On February 21, 2022 Sareum Holdings plc (AIM: SAR), the specialist drug development company delivering targeted small molecule therapeutics to improve the treatment of autoimmune diseases and cancer, reported its unaudited half-year results for the six months ended 31 December 2021 and provides an update on significant post-period developments (Press release, Sareum, FEB 21, 2022, View Source [SID1234608348]).

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The Company will be holding a presentation to investors on Monday, 28 February 2022, immediately following the planned extraordinary general meeting, via the Investor Meet Company platform – please click on this link to register to attend:

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OPERATIONAL HIGHLIGHTS (including post-period updates)

Proprietary Programmes – Selective TYK2/JAK1 Inhibitors

SDC-1801 (autoimmune diseases and severe Covid-19)

Progress made advancing SDC-1801 towards clinical development as a potential treatment for autoimmune diseases and the acute respiratory symptoms of Covid-19
Final toxicology and safety studies required to file for an exploratory Clinical Trial Authorisation ("CTA") were successfully completed in Q4 2021, and the final report is expected in Q1 2022
Preliminary findings from these studies continue to support Sareum’s plans to enter SDC-1801 into a first-in-human (Phase 1a) clinical study in healthy volunteers, and allow selection of an initial dose range
The CTA is expected to be filed during mid-2022
The synthesis of SDC-1801 drug substance under GMP conditions for formulating as an oral capsule is nearing completion. Development of the capsule formulation, also under GMP, intended for use in the Phase 1 trial is progressing to plan
Planning for first clinical study is underway and the trial is expected to begin in H2 2022, subject to CTA approval and drug product supply
SDC-1802 (cancer immunotherapy)

Translational studies underway to define the optimal cancer application prior to completing toxicology and manufacturing studies
New US patent granted (September 2021) strengthening patent protection for SDC-1802, which is now in place across all major territories
Licensed Programmes

SRA737: A Selective Chk1 inhibitor (cancer)

During the second half of 2021 and early 2022, Sierra Oncology, Inc. ("Sierra"), the licence holder for SRA737, noted it is finalising the design of several potential clinical trials to advance its pipeline candidates, including SRA737, which could start in 2022. These trials are expected to investigate SRA737 in combination with other agents in haematologic and solid tumour indications
The dosing of the first patient with SRA737 in any new clinical trial would result in a $2.0m payment from Sierra under the amended $290m licensing deal on SRA737 between Sierra and CRT Pioneer Fund LP. Under the amended agreement, Sareum continues to be eligible to receive a 27.5% share of this and any future milestone payments as well as royalties on any future sales
FINANCIAL HIGHLIGHTS (unaudited)

Raised £3.9m before expenses in the second half of 2021 largely through three subscriptions by high-net-worth individuals, bringing the total raised before expenses in 2021 to £6.3m
Cash at bank as of 31 December 2021 of £5.6m (£2.7m as of 30 June 2021; £1.3m as of 31 December 2020)
R&D tax credit of £0.2m received in December 2021
Loss on ordinary activities (after taxation) for the six months ended 31 December 2021 of £0.9m (2020: loss of £0.5m), reflecting the increased R&D expenditure required for preclinical development
Post Period End

On 4 February 2022, the Company published a circular containing details of the proposed adoption of new articles of association (the "New Articles") and a proposed 50:1 consolidation of the Company’s Ordinary Shares (the "Consolidation"). Implementation of the Consolidation and adoption of New Articles are both conditional upon approval by the Company’s shareholders at an extraordinary general meeting to be held at 2:30 p.m. on 28 February 2022 at The City Centre, 80 Basinghall Street, London EC2V 5AG. Copies of the Circular and Notice are available at www.sareum.com
Dr Tim Mitchell, CEO of Sareum, commented:

"We continue to advance SDC-1801 towards its first clinical trial as a potential new treatment for autoimmune diseases including the acute respiratory symptoms of Covid-19. The preliminary findings from the safety and toxicology studies completed in late 2021 were highly encouraging and give us confidence in the promising safety profile of SDC-1801. We look forward to receiving the final report in the coming weeks, and to progressing our plan to begin the first clinical trial with SDC-1801 during H2 2022 – an important and exciting milestone for Sareum and supported by the substantial additional funding raised during 2021. These new funds will also enable us to accelerate the preclinical development of SDC-1802 through preclinical development.

