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KAIMRC NEWSLETTER ISSUE 11 OCT 2020 THE RESEARCHERinnovations.kaimrc.med.sa/en/newsletters

Highlights

KAIMRC research on MERS paves the 2 way for a COVID-19 candidate vaccine

Out-of-the-box approaches to 3 dental and cancer challenges

New initiative helps to turn 5 research into useful applications

KAIMRC and KAUST partnership in big 6 data heralds future R&D collaboration

the root canal wall. The key can be reversed to remove the post. Srayeddin hopes this will make LAYING THE FOUNDA- canal treatment safer and more comfortable. TIONS FOR A COVID-19 Cancer cues In a bid to improve the accuracy of targeted ra- CANDIDATE VACCINE diotherapy treatment, Mamdooh Alqathami developed a liquid nanocomposite which acts as a 3D biomarker for highlighting the borders of KAIMRC research on MERS contributed data for cancerous tumours. “The precise location of tu- adenovirus vector safety mours change continuously – for example, lung tumours move with every breath, and prostate

Some 18,000 people around the 2020 tumours shift depending on bowel fullness,” ex- world have received the vaccine plains Alqathami. “Targeted radiotherapy risks candidate AZD1222 as part of hitting healthy surrounding tissues, rather than PHASE III TRIALS OF a global effort to control the the tumour itself.” ASHRAF HABIB HABIB ASHRAF COVID-19 pandemic. AZD1222, Existing markers require large needles -to in COVID-19 VACCINE developed by the UK’s Oxford sert, and they sometimes migrate from their University, is one of nine can- target destination, causing side effects and treat- IN SAUDI ARABIA didates currently in Phase III ment errors. “Our biocompatible liquid reacts clinical trials for SARS-CoV-2. when exposed to moisture inside the body to KAIMRC and leading industry collaborators are working to The history of this candidate is form a 3D nano-composite, which attaches by intertwined with a KAIMRC-developed candidate vaccine to treat the covalent bonds to the border of the tumour, the bring one of the most promising COVID-19 vaccine candidates coronavirus that causes Middle East Respiratory Syndrome (MERS). tissue of interest, or both,” says Alqathami. “It can from the lab to the clinic AZD1222, previously known as ChAdOx1 nCov-19, is based on be detected using magnetic resonance imaging,

