On December 10, 2024 Daiichi Sankyo’s (TSE: 4568) reported the first patient has been dosed in the QuANTUM-Wild phase 3 trial evaluating VANFLYTA (quizartinib) in combination with standard intensive induction and consolidation chemotherapy followed by single-agent maintenance in adults with newly diagnosed FLT3-ITD negative acute myeloid leukemia (AML) (Press release, Daiichi Sankyo, DEC 10, 2024, View Source [SID1234649021]).

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AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%.1, 2 Targeted therapy with FLT3 inhibitors has improved survival for some patients with FLT3 gene mutations, which most commonly occur as FLT3-ITD.3 However, about 90% of patients with AML overexpress FLT3 regardless of mutational status.1, 4, 5 No FLT3 inhibitors are currently approved for patients without FLT3 mutations.

"Preliminary data have shown promising results for VANFLYTA in patients with FLT3-ITD negative acute myeloid leukemia, which includes patients without FLT3 mutations and patients with TKD mutations," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "We have initiated the QuANTUM-Wild trial to further confirm the potential role of VANFLYTA combined with standard chemotherapy and as subsequent maintenance monotherapy in this broader population of patients with AML who are in need of new treatment options to potentially reduce the risk of relapse and improve overall survival."

The QuANTUM-Wild trial was initiated based on results of the QUIWI phase 2 trial evaluating VANFLYTA in combination with standard intensive chemotherapy and as subsequent maintenance monotherapy in adult patients with newly diagnosed FLT3-ITD negative AML. The final results of QUIWI were presented at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.6

About the QuANTUM-Wild Trial
QuANTUM-Wild is a randomized, double-blind, placebo-controlled global phase 3 trial evaluating the efficacy and safety of VANFLYTA in combination with standard intensive induction and consolidation therapy, including allogenic hematopoietic stem cell transplant (HSCT), followed by maintenance monotherapy, in adult patients aged 18 to 70 with newly diagnosed FLT3-ITD negative AML. Patients will be randomized 2:2:1 into three treatment arms. In Arms A and B, patients will receive VANFLYTA or placebo, respectively, in combination with cytarabine and anthracycline induction and cytarabine consolidation chemotherapy, followed by up to three years of single-agent maintenance therapy. The primary endpoint for Arms A and B is overall survival. Secondary endpoints include event-free survival, duration of complete response, relapse-free survival, complete remission rate (CR), CR with minimal or measurable residual disease negativity, pharmacokinetic assessments and safety measures including treatment emergent adverse events.

For purposes of exploratory analyses in the maintenance setting, patients in a third study arm (Arm C), will receive VANFLYTA in combination with intensive induction and consolidation chemotherapy followed by placebo maintenance monotherapy.

QuANTUM-Wild is expected to enroll approximately 700 patients across Asia, Australia, Europe, North America and South America. For more information, please visit ClinicalTrials.gov.

About Acute Myeloid Leukemia
One of the most common forms of leukemia in adults, AML is an aggressive blood cancer with a five-year overall survival rate of approximately 32%.1, 2, 3 Approximately 144,000 new cases of AML were diagnosed globally with more than 130,000 deaths reported in 2021.7

Targeted therapy with FLT3 inhibitors has improved survival for some patients with FLT3 gene mutations, which most commonly occur as FLT3-ITD.3 However, about 90% of all patients with AML overexpress FLT3 regardless of activating mutations.1, 4, 5 No FLT3 inhibitors are currently approved for patients without FLT3 mutations.

FLT3 is a receptor tyrosine kinase protein that plays an important role in blood cell development but, when constitutively activated, FLT3 can contribute to AML development and growth.8

About VANFLYTA
VANFLYTA is an oral, highly potent and selective type II FLT3 inhibitor approved in more than 30 countries in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as maintenance monotherapy following consolidation, for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive based on the results from the QuANTUM-First trial. In the U.S., VANFLYTA is not indicated as maintenance monotherapy following allogeneic HSCT; improvement in overall survival with VANFLYTA in this setting has not been demonstrated.

VANFLYTA also is approved in Japan for the treatment of patients with relapsed/refractory AML that is FLT3-ITD mutation positive, as detected by an approved test, based on results from the QuANTUM-R trial.

