining maximal PD-1 blockade on all PD-1-expressing cells.

Enrollment is now complete in the ongoing LORIKEET Phase 2 trial, a 150 patient randomized study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). The Company expects to provide a clinical update in the second half of 2025.
Based on MacroGenics’ cumulative experience to date from its Phase 1 and Phase 2 studies of lorigerlimab, including in mCRPC – a tumor setting historically insensitive to checkpoint inhibition – the Company plans to conduct the LINNET Phase 2 study. This clinical trial will evaluate lorigerlimab as monotherapy in patients with either platinum-resistant ovarian cancer (PROC) or clear cell gynecologic cancer (CCGC); both represent areas of unmet need and historically have been relatively insensitive to checkpoint inhibitor therapy. The study’s primary endpoint is ORR, with multiple secondary endpoints to be explored. The Company anticipates enrolling up to 40 patients with PROC and up to 20 patients with CCGC in LINNET, which is expected to commence by mid-2025.
Emerging ADC Pipeline. MacroGenics is developing two clinical and one preclinical antibody-drug conjugate (ADC) molecules that each incorporate a novel, glycan-linked topoisomerase I inhibitor (TOP1i)-based payload developed by the Company’s collaboration partner, Synaffix (a Lonza company). These three candidates are described below.

MGC026 is a TOP1i-based ADC that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation. MGC026 shares the same variable domain as that of vobra duo. MGC026 is currently being evaluated in a Phase 1 dose escalation study in patients with advanced solid tumors, with dose expansion in selected indications expected to initiate in 2025.
MGC028 is a TOP1i-based ADC that targets ADAM9, a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers. The Company previously presented preclinical data showing antitumor activity of MGC028 in in vivo models. Also, in a non-human primate study, MGC028 was well tolerated at high dose levels with mild, reversible side effects and no ocular toxicity, which is often a concern with tubulin-inhibitor-based ADCs. The first patient was recently dosed in a Phase 1 study of MGC028 in patients with advanced solid tumors.
MGC030 is a preclinical TOP1i-based ADC that targets an undisclosed antigen expressed across several solid tumors. There are currently no approved therapeutics to this target. An Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for MGC030 is planned for 2026.
Updates on Selected Partnered Programs

MGD024 is a next-generation CD123 × CD3 DART molecule. Under an October 2022 exclusive option and collaboration agreement with Gilead Sciences, Inc. (Gilead), MacroGenics continues to enroll patients in a Phase 1 dose escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia and myelodysplastic syndromes. Gilead has the option to license MGD024 at predefined decision points during the Phase 1 study.
ZYNYZ (retifanlimab-dlwr) is a monoclonal antibody targeting PD-1 that the Company licensed to Incyte Corporation (Incyte) in 2017. In July 2024, Incyte announced positive Phase 3 top-line results for its registrational studies of retifanlimab in squamous cell carcinoma of the anal canal (SCAC) and non-small cell lung cancer (NSCLC) and continues to conduct global studies of retifanlimab across multiple indications. In February 2025, Incyte disclosed that its supplemental Biologics License Application (sBLA) for retifanlimab in advanced/metastatic SCAC was filed with the FDA in December 2024, with approval anticipated in the second half of 2025. To date, MacroGenics has received $365.0 million in upfront and milestone payments from Incyte under the agreement and remains eligible for up to $540.0 million in additional development, regulatory and commercial milestones.
MARGENZA (margetuximab-cmkb) global rights were sold to TerSera Therapeutics LLC (TerSera), a privately-held biopharmaceutical company with a focus on oncology and non-opioid pain management, pursuant to an agreement previously announced. TerSera made a payment of $40.0 million to MacroGenics at closing in November 2024 and MacroGenics may receive additional sales milestone payments of up to an aggregate of $35.0 million. MacroGenics subsequently paid an $8.0 million amendment fee to its former commercialization partner during the fourth quarter of 2024. MacroGenics will manufacture MARGENZA drug substance on behalf of TerSera going forward.
Update on Vobramitamab Duocarmazine

Vobramitamab duocarmazine (vobra duo) is an ADC with a cleavable peptide linker designed to deliver a DNA-alkylating duocarmycin payload to solid tumors that express B7-H3.

Results for the concluded TAMARACK Phase 2 study included, based on a February 21, 2025 data cut-off, mature median radiographic progression-free survival (rPFS) of 9.5 months for the 2.0 mg/kg cohort (95% CI, 8.5-11.2) and 10.0 months for the 2.7 mg/kg cohort (95% CI, 7.4-11.4) in patients with mCRPC. Safety data from the study remained consistent with prior data disclosures.
Based on its assessment of the vobra duo safety and efficacy profile and an internal resource and portfolio review, MacroGenics has decided not to pursue further internal development of vobra duo and will instead explore potential alternatives for partnering this program.
2024 Financial Results

