On October 20, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM; HKEX: 13) reported that on October 20, 2021, it granted conditional awards ("LTIP Awards") under the Long Term Incentive Plan adopted by HUTCHMED in 2015 ("LTIP") (Press release, Hutchison China MediTech, OCT 20, 2021, View Source [SID1234591587]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Aimed at attracting and retaining top talent, the Remuneration Committee of HUTCHMED appointed an independent advisor to conduct a compensation benchmarking research on peer group U.S. and China biotech companies. The Remuneration Committee comprehensively reviewed the compensation and share-based incentives policies of HUTCHMED and its subsidiaries (the "Group") and established an attractive policy to ensure the Group is able to recruit and retain top talent. Vesting of share-based awards under the policy is in line with that peer group.

The compensation of the Independent Non-executive Directors ("INEDs") of HUTCHMED is structured approximately as one-third cash (in the form of Directors’ fees) and two-thirds restricted share units (in the form of non-performance related LTIP awards). Such restricted share units vest over four years in lieu of cash. All Directors’ compensation arrangements are approved by the Board of Directors with the relevant Directors declaring their interest and abstaining from voting where it relates to their fees/restricted share units. In addition, the Nomination Committee of HUTCHMED assesses the independence of all the INEDs every year having regard to the criteria under the applicable corporate governance code adopted by the Company. Therefore, the current compensation arrangements will not compromise the INEDs independence.

Non-performance-related LTIP Award for the HUTCHMED Financial Year 2021 ("Non-performance LTIP Awards") – a one-off cash amount was granted to each grantee and will be used by the trustee administering the LTIP (the "Trustee") to purchase shares in HUTCHMED ("Shares") which will be subject to a vesting period of four years. HUTCHMED has granted the following Non-performance LTIP Awards to the following Directors:

Award Holder Cash amount for the Non-performance LTIP Awards
Mr Simon To (Executive Director) US$250,0001
Dr Dan Eldar (Non-executive Director ("NED")) US$250,000
Ms Edith Shih (NED) US$250,0002
Mr Paul Carter (INED) US$250,000
Dr Karen Ferrante (INED) US$250,000
Mr Graeme Jack (INED) US$250,000
Professor Tony Mok (INED) US$250,000

Notes:

(1) Similar to the arrangement for his Director’s fees, this cash amount would be used by the Trustee to buy Shares which will be held by the Trustee until the LTIP concerned is vested, with 25% to be vested in each of the next four years, whereupon the Shares will be received by or for the account of his employer, Hutchison Whampoa (China) Limited.
(2) Similar to the arrangement for her Director’s fees, this cash amount would be used by the Trustee to buy Shares which will be held by the Trustee until the LTIP concerned is vested, with 25% to be vested in each of the next four years, whereupon the Shares will be received by or for the account of her employer, Hutchison International Limited

The cash amount will be used by the Trustee to buy Shares which will be held by the Trustee until the underlying Non-performance LTIP Awards are vested. 25% of the Shares bought by the Trustee will vest on each anniversary of the grant of the Non-performance LTIP Awards for the next four years.

As each of the Directors is a connected person of HUTCHMED, the grant of the LTIP Awards to each of them constitutes a connected transaction of HUTCHMED under Chapter 14A of the Rules Governing the Listing of Securities on The Stock Exchange of Hong Kong Limited (the "Hong Kong Listing Rules"). As the grant of the LTIP Awards to each of the Directors involves an amount less than the relevant de minimis level, it is fully exempt from the connected transaction requirements under Chapter 14A of the Hong Kong Listing Rules pursuant to the exemption under Rule 14A.76.

Further announcements will be made in due course at the time the Non-performance LTIP Awards are vested, when the number of the Shares to which each Director is entitled will be known. The above Directors additionally have the right to elect on acceptance of the grant of their awards to have part of their awards held (on behalf of the Director by the Trustee) pending vesting in the form of cash in order to satisfy any tax liability in respect of their awards.

