On March 29, 2021 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported the publication of Phase I data in The Journal of ImmunoTherapy of Cancer (JITC) (Press release, ImmunityBio, MAR 29, 2021, View Source [SID1234577246]). The publication, titled "Phase I study of a multitargeted recombinant Ad5 PSA/MUC-1/ brachyury-based immunotherapy vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC)" highlighted the safety, T-cell immunogenicity, and clinical activity of ImmunityBio’s second-generation human adenovirus (hAd5) in patients with incurable mCRPC. ImmunityBio’s hAd5 is designed to deliver tumor-associated antigens, or TAAs, and neoepitopes (expressed only by cancer cells) and has the capability to induce T-cell memory due to the activation of both CD4+ and CD8+ T cells along with antibody (or humoral) responses.

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"The finding of T-cell-mediated immunity induced in 100% of 17 prostate cancer patients whose white blood cells were evaluated in the study validates the ability of our hAd5 vaccine platform to generate a potent response to antigens delivered," said Patrick Soon-Shiong, M.D., Founder and Executive Chairman of ImmunityBio. "Furthermore, the demonstration that the vaccine can be administered repeatedly, without adverse effects at the dose of 5x 1011 viral particles, supports the application of this hAd5 platform in both cancer and infectious diseases such as COVID-19. These early results, which include signals of clinical activity and durable stable disease, are encouraging for patients with highly resistant advanced metastatic prostate cancer and warrants further study."

Study Highlights:

Eligible patients had to have incurable metastatic castration-resistant metastatic prostate cancer with radiologic evidence of progression or PSA progression
The vaccine was safe and well tolerated with no grade >3 treatment-related adverse events or dose-limiting toxicities (DLTs) observed
The recommended Phase II dose was 5×1011viral particles (VPs) administered three times repeatedly every 3 weeks
One patient achieved a partial response (PR), 5 patients had confirmed stable disease (SD) for greater than 6 months, with confirmed PSA decline
Median progression-free survival (PFS) was 22 weeks (95% confidence interval: 19.1 to 34)
Median overall survival (OS) was not reached, and the 12-month OS probability for all patients was 83.3% (95% confidence interval: 56.8% to 94.3%)
100% (17 out of 17) of patients mounted T-cell responses to at least one tumor-associated antigen and 16 of 17 (94%) patients developed T-cell responses to >1 antigen encoded by the vaccine
In the Phase 1 study undertaken in collaboration with Investigators at the Genitourinary Malignancy Branch of the National Cancer Institute, 18 patients with mCRPC who had advanced, incurable disease were given concurrently three hAd5 vaccines targeting PSA, brachyury, and MUC-1 at 5×1011 (VPs) each, subcutaneously every 3 weeks for a maximum of three doses (dose de-escalation cohort), followed by a booster vaccine every 8 weeks for 1 year (dose-expansion cohort only). Additional trial details can be found at clinicaltrials.gov-NCT03481816.

ImmunityBio has developed multiple product candidates that use this hAd5 viral vector to deliver tumor-associated antigens, which are being studied in multiple Phase I and Phase II clinical trials as potential vaccines for the treatment of solid tumors including breast, pancreatic, lung, head and neck, and prostate cancers. Importantly, these hAd5-based vaccines have shown an ability to overcome previous adenovirus immunity in cancer patients and in preclinical models. This same hAd5 viral vector has been applied for the treatment of infectious diseases and is in clinical trials for SARS-CoV-2 using hAd5 S+N as antigen constructs.

On March 29, 2021 Hutchison China MediTech Limited ("HUTCHMED") (Nasdaq/AIM: HCM) reported that on March 26, 2021, it granted conditional awards ("LTIP Awards") under the Long Term Incentive Plan adopted by HUTCHMED in 2015 ("LTIP") and share options under the Share Option Scheme adopted by HUTCHMED in 2015 as refreshed in April 2020 (the "Share Option Scheme") (Press release, Hutchison China MediTech, MAR 29, 2021, View Source [SID1234577245]).

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1. Performance-related LTIP Award for the HUTCHMED Financial Year 2021 ("Performance LTIP") – award based on a maximum cash amount, which amount is determined by the achievement of performance targets for the financial year ending 31 December 2021. The performance targets will be determined by the Remuneration Committee of HUTCHMED based on the strategic objectives of HUTCHMED.