Cash Position: Cash, cash equivalents and marketable securities balance as of December 31, 2024, was $201.7 million, compared to $229.8 million as of December 31, 2023.
Revenue: Total revenue was $150.0 million for the year ended December 31, 2024, compared to total revenue of $58.7 million for the year ended December 31, 2023. The increase was primarily due to a net increase of $85.0 million in revenue recognized from milestones achieved under the Incyte License Agreement.
R&D Expenses: Research and development expenses were $177.2 million for the year ended December 31, 2024, compared to $166.6 million for the year ended December 31, 2023. The increase was primarily due to increased research, development, manufacturing and clinical costs related to MGC028, the Company’s preclinical ADC pipeline and lorigerlimab, offset by decreased development and clinical trial costs related to the Company’s discontinued projects and margetuximab.
SG&A Expenses: Selling, general and administrative expenses were $71.0 million for the year ended December 31, 2024, compared to $52.2 million for the year ended December 31, 2023. The increase was due to an amendment fee paid by MacroGenics to its former commercial partner pursuant to the sale of MARGENZA and increased non-cash stock-based compensation and accrued severance expenses related to the separation agreement with the Company’s Chief Executive Officer.
Other Income: Other income for the year ended December 31, 2024, reflected a $36.3 million gain recognized on the sale of MARGENZA.
Net Loss: Net loss was $67.0 million for the year ended December 31, 2024, compared to net loss of $9.1 million for the year ended December 31, 2023.
Shares Outstanding: Shares of common stock outstanding as of December 31, 2024 were 62,819,857.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities balance of $201.7 million as of December 31, 2024, in addition to projected and anticipated future payments from partners should extend its cash runway into the second half of 2026. The Company’s expected funding requirements reflect anticipated expenditures related to the ongoing Phase 2 LORIKEET study of lorigerlimab in mCRPC as well as MacroGenics’ other clinical and preclinical studies currently ongoing.
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On March 20, 2025 Linnaeus Therapeutics, Inc. ("Linnaeus"), a privately held biopharmaceutical company focused on the development and commercialization of novel, small molecule oncology therapeutics, reported that seminal data describing Linnaeus’s clinical candidate, LNS8801, was published in Cancer Research Communications (Press release, Linnaeus Therapeutics, MAR 20, 2025, View Source [SID1234651326]). This paper characterizes LNS8801 as a developable pharmaceutical drug candidate, demonstrating its activity in cancer and highlighting a predictive biomarker.

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The manuscript, entitled "LNS8801: An enantiomerically pure agonist of the G protein-coupled estrogen receptor suitable for clinical development," was authored by Natale et al. The publication can be viewed at: View Source

This new study highlights the potential of LNS8801, a first-in-class, oral compound targeting the G protein estrogen receptor (GPER), to be used as a novel cancer therapy. Linnaeus researchers and collaborators discovered that LNS8801 is the active component of the widely studied GPER agonist, G-1. In preclinical models, LNS8801 demonstrated potent, oral, GPER-dependent anticancer effects. This study also demonstrates that a common genetic variant of GPER may influence patient response, offering a potential mechanism-linked biomarker for patient selection and personalized therapy. These findings complement the data generated in ongoing clinical trials of LNS8801 for cancer.

"The validation of our science by the acceptance of this paper in Cancer Research Communications underscores the importance of GPER as a therapeutic target," said Patrick Mooney, MD, Chief Executive Officer of Linnaeus. "This data demonstrates that using LNS8801 to target GPER has therapeutic effects in melanoma and other GPER-positive cancers and is the appropriate molecule for clinical development. We are excited by the data we have seen in our clinical phase 1/2 study, and we are poised to open enrollment in a randomized, controlled study in the near future."

Linnaeus anticipates initiating a randomized controlled clinical trial testing LNS8801 in unresectable, treatment-refractory, cutaneous melanoma patients this year. This study will randomize 135 biomarker-positive patients to receive either LNS8801 monotherapy, LNS8801 in combination with pembrolizumab, or physician’s choice therapy. The study will assess progression-free survival and overall survival between the groups.

About LNS8801

LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing clinical study in humans, LNS8801 has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancers, and a predictive biomarker has been identified.

On March 19, 2025 HUTCHMED (China) Limited ("HUTCHMED", the "Company" or "we") (HKEX: 13; Nasdaq/AIM: HCM) reported its financial results for the year ended December 31, 2024 and provides updates on key clinical and commercial developments (Press release, Hutchison China MediTech, MAR 19, 2025, View Source [SID1234651257]).

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HUTCHMED to host results webcasts today at 8:00 a.m. EDT / 12:00 noon GMT / 8:00 p.m. HKT in English on Wednesday, March 19, 2025, and tomorrow at 8:30 a.m. HKT in Chinese (Putonghua) on Thursday, March 20, 2025. After registration, investors may access the live webcast via HUTCHMED’s website at www.hutch-med.com/event.

All amounts are expressed in US dollars unless otherwise stated.

Global commercial progress and delivery of sustainable growth

· FRUZAQLA (fruquintinib) ex-China in-market sales1 of $290.6 million in 2024 by Takeda, sustaining momentum in its first full year driven by rapid US patient uptake, and EU and Japan launches, triggering a sales milestone from Takeda2. Total oncology products in-market sales up 134% to $501.0 million.

· Consolidated revenue from oncology products of $271.5 million, up 65%.

· Net income of $37.7 million was achieved in 2024, with a cash balance of $836.1 million as of December 31, 2024, achieving financial self-reliance ahead of schedule.

· Agreed partial disposal of equity in SHPL3 joint venture for $608 million.

Pipeline progress and new technology platform

· Primary endpoint met in SACHI China Phase III interim analysis for savolitinib for EGFRm4 NSCLC5 with MET amplification, followed by swift NDA6 filing, acceptance and priority review granted by the NMPA7.

· Positive SAVANNAH global pivotal Phase II results for savolitinib in combination with TAGRISSO for EGFRm NSCLC patients that progressed on TAGRISSO treatment with MET overexpression or amplification, achieving high, clinically meaningful and durable response rate and shared with global regulatory authorities by AstraZeneca8.

· Positive FRUSICA-2 China Phase III results for fruquintinib with sintilimab in 2L9 RCC10.