The Directors are persons discharging management responsibility (PDMRs) for the purposes of the Market Abuse Regulation (EU) 596/2014 ("MAR") and the information in this announcement is provided in accordance with the requirements of Regulation 19(3) of MAR.

The LTIP does not constitute a share option scheme or an arrangement analogous to a share option scheme for the purpose of Chapter 17 of the Hong Kong Listing Rules.

On October 20, 2021 Biological Dynamics, Inc., a multiomics liquid biopsy company focused on detecting cancers at the earliest stages, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Device Designation for its liquid biopsy assay, Exo-PDAC (Press release, Biological Dynamics, OCT 20, 2021, View Source [SID1234591607]). The test is designed to provide early detection for pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive and lethal forms of cancer worldwide.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Early detection of pancreatic cancer in elevated risk individuals may help save a lot of lives," said Scott Lippman, MD, Director of Moores Cancer Center at UC San Diego Health. "The promise of Biological Dynamics’ cutting-edge exosomal isolation technology is addressing a critical, unmet medical need in our multidisciplinary and multi-dimensional fight against pancreatic cancer."

PDAC is projected to become the second leading cause of cancer-related deaths by 2040, due primarily to the fact that the disease is asymptomatic in its early stages. Therefore, patients are typically diagnosed during advanced stages of disease progression when treatments are limited. Detecting early PDAC biomarkers could help identify vulnerable patients before the disease progresses or metastasizes. However, it requires a high degree of sensitivity and specificity that conventional laboratory testing methods lack.

The Exo-PDAC diagnostic assay identifies exosomal biomarkers related to an elevated risk of pancreatic cancer, such as individuals with new-onset diabetes, a family history of pancreatic cancer, certain germline mutations, and other relevant factors that might be determined by the United States Preventive Services Task Force (USPSTF). Exo-PDAC is the first assay to use Biological Dynamics’ Verita platform, a novel alternating current electrokinetic-based technology applied for early disease detection, including cancer, Alzheimer’s disease, and infectious diseases. The test requires a small amount of blood from patients, which is then analyzed with minimal sample preparation or processing.

"For far too long, patients have needed innovative technologies with the potential to detect cancer at the earliest stages, and we look forward to working closely with the FDA, to do exactly that, with our pancreatic cancer test," said Biological Dynamics CEO Raj Krishnan, PhD. "And for us, this is an important milestone as we accelerate our vision of improving global health outcomes by advancing our unique multiomics platform for multiple cancers and other diseases."

According to the FDA, "The goal of the Breakthrough Devices Program is to provide patients and health care providers with timely access to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and de novo marketing authorization, consistent with the Agency’s mission to protect and promote public health."

On October 20, 2021 Herantis Pharma Plc ("Herantis or the Company"), focusing on disease modifying therapies for debilitating neurodegenerative diseases reported that it will October 26th, 2021 host an R&D Update Webinar (Press release, Herantis Pharma, OCT 20, 2021, View Source;2021,c3436290 [SID1234591571]). Herantis’ CEO Dr. Craig Cook and CSO Dr. Henri Huttunen will share progress in advancing Herantis’ HER-096 and rhCDNF programs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The R&D update will cover:

Information about Herantis’ novel biomarker focused development program
Data on efficient blood brain barrier (BBB) crossing
Results from pre-clinical experiments showing potent neuroprotective effects
Update on progress of its programs including non-invasive routes of administration
Registration Details:

Herantis Pharma’s R&D Update Webinar

Registered Here

The webcast will also be available under "Company Live Presentations" in the Investors section of the Herantis’ website at www.herantis.com/news-events/video-presentations/. There will also have an opportunity to ask questions in a live Q&A session with speakers. A replay of the webcast will be archived on Herantis’ website following the presentation.

