On August 28, 2026 CREATE Medicines, Inc. ("CREATE"), a clinical-stage biotechnology company pioneering in vivo immune programming, reported a strategic research and development collaboration and license agreement with WestGene Biopharma, a Chengdu, China-based biotechnology company developing targeted lipid nanoparticle (LNP) delivery technology and next-generation mRNA therapeutics.

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The collaboration expands CREATE’s access to cutting edge targeted LNP technologies, combining CREATE’s leading in vivo CAR platform with WestGene’s proprietary tLNP delivery platform. It will evaluate their synergistic potential across three product candidates, providing research, development, and early clinical evaluation of initial programs, and further development activities to advance candidate products.

"Pioneering a new therapeutic class requires us to be fast, smart, and global," said Daniel Getts, Ph.D., Chief Executive Officer and Co-founder of CREATE Medicines. "We are excited to collaborate with WestGene and gain new exposure to its exceptional targeted-LNP expertise and technology. WestGene brings a highly productive translational organization and the ability to advance innovative programs rapidly through clinical studies, which will support CREATE’s efforts to develop the deepest pipeline and most informative human dataset in in vivo cell therapy. By combining these capabilities, we can accelerate the speed of clinical breakthroughs as we continue building the most integrated in vivo immune programming company in the world."

The collaboration will initially advance three programs spanning autoimmune disease, solid tumors, and durable gene delivery:

CRT-403, a dual-target CD19 × BCMA in vivo CAR-T therapy for autoimmune disease that targets both B cells and antibody-producing plasma cells.
CRT-401, a dual-component HER2 × TROP2 multi-immune in vivo CAR program for solid tumors.
A CD19 × BCMA RetroT-enabled in vivo CAR program, combining CREATE’s proprietary site-specific RNA gene integration platform with WestGene’s targeted delivery technology to evaluate durable CAR expression following a single administration.
"We are pleased to collaborate with CREATE Medicines to explore the potential of targeted LNP delivery in next-generation in vivo CAR therapies," said Xiangrong Song, Ph.D., Chairman and Chief Executive Officer of WestGene. "CREATE brings a broad clinical and technology platform spanning multiple immune-cell populations and RNA expression strategies, while WestGene brings targeted delivery technology and extensive experience in translating mRNA innovation in the clinic. Together, we aim to move differentiated programs into patients efficiently and generate data with global relevance."

The collaboration, which may be expanded by mutual agreement, builds on CREATE’s existing autoimmune pipeline, led by CRT-402, its CD19-directed, transient and repeat-dose in vivo CAR-T program, currently in a first-in-human Phase 1/2 clinical study (NCT07778446). CRT-402 establishes the foundation of CREATE’s CD19 development strategy, which the company is expanding through dual-target CD19 × BCMA immune programming with CRT-403 and potentially durable CAR expression through its RetroT platform.

CREATE’s growing global footprint now includes three targeted-delivery partnerships across three continents: WestGene in China, a research collaboration with Monash University in Australia, and a strategic collaboration with Acuitas Therapeutics in Canada. Partnerships are built on CREATE’s clinical dataset, which is the largest in the in vivo CAR field, with more than 60 patients dosed across its in vivo CAR clinical programs. Data generated across its candidates inform each of its subsequent programs, leveraging insights across targets, immune-cell populations, delivery systems, CAR architectures, expression profiles, dosing strategies, and disease settings.

(Press release, Create Medicines, AUG 28, 2026, View Source [SID1234670419])

On August 28, 2026 InxMed Co., Ltd ("InxMed"), a clinical-stage biotechnology company dedicated to developing innovative therapies targeting cancer treatment resistance and metastasis, reported that the clinical results of ifebemtinib (IN10018), a highly selective focal adhesion kinase (FAK) inhibitor, in combination with garsorasib (D-1553), a potent KRAS G12C inhibitor, in previously treated KRAS G12C-mutant metastatic colorectal cancer (CRC), have been published online in The Lancet Oncology.

