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Precision Medicine World Conference (PMWC 2020) Opened First of Three Full-Day Sessions on Wednesday, January 22, in California’s Silicon Valley

On Wednesday, January 22, the full meeting of the Precision Medicine World Conference 2020 (PMWC 2020) opened in California’s Silicon Valley, with seven parallel tracks of talks focusing on different aspects of precision medicine (https://www.pmwcintl.com/). The tracks were Emerging Therapeutics; AI and Data Intelligence; Diagnostics in Clinical Practice; Molecular Profiling—From Research to Clinic; Health Data, Microbiome, and Patient Education; Showcase 1; and Showcase 2. The first five tracks consisted of leaders in the field discussing the latest advances, sometimes in individual presentations and sometimes in panel discussions. The two Showcase tracks gave new companies the opportunity to present their work in crisp 15-minute talks. This year’s PMWC, the 11th annual PMWC conference in Silicon Valley, and the 17th PMWC meeting overall, including small, more regional meetings, was the largest annual meeting ever, with over 2,300 attendees from around the world and over 400 presentations given over the full three days. The meeting took place in the Santa Clara Convention Center in the heart of California’s Silicon Valley. The theme of this year’s conference was “How Do We Accelerate Precision Medicine and Deliver on Its Promises?” This year’s conference was co-hosted by UCSF, Stanford Health Care/Stanford Medicine, the University of Michigan, the University of Pittsburgh, and Duke Health. Sponsors of the conference included Illumina, Agendia, Bio-Rad, QIAGEN, RubAdaptive, Agilent, Caprion, GO, Google Cloud, Gritstone, Karius, Molecular Health, RubrYc, Oncocyte, Siemens Healthineers, Sophia, Thermo-Fisher Scientific, Quanterix, and Tabula Rasa HealthCare. Nearly 100 companies were exhibitors at the meeting. The conference was organized, as always, by Tal Behar, Co-Founder & President, PMWC LLC, and her husband Gadi Behar, Co-Founder & Chairman, PMWC LLC, Silicon Ventures. The PMWC 2020 Program Chairs were Tal Behal and Michael Pellini, MD, MBA, Managing Partner, Section 32 (a venture fund), and Former CEO, Foundation Medicine. Track 1 (Emerging Therapeutics) of Wednesday’s opening day kicked off with a Fireside Chat between Track 1 Chair Theresa LaVallee, PhD, and Philip Greenberg, MD, PMWC 2020 Luminary Award Winner, on the topic of immunotherapy. Doctor LaVallee is VP of Translational Medicine and Regulatory Affairs, Parker Institute of Cancer Immunotherapy and previously served as Senior Vice President, Celldex Therapeutics and Kolltan Pharmaceuticals. She also was Senior Director of Translational Medicine at MedImmune and EntreMed. In these roles, she has advanced drugs in oncology, immunology and inflammatory diseases from discovery through late stage development. Dr. LaVallee has a depth of expertise in Translational Medicine enabling science-driven development decisions and implementing effective use of biomarker assays in clinical studies. You may view a prepmeeting Q&A interview that the PMWC did with Dr. LaVallee at the following link (https://www.pmwcintl.com/theresa-lavallee-2020sv-qa/).

Dr. Greenberg, who the evening before received the PMWC 2020 Luminary Award for his seminal work in immunotherapy and work on the development of adoptive T-cell therapy, is Head, Program in Immunology, Fred Hutchinson Cancer Research Center; Professor of Medicine and Immunology, University of Washington; and Member, Parker Institute for Cancer Immunology. Dr. Greenberg received his Luminary Award for “discoveries that led to adoptive immunotherapy with genetically engineered T cells.” You may view a gthe pre-meeting Q&A interview that the PMWC did with Dr. Greenberg at the following link (https://www.pmwcintl.com/philip-greenberg-2020sv-qa/).

At the beginning of Wednesday’s discussion, Dr. LaVallee noted that Dr, Greenberg had early on envisioned the possible expansion of a patient’s own T-cells into a force for providing targeted anti-cancer therapies, but that this vision had taken almost four decades to finally realize.