About the Speakers

Dr. Craig Cook, MD, CEO of Herantis

Dr. Craig Cook, MD, is a medical doctor with an MBA from the London Business School and brings more than 20 years of experience in the international pharmaceutical and biotechnology sectors. Dr. Cook’s career has included increasingly senior roles in drug development and commercialization at major life science companies such as Eli Lilly, Johnson & Johnson, Novartis and EMD Serono, as well as entrepreneurial success in several healthcare initiatives. He was CEO of Midatech Pharma PLC, a dual Nasdaq and AIM listed biotech company, before deciding to join Herantis Pharma in 2020. He has worked across several therapeutic areas including neurology, immunology, and oncology.

Dr. Henri Huttunen, CSO of Herantis

Henri Huttunen co-founded Herantis Pharma Plc. in 2008 and served as the company’s founding CEO for the first two years. Dr. Huttunen is currently the Chief Scientific Officer of Herantis. Dr. Huttunen has previously held research positions at the University of Helsinki, Orion Pharma, and Massachusetts General Hospital, Harvard Medical School (USA). Dr. Huttunen has a PhD in biochemistry from the University of Helsinki and 25 years of experience in neuroscience research. While he was an adjunct professor, Dr. Huttunen lead an academic research group focusing on molecular mechanisms of neurodegenerative diseases at the Neuroscience Center, University of Helsinki.

On October 20, 2021 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported new data supporting novel capabilities of its CRISPR/Cas9 genome editing platform, which the Company plans to leverage for the development of future therapeutic candidates (Press release, Intellia Therapeutics, OCT 20, 2021, View Source [SID1234591588]). The data shared showed that Intellia’s allogeneic platform, leveraging a novel combination of sequential gene edits, can prevent immune rejection of allogeneic T cells in in vitro and in vivo models for future application in TCR-T and CAR-T therapy. Additionally, data highlighted that lipid nanoparticles (LNPs) can replace electroporation for delivery of CRISPR/Cas9 gene edits to T cells, avoiding the risk of chromosomal translocations observed when multiple edits are performed simultaneously, as well as the negative effect of electroporation on T cell health. Finally, results from an ongoing study demonstrated proof-of-concept in non-human primates (NHPs) for in vivo gene insertion and knockout for the treatment of alpha-1 antitrypsin deficiency (AATD), which resulted in sustained production of normal human levels of healthy alpha-1 antitrypsin (A1AT) protein and reduction of the endogenous disease-associated protein. The data were presented at the 29th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT) meeting, taking place virtually from October 19 – 22, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Preclinical data presented at ESGCT’s Annual Congress show that using our proprietary genome editing platform, Intellia is able to accomplish multiple CRISPR/Cas9 edits in both in vivo and ex vivo applications, advancing our efforts to develop treatments for challenging genetic diseases like alpha-1 antitrypsin deficiency and to potentially expand both the effectiveness and availability of engineered cell therapies for the treatment of cancer and autoimmune diseases," said Intellia President and Chief Executive Officer John Leonard, M.D. "This important preclinical work supports our mission as we look ahead to initiating a first-in-human study of NTLA-5001, our first ex vivo candidate, in patients with acute myeloid leukemia, and nominating at least one new development candidate before the end of this year as well as additional candidates in 2022."

Proprietary allogeneic solution that can be readily deployed for TCR-T and CAR-T therapy

Key immunological challenges remain unaddressed by allogeneic, or "off-the-shelf", T cell therapies currently in development for cancer treatment. Leveraging Intellia’s CRISPR/Cas9 platform and an innovative sequential gene editing process, the Company has developed a proprietary allogeneic solution that may avoid the need for long-term or aggressive immunosuppressive regimens and could be readily deployed for TCR-T and CAR-T therapy. The data shared at ESGCT demonstrate that a novel combination of targeted gene edits protected therapeutic T cells from host T cell as well as NK cell-mediated killing in in vitro and in vivo mouse models. Furthermore, these engineered cells showed no impairment in their tumor-killing ability in in vitro assays compared to their autologous counterparts. As part of these efforts, Intellia intends to nominate its first allogeneic cell therapy development candidate by the first half of 2022.