The Shares, to be purchased by the Trustee following determination of the cash amount based on actual achievement of performance targets, will then be held by the Trustee until the underlying LTIP Awards are vested. Vesting will occur two business days after the date of announcement of the annual results of HUTCHMED for the financial year ending December 31, 2023. Vesting will also depend upon the continued employment of the award holder with the HUTCHMED group and will otherwise be at the discretion of the Board of Directors of HUTCHMED.

HUTCHMED has granted the following LTIP Awards for the Performance LTIP to the following PDMRs:

Award Holder Maximum amount for the Performance LTIP
Mr Christian Hogg (Executive Director and Chief Executive Officer) US$1,616,538
Mr Johnny Cheng (Executive Director and Chief Financial Officer) US$657,211
Dr Weiguo Su (Executive Director and Chief Scientific Officer) US$1,622,123
An additional 585 employees of HUTCHMED and its subsidiaries have simultaneously been granted LTIP Awards under the Performance LTIP.

2. Share Option Scheme

HUTCHMED granted share options under its Share Option Scheme to 147 employees to subscribe for a total of 8,279,900 Ordinary Shares represented by 1,655,980 American Depositary Shares ("ADSs") (each equating to five Ordinary Shares) subject to the acceptance of the grantee. Details of such share options granted prescribed are as follows:

Date of grant : March 26, 2021
Exercise price of share options granted : US$27.94 per ADS
Number of share options granted : 8,279,900 represented by 1,655,980 ADSs (five share options shall entitle the holder thereof to subscribe for one ADS)
Closing market price of ADSs on the date of grant : US$27.66 per ADS
Validity period of the share options : From March 26, 2021 to March 25, 2031
Among the share options granted, a total of 1,391,800 share options represented by 278,360 ADSs were granted to Mr Christian Hogg, Dr Weiguo Su and Mr Johnny Cheng (Executive Directors of the Company), being persons discharging managerial responsibility under the EU Market Abuse Regulation as follows:-

Grantee Number of share options granted
Mr Christian Hogg (Executive Director and Chief Executive Officer) 868,900 Ordinary Shares represented by 173,780 ADSs
Mr Johnny Cheng (Executive Director and Chief Financial Officer) 240,500 Ordinary Shares represented by 48,100 ADSs
Dr Weiguo Su (Executive Director and Chief Scientific Officer) 282,400 Ordinary Shares represented by 56,480 ADSs

(a) Mr Christian Hogg
1 Details of the person discharging managerial responsibilities/person closely associated
a) Name Mr Christian Hogg
2 Reason for the notification
a) Position/status Executive Director and Chief Executive Officer
b) Initial notification/Amendment Initial notification
3 Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor
a) Name Hutchison China MediTech Limited
b) LEI 2138006X34YDQ6OBYE79
4 Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted
a) Description of the financial instrument, type of instrument
Identification code
Option over American Depositary Share (each equating to five Ordinary Shares of US$0.10)

Option over American Depositary Share with ADS ISIN: US44842L1035

b) Nature of the transaction
Grant of options in respect of 868,900 Ordinary Shares represented by 173,780 ADSs under the Share Option Scheme.

The share options granted are exercisable subject to a vesting schedule of 25% on each of the first, second, third and fourth anniversaries of the effective date of grant.

c) Price(s) and volume(s)
Price(s) Volume(s)
Nil 173,780
d) Aggregated information
— Aggregated volume
— Price N/A
e) Date of the transaction 2021-03-26
f) Place of the transaction Outside a trading venue

(b) Mr Johnny Cheng
1 Details of the person discharging managerial responsibilities/person closely associated
a) Name Mr Johnny Cheng
2 Reason for the notification
a) Position/status Executive Director and Chief Financial Officer
b) Initial notification/Amendment Initial notification
3 Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor
a) Name Hutchison China MediTech Limited
b) LEI 2138006X34YDQ6OBYE79
4 Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted
a)
Description of the financial instrument, type of instrument

Identification code

Option over American Depositary Share (each equating to five Ordinary Shares of US$0.10)

Option over American Depositary Share with ADS ISIN: US44842L1035

b) Nature of the transaction
Grant of options in respect of 240,500 Ordinary Shares represented by 48,100 ADSs under the Share Option Scheme.

