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SQZ Biotechnologies and Collaborators Publish Technology Review on SQZ® APCs and Effective CD8 T Cell Activation

On July 12, 2022 SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported the publication of a technical review examining the ability of SQZ Antigen Presenting Cells (APCs) to activate CD8 T cells through MHC-I antigen presentation, an approach that may enable a more powerful T cell response and infiltration into solid tumors (Press release, SQZ Biotech, JUL 12, 2022, View Source [SID1234616625]). Published in ESMO (Free ESMO Whitepaper)’s Immuno-Oncology and Technology (IOTECH) journal, the review further explores the advantages of the company’s Cell Squeeze technology in cell engineering and manufacturing as well as potential opportunities to develop additional clinical candidates with enhanced capabilities.

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"In this review, for patients with solid tumors, we discuss the critical need to generate CD8 T cell penetration into the tumor microenvironment," said lead author Jong Chul Park, MD, Medical Oncologist, Massachusetts General Hospital Cancer Center, and SQZ cell therapy trial site investigator. "Activation of CD8 T cells through MHC-I antigen presentation is a promising approach and is being tested in the SQZ-PBMC-HPV-101 clinical trial where we’ve seen increases in CD8 T cell tumor infiltration and clinical benefit in a refractory patient with HPV16-mediated cancer. We look forward to potentially building on these early results through combination with various immunomodulatory drugs, such as checkpoint inhibitors."

SQZ has three ongoing Phase 1/2 clinical trials aiming to drive CD8 T cell responses against HPV16+ solid tumors. Given the broad relevance of CD8 T cell responses across tumors, the authors highlight potential for future expansion of development programs into additional areas such as mutant KRAS, mutant TP53, EBV, and other patient-specific antigens.

Review Highlights:

Comparison of Intracellular Delivery Approaches: The Cell Squeeze engineering method has compelling features compared to viral or electroporation approaches across a number of categories, including cell perturbation, scalability, cell types, cargo types, targeting, dosage control, and cost per dose
Enabling MHC-I Presentation and Multi-Dimensional Immune Engineering: SQZ’s approach has demonstrated preclinically dramatic improvements in potential CD8 T cell activation as well as synergy with next generation immuno-oncology drugs such as PD-1 IL2v
Manufacturing and Patient Dose Timing: SQZ clinical candidates experienced an average vein-to-vein time of roughly one week, faster than most other therapeutic approaches for delivering sterile cell therapy
About SQZ-PBMC-HPV
SQZ-PBMC-HPV is the company’s Antigen Presenting Cell (APC) autologous cell therapy clinical candidate and is derived from peripheral blood mononuclear cells (PBMCs), primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with tumor specific E6 and E7 peptide antigens. It received FDA fast track designation in April 2022. In December 2021, the company presented clinical data at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) congress that included a checkpoint refractory head-and-neck cancer patient who demonstrated a radiographic, symptomatic, and immune response in the monotherapy cohort of the Phase 1/2 clinical trial.

SQZ-PBMC-HPV-101 Trial Design
SQZ-PBMC-HPV is being evaluated in a Phase 1/2 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination phases of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a dose-limiting toxicity (DLT) window of 28 days and is designed to identify a recommended phase 2 dose. The planned combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors. DLT will be measured over 42 days.

About Human Papillomavirus Positive Cancers
Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years, often leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer, HPV+ tumors account for 4.5% of all cancers worldwide resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

Orion Biotechnology and Peptilogics Enter Strategic Research Collaboration to Enable AI-Driven Drug Discovery Against Undrugged GPCR Target

On July 12, 2022 Orion Biotechnology Canada Ltd, a drug discovery company targeting previously undruggable G Protein-Coupled Receptors (GPCRs), and Peptilogics, a biotech company engineering peptide therapeutics by combining computation and biology to improve the treatment landscape for patients with life-threatening diseases, reported that they have entered a research and development collaboration to leverage AI for drug discovery against an undrugged GPCR target (Press release, Orion Biotechnology, JUL 12, 2022, View Source [SID1234616624]).

The collaboration will combine the capabilities of Peptilogics’ AI platform (NautilusTM) with Orion Biotechnology’s proprietary drug discovery platform. The companies will leverage expertise in peptide design and engineering to drive drug discovery against an undrugged peptidergic GPCR linked to highly prevalent, life-threatening diseases.

Peptilogics’ Nautilus platform enables in silico predictive peptide design across diverse targets to efficiently access new functional chemical space and custom-design therapeutics. Additionally, Peptilogics’ supercomputer accelerates model development, prediction and evaluation of peptide sequences to produce higher quality hits with greater chance of success. Synergistically, Orion Biotechnology’s platform explores receptor-ligand shape space using proprietary multiplex synthesis technology to generate precision-engineered peptides with enhanced potency and tailored signaling activity. Orion’s platform generates data matrices for AI-assisted lead optimization, offering one of the fastest drug discovery and development solutions to target peptidergic GPCRs.

