On June 12, 2025 Incyte (Nasdaq:INCY) reported that primary results from the Phase 3 POD1UM-303/InterAACT 2 trial of retifanlimab (Zynyz), a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), in combination with carboplatin and paclitaxel (platinum-based chemotherapy) in adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal cancer (SCAC) who have not been previously treated with systemic chemotherapy, were published in The Lancet (Press release, Incyte, JUN 12, 2025, View Source [SID1234653866]).

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"The publication of the POD1UM-303/InterAACT 2 trial in The Lancet is a testament to the strength of the data generated for retifanlimab in patients with inoperable locally recurrent or metastatic SCAC, a disease which until recently had seen limited innovation for decades," said Steven Stein, M.D., Chief Medical Officer, Incyte. "SCAC can be a devastating disease, and patients often have a poor prognosis. These data supported the U.S. Food and Drug Administration (FDA) approval of Zynyz (retifanlimab-dlwr) in May 2025, providing U.S. patients the first and only first-line treatment for inoperable locally recurrent or metastatic SCAC."

The POD1UM-303/InterAACT2 trial results, which were also featured at a Presidential Symposium on Practice-Changing Trials at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in 2024, showed that the study met its primary endpoint by demonstrating a statistically significant improvement in progression-free survival (PFS) in patients with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy, as assessed by blinded independent central review (BICR) using RECIST v1.1.2 Adding retifanlimab to carboplatin and paclitaxel resulted in a clinically meaningful 37% reduction in the risk of progression or death (Hazard Ratio [HR]: 0.63; 95% Confidence Interval [CI] (0.47, 0.84); P=0.0006).2 Patients in the retifanlimab and chemotherapy combination group achieved a median PFS of 9.3 months compared to 7.4 months for patients in the placebo combination group.2

New data published today in The Lancet show that in patients treated with retifanlimab plus chemotherapy:1

A consistent benefit in PFS in favor of retifanlimab plus chemotherapy was observed for all pre-defined subgroups with sufficient patients for comparison.
A clinically meaningful 6-month difference in overall survival (OS) was observed at the interim analysis (29.2 months in the retifanlimab plus carboplatin and paclitaxel group vs 23.0 months in the placebo plus carboplatin and paclitaxel group). Interim OS results were not statistically significant, and patients continue to be followed for the final key secondary OS analysis.
The overall response rate (ORR) to treatment was improved by the addition of retifanlimab to the chemotherapy (55.8% in the retifanlimab plus carboplatin and paclitaxel group vs 44.2% in the placebo plus carboplatin and paclitaxel group) and the median duration of response was approximately doubled (14 months in the retifanlimab plus carboplatin and paclitaxel group vs 7.2 months in the placebo plus carboplatin and paclitaxel group) when compared to placebo.
As reported in The Lancet, no new safety signals were observed in POD1UM-303/InterAACT2, and safety was consistent with chemotherapy plus checkpoint inhibitor regimens. Serious and Grade 3 or worse adverse events were more frequent in the retifanlimab plus carboplatin and paclitaxel group compared with placebo plus carboplatin and paclitaxel group (47.4% vs 38.8% and 83.1% vs 75.0%, respectively). The most common Grade ≥3 adverse events were neutropenia (35.1% for retifanlimab plus carboplatin and paclitaxel vs 29.6% for placebo plus carboplatin and paclitaxel) and anemia (19.5% vs 20.4%). Despite the higher rate of serious, Grade 3 or worse, and fatal adverse events with retifanlimab plus carboplatin and paclitaxel than placebo plus carboplatin–paclitaxel, these toxicities were manageable with standard measures and carboplatin and paclitaxel delivery was not compromised.

The publication, entitled "Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial," can be found online here.

"The incidence of SCAC is increasing by approximately 3% annually, driven mainly by endemic human papillomavirus (HPV infection). With no approved treatments available for advanced cases until recently, it is crucial to develop effective therapies for this orphan disease," said Sheela Rao, M.D., Consultant Medical Oncologist, The Royal Marsden National Health Service Foundation Trust.