Using lipid nanoparticles to engineer next-generation CRISPR-based cell therapies

Adoptive cell therapies have been successful in certain cancers but have encountered technical and biological barriers, such as reliance on electroporation for editing of T cells, which impacts T cell viability, expansion and gene expression, and can lead to chromosomal translocations when used to introduce multiple simultaneous gene edits. At ESGCT, Intellia presented data demonstrating the use of LNPs to engineer CRISPR-based T cell therapies without the need for electroporation, advancing a robust, modular and scalable platform with the potential to enable future allogeneic and solid tumor therapies requiring multiple genome edits. The data showed that T cells engineered with LNPs showed efficient editing rates, with improved cell properties and performance both in vitro and in vivo, as compared to electroporation. In addition, the lower toxicity associated with LNP delivery allows Intellia’s platform to produce sequentially edited T cells with high efficiency, faster expansion and minimal translocations as compared to electroporation – demonstrated by targeting up to five or more loci (four knockouts and one to two targeted, in-locus insertions). The data support the ability of this platform to be used for a variety of targeting modalities, including CARs and TCRs, to support both autologous or allogeneic T cell candidates, including those requiring multiple edits to address immune rejection and activity in solid or other immune-suppressive tumors. This LNP-based approach is already being used for NTLA-5001, the Company’s first wholly owned ex vivo genome editing candidate, which is in development for acute myeloid leukemia. Intellia expects to initiate patient screening for the Phase 1/2a study of NTLA-5001 by year-end.

Tailored genome editing approach offers potential to independently treat liver and lung manifestations of alpha-1 antitrypsin deficiency (AATD)

New data shared at ESGCT represent the first reported demonstration of consecutive in vivo gene insertion and gene knockout in NHPs. This is an important step toward treating diseases such as AATD, which can manifest as lung disease (due to insufficient functional A1AT protein levels) or liver disease (due to accumulation of mutant A1AT protein) and thus require either inserting a functional gene, removing a disease-associated gene or both. The Company reported data showing that insertion of a healthy form of the SERPINA1 gene, which encodes the A1AT protein, led to normal human A1AT levels in NHPs which were durable through 52 weeks in an ongoing study. Intellia has also now tested the ability to knock out the endogenous cynomolgus SERPINA1 gene while leaving the inserted healthy human version intact. This insertion followed by knockout led to the continued production of normal human levels of functioning A1AT protein — substantially higher than what has been seen with other treatment approaches — as well as reduction of the disease-associated protein. Together, these data support the ability of Intellia’s in vivo genome editing platform to address the lung and/or liver manifestations of AATD as needed for a given patient.

Presentations will be available on Intellia’s website at www.intelliatx.com.

On October 20, 2021 Oncoinvent AS, a clinical stage company advancing a pipeline of radiopharmaceutical products across a variety of solid cancers, reported that it will present new preclinical data supporting the future clinical development of Radspherin, a novel alpha-emitting radioactive microsphere suspension designed for treatment of metastatic cancers in body cavities, in four digital presentations at the 34th Annual Congress of the European Association of Nuclear Medicine (EANM) (Press release, Oncoinvent, OCT 20, 2021, View Source [SID1234591608]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are thrilled to present these data at EANM, furthering our confidence in the potential of alpha-emitting radioactive particles for the treatment of metastatic cancers in body cavities," said Jan A. Alfheim, Chief Executive Officer of Oncoinvent. "These data demonstrate that Radspherin has potentially robust and retained biodistribution in body cavities, and give us important insights into the safety of clinical doses. We look forward to the continued clinical development of Radspherin in colorectal and ovarian cancer patients suffering from peritoneal carcinomatosis."

