On June 18, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported that BRUKINSA (zanubrutinib) has received conditional approval from the China National Medical Products Administration (NMPA) for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy (Press release, BeiGene, JUN 18, 2021, View Source [SID1234584126]). The supplemental new drug application was previously granted priority review by the Center for Drug Evaluation (CDE) of the NMPA in October 2020.

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"With NMPA approval for BRUKINSA, our next generation BTK inhibitor, we are proud to be able to offer patients, their families, and physicians a new option for treating WM, an incurable disease that can cause significant morbidities," said Xiaobin Wu, Ph.D., General Manager of China and President of BeiGene. "This marks BRUKINSA’s third approval for the treatment of B-cell malignancies in China, and we believe it may serve an important role in addressing unmet needs for patients with blood cancers around the world."

"WM often impacts older adults, and tolerability is a particular concern for these patients as longer duration of treatment has the potential to improve outcomes," said Lugui Qiu, M.D., Professor, Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and a clinical trial leading principal investigator of BRUKINSA. "As shown in the trial, patients in China will now have access to an innovative treatment that offers cardiovascular safety advantages and deep and durable responses."

"BRUKINSA was specifically designed by BeiGene scientists to limit off-target effects seen with first-generation BTK inhibitors and we have built a broad clinical development program to assess clinical benefit, including the head-to-head ASPEN trial," said Jane Huang, M.D., Chief Medical Officer, Hematology, BeiGene. "We are grateful to all of the patients and clinicians who participated in the trial and hope to increase access for additional people impacted by WM and other hematologic malignancies as we advance global registration for BRUKINSA."

The conditional approval granted by the NMPA was based on findings from a single-arm pivotal Phase 2 trial (NCT03332173) in China evaluating the safety and efficacy of BRUKINSA in patients with WM who have received at least one prior therapy. With a median study follow-up time of 14.9 months, the primary endpoint of major response rate (MRR) as assessed by independent review committee (IRC) was 72.1% (95% CI: 56.3, 84.7); MRR is defined as the combined rate of complete responses, very good partial responses, and partial responses. The adverse reaction profile was generally consistent with previous findings.

The recommended total daily dose of BRUKINSA for WM in China is 320mg.

About Waldenström’s Macroglobulinemia

Waldenström’s macroglobulinemia is a rare, slow-growing lymphoma that occurs in less than two percent of patients with non-Hodgkin’s lymphoma (NHL). 1 The disease usually affects older adults and is primarily found in the bone marrow, although it may also impact lymph nodes and the spleen.2 In China, there are an estimated 88,200 patients diagnosed with lymphoma each year. Approximately 91% of these cases are classified as NHL, amounting to ~1,000 newly diagnosed WM patients per year in China.3

About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the following indications and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy (China, June 2021)**;
For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021); and
For the treatment of WM in adult patients (Canada, March 2021).
To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of the United States and China, covering countries in the European Union and more than 20 other countries.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (27%), thrombocytopenia (10%), and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.

Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia (18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For co-administration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

INDICATION

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

On June 18, 2021 Bristol Myers Squibb (NYSE: BMY) reported that the European Commission (EC) has granted full Marketing Authorization for Onureg (azacitidine tablets) as a maintenance therapy in adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT) (Press release, Bristol-Myers Squibb, JUN 18, 2021, View Source [SID1234584127]). Onureg isthe first and only once-daily, frontline oral maintenance therapy to demonstrate significant overall survival and show a relapse-free survival benefit in patients with a broad range of AML subtypes.

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The centralized Marketing Authorization approves use of Onureg in all EU member states, as well as Norway, Iceland and Liechtenstein.* Onureg is approved in the United States for the continued treatment of adult patients with AML who achieved first CR or CRi following intensive induction chemotherapy and who are not able to complete intensive curative therapy.1 In Canada, Onureg is approved as a maintenance therapy for adult patients with AML who achieved CR or CRi following induction therapy with or without consolidation treatment, and who are not eligible for HSCT.2

"An unmet need exists for maintenance therapy options for acute myeloid leukemia in the European Union, given responses to induction therapy may be of short duration and the risk of relapse is high, especially for patients not eligible for stem cell transplant," said Andrew Wei, MBBS, Ph.D., QUAZAR AML-001 lead investigator, Alfred Hospital and Monash University, Melbourne, Australia. "The approval of Onureg by the European Commission has the potential to clinically benefit and change the treatment paradigm of patients with acute myeloid leukemia, across a range of subtypes."