ChAdOx1, a weakened form of an adenovirus that natively infects computed tomography, ultrasound, and X-ray.” ANDRIY SHUTTERSTOCK.COM B/ King Abdullah International Medical Research Center (KAIMRC) is prepar- chimpanzees. To protect against coronavirus, the chimpanzee virus Another cancer-related patent has been regis- ing to start phase III clinical trials of one of the most advanced promis- is modified with genetic material encoding the SARS-CoV-2 spike tered by Ahmad Samir Aljada, who has developed ing COVID-19 vaccine candidates, CoronaVac, in partnership with Chinese protein so that it will instruct the patient’s cells to produce this vi- a simple, low-cost assay for diagnosing breast company Sinovac Biotech, who developed the drug. ral particle. The hope is that this trains the immune system to fight INVENTIVE cancer and other types of cancer. The assay does Abdelali Haoudi, Head of Strategy and Business Development at KAIM- COVID-19 if it is encountered. not require specialist knowledge to interpret, im- RC, lauded the “important, strategic, and exciting partnership” between ChAdOx1, developed by Oxford University in 2012, also forms proving the ease of use for physicians. the two organizations and with Pharmaserve, the Saudi pharmaceutical the basis of other vaccines that have been successful in trials. These APPROACHES “Our technique measures the ratio of lamin services company that will distribute the vaccine if it gets approved. include prophylaxes against tuberculosis, rabies, Zika, and MERS – a C to lamin A, two genes whose expression level KAIMRC and its partners are awaiting Saudi Food and Drug Administra- zoonotic disease that passed from camels to humans. MERS-CoV tion (SFDA) approval to begin phase III trials, which are the final stage of was identified for the first time in Saudi Arabia in 2012. After a string TO MEDICAL trials before a drug reaches the market. These are conducted after success- of infections and deaths leading up to a 2015 outbreak at a Riyadh “Current technology ful completion of preclinical studies and phase I and II trials, which assess hospital, KAIMRC began conducting clinical investigations to combat uses a tiny screw- safety and efficacy. the spread of MERS. CHALLENGES driver to insert posts The SFDA is in its final stages of review, which involves inspecting -Si In 2012, Naif Alharbi, now director of KAIMRC’s Vaccine Develop- manually, relying novac’s facilities in China. Once approved, clinical trials teams at multiple ment Unit, was studying for his PhD at Oxford University under the Innovation at KAIMRC and KSAU-HS leads to promising patent sites will begin recruiting volunteers, and Saudi Arabia will join Brazil and supervision of Sarah Gilbert at the time her team first reported the heavily on the practi- Indonesia in conducting phase III trials on CoronaVac. It is thought that the use of ChAdOx1 as a promising viral vector for vaccine research. In submissions for improved dental treatments, targeted radiotherapy, trials will last from four to six months. the wake of MERS, this led to the founding of a KAIMRC-Oxford col- and cancer diagnostics tioner’s skill.” “KAIMRC, Sinovac, and Pharmaserve have been ready to sign agreed laboration and the development of ChAdOx1 MERS. After promising contracts and collaborative agreements for about two months,” Haoudi ex- results in mice and camels, the Saudi Food and Drug Administration In 2020, scientists affiliated with KAIMRC and weaker than healthy teeth, and so a threaded ratio changes over time in cancer cells,” says -Al plains, adding that once they’re given the go-ahead, the three parties will gave its approval in late 2019 for a Phase I (first-in-human) clinical trial KSAU-HS registered patents for a dental tool root post is typically inserted to strengthen the jada. “The assay is particularly sensitive to stage conduct a signing ceremony to share their latest developments. of the vaccine, the first Phase I trial to ever conducted in the Kingdom. for use in root canal surgery, a liquid nanocom- tooth before restoration. 1 cancer and could provide rapid early diagnosis The partnership is very promising even in its infancy, says Haoudi. He The main difference between AZD1222 and ChAdOx1 MERS, says posite marker that pinpoints the borders of “Current technology uses a tiny screwdriver and inform patient treatment options.” describes the building of a solid foundation of “coordination, information Alharbi, is the use of either the SARS-CoV-2 or MERS-CoV spike pro- cancerous tumours, and a novel assay for diag- to insert posts manually, relying heavily on the KAIMRC actively encourages scientists to use sharing, and trust,” and says the collaboration will expand in scope in the tein. Combined with the relationship between these two pathogens, nosing cancers. practitioner’s skill,” says Srayeddin. “If the post their knowledge and skills to develop tools and future to develop new therapeutics and medical devices. The three entities both being of the genus Betacoronavirus, this means that studies into is fitted too forcefully, the stress creates cracks in techniques to further scientific progress. “I’m communicate continually to ensure their activities are in line with the most ChAdOx1 MERS yield transferrable knowledge that benefits AZD1222 Delicate dentistry the inner root canal.” delighted that KAIMRC applauds ‘out of the box’ stringent national and international regulations. research. “Previous safety and immunogenicity data resulting from Bassam Nawaf Srayeddin developed the den- Srayeddin’s post key incorporates springs that thinking,” says Imadul Islam, a senior KAIMRC re- “In history, few scientists working in isolation made important discov- the joint work between KAIMRC and Oxford” have helped the latter tal root post key to reduce the incidence of exert a dynamic but limited force when com- search scientist. “Our management teams give us eries,” Haoudi reflects. “But the world is changing. Collaboration, coopera- to be “much more ready” for SARS-CoV-2, says Alharbi. biomechanical tooth failures following root pressed. This allows for smoother insertion, and time and space to explore new concepts, and full tion, and shared insights are the keys to success.” canal treatment. Root canal-treated teeth are the post stops automatically when it contacts support for filing patents.” KAIMRC NEWSLETTER 4 THE RESEARCHER ISSUE 11 5

RESEARCHERS AT KAIMRC JOIN THE INTERNATIONAL RACE TO COMBAT SARS-COV-2

KAIMRC has joined with international partners to find a treatment for COVID-19 and a vaccine for its prevention

