OUR APPROACH

We generate immune cells that lack specific surface molecules, thus enhancing their anti-cancer activity.

To generate these immune cells, there are many tools at our disposal including endonucleases, TALEN and CRISPR/cas systems. A unique tool that MediSix has for this purpose is PEBL, which has many potential advantages over gene editing technologies.

ENHANCED ACTIVITY AGAINST:

  • T-cell malignancies by engineering CAR T-cells lacking CD7, CD3, CD2 and/or other T-cell antigens

 

  • Other tumors by engineering CAR T-cells, TCR T-cells, TILs, or other immune cells that lack inhibitory molecules such as NKG2A, PD1, CTLA4, and TIM3

FACILITATED DEVELOPMENT OF:

  • T-cells devoid of graft-versus-host disease capacity by suppressing expression of the TCR/CD3 complex, a key step for allogeneic T-cell therapies
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PEBL

Our unique PEBL has been designed to circumvent current industry challenges, and thus provide much-needed new therapeutic options for patients

DESIGN AND DEVELOPMENT

The concept behind the PEBL is simple. It traps specific proteins deep inside the cell, thus preventing their expression.
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PEBL-CAR

When coupled with a CAR, we can therefore treat patients with T-cell malignancies, without the fratricide experienced by traditional CAR therapies to date and avoiding the need for gene editing

CAR T-cells have been used to treat B-cell lymphomas with great success. However, their use in T-cell malignancies comes with a new set of challenges to overcome, such as fratricide. Fratricide occurs when CAR T-cells kill each other, due to expression of shared target antigens.

CAR T-CELL

Without PEBL, the target protein (eg CD7) is synthesized in the endoplasmic reticulum and then expressed on the cell surface

PEBL CAR T-CELL

With PEBL, any newly synthesized protein (eg CD7) remains anchored in the ER and/or Golgi and is not expressed on the cell surface, thus preventing fratricide
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ADVANTAGES OF THE PEBL-CAR

Our PEBL-CAR pipeline will allow for application in multiple diseases through a variety of treatment modalities.

CAR T-cell
therapy

Using PEBL-CAR T cells to address challenging T-cell malignancies is at the heart of our business

Next-generation
CAR T

Our teams are constantly working to improve and enhance the effectiveness of our platform

Development of
allogeneic therapies

Deeper exploration of the PEBL technology to create allogeneic CAR T-cell therapy is currently underway

Expansion outside
oncology

Additional targets such as checkpoint proteins pave the way for application in multiple diseases

Alongside MediSix’s manufacturing and clinical strategies, PEBL technology provides solutions to all the major industry challenges associated with CAR T-cell therapy for T-cell malignancies.

Limitations and Solutions

Fraticide

Limitation

Car T-cells killing other CAR T cells

MediSix's solution

Development of novel PEBL to anchor target proteins intracellulary and downregulate cell surface expression, thus preventing fratricide

Long-term T-cell aplasia

Limitation

Car T-cells killing normal T cells

MediSix's solution

Initial application as bridging therapy to stem cell therapy ensures reconstitution of the compartment from donor stem cells, avoiding long-term T-cell aplasia
Residual CD7-low or CD7-negative cell subsets may also help to overcome the hostile tumor microenvironment and repopulate the T-cell repertoire

Product contamination

Limitation

Contamination with malignant cells during production

MediSix's solution

Flow cytometry quantification for each product lot prior to infusion minimizes risk of product contamination

Complex manufacturing processes

Limitation

Major protocol modifications to existing processes required for clinical-grade large-scale cell processing

MediSix's solution

The bi-cistronic vector enables expression of both PEBL and CAR proteins from a single mRNA, streamlining manufacturing to one transduction step and using components similar to those used for commercially-available CAR T products

Poor cell quality and insufficient quantity

Limitation

Low cell viability or poor manufacturing yield

MediSix's solution

Lack of requirement for electroporation helps to preserve cell viability and reduce cell loss during manufacturing, and may enable patients with lower T-cell count or proliferative capacity to benefit from therapy

PEBL has many advantages over gene editing technologies

  • Only single cell manipulation required when combined with CAR or TCR expression
  • Fits seamlessly in current GMP CAR T-cell manufacturing
  • No risk of non-specific gene editing
  • Possible down-regulation of isoforms
  • Possible tuning of downregulation
PEBL and gene editing methodologies are not mutually exclusive and can be used in combination. For example, PEBL could be expressed by using CRISPR instead of viral transduction, and multiple targets could be downregulated by combining the two approaches.