The EC approval of Onureg was based on results from the QUAZAR AML-001 study, a Phase 3, international, randomized, double-blind trial. Eligible patients were ages 55 years or older, had newly diagnosed AML, intermediate or poor cytogenetics, had achieved first CR or CRi following intensive induction chemotherapy with or without consolidation treatment (per investigator preference prior to study entry), and were not candidates for HSCT at the time of screening.3

"Today’s approval of Onureg represents a significant advance for patients in the European Union living with acute myeloid leukemia, who have remained in urgent need of maintenance therapies for this aggressive blood cancer," said Noah Berkowitz, M.D., Ph.D., senior vice president, Hematology Development, Bristol Myers Squibb. "We are committed to helping to improve long-term outcomes and greatly extending survival for patients with hard-to-treat diseases, as we work collaboratively with European Union member states to make Onureg available to eligible patients as quickly as possible."

*Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland and Wales).

About QUAZAR AML-001

QUAZAR AML-001, is a Phase 3, international, randomized, double-blind study. Eligible patients were ages 55 years or older, had newly diagnosed AML, intermediate or poor cytogenetics, had achieved first CR or CRi following intensive induction chemotherapy with or without consolidation treatment (per investigator preference prior to study entry) within four months (+/- 7 days) before randomization, and were not candidates for HSCT at the time of screening. The study enrolled 472 patients, randomized 1:1 to receive either Onureg 300 mg (N=238) or placebo (N=234) orally, once daily, for 14 days of a 28-day cycle, plus best supportive care and results were published in the New England Journal of Medicine in December 2020.*3,4

Median OS, the primary endpoint, from time of randomization was greater than two years (24.7 months; 95% CI: 18.7 to 30.5) in the Onureg arm compared to 14.8 months for placebo (HR: 0.69, 95% CI: 0.55 to 0.86; p=0.0009). The median duration of treatment was 12 cycles (1 to 82) for Onureg and 6 cycles with placebo (1 to 76).Median relapse-free survival was also significantly longer with Onureg than with placebo (10.2 months and 4.8 months, respectively; p<0.001). Overall health-related quality of life was preserved during Onureg treatment.4

The most common adverse events in both treatment arms were Grade 1 or 2 gastrointestinal events. Common Grade 3 or 4 adverse events were neutropenia (41% of patients treated with Onureg and 24% of patients with placebo) and thrombocytopenia (22% and 21%, respectively).4

*Individual results associated with regulatory authorities may differ from publication.

About AML

AML is one of the most common acute leukemias in adults.5 The worldwide incidence of AML has been estimated at more than 350,000 cases, and the estimated 5-year survival rate for AML in Europe is 17%.6 AML is characterized by the rapid growth of abnormal cells in the bone marrow and as such interferes with normal blood cell production and function. Because of the impaired production of red blood cells, platelets and white blood cells, it can present with signs of anemia, bleeding and infections.5 AML is a heterogeneous disease associated with diverse genetic mutations, and can rapidly progress and lead to death if not promptly treated.7 AML response to treatment may be of short duration, meaning following patients’ initial response to chemotherapy, about 50% of patients relapse within one year, thus representing a significant unmet need for maintenance treatment options that prolong overall survival.8

About Onureg

Onureg, the first and only frontline maintenance therapy approved in the European Union for patients with a broad range of AML subtypes, is a once-daily oral hypomethylating agent that incorporates into DNA and RNA. The main mechanism of action is thought to be hypomethylation of DNA, as well as direct cytotoxicity to abnormal hematopoietic cells in the bone marrow. Hypomethylation may restore normal function to genes that are critical for cell differentiation and proliferation.9,10 Onureg is approved in the U.S. for continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy. Onureg is also approved in Canada as maintenance therapy for adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment, and who are not eligible for hematopoietic stem cell transplantation (HSCT).