The share options granted are exercisable subject to a vesting schedule of 25% on each of the first, second, third and fourth anniversaries of the effective date of grant.

c) Price(s) and volume(s)
Price(s) Volume(s)
Nil 48,100
d) Aggregated information
— Aggregated volume
— Price N/A
e) Date of the transaction 2021-03-26
f) Place of the transaction Outside a trading venue

(c) Dr Weiguo Su
1 Details of the person discharging managerial responsibilities/person closely associated
a) Name Dr Weiguo Su
2 Reason for the notification
a) Position/status Executive Director and Chief Scientific Officer
b) Initial notification/Amendment Initial notification
3 Details of the issuer, emission allowance market participant, auction platform, auctioneer or auction monitor
a) Name Hutchison China MediTech Limited
b) LEI 2138006X34YDQ6OBYE79
4 Details of the transaction(s): section to be repeated for (i) each type of instrument; (ii) each type of transaction; (iii) each date; and (iv) each place where transactions have been conducted
a)
Description of the financial instrument, type of instrument

Identification code

Option over American Depositary Share (each equating to five Ordinary Shares of US$0.10)

Option over American Depositary Share with ADS ISIN: US44842L1035

b) Nature of the transaction
Grant of options in respect of 282,400 Ordinary Shares represented by 56,480 ADSs under the Share Option Scheme.

The share options granted are exercisable subject to a vesting schedule of 25% on each of the first, second, third and fourth anniversaries of the effective date of grant

c) Price(s) and volume(s)
Price(s) Volume(s)
Nil 56,480
d) Aggregated information
— Aggregated volume
— Price N/A
e) Date of the transaction 2021-03-26
f) Place of the transaction Outside a trading venue

On March 29, 2021 Hutchison China MediTech Limited ("HUTCHMED") (Nasdaq/AIM: HCM) reported that it has initiated two international Phase I studies of HMPL-306, its novel selective small molecule dual inhibitor of isocitrate dehydrogenase ("IDH") 1 and 2 mutations (Press release, Hutchison China MediTech, MAR 29, 2021, View Source [SID1234577242]). One trial is in patients with advanced solid tumors and one trial is in patients with hematological malignancies. Both trials have sites in the US and Europe. The first international patient was dosed on March 25, 2021, following a Phase I trial that was initiated in China in the second half of 2020. This new program is a demonstration of HUTCHMED’s accelerating and expanding global clinical development presence.

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These two trials are multi-center studies to evaluate the safety, tolerability pharmacokinetics, pharmacodynamics and preliminary efficacy of HMPL‑306. The first trial is in solid tumors (including but not limited to gliomas, chondrosarcomas, or cholangiocarcinomas), while a second trial is in advanced relapsed, refractory or resistant hematological malignancies that harbor IDH1 or IDH2 mutations. The first stage of each study is a dose escalation phase where cohorts of patients will receive ascending oral doses of HMPL‑306 to determine the maximum tolerated dose and/or the recommended Phase II dose ("RP2D"). The second stage is a dose expansion phase where patients will receive HMPL‑306 to further evaluate the safety, tolerability, and clinical activity at the RP2D. Additional details may be found at clinicaltrials.gov, using identifiers NCT04762602 and NCT04764474, respectively.

The MD Anderson Cancer Center ("MDACC") is the lead institution on both studies. The lead investigator for the hematological malignancies study is Dr. Farhad Ravandi, the Janiece and Stephen A. Lasher Professor of Medicine and Chief of Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MDACC. The lead investigator for the solid tumor study is Dr. Filip Janku, Associate Professor, Department of Investigational Cancer Therapeutics at The University of Texas MDACC.

A Phase I study of HMPL-306 is underway in China, with the first patient dosed in July 2020. Additional details of that study may be found at clinicaltrials.gov, using identifier NCT04272957.

HMPL-306 is HUTCHMED’s ninth innovative oncology drug candidate that it has discovered that has entered clinical development and the sixth to enter global clinical development. Cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 have been known to switch to the other form when targeted by an inhibitor of IDH1 mutant alone or IDH2 mutant alone. By targeting both IDH1 and IDH2 mutations, HMPL-306 could potentially provide therapeutic benefits in cancer patients harboring either IDH mutation, and may address acquired resistance to IDH inhibition through isoform switching.