Synergy of 224Ra-labeled microparticles and chemotherapy in a murine ovarian cancer model
Presenting Author: Roxanne Wouters
Abstract Number: OP-0108

This preclinical study aimed to evaluate the effects of combining 224Ra-CaCO3-MP, radium-224-labeled calcium carbonate microparticles, with either first line chemotherapy for ovarian cancer, carboplatin-paclitaxel, or second line chemotherapy, carboplatin-pegylated liposomal doxorubicin (PLD), in an ovarian cancer model. Ovarian cancer mouse models were treated with 224Ra-CaCO3-MP (5 mg, 14-22 kBq/animal) one day following tumor cell inoculation. Additionally, 224Ra-CaCO3-MP treatment was combined with either carboplatin (100 mg/kg)-paclitaxel (10 mg/kg) on day 14, 21 or 28, or carboplatin (80 mg/kg)-PLD (1.6 mg/kg) on day 14.

Key results:

As a single treatment, 224Ra-CaCO3-MP delayed the onset of malignant ascites development compared to control.
When 224Ra-CaCO3-MP was administered in combination with carboplatin-PLD, survival was significantly prolonged compared to mice that received carboplatin-PLD alone.
Synergy when treating ovarian cancer cell lines with Radium-224 and PARP inhibitors
Presenting Author: Marion Masitsa Malenge
Abstract Number: EPS-064

This study evaluated the potential of combining radium-224 (224Ra), an alpha-emitter with 3.6 days half-life with the PARP inhibitors olaparib and niraparib to inhibit growth of ovarian cancer cell-lines. The effect of 224Ra in combination with olaparib and in combination with niraparib were evaluated in two human non-BRCA-mutated ovarian cancer cell-lines, ES-2 and SKOV-3. Cells were simultaneously treated with 224Ra and PARP inhibitors at escalating concentrations, and cell proliferation was measured 72, 96 and 120 hours after initiation of treatment.

Key results:

The combination index (CI) between both evaluated cell-lines was heterogenous across the tested range depending on the PARP inhibitor used in the combination, the concentrations of the combined drugs and the timepoint of assessment.
Combination treatment with PARP inhibitors and 244Ra was seen to be synergistic.
Biodistribution and dosimetry after intraperitoneal injection of 224Ra-labeled microparticles in rats
Presenting Author: Sara Westrøm
Abstract Number: EP-118

The presentation highlights the ex vivo biodistribution 224Ra-CaCO3-MP in preclinical models. In addition, dosimetry was calculated and extrapolated to the absorbed doses to human. 224Ra-CaCO3-MP (89 kBq/animal, 30 mg CaCO3) or vehicle was administered to preclinical rat models intraperitoneal. Ex vivo biodistribution was assessed at time points ranging from 2 to 336 hours post injection. For dosimetry calculations, the cumulated activity was determined by linear interpolation between the measured values. The dosimetry results were extrapolated to humans and scaling with relative biologically effectiveness (RBE) factors was performed.

Key results:

The majority of 224Ra was retained after intraperitoneal administration of 224Ra-CaCO3-MP.
Analyses of clinical pathology showed no treatment-related adverse effects, apart from a transient depression of neutrophils.
Dosimetry demonstrated that based on the low absorbed doses for all tissues, administration of up to 7 MBq 224Ra-CaCO3-MP, the maximum activity in ongoing Phase 1 studies, is deemed safe.
Dose response of 212Pb-labeled calcium carbonate microparticles in mice with intraperitoneal ovarian cancer
Presenting Author: Ruth Gong Li
Abstract Number: OP-0111

This study evaluated the intraperitoneal retention and biodistribution of 212Pb-CaCO3 microparticles in mouse models of ovarian cancer. Mice received a single intraperitoneal injection of either 2-5mg with doses ranging from 57-390 kBq 212Pb-CaCO3 microparticles, or vehicle.

Key results:

Calcium carbonate microparticles can be labeled with 212Pb in an easy, fast and efficient process; no chelator or co-precipitants are necessary.
212Pb-CaCO3 microparticles were retained in the peritoneal cavity.
The increased survival of mice with tumors that were treated with 212Pb-CaCO3 was dose-dependent and significant for all evaluated doses.