Venn Therapeutics: Next Generation Cancer Immunotherapy

Equities Research  |

We've been following the progress of a privately held company called Venn Therapeutics that has been working to develop the next generation of immunotherapies to fight cancer. The company is focused on meeting the needs of the majority of cancer patients with immunologically "cold" tumors that do not benefit from current immunotherapy treatments. It is estimated that 70-80% of cancer patients have such immunologically cold tumors. Venn is focused on turning these cold tumors hot -- whereby their immune systems have been primed to recognize the tumors as foreign or aberrant -- and hence greatly increasing the patient population that will benefit from the cutting edge science of cancer immunotherapy.

While there is of course no shortage of young, aspirational biotechnology companies, we were particularly struck by the pedigrees of the scientific team at the helm of Venn at this critical early stage of development. We're further encouraged by the company's approach of identifying key immune system targets and developing drugs that are expected to rationally combine with big pharma's first generation therapies. Recent acquisitions and licensing deals clearly demonstrate the need for new and complementary approaches that are driving valuations in these next generation oncology assets.

Scientific Leadership

Venn's scientific team is led by Edith Janssen, PhD, the company's Chief Scientific Officer. Dr. Janssen collaborated with the 2011 recipient of the Nobel Prize in Medicine, Dr. Bruce Beutler, to understand the interaction between innate and adaptive immunity, and her pioneering work in defining T cell priming and memory development, a long-standing paradox in cellular immunology, was published in Nature and Nature Immunology. The Janssen Laboratory at Cincinnati Children's Hospital -- ranked #3 by US News & World Report in its survey of best children's hospitals -- is focused on immune oncology.

James Leahy, PhD, is Venn's Director of Medicinal Chemistry. Dr. Leahy is a Professor in the Department of Chemistry at the University of South Florida and a member of the Florida Center of Excellence for Drug Discovery and Innovation with an appointment in the Department of Molecular Medicine in the Morsani College of Medicine. Dr. Leahy was previously spent 14 years as the Senior Director of Chemistry at Exelixis. His work has resulted in three FDA approved cancer drugs as well as many candidates that are still in late stage clinical trials.

In April 2018, T. Shantha Raju, PhD, joined Venn Therapeutics as Head of Research and Development, bringing over 20 years of experience at companies including Genentech, Johnson & Johnson, and Medimmune. Dr. Raju has a successful track record of drug development in multiple therapeutic areas and has worked on all stages of development including discovery, licensing and regulatory filings with the FDA. He has 48 peer-reviewed scholarly publications and over 150 total scholarly presentations.

Venn's Scientific Advisory Board includes Darrell Irvine, Paul Rennert and Stefani Spranger, all of whom are PhDs, encompassing expertise in immunology and cancer. Dr. Irvine is a Professor of Biological Engineering and Materials Science & Engineering at the Massachusetts Institute of Technology (MIT), where he is also Associate Director of the Koch Institute for Integrative Cancer Research. Dr. Irvine is an Investigator of the Howard Hughes Medical Institute and a member of the steering committee of the Ragon Institute of MGH, MIT and Harvard.

Dr. Rennert is an experienced biotechnology executive, seasoned researcher and author. He has been involved extensively in the development of small molecule and biologic drugs for oncology, autoimmunity, chronic inflammation and fibrosis, primarily as a Principal Scientist at Biogen. He also worked intensively to prioritize and build the immunotherapy portfolio of Co-Stim Pharmaceuticals, which was subsequently acquired by Novartis.

Dr. Spranger, an Assistant Professor at the Koch Institute for Integrative Cancer Research and Department of Biology at MIT, is widely regarded as an expert in cancer immunology and cancer biology. She did her postdoctoral work at the University of Chicago with Dr. Thomas F. Gajewski, named as one of 12 "Giants of Cancer Care for 2017" by OncLive. Dr. Spranger's groundbreaking work in identifying the β-catenin pathway -- a melanoma-cell-intrinsic signaling pathway -- was published in Nature. She has co-authored significant scientific papers on key immunotherapeutic targets such as IDO, STING, Tregs and checkpoint inhibitors.

Pipeline

Venn's pipeline candidates are each designed to overcome the limitations of first generation therapies, including checkpoint inhibitors such as Keytruda and Opdivo. It is estimated that only 15% to 20% of cancer patients show a durable response to these adaptive immunotherapies. Venn aims to expand the therapeutic benefits of these drugs by regulating the body's innate immune system so that it becomes alerted to the presence of cancer.

Source: Venn Therapeutics

Venn's lead candidate is a STING agonist, or stimulator of interferon genes, that has been shown to enhance survival in a preclinical model. VTX-001 was highlighted at AACR17, the annual meeting of the American Association for Cancer Research, as being a highly potent STING agonist and having a superior safety profile as recognized by the panel chair. VTX-001 has a significant advantage over competing approaches as the drug converts the tumor cells into STING "factories” that generate STING up to 48 hours post treatment, versus only four to eight by competing approaches. Dr. Glen Barber, the Professor in the Department of Cell Biology at the University of Miami School of Medicine who discovered STING ten years ago, published a paper in March 2018 showing that long lasting expression of STING is a key to better responses against tumor.

In April 2018, the company licensed a novel integrin αvβ8 antibody from the University of California, San Francisco, created by Dr. Stephen Nishimura's esteemed scientific team. The antibody, now known internally as VTX-002, is designed to target and inhibit TGF-β (transforming growth factor β), a key signaling pathway in tumor expression. This antibody may have multiple applications beyond cancer, including inflammation and fibrotic lung diseases.

VTX-003 inhibits the active form of the β-catenin protein and has the potential to address many unmet medical needs, from MSS (micro satellite stable) colorectal cancers to liver and ovarian cancers. Even at this early stage, the drug has attracted interest from major pharmaceutical companies. According to Venn, VTX-003's big advantage is its high selectivity in only blocking the cancer causing transcription factors while not impairing the embryonic and other functions in a cell.

Outlook

We will now be focused on moving our pipeline programs rapidly towards the clinic and bring new therapeutics tools to the battlefield for the patients in their fight against cancer.

- Sam Shrivastava, Chairman and CEO, Venn Therapeutics.

Venn Therapeutics is currently raising a Series A round of $10 to $15 million. In light of the spate of early stage immuno-oncology companies whose assets have been captured through acquisition or licensing, we believe that Venn presents a significant value proposition on the risk-reward spectrum at this stage of its development. Notable transactions include Bristol-Myers Squibb's acquisition of IFM Therapeutics and its STING and NLRP3 agonist programs for $1.4 billion, AbbVie's $685 million licensing deal for Belgium's argenx and its GARP/TGF-β program and Novartis' $517 million deal for XOMA's TGF-β program. Last week, Lilly announced the acquisition of ARMO Biosciences and its pipeline of immune system activation candidates in cancer patients for $1.6 billion.

Venn Therapeutics has assembled a superior scientific leadership team that may be uniquely suited to leverage its clinical assets and drive development of its next generation oncology therapies. We believe the company merits close observation from investors, and we'll be eager to follow its progress through the clinic.


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