U.S. IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ONUREG is contraindicated in patients with known severe hypersensitivity to azacitidine or its components.
WARNINGS AND PRECAUTIONS

Risks of Substitution with Other Azacitidine Products: Due to substantial differences in the pharmacokinetic parameters, the recommended dose and schedule for ONUREG are different from those for the intravenous or subcutaneous azacitidine products. Treatment of patients using intravenous or subcutaneous azacitidine at the recommended dosage of ONUREG may result in a fatal adverse reaction. Treatment with ONUREG at the doses recommended for intravenous or subcutaneous azacitidine may not be effective. Do not substitute ONUREG for intravenous or subcutaneous azacitidine.
Myelosuppression: New or worsening Grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received ONUREG. Febrile neutropenia occurred in 12%. A dose reduction was required for 7% and 2% of patients due to neutropenia and thrombocytopenia. Less than 1% of patients discontinued ONUREG due to either neutropenia or thrombocytopenia. Monitor complete blood counts and modify the dosage as recommended. Provide standard supportive care, including hematopoietic growth factors, if myelosuppression occurs.
Increased Early Mortality in Patients with Myelodysplastic Syndromes (MDS): In AZA-MDS-003, 216 patients with red blood cell transfusion-dependent anemia and thrombocytopenia due to MDS were randomized to ONUREG or placebo. 107 received a median of 5 cycles of ONUREG 300 mg daily for 21 days of a 28-day cycle. Enrollment was discontinued early due to a higher incidence of early fatal and/or serious adverse reactions in the ONUREG arm compared with placebo. The most frequent fatal adverse reaction was sepsis. Safety and effectiveness of ONUREG for MDS have not been established. Treatment of MDS with ONUREG is not recommended outside of controlled trials.
Embryo-Fetal Toxicity: ONUREG can cause fetal harm when administered to a pregnant woman. Azacitidine caused fetal death and anomalies in pregnant rats via a single intraperitoneal dose less than the recommended human daily dose of oral azacitidine on a mg/m2 basis. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ONUREG and for at least 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ONUREG and for at least 3 months after the last dose.
ADVERSE REACTIONS

Serious adverse reactions occurred in 15% of patients who received ONUREG. Serious adverse reactions in ≥2% included pneumonia (8%) and febrile neutropenia (7%). One fatal adverse reaction (sepsis) occurred in a patient who received ONUREG.
Most common (≥10%) adverse reactions with ONUREG vs placebo were nausea (65%, 24%), vomiting (60%, 10%), diarrhea (50%, 21%), fatigue/asthenia (44%, 25%), constipation (39%, 24%), pneumonia (27%, 17%), abdominal pain (22%, 13%), arthralgia (14%, 10%), decreased appetite (13%, 6%), febrile neutropenia (12%, 8%), dizziness (11%, 9%), pain in extremity (11%, 5%).
LACTATION

There are no data regarding the presence of azacitidine in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with ONUREG and for 1 week after the last dose.
Please see full Prescribing Information and Summary of Product Characteristics for ONUREG.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

On June 18, 2021 Cyteir Therapeutics, Inc. ("Cyteir") (Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetically lethal therapies for cancer, reported the pricing of its initial public offering of 7,400,000 shares of its common stock at an initial public offering price of $18.00 per share (Press release, Cyteir Therapeutics, JUN 18, 2021, View Source [SID1234584166]). All of the shares are being offered by Cyteir. In addition, Cyteir has granted the underwriters a 30-day option to purchase up to an additional 1,110,000 shares of common stock at the initial public offering price, less the underwriting discounts and commissions. The shares are scheduled to begin trading on The Nasdaq Global Select Market on June 18, 2021 under the ticker symbol "CYT."

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The gross proceeds of the offering, before deducting underwriting discounts and commissions and other estimated offering expenses payable by Cyteir, are expected to be approximately $133 million excluding any exercise of the underwriters’ option to purchase additional shares. The offering is expected to close on June 22, 2021, subject to the satisfaction of customary closing conditions.

J.P. Morgan, Morgan Stanley and BofA Securities are acting as joint book-running managers for the offering and Wedbush PacGrow is acting as co-manager.

A registration statement relating to the shares being sold in this offering was declared effective by the Securities and Exchange Commission on June 17, 2021. The offering is being made only by means of a prospectus. Copies of the final prospectus relating to the offering may be obtained, when available, for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the final prospectus, when available, may be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014, or by telephone: 1-866-718-1649; or BofA Securities, Inc., NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department or by email at: [email protected].

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

On June 18, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, reported an update on the state of its business operations and other recent developments (Press release, Antengene, JUN 18, 2021, View Source,block%20CD73%20activity%20in%20vitro [SID1234606790]).