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The data were derived from a phase Ib/II trial (NCT06166836/NCT05379946) evaluating the efficacy and safety of ifebemtinib plus garsorasib in KRAS G12C-mutant solid tumors, where ifebemtinib plus garsorasib, as an all-oral, chemotherapy-free regimen, demonstrated encouraging antitumor activity in patients with previously treated KRAS G12C-mutant metastatic CRC. This is the first clinical study, to our knowledge, to evaluate the efficacy and safety of FAK inhibitors in combination with KRAS G12C inhibitors in KRAS G12C-mutant solid tumors.

Encouraging Antitumor Efficacy and Manageable Safety Profile

The CRC cohort of this trial contains two parts: Part 1-single-arm study and Part 2-randomized study. In Part 1-single-arm study, 15 previously-treated KRAS G12C-mutant metastatic CRC patients were enrolled and received ifebemtinib (100mg once a day) plus garsorasib (600mg twice a day) orally. And in Part 2-randomized study, 36 previously-treated KRAS G12C-mutant metastatic CRC patients were enrolled and randomly assigned (1:1) to receive ifebemtinib plus garsorasib or garsorasib alone (600mg twice a day) orally. By the data cutoff on June 30, 2025, the median follow-up was 23.8 months in the single-arm study, and in the randomized study the median follow-up was 10•3 months for the combination group and 10•9 months for the monotherapy group. Key findings published in this paper were summarized below:

Objective Response Rate (ORR): In the single-arm study, 15 patients were enrolled with 14 patients evaluable, and the confirmed ORR was 46.7% (95% CI: 21.3–73.4) in the full population and 50.0% (95% CI: 23.0–77.0) in the evaluable population. In the randomized study, the confirmed ORR was 38.9% (95% CI: 17.3–64.3) in the ifebemtinib plus garsorasib group versus 16.7% (95% CI: 3.6–41.4) in the garsorasib monotherapy group, representing an absolute improvement of 22.2% in the combination group.

Progression-Free Survival (PFS): In the single-arm study, the median PFS was 6.9 months (95% CI: 2.8–12.0). In the randomized study, ifebemtinib plus garsorasib achieved a median PFS of 7.7 months (95% CI: 3.0–NE) versus 4.0 months (95% CI: 2.0–5.6) with garsorasib monotherapy group (HR 0.48, 95% CI: 0.22–1.04), pointing to a favorable PFS trend in favor of the combination.

Overall Survival (OS): In the single-arm study, the median OS was 14.3 months (95% CI: 4.7–NE). In the randomized study, the median OS was not estimable (95% CI: 10.2–NE) in ifebemtinib plus garsorasib group versus 7.5 months (95% CI: 5.3–NE) in garsorasib monotherapy group (HR 0.34, 95% CI: 0.11–1.12), suggesting a favorable OS trend in the combination group.

Manageable safety profile: Across all 33 patients receiving ifebemtinib plus garsorasib, 32 patients (97%) reported treatment-related adverse events (TRAE) with most of them reported as grade 1-2 and grade 3 TRAEs reported in 30% of patients. No grade 4 TRAEs, treatment-related deaths or TRAEs leading to study drug discontinuation were reported across all cohorts. The most common TRAEs occurring in all 33 patients receiving ifebemtinib plus garsorasib were diarrhoea, proteinuria, and nausea.

Overcoming Resistance by FAK Inhibition When Targeting KRAS

KRAS G12C mutations occur in approximately 3–4% of patients with metastatic colorectal cancer. Currently, KRAS G12C inhibitor monotherapy shows limited efficacy in this patient population, and two KRAS G12C inhibitors plus anti-EGFR antibody regimens demonstrated synergistic activity and have been approved by FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. However, anti-EGFR antibody requires intravenous administration and are commonly associated with dermatological toxicities. How to further enhance the efficacy of KRAS G12C-targeted therapy while providing a more convenient and tolerable treatment option has become a clinical imperative.