About IDH and Malignancies
IDHs are critical metabolic enzymes that help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule that alters the cell’s genetic programming and prevents cells from maturing, 2-hydroxyglutarate ("2-HG"). Reduction in 2-HG levels can be used as a marker of target engagement by an IDH inhibitor. IDH1 or IDH2 mutations are common genetic alterations in various types of blood and solid tumors, including acute myeloid leukemia ("AML") with approximately 20% of patients having mutant IDH genes, myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), low-grade glioma and intrahepatic cholangiocarcinoma ("IHCC"). Mutant IDH isoform switching, either from cytoplasmic mutant IDH1 to mitochondrial mutant IDH2, or vice versa, is a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma.[1],[2],[3] Currently, the U.S. Food and Drug Administration (FDA) has approved one drug for IDH1 mutation and one drug for IDH2 mutation, but no dual inhibitor targeting both IDH1 and IDH2 mutants has been approved.

In the US, it is estimated that there were approximately 20,000 new cases of AML in 2020 and the five-year relative survival rate is 28.7%.[4]

IDH mutations are present in a number of solid tumors, including malignant glioma and IHCC. In the US, the annual incidence of malignant glioma is estimated to be 20,000, 50-70% of which are glioblastoma.[5],[6] Approximately 60-80% of Grade 2 or 3 glioma and secondary glioblastoma harbor IDH mutations.[7] IHCC accounts for 10-20% of primary liver cancer, which was estimated to be diagnosed in 42,810 US patients in 2020.[8],[9] Approximately 20-30% of IHCC harbors IDH mutations.[10]

On March 29, 2021 Genmab A/S (Nasdaq: GMAB) reported the initiation of a share buy-back program to mitigate dilution from warrant exercises and to honor our commitments under our Restricted Stock Units program (Press release, Genmab, MAR 29, 2021, View Source [SID1234577241]).

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The share buy-back program is expected to be completed no later than June 30, 2021 and comprises up to 200,000 shares.

The following transactions were executed under the program from March 22, 2021 to March 26, 2021:

Details of each transaction are included as an appendix to this announcement.

Following these transactions, Genmab holds 190,477 shares as treasury shares, corresponding to 0.29% of the total share capital and voting rights.

The share buy-back program is undertaken in accordance with Regulation (EU) No. 596/2014 (‘MAR’) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the "Safe Harbour Regulation." Further details on the terms of the share buy-back program can be found in our company announcement no. 11 dated February 23, 2021.

On March 29, 2021 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending an additional indication for the oral once-daily therapy XTANDITM (enzalutamide) for adult men with metastatic hormone-sensitive prostate cancer (mHSPC, also known as metastatic castration-sensitive prostate cancer or mCSPC) (Press release, Astellas, MAR 29, 2021, View Source [SID1234577240]).1 Men diagnosed with mHSPC tend to have a poor prognosis, with a median survival of approximately 3-4 years, underscoring the need for new treatment options.2

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If approved by the European Commission (EC), enzalutamide will be the only oral treatment approved by the EC to treat three distinct types of advanced prostate cancer — non-metastatic and metastatic castration-resistant prostate cancer (CRPC) and mHSPC.3 The CHMP decision is based on data from the pivotal Phase 3 ARCHES trial investigating enzalutamide in men with mHSPC.4

"This positive opinion from the CHMP is testament to our continuing commitment to addressing unmet needs for men with advanced prostate cancer," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas. "We are excited to be another step closer to approval of enzalutamide for the treatment of men with metastatic hormone-sensitive prostate cancer in Europe."

Data from the ARCHES trial showed that enzalutamide plus androgen deprivation therapy (ADT) significantly reduced the risk of radiographic progression or death by 61% versus placebo plus ADT in men with mHSPC (n=1,150; hazard ratio [HR]=0.39 [95% confidence interval (CI): 0.30-0.50]; P<0.0001).4

The safety analysis of the ARCHES trial appears consistent with the safety profile of enzalutamide in previous clinical trials in CRPC. In ARCHES, Grade 3 or greater adverse events (AEs) (defined as severe/disabling or life-threatening) were similar for patients receiving both enzalutamide plus ADT and those who received placebo plus ADT (24.3% vs. 25.6%).4

The positive opinion from the CHMP will now be reviewed by the EC, which has the authority to approve medicines for European Union member countries, as well as Iceland, Norway and Liechtenstein.5

Enzalutamide is currently approved in the EU for the treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) and adult men with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not yet clinically indicated, or following disease progression on or after docetaxel therapy.3 In the U.S., enzalutamide is approved in non-metastatic and metastatic CRPC as well as metastatic castration-sensitive prostate cancer (mCSPC) also referred to as mHSPC.6 In Japan, enzalutamide is indicated for the treatment of prostate cancer with distant metastasis, which includes mHSPC and CRPC.7,8