CITY OF HOPE SCIENTISTS SHOWCASE NEW FINDINGS AT THE 2020 AACR VIRTUAL ANNUAL MEETING II

On June 9, 2020 City of Hope scientists reported that it will showcase research at the AACR (Free AACR Whitepaper) Virtual Annual Meeting II that could one day lead to real-time diagnostic imaging and leading-edge genomic profiling that improve health outcomes for cancer patients, and much more (Press release, City of Hope, JUN 9, 2020, View Source [SID1234560930]).

"Innovative cancer immunotherapy and lifesaving precision medicine are areas City of Hope has doubled down on. In the years to come, we expect to yield research results that could be developed into therapies and practices that transform the delivery of cancer care," said Michael Caligiuri, M.D., president of City of Hope National Medical Center, former American Association for Cancer Research (AACR) (Free AACR Whitepaper) president and the Deana and Steve Campbell Physician-in-Chief Distinguished Chair.

AACR’s second virtual session will take place from June 22-24. More than 61,000 people from 140 countries registered to attend the first virtual session in April. The multidisciplinary meeting program will highlight the best cancer science and medicine in the world.

Using imaging biomarkers to deliver personalized care
Radiomic prediction of survival in recurrent high-grade glioma patients treated with CAR T-cell therapy
City of Hope physician-scientists are developing accurate theranostics (therapy + diagnostics) to deliver precision medicine in cancer care. Ammar Chaudhry, M.D., a diagnostic radiologist at City of Hope, and colleagues used machine learning models to compare the "survival prediction performance" of patients who have a type of brain tumor called high-grade glioma. Having accurate survival prediction performance equips doctors with the data necessary to determine the best treatment options for each patient. Physician-scientists performed baseline imaging, surgically removed the brain cancer and then delivered CAR T cell therapy. Using machine learning, the researchers found that labeling tumor voxels (3D pixels) as non-enhancing tumor (NET) was significantly more accurate at predicting prognosis than using other labeling methods. Further research is needed to make this model more robust.

Precision medicine: Full DNA and RNA genome profiling of all cancer patients
Identifying the genomic correlates of clinical benefit (CB) from immunotherapies (IO) and vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI) in metastatic renal cell carcinoma (mRCC)
City of Hope is working toward profiling the genomes of all patients to provide the most effective, personalized treatment. Sumanta Pal, M.D., co-director of City of Hope’s Kidney Cancer Program, led a study that looked at tumor-specific alterations resulting from specific cancer treatments. Using a proprietary tool that analyzes all DNA-coding regions, the City of Hope researchers found that having an abundance of mutations at the very end of certain RNA (known as telomeres or TERT promoter mutations) may be a biomarker that predicts immunotherapy will not work for a patient. Understanding how useful certain treatments will be for a specific patient can help physicians weed out ineffective treatments so that time and money can be spent on treatments that have a chance of bringing the patient into remission. Because the sample size was 58 patients, this research warrants further investigation with larger prospective cohorts.

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ERYTECH Provides Update on Phase 2 Investigator Sponsored Trial of Eryaspase in Second-Line Acute Lymphoblastic Leukemia

On June 9, 2020 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported an update on the ongoing Phase 2 trial, sponsored by the Nordic Society of Paediatric Haematology and Oncology (NOPHO) of eryaspase in second-line acute lymphoblastic leukemia (ALL) patients (Press release, ERYtech Pharma, JUN 9, 2020, View Source [SID1234560929]).

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The NOR-GRASPALL-2016 trial is evaluating the safety and activity of eryaspase in primarily pediatric acute lymphoblastic leukemia (ALL) patients who developed hypersensitivity reactions to pegylated asparaginase. The trial which is being conducted at 22 clinical sites in the Nordic and Baltic countries of Europe has reached its target enrollment of 50 patients.

Preliminary findings of the study suggest that eryaspase achieved the target level and duration of asparaginase activity in these patients. Additionally, the addition of eryaspase to the combination chemotherapy was associated with an acceptable tolerability profile, enabling the majority of these patients to receive their fully intended courses of asparginase. Recent data have confirmed that discontinuation of asparaginase therapy in ALL patients has been associated with inferior disease free survival1.

"Hypersensitivity to asparaginase remains an important concern in the treatment of ALL patients," said Dr Birgitte Klug Albertsen, Associate Professor at Aarhus University Hospital, Denmark, and Principal Investigator of the trial. "Based on the results we have observed thus far, eryaspase appears to have promise as a novel approach to continue asparaginase-based therapy for patients who develop hypersensitivity to pegylated asparaginase. We look forward to sharing the full results of the trial at a future medical congress."