In May 2025, the FDA approved Zynyz (retifanlimab-dlwr) in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic SCAC. In addition, the FDA granted approval for Zynyz as a single agent for the treatment of adult patients with locally recurrent or with metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. Incyte has also submitted a Type II variation Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for retifanlimab in advanced SCAC and in March 2025 submitted and received acceptance of a Japanese New Drug Application (J-NDA) by the Pharmaceuticals and Medical Devices Agency (PMDA) for retifanlimab in advanced SCAC.

About Squamous Cell Carcinoma of the Anal Canal (SCAC)

SCAC is the most common type of anal cancer, making up 85% of cases.3 It is a rare disease for which the incidence is increasing approximately 3% per year.4 About 90% of cases are associated with human papillomavirus (HPV) infection—the number one risk factor for anal cancer.5 HIV is an important amplifier of anal cancer, as people with HIV are 25 to 35 times more likely to develop it.6,7 Anal cancer shares many of the same symptoms as non-cancerous conditions, such as hemorrhoids—including pain, itching, a lump or mass and changes in bowel movements—and as a result can go undetected leading to the majority of patients presenting with locally advanced disease.8,9 More information about SCAC is available by visiting www.analcancer.com.

About POD1UM

The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-303, POD1UM-202 and several other Phase 1, 2 and 3 studies for patients with solid tumors, including a registration-directed trial evaluating retifanlimab in combination with platinum-based chemotherapy for patients with non-small cell lung cancer.

About POD1UM-303/InterAACT 2

POD1UM-303/InterAACT 2 (NCT04472429) is a Phase 3, randomized, multicenter, double-blind, placebo-controlled study evaluating retifanlimab or placebo in combination with platinum-based chemotherapy (carboplatin and paclitaxel) in adult patients with inoperable locally recurrent or metastatic SCAC who have not been previously treated with systemic chemotherapy.

During the blinded portion of the study, patients, including those with well-controlled HIV infection, were randomized 1:1 to receive retifanlimab 500 mg intravenously or placebo during each 28-day cycle for up to 6 months in combination with standard therapy of carboplatin and paclitaxel, followed by retifanlimab or placebo monotherapy for up to 1-year total treatment in the absence of disease progression or unacceptable toxicity. Crossover to retifanlimab monotherapy was allowed for patients assigned to placebo upon verification of progression by blinded independent central review (BICR).

The primary endpoint was progression-free survival (PFS) as determined by BICR using RECIST v1.1. The key secondary endpoint was overall survival (OS). Other secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR) by BICR, safety and pharmacokinetics.

For more information about the study, please visit View Source

About Zynyz (retifanlimab-dlwr)

Zynyz (retifanlimab-dlwr) is a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), indicated in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) and as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression or intolerance to platinum-based chemotherapy in the U.S.

Zynyz is also indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) in the U.S. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Zynyz is marketed by Incyte in the United States. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab.

Zynyz is a registered trademark of Incyte.

Important Safety Information

What is the most important information I should know about Zynyz?

Zynyz is a medicine that may treat certain types of cancers by working with your immune system. Zynyz can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your doctor right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, chest pain

Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus; severe stomach-area (abdomen) pain or tenderness

Liver problems: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); dark urine (tea colored); bleeding or bruising more easily than normal

Hormone gland problems: headaches that will not go away or unusual headaches; eye sensitivity to light; eye problems; rapid heartbeat; increased sweating; extreme tiredness; weight gain or weight loss; feeling more hungry or thirsty than usual; urinating more often than usual; hair loss; feeling cold; constipation; your voice gets deeper; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, loss of appetite

Skin problems: rash; itching; skin blistering or peeling; painful sores or ulcers in your mouth or nose, throat, or genital area; fever or flu-like symptoms; swollen lymph nodes

Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Zynyz. Call or see your doctor right away for any new or worsening signs or symptoms, which may include:

chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
persistent or severe muscle pain or weakness, muscle cramps
low red blood cells, bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain.