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Significant progress has been made with respect to our pipeline and business operations since the company’s IPO on November 20, 2020. During this period, Antengene continued to execute its dual-engine growth strategy leveraging both external partnerships and in-house discovery and have built a pipeline of thirteen assets, five with APAC rights and eight with global rights. Antengene has advanced the clinical trials of our six in-licensed assets in APAC and have continued to expand its pipeline through internal discovery efforts with the announcement of two additional novel targets into our pipeline. In addition, Antengene is reaching an inflection point in its transition from a clinical stage to a commercial stage company, and has further built out its commercial infrastructure in multiple APAC markets in preparation for the commercial launch of selinexor towards the end of 2021.

Corporate Updates

As of June 18, 2021, Antengene has built a strong and dedicated team of over 200 full time employees, over a third of whom are in research and development.
With the expected approvals for selinexor across multiple APAC markets towards the end of 2021, Antengene has continued to build up its experienced commercial team across China and the APAC region with plans to grow its commercial organization to up to 200 full time employees in functions including in-house marketing, field force, pricing and market access by the end of 2021.
In May 2021, Antengene completed its manufacturing center in Shaoxing. To date, Antengene has finished the GMP renovation of plant buildings that will house the packaging line for solid dose formulation, installed supporting facilities, and set up a quality control laboratory for raw materials and finished products.
In May 2021, Antengene has entered into a framework agreement with the Hangzhou Qiantang New Area Administrative Committee to build a drug discovery and manufacturing center for antibody biologics.
An Update on Pipeline Candidates

Asia Pacific Rights Portfolio

Selinexor

Selinexor is a first-in-class, only-in-class orally available XPO1 inhibitor being developed for the treatment of hematologic malignancies and solid tumors.

Data from the MARCH trial of selinexor published at ASCO (Free ASCO Whitepaper) annual meeting in June 2021 include an objective response rate (ORR) of 26.7% in all analyzed patients with relapsed or refractory multiple myeloma (RRMM) and an ORR of 33.3% in patients with triple-class-exposed RRMM. These data are consistent with that observed in the STORM trial, from which, data had supported the accelerated approval of selinexor by the U.S. Food and Drug Administration (FDA). In addition, the data also showed an ORR of 44.4% in patients who had received prior CAR-T therapies.
Antengene has submitted a new drug application (NDA) for selinexor to the National Medical Products Administration (NMPA) in January 2021 with priority review granted to the NDA in February 2021.
Multiple combination regimens of selinexor have already included in the 2021 Chinese Society of Clinical Oncology (CSCO) Guidelines.
Antengene submitted NDAs for selinexor in Australia, Korea, Singapore and Hong Kong, and plans to submit an NDA for three indications in hematologic malignancies in Taiwan in Q3 2021.
Antengene is exploring additional indications of selinexor through two global Phase III registrational trials for the treatment of relapsed or refractory diffuse large B-cell lymphoma (RRDLBCL, the XPORT-DLBCL-030 trial) and endometrial cancer (the SIENDO trial); two registrational trials for the treatment of RRDLBCL (the SEARCH trial) and RRMM (the BENCH trial) in China; and China-only trials including for the treatment of relapsed or refractory T-cell and NK/T-cell lymphoma (the TOUCH trial).
ATG-016 (Eltanexor)

Eltanexor is a next-generation XPO1 inhibitor being developed for the treatment of patients with myelodysplastic syndromes (MDS) or solid tumors.

Data with eltanexor published at ASCO (Free ASCO Whitepaper) annual meeting in June 2021 showed a bone marrow complete response (mCR) in 7 patients (47%) and a total disease control rate (DCR) of 80%, of the 15 efficacy-evaluable patients with MDS refractory to hypomethylating agents.
In May 2021, Antengene has treated the first patient in a Phase I/II trial of eltanexor in patients with MDS (the HATCH trial).
A Phase Ib/II trial of eltanexor in patients with advanced solid tumors (the REACH trial) is currently on-going in Mainland China.
ATG-008 (Onatasertib)

Onatasertib is a next-generation dual mTORC1/2 inhibitor being developed for the treatment of advanced solid tumors.