· Presented ESLIM-01 China Phase III data at ASH (Free ASH Whitepaper)11 and EHA (Free EHA Whitepaper)12, highlighting strong, sustained, and long-term durable response rates of sovleplenib for ITP13 patients, with the NDA under review by the NMPA. Additional data were requested by CDE14 and subsequently submitted by HUTCHMED. Review of the supplementary data is currently under review by CDE.

· FRUSICA-1 Phase II results presented at ASCO (Free ASCO Whitepaper)15, leading to NMPA approval of a second indication of ELUNATE (fruquintinib) for EMC16 with pMMR17 status.

· First candidates from new ATTC18 platform, starting development of a new wave of drug candidates potentially more selective and tolerable than previous generations of antibody drug conjugates.

Dr Dan Eldar, Non-executive Chairman of HUTCHMED, said, "The successful commercialization of FRUZAQLA outside of China by our partner Takeda and the resulting milestones achieved during the year were pivotal in helping HUTCHMED reach its profitability goals. I am proud that, at times of uncertainty in the global environment and in the capital markets, we have successfully established an independent ability to support our valuable discovery engine and development pipeline while mitigating operational risks. We expect to continue our global growth with further sales in the US and in other regions of the world, while continuing to develop our pipeline in new and promising directions. The long-term interests of our shareholders and benefits to patients around the world will always remain our top priorities."

"At the end of 2024, we decided to dispose of our 45% equity interest in SHPL for $608 million, subject to closing conditions. I would like to take this opportunity to express my appreciation to the management team at SHPL for their contribution to its impressive growth over the last 20 years, which has delivered consistent benefits to consumers and shareholders alike. The commercial success and monetary contribution were important in supporting HUTCHMED’s novel drug R&D19, helping us to weather challenges in our industry as we developed innovative medicines for patients in need. As our innovative drugs business has become more self-reliant, we believe it is time for HUTCHMED to move on to our next phase of evolution, particularly as we focus on global clinical development of our ATTCs. The proceeds from the SHPL disposal, on top of the ongoing profits of our globally commercialized portfolio, enables us to expedite the roll-out of this differentiated platform, which will be key to our long-term value creation."

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said, "We’ve had a highly successful year, delivering against our strategy, in the clinic and commercially with our transformational medicines. This has culminated in HUTCHMED reaching profitability, which has been a key focus of ours. I’d like to thank and congratulate the team for this milestone, as we turn our attention to further growth and cultivating HUTCHMED’s next wave of medicines through our ATTC platform."

"Our pioneering ATTC platform turns a new page in HUTCHMED’s innovative drug development story, establishing a new frontier in antibody-drug conjugates. This new portfolio of molecules is well placed to target a wide range of oncology indications with sizable market potential, including in first-line combinations. With the expertise and the financial strength to execute global clinical trials, we plan to move expeditiously into clinical development this year."

"Our commercial medicines hit new milestones and expanded clinical development, reaching more patients in need around the world. Fruquintinib is now treating colorectal cancer patients in over a dozen countries, with more to come. FRUZAQLA in-market sales exceeded $200 million within a year of launch, triggering the first sales milestone. In China, it was approved in second-line endometrial cancer, with average duration of treatment almost double that of fruquintinib’s first indication, and a third registrational study FRUSICA-2 has read out positively in kidney cancer."

"For savolitinib, positive data from SACHI interim analysis in patients progressed on first line EGFR20 TKI21 treatment with MET amplification led us to file a NDA in China, which was accepted and granted priority review. We are hopeful that SAVANNAH/SAFFRON trials will support bringing this innovative medicine to patients globally. With recent full approval in both first-line and second-line MET exon 14 skipping alteration lung cancer, savolitinib remains one of the best-in-class medicines. A registration-intent study in MET-amplified gastric cancer is currently enrolling in China. We look forward to potentially expanding its indication as the first medicine for MET amplified EGFRm NSCLC and gastric cancer. Our marketed medicines will continue to support the revenue and earnings growth of HUTCHMED."

"ESLIM-01 data for sovleplenib was presented at EHA (Free EHA Whitepaper) and ASH (Free ASH Whitepaper), with durable response rate of 51.4% and overall response rate of 81.0%, significantly better than many different modalities of ITP medicines under development. These clinical results of sovleplenib again illustrate HUTCHMED’s R&D competency in selectivity, resulting in desirable efficacy and safety. We are working closely with the NMPA and look forward to bringing this innovative medicine to patients in need. ESLIM-02 registration Phase III in warm AIHA22 patients is enrolling and on-track to read out next year. A NDA is under review in China for tazemetostat for recurrent/refractory follicular lymphoma and approval is expected by mid-2025. We look forward to being able to add sovleplenib and tazemetostat to our commercial portfolio and their contributions to HUTCHMED’s continued growth."

2024 Full Year Results & Business Updates

I. COMMERCIAL OPERATIONS

Oncology product in-market sales were up 134% (136% at CER23) to $501.0 million in 2024 (2023: $213.6m), leading to strong growth in oncology product consolidated revenue of 65% (67% at CER) to $271.5 million (2023: $164.2m).