About the VANFLYTA Clinical Development Program
The VANFLYTA clinical development program includes the QuANTUM-Wild phase 3 trial in adult patients with newly diagnosed FLT3-ITD negative AML, a phase 1/2 trial in pediatric and young adult patients with relapsed/refractory FLT3-ITD positive AML in Europe, Asia and North America and several phase 1/2 combination studies as part of a strategic collaboration with The University of Texas MD Anderson Cancer Center.

VANFLYTA U.S. Important Safety Information

WARNING: QT PROLONGATION, TORSADES DE POINTES, and CARDIAC ARREST

VANFLYTA (quizartinib) prolongs the QT interval in a dose- and concentration-related manner. Prior to VANFLYTA administration and periodically, monitor for hypokalemia or hypomagnesemia, and correct deficiencies. Perform electrocardiograms (ECGs) to monitor the QTc at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter.
Torsades de pointes and cardiac arrest have occurred in patients receiving VANFLYTA. Do not administer VANFLYTA to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome.
Do not initiate treatment with VANFLYTA or escalate the VANFLYTA dose if the QT interval corrected by Fridericia’s formula (QTcF) is greater than 450 ms.
Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required.
Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure.
Because of the risk of QT prolongation, VANFLYTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VANFLYTA REMS.
Indication
VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive as detected by an FDA-approved test.

Limitations of Use
VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.

Contraindications
VANFLYTA is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes.

Warnings and Precautions
QT Prolongation, Torsades de Pointes, and Cardiac Arrest (See BOXED WARNING)
VANFLYTA prolongs the QT interval in a dose- and concentration-dependent manner. The mechanism of QTc interval prolongation is via inhibition of the slow delayed rectifier potassium current, IKs, as compared to all other medications that prolong the QTc interval, which is via the rapid delayed rectifier potassium current, IKr.

Therefore, the level of QTc prolongation with VANFLYTA that predicts the risk of cardiac arrhythmias is unclear. Inhibition of IKs and IKr may leave patients with limited reserve, leading to a higher risk of QT prolongation and serious cardiac arrhythmias, including fatal outcomes. Torsades de pointes, ventricular fibrillation, cardiac arrest, and sudden death have occurred in patients treated with VANFLYTA.

Of the 1,081 patients with AML treated with VANFLYTA in clinical trials, torsades de pointes occurred in approximately 0.2% of patients, cardiac arrest occurred in 0.6% of patients, including 0.4% with a fatal outcome, and 0.1% of patients experienced ventricular fibrillation. These severe cardiac arrhythmias occurred predominantly during the induction phase.

Of the 265 patients with newly diagnosed FLT3-ITD–positive AML treated with VANFLYTA in combination with chemotherapy in the clinical trial, 2.3% were found to have a QTcF greater than 500 ms and 10% of patients had an increase from baseline QTcF greater than 60 ms. The clinical trial excluded patients with a QTcF ≥450 ms or other factors that increased the risk of QT prolongation or arrhythmic events (eg, NYHA Class III or IV congestive heart failure, hypokalemia, family history of long QT interval syndrome).

Therefore, avoid use in patients who are at significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism.

Do not initiate treatment with VANFLYTA if the QTcF interval is greater than 450 ms. Do not use VANFLYTA in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes. Perform an ECG and correct electrolyte abnormalities prior to initiation of treatment with VANFLYTA.

During induction and consolidation, perform an ECG prior to initiation and then once weekly during VANFLYTA treatment or more frequently as clinically indicated. During maintenance, perform ECGs prior to initiation, once weekly for at least the first month following dose initiation and escalation, and as clinically indicated thereafter.

Do not escalate the dose if QTcF is greater than 450 ms. Perform ECG monitoring of the QT interval more frequently in patients who are at significant risk of developing QT interval prolongation and torsades de pointes, or following dose escalation.

Monitor and correct hypokalemia and hypomagnesemia prior to and during treatment with VANFLYTA. Maintain electrolytes in the normal range. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea or vomiting. Monitor patients more frequently with ECGs if coadministration of VANFLYTA with drugs known to prolong the QT interval is required.

Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure. Reduce VANFLYTA if QTc increases to greater than 480 ms and less than 500 ms. Interrupt and reduce VANFLYTA if QTc increases to greater than 500 ms. Permanently discontinue VANFLYTA in patients who develop recurrent QTc greater than 500 ms or QTc interval prolongation with signs or symptoms of life-threatening arrhythmia. VANFLYTA is available only through a restricted program under a REMS.