"Furthermore, we are also very encouraged that Sierra Oncology is considering several clinical combination studies with SRA737 and that these may begin in the first half of 2022. We look forward to further updates on the clinical development of this candidate as the programme progresses."

On February 21, 2022 AstraZeneca reported that Positive high-level results from the pivotal DESTINY-Breast04 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer regardless of hormone receptor (HR) status versus physician’s choice of chemotherapy (Press release, AstraZeneca, FEB 21, 2022, View Source [SID1234608350]).

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Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

All patients in the trial received a HER2 test, and the results were centrally confirmed. HER2-low status was defined as an immunohistochemistry (IHC) score of 1+ or IHC 2+ with a negative in-situ hybridisation (ISH) score.

Up to 55% of all patients with breast cancer have tumours with a HER2 IHC score of 1+, or 2+ in combination with a negative ISH test, a level of HER2 expression not currently eligible for HER2-targeted therapy.1,2 HER2-low expression occurs in both HR-positive and HR-negative disease.3

HER2 testing is well established to determine an appropriate treatment strategy in metastatic breast cancer. Targeting the lower range of HER2 expression may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer.4 Currently, chemotherapy remains the only treatment option both for patients with HR-positive tumours following progression on endocrine (hormone) therapy, and for those who are HR-negative.5

DESTINY-Breast04 met its primary endpoint, where Enhertu demonstrated superior PFS in previously treated patients with HR-positive HER2-low metastatic breast cancer compared to the standard-of-care chemotherapy. The trial met the key secondary endpoint of PFS in patients with HER2-low metastatic breast cancer regardless of HR status (HR-positive or HR-negative). The trial also met the key secondary endpoints of OS in patients with HR-positive disease and in patients regardless of HR status at interim analysis.

The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified. Overall interstitial lung disease (ILD) rates were consistent with that observed in late-line HER2-positive breast cancer trials of Enhertu, with a lower rate of Grade 5 ILD observed as determined by an independent adjudication committee.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said: "Today’s historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated. A HER2-directed therapy has never-before shown a benefit in patients with HER2-low metastatic breast cancer. These results for Enhertu are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorise and treat breast cancer."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo said: "Enhertu continues to redefine the treatment of HER2-targetable cancers. DESTINY-Breast04 is the first ever Phase III trial of a HER2-directed therapy in patients with HER2-low metastatic breast cancer to show statistically significant and clinically meaningful benefit in progression-free and overall survival compared to standard treatment. We look forward to sharing the detailed findings of DESTINY-Breast04 with the medical community and initiating discussions with regulatory agencies globally with the goal of bringing Enhertu to patients with metastatic breast cancer previously considered to be HER2-negative."

The data will be presented at a forthcoming medical meeting and shared with global health authorities.

Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

Notes

Breast cancer and HER2 expression
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.6 More than two million cases of breast cancer were diagnosed in 2020 resulting in nearly 685,000 deaths globally.6

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers, and is one of many biomarkers expressed in breast cancer tumours.7 HER2 expression is currently defined as either positive or negative, and is determined by an IHC test which measures the amount of HER2 protein in a cancer cell, and/or an ISH test which counts the copies of the HER2 gene in cancer cells.7,8 HER2-positive cancers are defined as IHC 3+ or IHC 2+/ISH+, and HER2-negative cancers are currently defined as IHC 0, IHC 1+ or IHC 2+/ISH-.7

DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive (n=480) or HR-negative (n=60) HER2-low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomised 2:1 to receive either Enhertu or chemotherapy.