· FRUZAQLA (fruquintinib ex-China) in-market sales were $290.6 million in 2024 (2023: $15.1m) by Takeda, with strong performance reflecting rapid US patient uptake, as well as launches in over a dozen countries. Reaching $200.0 million sales triggered a $20 million milestone payment from Takeda.
· ELUNATE (fruquintinib China) in-market sales increased 7% (9% at CER) to $115.0 million in 2024 (2023: $107.5m), maintaining its leading market share position in metastatic CRC24 and demonstrating resilience against rising pressure from competing products and their generics. New indication for EMC was approved in December 2024.
· SULANDA (surufatinib) in-market sales increased 12% (14% at CER) to $49.0 million in 2024 (2023: $43.9m), as increasing brand awareness amongst doctors and improving NET25 diagnosis drives prescription growth and market share to 27% in 2024 (2023: 21%).
· ORPATHYS (savolitinib) in-market sales approximated prior year (-2%, flat at CER) to $45.5 million in 2024 (2023: $46.1m), impacted by the launch and NRDL26 inclusion of several competing same-class MET TKIs for 2L METex1427 NSCLC. Results do not reflect full approval in 1L28 setting received in January 2025.

Total Oncology/Immunology consolidated revenue was $363.4 million in 2024 (2023: $528.6m), within guidance of $300 million to $400 million.

· Oncology product consolidated revenue (royalties, manufacturing revenue, promotion and marketing services revenue and commercial milestone) increased 65% (67% at CER) to $271.5 million (2023: $164.2m), driven by FRUZAQLA and exceeding guidance of 30% to 50% growth.
· Takeda upfront, regulatory milestones and R&D services revenue were $67.0 million (2023: $345.9m), which included recognition of $48.1 million of the $450.0 million upfront and regulatory milestone payments achieved. This compared to recognition of $312.0 million in 2023.
· Other revenue was $24.9 million (2023: $18.5m), including milestone payment of $6.0 million from AstraZeneca following NDA acceptance in China for ORPATHYS combined with TAGRISSO.

$630.2 million total consolidated revenue (2023: $838.0m) including Other Ventures of $266.8 million (2023: $309.4m).

($ in USD millions) In-market Sales* Consolidated Revenue**
2024 2023 %Δ (CER) 2024 2023 %Δ (CER)
FRUZAQLA $290.6 $15.1 +1,825% (+1,825%) $110.8 $7.2 +1,450% (+1,450%)
ELUNATE $115.0 $107.5 +7% (+9%) $86.3 $83.2 +4% (+6%)
SULANDA $49.0 $43.9 +12% (+14%) $49.0 $43.9 +12% (+14%)
ORPATHYS $45.5 $46.1 -2% (+0%) $24.5 $28.9 -15% (-13%)
TAZVERIK $0.9 $1.0 -8% (-7%) $0.9 $1.0 -8% (-7%)
Oncology Products $501.0 $213.6 +134% (+136%) $271.5 $164.2 +65% (+67%)
Takeda upfront, regulatory milestones and R&D services $67.0 $345.9 -81% (-81%)
Other revenue (R&D services and licensing) $24.9 $18.5 +34% (+36%)
Total Oncology/Immunology $363.4 $528.6 -31% (-31%)
Other Ventures $266.8 $309.4 -14% (-12%)
Total Revenue $630.2 $838.0 -25% (-24%)
* = FRUZAQLA, ELUNATE and ORPATHYS mainly represent total sales to third parties as provided by Takeda, Lilly29 and AstraZeneca, respectively.

** = FRUZAQLA represents manufacturing revenue, royalties and commercial milestone paid by Takeda; ELUNATE represents manufacturing revenue, promotion and marketing services revenue and royalties paid by Lilly to HUTCHMED, and sales to other third parties invoiced by HUTCHMED; ORPATHYS represents manufacturing revenue and royalties paid by AstraZeneca and sales to other third parties invoiced by HUTCHMED; SULANDA and TAZVERIK represent the Company’s sales of the products to third parties.

II. REGULATORY UPDATES

China

· Savolitinib NDA accepted by the NMPA with Priority Review status and Breakthrough Therapy designation for 2L EGFRm NSCLC patients with MET amplification, in combination with TAGRISSO (osimertinib), in December 2024, triggering a milestone from AstraZeneca.

· Savolitinib sNDA30 approved by the NMPA for 1L and 2L (converted from conditional to full approval) METex14 NSCLC in January 2025.

· Fruquintinib sNDA approved by the NMPA, in combination with TYVYT (sintilimab), for 2L EMC patients with pMMR status in December 2024.

· Fruquintinib approved in Hong Kong for 3L31 CRC under the new 1+ Mechanism in January 2024, and subsequently the first innovative oncology medicine enlisted with Full Subsidy under the Special Drug category in October 2024.

· Tazemetostat approved in Hong Kong for 3L R/R32 EZH2m33 follicular lymphoma in May 2024.

· Savolitinib approved in Hong Kong for METex14 NSCLC under the 1+ Mechanism in February 2025.

· Tazemetostat NDA accepted by the NMPA with Priority Review status for 3L R/R follicular lymphoma in July 2024.

· Fruquintinib sNDA voluntarily withdrawn for 2L gastric cancer, in combination with paclitaxel, in August 2024, in light of discussions with the NMPA and internal review of current data package.

Ex-China

· Fruquintinib approved in the EU for CRC in June 2024, followed by first European reimbursement in Spain in December 2024, triggering a $10.0 million milestone from Takeda.

· Fruquintinib approved in Japan for CRC in September 2024, followed by pricing approval and launch in November 2024, triggering a milestone from Takeda.

· Fruquintinib approved in Argentina and Switzerland in August 2024, in Canada (also with reimbursement) and the United Kingdom in September 2024, in Australia and Singapore in October 2024, in Israel and the United Arab Emirates in December 2024, and in South Korea in March 2025.

