RTEL1

Researchers introduce the 'Telomouse'. By making a subtle genetic alteration in standard lab mice, they've made the mouse telomeres, which protect the chromosome ends, more closely resemble those in humans. The Telomouse model, developed by incorporating a genetic variation from a mouse species with naturally shorter telomeres, provides a valuable resource for in-depth aging and cancer research. This discovery promises to reveal new insights into the genetics of aging and may contribute to enhanced longevity and well-being. In an exciting scientific breakthrough, a team of researchers led by Professor Yehuda Tzfati from the Institute of Life Science at the Hebrew University and Professor Klaus Kaestner from the University of Pennsylvania Perelman School of Medicine, has introduced the "Telomouse." This discovery involves changing just one tiny building block in one gene of ordinary lab mice, Mus musculus, to make their telomeres (our chromosome caps) look much more like the telomeres in humans. Telomeres hold a pivotal responsibility in safeguarding our genetic material and ensuring the orderly division of our cells. Maintaining their structural integrity and optimal length holds the potential to diminish the risk of cancer and facilitate a healthier aging process. However, a significant hurdle has emerged: conventional laboratory mice possess telomeres approximately five times longer than those in humans. This disparity has posed a formidable challenge in using mice models for comprehending the implications of telomeres for human aging and cancer. In the development of the Telomouse model, researchers turned their attention to a distinct mouse species, M. spretus, notable for its inherently shorter telomeres. Within the genetic code of these mice, a subtle variation within a pivotal protein known as RTEL1 was identified. By transferring this genetic distinction into typical laboratory mice, they succeeded in producing a lineage of mice with human-length telomeres. These novel Telomice exhibit robust health and reproductive capabilities, making them an exceptional resource for in-depth investigations into the complex realms of aging and cancer. This study illuminates the central role of RTEL1 as the arbiter of telomere length. A nuanced modification to this crucial protein has enabled scientists to fashion a mouse model that closely approximates the human telomere length. During the reaseach, the researchers also achieved an invaluable breakthrough in our ability to measure the length of each single telomere, and particularly the shortest telomeres in the cell which are the ones to dictate the cellular function and fate. They developed a novel method for measuring the precise length of individual telomeres using a new generation of DNA sequencing called nanopore sequencing. This method, termed 'NanoTelSeq', enables evaluating the 'telomeric health' in samples from blood or other tissues of healthy individuals, as well as patients of cancers and aging diseases, and improve diagnosis, prognosis and treatment of these patients. Professor Yehuda Tzfati, the principal investigator of this endeavor, posits, "The Telomouse model is promising to enrich our comprehension of the intricate nexus between telomeres, cancer and the aging process. I believe that NanoTelSeq will replace currently used methods, enable acurate evaluation of the telomere state in patients and healthy individuals, and reveal how it affects human health. Such insights will hopefully culminate in innovative strategies for combating cancer and fostering the well-being of aging individuals."

HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., Feb. 27, 2023 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM, HKEX:​13) today announces that it has completed patient enrollment of Phase II registration trial of amdizalisib in patients with relapsed or refractory follicular lymphoma (“FL”), a subtype of non-Hodgkin’s lymphoma (“NHL”). The last patient was enrolled on February 24, 2023. The clinical trial is a multi-center, single-arm, open-label clinical study to evaluate the efficacy and safety of amdizalisib once a day oral monotherapy in patients with relapsed/refractory FL or marginal zone lymphoma (“MZL”). The primary endpoint is objective response rate (“ORR”), with secondary endpoints including complete response rate (CRR), progression-free survival (PFS), time to response (TTR) and duration of response (DoR). A total of 108 relapsed/refractory FL patients were enrolled. The trial is being conducted in over 35 sites in China. Additional details may be found at clinicaltrials.gov, using identifier NCT04849351. Topline results on the FL patients in this trial are expected to be reported in the second half of 2023, followed by submission of results for presentation at an appropriate medical conference. If positive, HUTCHMED would initiate plans to apply for marketing authorization of amdizalisib for relapsed/refractory FL from the China National Medical Products Administration (NMPA). About PI3Kδ and NHL PI3Kδ (phosphoinositide 3-kinase delta) is a lipid kinase that controls the activation of several important signaling proteins. Upon an antigen binding to B-cell receptors, PI3Kδ can be activated through the Lyn and Syk signaling cascade. The abnormal activation of B-cell receptor signaling is closely related to the development of B-cell type hematological cancers, which represent approximately 85% of all NHL cases. Therefore, PI3Kδ is a target for drugs that aim to prevent or treat hematologic cancer. FL accounts for approximately 17% of NHL and MZL accounts for approximately 8% of NHL. In the U.S., there were estimated 13,000 and 6,000 new cases of FL and MZL in 2020, respectively. In China, there were estimated 16,000 and 7,000 new cases of FL and MZL in 2020, respectively.1,2,3 About Amdizalisib Amdizalisib (HMPL-689) is a novel, selective and potent oral inhibitor targeting the isoform PI3Kδ. Amdizalisib’s pharmacokinetic (“PK”) properties are favorable with good oral absorption, moderate tissue distribution and low clearance in preclinical PK studies, suggesting a low risk of drug accumulation and drug-to-drug interaction. Because of its high target selectivity and optimal PK profile, amdizalisib has the potential to demonstrate an optimal benefit-risk pro this class. In addition to the current Phase II trial and the supportive Phase I trial in China, amdizalisib is also being evaluated in combination with tazemetostat (a methyltransferase inhibitor of EZH2) in patients with relapsed or refractory lymphoma in a Phase II study in China. HUTCHMED currently retains all rights to amdizalisib worldwide. About HUTCHMED HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/​immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs now approved and marketed in China. For more information, please visit: or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of amdizalisib for patients with NHL, the further clinical development for amdizalisib, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of amdizalisib, including as a combination therapy, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of amdizalisib for a targeted indication, the sufficiency of funding and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. CONTACTS Investor Enquiries Mark Lee, Senior Vice President +852 2121 8200 Annie Cheng, Vice President +1 (973) 567 3786 Media Enquiries Americas – Brad Miles, Solebury Trout +1 (917) 570 7340 (Mobile) / bmiles@soleburystrat.com Europe – Ben Atwell / Alex Shaw, FTI Consulting +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com Asia – Zhou Yi, Brunswick +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley, Panmure Gordon +44 (20) 7886 2500 ______________________ 1 Source: NCCN® - 2 Source: SEER - 3 Source: GLOBOCAN -