Rejection of a transplanted organ or tissue. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ or tissue transplant that you have had.

Complications, including graft-versus-host disease, in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Zynyz. Your doctor will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your doctor will check you for these problems during your treatment. Your doctor may treat you with corticosteroid or hormone replacement medicines and may also need to delay or completely stop treatment if you have severe side effects.

Before you receive Zynyz, tell your doctor about all of your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant or tissue transplant, including corneal transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Zynyz can harm your unborn baby
Females who are able to become pregnant:

Your doctor should do a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for 4 months after your last dose. Talk to your doctor about birth control methods that you can use during this time.
Tell your doctor right away if you become pregnant or think you may be pregnant during treatment.
are breastfeeding or plan to breastfeed. It is not known if Zynyz passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Zynyz when given with the chemotherapy medicines carboplatin and paclitaxel in people with SCAC include tiredness, numbness, pain, tingling, or burning in your hands or feet; nausea; hair loss; diarrhea; muscle and bone pain; constipation; bleeding; rash; vomiting; decreased appetite; itching; stomach-area pain.

The most common side effects of Zynyz when used alone in people with SCAC include tiredness, muscle and bone pain, diarrhea, infection, rectal or genital-area pain, bleeding, urinary tract infection (UTI), rash, nausea, loss of appetite, constipation, stomach-area pain, shortness of breath, fever, vomiting, cough, itching, low levels of thyroid hormone, headache, decreased weight.

The most common side effects of Zynyz when used alone in people with MCC include tiredness, muscle and bone pain, itching, diarrhea, rash, fever, nausea.

These are not all the possible side effects of Zynyz. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Incyte Corporation at 1-855-463-3463.

General information about the safe and effective use of Zynyz

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about Zynyz, talk with your doctor. You can ask your doctor for information about Zynyz that is written for health professionals.

Please see the full Prescribing Information, including the Medication Guide, for Zynyz.

You may also report side effects to the FDA View Source or to Incyte Corporation at 1-855-463-3463.

On June 12, 2025 Silence Therapeutics plc ("Silence" or the "Company") (Nasdaq: SLN), a global clinical-stage company developing novel siRNA (short interfering RNA) therapies, reported additional data showcasing the SANRECO Phase 1 study of divesiran in patients with polycythemia vera (PV) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Annual Meeting in Milan, Italy (Press release, Silence Therapeutics, JUN 12, 2025, View Source [SID1234653867]).

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"The latest data presented at EHA (Free EHA Whitepaper) today continue to demonstrate divesiran’s potential to maintain rapid and durable control of hematocrit and essentially eliminate the need for phlebotomies in phlebotomy-dependent PV patients," said Marina Kremyanskaya, MD, PhD, Associate Professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai. "These early findings also suggest the potential for infrequent dosing and continue to support a favorable safety profile. I’m very encouraged by the consistency of the Phase 1 dataset and look forward to further development."

"Divesiran continues to demonstrate a very compelling profile as the first-in-class siRNA for PV," said Craig Tooman, President and Chief Executive Officer at Silence Therapeutics. "We are extremely encouraged by the support we are garnering from the physician community and that’s reflected in the positive momentum we’re seeing in the SANRECO Phase 2 study. The Phase 2 study is over 50-percent enrolled, and we remain on-track to complete patient enrollment by the end of this year."