Early in his career, Dr. Greenberg had worked with Dr. Don Thomas at the Fred Hutchinson Cancer Research Center. Dr. Thomas was then a leader of work on the use of bone marrow transplants to cure blood cancers and also to diminish the graft-versus-host reactions that often doomed organ and cell transplants. Dr. Greenberg noted that, although this bone marrow transplant approach was considered highly controversial at that time, strategies to improve efficacy and reduce toxicity were identified, and, in 1990, Dr. Thomas shared the 1990 Nobel Prize in Physiology or Medicine “for discoveries that have enabled the development of organ and cell transplantation into a method for the treatment of human disease.” Dr. Greenberg noted that Dr. Thomas established bone marrow transplants as a standard of care for leukemia, with the 1,000,000 such transplants performed as of 2012.

In his lab, Dr. Greenberg focused on strategies to modulate the patient’s own immune system to specifically target cancer cells. This approach was also perceived as very controversial at the time, but offered the possibility of avoiding the need for bone marrow transplants and the troublesome side effects often associated with such transplants.

Dr. Greenberg noted in his Q&A session with the PMWC, “studies in preclinical models began providing evidence that the immune system could be effectively modulated to treat cancer, and the big breakthrough came with evidence in patients that blockade of immunologic checkpoints with antibodies could unleash therapeutic immune responses. This was followed shortly by demonstrations in patients of the therapeutic activity of engineered T cells and the development of vaccines to induce responses to tumor mutations, which have, with other advances, resulted in immune therapies becoming a permanent and expanding component of cancer therapies.”

Dr. LaVallee remarked that Dr. Greenberg is known as an outstanding mentor, with many of his students having gone on to great successes of their own, and she asked him what qualities he looked for in students he selected to work in his lab. Dr. Greenberg responded that he looked for intelligence, of course, and evidence of productivity in the past. Other key qualities for him were inquisitiveness, the ability to ask good questions, passion, and a sense of humor.

He noted that lab work often involves much delayed gratification and requires the ability to persevere fitful starts and stops, failures and successes. He also emphasized the huge importance of collaborations in enabling advances and moving them forward as quickly as possible, from the lab to the clinic. He particularly stressed the significance of academia-industry collaborations as being of great mutual benefit. He mentioned the Parker Institute for Cancer Immunotherapy, to which both he and Dr. La Vallee belong, as an organization trying to speed the movement of lab advances as quickly as possible into the clinic.

Dr. Greenberg noted that, is his career, Dr. Thomas had, particularly with his huge energy, been an outstanding mentor. He also mentioned the great importance and influence of interactions with Dr. Jim Allison and Dr. Ira Mellman, as well as many others.

In closing, Dr.Greenberg emphasized the growing importance of using synthetic biology to engineer cells to turn on activity, rather than to turn off activity. This work is just beginning, Dr. Greenberg said.

SECOND FIRESIDE CHAT ON IMMUNOTHERAPY

The fireside chat between Dr. LaVallee and Dr. Greenberg was followed by a second fireside chat on immunotherapy between Harold Robbins, PhD, CSO and Co-Founder of Adaptive Biotechnologies, and Ira Mellan, PhD, VP of Cancer Immunology at Genentech. Dr. Mellman had come to Genentech in 2007 after 20 years as on the faculty of Yale University School of Medicine where he had ben chair of the Cell Biology Department. Dr. Mellman ran all of oncology research at Genentech until the end of 2013 when he decided to concentrate his efforts on the rapidly developing area of cancer immunotherapy and became Vice President of Cancer Immunology.

Prior to co-founding Adaptive Technologies in 2009, Dr. Robbins had earned his PhD in theoretical physics at UC Berkeley and had postdoctoral fellowships in theoretical physics at the Weizmann Institute and at the Advance Study in Princeton where he worked under famed biologist Arnold Levine to develop bioinformatic algorithms for micro RNA targets and bacterial genome analysis.

Adaptive (https://www.adaptivebiotech.com/) has as its aim to improve people’s lives by translating the scale and precision of their adaptive immune systems into products to help diagnose, treat, and monitor disease. The company has developed an immune medicine platform that has already registered significant successes in the last two years.

The company’s first clinical diagnostic (clonoSeq) has been cleared by FDA, and Adaptive has demonstrated the ability to commercialize this diagnostic. The test is used by clinicians for the detection and monitoring of minimal residual disease (MRD) in bone marrow samples from multiple myeloma and B-cell acute lymphoblastic leukemia (ALL) patients. It is also used by the company’s pharmaceutical partners to monitor response to innovative cancer treatments in clinical trials, and it is the first-ever diagnostic assay powered by immunosequencing to be cleared by the FDA.