III. LATE-STAGE CLINICAL DEVELOPMENT ACTIVITIES

Savolitinib (ORPATHYS in China), a highly selective oral inhibitor of MET

· Positive SAVANNAH global pivotal Phase II top-line results for 2L EGFRm NSCLC patients with MET amplification or overexpression, in combination with TAGRISSO (osimertinib), achieving high, clinically meaningful and durable response rate (NCT03778229).

· Primary endpoint met in SACHI China Phase III interim analysis for 2L EGFRm NSCLC patients with MET amplification (NCT05015608).

· Presented Phase II small randomized controlled study results at AACR (Free AACR Whitepaper)34 for 2L EGFRm NSCLC patients with high MET amplification, in combination with TAGRISSO (osimertinib), showing ORR35 of 63% and median PFS36 of 8.2 months (NCT04606771).

· Continued enrolling SAFFRON global Phase III study for 2L EGFRm NSCLC patients with MET amplification or overexpression (NCT05261399) supporting SAVANNAH; and SANOVO China Phase III study for 1L EGFRm NSCLC patients with MET overexpression (NCT05009836).

Potential upcoming clinical and regulatory milestones for savolitinib:

· Presentation of SAVANNAH and SACHI data at upcoming scientific conferences.

· Complete SACHI NMPA NDA review in late 2025.

· Complete SAFFRON enrollment in the second half of 2025.

· Complete enrollment and potential NDA submission for gastric cancer with MET amplification in the second half of 2025.

Fruquintinib (ELUNATE in China, FRUZAQLA outside of China), a highly selective oral inhibitor of VEGFR37

· Presented FRUSICA-1 China pivotal Phase II results at ASCO (Free ASCO Whitepaper), in combination with TYVYT (sintilimab), for previously treated EMC with pMMR status, showing IRC38-assessed confirmed ORR of 35.6%, median PFS of 9.5 months and median OS39 of 21.3 months with a manageable safety profile (NCT03903705). This indication was approved by the NMPA in December 2024.

· Presented FRESCO-2 subgroup analyses for CRC patients at ASCO (Free ASCO Whitepaper), biomarker analysis at AACR (Free AACR Whitepaper) and quality-of-life analysis at ASCO (Free ASCO Whitepaper) GI40, showing meaningful quality-adjusted survival benefit, efficacy regardless of prior therapy or sequence as well as CEA41 potentially a predictor of efficacy (NCT04322539).

· Published FRUTIGA China Phase III results in Nature Medicine for 2L gastric cancer, in combination with paclitaxel, and presentations at ASCO (Free ASCO Whitepaper), showing statistically significant improvements in ORR and PFS, as well as OS benefits in sub-group without taking subsequent antitumor therapy (NCT03223376).

· Positive result of FRUSICA-2 China Phase III in 2L RCC in March 2025 (NCT05522231).

Sovleplenib (HMPL-523), an investigative and highly selective oral inhibitor of Syk42

· Published ESLIM-01 China Phase III results for adult patients with primary ITP in China in The Lancet Haematology concurrently with presentations at EHA (Free EHA Whitepaper), showing durable response rate of 48.4%, tolerable safety profile and improved quality of life regardless of prior lines of therapies (NCT05029635).

· Presented ESLIM-01 China Phase III long-term results at ASH (Free ASH Whitepaper), showing durable response rate of 51.4% and long-term durable response rate of 59.8% as well as consistent safety profile.

· Published China Phase II results in warm AIHA in China at EHA (Free EHA Whitepaper) and in The Lancet Haematology in 2025, demonstrating overall response rate of 66.7% and a favorable safety profile (NCT05535933).

· Initiated ESLIM-02 China Phase III stage in warm AIHA (NCT05535933).

Potential upcoming clinical milestones for sovleplenib:

· Complete ESLIM-01 NMPA NDA review around end 2025 (NCT05029635).

· Complete enrollment of ESLIM-02 Phase III in the second half of 2025 (NCT05535933).

Surufatinib (SULANDA in China), an oral inhibitor of VEGFR, FGFR43 and CSF-1R44

· Completed enrollment of Phase II part of a China Phase II/III trial for 1L metastatic PDAC45 patients, in combination with AiRuiKa (camrelizumab), nab-paclitaxel and gemcitabine (NCT06361888). This study was informed in part by an investigator-initiated trial presented at ASCO (Free ASCO Whitepaper) GI 2024 of a similar combination.

Potential upcoming clinical milestone for surufatinib:

· Data readout of the PDAC Phase II trial in late 2025.

Tazemetostat (TAZVERIK in Hainan, Macau and Hong Kong), a first-in-class, oral inhibitor of EZH2

· Positive bridging study in 3L follicular lymphoma leading to NDA submission with Priority Review status (NCT05467943).

· Continued enrolling SYMPHONY-1 Phase III China portion of the global study, in combination with lenalidomide and rituximab, in follicular lymphoma patients (NCT04224493).

Potential upcoming clinical milestone for tazemetostat:

· Complete NDA review in China in mid 2025.

Fanregratinib (HMPL-453), a novel, highly selective and potent inhibitor targeting FGFR 1, 2 and 3

· Completed enrollment of registrational China pivotal Phase II for IHCC46 with FGFR2 fusion/rearrangement in March 2025 (NCT04353375).

Ranosidenib (HMPL-306), an investigative and highly selective oral dual-inhibitor of IDH1 and IDH247 enzymes

· Presented and published results from China and US/European Phase I studies at EHA (Free EHA Whitepaper) and the journal Med for R/R IDH1/2m48 AML49 patients (NCT04272957, NCT04764474).

· Initiated RAPHAEL China Phase III trial for 2L R/R IDH1/2m AML (NCT06387069).