Summary of Updated SANRECO Phase 1 Study Results

Results included 21 phlebotomy-dependent PV patients with a combined history of 79 phlebotomies prior to dosing. Therapeutic phlebotomies were essentially eliminated and mean hematocrit (HCT) levels were lowered and maintained to ≤ 45% for all cohorts regardless of baseline levels.
Divesiran increased hepcidin and ferritin, resulting in elevation of iron body content and improved iron deficiency.
Divesiran demonstrated similar results in all patient groups, independent of baseline risk or prior and concurrent therapy.
White blood cells were not altered over the time-course of the study.
Platelets increased, reaching a plateau with no dose dependent effect.
Divesiran was well tolerated with no dose-limiting toxicities.
SANRECO Phase 1 Study Design
The Phase 1 portion of SANRECO was a 34-week, open-label study evaluating divesiran (3 mg/kg, 6 mg/kg and 9 mg/kg) administered subcutaneously every 6 weeks for four doses, with a 16-week follow-up period following the date of the last administered dose in 21 PV patients. Key inclusion criteria included a PV diagnosis and a history of requiring at least three phlebotomies in the last six months or five in the last year prior to screening. Patients were allowed to be on stable doses of cytoreductive agents. Given the exploratory nature of this Phase 1 study, both well-controlled patients – defined as those with HCT levels at 45% or less – as well as those with HCT levels greater than 45% at baseline on current standard of care treatment were enrolled.

SANRECO Phase 2 Study Design
The Phase 2 portion of SANRECO is now enrolling PV patients and is a randomized, double-blind study evaluating two different divesiran regimens versus placebo. Key inclusion criteria include a PV diagnosis and a history of requiring at least three phlebotomies in the last seven months or five in the last year prior to dosing. Patients are allowed to be on stable doses of cytoreductive agents. Patients must have HCT levels less than 45% prior to dosing. For more information, please click here.

About PV
PV is a rare, myeloproliferative neoplasm – a type of blood cancer – characterized by the excessive production of red blood cells, often resulting in elevated hematocrit levels. Elevated hematocrit above 45-percent is associated with a four-times higher rate of death from cardiovascular or thrombotic events. PV is associated with a range of burdensome symptoms including fatigue, cognitive disturbance and pruritus and additionally, longer term can transform to myelofibrosis and Acute Myeloid Leukemia. The aim of treatment is to maintain hematocrit less than 45%, a level that is associated with a reduced incidence of thrombosis and CV-associated death. The current standard of care includes repeated phlebotomies to reduce hematocrit and/or cytoreductive agents to reduce red blood cell production. There are currently no approved therapies that specifically target red blood cells and hematocrit.

About Divesiran
Divesiran is Silence’s wholly owned siRNA product candidate developed from its proprietary mRNAi GOLD platform that "silences" TMPRSS6 expressed almost exclusively in the liver. TMPRSS6 is a negative regulator of hepcidin, the body’s master regulator of iron metabolism including its absorption, distribution, and storage. By silencing TMPRSS6 in PV patients, divesiran aims to increase hepcidin production and release by liver hepatocytes, leading to the restriction of iron to the bone marrow and, thus, reducing the excessive production of red blood cells, a process dependent on availability of iron. Divesiran is currently in Phase 2 development for PV and has FDA Fast Track and Orphan Drug designations for PV.

On June 12, 2025 AIM ImmunoTech Inc. (NYSE American: AIM) (OTC Pink: AIMID) ("AIM" or the "Company") reported the United States Patent and Trademark Office has granted U.S. patent No. 12312376, titled "Therapeutic Double Stranded RNA and Methods for Producing the Same (Press release, AIM ImmunoTech, JUN 12, 2025, https://aimimmuno.com/aim-immunotech-granted-u-s-patent-covering-methods-of-manufacturing-therapeutic-dsrna-including-ampligen/ [SID1234653836])." The patent expires January 25, 2041.

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The new patent covers methods involving the manufacture of a range of therapeutic double-stranded RNA (dsRNA) products, of which Ampligen is included. Combined with AIM’s multiple compositions and methods patents involving Ampligen, this manufacturing patent, along with AIM’s other issued patents, further secures the Company’s control over the synthesis and use of the first-in-class drug, and provides patent protection for manufacturing until 2041.

