Dr. Zhang is the founder and CEO of Yinuoke Ltd, a clinical stage biotech company developing First-in-Class cancer immunotherapies based on a new concept. Dr. Zhang graduated from Jilin University with a doctoral degree of immunology in 2007. From 2008 to 2012, Dr.Zhang did a postdoctoral fellowship at Stanford School of Medicine studying cancer immunology and immunotherapy. After the postdoctoral fellowship, Dr.Zhang continued to study cancer immunology for another four years at Stanford School of Medicine, focusing on the immune system dynamics during cancer progression and its impact on the host. Read his full bio.

Interview with Lingbing Zhang of Yinuoke Ltd

Q: The Nobel Prize in Medicine was awarded recently to James Allison and Tasuku for their work on unleashing the body’s immune system to attack cancer, a breakthrough that has led to an entirely new class of drugs and brought lasting remissions to many patients who had run out of options. The Nobel committee hailed their accomplishments as establishing “an entirely new principle for cancer therapy.” What is your first-hand experience the impact that those new drugs had on patients?

A: Although I don’t have first-hand experience with those new drugs, several of my friends asked me for suggestions because they know I have been studying cancer immunotherapy for 15 years. Some of my friends have tried the PD-1 inhibitors and encountered organ inflammation, which is a severe side effect. As a result, they had to stop the treatment. One main limitation of the new drugs is: they do not work in all cancer patients—they are efficacious in a group of cancer patients. Many patients with advanced cancer have been cured by the new drugs. Because of the improved efficacy, people have begun to realize and accept the potential of cancer immunotherapy. Five years ago, most people were skeptical that cancer immunotherapy could make a big difference in the lives of cancer patients. This Nobel prize will greatly increase awareness in cancer immunotherapy, which is very good. With more resources entering the field, I believe we will accelerate the product development process and deepen our knowledge of cancer immunology and develop better cancer immunotherapy drugs.

Q: What will the next generation of immune therapies look like for cancer?

A: I believe the next generation of immune therapies will come more rapidly than the first generation of cancer therapies. With that said, it is very difficult to fully describe the new generation of therapies since we are still in the infancy stage and the field develops rapidly. However, I am confident that we will see great progress in the following three areas, which will fundamentally improve cancer care, especially late stage cancer. First, immune therapies that modulate tumor-induced immune disorder will appear. The new term ‘tumor-induced immune disorder (TID)’ was first proposed by Yinuoke, because we believe it more accurately describes the immune status of cancer patients at late stage. If you look at the blood of patients with late stage cancer, you will always see severely imbalanced immune cell populations, such as high neutrophils and low lymphocytes, and you will see multiple dramatically elevated cytokines. Historically this phenomenon is called systemic inflammation, but this causes some confusion since people tend to think systemic inflammation can be treated with traditional anti-inflammatory drugs, but in clinical reality, the effect of traditional anti-inflammatory drugs in treating this condition is very limited. We believe TID more accurately describes systemic inflammation as tumor induced. Currently we have very strong clinical data showing that TID is the major cause of most late stage cancer symptoms, such as: fatigue, body weight loss, pain, etc., but there are NO approved drugs that can safely and effectively modulate TID. At Yinuoke, one of our major efforts is to develop products that can safely modulate TID and we have generated very promising animal efficacy data. By modulating TID, we could not only eliminate the symptoms and improve physical condition of mice mimicking late-stage cancer, but also dramatically increase mice survival. In fact, we usually need to terminate mice in the treatment group because they survive too long. Our first product was approved by the FDA for a human clinical trial to be initiated in early 2019. We look forward to seeing patients’ response to our TID therapy next year. Second, we will see immunotherapy products that could rebuild patients’ anti-tumor immunity. The mechanism of action of currently approved checkpoint inhibitors is to remove the ‘brake’ on T-cells, which means it needs T cells existing in a tumor microenvironment, but from our own and other’s studies we know in majority of late stage cancer patients, T cells in both in circulations and tumor microenvironment have become extremely low. In my mind, that is the reason why a majority of advanced cancer patients do not respond to the approved checkpoint inhibitors. So, the obvious need is products that can rebuild the anti-tumor immunity including increasing anti-tumor T-cells in tumor microenvironments. The CAR-T therapies can help, but are not enough, since for solid cancer there are too many hurdles for the engineered T-cells to work effectively in an extremely unsupportive tumor microenvironment. Fortunately, we have many theoretically possible ways to alter the tumor microenvironment. At Yinuoke, we are developing products that can modulate the tumor microenvironment to generate more anti-tumor T-cells and support them to be more effective. But for most late-stage cancer patients, the first step is to modulate the TID to remove the constant immune attack on a patient’s body and thus improve the patient’s overall health. Otherwise patients may not have the chance to generate a strong anti-tumor immune response in their body. Lastly, I think is also very important is to establish more accurate diagnostic methods that can precisely measure anti-tumor immunity status in real time in each cancer patient. When we talk about precision medicine in the field of cancer, most people are thinking about tumor genetic mutations. The mutation burden will influence the anti-tumor immunity and can be used as one method. But we have observed in animal studies that the anti-tumor immunity is very dynamic, which keeps changing even without any new mutations. So, we also need more methods to capture the status of anti-tumor immune cells in real time. Eventually we will develop a system to score the level of anti-tumor immunity in each cancer patient at each specific time point, just like we have the staging system for tumor burden in current cancer care. Thus, oncologists could prescribe the most appropriate cancer immunotherapy drug for each cancer patient at specific time points based on this score. The above are the three aspects I believe will experience great progress. I also would like to see next generation therapies that can benefit cancer patients. We may need more generations of therapies to reach our ultimate goal—to make a cure for all cancer patients.