"Initial feedback obtained from FDA has confirmed that ALL patients experiencing hypersensitivity to pegylated asparaginase represents an unmet medical need given the limited available treatment choices for these patients," said Dr Iman El Hariry, Chief Medical Officer of ERYTECH Pharma. "The encouraging evidence of activity in the NOPHO trial could provide support that eryaspase may serve as an additional potential therapeutic option in this patient population. We plan to further discuss these data with FDA as they mature to determine the appropriate next steps and assess a potential path forward for eryaspase in this setting."

About Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that is the most common type of cancer in children in the US and Europe.2,3 More than 13,000 cases are diagnosed in the US and Europe each year with the majority of patients diagnosed before age 20.4-6 Asparaginase has been an integral component of ALL treatment for several years but is associated with treatment-limiting hypersensitivity in up to 30% of patients7. Discontinuation of asparaginase therapy in ALL patients has been associated with inferior event free survival highlighting the need for additional asparaginase based treatment options.

Cardiff Oncology Announces Expanded Access Program for Onvansertib in KRAS-Mutated Metastatic Colorectal Cancer as Follow-On to Fast Track Designation

On June 9, 2020 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology therapeutics company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, Zytiga-resistant prostate cancer and leukemia, reported initiation of its Expanded Access Program (EAP) for its investigational drug onvansertib, in combination with standard-of-care FOLFIRI and bevacizumab, for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, JUN 9, 2020, View Source [SID1234560928]).

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"We are excited to offer expanded access to our investigational drug for patients with KRAS-mutated mCRC who may benefit from treatment with onvansertib, but may not be able to participate in our clinical trial," said Dr. Mark Erlander, Chief Executive Officer of Cardiff Oncology. "The granting of Fast Track Designation coupled with the initiation of our Expanded Access Program underscores the medical need for a new therapeutic option to treat these patients who are facing a devastating prognosis. We are dedicated to advancing the clinical development of onvansertib so that many more patients will have access to treatment in our ongoing trials and through our compassionate use program."

The Expanded Access Program (or compassionate use) is a program recognized by the FDA as a follow-on to their granting Fast Track Designation to onvansertib. An EAP provides a potential pathway for patients with a serious or life-threatening condition to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP is intended for use in combination with FOLFIRI and bevacizumab for the second-line treatment of patients with KRAS-mutated mCRC that have progressed on prior FOLFOX (with or without bevacizumab) therapy.

Requests for expanded access to onvansertib must be made by a U.S. licensed, treating physician. Physicians can learn more about the onvansertib expanded access program protocol at clinicaltrials.gov and can request access for a patient by sending an e-mail to [email protected]

The FDA’s Fast Track program facilitates the development of drugs intended to treat serious conditions and that have the potential to address unmet medical needs. A drug program with Fast Track status is afforded greater access to the FDA for the purpose of expediting the drug’s development, review and potential approval. In addition, the Fast Track program allows for eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, as well as for Rolling Review, which means that a drug company can submit completed sections of its New

Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be submitted for review.

About the Phase 1b/2 Clinical Trial of Onvansertib in KRAS-Mutated mCRC
In this open-label, Phase 1b/2 trial, onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) is being evaluated for safety and efficacy for second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for SecondLine Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, will enroll up to 44 patients with a KRAS mutation and histologically confirmed metastatic and unresectable disease. In addition, patients must have failed treatment or be intolerant of FOLFOX (fluoropyrimidine and oxaliplatin) with or without bevacizumab. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.
About Onvansertib
Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported.
Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Cardiff Oncology believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), KRAS-mutated colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.
Cardiff Oncology has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 2 clinical trial of onvansertib in combination with decitabine in patients with relapsed or refractory AML (NCT03303339).
Cardiff Oncology licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array/Pfizer, Ignyta/Roche and Genentech.

PRESS RELEASEBolt Biotherapeutics Announces Issuance of U.S. Patent for the Boltbody™ ISAC Technology and its Lead Development Candidate, BDC-1001

On June 9, 2020 Bolt Biotherapeutics, Inc., a private clinical-stage biotechnology company developing its Immune-Stimulating Antibody Conjugate (ISAC) platform technology to harness the power of the immune system to treat cancer, reported that the U.S. Patent and Trademark Office (USPTO) has issued U.S. Patent No. 10,675,358 entitled "Antibody Adjuvant Conjugates (Press release, Bolt Biotherapeutics, JUN 9, 2020, View Source [SID1234560927])." The patent provides protection for immunoconjugates of a piperazinyl imidazoquinoline adjuvant bound to any antibody, including Bolt’s BDC-1001 ISAC embodiment.

