Quentis Therapeutics Debuts with $48 Million Series A Financing to Advance First-in-Class Immunotherapies Targeting Endoplasmic Reticulum Stress Response Pathways

Quentis is pioneering first-in-class cancer immunotherapies that modulate endoplasmic reticulum (ER) stress response pathways in the tumor microenvironment. The Series A proceeds will support the advancement of Quentis’ lead program, a small molecule IRE1α inhibitor, into the clinic in 2019 and through clinical proof-of-concept. Additional uses of the capital include developing a pipeline of preclinical programs and building out Quentis’ team.

The company was enabled by Highline Therapeutics, a Versant Ventures Discovery Engine, under an agreement with Weill Cornell Medicine through its office of Biopharma Alliances and Research Collaborations to establish New York-based spinout companies to advance breakthroughs emerging from Weill Cornell Medicine research.

Quentis’ scientific foundation is based on landmark research conducted by Laurie Glimcher, M.D., previously Dean of Weill Cornell Medicine, now President and Chief Executive Officer of Dana-Farber Cancer Institute and Professor at Harvard Medical School, and Juan Cubillos-Ruiz, Ph.D., Assistant Professor of Microbiology and Immunology in Obstetrics and Gynecology at Weill Cornell Medicine. Drs. Glimcher and Cubillos-Ruiz’s research revealed critical roles that the ER stress response plays in compromising the immune system’s ability to detect and fight cancer.

Chronic activation of the ER stress response correlates with poor outcomes in multiple tumor types, including ovarian cancer, triple-negative breast cancer, pancreatic adenocarcinoma and glioblastoma. By modulating ER stress response pathways, Quentis aims to boost a patient’s own anti-cancer immunity and enable more patients to benefit from immunotherapy. The company is pursuing multiple ER stress pathway targets in the tumor microenvironment, as well as in other diseases where ER stress plays an important role.

“We’ve witnessed great progress in our ability to harness the immune system to fight cancer. However, despite these advances, the effectiveness of immunotherapy remains limited, and many patients and many types of cancer don’t respond to treatment,” said Michael Aberman, M.D., president and CEO of Quentis Therapeutics. “The scientific community continues to learn about important mechanisms, like the ER stress response, that impact cancer immunity. At Quentis, we are excited to be part of the next generation of immuno-oncology companies that are pursuing new therapeutic approaches to hopefully enable more cancer patients to benefit from immunotherapy.”

Dr. Aberman continued, “We are thrilled to introduce Quentis today, and we are grateful for the dedication and support of our investors and all those who have helped us reach this important milestone. We look forward to continuing to build out our team in the coming months as we advance toward entering the clinic in 2019.”

“It is profoundly gratifying to see our discoveries on the key role played by the ER stress response in inhibiting effective anti-tumor immunity translate into the advancement of potentially meaningful medicines for patients,” said Dr. Glimcher, a scientific co-founder of Quentis and chair of the company’s Scientific Advisory Board. “I look forward to continuing to work closely with the Quentis team as they advance development programs toward clinical study.”

“Immunotherapy is changing the face of cancer treatment, but harsh conditions within tumors inhibit the protective activity of immune cells and present an impediment to broad efficacy with immunotherapies. We’ve made important strides in understanding how aberrant ER stress responses in cancer promote immune cell dysfunction, and we continue to expand our knowledge of this novel biology,” said Dr. Cubillos-Ruiz, a scientific co-founder of Quentis and member of the company’s Scientific Advisory Board. “I look forward to seeing Quentis translate this maturing knowledge in the drug development setting.”

“Quentis is assembling all the necessary elements to become a leading company in the ER stress response and immuno-oncology fields,” said Carlo Rizzuto, Ph.D., a partner at Versant and a Quentis board member. “We have great confidence in Michael’s ability to build the company and advance its programs to develop new treatments for patients.”