The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomised patients (regardless of HR status), OS in patients with HR-positive disease and OS in all randomised patients (regardless of HR status). Other secondary endpoints include PFS based on BICR and investigator assessment, duration of response based on BICR and safety.

DESTINY-Breast04 enrolled approximately 540 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for Enhertu are currently under review in Europe, Japan, the US and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

Enhertu also is currently under review in Europe for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2 based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. Lynparza has also demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival versus placebo in the adjuvant treatment of patients with germline BRCA-mutated HER2-negative early breast cancer. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

On February 20, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported the first patient dosing for its first-in-class IgG-based universal "modular" Claudin 18.2-targeting chimeric antigen receptor T (CAR-T) cell product (development code: IBI345) for the treatment of advanced Claudin18.2-positive solid tumors in an investigator-initiated-trial (IIT) (Press release, Innovent Biologics, FEB 20, 2022, View Source [SID1234608339]). Since Innovent announced its strategic cooperation with Roche on June 9, 2020, this is the first disclosure of the development milestone for the cell therapy products based on Roche’s proprietary innovative technology platform.

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The study (NCT05199519) is an investigator-initiated clinical trial with the primary objective of evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345 in subjects with Claudin18.2-positive solid tumors.

CAR-T cell therapy has established a meaningful role in the treatment of hematological tumors with 5 products approved by the FDA, and 2 by the NMPA in China, respectively; however, antitumor efficacy for solid tumors remains a challenge calling for technological breakthroughs. As the world’s first universal "modular" CAR-T cell product, IBI345 has potentially differentiated advantages over conventional CAR-T cell therapy products, including: 1) leveraging antibody function to target tumor antigens and consequently amplifying the tumor antigen signal to guide CAR-T cells to enter the tumor, thus aiding in the initiation of tumor recognition and killing; 2) controlling the functional activity of the CAR-T cells via concomitantly administered antibodies which act as a bridge between the target cell and CAR-T cell, potentially providing a better safety profile; 3) allows for the sequential or simultaneous administration of more than one antibody targeting different antigen targets without changing CAR-T cells, to treat tumors with highly heterogeneous antigen expression or relapsed tumors due to antigen-loss, thereby improving the accessibility and increasing the flexibility of CAR-T cell therapy for patients.

The principal investigator of the study, Professor Weichang Chen, the Secretary of the Party Committee and Chief Physician of the Department of Gastroenterology of the First Hospital Affiliated to Soochow University, pointed out: "As gastric and pancreatic cancer are highly aggressive tumors with high incidence rates in the world, patients are in urgent need of novel treatment options to improve clinical outcomes. IBI345, with its unique design to control CAR-T functional activity through the antibody bridging, will likely provide improved safety and efficacy. We look forward to the positive results of the safety, tolerability and efficacy data of IBI345 in patients with solid tumors, which will potentially provide a new option for the treatment of patients with advanced gastric or pancreatic cancer."

Dr. Xu Wei, VP of Innovent, R&D Head of Cell Therapy, said: "IBI345 is a highly differentiated CAR-T cell product with a new mechanism of action developed by Innovent based on Roche’s proprietary technology. As a universal "modular" CAR-T cell therapy product, equipped with a precisely targeted antibody switch, it regulates the expansion of CAR-T cells to control side effects, potentially providing an opportunity to switch to another antibody that targets different antigens to prevent recurrence and treat different tumors. Our preclinical studies have validated this "modular" CAR-T technology, which provides us with the sufficient scientific data to initiate clinical studies. In the following clinical studies, we will explore the safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345, and optimize the clinical dosage and regimen to support the subsequent IND application. We firmly believe that Innovent will be able to introduce more innovative cell therapies through platform technology innovation, product transformation and in-depth collaboration with the clinical academic community that will ultimately benefit more patients and families."