InxMed’s translational research found out that KRAS G12C inhibition alone triggers adaptive hyperactivation of the FAK–YAP signaling pathway, promotes fibrogenesis in the tumor microenvironment, and thereby enhances tumor cell survival. FAK inhibition by ifebemtinib disrupts this resistance mechanism, sensitizing tumor cells to KRAS G12C inhibition and prolonging the duration of treatment response. The clinical data reported herein provide further support for ifebemtinib in combination with KRAS G12C inhibitors in the treatment of previously treated KRAS G12C-mutant metastatic CRC.

Advancing the Clinical Development

The study demonstrates that the dual-oral, chemotherapy-free regimen of ifebemtinib plus garsorasib has shown encouraging antitumor activity and a manageable safety profile in patients with previously treated KRAS G12C-mutant metastatic CRC. These findings warrant a pivotal trial of this combination regimen to further establish its clinical benefit. The company has submitted an IND application in China, for a phase III trial evaluating the efficacy and safety of ifebemtinib plus garsorasib versus investigators’ choice of standard therapy for treatment of previously treated metastatic colorectal cancer harboring KRAS G12C mutation.

Based on a robust translational medicine foundation and compelling clinical evidence, Ifebemtinib is poised to become a revolutionary therapeutic that could fundamentally reshape the RAS-targeted treatment paradigm. InxMed is strategically driving a comprehensive development program for Ifebemtinib across RAS-mutant tumors, with combination regimens already initiated or in preparation not only with KRAS G12C inhibitors, but also with KRAS G12D inhibitors and multi-RAS inhibitors, among other novel classes, underscoring the company’s commitment to transforming the future of RAS-addicted cancers.

About Ifebemtinib (IN10018)

Ifebemtinib (IN10018) is an orally available, highly potent, and selective small-molecule inhibitor of focal adhesion kinase (FAK). InxMed holds exclusive global development and commercialization rights. Clinically, ifebemtinib has demonstrated excellent safety and tolerability in over 700 subjects globally, showing vast potential as a "backbone" combination partner across multiple modalities, including RAS inhibitors, immune checkpoint blockades, and antibody-drug conjugates (ADCs). It has received multiple Breakthrough Therapy Designations from the NMPA and Fast Track Designation from the U.S. FDA.

(Press release, InxMed, AUG 28, 2026, View Source [SID1234670418])

On August 28, 2026 Kazia Therapeutics Limited (NASDAQ: KZIA) ("Kazia" or the "Company"), an oncology-focused biotechnology company developing therapies that selectively reprogram cancer biology, restore anti-tumor immunity and overcome treatment resistance, reported the pricing of its previously announced tranched registered public offering (the "Offering") of (i) 2,580,000 American Depositary Shares ("ADSs"), each representing five hundred (500) ordinary shares of the Company, no par value per share, or in lieu of ADSs to certain investors, pre-funded warrants to purchase ADSs, (ii) accompanying Series A Warrants to purchase up to 2,243,478 ADSs (or pre-funded warrants in lieu thereof), which are exercisable immediately at a purchase price of $17.825 per ADS and will expire upon the earlier of 30 days following the Company’s Stage IV triple-negative breast cancer (TNBC) data readout, expected in the second half of 2027, or the five-year anniversary of issuance, and (iii) accompanying Series B Warrants to purchase up to 2,064,000 ADSs (or pre-funded warrants in lieu thereof), which are exercisable immediately at a purchase price of $19.375 per ADS and will expire upon the earlier of 30 days following the Company’s HR+/HER2- data readout, expected in the first half of 2028, or the five-year anniversary of issuance. All of the securities in the Offering are being sold by Kazia. The combined public offering price for each ADS and accompanying warrants is $15.50, and the combined public offering price for each pre-funded warrant and accompanying warrants is $15.4999 (equal to the combined public offering price per ADS and accompanying warrants less $0.0001), for expected gross proceeds to Kazia of approximately $40 million, before deducting underwriting discounts and commissions and offering expenses. If all of the Series A Warrants and Series B Warrants are exercised in full, the Company would receive additional gross proceeds of approximately $80 million, before deducting applicable expenses.

