On August 23, 2022 Daiichi Sankyo (TSE: 4568) reported that the European Medicines Agency (EMA) has validated the marketing authorization application (MAA) for quizartinib in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) positive (Press release, Daiichi Sankyo, AUG 23, 2022, View Source [SID1234618575]).

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AML is one of the most common forms of leukemia in adults, representing about one-third of all cases.1 In Europe, approximately 18,000 people are diagnosed with AML each year and the five-year survival rate is reported at 17% for adult patients.2,3 Of all newly diagnosed cases of AML, approximately 25% carry the FLT3-ITD gene mutation, which is associated with a particularly unfavorable prognosis including increased risk of relapse and shorter overall survival.4

"There is a need to improve survival for the majority of patients with acute myeloid leukemia, particularly those with the FLT3-ITD subtype, which is aggressive and difficult to treat," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We look forward to working with the EMA to support their review of quizartinib as a potential option for patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia."

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The application is based on data from the QuANTUM-First phase 3 trial recently presented at the European Hematology Association (EHA) (Free EHA Whitepaper) (#EHA2022) Congress. In QuANTUM-First, quizartinib combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and continued as monotherapy following consolidation, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in adult patients with newly diagnosed FLT3-ITD positive AML compared to chemotherapy alone. The safety of quizartinib combined with intensive chemotherapy and as continuation monotherapy in QuANTUM-First was generally manageable and consistent with previous clinical trials. The incidence of Grade ≥3 QT prolongation was low, with uncommon ventricular arrythmia events. Overall, the risk of QT prolongation was manageable with ECG monitoring, quizartinib dose modification and correction/elimination of additional risk factors.

About QuANTUM-First

QuANTUM-First is a randomized, double-blind, placebo-controlled global phase 3 study evaluating quizartinib in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, in adult patients aged 18-75 with newly diagnosed FLT3-ITD positive AML. Patients were randomized 1:1 into two treatment groups to receive quizartinib or placebo combined with anthracycline- and cytarabine-based regimens. Eligible patients, including those who underwent hematopoietic stem cell transplant (HSCT), continued with quizartinib or placebo for up to 36 cycles.

The primary study endpoint was OS. Secondary endpoints include event-free survival (EFS), post-induction rates of complete remission (CR) and composite complete remission (CRc), and the percentage of patients who achieve CR or CRc with FLT3-ITD minimal residual disease negativity. Safety and pharmacokinetics, along with exploratory efficacy and biomarker endpoints, also were evaluated. QuANTUM-First enrolled 539 patients at 193 study sites across Asia, Europe, North America, Oceania and South America. For more information, visit Clinicaltrialsregister.eu or ClinicalTrials.gov.

About Acute Myeloid Leukemia (AML)

More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths.5 AML is one of the most common types of leukemia in adults, representing about one-third of all cases, and the average age of diagnosis is 68 years old.1 In Europe, approximately 18,000 people are diagnosed with AML each year and the five-year survival rate is reported at 17% for adult patients.2,3 The conventional treatment for newly diagnosed AML is intensive induction and consolidation chemotherapy with HSCT for eligible patients.6,3

About FLT3-ITD

FLT3 (FMS-like tyrosine kinase 3) is a tyrosine kinase receptor protein normally expressed by hematopoietic stem cells that plays an important role in cell development, promoting cell survival, growth and differentiation through various signaling pathways.4 Mutations of the FLT3 gene, which occur in approximately 30% of AML patients, can drive oncogenic signaling.4 FLT3-ITD (internal tandem duplication) is the most common type of FLT3 mutation in AML, occurring in about 25% of all newly diagnosed patients, and is associated with increased risk of relapse and shorter overall survival.4

About Quizartinib

Quizartinib is an oral, selective type II FLT3 inhibitor currently in clinical development for treatment of FLT3-ITD positive AML. In addition to QuANTUM-First, the quizartinib development program includes a phase 1/2 trial in pediatric and young adult patients with relapsed/refractory FLT3-ITD positive AML in Europe and North America. Several phase 1/2 combination studies with quizartinib are also underway at The University of Texas MD Anderson Cancer Center as part of a strategic research collaboration focused on accelerating development of Daiichi Sankyo pipeline therapies for AML.

Quizartinib, which is currently not approved in Europe, has been granted Orphan Drug Designation for the treatment of AML in Europe, Japan and the U.S. Quizartinib has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive, in combination with standard cytarabine and anthracycline induction and cytarabine consolidation chemotherapy. Quizartinib is currently approved for use in Japan for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, as detected by an approved test. Quizartinib is an investigational medicine in all countries outside of Japan.

On August 23, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that recombinant trypsinogen and chmyotrypsinogen were synthesized via the Proenzyme Optimization Project (POP1) joint research and drug discovery program (Press release, Propanc, AUG 23, 2022, View Source [SID1234618574]). In the case of trypsinogen, the initial success of producing trypsinogen synthetically has now advanced to the stage where optimization of protein production is underway, whereas purification and yield of chymotrypsinogen is currently the focus of research. The program is designed to produce a backup clinical compound to the Company’s lead product candidate, PRP, which is targeting metastatic cancer from solid tumors. According to Emergen Research, the global metastatic cancer market is projected to be worth $111 Billion by 2027.

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A synthetic version of trypsinogen and chymotrypsinogen could have additional benefits to the global healthcare system that could further capitalize on the new therapeutic approach to treating cancer that the Company’s lead product candidate PRP offers cancer sufferers. For example, both proenzymes synthesized by an in vivo (living organism) system to produce crystalized proteins that could be maintained for long periods without suffering degradation, even in the absence of refrigeration. This will be particularly useful for a longer shelf life as well as global distribution of the drug product, particularly in warmer climates and developing regions where refrigeration may not be available. The program’s lead research scientist, Mr. Aitor González is consulting with Professor Diethard Mattanovich, Institute of Microbiology and Microbial Biotechnology, at the University of Natural Resources and Life Sciences, Vienna, Austria, Europe, and is working towards full scale manufacture of a synthetic recombinant formulation to PRP.

