ADC Trigger Selective Cancer Cell Death

Chemotherapy has been used to treat cancer for almost 80 years now[1] and its side effects are well known and documented. One of the main limitations associated with standard chemotherapy is the unspecific killing of healthy cells (e.g. rapidly dividing cells in the bone marrow) which is associated with high-dose requirement and low therapeutic indices. In order to significantly reduce systemic side effects, it is fundamental to develop a new generation of anticancer drugs, specifically targeting cancer cells and therefore better tolerated by patients. One approach relies on the use of monoclonal antibodies, the so-called “magic bullets” envisioned by Paul Ehrlich more than 100 years ago[2]. Monoclonal antibodies (mAbs) belong to the broad class of biological drugs, or biologics (i.e. products derived from living organisms). MAbs have fueled research in many scientific fields with four dedicated Nobel prize winners in 2018 (https://www.nobelprize.org/nobel-prizes-2018/) and can be considered today a strong clinical reality with over 80 pharmaceuticals already on the market in indications not limited to oncology[3].

Spotlight

Cepheid

Over a decade ago, Cepheid set the standard for innovation in automated molecular diagnostics with our first system and we’ve never looked back. And now, even with the largest installed base of any molecular platform, Cepheid is constantly innovating and evolving our capabilities. Our technology has been heralded as game-changing by healthcare leaders world-wide. We envision a better way for clinical institutions of any size, from small medical clinics to high-volume reference laboratories and major hospitals, to access the power of molecular diagnostics. Our GeneXpert® System delivers fast, scalable, and accurate diagnostic results while our expanding Xpert® test menu spans multiple clinical applications such as healthcare-associated infections, sexual health, critical infectious disease, virology, and oncology. Make a difference in healthcare and join us on this mission! For more details, please visit us at www.cepheid.com.

OTHER ARTICLES
MedTech

Wisconsin biotech companies could play key roles in long-term economic recovery from COVID-19 pandemic

Article | July 16, 2022

Whether it’s called a modern “Manhattan Project” or a medical moon shot, the concept of long-term economic recovery rests on how confident people are they won’t risk serious illness by venturing forth in public again. Wisconsin stands to be a significant part of such an undertaking, whatever it’s called. The shorter-term debate is well under way over the gradual lifting of COVID-19 emergency rules, such as the now-extended “safer-at-home” order in Wisconsin. At least a dozen states, including regional coalitions on the East and West coasts, are exploring next steps as they seek to balance responses to the virus with calls for reopening the economy, at least, in part. Wisconsin’s ability to shape longer-term responses will come from private and public resources, which range from companies engaged in production of diagnostics.

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MedTech

Making Predictions by Digitizing Bioprocessing

Article | July 13, 2022

With advances in data analytics and machine learning, the move from descriptive and diagnostic analytics to predictive and prescriptive analytics and controls—allowing us to better forecast and understand what will happen and thus optimize process outcomes—is not only feasible but inevitable, according to Bonnie Shum, principal engineer, pharma technical innovation, technology & manufacturing sciences and technology at Genentech. “Well-trained artificial intelligence systems can help drive better decision making and how data is analyzed from drug discovery to process development and to manufacturing processes,” she says. Those advances, though, only really matter when they improve the lives of patients. That’s exactly what Shum expects. “The convergence of digital transformation and operational/processing changes will be critical for the facilities of the future and meeting the needs of our patients,” she continues. “Digital solutions may one day provide fully automated bioprocessing, eliminating manual intervention and enabling us to anticipate potential process deviations to prevent process failures, leading to real-time release and thus faster access for patients.” To turn Bioprocessing 4.0 into a production line for precision healthcare, real-time release and quickly manufacturing personalized medicines will be critical. Adding digitization and advanced analytics wherever possible will drive those improvements. In fact, many of these improvements, especially moving from descriptive to predictive bioprocessing, depend on more digitization.

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MedTech

Biotech in 2022

Article | October 7, 2022

The robust global channel of more than, 800 gene and cell curatives presently in trials will produce clinical readouts in 2022, revealing what lies ahead for advanced curatives. The impact will be felt in 2022, no matter how you slice it. Eventually, how well industry and non-supervisory bodies unite to produce new frameworks for advanced therapies will shape the year 2022 and further. Pacific Northwest talent will continue to contribute to the advancement of gene and cell curatives in both the short and long term, thanks to its deep pool of ground-breaking scientific developers, entrepreneurial directorial leadership, largely skilled translational scientists, and endured bio manufacturing technicians. We may see continued on-life science fund withdrawal from biotech in 2021, but this can be anticipated as a strong comeback in 2022 by biotech industry, backed by deep-pocketed life science investors who are committed to this sector. A similar investment, combined with pharma's cash-heavy coffers, can result in increased junction and acquisition activity, which will be a challenge for some but an occasion for others. Over the last five years, investment interest in Seattle and the Pacific Northwest has grown exponentially, from Vancouver, British Columbia, to Oregon. The region's explosive portfolio of new biotech companies, innovated out of academic centres, demonstrates the region's growing recognition of scientific invention. This created a belief that continued, especially because Seattle's start-ups and biotech enterprises are delivering on their pledge of clinical and patient impact. Talent and staffing will continue to be difficult to find. It's a CEO's market, but many of these funds' return, and are not rising in proportion to the exorbitant prices they're paying to enter deals. This schism has become particularly pronounced in 2021. Hence, everyone in biotech is concerned about reclamation and retention.

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MedTech

Next-Gen Gene Therapy to Counter Complex Diseases

Article | July 13, 2022

Gene therapy has historically been used to treat disorders with in-depth knowledge caused by a single genetic mutation. Thanks to the introduction of new generation technologies, the potential of gene therapy is expanding tAo treat diseases that were previously untreatable. Evolution of Gene Therapy One of the major success stories of the twenty-first century has been gene therapy. However, it has not been the same in the past. The field's journey to this point has been long and mostly difficult, with both tragedy and triumph along the way. Initially, genetic disorders were thought to be untreatable and permanently carved into the genomes of individuals unfortunate enough to be born with them. But due to the constant technological advancement and research activities, gene therapy now has the potential to treat various genetic mutation-causing diseases with its ability to insert a new copy and replace faulty genes. Gene Therapy is Finding New Roads in the Medical Sector Gene therapy can help researchers treat a variety of conditions that fall under the general heading of epilepsy, instead of only focusing on a particular kind of disorder brought on by a genetic mutation. Following are some of the domains transformed by gene therapy. Neurology – Gene therapy can be used for the treatment of seizures by directly injecting it into the area causing an uncontrolled electrical disturbance in the brain. Furthermore, by using DNA sequences known as promoters, gene therapy can be restricted to specific neurons within that area. Ophthalmology – Genetic conditions such as blindness can be caused due to the mutation of any gene out of over 200 and resulting in progressive vision loss in children. With advanced gene therapies such as optogenetics, lost photoreceptor function can be transferred to the retinal cells, which are responsible for relaying visual information to the brain. This might give patients the ability to navigate in an unknown environment with a certain level of autonomy. The Future of Gene Therapy The news surrounding gene therapy has been largely favorable over the past few years, with treatment after treatment obtaining regulatory approvals, successful clinical trials, and garnering significant funds to begin development. With more than 1,000 clinical trials presently underway, the long-awaited gene therapy revolution might finally be here.

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Spotlight

Cepheid

Over a decade ago, Cepheid set the standard for innovation in automated molecular diagnostics with our first system and we’ve never looked back. And now, even with the largest installed base of any molecular platform, Cepheid is constantly innovating and evolving our capabilities. Our technology has been heralded as game-changing by healthcare leaders world-wide. We envision a better way for clinical institutions of any size, from small medical clinics to high-volume reference laboratories and major hospitals, to access the power of molecular diagnostics. Our GeneXpert® System delivers fast, scalable, and accurate diagnostic results while our expanding Xpert® test menu spans multiple clinical applications such as healthcare-associated infections, sexual health, critical infectious disease, virology, and oncology. Make a difference in healthcare and join us on this mission! For more details, please visit us at www.cepheid.com.

Related News

Research, Diagnostics

Xilio Therapeutics Releases Preliminary Results of XTX101 Phase 1 Trial

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.).

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Industrial Impact

iNtRON Confirms Efficacy of CDL200 Against CDI Clinical Isolates

iNtRON Biotechnology | July 12, 2022

iNtRON Biotechnology announced that CDL200, a novel biological drug candidate under the development of the world's first enteric colon-targeted capsule formulation for the treatment of intractable and recurrent CDI confirmed the strong efficacy against clinical isolates from CDI patients. A company official explained that the antibacterial activity of CDL200 was evaluated for 20 clinical isolates from patients in Europe and Korea, and rapid lysis effect within few minutes after treatment was confirmed from all of the tested strains. In particular, even though majority of the tested strains are resistant strains to the commonly used antibiotics such as Metronidazole, Vancomycin, and Rifaximin, CDL200 showed very potent and rapid bactericidal activity. CDL200 is an endolysin-based novel biological drug candidate for the treatment of Clostridioides difficile infection, a hard-to-treat and recurrent bowel diseases. CDL200 has innovative drug properties that can eradicate bacteria much faster than the conventional antibiotics in the market, and also can be used for the infection caused by antibiotic-resistant bacteria and/or highly virulent bacteria. CDI patient population has been increasing globally and resulting in high mortality rate due to resistance to the existing antibiotics and serious complications such as toxic megacolon, sepsis, and intestinal perforation. Although there is growing interest in refractory CDI that does not respond well to primary treatment, there are only few studies on effective treatment yet. The more serious problem is the frequency of recurrent CDI is increasing, since the risk of subsequent recurrence is over 45% in patients who have had at least one recurrence. The conventional treatment based on Metronidazole and Vancomycin is not effective for CDI with severe intractability and repeating recurrence. And the recently attempted FMT (fecal microbiota transplantation), that is, the treatment of administering donor feces to the patient's intestinal tract, has advantages such as not suppressing the intestinal flora and not creating resistant strains, but the treatment brings objection to the general public and is limited in that there is a possibility that other pathogens from the donor may be transmitted. The mortality rate of CDI was about 3-4% in the past, but due to intensification of antibiotic-resistant bacteria and the emergence of highly virulent strain (NAP1/027), the recent mortality rate has been rapidly increased to over 10%, which makes global awareness growing. Dr. KANG, Sang Hyeon, CTO of iNtRON, said, "We have a number of new endolysin pipelines under the development utilizing our unique itLysin® technology for the serious infection that the development of effective therapeutic agents are urgently needed." "Based on the development experience of SAL200, we will strive to enhance the value of our rich itLysin® pipelines and will continue to secure global competitiveness in the endolysin field." Mr. YOON, Kyung Won, CEO of iNtRON About CDL200 CDL200 is a novel endolysin-based anti- Clostridioides difficile causes an infection of the large intestine which is often referred to as C. difficile or C. diff. CDL200 showed potent and rapid activity against 100% clinical isolates from multi-nation and has no disturbance of the normal flora in human's gut. The potential clinical usage and indications are CDI and IBD (Inflammatory Bowel Disease), and the targeted administration route of CDL200 is oral in capsule formulation. CDL200 is under non-clinical stage development and IND enabling studies will be conducted throughout the year. About iNtRON Biotechnology, Inc. iNtRON is a leader in bacteriophage-based technology with aim to develop and investigate into the 'Immune & Immunotherapeutics' market. While pursuing global research and business development investments since their foundation and accelerated development after entering its IPO in KOSDAQ, the company honed in on innovating BIO New Drugs by developing various 'First-in-Concept' bio-drugs and conducting clinical studies in phases. The Company is committed to development of innovative innovation in the infectious diseases and 'Immune & Immunotherapeutics' area. About iNtODEWORLD, Inc. iNtRON has established its wholly owned US subsidiary, iNtODEWORLD, Inc. in 2017. iNtODEWORLD was initially registered in Delaware and the headquarter office is currently located in Boston. iNtODEWORLD provides news, updates and platform development progresses of iNtRON to its potential global partners and collaborators along with its own R&BD works in the US.

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Cell and Gene Therapy

iTolerance to Collborate with LyGenesis for Joint Research

iTolerance | July 01, 2022

iTolerance, Inc., an early-stage privately held regenerative medicine company developing technology to enable organoid, tissue, and cell therapy, announced entering into a joint collaboration with LyGenesis, Inc., a clinical-stage biotechnology company with an organ regeneration technology platform. The joint collaboration is aimed at evaluating the potential of iTOL-201, a product candidate being developed combining LyGenesis' LYG-LIV-100 liver cell therapy and iTolerance's SA FasL microgel immune tolerance platform to permit the growth of ectopic livers without the requirement for immune suppression. The joint research effort of iTolerance and LyGenesis has produced in vitro data using iTOL-201 and is now moving toward small animal proof of concept work to assess the potential of the combined technology for producing ectopic livers capable of saving the animals from fatal liver disorders without the requirement for immune suppression. With our lead therapy now in the clinic in a Phase 2a trial in patients with End Stage Liver Disease, we have turned our attention toward a second-generation therapy capable of growing ectopic organs without the need for immune suppression. iTolerance's platform holds enormous promise in this respect and we look forward to the results from our joint proof of concept work." Dr. Michael Hufford, Co-Founder and Chief Executive Officer of LyGenesis. While long-term immunosuppression continues to be an obstacle for the use of cell and regenerative therapies, the research being conducted between both LyGenesis and iTolerance could allow for a major advancement in organ regeneration, As we advance our own pipeline of therapies focused on supporting pancreatic islet engraftments, I believe this synergistic collaborative research with LyGenesis has the potential to successfully combine technologies to drive significant value for both biotech companies and importantly, the patients we work to serve." Dr. Anthony Japour, Chief Executive Officer of iTolerance.

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Research, Diagnostics

Xilio Therapeutics Releases Preliminary Results of XTX101 Phase 1 Trial

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.).

Read More

Industrial Impact

iNtRON Confirms Efficacy of CDL200 Against CDI Clinical Isolates

iNtRON Biotechnology | July 12, 2022

iNtRON Biotechnology announced that CDL200, a novel biological drug candidate under the development of the world's first enteric colon-targeted capsule formulation for the treatment of intractable and recurrent CDI confirmed the strong efficacy against clinical isolates from CDI patients. A company official explained that the antibacterial activity of CDL200 was evaluated for 20 clinical isolates from patients in Europe and Korea, and rapid lysis effect within few minutes after treatment was confirmed from all of the tested strains. In particular, even though majority of the tested strains are resistant strains to the commonly used antibiotics such as Metronidazole, Vancomycin, and Rifaximin, CDL200 showed very potent and rapid bactericidal activity. CDL200 is an endolysin-based novel biological drug candidate for the treatment of Clostridioides difficile infection, a hard-to-treat and recurrent bowel diseases. CDL200 has innovative drug properties that can eradicate bacteria much faster than the conventional antibiotics in the market, and also can be used for the infection caused by antibiotic-resistant bacteria and/or highly virulent bacteria. CDI patient population has been increasing globally and resulting in high mortality rate due to resistance to the existing antibiotics and serious complications such as toxic megacolon, sepsis, and intestinal perforation. Although there is growing interest in refractory CDI that does not respond well to primary treatment, there are only few studies on effective treatment yet. The more serious problem is the frequency of recurrent CDI is increasing, since the risk of subsequent recurrence is over 45% in patients who have had at least one recurrence. The conventional treatment based on Metronidazole and Vancomycin is not effective for CDI with severe intractability and repeating recurrence. And the recently attempted FMT (fecal microbiota transplantation), that is, the treatment of administering donor feces to the patient's intestinal tract, has advantages such as not suppressing the intestinal flora and not creating resistant strains, but the treatment brings objection to the general public and is limited in that there is a possibility that other pathogens from the donor may be transmitted. The mortality rate of CDI was about 3-4% in the past, but due to intensification of antibiotic-resistant bacteria and the emergence of highly virulent strain (NAP1/027), the recent mortality rate has been rapidly increased to over 10%, which makes global awareness growing. Dr. KANG, Sang Hyeon, CTO of iNtRON, said, "We have a number of new endolysin pipelines under the development utilizing our unique itLysin® technology for the serious infection that the development of effective therapeutic agents are urgently needed." "Based on the development experience of SAL200, we will strive to enhance the value of our rich itLysin® pipelines and will continue to secure global competitiveness in the endolysin field." Mr. YOON, Kyung Won, CEO of iNtRON About CDL200 CDL200 is a novel endolysin-based anti- Clostridioides difficile causes an infection of the large intestine which is often referred to as C. difficile or C. diff. CDL200 showed potent and rapid activity against 100% clinical isolates from multi-nation and has no disturbance of the normal flora in human's gut. The potential clinical usage and indications are CDI and IBD (Inflammatory Bowel Disease), and the targeted administration route of CDL200 is oral in capsule formulation. CDL200 is under non-clinical stage development and IND enabling studies will be conducted throughout the year. About iNtRON Biotechnology, Inc. iNtRON is a leader in bacteriophage-based technology with aim to develop and investigate into the 'Immune & Immunotherapeutics' market. While pursuing global research and business development investments since their foundation and accelerated development after entering its IPO in KOSDAQ, the company honed in on innovating BIO New Drugs by developing various 'First-in-Concept' bio-drugs and conducting clinical studies in phases. The Company is committed to development of innovative innovation in the infectious diseases and 'Immune & Immunotherapeutics' area. About iNtODEWORLD, Inc. iNtRON has established its wholly owned US subsidiary, iNtODEWORLD, Inc. in 2017. iNtODEWORLD was initially registered in Delaware and the headquarter office is currently located in Boston. iNtODEWORLD provides news, updates and platform development progresses of iNtRON to its potential global partners and collaborators along with its own R&BD works in the US.

Read More

Cell and Gene Therapy

iTolerance to Collborate with LyGenesis for Joint Research

iTolerance | July 01, 2022

iTolerance, Inc., an early-stage privately held regenerative medicine company developing technology to enable organoid, tissue, and cell therapy, announced entering into a joint collaboration with LyGenesis, Inc., a clinical-stage biotechnology company with an organ regeneration technology platform. The joint collaboration is aimed at evaluating the potential of iTOL-201, a product candidate being developed combining LyGenesis' LYG-LIV-100 liver cell therapy and iTolerance's SA FasL microgel immune tolerance platform to permit the growth of ectopic livers without the requirement for immune suppression. The joint research effort of iTolerance and LyGenesis has produced in vitro data using iTOL-201 and is now moving toward small animal proof of concept work to assess the potential of the combined technology for producing ectopic livers capable of saving the animals from fatal liver disorders without the requirement for immune suppression. With our lead therapy now in the clinic in a Phase 2a trial in patients with End Stage Liver Disease, we have turned our attention toward a second-generation therapy capable of growing ectopic organs without the need for immune suppression. iTolerance's platform holds enormous promise in this respect and we look forward to the results from our joint proof of concept work." Dr. Michael Hufford, Co-Founder and Chief Executive Officer of LyGenesis. While long-term immunosuppression continues to be an obstacle for the use of cell and regenerative therapies, the research being conducted between both LyGenesis and iTolerance could allow for a major advancement in organ regeneration, As we advance our own pipeline of therapies focused on supporting pancreatic islet engraftments, I believe this synergistic collaborative research with LyGenesis has the potential to successfully combine technologies to drive significant value for both biotech companies and importantly, the patients we work to serve." Dr. Anthony Japour, Chief Executive Officer of iTolerance.

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