KAIMRC has invited Saudi Arabia’s hospitals to tigators are recruiting 520 adult patients- diag ers are generally at a higher risk of contracting participate in several clinical trials approved by nosed with moderate or severe COVID-19 for a SARS-CoV-2 than the general population. “It’s the Saudi Food and Drug Authority (SFDA) on randomized trial. easier to get concrete results by conducting the the novel Coronavirus in the hope of alleviating Bosaeed expects to get results by the end of trial on this high-risk group,” says Alharbi. “As in the COVID-19 pandemic. Researchers are taking the year. any other Phase 3 vaccine trial, to get reliable part in a global vaccine trial, while also working results on safety and efficacy, we need a sample to develop treatments that could help until a Global vaccine trial size of several thousand.” vaccine is ready. There are also plans for KAIMRC to take part in

a global Phase 3 trial of a vaccine developed by 2020 Unique combination therapy China’s Sinovac, pending approval by SFDA. “As in any other A clinical trial led by Mohammad Bosaeed, an Sinovac’s vaccine is one of the few around Phase 3 vaccine infectious diseases consultant, aims to evalu- the globe that have successfully reached trial, to get reliable HABIB ASHRAF ate the efficacy and safety of a unique combi- Phase 3 trials with promising results, accord- nation therapy. ing to Ahmad Alharbi, a consultant in adult results on safety and Funding Committee for final approval. The treatment developed by the Saudi infectious diseases at King Abdulaziz Medical efficacy, we need a The fund provides monetary support, resourc- team is a combination of Favipiravir and hy- City in Riyadh who will lead the trial. The vac- INCUBATOR FUND ES- es, guidance and services to principal investiga- droxychloroquine. Favipiravir is approved for cine has passed animal testing and two phases sample size of several tors. Researchers will get access to the Medical sale as an influenza antiviral drug in Japan, of clinical trials in humans, testing its efficacy thousand.” TABLISHED TO FOSTER Biotechnology Park, an incubator facility located where it is available under the brand name and immunogenicity. within KAIMRC building. In addition to the park’s Avigan. Hydroxychloroquine is an antimalarial The Saudi phase 3 clinical trial intends to The trial will be a randomized, double-blind facilities and technical resources, investigators that was found to be a potential broad-spec- test efficacy, safety and persistence of immuni- study with a placebo-controlled arm. Alharbi THE DEVELOPMENT OF will receive guidance and support by experts. trum antiviral. ty following the vaccination of 6,000 volunteer believes preliminary results may be available six The type of support a project needs depends In eight hospitals across the Kingdom, inves- healthcare workers in 15 cities. Healthcare work- months after the trial begins. NEW TECHNOLOGIES on which stage it is at, explains Shuruq Al Yousef, Research Project Manager at Medical Biotech- nology Park. Some scientists need monetary sup- New initiative to help transform research into useful applications port, while others need to be connected to the private sector. “We help them at both stages,” she A funding initiative launched in August aims to -ac “The fund is designed to transition a research says. Al Yousef also underlines the fund’s unique- celerate the translation of innovative research con- finding from proof-of-concept to a functional ness. “It will encourage brilliant minds to contrib- cepts into commercial products in the health sector. medical product through prototype develop- ute and have this competition in order to transfer “There is usually very little opportunity to ment and ultimately product development and their working results into products.” translate new knowledge or innovation into im- commercialization,” explains Haoudi. “This - set Only a few weeks after its launch, the fund pactful products and solutions, which is a serious up is appealing to biotech start-up creation and was already supporting the development of an gap in the R&D and innovation journey,” says pharmaceutical industry partnerships, which is at innovative and promising medical device. The Abdelali Haoudi, head of KAIMRC’s strategy and the heart of diversification, and knowledge-based patented ‘Artificial Hypothalamus for Body Tem- business development and managing director of economy in the Kingdom of Saudi Arabia.” perature Regulation’ will help cool patients who the Medical Biotechnology Park. The new initia- Principal investigators from all fields of bio- may suffer from heatstroke during the Hajj, ad- tive is designed to bridge this gap by supporting medical research are invited to submit a pro- dressing a need identified through a clinical study. researchers in the development of proof-of-con- posal to the fund provided that they meet the “We anticipate that this fund will create a vi-