"The work undertaken by Aitor in Professor Mattanovich’s laboratory is very careful, detailed work, and it looks like we’re getting close to getting chymotrypsinogen production, as we are already able to produce trypsinogen," said Dr. Julian Kenyon, Propanc’s Chief Scientific Officer. "A fully synthetic recombinant version of PRP would have tremendous implications from a regulatory perspective, but also a practical, commercial benefit for global distribution."

The objective of the POP1 program is to produce large quantities of trypsinogen and chymotrypsinogen for commercial use that exhibits minimal variation between lots and without sourcing the proenzymes from animals. Propanc is undertaking the challenging research project in collaboration with the Universities of Jaén and Granada, led by Mr. González, supported by Prof. Macarena Perán, Ph.D. and Prof. Juan Antonio Marchal M.D., representing the Universities, respectively, and Dr. Kenyon.

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

On August 23, 2022 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported its liver drug candidate Namodenoson has been approved for compassionate use for the treatment of patients with advanced liver cancer in Romania (Press release, Can-Fite BioPharma, AUG 23, 2022, View Source [SID1234618573]). Namodenoson was previously approved for compassionate use in Israel, where advanced liver cancer patients have been treated for several years.

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In parallel, Can-Fite’s pivotal Phase III study in patients with advanced liver cancer (hepatocellular carcinoma), is open for patient enrolment and will recruit patients in Israel, the U.S., and five countries in Europe. This pivotal study received a ‘green light’ to proceed from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and if successfully concluded, the Company will be in a position to submit the drug for approval with each of the regulatory authorities. Namodenoson has Orphan Drug Status with both the FDA and EMA and Fast Track Status with the FDA. A registration plan has been submitted to and accepted by the FDA.

"We are committed to providing Namodenoson, with an excellent safety profile and strong efficacy in this patient population in clinical trials to date, to fulfill an urgent unmet medical need. The anti-cancer effect of Namodenoson together with its liver protective properties make it unique among anti-cancer drugs for this devastating disease," stated Can-Fite CEO Dr. Pnina Fishman.

The hepatocellular carcinoma (HCC) drug market is expected to reach $3.8 billion in 2027 in the G8 countries according to DelveInsight. The American Cancer Society estimates that in the U.S., liver cancer incidence has tripled since 1980, with an estimated 41,000 cases diagnosed and 31,000 deaths annually. Incidence of liver cancer is much higher in other countries, with more than 800,000 diagnoses and 700,000 deaths estimated globally each year.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated as a second line treatment for advanced hepatocellular carcinoma in a pivotal Phase III trial. The drug is currently in an ongoing Phase II trial as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On August 23, 2022 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported positive results from a pivotal study of Abivertinib on 209 response evaluable, heavily pretreated NSCLC patients by an IRC assessment with matured long-term follow up data (Press release, Sorrento Therapeutics, AUG 23, 2022, View Source [SID1234618572]).

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Abivertinib is a pyrrolopyrimidine-based, third-generation EGFR inhibitor, which is structurally distinct from osimertinib. Abivertinib selectively inhibits EGFR-activating and resistant mutation with nearly 300-fold greater potency as compared with wild-type EGFR. Previously, a positive interim result assessed by investigators was published in the peer-reviewed Clinical Cancer Research journal with interim data (View Source). In these IRC-assessed preliminary topline results with more matured long-term follow up data (previously 16.8 months, now 38.8 months), Abivertinib showed significant treatment benefits in 209 response evaluable, heavily treated NSCLC patients with ORR of 56.5%, and notably a significant CR rate was seen with Abivertinib (5.3%) in comparison with that of osimertinib (Tagrisso) (0.5%)*, while the ORR rate is comparable between the two drugs. This combined data, the ORR of 56.5%, the CR rate of 5.3%, and median OS of 28.2 months (versus Tagrisso’s median OS of 26.8 months)**, is potentially superior to that of the approved third generation EGFR inhibitor (osimertinib). Abivertinib demonstrated significantly efficacious effects in overcoming the resistant mutation in NSCLC. Based on these results, Sorrento is closing the study and preparing the pre-NDA materials and NDA package. Sorrento will request a pre-NDA meeting with the FDA and other regulatory agencies around the world with potential NDA filings pending agreements with the regulatory agencies in different countries.

"We are very encouraged by the significant positive results of Abivertinib assessed by the IRC with long-term follow up data and look forward to meeting with the FDA and other regulatory authorities for the possibility of bringing Abivertinib to the U.S. and global markets," said Dr. Henry Ji, Chairman and CEO of Sorrento. Abivertinib is one of the multiple clinical and pre-clinical stage assets obtained by Sorrento in the previously completed acquisition of ACEA Therapeutics, Inc. in June of 2021.

On August 23, 2022 Sensei Biotherapeutics, Inc. (NASDAQ: SNSE), an immuno-oncology company focused on the discovery and development of next generation therapeutics for cancer, reported that Company management will participate in the following investor conferences in September 2022 (Press release, Sensei Biotherapeutics, AUG 23, 2022, View Source [SID1234618571]):

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Citi’s 17th Annual Biopharma Conference
September 7th-8th
Boston, MA

Wells Fargo’s 2022 Healthcare Conference
September 7th-9th
Boston, MA

Portfolio managers and analysts who would like to request a meeting with management should contact their representative at the respective hosting firms.