On the announcement of this collaboration, Dr. Oliver Hartley, VP Drug Discovery at Orion Biotechnology, commented, "We are pleased to be partnering with Peptilogics to push the boundaries of receptor pharmacology and AI computing to accelerate innovation for improved patient outcomes. An AI-driven paradigm shift is happening in drug discovery, and Orion is pleased to be at the forefront of applying AI to the highly valuable space around GPCRs. The ideal fit between Orion’s platform and unique knowledge of receptor-ligand interactions with Peptilogics’ machine learning models will position us to make AI-driven GPCR drug discovery a reality."

"Using Peptilogics’ Nautilus platform, we combine proprietary deep generative models, predictive models and biophysical simulation to design multiparameter-optimized peptides that have the potential to address historically challenging and novel drug targets. Our AI algorithms enable efficient navigation of the vast peptide design space, allowing us to uncover molecules that may not be discovered through traditional screening," said Nicholas Nystrom, Ph.D., Chief Technology Officer of Peptilogics. "We are excited to partner with Orion Biotechnology for their deep GPCR expertise. By combining the strengths of Peptilogics’ Nautilus AI-driven peptide design platform and Orion’s GPCR platform, we aim to reduce the risk, time and cost for drug design."

Worldwide Clinical Trials Enters Into a Strategic Collaboration With Invitae to Accelerate Clinical Trials for Rare Disease Patients

On July 12, 2022 Worldwide Clinical Trials, Inc. (Worldwide), the industry’s leading global, midsize, full-service contract research organization (CRO), reported its strategic partnership with Invitae, a leading medical genetics company (Press release, Invitae, JUL 12, 2022, View Source [SID1234616623]). The partnership makes Worldwide the first CRO to use Invitae’s Explorer tool – part of its real-world data platform that enables access to aggregated genetic testing results.

Around the world, 300 million people have a rare disease, and 72 percent of those diseases have genetic origins (source). This partnership underscores Worldwide’s global leadership in rare disease research – one of its five major therapeutic areas of focus. A rare disease is generally considered to be a disease that affects fewer than 200,000 people in the United States or 5 in 10,000 people in the European Union at any given time. Patient populations for these diseases are small and geographically widespread – a challenge for achieving access to conduct patient education and rare disease clinical research.

Through this partnership, Worldwide has access to data insights based on prevalence, incidence, demographics, geography, and epidemiology for rare disease patients. This aggregated data enables Worldwide to recruit patients faster and pinpoint optimal study locations to help its sponsors uncover new and potentially lifesaving treatments for people suffering from rare diseases.

"This is a game-changer for both our sponsors and patients enrolled in clinical trials," said Peter Benton, President and Co-CEO, Worldwide. "Our unique access to Invitae’s database provides us with superior visibility to an aggregate-level view of patients we otherwise wouldn’t be aware of and enables us to offer advanced clinical trial strategies to our sponsors. This also helps us boost much-needed patient recruitment efforts, expanding our reach and ability to connect the right patients with the right clinical trial opportunities."

"Our strategic collaboration enables Worldwide to gain valuable insight into the genetic etiology of rare disease to help shape and improve the future of clinical trials," said Sean George, Ph.D., Co-Founder and CEO of Invitae. "Our cutting-edge tools empower Worldwide with the opportunity to set clinical trial strategies based on specific disease and geographic prevalence to yield the data needed to treat genetic disorders globally."

With access to Invitae’s aggregated genetic testing data, Worldwide has enhanced its capability to combat the complexities of rare disease trials through quicker visibility of where patients are – with the ultimate goal of providing much-needed and meaningful treatments.

Aligned with their commitment to excellence in rare disease clinical trial design, Worldwide team members are attending and contributing to the World Orphan Drug Congress at the Hynes Center in Boston. Speakers include Dr. Michael Murphy, Chief Medical and Scientific Officer, Worldwide, on the topic of "Endpoints – Where Are We Now and How Does the Development Process Need to Evolve?" on 12 July at 12:15 p.m. ET; and Derek Ansel, Senior Director, Therapeutic Strategy Lead, Rare Diseases, Worldwide, on the topic of "Trends & Challenges: Patient-Focused Rare Disease Research in 2022" on 12 July at 2:00 p.m. ET.

Mercy Offers New GRAIL Blood Test to Detect 50+ Types of Cancer

On July 12, 2022 Mercy and GRAIL, LLC, a health care company whose mission is to detect cancer early when it can be cured, reported plans to offer a multi-cancer early detection (MCED) blood test (Press release, Grail, JUL 12, 2022, View Source [SID1234616622]). GRAIL’s Galleri test uses advanced testing capabilities to detect early cancer signals of more than 50 types of cancer. Mercy is early among health systems to offer this first-of-its-kind test.