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Leerink Partners and Guggenheim Securities are acting as joint bookrunning managers for the Offering. BTIG and Needham & Company are acting as lead managers for the Offering. Laidlaw & Company (UK) Ltd. is acting as co-manager for the Offering.

The Offering is expected to close on or about August 31, 2026, subject to satisfaction of customary closing conditions.

Kazia intends to use the net proceeds from the Offering primarily to fund clinical development of paxalisib, including ongoing and planned studies in triple-negative breast cancer and HR+/HER2- breast cancer and other oncology indications, and for working capital and general corporate purposes.

The ADSs and warrants are being offered pursuant to a registration statement on Form F-3 (File No. 333-294392), which was previously filed with and subsequently declared effective by the Securities and Exchange Commission (the "SEC"). The Offering is being made only by means of a prospectus supplement and accompanying prospectus that form a part of the effective registration statement. A final prospectus supplement and the accompanying base prospectus relating to the Offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Additionally, electronic copies of the preliminary prospectus supplement and the accompanying base prospectus may be obtained from Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, or by telephone at (800) 808-7525, ext. 6105, or by email at [email protected], or from Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, telephone: (212) 518-9544, email: [email protected].

This press release does not constitute an offer to sell or a solicitation of an offer to buy the securities in the Offering, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

(Press release, Kazia Therapeutics, AUG 28, 2026, View Source [SID1234670417])

On August 28, 2026 Takeda (TSE:4502/NYSE:TAK) reported U.S. Food and Drug Administration (FDA) approval of the New Drug Application (NDA)* for MIMRYLO (rusfertide) for the treatment of erythrocytosis in adults with polycythemia vera (PV), a blood cancer.

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MIMRYLO is a first-in-class hepcidin mimetic designed to regulate iron distribution in the body and red blood cell overproduction to control hematocrit levels, which is the ratio of red blood cells to the total amount of blood in the body. Maintaining controlled hematocrit levels below 45% is the primary treatment goal in PV.1

"For patients living with PV, uncontrolled hematocrit can have serious consequences, including an elevated risk of life-threatening thrombotic events," said Andrew T. Kuykendall, M.D., VERIFY lead investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. "Current treatments, such as phlebotomy, leave a significant gap for too many patients and can pose challenges to daily life and routines. The approval of MIMRYLO offers clinicians and patients a novel, first-in-class therapy that targets erythrocytosis, which drives excess red blood cell production in PV. The strength and consistency of the VERIFY data give me real confidence in MIMRYLO’s potential to advance how we treat PV in everyday practice and to maintain hematocrit control."

Uncontrolled Hematocrit is a Challenge in the Treatment of PV
Affecting approximately 90,000 people in the U.S., PV is characterized by the overproduction of red blood cells (erythrocytosis), leading to elevated hematocrit which can increase blood viscosity, or thickness.2,3 This has the potential to result in life-threatening thrombotic events, including stroke, deep vein thrombosis and pulmonary embolism.4 Maintaining hematocrit levels consistently below 45% can prevent thrombotic events and alleviate burdensome symptoms, including severe fatigue, pruritus (itching), difficulty concentrating and night sweats.4 An estimated 78% of patients still experience uncontrolled hematocrit with current standard of care, including phlebotomy and cytoreductive therapies.5 Patients with PV experiencing uncontrolled hematocrit have a four times higher risk of cardiovascular death or major cardiovascular events.4

"People living with PV often experience complex and invisible symptoms, from extreme fatigue to the emotional strain of living with a chronic blood cancer," said Kapila Viges, Chief Executive Officer, MPN Research Foundation. "At the same time, we know that every patient’s experience with PV is different, underscoring the need to continue to listen closely to the community to understand what matters most. There remains a need for treatments that better address these daily challenges. This meaningful approval reflects important progress and brings forward a new treatment option in a disease where patients have long needed innovation and more choices. We are encouraged by MIMRYLO’s potential to help patients meet their treatment goals."