Q: The checkpoint inhibitors and CAR-T therapies now on the market have only been approved for some cancer types and benefit only a small subset of those patients. What do you project the role of immunotherapy in cancer care will be ten years from now?

A: I believe cancer immunotherapy will play a much more important role ten years from now. Firstly, we will have new drugs to modulate the tumor-induced immune disorder (TID) I mentioned above; thus, many terminally-ill cancer patients could be saved and receive tumor-targeted treatments. The number of cancer patients that can benefit from the TID modulating drugs is large and the clinical impact will be massive. According to published data, 30% of cancer deaths could be prevented. Secondly, more checkpoint inhibitors and anti-tumor immunity rebuilding drugs will be available and patients will have many more treatment options. Lastly, cancer immunotherapy will be routinely incorporated into the clinical care of many types of cancer. Armed with an established anti-tumor immunity scoring system, doctors would be able to assign an anti-tumor immunity score on the diagnostic report of cancer patients in addition to their tumor stage and gene mutations. Based on this report, oncologists would design the best treatment regimen for each cancer patient. To be clear, the treatment regimen may not only include immunotherapy, but may also include other cancer treatments that have proven effective via clinical practice. For example, if a cancer patient could undergo an operation to remove a large tumor burden, an optimal regimen may include operation combined with appropriate immunotherapy drugs determined by his real time immunity score. The immunotherapy drug is of paramount importance to rebuild or maintain high level anti-tumor immunity in a patient’s body; thus, the patient will avoid tumor relapse and reach a cure. This is an ideal scenario, the reality is more complicated, but I believe more cancer patients will have the chance to be treated more effectively with the development of cancer immunotherapy and its gradual incorporation into clinical practice.

Q: Approved immunotherapy drugs have severe side effects, turning the fury of the immune system against the patient own healthy cells, and they are expensive, costing more than $100,000 a year. Do you expect any of those to change in the near future?

A: I am confident both side effects and high treatment costs will improve, especially the issue of side effects of currently approved immunotherapy drugs. Since people have realized the potential of cancer immunotherapy, companies are working hard to develop better solutions. At Yinuoke we are developing products that aim to reduce the side effects of other cancer therapies, including chemotherapy and checkpoint inhibitors. One of our products under preclinical development could significantly reduce the side effect of PD1 inhibitors. Mice receiving a combined treatment have a significant reduction in side effects and thus better-quality outcomes than mice receiving only an anti-PD1 antibody. More importantly, the combined treatment has much better efficacy, both in anti-tumor effect and in efficacy on survival. This result is very important, since a major concern is you are likely to sacrifice the efficacy of cancer immunotherapy if you try to remove the side effects, because the side effects are also mediated by the immune response. These findings provide us with the confidence that we could have better therapeutic efficacy of cancer immunotherapy by shutting down the unwanted side effects. Based on our research and the rapid development of the whole field, I am very optimistic that we will have better cancer immunotherapy (combination) treatments with better clinical performance (strong efficacy with minimum side effects) in the future. Regarding high treatment cost (usually more than $100,000 a year), I think it’s mainly driven by the high costs of drug development. The price should gradually decrease as more immunotherapy products enter the market, creating more treatment options.

Q: Is there anything you would like to share with the PMWC audience?

A: We are entering a new era of cancer immunotherapy. The potential of this class of therapies are far from being fully realized. So far most of the efforts have only focused on stimulating the immune system to attack cancer cells, but the impact of the immune system on cancer patients is much more than that. Strong clinical and experimental data have suggested that tumors can induce severe immune disorders (TID) in advanced cancer patients. These immune disorders could bring massive damage to a patient’s body. We believe that many advanced cancer patients (i.e. 30%) could be saved if we have drugs that could safely modulate the tumor-induced immune disorder toward a normal state. At Yinuoke, we are dedicated to developing this new class of cancer immunotherapy drugs.

