Versantis | November 15, 2021
Versantis, a clinical-stage biotechnology company developing novel therapies for orphan liver and pediatric diseases, announced that positive Phase 1b clinical data from a study of its lead investigational, orphan-designated product, VS-01, in 12 hospitalized patients with decompensated liver cirrhosis will be presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting. The data show that VS-01 was safe and well tolerated in these patients, and demonstrated promising early indications of efficacy in this clinical study. VS-01 is a potentially lifesaving, multi-organ support therapy that aims to timely reverse Acute-on-Chronic Liver Failure (ACLF) by enhancing the clearance of ammonia and other toxins following paracentesis.
The Abstract selected for oral presentation is as follows
Oral Presentation Title: Safety and Preliminary Efficacy and Pharmacokinetics of Intraperitoneal VS-01 Infustions in Patients with Decompensated Liver Cirrhosis: A First-in-Human, Open-label, Phase 1b Clinical Trial
Presenter: Dr. Frank Erhard Uschner, Section for Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt,
Session Date/Time: Monday, November 15, 2021, 12:30 p.m. EST
The annual Liver Meeting, held by AASLD, brings together attendees from around the world to exchange the latest research, discuss new developments in treatments, and network with others in the field.
The primary objective of this single-center first-in-human study was to evaluate the safety and tolerability of i.p.-administered VS-01 on top of standard of care in cirrhotic patients with ascites and mild hepatic encephalopathy following single and multiple intraperitoneal administrations. The secondary objectives were to gather preliminary PK, PD, and clinical efficacy data. In total, all 12 patients completed treatment in the Department of Internal Medicine I, Goethe University Frankfurt and were assigned to receive either a single dose of VS-01 (Part A; n=9) or four consecutive doses (Part B; n=3). Following the drainage of ascites in these patients, VS-01 was then infused into the peritoneal cavity via the existing paracentesis catheter and removed after a dwell time of 2-3 hours. No treatment-related serious adverse events were reported and no patient discontinued treatment due to an adverse event. VS-01 also demonstrated promising clinical efficacy results, including a high and dose-dependent ammonia clearance, promising improvement in hepatic encephalopathy based on psychometric tests, and increased peritoneal clearance of ACLF-related metabolites.
“The data show that VS-01 is safe and well tolerated in cirrhotic patients with ascites and covert (mild) hepatic encephalopathy, so very promising. We were able to administer VS-01 using standard hospital equipment via the therapeutic paracentesis catheter, which we believe can easily be incorporated into standard of care for patients There are very few treatments available for these patients and VS-01 is complementary to those, so we are excited to continue advancing it’s development and hopefully generate the data supporting this ground-breaking clinical approach.”
Prof. Dr. Trebicka, the principal investigator and head of the Section of Translational Hepatology in Goethe University Frankfurt
“VS-01 represents a promising new therapeutic for the potential treatment of patients with ascites and acute complications of cirrhosis. The data from this early study were very promising and importantly show that VS-01 appears to be safe and well tolerated in these patients. The amomonia and ACLF metabolites clearance data is particularly encouraging,” added Vincent Forster, CEO and co-Founder of Versantis. “The successful completion of this study supports future development of VS-01. We are now preparing to initiate a multi-center Phase 2a study in patients with ACLF, a seriously underserved and under-resourced indication. Together with our pipeline of innovative products, we are committed to developing and commercializing new treatment options for patients suffering from acute liver diseases.”
About Acute-on-Chronic Liver Failure (ACLF)
ACLF is an underserved medical condition, which, despite best possible available care, is associated with high short-term mortality. It is characterized by an abrupt life-threatening worsening of a pre-existing chronic liver disease (e.g., cirrhosis) resulting in liver and extrahepatic organ failure rapidly progressing into coma and death. Every year at least 150’000 patients are hospitalized with ACLF in the US and EU. The incidence is growing due to a higher prevalence of diabetes, obesity, fatty liver diseases, and alcohol consumption. By timely reversing ACLF and the multi-organ complications arising from cirrhosis, VS-01 aims to improve outcomes in these patients and relieve the growing health and economic burden of this advanced liver disease.