MIMRYLO is a First-In-Class Treatment Option for Adults with PV
The approval was supported by data from the global randomized Phase 3 VERIFY study (NCT05210790) that included 293 patients with PV, showing that MIMRYLO met all efficacy endpoints and demonstrated a favorable safety profile. In the study, patients receiving MIMRYLO plus current standard of care demonstrated a higher response rate compared to placebo plus current standard of care. This included hematocrit control, a reduction in the need for phlebotomy and improvement in fatigue as measured by PROMIS Fatigue Short Form 8a.

MIMRYLO was generally well-tolerated through 52 weeks of treatment in the VERIFY trial. The most common treatment-emergent adverse events in MIMRYLO-treated patients were injection site reactions and anemia. Learn more about the Phase 3 data results here.

"The approval of MIMRYLO underscores the strength of Takeda’s late-stage pipeline and our focus on developing genuinely differentiated therapies for patients who are urgently waiting for new options," said Julie Kim, President and Chief Executive Officer, Takeda. "We are at an important inflection point as we prepare to deliver three new medicines, which have the potential to drive our future growth and are a reflection of our commitment to advancing innovation that doesn’t just add to the treatment landscape, but reshapes it. We are grateful to the patients, care partners, advocates and investigators who helped make this approval possible."

The open-label extension of the VERIFY trial is ongoing and Takeda will share further findings at upcoming medical conferences. Takeda is working with regulators outside of the U.S. to potentially bring MIMRYLO to more patients worldwide.

This approval does not result in any changes to Takeda’s consolidated financial forecast for the fiscal year ending March 31, 2027 (FY2026).

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
New or Worsening Thrombocytosis: MIMRYLO may increase platelet counts in patients with PV. Platelet counts generally plateaued on treatment by Week 8. After initiating MIMRYLO and during dose modifications, monitor CBC every 2 to 4 weeks or as clinically indicated. Platelet elevations associated with MIMRYLO may require cytoreductive therapy initiation, modification, or MIMRYLO dose modifications or discontinuation.
Injection-Site Reactions: Injection site reactions (including Grade 3 reactions) have been reported in patients treated with MIMRYLO. The most common injection site reactions reported were erythema, pruritus, pain, and swelling. Use ice, topical corticosteroid creams, antihistamines or analgesics, as needed, to treat injection site pain and swelling.
Embryo-Fetal Toxicity: Based on findings from animal reproduction studies, MIMRYLO may cause fetal harm when administered to a pregnant woman. Advise patients to stop taking MIMRYLO if they become pregnant.
ADVERSE REACTIONS
The most common (>15%) adverse reactions were injection site reactions (56%) and anemia (16%).

USE IN SPECIFIC POPULATIONS
Lactation: Because of the potential for serious adverse reactions in the breastfed child, including impaired iron absorption, advise patients not to breastfeed during treatment with MIMRYLO and for 30 days after the final treatment.
Females and Males of Reproductive Potential
Pregnancy Testing: Prior to initiating MIMRYLO, pregnancy testing is recommended for females of reproductive potential.
Contraception: Advise female patients of reproductive potential to use effective contraception during treatment with MIMRYLO and for at least 30 days after the final dose of MIMRYLO.
To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-662-8532 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see MIMRYLO (rusfertide) full Prescribing Information.

About MIMRYLO
MIMRYLO is a first-in-class subcutaneous treatment that mimics the action of hepcidin, a natural hormone that regulates iron homeostasis and erythrocytosis. By targeting the underlying mechanism of iron dysregulation in polycythemia vera, MIMRYLO aims to reduce excess red blood cell production and help patients maintain hematocrit control. MIMRYLO is administered once weekly via subcutaneous injection and has been generally well-tolerated in clinical trials to date. Protagonist discovered MIMRYLO and led its development through Phase 3. Takeda now has exclusive global development and commercialization rights for MIMRYLO.