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BDC-1001 is being developed as a monotherapy for patients with HER2-expressing solid tumors. BDC1001 is an ISAC comprised of trastuzumab conjugated to a Bolt proprietary TLR7/8 agonist payload.

Michael N. Alonso, Ph.D., scientific co-founder and vice president of immunology and pharmacology of Bolt, stated "The development of Boltbody ISACs is motivated by the insatiable need to translate scientific discoveries into products that will help cancer patients become survivors. This patent issuance is an important milestone that provides protection for our BDC-1001 clinical asset and our Boltbody ISAC technology platform. Our dedicated and talented teams will continue to aggressively build a robust patent portfolio to protect our pipeline, our platform, and our commitment to patients."

About Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) Platform Technology The Boltbody platform consists of Immune-Stimulating Antibody Conjugates (ISAC) that harness the ability of innate immune agonists to convert cold tumors into immunologically hot tumors thereby illuminating tumors to the immune system and allowing them to be invaded by tumor killing cells. Boltbody ISACs have demonstrated the ability to eliminate tumors following systemic administration in preclinical models and have also led to the development of immunological memory, which is predicted to translate into more durable clinical responses for patients. The company’s first Boltbody to enter clinical development, BDC-1001, is currently being evaluated in patients with HER2-expressing solid tumors

Versant Ventures Launches Lycia Therapeutics with $50 Million

On June 9th, 2020 Lycia Therapeutics, Inc. exited stealth mode with a $50 million commitment from founding investor Versant Ventures (Press release, Lycia Therapeutics, JUN 9, 2020, View Source [SID1234560925]). Proceeds are being used to develop lysosomal targeting chimeras, or LYTACs, as therapeutics for a broad set of currently intractable cell surface targets.

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"I look forward to working closely with the team to advance the science and explore the broader applications to developing effective therapeutics for intractable cancers and many other challenging diseases."

Interest in the field of protein degradation continues to grow, as classical approaches to developing small molecule and biologic therapeutics have proven to be ineffective on many disease-relevant targets. This is especially the case for extracellular and secreted proteins that have inaccessible active sites, complex and challenging molecular structures, and other limiting factors.

"Our understanding of the biological pathways and targets relevant to certain diseases has far outreached our ability to develop effective therapeutic modalities," said Lycia CEO Aetna Wun Trombley, Ph.D. "LYTACs offer the promise of targeting a wider array of proteins on the cell surface or in the extracellular compartment. Many of these have been linked to cancer, autoimmune and other serious diseases."

Targeting extracellular proteins with LYTACs

Versant established Lycia in 2019 within the firm’s San Diego-based Inception labs in collaboration with academic founder Carolyn Bertozzi, Ph.D., professor of chemistry and HHMI investigator at Stanford University. The initial aim was to develop and validate a drug discovery platform.

The LYTACs platform leverages decades of work in the field of lysosomal biology. In a 2019 publication, Dr. Bertozzi’s team at Stanford demonstrated that a cation-independent receptor called CI-M6PR could be exploited to capture and drag extracellular proteins into cells, trafficking them to the lysosome for destruction.

In addition to CI-M6PR, Lycia has now extended this approach and leveraged other tissue-specific internalizing receptor systems to further expand the technology’s therapeutic potential.

"Our understanding of multiple receptor systems including M6PR offered Lycia the opportunity to take the protein degradation field in a new direction," said Dr. Bertozzi. "I look forward to working closely with the team to advance the science and explore the broader applications to developing effective therapeutics for intractable cancers and many other challenging diseases."

Relevance to numerous diseases and modalities

With the Inception team, Lycia has been able to validate, optimize and expand this approach. Confirmatory studies have shown targeted degradation of cell surface proteins such as EGFR, PD-L1, as well as secreted proteins like ApoE4. Collectively these results suggest that LYTACs can potentially serve as effective therapeutics for a wide range of difficult-to-treat conditions. Further work continues to target other membrane proteins, including receptor tyrosine kinases, and pathogenic immune complexes in circulation.

Moreover, the platform has the potential to extend the reach of other modalities including gene therapy, which cannot be chronically dosed due to the production of autoantibodies. The platform can be exploited to develop a LYTAC binder able to capture and drag the autoantibodies into a lysosomal trafficking pathway.

Advisors and operating plans

The Lycia team will work alongside experienced entrepreneurs and leading scientists who have made important contributions in the field and bring relevant experience to the company.

Carolyn Bertozzi, Ph.D., who chairs Lycia’s Scientific Advisory Board, is the Anne T. and Robert M. Bass Professor of Chemistry and Professor of Chemical & Systems Biology and Radiology at Stanford University, and an Investigator of the Howard Hughes Medical Institute. Dr. Bertozzi’s research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface glycosylation pertinent to disease states. She is an elected member of the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. She has been awarded the Lemelson-MIT Prize, the Heinrich Wieland Prize, and a MacArthur Foundation Fellowship, among many others.