Versantis is a clinical stage biotechnology company focused on addressing the growing, un-met medical need in liver diseases. With a pipeline of drug and diagnostic products covering chronic and acute indications, Versantis believes it can revolutionize current standard of care for patients suffering from acquired and genetic hepatic deficiencies. Versantis’ lead program, VS-01, is in clinical development as a first-line therapy for the timely reversal of acute-on-chronic liver failure (ACLF). It harnesses Versantis’ proprietary scavenging liposomes to extract toxins from the body and, if approved, will be the first drug to take advantage of the intraperitoneal route to potentially support the liver, kidneys and brain, the organs that most often fail in cirrhotic patients. VS-01 has received orphan drug designation (ODD) from the EMA and U.S. FDA, as well as a Rare Pediatric Diseases Designation from the U.S. FDA for Urea Cycle Disorders. Founded by scientists from ETH Zurich with entrepreneurial drive, Versantis has built a team and Board of seasoned industry executives with a proven ability to advance novel therapies from the idea stage into clinical development. The company is headquartered in Zurich, Switzerland.
Ori Biotech | October 15, 2020
Ori Biotech Ltd (Ori), a leading innovator in cell and gene therapy (CGT) manufacturing, today announced the successful close of a $30 million Series A financing round, bringing the company's total funding to date to $41 million. The new funding will be used to help bring Ori's innovative manufacturing platform to the market. The Ori platform delivers scalable solutions to flexibly address the critical clinical and commercial manufacturing needs of CGT developers. The Series A investor syndicate was led by the experienced life sciences investment team at Northpond Ventures, a leading global science, medical, and technology-driven venture fund, alongside Octopus Ventures, a leading European venture fund. Northpond and Octopus invested alongside significant support from Ori's existing institutional investors, Amadeus Capital Partners, Delin Ventures, and Kindred Capital. "Closing a significant Series A round, during these uncertain times, further validates Ori's disruptive approach to fully automating cell and gene therapy manufacturing to increase throughput, improve quality, and decrease costs," said Jason C. Foster, CEO of Ori Biotech. "We are excited to work with our top tier investors and development partners to bring our platform to market as fast as possible to achieve our mission of enabling patient access to life-saving cell and gene therapies." "As early investors in disruptive life sciences platform technology companies, we have seen how cutting-edge technologies like Ori's can bring significant value to the industry and lead to breakthroughs for patients," said Michael Rubin, M.D., Ph.D., Founder and CEO of Northpond Ventures. "We believe that the Ori team has developed a truly innovative technology that can enable millions of patients to gain access to these important treatments." Ori's bespoke platform was designed specifically to address the unique requirements of a new generation of personalized cell and gene therapies. By fully automating and standardizing CGT manufacturing in a closed platform, Ori offers therapeutics developers the opportunity to seamlessly scale from pre-clinical process development to commercial-scale manufacturing. Its flexible platform enables increased throughput, improved quality, and decreased costs.
Pfizer Inc | August 24, 2021
Pfizer Inc. and Trillium Therapeutics Inc. today announced that the companies have entered into a definitive agreement under which Pfizer will acquire Trillium, a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer. Under the terms of the agreement, Pfizer will acquire all outstanding shares of Trillium not already owned by Pfizer for an implied equity value of $2.26 billion, or $18.50 per share, in cash. This represents a 118% premium to the 60-day weighted average price for Trillium.
Trillium’s portfolio includes biologics that are designed to enhance the ability of patients’ innate immune system to detect and destroy cancer cells. Its two lead molecules, TTI-622 and TTI-621, block the signal-regulatory protein α (SIRPα)–CD47 axis, which is emerging as a key immune checkpoint in hematological malignancies. TTI-622 and TTI-621 are novel, potentially best-in-class SIRPα-Fc fusion proteins that are currently in Phase 1b/2 development across several indications, with a focus on hematological malignancies.
“Today’s announcement reinforces our commitment to pursue scientific breakthroughs with the addition of potentially best-in-class molecules to our innovative pipeline,” said Andy Schmeltz, Global President & General Manager, Pfizer Oncology. “The proposed acquisition of Trillium builds on our strong track record of leadership in Oncology, enhancing our hematology portfolio as we strive to improve outcomes for people living with blood cancers around the globe. Our deep experience in understanding the science of blood cancers, along with the diverse knowledge base we have developed across our growing hematology portfolio of eight approved and investigational therapies, provide us with a foundation to advance these important potential medicines to patients who need them.”
Hematological malignancies are cancers that affect the blood, bone marrow, and lymph nodes. This classification includes various types of leukemia, multiple myeloma, and lymphoma. More than 1 million people worldwide were diagnosed with a blood cancer in 2020, representing almost 6% of all cancer diagnoses globally. In 2020, more than 700,000 people worldwide died from a form of blood cancer.