In connection with the financing, Amy Schulman, partner with Polaris Partners and LS Polaris Innovation Fund, will join Dr. Rizzuto, Michael A. Foley, Ph.D., Sanders Director, Tri-Institutional Therapeutics Discovery Institute, and Dr. Aberman on Quentis’ Board of Directors.

About Quentis’ Management Team and Scientific Advisors

Quentis is amassing a team with exceptional expertise in immunology, immuno-oncology, the tumor microenvironment, endoplasmic reticulum stress biology, and drug development.

Key Management Team Hires:

• Michael Aberman, M.D., former Senior Vice President of Strategy and Investor Relations with Regeneron and biotech analyst with Credit Suisse and Morgan Stanley, has been appointed president and CEO of Quentis
• Joseph Vacca, Ph.D., former Vice President of Chemistry at Merck, as well as Head of Early Success Sharing Partnerships at Wuxi Apptec, is serving as Head of Chemistry at Quentis
• Scientific co-founder Sarah Bettigole, Ph.D., is serving as Quentis’ Director of Biology

Scientific Advisory Board (SAB) Appointments:

• Laurie Glimcher, M.D., Chair of SAB, President and Chief Executive Officer of Dana-Farber Cancer Institute and Professor at Harvard Medical School
• Jeffrey A. Bluestone, Ph.D., the A. W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology at the University of California, San Francisco (UCSF), and the president and CEO of the Parker Institute for Cancer Immunotherapy
• Juan Cubillos-Ruiz, Ph.D., Assistant Professor of Microbiology and Immunology in Obstetrics and Gynecology, Weill Cornell Medicine
• Andrew Dannenberg, M.D., Professor of Medicine in Cardiothoracic Surgery and Henry R. Erle, M.D. - Roberts Family Professor of Medicine, Weill Cornell Medicine
• Dmitry Gabrilovich, M.D., Ph.D., a Christopher M. Davis Professor in Cancer Research and Program Leader, Immunology, Microenvironment, and Metastasis at the Wistar Institute in Philadelphia, and Wistar Professor at the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
• Ira Tabas, M.D., Ph.D., Richard J. Stock Professor of Medicine, Cell Biology, and Physiology at Columbia University Medical Center

About the Endoplasmic Reticulum Stress Response

The endoplasmic reticulum (ER) is a structure within cells responsible for multiple functions, including serving as a sensor of cellular stress. Many diseases, including cancer, can cause persistent ER stress, triggering aberrant responses that disrupt normal cellular functions.

Quentis’ lead program is an inhibitor of IRE1α, a central enzyme in the ER stress-response signaling pathway that activates the normally dormant XBP1 protein. Persistent IRE1α-XBP1 signaling in innate immune cells in the tumor microenvironment has been shown to disrupt the immune system’s ability to fight cancer in several ways:

• Disabling dendritic cells’ ability to activate cancer-fighting T cells through inhibition of antigen presentation
• Driving formation of myeloid-derived suppressor cells (MDSCs), which suppress T cell function
• Causing macrophages (a type of white blood cell) to promote tumor cell metastases
• Increasing regulatory T cells that suppress the immune system

With anti-cancer immunity blocked, cancer can more easily grow and spread throughout the body.

Quentis has developed potent and selective small molecule inhibitors of IRE1α that suppress XBP1 activity in the tumor microenvironment and awaken the immune system’s ability to fight cancer.

About Quentis Therapeutics

Quentis Therapeutics is a preclinical stage biotechnology company that is translating novel biology into new therapeutic approaches to help more cancer patients benefit from immunotherapy. Based on our deep expertise in endoplasmic reticulum (ER) stress biology and the tumor microenvironment, we are pioneering first-in-class ER stress response modulators to boost the immune system’s ability to fight cancer. Our lead program is a first-in-class IRE1α inhibitor. We are pursuing multiple additional ER stress pathway targets in the tumor micro-environment, as well as in other diseases where ER stress plays an important role. Privately held, Quentis is headquartered in New York City. To learn more, please visit www.quentistx.com and follow us on Twitter at @QuentisTx.

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