VANFLYTA REMS
VANFLYTA is available only through a restricted distribution program under a REMS called the VANFLYTA REMS because of the serious risk of QT prolongation, torsades de pointes, and cardiac arrest.

Notable requirements of the VANFLYTA REMS include the following:

Prescribers must be certified in the VANFLYTA REMS by enrolling and completing training.
Prescribers must counsel patients receiving VANFLYTA about the risk of QT prolongation, torsades de pointes, and cardiac arrest, and provide patients with a Patient Wallet Card.
Pharmacies that dispense VANFLYTA must be certified with the VANFLYTA REMS and must verify prescribers are certified through the VANFLYTA REMS.
Further information about the VANFLYTA REMS is available at www.VANFLYTAREMS.com or by telephone at 1-855-212-6670.

Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose.

Adverse Reactions
The safety of VANFLYTA (35.4 mg orally once daily with chemotherapy, 26.5 mg to 53 mg orally once daily as maintenance) in adult patients with newly diagnosed FLT3-ITD positive AML is based on QuANTUM-First.

Serious adverse reactions in ≥5% of patients who received VANFLYTA plus chemotherapy were: febrile neutropenia (11%). Fatal adverse reactions occurred in 10% of patients who received VANFLYTA plus chemotherapy, including sepsis (5%), fungal infections (0.8%), brain edema (0.8%), and one case each of febrile neutropenia, pneumonia, cerebral infarction, acute respiratory distress syndrome, pulmonary embolism, ventricular dysfunction, and cardiac arrest.

Permanent discontinuation due to an adverse reaction in patients in the VANFLYTA plus chemotherapy arm occurred in 20% of patients. The most frequent (≥2%) adverse reaction which resulted in permanent discontinuation in the VANFLYTA arm was sepsis (5%).

Dosage interruptions of VANFLYTA due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥2% of patients in the VANFLYTA arm included neutropenia (11%), thrombocytopenia (5%), and myelosuppression (3%).

Dose reductions of VANFLYTA due to an adverse reaction occurred in 19% of patients. Adverse reactions which required dosage reductions in ≥2% of patients in the VANFLYTA arm were neutropenia (9%), thrombocytopenia (5%), and electrocardiogram QT prolonged (4%).

The most common adverse reactions (≥10% with a difference between arms of ≥2% compared to placebo), including laboratory abnormalities, were decreased lymphocytes, decreased potassium, decreased albumin, decreased phosphorus, increased alkaline phosphatase, decreased magnesium, febrile neutropenia, diarrhea, mucositis, nausea, decreased calcium, abdominal pain, sepsis, neutropenia, headache, increased creatine phosphokinase, vomiting, upper respiratory tract infections, hypertransaminasemia, thrombocytopenia, decreased appetite, fungal infections, epistaxis, increased potassium, herpesvirus infections, insomnia, QT prolongation, increased magnesium, increased sodium, dyspepsia, anemia, and eye irritation.

Drug Interactions
Strong CYP3A Inhibitors
VANFLYTA is a CYP3A substrate. Concomitant use of VANFLYTA with a strong CYP3A inhibitor increases quizartinib systemic exposure, which may increase the risk of VANFLYTA adverse reactions. Reduce the dosage of VANFLYTA.

Strong or Moderate CYP3A Inducers
Concomitant use of VANFLYTA with strong or moderate CYP3A inducers decreases quizartinib systemic exposure, which may reduce VANFLYTA efficacy. Avoid concomitant use of VANFLYTA with strong or moderate CYP3A inducers.

QT Interval–Prolonging Drugs
VANFLYTA prolongs the QT/QTc interval. Coadministration of VANFLYTA with other drugs that prolong the QT interval may further increase the incidence of QT prolongation. Monitor patients more frequently with ECG if coadministration of VANFLYTA with drugs known to prolong the QT interval is required.

Use in Specific Populations
Pregnancy
VANFLYTA can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus.

Lactation
Advise women not to breastfeed during treatment with VANFLYTA and for one month after the last dose.

Females and Males of Reproductive Potential
Pregnancy Testing
Verify pregnancy status in females of reproductive potential within 7 days before starting treatment with VANFLYTA.

Contraception
Females
Advise female patients of reproductive potential to use effective contraception during treatment with VANFLYTA and for 7 months after the last dose.
Males
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VANFLYTA and for 4 months after the last dose.

