On December 20, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported certain amendments ("2018 Amendment") to the 2013 License and Collaboration Agreement ("2013 Agreement") on fruquintinib with Lilly Shanghai an affiliate of Eli Lilly and Company ("Lilly") (Press release, Hutchison China MediTech, DEC 20, 2018, View Source [SID1234532206]). The 2018 Amendment covers adjustments in the respective roles and responsibilities of Chi-Med and Lilly, in China, for the development and commercialization of fruquintinib in the areas of future life cycle planning and development, collaborations for co-development of fruquintinib with other third-party anti-cancer agents as well as promotion and distribution rights of fruquintinib.

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"Through this amendment, Chi-Med is stepping forward to take on greater responsibility in return for a broader role and a larger share of the future economic interest on fruquintinib," commented Simon To, Chairman of Chi-Med. "Lilly has been and will continue to be a most important partner for Chi-Med in bringing fruquintinib to as broad a patient population as possible and we share a common goal to maximize the commercial success of fruquintinib in China." He added, "The recent approval and launch of fruquintinib for colorectal cancer in China is an important first step on this journey."

Fruquintinib Life Cycle Indications ("LCI"):

Under the terms of the 2013 Agreement, decision making on LCI development beyond the initial indications of third-line colorectal cancer ("CRC"), third-line non-small cell lung cancer ("NSCLC") and second-line gastric cancer was controlled by Lilly. The majority of development costs for LCIs were to be paid by Lilly, with the minority by Chi-Med.

The 2018 Amendment now gives Chi-Med all planning, execution and decision making responsibilities for LCI development on fruquintinib in China. Chi-Med will pay all of the costs associated with fruquintinib LCI development in China. In return for this investment of capital and resources, Lilly will pay Chi-Med a $20 million milestone upon approval of each fruquintinib LCI in China, for up to three LCIs, totaling up to $60 million in LCI approval milestone payments. Furthermore, upon the launch of the first LCI, the tiered royalty structure, payable by Lilly to Chi-Med on total molecule sales in China, has been raised from the range of 15-20% in the 2013 Agreement to a new level of 15-29% under the 2018 Amendment.

China commercial – Co-Promotion rights:

Under the terms of the 2013 Agreement, Lilly held full commercialization rights to fruquintinib in China.

The 2018 Amendment provides Chi-Med the right to promote fruquintinib in provinces that represent 30% of the sales of fruquintinib in China ("Chi-Med Territory") upon the occurrence of certain commercial milestones. The Chi-Med Territory will expand to provinces that represent 40% of the sales of fruquintinib in China subject to additional criteria being met. Lilly will pay Chi-Med a fee for service to conduct all promotional activities in the Chi-Med Territory.

Immunotherapy collaborations:

Lilly has provided consent, and freedom to operate, for Chi-Med to enter into joint development collaborations with certain third-party pharmaceutical companies to explore combination treatments of fruquintinib and various immunotherapy agents. The first such collaborations with Innovent Biologics (Suzhou) Co. Ltd. ("Innovent") and Genor Biopharma Co. Ltd. ("Genor") will explore the combination of fruquintinib and their respective programmed cell death protein-1 ("PD-1") antibodies, sintilimab (IBI308) and genolimzumab (GB226), in several solid tumor settings.

FINANCIAL GUIDANCE:

Our updated guidance for 2018, compared to the most recent guidance in our 2018 Interim Results announcement for the period ended June 30, 2018 dated July 27, 2018, includes a $12 million increase in expected full year Innovation Platform R&D expense to $142-152 million. This increase reflects the 2018 Amendment of the fruquintinib collaboration with Lilly; our recent co-development collaborations with multiple partners to explore immunotherapy (PD-1) combinations with our vascular endothelial growth factor receptor (VEGFR) inhibitors; as well as a general rise in clinical trial spending on our eight clinical drug candidates and discovery programs including a one-time non-cash adjustment relating to one of our joint ventures. Further, while progress has been made towards realizing the one-time property compensation gain under the Commercial Platform, it is not expected to occur in 2018. We make no other changes to the full year 2018 financial guidance as detailed below:

2018 Previous Guidance

2018 Current Guidance

Adjustment

Group Level:

– Consolidated revenue

$155-175m

$155-175m

None

– Admin., interest & tax

$(16)-(18)m

$(16)-(18)m

None

– Net loss[1]

$(39)-(72)m

$(71)-(84)m

$(12)-(32)m increase

Innovation Platform:

– Consolidated revenue

$40-50m

$40-50m

None

– Adjusted (non-GAAP) R&D expenses

$(130)-(140)m

$(142)-(152)m

$(12)m increase

– Net loss[1]

$(80)-(100)m

$(92)-(112)m

$(12)m increase

Commercial Platform:

– Sales (consolidated)

$115-125m

$115-125m

None

– Sales of non-consolidated JVs[2]

$460-480m

$460-480m

None

– Net income on an adjusted (non-GAAP) basis excl. one-time gains[1]

$41-43m

$41-43m

None

– One-time gains[1]

$0-20m[3]

$0m

$0-(20)m decrease

– Net income[1]

$41-63m

$41-43m

$0-(20)m decrease

Notes: [1] Attributable to Chi-Med; [2] Joint ventures; [3] One-time property compensation, timing of which is dependent on Guangzhou government policy.

All dollars are expressed in US dollar currency unless otherwise stated.

About Fruquintinib

Fruquintinib (brand name: Elunate) is a small molecule, selective and highly potent inhibitor of VEGFR 1, 2 and 3. VEGFR inhibitors play a pivotal role in tumor-related angiogenesis, cutting off the blood supply that a tumor needs to grow rapidly. The global market for anti-angiogenesis therapies was estimated at over $18 billion in 2017, including both monoclonal antibodies and small molecules approved in around 30 tumor settings. During the discovery research process, which began at Chi-Med in 2007, fruquintinib was successfully designed to be differentiated by improving kinase selectivity in comparison to other approved small molecule tyrosine kinase inhibitors (TKIs), to minimize off-target toxicities, improve tolerability and provide more consistent target coverage, resulting in better clinical efficacy.

The superior tolerability, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may be highly suitable for innovative combinations with other anti-cancer therapies. The most common adverse reactions included hypertension, hand-foot syndrome and proteinuria. Clinically effective management of these adverse effects is feasible. For important safety information about fruquintinib, please see www.chi-med.com.

About Other Fruquintinib Development Programs

Global Development

Phase I monotherapy in the U.S.: In December 2017, Chi-Med initiated a multi-center, open-label, Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors (clinicaltrials.gov identifier NCT03251378). This study is almost complete, and proof-of-concept ("POC") studies are expected to begin in 2019.

PD-1 checkpoint inhibitor combination: It is an important part of Chi-Med’s strategy to explore the potential synergies of its drug candidates in combination with other anti-cancer treatments in several solid tumor settings. In November 2018, Chi-Med entered into a global collaboration agreement to evaluate the safety, tolerability and efficacy of fruquintinib in combination with sintilimab (IBI308), a PD-1 inhibitor being developed by Innovent.

China Development

CRC in China: The National Medical Products Administration (NMPA) approved the first New Drug Application ("NDA") for fruquintinib for the treatment of patients with advanced CRC in September 2018. The NDA is supported by data from the successful FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with CRC in China, which was highlighted in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held on June 5, 2017 and was published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier NCT02314819).