Interview with Gabriel Bien-Willner of Palmetto GBA

Q: What does your role entail as the director of the MolDX program at Palmetto GBA?

A: The job directing MolDX is multifaceted; first and foremost the MolDX program is responsible for assessing molecular diagnostic tests on the market and makes coverage and pricing determinations for such tests and technology. This is usually done through local coverage determination policies or technical assessments.

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Interview with Peter Marks of FDA

Q: The CBER’s Regenerative Medicine Advanced Therapy Designation program has been very successful, with about 100 requests for designation in the two years of its existence. Can you please tell us about the program and how it was put together?

A: The Regenerative Medicine Advanced Therapy (RMAT) Designation program came into being as part of the 21st Century Cures Act that was signed into law on December 13, 2016.

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Interview with Calum MacRae of Harvard Medical School

Q: What patient data do we need to better understand the underlying cause of disease and how to prevent it?

A: Medicine at present is highly underdetermined and data poor. To be precise, one must be comprehensive, so medicine (with our consent) will use not only what we currently conceive of as biomedical information, but also data from across our lives.

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Headlines from PMWC 2019 Silicon Valley

A big ‘Thank You’ to all of our presenters and attendees for celebrating 10 years of precision medicine progress with us! PMWC 2019 Silicon Valley was attended by 2000 participants from 35 countries, which included over 400 speakers in 5 parallel tracks!

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Interview with Ken Bloom of Ambry Genetics

Q: Tell us more about your organization/company. What patient population are you serving and which services are you specializing in?

A: Ambry Genetics is a recognized leader in high quality complex genetic testing. We seek to find the genomic cause or contributors to rare diseases, abnormal phenotypes and hereditary disorders.

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Interview with Lee Pierce of Sirius Computer Solutions

Q: What is the state of big data and analytics in healthcare, and how to best use the reams of data available?

A: More than ever, Healthcare organizations are achieving measurable value through use of their data and analytics assets. There is more raw material available than ever to create value. This raw material is the data flowing from internal systems and applications and also from devices and systems external to healthcare organizations.

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Interview with Anita Nelsen of PAREXEL

Q: There are various new, emerging technologies that bring us closer towards a cure for life-threatening disorders such as cancer, HIV, or Huntington’s disease. Prominent examples include the popular gene editing tool CRISPR or new and improved cell and gene therapies. By when can we expect these new technologies being part of routine clinical care?

A: Today’s emerging technologies are making the promise of individualized treatment a reality.

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Interview with Ilan Kirsch of Adaptive Biotechnologies

Q: The Nobel Prize in Medicine was awarded recently to James Allison and Tasuku Honjo for their work on unleashing the body’s immune system to attack cancer, a breakthrough that has led to an entirely new class of drugs and brought lasting remissions to many patients who had run out of options. The Nobel committee hailed their accomplishments as establishing “an entirely new principle for cancer therapy.” What is your first-hand experience the impact that those new drugs had on patients?

A: For decades cancer was viewed as solely a cell-autonomous condition.

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BMS buys Celgene | Lilly buys Loxo Oncology – Does this Signal a Return to Strong Deal-Making Activities in 2019?

Bristol-Myers Squibb’s blockbuster $74B deal to buy Celgene creates an oncology powerhouse amid industrywide excitement about the rapidly evolving science and explosive growth of the sector. The agreement could signal a return to deal-making for the pharmaceutical industry in the $133B global oncology therapeutics market.

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Interview with Gini Deshpande of NuMedii

Q: What need is NuMedii addressing?

A: NuMedii, has been pioneering the use of Big Data, artificial intelligence (AI) and systems biology since 2010 to accelerate the discovery of precision therapies to address high unmet medical needs. Artificial Intelligence approaches are a natural fit to harness Big Data as they provide a framework to ‘train’ computers to recognize patterns and sift through vast amounts of new and existing genomic

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Interview with Minnie Sarwal of UCSF

Q: Genomic medicine is entering more hospitals and bringing with it non-invasive technology that can be used to better target and treat diseases. What are some key milestones that contributed to this trend?

A: Completion of complete sequence data from the human genome project, and the advances in proteomic, microRNA and epigenetic assays added a layer of pathway biology to the understanding of human diseases.

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Interview with Shidong Jia of Predicine

Q: Once sequencing has been validated as a clinical solution via trusted workflows, and coinciding with the technological developments driving costs lower, we can expect accelerated human genome profiling for clinical Dx. How soon, do you think, will we see accelerated growth and what can we expect?

A: We will see accelerated human genome profiling for clinical Dx in 2019 and the coming years as more biomarker-based cancer drugs are gaining approval.