Infertility
Females
Based on findings from animal studies, VANFLYTA may impair female fertility. These effects on fertility were reversible.
Males
Based on findings from animal studies, VANFLYTA may impair male fertility. These effects on fertility were reversible.

Pediatric Use
Safety and effectiveness of VANFLYTA have not been established in pediatric patients.

Geriatric Use
No overall differences in safety or efficacy were observed between patients 65 years of age and older and younger adult patients.

Renal Impairment
No dosage adjustment is recommended in patients with mild to moderate renal impairment (CLcr 30 to 89 mL/min). VANFLYTA has not been studied in patients with severe renal impairment (CLcr <30 mL/min).

Hepatic Impairment
No dosage adjustment is recommended in patients with mild hepatic impairment or moderate hepatic impairment. VANFLYTA has not been studied in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc, at 1-877-437-7763 or the FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see Full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

On December 10, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported positive initial data from CRDF-004, a randomized, Phase 2 clinical trial evaluating onvansertib in combination with standard-of-care (SoC) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, DEC 10, 2024, View Source [SID1234648975]). Efficacy and safety data are for all evaluable patients as of a November 26, 2024 data cut-off date, and all efficacy data are determined by a blinded, independent central review (BICR) of each patient’s tumor scan.

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"We are highly encouraged by the robust efficacy signal and favorable safety profile observed with onvansertib plus standard-of-care from the first 30 evaluable patients in our randomized first-line RAS-mutated mCRC CRDF-004 trial," said Fairooz Kabbinavar, MD, FACP, Chief Medical Officer of Cardiff Oncology. "Our data shows an objective response rate of 64% in patients receiving the 30 mg dose of onvansertib in combination with standard of care, significantly higher than the 33% objective response rate observed in the control arms of standard of care alone. In addition, as can be seen in the spider plots, we are observing deeper tumor response in patients receiving the 30mg dose of onvansertib compared to those receiving the 20mg dose with similar safety profiles for both doses."

Study Design

The CRDF-004 phase 2 trial is currently enrolling patients with mCRC who have a documented KRAS or NRAS mutation. Onvansertib is added to SoC consisting of FOLFIRI plus bevacizumab or FOLFOX plus bevacizumab. Patients are being randomized in a 1:1:1 ratio to either 20mg of onvansertib plus SoC, 30mg of onvansertib plus SoC, or SoC alone. The primary endpoint is objective response rate (ORR), and the secondary endpoints include progression-free survival (PFS), duration of response (DOR) and safety.

Efficacy Data

Objective Response Rates observed in the CRDF-004 clinical trial, as of the data cut-off date of November 26, 2024, are shown below.

Control Arm

(SoC alone)

20mg dose of onvansertib + SoC

30mg dose of onvansertib + SoC

All onvansertib patients

33% ORR

(3 of 9)

50% ORR

(5 of 10)

64% ORR

(7 of 11)

57% ORR

(12 of 21)

Spider Plots, displaying the change in tumor size from baseline for each patient over time, demonstrate deeper responses observed in patients receiving the 30mg dose of onvansertib in combination with the SoC compared to both the control arms and 20mg dose of onvansertib arms.

Safety and Tolerability

Onvansertib in combination with chemo/bevacizumab was well-tolerated and there have been no major or unexpected toxicities observed.

"Overall, these data support our belief that onvansertib has potential to change the treatment paradigm for the entire first-line RAS-mutated mCRC patient population of almost 50,000 new patients diagnosed in the U.S. annually," said Mark Erlander, Chief Executive Officer of Cardiff Oncology. "In addition to the efficacy signal observed, the data demonstrate that onvansertib can safely be combined with the two different chemo backbones that are currently approved as standard of care in the first-line setting, thus providing a key differentiated profile over previous generation PLK1 inhibitors. We look forward to providing additional clinical updates from our CRDF-004 trial in the first half of 2025."

Upcoming expected milestones

•
Additional clinical data from CRDF-004 trial expected in 1H 2025

Conference Call and Webcast

Cardiff Oncology will host a conference call and live webcast at 8:00 a.m. ET / 5:00 a.m. PT on December 10, 2024. Individuals interested in listening to the live conference call may do so by using the webcast link in the "Events" section of the company’s website. A webcast replay will be available in the investor relations section on the company’s website following the completion of the call.