Gastric cancer in China: In October 2017, Chi-Med initiated a pivotal Phase III clinical trial of fruquintinib in combination with Taxol (paclitaxel), known as the FRUTIGA study, in approximately 500 patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after first-line standard chemotherapy (clinicaltrials.gov identifier NCT03223376). An interim analysis on FRUTIGA, to establish POC, is anticipated during the first half of 2019 and if successful could trigger a POC milestone payment from Lilly. The FRUTIGA study followed a Phase I/II clinical trial in 34 patients with gastric cancer that demonstrated that combination therapy of fruquintinib and Taxol was generally well-tolerated with promising tumor response (clinicaltrials.gov identifier NCT02415023).

Lung cancer in China: The FALUCA trial is a randomized, double-blind, placebo-controlled, multi-center, Phase III registration study targeted at treating patients with advanced non-squamous NSCLC, who have failed two lines of systemic chemotherapy. 527 patients were randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus best supportive care ("BSC"); or placebo plus BSC. On November 16, 2018, Chi-Med announced that FALUCA did not meet the primary endpoint to demonstrate a statistically significant increase in overall survival (OS) compared to placebo, however the data did show statistically significant improvement in all secondary endpoints including progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and duration of response (DoR) as compared to the placebo. The safety profile of the trial was in line with that observed in prior clinical studies. Full detailed results are expected to be disclosed at an upcoming scientific meeting. Additional details about this study can be found at clinicaltrials.gov, using identifier NCT02691299.

Along with FALUCA, fruquintinib is concurrently being studied in a Phase II study in combination with Iressa (gefitinib) in patients with untreated advanced or metastatic NSCLC (clinicaltrials.gov identifier NCT02976116). Preliminary results were highlighted in an oral presentation at the 18th World Conference on Lung Cancer on October 16, 2017.

PD-1 checkpoint inhibitor combination: In October 2018, Chi-Med entered into a further collaboration in China to evaluate the combination of fruquintinib with genolimzumab (GB226), a PD-1 inhibitor being developed by Genor.

On December 19, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed a new drug application to the Ministry of Health, Labour and Welfare (MHLW) for a ROS1/TRK inhibitor entrectinib for the treatment of NTRK fusion-positive solid tumors (Press release, Chugai, DEC 19, 2018, View Source [SID1234532139]). Entrectinib received Sakigake designation and orphan drug designation from MHLW.

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"Entrectinib obtained the first Sakigake designation for Chugai. Entrectinib demonstrated efficacy across tumor types in extremely rare NTRK fusion-positive solid tumors in the global studies," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "Chugai is committed to seek approval of entrectinib so that we may contribute to advancing personalized healthcare which may enable the most optimal treatment decision for patients based on genetic profiles of individual tumors."

This application for approval is based on an integrated analysis of an open-label, multicenter, global phase II study (the STARTRK-2 study) and three overseas phase I studies (the STARTRK-NG study, the STARTRK-1 study and the ALKA-372-001 study). Efficacy was evaluated in 54 patients with untreated NTRK fusion-positive solid tumors while safety assessment was conducted with 355 patients registered in the four trials.

[Reference information]
About the integrated analysis results
Media release issued by Roche on October 21, 2018
Title: Roche’s investigational personalised medicine entrectinib shrank tumours in people with NTRK fusion-positive solid tumours
View Source

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) in May 2017, Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) in October 2017 for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.

As the top pharmaceutical company in the field of oncology in Japan, Chugai will work for the early approval to provide entrectinib as a new treatment option for patients and medical professionals.

About entrectinib
Entrectinib is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 or ROS1 gene fusions. It is a selective, CNS-active tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and inhibit proliferation of cancer cells with ROS1 or NTRK gene fusions. Entrectinib is being investigated across a range of solid tumor types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

About NTRK fusion gene positive cancer
NTRK fusion gene is an abnormal gene that can be formed by fusing the NTRK genes (NTRK1, NTRK2, NTRK3 encode TRKA, TRKB, TRKC protein, respectively) and other genes (ETV6, LMNA, TPM3, etc.) as a result of chromosomal translocation. The TRK fusion kinase made from NTRK fusion gene is thought to promote cancer cell proliferation. There is very rare expression of NTRK fusion but in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor (GIST), infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas.