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Interview with Iya Khalil of GNS Healthcare

Q: Artificial intelligence (AI) techniques have sent vast waves across healthcare, even fueling an active discussion of whether AI doctors will eventually replace human physicians in the future. Do you believe that human physicians will be replaced by machines in the foreseeable future? What are your thoughts?

A: I think that there’s a lot of speculation and uncertainty around AI, but I don’t foresee a time when we won’t need physicians.

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Interview with Ilya Michael Rachman of Immix Biopharma Inc.

Q: The Nobel Price in Medicine was awarded recently to James Allison and Tasuku for their work on unleashing the body’s immune system to attack cancer, a breakthrough that has led to an entirely new class of drugs and brought lasting remissions to many patients who had run out of options. The Nobel committee hailed their accomplishments as establishing “an entirely new principle for cancer therapy.” Besides CAR T-cell therapy what do you think next generation immunotherapies will look like to successfully combat cancer?

A: The next generation of immunotherapies will build on the insights discovered by immunologists like James Allison and Tasuku Honjo and extend them to modify the body’s response to tumors.

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Join me to Kick off PMWC Silicon Valley in the Santa Clara Convention Center, Focusing on Every Element of Precision Medicine

My team worked in collaboration with Bill Dalton, Kim Blackwell, Atul Butte / India Hook Barnard, Nancy Davidson and Sharon Terry to create a program that touches every component of precision medicine while bringing together all of its key stakeholders. Leading participating institutions including Stanford Health Care, UCSF, Duke Health, Duke University, John Hopkins University, University of Michigan and more will share their learnings and experiences and their successes and challenges, as they make precision medicine the new standard of care for all.

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Johns Hopkins
University Of Michigan

The Precision Medicine World Conference (PMWC), in its 17th installment, will take place in the Santa Clara Convention Center (Silicon Valley) on January 21-24, 2020. The program will traverse innovative technologies, thriving initiatives, and clinical case studies that enable the translation of precision medicine into direct improvements in health care. Conference attendees will have an opportunity to learn first-hand about the latest developments and advancements in precision medicine and cutting-edge new strategies and solutions that are changing how patients are treated.

See 2019 Agenda highlights:

  • Five tracks will showcase sessions on the latest advancements in precision medicine which include, but are not limited to:
    • AI & Data Science Showcase
    • Clinical & Research Tools Showcase
    • Clinical Dx Showcase
    • Creating Clinical Value with Liquid Biopsy ctDNA, etc.
    • Digital Health/Health and Wellness
    • Digital Phenotyping
    • Diversity in Precision Medicine
    • Drug Development (PPPs)
    • Early Days of Life Sequencing
    • Emerging Technologies in PM
    • Emerging Therapeutic Showcase
    • FDA Efforts to Accelerate PM
    • Gene Editing
    • Genomic Profiling Showcase
    • Immunotherapy Sessions & Showcase
    • Implementation into Health Care Delivery
    • Large Scale Bio-data Resources to Support Drug Development (PPPs)
    • Microbial Profiling Showcase
    • Microbiome
    • Neoantigens
    • Next-Gen. Workforce of PM
    • Non-Clinical Services Showcase
    • Pharmacogenomics
    • Point-of Care Dx Platform
    • Precision Public Health
    • Rare Disease Diagnosis
    • Resilience
    • Robust Clinical Decision Support Tools
    • Wellness and Aging Showcase

See 2019 Agenda highlights:

    • Five tracks will showcase sessions on the latest advancements in precision medicine which include, but are not limited to:
      • AI & Data Science Showcase
      • Clinical & Research Tools Showcase
      • Clinical Dx Showcase
      • Creating Clinical Value with Liquid Biopsy ctDNA, etc.
      • Digital Health/Health and Wellness
      • Digital Phenotyping
      • Diversity in Precision Medicine
      • Drug Development (PPPs)
      • Early Days of Life Sequencing
      • Emerging Technologies in PM
      • Emerging Therapeutic Showcase
      • FDA Efforts to Accelerate PM
      • Gene Editing / CRISPR
      • Genomic Profiling Showcase
      • Immunotherapy Sessions & Showcase
      • Implementation into Health Care Delivery
      • Large Scale Bio-data Resources to Support Drug Development (PPPs)
      • Microbial Profiling Showcase
      • Microbiome
      • Neoantigens
      • Next-Gen. Workforce of PM
      • Non-Clinical Services Showcase
      • Pharmacogenomics
      • Point-of Care Dx Platform
      • Precision Public Health
      • Rare Disease Diagnosis
      • Resilience
      • Robust Clinical Decision Support Tools
      • Wellness and Aging Showcase
  • Luminary and Pioneer Awards, honoring individuals who contributed, and continue to contribute, to the field of Precision Medicine
  • 2000+ multidisciplinary attendees, from across the entire spectrum of healthcare, representing different types of companies, technologies, and medical centers with leadership roles in precision medicine
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