Adaptive has partnered with Microsoft Healthcare NExT initiative to map and decode the human immune system, nature’s most finely tuned diagnostic. Together, the companies are using immunosequencing, proprietary computational modeling, and machine learning to map T-cell receptor (TCR) sequences to the antigens they bind. Using this data, Adaptive aims to translate the natural diagnostic capability of the immune system into the clinic.

We are building a map that links trillions of TCRs with the millions of clinically-relevant antigens they are specifically targeted to attack, making the diagnosis of disease far more efficient and precise. This will make it possible to read what an immune system has fought or is currently fighting, with the goal of creating a better diagnostic for all diseases—from cancer to autoimmune conditions to infectious diseases.

As part of this collaboration, Adaptive is interested in investigating sample sets that can be mined for disease-associated TCRs, on the scale of 100s to 1000s of samples, in the certain disease areas, including pancreatic and ovarian cancer, type 1 diabetes and celiac disease, and Lyme disease, as well as in other diseases with an unmet need for blood-based diagnostics.

This landmark collaboration is a cornerstone of the Microsoft Healthcare NExT initiative, and the first and only biotech and tech effort focused on revealing and translating insights about the immune system into actionable tools for clinicians.

The core of the TCR-Antigen Map is the biological data and models derived from Adaptive’s high-throughput, patented sequencing and antigen-mapping technologies (immunoSEQ and MIRA, respectively) to determine all possible T-cell receptors that bind to clinically relevant antigens across diseases. A proof-of-concept for this initiative was published in Nature Genetics (Emerson, et al. Nat Genet. 2017), demonstrating Adaptive’s ability to identify TCRs capable of diagnosing cytomegalovirus (CMV). Now we are working to expand this effort to develop diagnostic tests in other diseases, with the vision of ultimately developing a diagnostic for multiple diseases from a single blood test based on the breadth of knowledge within the adaptive immune system.

After two years in partnership, Adaptive and Microsoft have made enormous strides in building the infrastructure to solve this biological puzzle. To accelerate progress, Adaptive has integrated the distinct capabilities of each its teams to an unprecedented degree. In 2019, Adaptive achieved a key milestone of establishing a proof of concept in acute Lyme disease.

Looking ahead to Adaptive’s next milestones, the company plans to confirm the first indications to bring to the FDA for review while continuing signal validation in several additional indications. Adaptive is currently seeking samples to validate our technology in several areas of focus, including but not limited to: pancreatic and ovarian cancer, type 1 diabetes and celiac disease, and Lyme disease, as well as in other diseases with an unmet need for blood-based diagnostics.

The application of machine learning, in collaboration with Microsoft, exponentially accelerates the growth of novel insights from the Adaptive database, which drives the company’s ability to rapidly discover and develop potential diagnostic and therapeutic applications.
In January 2019, Adaptive partnered with Genentech to develop, manufacture and commercialize novel neoantigen-directed T-cell therapies for the treatment of a broad range of cancers. The collaboration will combine Genentech’s global cancer immunotherapy research and development leadership with Adaptive’s proprietary T-cell receptor (TCR) discovery and immune profiling platform (TruTCR™) to accelerate a transformational new treatment paradigm of tailoring cellular therapy for each patient’s individual cancer.