In April 2021, a Phase II trial of ATG-008 (the BUNCH trial) in patients with advanced solid tumors harboring NFE2L2, STK11, RICTOR or other specific genetic alterations has enrolled and treated its first patient in Mainland China.
The TORCH trial, as the first trial of ATG-008 for the treatment of Asian patients, is now enrolling at the 45mg cohort in this dose-optimization trial in late-stage HBV+ HCC patients.
The TORCH-2 trial, a combination trial of ATG-008 with a PD-1 antibody (Toripalimab) in advanced solid tumors and HCC, is now enrolling patients at its third dose cohort.
Preclinical data demonstrating the synergistic effect of the combination of selinexor and ATG-008 for the treatment of triple-hit diffuse large B-cell lymphoma were presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.
ATG-019 (PAK4 / NAMPT inhibitor)

ATG-019 is an orally bioavailable dual PAK4/NAMPT inhibitor with first-in-class potential in the treatment of non-Hodgkin lymphoma (NHL) and advanced solid tumors.

A Phase I clinical trial (TEACH) of ATG-019 in patients with advanced solid tumors or NHL has been initiated in Mainland China following the initial dose-escalation phase in Taiwan.
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ATG-017 (ERK 1/2 inhibitor)

ATG-017 is a potent and selective small molecule extracellular signal–regulated kinases 1 and 2 (ERK1/2) inhibitor in clinical development for advanced solid tumors and hematologic malignancies.

The on-going dose-escalation study of ATG-017 for the treatment of advanced solid tumors and hematologic malignancies in Australia (the ERASER trial) has completed the first 3 cohorts in solid tumors (5 mg QD, 5 mg BID and 10 mg BID), and has started treating patients in the fourth cohort (20 mg BID).
Preliminary data from the ERASER trial will be announced in 4Q 2021.
ATG-101 (PD-L1/4-1BB bi-specific antibody)

ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of cancer. ATG-101 can activate anti-tumor immune effectors by simultaneously blocking PD-L1/PD-1 binding and inducing 4-1BB stimulation. In the presence of PD-L1 over-expressed cancer cells, ATG-101 showed a significant and PD-L1 crosslinking-dependent 4-1BB agonist activity, thus enhancing therapeutic efficacy, and mitigating hepatoxicity simultaneously.

Antengene will initiate a first-in-human Phase I trial of ATG-101 in patients with metastatic/advanced solid tumors or non-Hodgkin’s B-cell lymphoma (B-NHL).
Antengene has submitted clinical trial applications to the Human Research Ethics Committee (HREC) in Australia for the first-in-human trial of ATG-101 in patients with metastatic/advanced solid tumors or non-Hodgkin’s B-cell lymphoma (B-NHL).
In addition, Antengene plans to submit Investigational New Drug (IND) applications for ATG-101 in the US and China in 4Q 2021.
ATG-101 demonstrated potent activity in preclinical animal models, including strong tumor-suppressing effect in models of PD-1/PD-L1 inhibitor-resistant or -relapsed tumors. Meanwhile, the GLP toxicology study of ATG-101 has produced results highlighting a favorable safety profile.
ATG-037 (Small molecule inhibitor of CD73)

ATG-037 is a highly potent, selective, orally-bioavailable small molecule inhibitor of CD73 that has best-in-class potential as either a monotherapy or in combination against a range of tumor types. It overcomes the ‘hook-effect’ of clinical anti-CD73 antibodies and could completely block CD73 activity in vitro.

On May 17, 2021, Antengene and Calithera Biosciences entered into an exclusive, worldwide license agreement for the development and commercialization of ATG-037, a small molecule inhibitor of CD73.
Antengene plans to submit IND application for ATG-037 in Australia, United States and China by the end of 2021.
ATG-018 (ATR inhibitor)

ATG-018 is a small molecule inhibitor targeting ataxia telangiectasia and Rad3 related (ATR) kinase being developed for the treatment of hematological malignancies and solid tumors.

ATG-018, an in-house discovered ATR inhibitor, is at the IND-enabling stage, targeting IND submissions in Australia, United States and China by the end of 2021, or the beginning of 2022.
ATG-022 (ADC Targeting Claudin 18.2)

ATG-022, an antibody drug conjugate targeting Claudin 18.2, is in the late pre-clinical research and GMP CMC stage. IND submissions are expected in 2022.
ATG-012 (KRAS inhibitor)

ATG-012, a KRAS inhibitor, and a potential combination agent with ATG-017 and ATG-101, is in late pre-clinical research stage, with IND submissions expected in 2022.
New Targets

ATG-031 is a potential first-in-class anti-CD24 monoclonal antibody being developed for the treatment of hematologic malignancies and solid tumors. ATG-031 potently stimulates macrophage-mediated phagocytosis and induces the destruction of cancer cells by blocking the ‘Don’t eat me’ signals characterizing the growth of many cancers. In pre-clinical research, ATG-031 demonstrated single agent anti-tumor activity in animal models and showed synergy with chemotherapies, checkpoint inhibitors, and other therapeutic agents. ATG-031 is at IND enabling stage.