The new patent significantly extends the potential development runway for the drug, securing AIM additional time to safely and confidently develop its drug program as it seeks U.S. Food and Drug Administration ("FDA") approval for Ampligen in any of a series of indications. Ampligen has demonstrated broad spectrum activity in clinical trials for globally important cancers, viral diseases and disorders of the immune system.

AIM’s overall intellectual property portfolio covers the manufacture and use of Ampligen. AIM’s patents include Ampligen in the treatment of cancer (U.S. patent 11,813,279, expires August 9, 2039), the Post-COVID condition of fatigue (Netherlands’ patent 2032813, expires August 21, 2042) and endometriosis (U.S. patent 12,102,649, expires October 22, 2040).

AIM CEO Thomas K. Equels commented, "This patent is a significant milestone for AIM as it represents the final step in a multi-year project to strengthen and secure our global patent portfolio surrounding Ampligen. AIM now has extended patent protection for the manufacture of Ampligen, the composition of Ampligen and the way in which Ampligen can be utilized as a therapeutic for a diverse collection of unmet medical needs, from deadly cancers to Post-COVID conditions to endometriosis."

Significantly, AIM’s intellectual property protection for Ampligen also includes multiple Orphan Drug Designations ("ODD") from the FDA and the European Medicines Agency ("EMA"). FDA designation grants seven years of market exclusivity after commercial approval and EMA designation grants 10 years of market exclusivity after such approval. AIM’s orphan drug designations include Metastatic Melanoma (US), Renal Cell Carcinoma (US), Pancreatic Adenocarcinoma (US and EU), Ebola Virus Disease (US and EU), Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (US) and HIV (US).

On June 12, 2025 Debiopharm (www.debiopharm.com), a privately-owned Swiss biopharmaceutical company committed to establishing tomorrow’s standard of care to cure cancer and infectious diseases and Alkyon Therapeutics, Inc., a biotechnology company pioneering precision-targeted therapies, reported the signing of a co-research agreement to evaluate the feasibility of developing targeted radioligand therapies (RLTs) using Debiopharm’s proprietary AbYlink conjugation technology for Alkyon’s modular antibody platform directed against undisclosed tumor-associated antigens (Press release, Debiopharm, JUN 12, 2025, View Source [SID1234653868]).

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This collaboration marks a promising step toward a new generation of RLTs designed to deliver potent radiation targeted directly to cancer cells while minimizing damage to healthy tissues. By leveraging the unique strengths of both platforms, the goal is to create more effective, better-tolerated cancer treatments that improve patient quality of life and expand therapeutic options for difficult-to-treat tumors. AbYLink technology enables regio-selective lysine conjugation, ensuring the radioligand avoids the target binding site and facilitating streamlined, consistent manufacturing.

"We’re intrigued to explore the potential of applying AbYlink conjugation technology to the radio-oncology field," expressed Frederic Levy, Chief Scientific Officer, Debiopharm. "Leveraging our innovative conjugation platform with Alkyon’s engineered antibody scaffolds could open new possibilities for next-generation radiopharmaceuticals with enhanced precision and therapeutic impact."

"This collaboration reflects our shared commitment to expanding the potential of radioligand therapies," said Benjamin Titz, Co-Founder and CEO of Alkyon Therapeutics. "By applying AbYlink to our specialized antibody scaffolds and targeting strategies tailored to the unique architecture of solid tumors, we aim to unlock new therapeutic possibilities and advance care for patients with difficult-to-treat solid tumors."

About AbYlink

AbYlink is a versatile and rapid regio-selective chemical conjugation technology for use in preparing diagnostic or therapeutic conjugates. This one-step method results in stable conjugation at defined and invariable sites on the Fc domain of an antibody or the like, with no impact on antigen-binding regions. It enables a seamless and reproducible conjugation of payloads (e.g., a chelator for radiolabeling, a fluorescent dye or a drug) to antibodies or ADCs. The universal applicability of the technology has been demonstrated for various antibody isotypes and payloads.