Copyright MediSix Therapeutics 2022

Yunqin Lee, PhD

Director of Discovery Sciences

Dr Lee is our Director of Discovery Sciences, where she evaluates and manages the transition of technologies or assets of interest into MediSix. She joined MediSix in 2018 and has more than 13 years of experience in immunology research.

 

Prior to joining Medisix, she was a Postdoctoral Research Fellow at the Singapore Immunology Network, where she studied the immunoprofile of solid tumors and the phenotype of tumor-associated macrophages. Yunqin holds a BEng in Biomedical Engineering from Imperial College London and her PhD in Immunology from Stanford University, where she studied immune evasion in cancer.

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Alicia Chua, BEng (Mech)

Assoc. Director of Development

Alicia joined MediSix as our Assoc. Director of Development, spearheading our Development team’s efforts to transition Discovery assets into clinical trials. She earned her B.Eng from Nanyang Technological University and worked as a Product Engineer for four years before making a daring career switch to Cell Therapy. She has since been a key contributor to developing manufacturing processes for Cell Therapy Products.

 

Before joining MediSix, Alicia was the Product Development Manager at Lion TCR. She specialised in crafting the production process for their TCR-T product had her work published in Hepatology and was integral to securing Phase 1B/2 FDA approval for their TCR-T product.

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George Poste, BSc, PhD, DVM

Board Member

Professor Poste has served on our Board of Directors since 2016. He is the Del E Webb Professor of Health Innovation and chief scientist with the Complex Adaptive Systems Initiative at Arizona State University (ASU). This program integrates research in genomics, synthetic biology and high performance computing to study the altered regulation of molecular networks in human diseases to develop new diagnostic tests for precision medicine and the remote monitoring of health status using miniaturized body sensors and mobile devices. He assumed this post in 2009. From 2003 to 2009, he directed and built the Biodesign Institute at ASU.

 

He is a fellow of the UK Royal Society, the Royal College of Pathologists and the UK Academy of Medicine, a member of the Council for Foreign Relations, and US National Academy of Medicine Board on Global Health. He has served as a member of the Defense Science Board of the US Department of Defense and currently serves on advisory committees for several US government agencies in defense, intelligence, national security and healthcare. George was recipient of the Scrip Lifetime Achievement Award in 2009 and named Scientist of the Year by R&D Magazine in 2004. George received his BSc, PhD and DVM at the University of Bristol, UK.

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William Harrington, BSc, MBA, MD

Board Member

Dr Harrington has served on our board since 2016. Bill has spent the last 20 years in venture capital and currently has been one of the managing partners at Osage University Partners (OUP) since 2011. Prior to this, he was General Partner at Three Arch Partners, a west coast venture capital firm with over $1 billion under management, where he focused on investing in life science companies including therapeutics, medical devices, and healthcare services. Bill was previously a practicing Interventional Radiologist in the San Francisco Bay Area.

 

Bill earned his BSc from Tufts University, summa cum laude, an MD from Harvard Medical School, and an MBA from the Haas Business School, University of California, Berkeley. Bill is a holder of the Chartered Financial Analyst designation. Bill is a member of the Board of Trustees at The Haverford School in Haverford, PA.

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Michael Carusi

Board Member

Michael Carusi has served on our board of directors since 2016. He is an experienced venture capitalist focusing on investments in the biopharmaceutical and medical device sectors. He serves as a general partner for Lightstone Ventures based out of Palo Alto, CA where he is also a General Partner for Advanced Technology Ventures.

 

Featured on the Forbes Midas List of top technology investors, Mike is a recognized thought leader in the industry and a frequent speaker at healthcare conferences. He serves as a faculty member of the Stanford Biodesign Emerging Entrepreneurs Forum, sits on the Tuck MBA Advisory Board, and is an advisory board member to the UCSF/Berkeley Venture Innovation Program.

 

Earlier in his career, Mike served as a Director of Business Development for Inhale Therapeutic Systems and was a Principal at The Wilkerson Group. Mike has a BSc in Mechanical Engineering from Lehigh University, and an MBA from the Tuck School of Business.