CAR-T CELL THERAPY PANEL

This fireside chat was followed by a panel discussion of chimeric antigen receptor T-cell (CAR-T) therapy led by Chair Sarah Warren, PhD, Director of Advanced Applications, NanoString Technologies. The panelists were Sean McKay, CEO & Co-Founder, IsoPlexis; David Miklos, MD, PhD, Associate Professor of Medicine, Stanford University; Joseph Melenhorst, PhD, Adjunct Associate Professor, University of Pennsylvania; Avery Posey, PhD, Assistant Professor, University of Pennsylvania Perelman School of Medicine; and Eric Ostertag, MD, CEO, Poseida Therapeutics. A key point of the panel discussion was that there is considerable room for improvement over the first-generation of CAR-T therapies, which are often associated with high toxicities and high costs of treatment. In addition, the need to address the difficulties in treating solid tumors with CAR-T therapy was voiced. Dr. Ostertag’s company is currently using its proprietary technologies in an effort to create and maintain early-memory T cells that are omnipotent, self-renewing, and long-lived, potentially giving them the capability to respond to relapses and deliver wave after wave of immune response from a single treatment. CAR-T therapeutics comprised of a high percentage of stem cell memory T cells exhibit unique properties that could potentially solve most of the limitations of early-generation CAR-T products, including significant toxicities, historically poor efficacy against solid tumors, and high costs, Dr. Ostertag believes. Poseida’s most mature product candidate, P-BCMA-101, is an autologous CAR-T therapy targeting BCMA, a protein that promotes the survival of multiple myeloma cells

With regard to panel chair Dr. Warren of Nanostring, that company’s products are based on a novel digital molecular barcoding technology invented at the Institute for Systems Biology (ISB) in Seattle under the direction of Dr. Leroy Hood. In 2008, NanoString launched its first commercial instrument system and began international sales operations with its first multiplexed assays for gene expression analysis. In 2010, the company launched new applications for the system to support microRNA analysis and copy number variation detection. In 2019, the company launched the GeoMx™ Digital Spatial Profiler enabling highly-multiplexed spatial profiling of RNA and protein targets in a variety of sample types, including FFPE tissue sections.

NanoString notes on its web site that “The next generation of highly predictive biomarkers in immuno-oncology will need to measure and integrate the complexity of host, tumor, and environment interaction. The measurement of DNA, RNA, and proteins simultaneously with the same sample will enable researchers to obtain a more complete understanding of the immune system response to disease and support the development of new, highly effective therapies.”

GENOMIC PROFILING AND CLINICAL DIAGNOSTICS SHOWCASES

In addition to the five topical tracks, two so-called “Showcase” tracks took place throughout each day and gave an opportunity, in 15-minute slots, to selected organizations, including commercial companies, clinical testing labs, and medical research institutions, to present their latest advancements, insights, applications, and technologies to an audience of clinicians, leading investigators, academic institutions, pharma and biotech, investors, and potential clients. These showcases allowed attendees to learn about new technologies and findings that promise expedited, cost-effective, and accurate clinical diagnosis for early disease detection, treatment decisions, and disease prevention.

WEDNESDAY SHOWCASES

BIOLGICAL DYNAMICS

In one of the afternoon showcases on Clinical Diagnostics, Raj Krishnan, PhD, CEO of Biological Diagnostics (https://biologicaldynamics.com/), explained how his company has pioneered the use of alternating current (AC) electrokinetics to directly isolate blood-based nanoparticles. This foundational technology powers Biological Dynamics’ novel isolation platform, Verita™. According to Dr. Krishnan, this technology excels at isolating nanoparticles - such as DNA, RNA, and exosomes - from unprocessed blood-based samples, driving a radically simplified workflow. The Company is developing a portfolio of novel oncology and infectious disease products designed to enable early detection and individualized treatment response monitoring. In addition to lab-focused products, Biological Dynamics is also developing a smartphone-enabled portable version of the platform with the goal of bringing blood-based DNA testing into the home.

AGENDIA

In a Genomic Profiling Showcase, William Audeh, MD, CMO, Agendia (https://www.agendia.com/), an oncologist and long-time specialist in breast cancer, outlined the ongoing contribions of Agendia to the fight agains breast cancer. Prior to joining Agendia, in May 2016, in addition to his clinical practice, Dr. Audel served as Director of the Cedars-Sinai Cancer Center, Clinical Chief of the Division of Hematology/Oncology, and Medical Director of the Wasserman Breast Cancer Risk Reduction Program. In the showcase, Dr. Audeh highlighted the success of Agendia’s MammaPrint (70-marker) test when combined with Agendia’s BluePrint (80-gene test) in helping to navigate the complexity of early breast cancer and in often permitting a determination of the best personalized medicine approach going forward for individual patients.

BluePrint, a molecular subtyping test, analyzes the activity of 80 genes to enable stratification of the breast tumor into one of the three following subtypes: Luminal-type, HER2-type, and Basal-type. By combining the 70-marker MammaPrint test with the BluePrint 80-gene test, patients can be stratified into the following four subgroups: Luminal-type/MammaPrint Low Risk (Luminal A); Luminal-type/MammaPrint High Risk (Luminal B); HER2-type; and Basal-type patients.