On June 12, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (TSX: APS; OTC: APTOF), a clinical-stage precision oncology company, reported data from its Phase 1/2 TUSCANY trial in newly diagnosed AML patients treated with tuspetinib (TUS) in combination with standard of care dosing venetoclax and azacitidine (TUS+VEN+AZA triplet) in an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA 2025), being held June 12-15, 2025, in Milan, Italy (Press release, Aptose Biosciences, JUN 12, 2025, View Source [SID1234653837]).

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The TUS+VEN+AZA triplet is being developed as a mutation agnostic frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. Dr. Gabriel Mannis, Associate Professor of Medicine, Stanford University School of Medicine, and an investigator in the TUSCANY study, reported safety and efficacy data from the first two dose cohorts at 40 mg of TUS or 80 mg of TUS in the TUS+VEN+AZA triplet. Dr. Mannis also noted three patients were rapidly enrolled on the third dose cohort of 120 mg TUS in the TUS+VEN+AZA triplet, and that no DLTs have been observed to date.

The oral presentation at EHA (Free EHA Whitepaper) included updated safety, complete remission, minimal residual disease (MRD) assessments, and longer duration of follow-up:
Title: TUSCANY Study of Safety and Efficacy of Tuspetinib Plus Standard of Care Venetoclax and Azacitidine in Study Participants with Newly Diagnosed AML Ineligible for Induction Chemotherapy
Presenter: Dr. Gabriel Mannis, Associate Professor of Medicine, Stanford University School of Medicine
Abstract #: S139

Key findings:

To date, ten newly diagnosed AML patients have received the TUS+VEN+AZA combination:
Four received the 40 mg dose of TUS, three received the 80 mg dose of TUS, and three received the 120 mg dose of TUS
At the initial dose of 40 mg TUS (n=4), with patients on longest duration of drug:
Three subjects achieved CRs and were MRD-negative, including
Patient with FLT3-ITD
Patient with FLT3-WT
Patient with TP53/CK
At the 80 mg TUS dose level (n=3):
All three patients (100%) already achieved composite complete remissions (CR and CRi)
A TP53-mutated/CK AML patient achieved an early CRi
Too early in treatment for final MRD assessment
At the 120 mg TUS dose level (n=3):
All three patients at the 120 mg TUS dose level remain on therapy
Too early in treatment for formal response and MRD assessments
Regardless of mutation status, TUS is active in newly diagnosed AML patients
MRD-negative responses achieved across diverse genetic populations, including adverseTP53 mutations and CK
Responses continue to evolve, and the triplet continues to be well tolerated with no DLTs
TUS can be administered safely with standard-of-care dosing of VEN/AZA
TUS PK properties not altered by VEN, AZA, antifungals or food
No prolonged myelosuppression in Cycle 1 in the absence of AML
No treatment-related deaths; all 10 subjects treated to date remain alive
No treatment related QTc prolongation, CPK elevations, differentiation syndrome or non-hematologic SAEs
"The TUSCANY triplet trial is well under way, and we are observing exciting activity with the addition of TUS to the VEN+AZA standard treatment," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. "The data presented today reveal complete responses across patients with diverse mutations, including TP53-mutated/CK AML and FLT3-wildtype AML patients. TUS appears to have tremendous opportunity in the largest markets and the most challenging of AML cases."

Abstracts are available on the EHA (Free EHA Whitepaper)2025 website here. The presentation is available on the Aptose website here.

TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study

The tuspetinib-based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 clinical study with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Indeed, responses were also in R/R AML patients with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes.

The TUSCANY Phase 1/2 study, being conducted at 10 leading U.S. clinical sites by elite clinical investigators, is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS, is being administered in 28-day cycles. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available.