Single-arm study in ~180 patients, with ORR as primary endpoint Relapsed/refractory FL and MZL constitute approximately 25% of all NHL HMPL-689 trials are also underway in these and other NHL subtypes in the U.S., Europe and China HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., April 29, 2021 (GLOBE NEWSWIRE) -- Hutchison China MediTech Limited (“HUTCHMED”) (Nasdaq/AIM: HCM) has initiated a registration-intent Phase II clinical trial of HMPL-689, its highly selective and potent PI3Kδ inhibitor, in China in patients with relapsed or refractory follicular lymphoma (“FL”) and marginal zone lymphoma (“MZL”), two subtypes non-Hodgkin’s lymphoma (“NHL”). The first patient was dosed today. The clinical trial is a multi-center, single-arm, open-label clinical study to evaluate the efficacy and safety of HMPL-689 once a day oral monotherapy in approximately 100 patients with relapsed/refractory FL and approximately 80 patients with relapsed/refractory MZL. Relapsed/refractory is defined when a patient has not achieved response (complete response or partial response) after the latest line of systemic treatment, or has progressive disease or relapse after achieving response. The primary endpoint is objective response rate (“ORR”), with secondary endpoints including complete response rate (CRR), progression-free survival (PFS), time to response (TTR) and duration of response (DoR). The trial is being conducted in over 35 sites in China. More information will be available at clinicaltrials.gov, using identifier NCT04849351. The initiation of the Phase II trial is based on the highly promising preliminary results from the Phase Ib expansion study ongoing in China, which show that HMPL-689 was well tolerated, exhibiting dose-proportional pharmacokinetics (“PK”), a manageable toxicity profile, and single-agent clinical activity in relapsed/refractory B-cell lymphoma patients. Additional details may be found at clinicaltrials.gov, using identifier NCT03128164. About PI3Kδ and NHL PI3Kδ (phosphoinositide 3-kinase delta) is a lipid kinase that controls the activation of several important signaling proteins. Upon an antigen binding to B-cell receptors, PI3Kδ can be activated through the Lyn and Syk signaling cascade. The abnormal activation of B-cell receptor signaling is closely related to the development of B-cell type hematological cancers, which represent approximately 85% of all NHL cases. Therefore, PI3Kδ is considered to be a promising target for drugs that aim to prevent or treat hematologic cancer. FL accounts for approximately 17% of NHL and MZL accounts for approximately 8% of NHL. In the U.S., there were estimated 13,000 and 6,000 new cases of FL and MZL in 2020, respectively. In China, there were estimated 16,000 and 7,000 new cases of FL and MZL in 2020, respectively 1,2,3. About HMPL-689 HMPL-689 is a novel, selective and potent oral inhibitor targeting the isoform PI3Kδ. HMPL-689’s PK properties are favorable with good oral absorption, moderate tissue distribution and low clearance in preclinical PK studies, suggesting a low risk of drug accumulation and drug-to-drug interaction. Because of its high target selectivity and optimal PK profile, HMPL-689 has the potential to demonstrate an optimal benefit-risk profile in this class. HUTCHMED has initiated an extensive, globally-focused clinical development pathway for HMPL-689. In addition to the currently Phase II trial and the supportive Phase I trial in China, HMPL-689 is also being evaluated in an ongoing Phase I/Ib study in the U.S. and Europe in patients with relapsed or refractory NHL. HUTCHMED currently retains all rights to HMPL-689 worldwide. About HUTCHMED HUTCHMED (Nasdaq/AIM: HCM) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. A dedicated organization of over 1,200 personnel has advanced ten cancer drug candidates from in-house discovery into clinical studies around the world, with its first two oncology drugs now approved and launched. For more information, please visit: or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of HMPL-689 for patients with FL, MZL and NHL, the further clinical development for HMPL-689, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of HMPL-689, including as a combination therapy, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of HMPL-689 for a targeted indication, the sufficiency of funding and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. CONTACTS ____________________________________________________________ 1 Source: NCCN® - 2 Source: SEER - 3 Source: GLOBOCAN