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Peiying Chuan, PhD

Vice President, Strategy and Intellectual Property

With over 15 years of experience in the biomedical industry, Dr Chuan is our Vice President of Strategy and Intellectual Property Development, overseeing MediSix’s collaborative research and development efforts, intellectual property strategy and assets. Prior to Medisix, Peiying held various portfolios at the Agency for Science, Technology and Research (A*STAR).

 

Most recently, she spearheaded the creation of a large scale, first-of-its-kind research programme in Singapore, and was pivotal in forging global strategic alliances with public and private organisations.

 

Her other portfolios included shaping of public research and development policies, research grant administration, and project management. Peiying holds a BSE in Bioengineering from the University of Pennsylvania, and a PhD in Biochemistry from Stanford University.

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Ying Xim Tan, PhD

Director of Discovery Operations

Dr Tan is our Director of Discovery Operations, leading the Discovery team’s research efforts to advance MediSix’s pipeline. She joined MediSix in 2018 as a Research Scientist, and was a key driver in guiding the successful transition of our lead asset, PCART7, from discovery to development. Ying Xim has over 14 years of experience in immunology and cancer biology research.

 

She earned her BSc in Molecular and Cell Biology from the University of California, Berkeley and her PhD in Immunology from the University of California, San Francisco, where she studied the negative regulation of T cell receptor signaling. Prior to working with MediSix, Ying Xim was a Research Fellow at the Institute of Molecular and Cell Biology, studying the role of methytransferases in liver biology and cancer.

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Cecilia Sim, MBA, CFA

Vice President, Finance

Cecilia joined MediSix in May 2021 and is our Vice President, Finance. She has more than 18 years of corporate finance, fund raising, deal structuring, portfolio management and business advisory.

Prior to joining Medisix, she was the Head of Syndication at CapBridge, a fintech fund-raising platform. Cecilia holds a Master of Business Administration from the Wharton School of University of Pennsylvania, USA and a Bachelor of Accounting from Nanyang Technology University, Singapore. She is also a Chartered Financial Analyst.

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Andrew Bruce, BSc

Chief Executive Officer

As the CEO of MediSix Therapeutics based from our headquarters in Singapore, Andrew Bruce leads a strong and growing team in further developing the work of Professor Dario Campana in T-cell engineering. Andrew is an accomplished professional with more than 36 years in the pharmaceutical industry.

 

He has gained broad experience across a range of functions from sales and marketing to supply chain and logistics, medical affairs, therapy area strategy and corporate development. Andrew has held leadership positions within the pharmaceutical, biotech and medical consulting industries, in addition to commercial and strategy roles, including founding and subsequent sale of a global specialist medical consulting leader.

 

He moved to Singapore in March 2021. Andrew gained his BSc at the University of Bradford.

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Professor Dario Campana, MD, PhD

Scientific Founder

Professor Campana is the scientific founder of MediSix Therapeutics. An internationally renowned expert in cell therapy, he was the creator of the first anti-CD19-41BB-CD3z CAR that is the key component of Kymriah, the first CAR T-cell therapy approved by the FDA and marketed globally. Currently, Dario is Professor of Pediatrics at the National University of Singapore, and holds the Mrs Lee Kong Chian Chair in Advanced Cellular Therapy.

 

He is the recipient of consecutive Singapore Translational Research Investigator awards, the Jacob and Louise Gabbay Award in Biotechnology and Medicine and the Republic of Singapore President’s Technology Award. Dario is an elected member of the American Society for Clinical Investigation and the Association of American Physicians. In addition to MediSix, Dario is also the scientific founder of cell therapy start-ups Unum Therapeutics (Cambridge, MA) and Nkarta Therapeutics (San Francisco, CA) and holds several patents.

 

Dario obtained his MD and PhD in Italy at the University of Torino and the University of Milano, respectively. He trained as a scientist at the Royal Free Hospital, University of London, before moving to St. Jude Children’s Research Hospital in Memphis, where he was Full Member in the Departments of Oncology and Pathology, and Professor of Pediatrics at the University of Tennessee. Dario’s main interest is translational research in oncology, focusing on monitoring response to treatment in leukemia, and on immunotherapy of leukemia, lymphoma and solid tumors.

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