“We’re delighted to announce Pfizer’s proposed acquisition of Trillium. Today’s announcement reflects Trillium’s potentially best in class SIRPα–CD47 status and contribution to immuno-oncology,” said Dr. Jan Skvarka, Chief Executive Officer of Trillium. “Trillium has the only known SIRPα–CD47 targeting molecules with clinically meaningful monotherapy responses as well as a strong basis for combination therapies, which is supported by preclinical evidence with a diverse set of therapeutic agents. With Pfizer’s global reach and deep capabilities, we believe our programs will advance more quickly to the patients we’ve always aspired to serve. We believe this is a good outcome for patients and our shareholders.”
In clinical studies to-date, TTI-622 and TTI-621 have demonstrated activity as monotherapy in relapsed or refractory lymphoid malignancies, including Diffuse Large B-cell Lymphoma (DLBCL), Peripheral T-cell lymphoma (PTCL), Follicular Lymphoma (FL), and other lymphoid malignancies. As of July 26, 2021, Phase 1 data for TTI-622 in 30 response-evaluable patients have shown deep and durable responses in heavily pretreated patients, including two complete responses (CRs), one lasting over 114 weeks, with responses ongoing. TTI-622 and TTI-621 are currently the only known CD47-targeted molecules that have demonstrated meaningful single agent activity and CRs in multiple hematological malignancies. Thus far, adverse events (AEs) reported with TTI-622 and TTI-621 have been manageable. Related Grade 3 and 4 AEs with TTI-622 were rare and limited to transient cytopenias. In particular, the molecules demonstrate minimal red blood cell binding and few reported cases of anemia, an observed risk with other CD47-targeted approaches. Further data are expected to be shared at a forthcoming medical conference.
“We are encouraged by the early clinical data for TTI-622 and TTI-621 monotherapy for patients with heavily pretreated lymphoid malignancies and early encouraging activity for TTI-622 in patients with multiple myeloma. Just as PD-1 and PD-L1 blockers have proven to be effective immuno-therapeutics for many solid tumors, the SIRPα-CD47 interaction defines a second key immune checkpoint for which disrupting agents are expected to become another important backbone immunotherapy for multiple types of cancer, especially hematological cancers,” said Chris Boshoff, MD, PhD, Chief Development Officer, Oncology, Pfizer Global Product Development. “Utilizing Pfizer’s leading research and global development capabilities, we plan to accelerate the clinical development of SIRPα fusion proteins as a potential new scientific breakthrough and explore combinations within our own portfolio and with innovative next-generation medicines for hematological malignancies.”
In September 2020, as part of the Pfizer Breakthrough Growth Initiative (PBGI), Pfizer invested $25 million in Trillium and Jeff Settleman, Senior Vice President and Chief Scientific Officer of Pfizer’s Oncology Research & Development Group, was named to Trillium’s Scientific Advisory Board. Established in June 2020, PBGI’s goal is to provide funding for scientific research as well as access to Pfizer’s experts to ensure the continuity of clinical programs that could be of potential strategic interest for Pfizer. Pfizer has committed to providing up to $500 million in total funding to the PBGI.
Additional Transaction Details
The proposed acquisition of Trillium is to be completed by way of a statutory plan of arrangement under the Business Corporations Act (British Columbia) and subject to customary closing conditions, including approval of 66⅔% of the votes cast by Trillium shareholders, voting together as one class, at a special meeting of Trillium and approval of 66⅔% of the votes cast by Trillium shareholders and warrant holders, voting together as one class, at a special meeting of Trillium. Completion of the acquisition is also subject to court and regulatory approval, as well as certain other closing conditions customary for transactions of this nature.
Pfizer’s financial advisors for the transaction are BofA Securities, Inc., with Ropes & Gray LLP and Norton Rose Fulbright Canada LLP acting as its legal advisors. Centerview Partners LLC served as Trillium’s financial advisor, while Goodwin Procter LLP and Baker McKenzie LLP (Canada) served as its legal advisors.
Accumulating data suggest that the SIRPα–CD47 axis is a key immune checkpoint in hematologic malignancies, similar to the PD-L1 / PD-1 checkpoint for solid tumors. CD47 is a protein that is overexpressed in numerous cancer cells, and in general, high CD47 expression correlates with more aggressive disease and poorer clinical outcomes. SIRPα is an inhibitory receptor expressed on myeloid cells that binds to CD47, preventing the immune system from destroying cancer cells. Disruption of the CD47-SIRPα interaction has been proven to elicit tumor destruction through triggering of an innate immune response.
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us.
About Trillium Therapeutics
Trillium is an immuno-oncology company developing innovative therapies for the treatment of cancer. The company’s two clinical programs, TTI-622 and TTI-621, target CD47, a “don’t eat me” signal that cancer cells frequently use to evade the immune system.