Other early-stage investigational drug candidates

· Presented pre-clinical and Phase I results at AACR (Free AACR Whitepaper), ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) for ERK1/250 inhibitor HMPL-295, third-generation BTK51 inhibitor HMPL-760, Menin inhibitor HMPL-506, and anti-CD38 HMPL-A067.

· Initiated Phase I trial for HMPL-506 in hematological malignancies in China (NCT06387082).

IV. ANTIBODY-TARGETED THERAPY CONJUGATE (ATTC) PLATFORM

New in-house created platform with multiple potential IND52 candidates

Our ATTC next-generation technology platform leverages over 20 years of expertise in targeted therapies with small molecules inhibitors. ATTC drug candidates enrich the next wave of clinical development with potential key advantages over traditional antibody-drug conjugates and/or small molecule medicines:

· Better efficacy through synergistic antibody-small molecule targeted therapy combinations that will target specific mutations; overcome drug resistance and potentially support combinations with other targeted therapies, chemotherapy and immunotherapy, in early-line patient settings.

· Improved safety and prolonged treatment given lower off-tumor or off-target toxicity than small molecules, less myelosuppression and better quality of life than cytotoxin-based conjugates.

· Attractive pharmacokinetics tackles difficult drug targets, enabled by antibody-guided delivery to target sites which will improve bioavailability and reduce drug-drug interactions when compared to oral small molecules inhibitors.

V. COLLABORATION UPDATES

Further progress by Inmagene53 with two candidates discovered by HUTCHMED

· HUTCHMED received 7.5% shareholding interest in Inmagene following the latter’s exercise of an option to exclusively develop, manufacture and commercialize IMG-007, a nondepleting anti-OX40 antibody, and IMG-004, a reversible, non-covalent, highly selective oral BTK inhibitor.

· Inmagene and Ikena Oncology, Inc. (Nasdaq: IKNA) agreed to merge, which is expected to close in mid-2025, subject to closing conditions. HUTCHMED will have an interest in the merged company.

· Inmagene announced positive results of a Phase IIa trial with IMG-007 for atopic dermatitis, showing Week 16 mean change in EASI54 of 77% and EASI-75 response of 54% (NCT05984784). A Phase IIb dose-finding study with a subcutaneous formulation in moderate-to-severe atopic dermatitis is planned.

· Inmagene enrolled a Phase IIa trial with IMG-007 for alopecia areata (NCT06060977), and announced results of a Phase I study with IMG-004, indicating once daily dosing potential (NCT05349097).

VI. OTHER VENTURES

· Other Ventures consolidated revenue is predominantly from the prescription drug distribution business55 in China. It decreased by 14% (12% at CER) to $266.8 million (2023: $309.4m) primarily due to lower COVID-related prescription drug distribution sales in 2024.

· Share of equity in earnings of SHPL, a non-consolidated joint venture, slightly decreased by 2% (increased 1% at CER) to $46.5 million (2023: $47.4m) mainly due to increased clinical trial investment for new products.

· Consolidated net income attributable to HUTCHMED from Other Ventures decreased by 5% (2% at CER) to $47.7 million (2023: $50.3m), due to disposal of consumer products business in December 2023, lower COVID-related prescription drug distribution sales and fluctuation in net income contributed from SHPL.

SHPL Disposal: HUTCHMED entered into share purchase agreements to divest its 45.0% equity interest in SHPL for approximately $608 million in cash, retaining a 5.0% equity interest. It is estimated that HUTCHMED will record a pre-tax gain of approximately $477 million.

VII. SUSTAINABILITY

HUTCHMED is committed to progressively embedding sustainability into all aspects of its operations and creating long-term value for its stakeholders. Continued progress was made in 2024 including:

· Sustainability goals and targets: satisfactory progress made in 11 short- to long-term goals and targets; sustainability performance continued to be incorporated into management’s performance-based remuneration. To prepare for new targets setting, sustainability-related efforts were continually assessed and a target achievement roadmap focused on HUTCHMED’s five sustainability pillars is being developed.

· Enhanced climate actions: based on the 2022 climate risk assessment, HUTCHMED conducted another comprehensive assessment on the potential financial impacts of climate risks and opportunities for HUTCHMED with costs estimated under low-, mid-, and high-emission scenarios. This also prepares it for the latest climate-related disclosure requirements of the HKEX56 and other international disclosure standards.

· Biodiversity assessment: a biodiversity assessment was conducted to understand HUTCHMED’s dependency and impact on nature. Based on the results of the assessment, a Biodiversity Policy was prepared and approved by the Board for public disclosure.

· Supplier ESG57 assessment: this was conducted to understand the sustainability maturity of the supplier base and pave the way for a tailored supplier engagement program in 2025.

· Improvement on ESG ratings: MSCI ESG upgraded the rating of HUTCHMED from BBB to A. ISS ESG upgraded the rating of HUTCHMED from C to C+, which is classified as Prime. Its S&P Global ESG score continued to rise from 48 to 53, placing HUTCHMED in the 90th percentile of the industry. Additionally, HUTCHMED achieved an A- rating and a top quartile score in the Hang Seng Corporate Sustainability Index Series rating, particularly in the areas of environment and governance.

In recognition of its marked improvement in sustainability efforts within the pharmaceutical industry, HUTCHMED was honored with multiple ESG awards in 2024. These efforts will continue to guide HUTCHMED towards a more sustainable future. The 2024 Sustainability Report will be published alongside the 2024 Annual Report in April 2025 and will include further information on sustainability initiatives and performance.