On December 10, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, reported that it has released the latest clinical data from a global study of its novel drug candidate, olverembatinib (HQP1351), in patients with heavily pretreated chronic myeloid leukemia (CML), in a Poster Presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in San Diego, CA, the United States (Press release, Ascentage Pharma, DEC 10, 2024, View Source;1-5-year-follow-up-data-from-a-global-study-of-olverembatinib-reaffirms-potential-in-overcoming-resistanceintolerance-to-ponatinib-or-asciminib-302327550.html [SID1234649007]). Prof. Hagop Kantarjian, MD, and Prof. Elias Jabbour, MD, from the Department of Leukemia, The University of Texas MD Anderson Cancer Center, are the principal investigators of the study.

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The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, results from multiple clinical and preclinical studies on four of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at this year’s ASH (Free ASH Whitepaper) Annual Meeting. Furthermore, this is the seventh consecutive year for studies of olverembatinib to be selected for Oral Reports at the meeting.

After releasing the preliminary results from the global study of olverembatinib in an Oral Report at ASH (Free ASH Whitepaper) 2022 and the updated results from a larger patient sample at ASH (Free ASH Whitepaper) 2023, this year Ascentage Pharma presented the 1.5-year follow-up data in patients with heavily pretreated CML-CP. In the latest data, olverembatinib showed strong, durable and consistent antileukemic activity, the ability to overcome resistance/intolerance to the third-generation tyrosine kinase inhibitor (TKI) ponatinib or the allosteric STAMP inhibitor asciminib, as well as favorable tolerability in patients with heavily pretreated CML-CP.

As the first approved third-generation BCR-ABL inhibitor in China, olverembatinib has already been approved for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant CP-CML or accelerated-phase (AP-) CML harboring the T315I mutation; and adult patients with CP-CML resistant to and/or intolerant of first- and second-generation TKIs. In January 2024, olverembatinib was cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III trial in previously treated adult patients with CML-CP.

Prof. Elias Jabbour commented, "Olverembatinib is a very promising next-generation TKI, and existing data demonstrate its therapeutic ability in patients with resistant/intolerant to ≥2 TKIs CP-CML and above. The high response rate that Olverembatinib has shown in Ponatinib or Asciminib failed patients is encouraging. We continue to recruit for the global Phase III trial examining this novel therapy."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "The latest data from this global study further demonstrated olverembatinib’s therapeutic potential in patients with drug-resistant CML, including those who had failed prior treatment with ponatinib and asciminib, and once again underscored the drug candidate’s promise in addressing an unmet global clinical need in CML. At Present, a global registrational Phase III study of olverembatinib has been cleared by the US FDA and is already ongoing. We hope, in not too distant future, this innovative drug will become accessible to patients worldwide who are in desperate need of novel therapies. Fulfilling our founding mission of addressing unmet clinical needs in China and around the world, we will expedite the global clinical development of our key drug candidates such as olverembatinib to bring more safe and effective therapies to patients as soon as possible."

Highlights of the data this study reported at ASH (Free ASH Whitepaper) 2024 are as below:

Olverembatinib (HQP1351) Overcomes Resistance/Intolerance to Asciminib and Ponatinib in Patients (pts) with Heavily Pretreated Chronic-Phase Chronic Myeloid Leukemia (CP CML): A 1.5-Year Follow-up Update with Comprehensive Exposure-Response (E-R) Analyses

Format: Poster Presentation

Abstract#: 3151

Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II

Highlights:

Introduction: New treatment options are needed for patients with CP-CML resistant/intolerant to third-generation (3G) TKI ponatinib and/or asciminib, a specifically targeting the ABL myristoyl pocket (STAMP) inhibitor. Olverembatinib is a well-tolerated TKI with potential to overcome resistance. This update presents efficacy and safety data of olverembatinib in patients with heavily pretreated CP-CML.

Enrolled Patients and Study Methods:

Adults with CP-CML previously treated with ≥2 TKIs and/or a STAMP inhibitor, adequate organ function, and no major molecular response (MMR) were eligible.
As of July 28, 2024, 67 pts with CP-CML were enrolled; median (range) follow-up was 74.3 (0.1-217.1) weeks; median (range) age, 50 (21-80) years; and 38 (56.7%) patients were male.
Patients were randomly allocated to receive olverembatinib at doses of 30, 40, or 50 mg orally every other day (QOD) in 28-day cycles, with stratification based on T315I mutation status. Comprehensive E-R analyses were performed.
Efficacy Results:

No patient had efficacy at baseline. 35 of 60 (58.3%) evaluable patients achieved CCyR and 29/64 (45.3%) achieved MMR. At 12 months, the overall MMR rate was 61.4% (27/44). CCyR was achieved by 66.7% of patients with the T315I mutation vs 54.8% without it, and MMR was achieved by 50.0% vs 43.5%, respectively.
Of 28 cytogenetic response-evaluable patients with ponatinib-failed CP-CML, 15 (53.6%) achieved CCyR. The CCyR rates in patients with prior ponatinib resistance and intolerance were 52.2% (12/23) and 75.0% (3/4), respectively. In the 30 molecular response-evaluable patients who were previously treated with ponatinib, 12 (40.0%) achieved MMR, including 47.8% (11/23) of those with prior resistance and 16.7% (1/6) with intolerance. No patient above had efficacy at baseline.
In evaluable patients with asciminib treatment failure, 37.5% (6/16) achieved CCyR and 30% (6/20) achieved MMR, including a CCyR rate of 30.8% (4/13) and an MMR rate of 26.7% (4/15) in those with prior resistance, and a CCyR rate of 50.0% (1/2) and an MMR rate of 25.0% (1/4) in those with intolerance. No patient had efficacy at baseline.
Safety Results: Among 66 subjects receiving olverembatinib, a total of 62 (93.9%) reported treatment-emergent adverse events (TEAEs) of any grade, with 44 (66.7%) experiencing grade ≥ 3 TEAEs. In addition, 60 (90.9%) patients reported TRAEs of any grade. Common TRAEs (≥20%) were elevated creatine phosphokinase (37.9%), thrombocytopenia (24.2%), and increased alanine aminotransferase (22.7%).

Conclusions: Olverembatinib was well tolerated and showed strong and durable antileukemic activity in patients with heavily pretreated CP-CML. The registrational study is recruiting.

On December 10, 2024 Evariste, a TechBio using mathematics and AI to design small molecule therapeutics, reportedto have entered into a preclinical research agreement with Orion Corporation, a leading Finnish pharmaceutical company (Press release, Orion, DEC 10, 2024, View Source [SID1234649023]).

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As part of the agreement, Evariste will use its innovative discovery platform, Frobenius Discovery, to design small molecule inhibitors for a target selected by Orion. The collaboration will deploy Frobenius Discovery’s full suite of proprietary machine learning algorithms, automated compound designers, and accelerated free energy calculations to deliver potential candidate molecules.

"We are excited to work together with Evariste in utilizing cutting-edge AI-driven molecular design and mathematical algorithms to accelerate our drug discovery process," said Emilia Väisänen, Head of Medicinal Chemistry at Orion.

Anna Hercot, CEO of Evariste, commented: "We are very excited to leverage the Frobenius Discovery platform and work with an outstanding team at Orion to help accelerate the delivery of new medicines to patients."

On December 10, 2024 Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS) (the "Company"), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that it has drawn down the final tranche of €5 million ("Tranche C") under the credit facility agreement for up to €40 million entered into with the European Investment Bank (the "EIB) on December 28, 2022 (the "Finance Contract") (Press release, Cellectis, DEC 10, 2024, View Source [SID1234648976]). With the drawdown of Tranche C, the Company has drawn down the full €40 million available under the Finance Contract. Tranche C is expected to be disbursed by the EIB by December 18, 2024. The Company plans to use the proceeds of Tranche C towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22 and UCART20x22.

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As a condition to the disbursement of Tranche C the Company issued 611,426 warrants to the benefit of the EIB, in accordance with the terms of the 14th resolution of the shareholders’ meeting held on June 28, 2024 and articles L. 228-91 and seq. of the French Commercial Code (the "Tranche C Warrants").

Each Tranche C Warrant allows the EIB to subscribe for one ordinary share of the Company, at a price of €1.70, corresponding to 99% of the volume-weighted average price of the Company’s ordinary shares over the last 3 trading days preceding the decision of the board of directors of the Company to issue the Tranche C Warrants. The total number of shares issuable upon exercise of the Tranche C Warrants represent circa 0.6% of the Company’s outstanding share capital as at their issuance date.

Tranche C will mature six years from its disbursement date and will accrue interest at a rate of 6% per annum capitalized annually and payable at maturity.

The other terms of the Tranche C Warrants and prepayment events of Tranche C under the Finance Contract are as set forth in the Company’s press release of April 4, 2023 and Form 6-K filed with the U.S. Securities and Exchange Commission on such date.