About VERIFY
The Phase 3 VERIFY study (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled study evaluating MIMRYLO in 293 patients with polycythemia vera over a 156-week period, with treatment extension for participants who are continuing to derive benefit from MIMRYLO beyond the 156-week treatment period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered MIMRYLO in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment, which could include phlebotomy, 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%. Key secondary endpoints evaluated at Week 32 included mean number of phlebotomies, proportion of patients maintaining hematocrit <45%, mean change in fatigue score as measured by PROMIS Fatigue Short Form 8a and total symptom burden as measured by Myelofibrosis Symptom Assessment Form (MFSAF) Version 4.0.

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

About Polycythemia Vera (PV)
Polycythemia vera (PV) is a chronic blood cancer characterized by the overproduction of red blood cells (erythrocytosis), which increases blood viscosity, or thickness, and can result in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. Hematocrit is the ratio of red blood cells to the total amount of blood in the body. Achieving and maintaining controlled hematocrit levels of less than 45% is the primary treatment goal in PV to prevent thrombotic events and alleviate burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus.

(Press release, Takeda, AUG 28, 2026, View Source;utm_term=&utm_content=1033477&utm_id=9b2de23c-1b8d-432e-89da-925d65f93d07&sfmc_activityid=01bf63e4-57d1-4bca-96c8-9dad86fbb8f4&utm_medium=email&utm_campaign=PressReleases_EN_Automated_Gray_700px_Email1&sfmc_journey_id=9b2de23c-1b8d-432e-89da-925d65f93d07&sfmc_journey_name=rPse_seRelsa_eNEL_naJ_uonrye2_20_4rPdo&sfmc_activity_id=01bf63e4-57d1-4bca-96c8-9dad86fbb8f4&sfmc_activity_name=rPseRsleaees_sNEA_tumotadeG_ar_y07p0_xmEia1l&sfmc_asset_id=1033477&sfmc_channel=email [SID1234670416])

On August 28, 2026 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, reported the peer-reviewed publication of mature Phase 1b results from the fully enrolled C-800-01 cohort evaluating botensilimab (BOT), a multifunctional Fc-enhanced anti–CTLA-4 antibody, plus balstilimab (BAL), an anti–PD-1 antibody, in 123 heavily pre-treated patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases.

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The manuscript, titled "Extended Follow-Up of Botensilimab Plus Balstilimab in an Expanded Cohort of Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases," was published in Clinical Cancer Research. The publication builds on three-year efficacy data presented at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2026 and provides additional biomarker analyses offering insight into the biology underlying BOT+BAL activity.

MSS tumors account for the vast majority of mCRC cases and have historically derived little or no benefit from conventional checkpoint immunotherapy. In this fully enrolled cohort, patients received a median of three prior lines of therapy. BOT+BAL demonstrated a median overall survival of 21.2 months and a three-year overall survival rate of 33%. In this treatment setting, available later-line standard treatments have reported median overall survival of approximately 10-14 months in patients with refractory MSS, without active liver metastases.i

Durable clinical activity was observed in the context of limited drug exposure, with patients receiving a median of two BOT doses and six BAL doses. In exploratory analyses, responses were observed in tumors lacking the conventional markers of checkpoint sensitivity including low tumor mutational burden (TMB) and no detectable PD-L1 expression, and neither biomarker was associated with response. These findings are consistent with BOT’s Fc-enhanced design, intended role in promoting immune priming in immunologically "cold" tumors.

"These mature results are important because they show a pattern of durable activity in MSS colorectal cancer that is not limited to tumors with the conventional features associated with checkpoint sensitivity," said Benjamin L. Schlechter, M.D., of Dana-Farber Cancer Institute and lead author of the publication. "In a heavily pretreated setting where patients have few remaining options, BOT+BAL compares favorably with what is typically expected from available later-line standard therapies in terms of tolerability, depth of response and duration of response. That is a meaningful clinical difference and provides important evidence that antitumor immunity can be generated even in tumors traditionally considered immunologically cold."