On December 19, 2018 Kyn Therapeutics, a biotechnology company advancing new immunometabolism therapies for treating cancer, reported the initiation of two clinical trials of ARY-007 (also known as Grapiprant), an EP4 receptor antagonist, in collaboration with Merck (known as MSD outside the United States and Canada) (Press release, KYN Therapeutics, DEC 19, 2018, View Source [SID1234532156]). ARY-007 will be assessed in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in checkpoint-refractory and -resistant solid tumors, an area of high unmet medical need.

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Prostaglandin E2 (PGE2) has been shown to contribute to an immunosuppressive environment in cancer by enhancing the activity of regulatory immune cells and suppressing the activity of effector immune cells. EP4 is a high-affinity receptor of PGE2 and is known to facilitate these immunosuppressive activities. ARY-007 is an oral, potent and highly selective antagonist of EP4. In preclinical models, EP4 inhibition leads to antitumor activity and also significantly enhances the antitumor activity of checkpoint inhibitors. While in development for a non-oncology indication, ARY-007 was found to be well-tolerated in multiple studies which enrolled approximately 1000 human subjects.

The Phase 1b/2 multicenter, open-label, single arm clinical trials are designed to assess the safety and efficacy of ARY-007 in combination with pembrolizumab in patients with advanced or progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC), and with advanced or metastatic PD-1/L1 refractory Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma. MSS CRC is inherently resistant to anti-PD-1 therapies – these agents have only shown activity in the microsatellite instability-high (MSI-H) subset of CRC. The NSCLC study is enrolling patients who have progressed while on PD-1 or PD-L1 therapy. Both studies incorporate a robust translational biomarker strategy.

"The Kyn team believes immunometabolism pathways hold great promise as therapeutics that could deliver breakthrough improvements for patients non-responsive to immunotherapy regimens. We believe EP4 is the right target and ARY-007 is the right molecule for overcoming the immunosuppressive effects of PGE2 in these cancers where increased pathway expression is associated with poor outcome," said Mark Manfredi, Ph.D., president and chief executive officer of Kyn Therapeutics. "We welcome the opportunity to collaborate with Merck as we initiate clinical studies."

About ARY-007
ARY-007 is an orally available, potent and highly selective antagonist of the EP4 receptor, a component of the prostaglandin E2 (PGE2) pathway which significantly influences the composition of the tumor microenvironment. In preclinical studies, inhibition of EP4 has been shown to boost the immune response through modulation of multiple immune cell types, and in combination with checkpoint inhibitors has yielded significant reduction in tumor growth relative to either agent alone.

On December 19, 2018 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on using the body’s immune system to fight cancer, reported that it completed a Pre-Submission (Pre-Sub) meeting with the US FDA on December 17, 2018 (Press release, Anixa Biosciences, DEC 19, 2018, View Source [SID1234532175]).

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The meeting was focused on discussing Anixa’s Cchek test, an artificial intelligence (AI) based liquid biopsy for the early detection of cancer. Specifically, the discussion focused on using Cchek for prostate cancer testing, as prostate cancer will be the first commercial application.

Dr. Amit Kumar, President and CEO of Anixa Biosciences said, "The meeting was very positive and productive, with discussions that included the intended use of the test, the path for regulatory approval, and the use of AI. We are eager to move Cchek-Prostate towards commercialization." Dr. Kumar continued, "Standard of care for screening for prostate cancer includes a prostate specific antigen (PSA) measurement, followed by a digital rectal exam (DRE). It is well known that these current tests are imperfect, and cause hundreds of thousands of men to undergo painful, expensive and risk-laden biopsies that are negative and may be unnecessary. Our preliminary data, which we presented to the FDA, demonstrates that Cchek-Prostate could potentially eliminate a large number of these unnecessary procedures. The FDA was very supportive and appreciated us initiating the dialogue with them. As we continue through the regulatory process, we anticipate additional productive meetings and submissions with the FDA."