Each breast cancer subtype is markedly different in its degree of aggressiveness, long-term outcome, and response to chemotherapy. With the subtype information, provided by BluePrint, in combination with MammaPrint, physicians are better informed to make decisions about a patient’s specific options, thereby personalizing the treatment.

Dr. Audeh also mentioned the 2018 results of the I-SPY 2 breast cancer trial being run by Dr. Laura Esserman of UCSF, which demonstrated the ability of MammaPrint and BluePrint to predict treatment response in breast cancer.

CARIS LIFE SCIENCES

David Spetzler, PhD, Presidnt & CEO, Caris Life Sciences (https://www.carislifesciences.com/), presented a Genomic Profiling Showcase that highlighted the company’s development of its ADAPT Biotargeting System, a groundbreaking and proprietary method of profiling macro-molecular complexes in their native form in a highly multiplexed format. The innovative technology is the result of the convergence of Caris’ deep expertise in Next-Generation Sequencing, exosome biology, bioinformatics, and broad-based molecular profiling. Dr. Spetzler noted that Caris Life Sciences is an innovative biotechnology company, actively working to fulfill the promise of precision medicine through its unique and transformative platforms to help patients with cancer and other complex diseases. He mentioned that Caris’s next-generation profiling (NGP), powered by the company’s advanced machine learning platform, DEAN, helps define complex biomarkers that can improve patient outcomes. NGP identifies unique molecular signatures by cancer subtypes, predicts which patients might respond to specific treatments, and improves cancer diagnosis.

INFLAMMATIX

Tim Sweeney, MD, PhD, CEO, Inflammatix (https://inflammatix.com/) described the company he co-founded, after his clinical training as a surgeon at Stanford, as a novel molecular diagnostics company focused on bringing advanced host-response diagnostics to the point of care in a rapid, small device. The company’s flagship test, HostDx Sepsis, is focused on diagnosing acute infection, but the company also has a deep diagnostics pipeline in acute infections and inflammatory disease based on the same computational techniques. The HostDx tests combine advanced machine learning and computational biology to “read” the immune response to create actionable insights that fit into rapid workflows. The company's novel device can measure dozens of novel markers in under 30 minutes. In his talk, Dr. Sweeney noted that the impact of sepsis is enormous, being responsible for 50% of all hospital deaths, in fact, caused by sepsis. As many as 250,000 deaths are caused by sepsis in the US each year. And the need for rapid, accurate tests to address this problem is acute. According to the Inflammatix web site, physicians ae eager for a better diagnostic for sepsis, with 93% of physicians recommending that their institution incorporate the HostDx Sepsis test into routine care.

DRAWBRIDGE

Elisa Romeo, PhD, COO, Drawbridge Health, Inc. (https://www.drawbridgehealth.com/) described how her company has re-invented the blood-drawing experience by designing and developing the OneDraw™ A1C Test System, a blood collection device that is nearly painless, convenient, and easy-to-use, enabling the collection, stabilization, and transport of capillary blood samples to the laboratory for testing of HbA1c. Dr. Romeo oversees Research & Development, Manufacturing, and Regulatory activities at Drawbridge Health. She joined the company in late 2017, bringing her expertise and a wealth of experience in diagnostic test development for CLIA-certified, CAP-accredited commercial laboratories and medical device companies focused on in vitro diagnostic (IVD) test development. Prior to joining Drawbridge Health, Dr. Romeo served as VP of Research and Development at Gensignia Life Sciences, IVD Development Manager at Pathway Genomics, Associate Director of Operations at HistoRx, and Principal Scientist at Genoptix.

SUMMARY

The many presentations described here represent just a select subset of the nearly 150 talks and panel discussions that were presented on the first full day of PMWC 2020 in Silicon Valley, California.

NEXT PMWC CONFERENCES

A smaller regional PMWC East conference will be held this spring in Pittsburgh, Pennsylvania, June 4-5 (https://www.pmwcintl.com/east/), with over 90 speakers scheduled to present.

The next annual PMWC conference (PMWC 2021) will be held February 23-26, 2021 in California’s Silicon Valley.

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