"BOT was specifically engineered to add Fc-mediated immune engagement to CTLA-4 blockade, with the goal of priming antitumor immunity in cancers that have historically been resistant to conventional checkpoint inhibition," said Steven O’Day, M.D., Chief Medical Officer of Agenus. "This peer-reviewed publication connects the durable clinical activity observed in refractory MSS colorectal cancer with biomarker findings consistent with that biology. When considered alongside our emerging neoadjuvant data, these findings strengthen the rationale for evaluating BOT+BAL earlier in the disease course, where immune priming before surgery may offer the greatest opportunity to alter the trajectory of MSS colorectal cancer."

Mature Clinical Outcomes

The Phase 1b cohort included 123 patients with MSS mCRC without active liver metastases who had received a median of three prior lines of therapy.

Key findings reported in the publication include:

Overall survival: Median overall survival was 21.2 months, with 24-month and 36-month overall survival rates of 41% and 33%, respectively
Objective response: Confirmed objective response rate was 21%, including three complete responses and 23 partial responses
Duration of response: Median duration of response was not reached, with responses extending to at least 37.4 months
Disease control: Disease control rate was 69% at six weeks, and clinical benefit rate was 28% at 24 weeks
Treatment-free status: At last follow-up, 17% were alive and off all systemic anticancer therapy, including 13 responders
Activity Maintained in the Most Heavily Pretreated Patients

In an exploratory subgroup of 37 patients who had already exhausted available later-line therapies, patients had received a median of five prior lines of therapy. In this subgroup, BOT+BAL demonstrated a 22% confirmed objective response rate, median overall survival of 16.2 months, and a three-year overall survival rate of 30%. Median duration of response was 16.6 months, disease control rate was 70%, and clinical benefit rate at 24 weeks was 27%, indicating that clinical benefit was preserved even in the most refractory setting.

Biomarker Findings Support Fc-Enhanced Immune Priming Biology

Exploratory biomarker analyses showed that responses were observed among patients with low tumor mutational burden (TMB) and no detectable PD-L1–expression, and neither biomarker was associated with response in the evaluable population. These findings suggest that activity was not confined to tumors with conventional markers of checkpoint sensitivity.

These observations are consistent with BOT’s Fc-enhanced design, which is intended to engage activating Fc-gamma receptors on antigen-presenting and other myeloid cells, promote T-cell priming, reduce intratumoral regulatory T cells, and reshape the immunosuppressive tumor microenvironment rather than relying solely on pre-existing tumor immunogenicity.

Extended Safety Follow-Up Supports Optimized Dosing

No new safety signals were observed with extended follow-up, and there were no treatment-related deaths. Immune-mediated diarrhea/colitis, the most common immune-mediated adverse event, resolved in 98% of affected patients, with a median time to resolution of 14 days.

Efficacy was consistent across the two BOT dose levels evaluated, with a 21% objective response rate at both 1 mg/kg and 2 mg/kg. Lower rates of immune-mediated adverse events were observed with BOT 1 mg/kg plus BAL compared with the higher BOT dose.

From Durable Metastatic Activity to Curative Intent Neoadjuvant Setting

The publication follows the recent peer-reviewed report of updated NEST Phase 2 data evaluating neoadjuvant BOT+BAL in resectable colon cancer. The NEST results provide direct clinical evidence in the neoadjuvant setting, while the C-800-01 manuscript adds metastatic durability and biomarker evidence consistent with Fc-enhanced immune priming. This body of evidence supports continued evaluation of BOT+BAL in neoadjuvant, curative-intent MSS colon cancer, including Agenus’ planned Phase 3 ROBBIN trial.

About the C-800-01 Study

C-800-01 (NCT03860272) is a first-in-human Phase 1b clinical trial evaluating botensilimab with or without balstilimab in patients with advanced solid tumors. The MSS mCRC without active liver metastases cohort enrolled 123 patients who received BOT 1 mg/kg or 2 mg/kg every six weeks plus BAL 3 mg/kg every two weeks. The primary endpoint was safety and tolerability. Secondary efficacy endpoints included objective response rate, duration of response, disease control rate and progression-free survival; overall survival was an exploratory endpoint.

(Press release, Agenus, AUG 28, 2026, View Source [SID1234670415])