Anixa Biosciences expects the official minutes of the Pre-Sub meeting to be available in January. On January 24, 2019 Anixa plans to hold a conference call where it will discuss the commercialization path and timeline for Cchek-Prostate, as well as an update on its CAR-T therapeutics program. The details of the conference call will be provided at a later date.

On December 19, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the first patient has been dosed in the first novel-novel combination study evaluating two investigational agents within its AML Franchise (Press release, Daiichi Sankyo, DEC 19, 2018, View Source [SID1234532207]). The phase 1 study will evaluate the safety and activity of the combination of a FLT3 inhibitor, quizartinib, and an MDM2 inhibitor, milademetan (DS-3032), in patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML) or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy, a very aggressive form of the disease associated with poor prognosis.

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"We have initiated this combination study of quizartinib and milademetan in order to determine the safety and tolerability of the combination and if the addition of the MDM2 inhibitor milademetan may potentially further improve the outcomes of patients with relapsed/refractory FLT3-ITD AML beyond what has been previously reported with single agent quizartinib," said Arnaud Lesegretain, Vice President, Oncology R&D and Head, AML Franchise, Daiichi Sankyo. "In this study, we also are exploring the potential of the combination of quizartinib and milademetan in patients with newly-diagnosed FLT3-ITD AML who are unfit for intensive chemotherapy. This study is the first of several planned studies that will evaluate the potential of novel combinations within our investigational AML Franchise, as we are committed to continuously improving the standard of care for patients with AML."

Quizartinib is the first FLT3 inhibitor to demonstrate a survival benefit as an oral, single agent compared to chemotherapy in a randomized, phase 3 study (QuANTUM-R) in patients with FLT3-ITD AML, which was refractory or relapsed within six months of first remission, and single agent milademetan has demonstrated preliminary clinical activity in AML and myelodysplastic syndrome (MDS) in a phase 1 study.1,2 Additionally, preclinical research has shown that the combination of quizartinib and milademetan has greater activity in FLT3-ITD AML cells compared to the respective single agent treatments.3

In the QuANTUM-R study, the median treatment duration with quizartinib was 4 cycles of 28 days each versus 1 cycle in the salvage chemotherapy arm. Incidence of treatment-emergent adverse events was comparable between patients who received single agent quizartinib and those who received salvage chemotherapy. The most common adverse drug reactions (>30 percent, any Grade) in patients treated with quizartinib included infections, bleeding, nausea, asthenic conditions, pyrexia, febrile neutropenia and vomiting, and the most common Grade ≥ 3 adverse drug reactions (>20 percent) were infection and febrile neutropenia. The most common laboratory adverse reactions (incidence >50 percent) were decreased white blood cell count, decreased lymphocyte count, decreased hemoglobin, decreased neutrophil count and decreased platelet count. The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program.

In addition to the quizartinib and milademetan combination study, an ongoing phase 1 study of milademetan has been expanded to include evaluation of milademetan in combination with the hypomethylating agent 5-azacitidine, an inhibitor of DNA methylation, in patients with newly-diagnosed AML unfit for intensive chemotherapy, relapsed/refractory AML or high-risk MDS.

About the Quizartinib/Milademetan Combination Study

The multi-center, non-randomized, phase 1, open-label, two-part study is investigating the safety and efficacy of the combination of quizartinib and milademetan in patients with relapsed/refractory FLT3-ITD AML or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy. The first part of the study (dose escalation) will assess the safety and tolerability of the combination to determine the dosing schedule, maximum tolerated dose and recommended dose for expansion. The second part of the study (dose expansion) will confirm the safety and tolerability at the recommended dose for expansion of the combination and will identify a recommended phase 2 dose. The primary objective of the study is safety. Secondary objectives include evaluation of pharmacokinetics and preliminary efficacy. The study is expected to enroll approximately 110 patients in the U.S., EU and Japan. For more information about the study, visit ClinicalTrials.gov.