2020 cept systems or technology prototypes. These eligibility criteria. Proposals are reviewed by brant biotechnology and health entrepreneurial will demonstrate the value of research findings to the Medical Biotechnology Park, and qualified environment through the Medical Biotechnology attract private sector funding and partnerships. submissions are recommended to the KAIMRC Park,” says Haoudi. ASHRAF HABIB HABIB ASHRAF KAIMRC NEWSLETTER 6 THE RESEARCHER ISSUE 11 7

Brief summaries HIGHEST IMPACT Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations: Cooperation at local, regional, national and international levels will be necessary to determine the best KAIMRC PAPERS workflows for rapid diagnosis, isolation, management and prevention of COVID-19. In addition to increasing critical care bed capacity and other infrastructure and supplies, attention must be paid to appropriate staff IN 2020 management. Opportunities and challenges for telehealth within, and beyond, a pandemic: The COVID-19 pandemic has Title Journal KAIMRC Impact forced a revision of healthcare in the face of a rapidly authors factor evolving situation. Many countries have shifted towards quartile telehealth. This ranges from telephone and video con- sultations to sending patients home with devices such as pulse oximeters. Many of these changes may persist Intensive care management of Lancet YM Arabi 25.094 Q1 after the pandemic, but work practices and infrastruc- coronavirus disease 2019 (COVID-19): Respiratory ture must be in place to enable them. challenges and recommendations Medicine Ultrasound-Driven Two-Dimensional Ti3C2Tx MXene Hydrogel Generator: A tissue-mimicking hydrogel Opportunities and challenges for tele- Lancet Glob- R AlHazme, R 21.597 Q1 implantable generator was used to convert ultrasound into electric energy. The generator was able to quickly

