On August 17, 2022 Imperial College London reported that its spin out startup GlioQuell has the power to shut down cancer cells (Press release, GlioQuell, AUG 17, 2022, View Source [SID1234629314]). A new company using research from the Department of Brain Sciences will look for drugs to treat brain cancers and diseases of old age.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Cancer cells grow at an extraordinary rate inside the body. To do this, they need energy, which is provided by mitochondria, the powerhouses of the cell. Dr Kambiz Alavian in the Department of Brain Sciences has been looking for ways to turn off cancer cells’ power supply. He has now co-founded a company, GlioQuell, to accelerate the development of a new kind of cancer treatment.

"We think we have a new way of looking at the mitochondria of cancer cells, and of treating cancer, based on reducing the efficiency of these beasts inside the cells," he says

All cells in the human body contain mitochondria, structures that produce energy and biomolecules for whatever activity the cells need to carry out. Looking closely at the cells involved in glioblastoma, one of the most aggressive and deadliest forms of cancer, revealed that their mitochondria are extraordinarily efficient.

"There is almost no cell that I have seen that is as efficient as these particular cells, in terms of utilising their resources for growth," says Dr Alavian. "They resemble mini-embryos, growing very quickly inside the brain."

This characteristic can be exploited when looking for treatments, for example by seeking out molecules that undermine the electrochemical mechanism that mitochondria use to make energy.

"By allowing ions to leak through the mitochondrial membrane, we can render the mitochondria inefficient at supplying energy to the cells, and furthering cell growth," Dr Alavian says. "Although mitochondria have previously been considered as therapeutic targets, this is a new and elegant way of tackling this disease, because it goes after a mechanism that is particularly active in cancer cells."

It’s an approach that could be applied to many other kinds of cancer. "But we are particularly interested in glioblastoma, because there is no effective treatment and no cure."

To the clinic
Dr Alavian’s lab at Imperial has designed and patented a high-throughput assay for identifying potential drugs that have this effect on glioblastoma mitochondria. GlioQuell has been set up to advance this innovation and to raise enough funding to expedite the translation of discoveries into the clinic.

GlioQuell will also benefit from the knowledge built up during the research process at Imperial. "We have a unique knowledge-base and set of technologies in our lab, and would like to transfer that knowhow to the company. We want to ensure that the company is equipped to do a full spectrum of studies: to characterise the mechanism, to design and develop new drugs, and to test the new drugs in the most efficient way."

There is another, quite different situation in which it would be useful to slow down mitochondria, which GlioQuell will also investigate. In addition to energy production, mitochondria start the process by which cells shut down and eventually die. Changing the way they function through pharmaceutical and nutraceutical intervention could also promote healthy ageing and offer ways of slowing the degeneration of muscles, brain and other tissues in old age.

Dr Alavian has co-founded GlioQuell with Dr Travis Tierney, Dr Valentin Gribkoff, and Dr Carlos Sanchez, three colleagues in the USA with extensive expertise in cancer biology, neuroscience, clinical medicine and drug development.

On August 17, 2022 Tessa Therapeutics Ltd. (Tessa), a clinical-stage cell therapy company developing next-generation cancer treatments for hematological malignancies and solid tumors, reported the dosing of the first patient in a Phase 1b clinical trial investigating TT11, the company’s autologous CD30 chimeric antigen receptor T-cell (CAR-T) therapy, in combination with Bristol Myers Squib’s nivolumab as a potential second-line treatment for patients with relapsed or refractory CD30-positive classical Hodgkin lymphoma (cHL) (Press release, Tessa Therapeutics, AUG 17, 2022, View Source [SID1234623199]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 1b open-label trial (ACTION; NCT05352828) will enroll up to 14 patients with CD30+ cHL with relapsed or refractory disease after front-line therapy combining PD-1 antibody and CAR-T therapy in a "sandwich" study design. Patients will initially receive two cycles of nivolumab dosed at four-week intervals followed by lymphocyte depleting treatment with fludarabine/bendamustine chemotherapy. Patients will then receive a single infusion of TT11, followed by two additional cycles of nivolumab. The primary endpoint of the trial is safety and tolerability of the combination regimen. Secondary endpoints will evaluate key efficacy indicators including overall response rate, duration of response, and progression-free survival.

"Initiation of this Phase 1b clinical trial marks an important milestone for our autologous CD30.CAR-T program as we now have the opportunity to evaluate TT11 in combination with nivolumab as a potential second-line treatment for relapsed or refractory classical Hodgkin lymphoma," stated John Ng, CTO and Acting CEO of Tessa Therapeutics. "Data from our ongoing clinical program investigating TT11 as a monotherapy treatment for later lines of classical Hodgkin lymphoma has demonstrated the CAR-T therapy to be safe with promising measures of efficacy. We now welcome the opportunity to capitalize on this clinical progress by investigating TT11 as a second-line combination therapy, which offers the opportunity to greatly increase the patient population who could potentially benefit from this course of care."

TT11 is an autologous CD30 chimeric antigen receptor T-cell (CAR-T) therapy that harvests the patient’s own T-cells and modifies them to target cancer cells expressing the CD30 protein, a well-validated lymphoma target. Clinical data from the pilot part of the ongoing Phase 2 CHARIOT trial of TT11 presented at ASH (Free ASH Whitepaper) demonstrated a favorable safety profile and promising efficacy in 14 evaluable patients with relapsed or refractory classical Hodgkin lymphoma (cHL), with a complete response (CR) rate of 57.1 percent and an overall response rate (ORR) of 71.4 percent. Tessa expects to advance to the pivotal Phase 2 CHARIOT trial later this year.

Nivolumab is a human IgG4 monoclonal antibody that blocks PD-1. It has been approved by the U.S. Food and Drug Administration (FDA) as a treatment for numerous cancer indications, including classical Hodgkin lymphoma.

"The current standard of care for relapsed or refractory classical Hodgkin Lymphoma is associated with short-term toxicities and long-term morbidity, with particularly poor tolerability noted among elderly patients," said Dr. Ivan Horak, Chief Medical Officer and Chief Scientific Officer of Tessa Therapeutics. "TT11, Tessa’s CD30 CAR-T therapy, has demonstrated encouraging clinical results as monotherapy, and we believe the combination with nivolumab has the potential to further enhance efficacy and provide patients with a chemotherapy-sparing, second-line treatment option."

On August 17, 2022 Advanced Proteome Therapeutics Corporation (TSXV: APC) (FSE: 0E81) ("APC" or the "Company"), reported that its US subsidiary, Advanced Proteome Therapeutics Inc. ("APTI"), has had its technology featured in a peer-reviewed publication (Press release, Advanced Proteome Therapeutics, AUG 17, 2022, View Source [SID1234622592]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The manuscript entitled, "Lysine-Directed Site-Selective Bioconjugation for the Creation of Radioimmunoconjugates" by Sarrett, et al. has been published in the prestigious journal, Bioconjugate Chemistry. Bioconjugate Chemistry is a peer-reviewed journal focused on bioconjugation and published by the American Chemical Society. The manuscript is available online and will be included in a forthcoming issue of the journal. The publication represents the final results of the previously announced collaboration between APTI and the Zeglis lab at the City University of New York to investigate APTI’s site-selective conjugation in the rapidly growing field of radioimmunoconjugates (RICs). The collaboration evaluated APTI’s site-selective conjugation approach using the antibody pertuzumab, an antibody that targets the HER2 receptor, which is overexpressed on many malignancies including breast and gastric cancer. In the study, APTI’s conjugate was compared with conjugates prepared with two of the most common approaches to antibody conjugation – cysteine maleimide and NHS ester. The conjugates were tested in vitro for key characteristics including stability and target binding and in two in vivo models – BT-474 breast cancer (all 3 constructs) and SKOV-3 ovarian cancer (APTI and NHS ester). Key findings from the study include:

APTI’s radioconjugate was >99% stable in human serum over 5 days
APTI’s radioconjugate was >99% free from aggregation over 14 days
APTI’s radioconjugate exhibited higher immunoreactivity (binding) to the HER2 receptor than the cysteine maleimide construct.
APTI’s radioconjugate exhibited no interference with Fc receptor binding
In vivo – BT-474 model, PET biodistribution tumor activity concentrations at 144 h post-injection (%ID/g):
APTI conjugate: 126.9 ± 50.3
Cysteine maleimide control: 86.9 ± 53.2
NHS ester control: 92.5 ± 27.2
In vivo – SKOV-3 model, biodistribution at 144 h post-injection (%ID/g):
APTI conjugate: 34.5 ± 20.0
NHS ester control: 21.5 ± 13.4
Dr. Benjamin Krantz, President and CEO of APTI, commented, "I am thrilled by the publication of the results of our collaboration with the Zeglis lab in Bioconjugate Chemistry. Bioconjugate Chemistry is one of the most important journals in the field of bioconjugation and its publication there provides significant visibility to potential collaborators. Our results speak for themselves. We again demonstrated that our conjugation approach using simple chemistry creates highly homogeneous antibody conjugates that are rock solid stable and maintain the properties of the native antibodies. In vivo, in two challenging models, we demonstrated numerically higher tumor uptake than the comparator molecules made with the most common approaches to antibody conjugate production. It is easy to see why we are excited about our technology, this data, and the opportunities that will come as it is disseminated."

Dr. Brian Zeglis commented, "It has been wonderful working with APTI on this project. I have been impressed with APTI’s highly modular and facile approach to bioconjugate production. It is the easiest approach to site-specific conjugation. The study clearly showed that APTI’s radioimmunoconjugates exhibited exceptional in vitro and in vivo performance and were better-defined and more homogeneous than traditional methods. I also believe that APTI’s strategy holds several key advantages over existing approaches to site-selective bioconjugation including production for the clinic. I look forward to APTI’s continued development of this promising technology."

On August 17, 2022 NRG and Curium reported that they have signed a multi-year contract for the production of molybdenum-99, the starting material for technetium-99m (Tc-99m) (Press release, Curium, AUG 17, 2022, View Source [SID1234618491]). Tc-99m is the most used isotope in nuclear medicine for diagnosing life-threatening diseases, such as cardiovascular diseases, lung and brain disorders and cancer. With this renewed collaboration 30,000 patients a day can continue to rely on the Petten nuclear medicine manufacturing capabilities.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Every year, some 49 million treatments are carried out on patients with nuclear medicines, and Tc-99m is used in more than 80% of these examinations. Both NRG and Curium are market leaders and therefore important links in the supply chain of Tc-99m. NRG uses its High Flux Reactor (HFR) to produce the isotopes, which Curium then uses for its nuclear medicine products for the benefit of the patients.

Vinod Ramnandandal, CCO NRG PALLAS commented: "With this renewed collaboration we are taking a big step towards meeting the continuing demand and confirming our ongoing partnership. This is also particularly good news for the doctors and patients who need the isotopes."

Frank de Lange, Managing Director Curium Netherlands commented: " This multi-year agreement confirms our commitment to doctors and patients worldwide building on our trusted legacy in nuclear medicine."

On August 17, 2022 WuXi Biologics reported its interim results for the six months ended June 30, 2022 (Filing, 3 mnth, JUN 30, WuXi Biologics, 2022, AUG 17, 2022, View Source [SID1234618475]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!