About the Milademetan/5-Azacitidine Combination Study

The multi-center, non-randomized, phase 1, open-label, two-part study is investigating the safety and efficacy of milademetan as a single agent and in combination with the hypomethylating agent 5-azacitidine. The first part of the study (dose escalation) will evaluate the safety and tolerability and identify the maximum tolerated dose and recommended dose for expansion of milademetan as a single agent and in combination with 5-azacitidine in patients with relapsed/refractory AML or high-risk MDS. The second part of the study (dose expansion) will confirm the safety and tolerability at the recommended dose of milademetan in combination with 5-azacitidine and will identify a recommended phase 2 dose in patients with relapsed/refractory AML, newly-diagnosed AML unfit for intensive chemotherapy or high-risk MDS. The primary objectives of the study are safety and tolerability, maximum tolerated dose, recommended dose for expansion and response to treatment. Key secondary objectives include evaluation of pharmacokinetics and pharmacodynamic effects. The study is expected to enroll up to 200 patients in the U.S. For more information about the study, visit ClinicalTrials.gov.

About Acute Myeloid Leukemia and Myelodysplastic Syndrome

AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells.4 In the U.S. this year, it is estimated that there will be more than 19,000 new diagnoses of AML and more than 10,000 deaths from AML.5 The five-year survival rate of AML reported from 2007 to 2013 was approximately 27 percent, which was the lowest of all leukemias.4

FLT3 gene mutations are one of the most common genetic abnormalities in AML.6 FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML.7,8,9,10 FLT3-ITD is a driver mutation that presents with high leukemic burden and has poor prognosis and a significant impact on disease management for patients with AML.8,11 Patients with FLT3-ITD AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapse and a higher likelihood of relapse following hematopoietic stem cell transplantation as compared to those without this mutation.12,13

MDS is a type of cancer that can occur when blood-forming cells in the bone marrow become abnormal.14 There were over 14,000 new cases of MDS diagnosed each year from 2010 to 2014.4 In about one in three patients, MDS progresses to AML.14

About Quizartinib

Quizartinib, the lead investigational agent in the AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective type II FLT3 inhibitor currently in phase 3 development for relapsed/refractory FLT3-ITD AML (QuANTUM-R) in the U.S. and EU; phase 3 development for newly-diagnosed FLT3-ITD AML (QuANTUM-First) in the U.S., EU and Japan; phase 2 development for relapsed/refractory FLT3-ITD AML in Japan; and phase 1 development in combination with an investigational agent, milademetan, for relapsed/refractory FLT3-ITD AML and newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy in the U.S., EU and Japan.

Quizartinib has been granted Priority Review and Breakthrough Therapy designation for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, and Fast Track designation for the treatment of relapsed/refractory AML by the U.S. Food and Drug Administration (FDA). Quizartinib also has been granted accelerated assessment by the European Medicines Agency (EMA) for the treatment of adults with relapsed or refractory AML, which is FLT3-ITD positive, and granted Orphan Drug designation by both the FDA and the European Commission (EC) for the treatment of AML and by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of FLT3-mutated AML.

About Milademetan

Milademetan (DS-3032) is an oral selective MDM2 inhibitor currently in phase 1 clinical development for solid and hematologic malignancies, including a combination study with quizartinib in relapsed/refractory FLT3-ITD AML or newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy in the U.S., EU and Japan; a single agent and combination study with 5-azacitidine in newly-diagnosed AML unfit for intensive chemotherapy, relapsed/refractory AML or high-risk MDS in the U.S.; and two single agent studies in lymphomas and solid tumors in the U.S. and Japan.

Quizartinib and milademetan are investigational agents that have not been approved for any indication in any country. Safety and efficacy of these investigational agents have not been established.