2020 al Health health within, and beyond, a pandemic Allwihan charge electrical devices buried under a centimeter of beef. Ultrasound-Driven Two-Dimensional ACS Nano AA Alkenawi, 14.588 Q1 Evolution is the disguised friend of Islam: Religion and Ti3C2Tx MXene Hydrogel Generator HN Alshareef science should be treated separately in a balanced so- ASHRAF HABIB HABIB ASHRAF ciety. The theory of evolution should be taught freely in Muslim countries in the same manner as the theories Evolution is the disguised friend of Islam Nature M Alassiri 12.282 Q1 of gravity and relativity. “We anticipate Human NCKAP1L defects lead to a novel syndrome combining that this major Behaviour immunodeficiency, lymphoproliferation, and hyper- STRONG inflammation: Recessive mutation of the actin cyto- collaboration will skeleton regulator NCKAP1L causes immunodeficiency, NCKAP1L defects lead to a novel Journal of A Khan, W 11.743 Q1 lymphoproliferation, and hyperinflammation. There pave the way to syndrome combining immunodeficiency, Experimental Eyaid, F Alroqi was an inverted CD4/CD8 ratio, and patients’ T cells PARTNERSHIP lymphoproliferation, and Medicine showed impaired early activation, immune synapse future R&D between hyperinflammation morphology, and leading edge formation. In summary, NCKAP1L leads to broad immune dysregulation. our two institutions.” Biallelic MADD variants cause a phenotypic spectrum IN BIG DATA Biallelic MADD variants cause a phenotypic Brain M Alfadhel 11.337 Q1 ranging from developmental delay to a multisystem spectrum ranging from developmental disorder: data and artificial intelligence could yield- per Biallelic variants of MADD, the mitogen-acti- delay to a multisystem disorder vated protein kinase (MAPK) activating death domain Two of Saudi Arabia’s most distinguished research centers join forces to sonalized therapeutic opportunities that target protein, cause a pleiotropic disorder. Patients exhibit individual biological profiles. neurological, endocrine, exocrine, and haematological tackle key public health concerns Clinical, molecular, and biochemical Genetics in S Alameer, M 8.904 Q1 symptoms. MADD deficiency underlies multiple cellular With its prestigious centers spanning the delineation of asparagine synthetase Medicine Almuntashri, defects via changes in TNF-α-dependent signaling breadth of Saudi Arabia, KAIMRC is well placed, deficiency in Saudi cohort F Al-Hakami, pathways and defects in vesicular trafficking. King Abdullah International Medical Research led to the development of five major projects both geographically and academically, to de- W Eyadi, M Clinical, molecular, and biochemical delineation of Center (KAIMRC) is collaborating on a major spanning the disciplines of stem cell research, velop strong collaborative ties with other Saudi Alfadhel asparagine synthetase deficiency in Saudi cohort: Characterization of asparagine synthetase deficiency biomedical research initiative led by colleagues heat stroke, epigenetics, lung cancer, molecular institutions. The opening of KAIMRC’s Jeddah (ASNSD) revealed a range of phenotypes, including at the King Abdullah University of Science and imaging, and atherosclerosis. Each project will campus put the center on the doorstep of KAUST Defining clinical subgroups and genotype– Genetics in S Alameer 8.904 Q1 congenital microcephaly, facial dysmorphism, devel- Medicine opmental delay, brain abnormalities, spasticity, and Technology (KAUST). The KAUST Smart Health have a key investigator from each institution, and made it easy for scientists from both orga- phenotype correlations in NBAS-associated disease across 110 patients infantile-onset seizures. Initiative, launched in January 2020, is- ada with both organizations sharing equal funding nizations to “exchange visits and collaborate on Defining clinical subgroups and genotype–phenotype ta-driven research program which aims to bring responsibilities. research ideas of mutual interest,” says Haoudi. correlations in NBAS-associated disease across 110 Ribavirin and interferon therapy for Clinical YM Arabi, HH 8.313 Q1 together the expertise of clinicians, researchers, Haoudi reports that work is currently under- The academic cooperation that started sev- patients:Clinical subgroups were identified by analysis critically ill patients with Middle East Infectious Balkhy, F Alha- and the pharmaceutical industry to develop pre- way to finalize the collaborative agreements eral years ago through the drive of individual of individual from 97 families with biallelic pathogenic respiratory syndrome: a multicenter Diseases meed, E Alqa- NBAS variants. These subgroups can be used to guide cision therapies for some of the most pressing needed to officially launch the five projects. It researchers has since developed into a solid observational study sim, J Jose, JA patient management. medical concerns facing Saudi Arabians. is imperative that the framework underpinning institutional bond destined to further the aims Gramish, A Ribavirin and interferon therapy for critically ill KAIMRC is a key strategic partner in the the KAIMRC-KAUST partnership gives their re- of all involved. KAIMRC and KAUST share a pas- Aldawood patients with Middle East respiratory syndrome: a multicenter observational study: Smart Health Initiative, says Abdelali Haoudi, searchers the highest chance of success. sion for the pursuit of cutting-edge biomedical A retrospective study revealed that 90-day mortality of critically ill MERS KAIMRC’s head of strategy and business devel- In his presentation at KAUST’s WEP2020 research and a common focus on forming inno- Protein intake and outcome in Current YM Arabi, HM 3.775 Q2 patients was not reduced by RBV/rIFN therapy. Faster Opinion opment, and managing director of the Center’s conference , the director of the Smart Health vation-focused partnerships, Haoudi says. “We critically ill patients Al-Dorzi, M MERS-CoV RNA clearance rate was also not affected by in Clinical Sadat the treatment. Medical Biotechnology Park. Throughout this Initiative, Pierre Magistretti, said “biomedical anticipate that this major collaboration will Nutrition Protein intake and outcome in critically ill patients: year, KAIMRC and KAUST have extensively dis- innovation requires an integrated ecosystem of pave the way to future R&D between our two and A review of the impact of protein intake on the outcome cussed potential research themes in which they academia, hospitals, industry and service pro- institutions in the best interest of the local and Metabolic of critically ill patients found that the evidence is could launch joint explorations. The discussion viders,” and described how the power of big global research community.” Care inconclusive. The optimal amount remains unclear, and further research is needed. THE RESEARCHER innovations.kaimrc.med.sa/en/newsletters OCTOBER ISSUE NEWSLETTER KAIMRC 11

2020 NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH