INDUSTRIAL IMPACT, MEDICAL
Twist Bioscience | March 10, 2023
On March 9, 2023, Twist Bioscience Corporation, a leading firm providing high-quality synthetic DNA through its silicon platform, announced the launch of integrated antibody discovery services. This premium offering combines the company's synthetic libraries and AI machine learning with an in vivo immunization approach acquired through its acquisition of Abveris, also known as Twist Boston. This service provides customers with optimized, development-ready antibody candidates.
The combined team, now called Twist Biopharma Solutions, is led by Tracey Mullen, MBA, the senior vice president of biopharma for Twist Bioscience. This newly formed entity leverages years of industry expertise, scientific excellence, and proprietary technology to discover the best antibody candidate for therapeutic targets of interest.
Twist Biopharma Solutions offers an end-to-end workflow for centralized antibody discovery and optimization, including target validation, hit generation, lead selection, lead optimization, and lead characterization. Twist, supported by high-throughput DNA synthesis and IgG antibody production, constructs extensive and particular synthetic antibody libraries with discovery starting with either in vivo or in vitro diversity.
The newly integrated in vivo discovery approach from Abveris of single B cell screening and hybridoma discovery enables parallel paths where multiple technology methods can be leveraged to build a panel of highly diverse antibody leads with broad epitope coverage. In addition, this multi-pronged approach can increase the likelihood of discovering highly specific, high-affinity functional antibodies by sampling synthetic and natural diversity.
The South San Francisco and Boston biopharma teams were combined to create Twist Biopharma Solutions, led by Tracey Mullen. Aaron Sato, Ph.D., remains integrally involved in Twist Biopharma Solutions and, as a chief scientific officer of Twist Bioscience, extends his expertise across the organization. Tracey Mullen joined Twist Bioscience in November 2021 through the acquisition of Abveris. In April 2022, she took on the position of senior vice president of operations, driving the completion of the Factory of the Future in Wilsonville, Oregon, which began shipping products in January 2023. Before joining Twist, she served as CEO of Abveris and worked on the antibody discovery team at Biogen.
About Twist Bioscience
Twist Bioscience is a leading biotechnology company specializing in synthetic biology and genomics. It has developed a proprietary DNA synthesis platform that enables the production of custom-designed DNA strands faster, more accurately, and at a lower cost than traditional methods. In addition, Twist collaborates with partners across industries to develop customized DNA sequences for specific applications and offers a range of other products and services, such as oligonucleotides, synthetic genes, and custom panels for next-generation sequencing. The company has also developed a library of over 100 billion synthetic antibodies, which can be used for diagnostic and therapeutic applications.
CELL AND GENE THERAPY, DIAGNOSTICS
Businesswire | March 28, 2023
Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics announced that they have entered into a new non-exclusive licensing agreement for the use of CRISPR Therapeutics’ gene editing technology, known as CRISPR/Cas9, to accelerate the development of Vertex’s hypoimmune cell therapies for type 1 diabetes (T1D).
“We have multiple programs in our T1D portfolio including VX-880 and VX-264, which are in the clinic, as well as our hypoimmune program, in preclinical development,” said Bastiano Sanna, Ph.D., Executive Vice President and Chief of Cell and Genetic Therapies at Vertex. “Having successfully demonstrated clinical proof of concept in T1D in our VX-880 program, we are excited to deepen our relationship with CRISPR Therapeutics with this agreement, which will allow us to further accelerate our goal of generating fully differentiated, insulin-producing hypoimmune islet cells for T1D.”
“We are pleased to expand our long and successful relationship with Vertex with this collaboration which fully leverages our gene editing platform to develop hypoimmune cell therapies for T1D,” said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. “In parallel, we continue to expand our capabilities in regenerative medicine and advance our existing allogeneic gene-edited cell therapy programs.”
Under this agreement, Vertex will pay CRISPR Therapeutics $100 million up-front for non-exclusive rights to CRISPR Therapeutics’ technology for the development of hypoimmune gene-edited cell therapies for T1D. CRISPR Therapeutics will be eligible for up to an additional $230 million in research and development milestones and receive royalties on any future products resulting from this agreement.
CRISPR and ViaCyte, Inc., which was acquired by Vertex in 2022, will continue to collaborate on their existing gene-edited allogeneic stem cell therapies, using ViaCyte cells, for the treatment of diabetes under the terms of their collaboration. A Phase 1/2 study of VCTX211, an allogeneic, gene-edited, stem cell-derived product candidate for T1D, which originated under the CRISPR Therapeutics and ViaCyte collaboration, has been initiated and is ongoing. CRISPR Therapeutics will not obtain any interest in Vertex’s pre-existing pipeline of T1D products, including VX-880 and VX-264.
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) — a rare, life-threatening genetic disease — and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust clinical pipeline of investigational small molecule, cell and genetic therapies in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, pain, type 1 diabetes, and alpha-1 antitrypsin deficiency.
Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 13 consecutive years on Science magazine's Top Employers list and one of Fortune’s Best Workplaces in Biotechnology and Pharmaceuticals and Best Workplaces for Women.
Globenewswire | May 26, 2023
Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced preliminary data from its Phase 1 clinical trial evaluating XTX101, an investigational tumor-activated, Fc-enhanced anti-CTLA-4, in patients with advanced solid tumors.
“We are encouraged by the preliminary data from the Phase 1 trial for XTX101 showing evidence of tumor-selective activation,” said Martin Huber, M.D., president and head of research and development at Xilio. “Following treatment with XTX101 monotherapy at the recommended Phase 2 dose of 150 mg once every six weeks, we observed a partial response in a patient with PD-L1 negative advanced non-small cell lung cancer. Importantly, this anti-tumor activity occurred in the absence of meaningful observed activation of the immune system in the periphery, suggesting tumor-selective activation of XTX101. Based on these Phase 1 data, we plan to explore opportunities to evaluate XTX101 in combination with an anti-PD-(L)1 in historically immunotherapy-resistant tumor types.”
Data from the Ongoing Phase 1 Clinical Trial for XTX101
As of a data cutoff date of May 2, 2023, 25 patients had been treated with XTX101, including dose levels ranging from 7 mg to 180 mg administered once every three weeks (Q3W) and one dose level at 150 mg administered once every six weeks (Q6W). Of these patients, 20 patients were dosed in monotherapy dose-escalation (Part 1A) and five patients were dosed in monotherapy dose-expansion (Part 1B).
Patients had a wide range of advanced and treatment-refractory solid tumors, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and pancreatic cancer. In addition, 76% of patients had been previously treated with at least three prior lines of anti-cancer therapy, and 44% had been previously treated with at least one immuno-oncology (I-O) agent. As of the data cutoff date, three patients were continuing on treatment with XTX101, and 22 patients had discontinued treatment with XTX101.
Preliminary Safety Data
A recommended Phase 2 dose (RP2D) and schedule of 150 mg Q6W was determined based on the favorable preliminary safety, pharmacokinetic (PK) and pharmacodynamic (PD) data for XTX101. At the RP2D, no dose-limiting toxicities were observed, and there was no reported evidence of immune-related endocrine or skin adverse events (AEs) that are commonly associated with systemically active anti-CTLA-4 agents. In addition, evidence of effective masking of XTX101 was demonstrated by low levels of unmasked drug detected in peripheral circulation, and XTX101 achieved target PK exposure at the RP2D, reaching the targeted area under the curve (AUC) and peak concentration (Cmax).
As of the data cutoff date:
Across all dosing levels and dosing intervals, no Grade 4 or Grade 5 treatment-related AEs were reported by investigators.
Among seven patients who received XTX101 administered at the RP2D of 150 mg on a Q6W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (14%), fatigue (14%) and decreased appetite (14%). In these patients, no treatment-related colitis or infusion related reaction of any grade was observed. Investigators reported only one Grade 3 treatment-related AE of diarrhea, which occurred after two doses and resolved after five days without steroid use. This patient tolerated two additional doses of XTX101 after dose reduction to 75 mg Q6W without any symptom recurrence. At the RP2D of 150 mg Q6W, this was the only patient with a dose reduction due to an AE, and no patients discontinued treatment due to a treatment-related AE.
Among 18 patients who received XTX101 administered on a Q3W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (28%), colitis (28%), infusion related reaction (28%), nausea (17%), vomiting (17%) and abdominal pain (11%). Of these, investigators reported the following Grade 3 treatment-related AEs: diarrhea (6%), colitis (22%) and infusion related reaction (17%). Infusion related reactions were associated with antidrug antibodies. Across all dose levels administered Q3W, two patients had dose reductions due to AEs, and four patients discontinued treatment due to an infusion related reaction.
Preliminary Anti-Tumor Activity
A partial response was observed at nine weeks in one patient with advanced PD-L1 negative NSCLC with hepatic metastases treated with XTX101 at the 150 mg Q6W dose level and confirmed after the data cutoff date at week 27. The only treatment-related AE reported for this patient was Grade 1 fatigue. In addition, PD markers for anti-CTLA-4 reported for this patient showed minimal immune activation in peripheral circulation, demonstrating evidence of tumor-selective activation of XTX101. The patient is currently continuing on treatment with XTX101.
Clinical Development Plan for XTX101
Enrollment in monotherapy dose-expansion (Part 1B) of the Phase 1 trial is currently ongoing, with the goal of further characterizing the safety, PK and PD of XTX101 at the RP2D of 150 mg Q6W. In addition, mandatory tumor biopsies will be obtained from patients in Part 1B to examine intra-tumoral PK and PD for XTX101.
Xilio plans to continue to explore strategic opportunities to advance XTX101 with a partner beyond the current Phase 1 monotherapy cohorts, including in potential Phase 1 dose escalation evaluating XTX101 in combination with a PD-(L)1 and in a potential Phase 2 trial evaluating XTX101 in combination with a PD-(L)1 in patients with microsatellite stable CRC.
About XTX101 (anti-CTLA-4) and the Phase 1 Clinical Trial
XTX101 is an investigational tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of patients with advanced solid tumors. The primary outcome measures were the incidence of dose-limiting toxicities (DLTs) and the incidence of treatment-related adverse events, and changes in clinical laboratory abnormalities. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.
About Xilio Therapeutics
Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary geographically precise solutions (GPS) platform to build a pipeline of novel, tumor-activated molecules, including cytokines and other biologics, which are designed to optimize their therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as programs in preclinical development. Learn more by visiting www.xiliotx.com and follow us on Twitter (@xiliotx) and LinkedIn (Xilio Therapeutics, Inc.).