About Claudin 18.2
Claudin protein is a critical component of tight junction complex molecules which play an important role in the life activities of the human body. On the one hand, tight junctions can function as a "barrier" to select the size and charge of substances, thereby regulating the transport of substances in the para-cellular pathway. For example, brain vascular endothelial cells can pass through this barrier, preventing blood from mixing with the extracellular fluid in the brain. On the other hand, tight junctions can also function as "fences", maintaining cell polarity by regulating the free diffusion of lipids and proteins between the apical and the basolateral membrane.

Claudin18.2 is a member of the Claudin protein family, which is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer such as gastric cancer, pancreatic cancer, esophageal adenocarcinoma, and colorectal adenocarcinoma. The unique feature of limited expression in normal tissues and highly specific expression in cancer makes Claudin18.2 an ideal target for developing the immunotherapeutic for solid tumors.

Globally, there is currently no therapy targeting Claudin18.2 approved for marketing, but there are many candidate therapies in clinical development. The drug modalities under development include monoclonal antibodies, bispecific antibodies, antibody-conjugated drugs and CAR-T cell products.

About Gastric and Pancreatic adenocarcinoma
Gastric and pancreatic cancer are both malignant tumors of the digestive system that seriously endanger human life and health. The latest global cancer statistics show that there will be about 1.089 million new cases of gastric cancer worldwide in 2020, accounting for 5.6% of the global cancer incidence, and about 768,000 deaths, accounting for 7.7% of the global cancer deaths. There are about 495,000 new cases of pancreatic cancer, accounting for 2.6% of the global cancer incidence, and about 466,000 deaths, accounting for 4.7% of the global cancer deaths. According to the national cancer statistics released by the National Cancer Center of China in 2019, the incidence of gastric cancer in China in 2015 was about 403,000, accounting for 10.26% of the total cancer incidence, second only to lung cancer at 20.03%, with an incidence rate of 29.31/100,000 people, and about 291,000 deaths, accounting for 12.45% of the total cancer deaths, behind lung and liver cancer, with a mortality rate of 21.16/100,000 people. In 2015, the number of cases and deaths of pancreatic cancer nationwide were 95,000 and 85,000 respectively, ranking the 10th and 6th in the incidence and mortality of malignant tumors. The mortality ratio of pancreatic cancer was 0.89, making it a true "King of Cancer". Despite the treatment progress in recent years, drug resistance, recurrence and metastasis are still inevitable. The 5-year survival rate of patients with advanced gastric cancer is about 5-20%, and the median survival rate is about 10 months. Pancreatic cancer has a worse prognosis, with a 5-year survival rate of only 6 to 8%.

About IBI345
IBI345 is the first universal "modular" CAR-T cell product developed by Innovent based on Roche’s proprietary technology. It is an internationally pioneered highly differentiated CAR-T cell product with a new mechanism of action. Different from conventional CAR-T cells that directly recognize and kill tumor cells, IBI345 comprises of two components, anti-Claudin18.2 antibodies and "modular" CAR-T cells where anti-Claudin18.2 antibody recognizes tumor antigen, thus calibrating and amplifying the antigen signal, and guides "modular" CAR-T cells to enter the tumor to initiate the cytotoxic and antitumor activity of CAR-T cells. Compared with conventional CAR-T cells, IBI345 has a variety of potential advantages, including dual effects of antibodies and CAR-T cells to increase antitumor efficacy, and flexible control of side effects by regulating CAR-T cell activity through antibodies; in addition, as having a universal CAR molecule, "modular" CAR-T cells can be easily switched to different antibodies without changing CAR-T cells, by sequentially or simultaneously administering more than one antibody targeting different antigen targets, to treat tumors with highly heterogeneous antigen expression or antigen-loss relapsed tumors, which holds a great potential to reduce the cost of CAR-T cell therapy and improve the accessibility of CAR-T cell therapy for patients.

Innovent announced that first patient dosing has been completed in February 2022 in the investigator-initiated clinical trial of IBI345 for the treatment of advanced Claudin18.2-positive solid tumors, and enrollment is currently ongoing. The safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345 will be explored, and the clinical dosage and regimen will be explored to provide clinical data support for the subsequent IND application.