Financial Highlights

Foreign exchange impact: The RMB depreciated against the US dollar by approximately 3% during 2024 on average, which has impacted consolidated financial results as highlighted below.

Revenue for the year ended December 31, 2024 was $630.2 million compared to $838.0 million in 2023.

· Oncology/Immunology consolidated revenue amounted to $363.4 million (2023: $528.6m):

§ FRUZAQLA revenue was $110.8 million, reflecting its successful launch since November 2023 comprising royalties, manufacturing revenue and commercial milestone.

§ ELUNATE revenue increased 4% (6% at CER) to $86.3 million (2023: $83.2m) in its sixth year since launch, comprising of manufacturing revenue, promotion and marketing services revenue and royalties, maintaining its leading market share position while weathering greater market competition.

§ SULANDA revenue increased 12% (14% at CER) to $49.0 million (2023: $43.9m) due to continued sales growth after NRDL renewal as brand awareness amongst doctors continues to increase, leading to greater NET patient access and market share.

§ ORPATHYS revenue decreased 15% (13% at CER) to $24.5 million (2023: $28.9m), due to phasing of manufacturing revenue of $10.9 million (2023: $15.1m), and royalties of $13.6 million (2023: $13.8m).

§ TAZVERIK revenue was $0.9 million (2023: $1.0m) mainly from sales in Hainan and Hong Kong.

§ Takeda upfront, regulatory milestones and R&D services revenue decreased to $67.0 million (2023: $345.9m, of which $280.0m was the recognized portion of the $400.0 million upfront cash payment received from Takeda in April 2023).

§ Other revenue of $24.9 million (2023: $18.5m), primarily related to milestone payment of $6.0 million from AstraZeneca and fees from AstraZeneca and Lilly for development and regulatory activities.

· Other Ventures consolidated revenue decreased 14% (12% at CER) to $266.8 million (2023: $309.4m), primarily as a result of lower COVID-related prescription drug distribution sales in 2024. This excluded non-consolidated revenue at SHPL of $393.5 million (2023: $385.5m).

Net Expenses for 2024 were $592.5 million compared to $737.2 million in 2023, reflecting strong efforts on cost control.

· Cost of Revenue decreased by 9% to $348.9 million (2023: $384.4m), which was mainly due to lower revenue from Other Ventures. Cost of revenue as a percentage of oncology product revenue improved (from 56% in 2023 to 34% in 2024) due to favorable product mix and economies of scale.

· R&D Expenses reduced 30% to $212.1 million (2023: $302.0m), mainly due to restructuring of teams outside of China, with clinical and regulatory expenses in the US and Europe decreasing to $34.5 million (2023: $106.9m). China investment was $177.6 million (2023: $195.1m) which reflects both a decrease in cost for completed studies with NDAs under review and an ongoing commitment to key assets with global potential in our internal pipeline, including the development of the next-generation ATTC platform.

· S&A58 Expenses were $112.9 million (2023: $133.2m), which decreased primarily due to tighter controls over administrative spending $64.3 million (2023: $79.8m) and lower selling expenses $48.6 million (2023: $53.4m) as we realized efficiencies from a salesforce already scaled to support revenue growth.

· Other Items mainly comprised of equity in earnings of SHPL, interest income and expense, FX and taxes, generated net income of $81.4 million (2023: $82.4m).

Net Income attributable to HUTCHMED for 2024 was $37.7 million compared to $100.8 million in 2023.

· The net income attributable to HUTCHMED in 2024 was $0.04 per ordinary share / $0.22 per ADS59, (2023: $0.12 per ordinary share / $0.59 per ADS).

Cash, Cash Equivalents and Short-Term Investments were $836.1 million as of December 31, 2024 compared to $886.3 million as of December 31, 2023.

· Adjusted Group (non-GAAP60) net cash flows excluding financing activities in 2024 were -$19.5 million mainly due to net income attributable to HUTCHMED of $37.7 million offset by changes in working capital of $62.2 million from partner milestones achieved and receivable at the end of 2024 and ongoing recognition of Takeda deferred revenue (2023: $206.7m due to the receipt of $435 million in upfront and milestone payments from Takeda).

· Net cash used in financing activities in 2024 totaled $30.7 million mainly due to purchases for equity awards of $36.1 million (2023: net cash generated from financing activities of $48.7m mainly due to drawdowns of bank borrowings).

FINANCIAL GUIDANCE

HUTCHMED provides full year 2025 guidance for Oncology/Immunology consolidated revenue of $350 million to $450 million. HUTCHMED’s work in 2025 and beyond will be supported by its strong balance sheet. The Company will continue to be financially self-reliant while supporting investments to bring innovative medicines to patients globally.

Shareholders and investors should note that:

· The Company does not provide any guarantee that the statements contained in the financial guidance will materialize or that the financial results contained therein will be achieved or are likely to be achieved; and

· The Company has in the past revised its financial guidance and reference should be made to any announcements published by it regarding any updates to the financial guidance after the date of publication of this announcement.

On March 19, 2025 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a life sciences company developing innovative targeted oncology therapies and commercializing RenovoCath, a novel, FDA-cleared drug-delivery device, reported a presentation of a new pre-clinical clinical data abstract at the upcoming Society of Surgical Oncology (SSO) 2025 Annual Meeting (Press release, Renovorx, MAR 19, 2025, View Source [SID1234651274]).