ATG-027 is a potential first-in-class bispecific antibody being developed for the treatment of hematologic malignancies and solid tumors. ATG-027 blocks the PD-1/PD-L1 interaction and the B7H3 interaction with its ligand to stimulate the activation of immune cells and mediates anti-tumor effect. ATG-027 also leads to the elimination of B7H3-positive tumor cells through ADCC/CDC effect. ATG-027 showed potent in vivo anti-tumor activity in mouse tumor models. ATG-027 is at preclinical research stage.

"I am excited to announce Antengene’s discovery of two proprietary assets targeting two novel mechanistic pathways, namely ATG-031, a first-in-class CD24 antibody, and ATG-027, a first-in-class B7H3/PD-L1 bispecific antibody. These discoveries are yet another testament to our dual-engine drug development strategy. This year, we aim to advance ATG-101 into clinical development, as our internal development efforts continue to yield results. Moreover, we have recently obtained the global rights to ATG-037, an oral small molecule inhibitor of CD73 with best-in-class potential, and we are poised to advance the drug candidate into global clinical development in the near future," said Dr. Jay Mei, Founder, Chairman and CEO of Antengene.

"While in commercialization, we have built a world-class commercial organization in the APAC region, led by industry veterans with strong track record in successfully launching innovative oncology therapies in APAC markets, and deep expertise in the areas of multiple myeloma and lymphoma."

"In just half of a year, we further strengthened our pipeline through the addition of three assets that have enormous combinatory potential with other agents, broadening the therapeutic potential of our pipeline. Like many patients around the world, we have high expectations for these first-in-class therapies in the APAC region and we are committed to advancing the global development of these assets, and fulfilling our mission of ‘Treating Patients Beyond Borders’."

On June 18, 2021 Inhibikase Therapeutics, Inc. (Nasdaq: IKT) (Inhibikase), a clinical-stage pharmaceutical company developing therapeutics to modify the course of Parkinson’s disease and related disorders inside and outside of the brain, reported the closing of its previously announced underwritten public offering of 15 million shares of its common stock at a price to the public of $3.00 per share (Press release, Inhibikase Therapeutics, JUN 18, 2021, View Source [SID1234584129]). The gross proceeds to Inhibikase from the public offering, before deducting underwriting discounts and commissions and offering expenses payable by Inhibikase, were $45 million. Inhibikase has granted the underwriters a 45-day option to purchase up to an additional 2,250,000 shares of common stock, at the public offering price less discounts and commissions.

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Inhibikase intends to use the net proceeds from the public offering, together with existing funds, to fund the costs of a Phase 1b extension study for IkT-148009 in Parkinson’s patients and to validate target engagement markers in the central and peripheral nervous system; to fund production of IkT-148009 for Phase 1b and Phase 2 clinical studies and to fund a Phase 2 efficacy trial of IkT-148009 in Parkinson’s patients. This funding will further support the clinical dose calibration study(ies) of IkT-001Pro in healthy subjects to support approval under the Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act and to fund drug product production for IkT-001Pro. The balance will support general research and development activities, medicinal chemistry for additional molecules and IND-enabling studies, team building, and other general corporate activities.

ThinkEquity, a division of Fordham Financial Management, Inc., acted as sole book-running manager for the offering. JonesTrading Institutional Services LLC acted as the co-manager for the offering.

The offering was made pursuant to a registration statement on Form S-1 (File No. 333-257032) that was declared effective by the Securities and Exchange Commission (the "SEC") on June 15, 2021. A final prospectus related to the offering has been filed with the SEC and is available on the SEC’s website, located at www.sec.gov. Copies of the final prospectus relating to this offering may be obtained from the offices of ThinkEquity, a division of Fordham Financial Management, Inc., 17 State Street, 22nd Floor, New York, New York 10004, by telephone at (877) 436-3673, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Any offers, solicitations or offers to buy, or any sales of securities will be made in accordance with the registration requirements of the Securities Act of 1933, as amended.