On February 18, 2022 Minomic reported that it will be at the ASCO (Free ASCO Whitepaper) GU Symposium, San Francisco, where Dr Neal Shore, principal investigator, is presenting a poster on our study "MiCheck Prostate Blood Test for Aggressive Prostate Cancer Designed for the Clinical Lab Setting" (Press release, Minomic, FEB 18, 2022, View Source [SID1234608310]).

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Our poster will be displayed on Thursday Feb 17 at 11.30am Megan Henken will be there live and Doug Campbell and Brad Walsh will be joining online.

On February 18, 2022 Orion Biotechnology reported that Results from an Ongoing Phase I/II CYPIDES Trial of ODM-208 Presented at ASCO (Free ASCO Whitepaper)-GU Clinical phase I data on Orion Corporation’s ODM-208, a first-in-class oral, non-steroidal and selective inhibitor of CYP11A1, the first and rate-limiting enzyme of steroid biosynthesis, were presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) (Press release, Orion Biotechnology, FEB 18, 2022, View Source [SID1234608326]). CYPIDES phase 1 data shows that ODM-208 effectively blocked the production of all steroid hormones in men with metastatic castration-resistant prostate cancer (mCRPC) and showed promising anti-tumor activity in men progressing despite extensive prior treatment with both novel hormonal therapies (NHT’s) and taxanes. Treatment responses to ODM-208 especially occurred in men with activating androgen receptor (AR) mutations.

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ODM-208 is a complete blocker of steroid biosynthesis that suppresses the production of all steroid hormones and their precursors that may activate the androgen receptor (AR) signalling pathway. This is particularly relevant in patients with AR ligand binding domain (LBD) activating somatic point mutations, a mechanism of resistance to hormone-based therapies in metastatic castration-resistant prostate cancer (mCRPC). During treatment the patients receive hormone replacement therapy to ensure sufficient adrenal function.

In CYPIDES phase I, a total of 44 patients with median age of 70 years received ODM-208. Overall, 32% of the patients achieved a PSA (prostate specific antigen) decrease of ≥50%. Of patients with AR LBD mutation (17), 68% achieved a PSA decrease of ≥50%. Also, prolonged treatment responses were observed especially in patients with AR LBD mutation. Although tolerated by most patients, the main safety finding was adrenal insufficiency (AI). Overall, 14 (32%) patients experienced severe adrenal insufficiency despite the replacement therapy requiring further adrenal supplementation after which the ODM-208 treatment commonly continued. Non-adrenal adverse events were unremarkable.

Taru Blom (MD, PhD), Vice President, Global Development and CMO, Orion R&D comments:

"ODM-208 is a first-in-class CYP11A1-inhibitor and we are excited that this novel approach works in some of the patients who have only a few effective treatment options available. The first results of CYPIDES are encouraging, and more studies are needed to confirm the potential of ODM-208 as a treatment option for men with advanced prostate cancer. In addition, we are focusing on the safety findings of the study as well as are looking into the optimization of the adrenal balance of the patients through appropriate replacement therapy."

More information about the CYPIDES trial: www.clinicaltrials.gov, Identifier: NCT03436485

The Phase II dose expansion part of CYPIDES is ongoing.

Phase I/II clinical trial CYPIDES

The Phase I/II trial CYPIDES investigates the safety, pharmacokinetics and anti-tumor activity of ODM-208 in men with mCRPC. The Phase I started in 2018 and has recruited 44 patients. More information about the trial: www.clinicaltrials.gov, Identifier: NCT03436485

ODM-208 investigational drug

ODM-208 is a novel, oral, non-steroidal and selective inhibitor of CYP11A1 enzyme developed by Orion for the treatment of prostate cancer. CYP11A1 is the rate-limiting enzyme of the steroid biosynthesis. By inhibiting CYP11A1 enzyme activity, ODM-208 suppresses the production of all steroid hormones and their precursors that may activate AR signalling pathway. Orion is the first pharmaceutical company to develop a selective drug that works by this mechanism.