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The abstract, titled "Pharmacodynamics of Intra-arterial vs. Intravenous Gemcitabine in Locally Advanced Pancreatic Cancer: Results of a Phase III Randomized Clinical Trial," is co-authored by Dr. Ramtin Agah, RenovoRx’s Chief Medical Officer. The abstract supports RenovoRx’s proprietary Trans-Arterial Micro-Perfusion (TAMPTM) therapy platform via additional human PK data and pre-clinical data.

TAMP is designed to ensure targeted therapeutic delivery across the arterial wall near the tumor site to bathe the target tumor, while potentially minimizing a therapy’s toxicities versus systemic intravenous therapy. RenovoRx’s novel approach to locoregional treatment offers the potential for increased safety, tolerance, and improved efficacy.

RenovoRx’s ongoing Phase III TIGeR-PaC clinical trial is evaluating the Company’s novel investigational drug-device combination product candidate, (intra-arterial delivery of gemcitabine via RenovoCath) known as IAG, utilizing the TAMP drug delivery platform in patients with Locally Advanced Pancreatic Cancer (LAPC). RenovoRx currently anticipates the completion of both patient enrollment and the second interim analysis for TIGeR-PaC in mid-2025. This abstract is a sub-study of the TIGeR-PaC clinical trial. The combination product candidate (IAG), which is enabled by the FDA-cleared RenovoCath device, is currently under investigation and has not been approved for commercial sale.

SSO 2025 Abstract Details:

Title: Pharmacodynamics of Intra-arterial vs. Intravenous Gemcitabine in Locally Advanced Pancreatic Cancer: Results of a Phase III Randomized Clinical Trial
Authors: Emmanuel Zervos MD, Paula Novelli MD, Amer Zureikat MD, Michael Pishvaian MD, Kenneth Meredith MD, Hassan Hatoum MD, Reza Nazemzadeh MD, Sandeep Loria MD, Ramtin Agah MD
Location: ePoster P379 at Tampa Convention Center, Tampa, FL
Dates: March 27 – 29, 2025
About RenovoCath

Based on its FDA clearance, RenovoCath is intended for the isolation of blood flow and delivery of fluids, including diagnostic and/or therapeutic agents, to selected sites in the peripheral vascular system. RenovoCath is also indicated for temporary vessel occlusion in applications including arteriography, preoperative occlusion, and chemotherapeutic drug infusion. For further information regarding our RenovoCath Instructions for Use ("IFU"), please see: IFU-10004-Rev.-F-Universal-IFU.pdf.

About the TIGeR-PaC Clinical Trial

TIGeR-PaC is an ongoing Phase III randomized multi-center study evaluating the proprietary TAMP (Trans-Arterial Micro-Perfusion) therapy platform for the treatment of LAPC. RenovoRx’s first investigational drug-device combination product candidate (intra-arterial delivery of gemcitabine via RenovoCath, known as IAG) using the TAMP therapy platform enabled with the Company’s FDA-cleared RenovoCath device for the intra-arterial administration of chemotherapy, gemcitabine.

The first interim analysis in the Phase III clinical trial was completed in March 2023, with the Data Monitoring Committee recommending a continuation of the study. The TIGeR-PaC study is investigating TAMP in LAPC. The study’s primary endpoint is an overall survival benefit with secondary endpoints including reduced side effects versus standard of care. The second interim analysis for this study will be triggered by the 52nd event (i.e., patient death), which is estimated to occur in the second quarter of 2025. The second interim data readout would follow thereafter, with the timing for such readout depending on customary factors such as time needed for analysis. RenovoRx is also aiming to complete patient enrollment in the TIGeR-PaC study in mid-2025.

On March 19, 2025 Sona Nanotech Inc. (CSE: SONA) (OTCQB: SNANF) (the "Company", "Sona") reported updated data confirming efficacy of its Targeted Hyperthermia Therapy ("THT") cancer treatment in an immunotherapy resistant cancer (Press release, Sona Nanotech, MAR 19, 2025, View Source [SID1234652834]). In this follow-up data to the previously released preliminary study (see press release dated December 11, 2024), again using an industry-standard, immunotherapy resistant, CT-26 colon cancer model, Sona’s THT cancer treatment was 100% effective in activating a strong, effective immune system response. In these experiments, animals treated with a PD-1 checkpoint inhibitor, a standard of care immunotherapy, experienced no benefit with tumors growing similarly to tumors in the control group of untreated animals. However, in a new, second cohort of eight animals first treated with Sona’s THT and then treated with a PD-1 inhibitor, 100% of animals responded demonstrating near complete arrest in tumor growth in the majority of animals as highlighted by the dashed green line in Figure 1, below.

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Sona Nanotech CMO, Dr. Carman Giacomantonio, commented, "In this study, Sona’s THT cancer treatment is clearly the difference maker in inhibiting the growth of this notoriously difficult-to-treat cancer. THT’s ability to cause the expression of new antigens causes the immune system to engage, which we show permits immunotherapies to work better, making THT a powerful potential immunotherapy in its own right."

Sona Nanotech CEO, David Regan, commented, "While still an early preclinical study, we are nonetheless very excited to see the repeatability of our earlier successful preclinical colorectal study results. This data gives us additional confidence as to THT’s ability to enhance the response rates of immunotherapies used in humans, which we expect to be able to assess shortly in our first-in-human early feasibility study."

Further data from this experiment can be found in the Company’s updated corporate presentation, which can be accessed in the Investor Section of its website.

Sona’s THT cancer treatment uses the Company’s patented, biocompatible gold nanorods ("GNRs") to treat certain solid cancer tumors, shrinking them and stimulating the immune system, which has been shown in preclinical studies to enhance the response rates of two different immunotherapy drugs, IL-2 and PD-1.