Randy Schekman, Ph.D., is an investigator of the Howard Hughes Medical Institute and a Professor of Cell and Developmental Biology in the Department of Molecular and Cell Biology at the University of California at Berkeley. He was awarded the Nobel Prize in Physiology or Medicine in 2013.

Mark M. Davis, Ph.D. is the Director of the Stanford Institute for Immunology, Transplantation and Infection (ITI), a Professor of Microbiology and Immunology and a Howard Hughes Medical Institute Investigator at Stanford University. He received a B.A. from Johns Hopkins University and a Ph.D. from the California Institute of Technology. Dr. Davis is well known for identifying many of the T-cell receptor genes, which are responsible for the ability of these cells to recognize a diverse repertoire of antigens. His current research focuses on obtaining a systems level understanding of the human immune system.

Brian Druker, M.D., is Professor of Medicine and Director of the OHSU Knight Cancer Institute and the JELD-WEN Chair of Leukemia Research. His research focuses on activated tyrosine kinases with an emphasis on their role in cancer. His work resulted in Gleevec, the first drug to target the molecular defect of a cancer while leaving healthy cells unharmed. He has been recognized with numerous awards, including the Warren Alpert Prize from Harvard Medical School, the Lasker-DeBakey Award for Clinical Medical Research, the Japan Prize in Healthcare and Medical Technology, and most recently, the 2018 Tang Prize in Biopharmaceutical Science.

Alanna Schepartz, Ph.D., is the T.Z. and Irmgard Chu Distinguished Chair in Chemistry and Professor of Molecular and Cell Biology at the University of California at Berkeley. Her research spans the fields of chemical and synthetic biology. A primary focus is to uncover the chemistry that drives complex cellular processes and apply this knowledge to design or discover molecules – large and small – that possess unique or useful properties.

Monther Abu-Remaileh, Ph.D., is Assistant Professor of Chemical Engineering at Stanford University. His lab is focused on identifying novel pathways that enable cellular and organismal adaptation to metabolic stress and changes in environmental conditions, as well as how these pathways go awry in human diseases such as cancer, neurodegeneration and metabolic syndrome, in order to engineer new therapeutic modalities.

Laurent Fischer, M.D., who is an independent member of Lycia’s Board of Directors, was senior vice president and head of the liver therapeutic area at Allergan. Before that, he was CEO of Tobira Therapeutics, which Allergan acquired in 2016 for $1.7 billion. Dr. Fischer has held numerous CEO roles at biotechnology companies, as well as senior leadership positions at large pharmaceutical companies. He has been involved in the launch of multiple drugs.

Lycia will be headquartered in the San Francisco Bay Area and will continue collaborating with the San Diego-based Inception team during the startup phase. With this financing, the company plans to build out its foundational LYTAC platform, develop an internal pipeline, and will also consider discovery-stage partnerships to fully exploit the potential of this novel approach.

"The team at Lycia has begun to translate recent insights on the utility of targeted lysosomal trafficking into a new class of therapeutics," said Clare Ozawa, Ph.D., Versant managing director and a Lycia board member. "With this financing, we hope to build on this progress and to generate a broad pipeline of development candidates."

About Lycia Therapeutics, Inc.

Lycia Therapeutics, Inc. is a biotechnology company using its lysosomal targeting chimeras (LYTACs) platform to discover and develop first-in-class therapeutics that degrade extracellular and membrane-bound proteins that drive a range of difficult-to-treat diseases, including cancers and autoimmune conditions. Lycia was established in 2019 within founding investor Versant Ventures’ San Diego-based Inception Discovery Engine, and now is headquartered in the San Francisco Bay Area. Visit www.lyciatx.com for more information.

About Versant Ventures

Versant Ventures is a leading healthcare venture capital firm committed to helping exceptional entrepreneurs build the next generation of great companies. The firm’s emphasis is on biotechnology companies that are discovering and developing novel therapeutics. With $3.2 billion under management and offices in the U.S., Canada and Europe, Versant has built a team with deep investment, operating and R&D expertise that enables a hands-on approach to company building. Since the firm’s founding in 1999, more than 75 Versant companies have achieved successful acquisitions or IPOs. Versant is currently investing out of its seventh fund, Versant Venture Capital VII, a $600 million global biotech fund closed in December 2018. In parallel the firm co-invests out of its Canadian strategic fund Versant Voyageurs I and its later-stage biotech opportunity fund Versant Vantage I. For more information, please visit www.versantventures.com.