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

On March 29, 2021 Acacia Pharma Group plc ("Acacia Pharma", the "Group" or the "Company") (EURONEXT: ACPH), a hospital pharmaceutical company focused on the development and commercialization of new products aimed at improving the care of patients undergoing significant treatments such as surgery, other invasive procedures or cancer chemotherapy, reported its results for the year ended 31 December 2020 and provides an update on progress with the commercialization of BARHEMSYS and BYFAVO in the United States (Press release, Acacia Pharma, MAR 29, 2021, View Source [SID1234577239]).

A presentation by Acacia Pharma’s senior management team will be webcast live today at 14.30 CEST (08.30 EST) and participants can register by clicking here or from www.acaciapharma.com. A replay will be available after the event at the same link.

International conference call dial-in details are noted below.

The results report and presentation will be available at www.acaciapharma.com in the Investors section from 07.00 CEST today.

The full Annual Report and Financial Statements will be available on the Group’s website by 31 March.

Commenting on the results, Mike Bolinder, Chief Executive Officer, said: "Our vision to become a leading US hospital pharmaceutical company is on the road to being realized. The US approval and launch in the last year of two major new products in BARHEMSYS and BYFAVO is a tremendous achievement, practically unprecedented for a company of our size.

"Our early progress on formulary adoption for BARHEMSYS reflects the unmet need that exists in PONV and strong underlying demand for our product, our outstanding and extremely experienced commercial team and salesforce, as well as our well-constructed, well-executed launch plans. During 2021, we aim to continue gaining formulary access in our initial targeted accounts, as this will lay the strong foundation for significant revenue pull-through from 2022 onwards.

"Acacia Pharma is now at an exciting stage in its path to long-term commercial success, and we intend to continue to resolutely execute our plans as we bring these important new treatments to patients and at the same time build further significant value for our shareholders. I am once again truly grateful to our employees for their dedication and remarkable efforts during this year of outstanding progress against the challenging backdrop of the COVID-19 pandemic, and to our shareholders for their continued support."

Operating Highlights for 2020 and Significant Post-period Updates

US commercial infrastructure successfully built and fully operational
Highly experienced sales, marketing, medical affairs, commercial operations teams in place
Nationwide salesforce deployed against ~900 initial targeted hospital accounts since mid-October 2020
Two high-potential products approved by the US Food and Drug Administration (FDA) in 2020
BARHEMSYS (amisulpride injection)
Approved February 2020 in the US with a broad label for the treatment and prevention of postoperative nausea & vomiting (PONV)
First and only antiemetic approved for the rescue treatment of PONV in patients who have failed prior prophylaxis
Approximately 16m surgical patients each year in the US suffer from PONV despite receiving prophylaxis (ref.1)
Estimated $2.7 billion annual total addressable market (ref.2)
BYFAVO (remimazolam injection)
US commercial rights in-licensed from Cosmo Pharmaceuticals NV ("Cosmo") in January 2020
Approved July 2020 for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less
Key target: 40m procedures a year in US, including 25m gastro-intestinal procedures (ref.3)
Estimated >$1.5 billion annual total addressable market (ref.4)
Commercialization off to excellent start, with strong early formulary uptake
After deploying our sales team in mid-October, to date BARHEMSYS has been added to formulary at 120 institutions – Pharmacy & Therapeutics (P&T) Committee review success > 85%
Strong appreciation of clinical and health economic benefits of BARHEMSYS
BYFAVO launched at end of January 2021 and in eight weeks of launch is already approved on formulary in seven accounts
High level of enthusiasm from healthcare professionals for first major sedative launch in two decades
Management and Board Changes
Gary Gemignani appointed new CFO following planned succession succeeding Christine Soden who retired as CFO and from the Board in February 2020
Patrick Vink (Chairman), Pieter van der Meer and Johan Kördel stepped down from the Board of Directors at the 2020 AGM
Scott Byrd, a non-executive director of Acacia Pharma, was elected as Chairman at the AGM and Alessandro Della Chá, CEO of Cosmo Pharmaceuticals N.V. was appointed as a non-executive director
Named BEL Small Cap Company of the Year for the second consecutive year

Financial Highlights

Results are presented in US$, reflecting the currency of the majority of expected costs and revenues
Loss after tax for the year ended 31 December 2020 of $33.5m (2019: $22.8m):
The operating loss increased by $8.5m to $30.9m (2019: $22.4m), reflecting the investment in our US commercial infrastructure and product launch preparations
R&D expenses $0.1m (2019: $3.9m) with the reduction reflecting lower R&D activities on completion of BARHEMSYS clinical program, together with a $1.4m credit on reversing certain inventory provisions on the approval of BARHEMSYS
Sales and marketing expenses $19.4m (2019: $14.0m) reflecting increased activities leading up to the planned launch of BARHEMSYS and BYFAVO
General and administrative expenses $11.6m (2019: $4.4m) with 2020 costs higher as a result of fundraising activities, staff costs and amortisation of intangibles
Cash and cash equivalents as at 31 December 2020 of $46.7m (2019: $17.0m)
Balance sheet strengthened through €20m equity investment from Cosmo, €25m loan from Cosmo, together with €25m equity financing in August 2020
Additional equity financing undertaken in February 2021 with gross proceeds of €27m

Summary and Outlook for 2021

The Directors of Acacia Pharma are pleased with the excellent progress made since the beginning of 2020 in bringing two products forward to approval and now launch in the important US market. BARHEMSYS and BYFAVO are highly complementary products that together can efficiently utilize the commercial infrastructure that the Company has now built in the US.

The addition of the rights to BYFAVO along with the accompanying equity investment and debt facility from Cosmo as well as the recent equity raises have enhanced the Group’s ability to facilitate a successful launch and roll out of these products.

The early success with hospital formulary access for BARHEMSYS has confirmed the Directors’ belief in the strong product profile and compelling health economic arguments in favour of its adoption and use. This is an important first step to building a solid and growing sales platform for the product.

While it remains early days in the launch of BYFAVO, the Directors believe that it too offers significant medical and commercial value that will be viewed favorably by formulary committees and payors, as well as doctors and patients.

Conference call dial-in details

To join the conference call by telephone, please dial-in 5-10 minutes prior to the start using the password Acacia Pharma and any of the phone numbers provided below.

References
Calculations based on available procedural data, applied Compound Annual Growth Rate and quantitative market research responses as follows: National Hospital Discharge Survey, 2006; National Survey of Ambulatory Surgery, 2006 (as revised in 2009); Source Healthcare; NCHS 2005; Life Science Strategy Group, LLC Market Research; Apfel et al.,2004.
Based on the calculations in (1) multiplied by the number of doses per patient at a WAC price of $85 per 10mg dose.
iData Research, US Market Report Procedure Numbers for Gastrointestinal Endoscopic Devices February 2019; American Society of Anesthesiologists, Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018; and Quantitative Market Research prepared by The Link Group for Cosmo Technologies (March 2019).
Based on the calculation in (4) multiplied by the number of doses per patient at a WAC price of $39 per dose.

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