"Recommended cancer screenings in the U.S. currently cover only five types of cancer – breast, cervical, colon, lung and prostate – and can screen just one at a time," said Dr. Jay Carlson, clinical chair of Mercy Research, gynecologic oncologist and head of Mercy’s cancer specialty council. "This innovative test has shown the ability to screen for hard-to-detect, aggressive and often deadly types of cancer like pancreatic, ovarian and esophageal, which oftentimes have no warning signs and are caught too late."

The MCED test, which is intended to complement U.S. guideline-recommended cancer screenings, looks for a shared signal present in the bloodstream that has been associated with many cancers.

"Early detection can play a critical role in cancer treatment, allowing cancers to be caught when treatment is more likely to be successful," said Bob Ragusa, chief executive officer at GRAIL. "We believe new approaches, including multi-cancer early detection tests, are the new front in the war on cancer and one of our best chances to bend the cancer mortality curve. We’re excited to work with Mercy to offer Galleri to their patients."

The MCED test is recommended for adults with an elevated risk for cancer, such as those age 50 or older. Galleri is available by prescription only and use of the test is not recommended for those who are pregnant, 21 years or younger, or undergoing active cancer treatment. Patients interested in the test can visit mercy.net/EarlyCancerDetection to fill out a form and, if eligible, be contacted by a Mercy care navigator to walk them through the ordering and testing process. Results will be delivered through care navigators approximately two weeks after blood is drawn and, if a positive signal is detected, they will coordinate additional testing and care.

One of the first Mercy patients to schedule the test was Nancy Dixon, a Mercy co-worker in Oklahoma City.

"My dad died when he was 51 from pancreatic cancer, one of the worst cancers because once you know you have it, the cancer is too far gone," Dixon said. "It’s always been a lingering fear. I was 16 then; I’m now 55. This test gives me some peace of mind rather than not knowing and just waiting. I wish my dad had been able to have access to this blood test. He might be alive today and know my daughter, his grandchild."

In a clinical study, the Galleri test demonstrated the ability to detect a shared signal from more than 50 types of cancer, over 45 of which lack recommended screen tests today. Because the blood test is not currently covered by insurance, patients will pay out of pocket. Mercy will work with patients who qualify for but are unable to pay the total cost of the test.

"Technology continues to push the boundaries on what we are able to do in medicine, making it more predictive, proactive and personalized for patients," said Dr. John Mohart, Mercy chief clinical officer and communities president, who leads operations for all Mercy hospitals. "Early detection has the potential to give us more years with our loved ones, and that’s invaluable."

Romidepsin for Injection Available from Fresenius Kabi

On July 12, 2022 Fresenius Kabi reported the immediate availability in the United States of Romidepsin for Injection, the newest addition to the company’s broad portfolio of injectable oncology medicines (Press release, Fresenius Kabi Oncology, JUL 12, 2022, View Source [SID1234616621]).

Fresenius Kabi Romidepsin for Injection is the first approved generic equivalent for ISTODAX, providing clinicians and patients with a more affordable treatment option. Fresenius Kabi Romidepsin is supplied as a kit including one 10 mg single-dose vial of Romidepsin and one 2.2 mL vial of diluent.

"Generic oncology medicines continue to be vitally important to the protocols used in treating many forms of cancer," said John Ducker, president and CEO of Fresenius Kabi USA. "As a leading U.S. developer and supplier of oncology injectable medicines, Fresenius Kabi remains committed to continuing to expand access to affordable oncology therapies."

Fresenius Kabi Romidepsin is formulated, filled and finished in the United States. The company has invested nearly a billion dollars in U.S. manufacturing and distribution to further strengthen the domestic supply of essential medicines and technologies. To learn more, visit www.moreinamerica.com.

About Romidepsin for Injection

Romidepsin for Injection is a histone deacetylase (HDAC) inhibitor indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in adult patients who have received at least one prior systemic therapy.

Important Safety Information

Myelosuppression: romidepsin can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; monitor blood counts during treatment with romidepsin; interrupt and/or modify the dose as necessary.

Infections: Fatal and serious infections. Reactivation of DNA viruses (Epstein Barr and hepatitis B). Consider monitoring and prophylaxis in patients with evidence of prior hepatitis B.

Electrocardiographic (ECG) changes: Consider cardiovascular monitoring in patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking medicinal products that lead to significant QT prolongation. Ensure that potassium and magnesium are within the normal range before administration of romidepsin.

Tumor lysis syndrome: Patients with advanced stage disease and/or high tumor burden are at greater risk and should be closely monitored and appropriate precautions taken.

Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception.

The most common adverse reactions (≥ 30%), excluding laboratory abnormalities, are nausea, fatigue, infections, vomiting, anorexia, electrocardiogram ST-T wave changes, dysgeusia, constipation and pruritis. Grade 3-4 laboratory abnormalities (≥10%) include lymphopenia, neutropenia, anemia and thrombocytopenia.

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800‐551‐7176, option 5, or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

Carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered romidepsin and warfarin or coumarin derivatives.

Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors.

Avoid use with rifampin and strong CYP3A4 inducers.