On October 11, 2021 Exscientia (Nasdaq: EXAI), the Medical University of Vienna and the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, reported publication in Cancer Discovery, a journal of the American Association of Cancer Research, of final results from the EXALT-1 trial (Press release, Exscientia, OCT 11, 2021, View Source [SID1234591081]). The study, titled "Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Haematological Cancers and Identifies Exceptional Responders," illustrates the potential real-world impact of using Exscientia’s AI-supported precision medicine platform (referred to in the study as single-cell functional precision medicine or scFPM) to propose which therapy would be most effective for late-stage haematological cancer patients based on testing drug responses ex vivo in their own tissue samples. Interim data from the study was previously published in The Lancet Haematology.

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"Precision medicine is the right drug, for the right patient, at the right time. By enabling the robust and accurate assessment of drug effect on viable patient samples at single-cell resolution, we have created a technology that can provide hemato oncologists prediction of a patient’s response prior to deciding on a course of therapy," said Gregory Vladimer, Ph.D., VP of translational research at Exscientia and co-inventor of the platform technology. "While the use of genetics in precision cancer medicine can determine if a target is present, functionally characterizing available drug options on patient cells within a short time window provides evidence for cancer cell sensitivity."

"The EXALT-1 study was the first-ever prospective study of its kind, demonstrating the potential of a functional precision medicine platform to identify the optimal therapy for an individual patient. The results of the trial are clear: patients who were treated using recommendations guided by single-cell drug screenings from real-time biopsies remained progression-free longer as compared to their previous line of therapy," commented Philipp P. Staber, M.D., Ph.D., haematologist oncologist at Medical University Vienna and principal investigator of the study.

The prospective, single-arm, open label EXALT-1 study was a basket trial for patients with a variety of aggressive haematological cancers. The study evaluated a total of 76 patients. Of these, 56 patients were treated according to scFPM and 20 patients received treatment based on physician’s choice. At a median follow-up of 23.9 months, 54% of patients (30/56) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival (PFS) compared to their previous therapy, with 40% of responders (12/30) achieving exceptional responses lasting at least three times longer than expected for their respective disease. The PFS on scFPM-guided treatment was significantly increased (p=0.0093). Of note, 23% of patients (13/56) were progression-free after 12 months after scFPM-guided therapy, compared to only 5% of patients (3/56) on their previous treatment. The objective response rate was 55% for patients treated according to scFPM results.

Giulio Superti-Furga, Scientific Director of the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences said, "The current study is a wonderful example of how successful collaboration with academic research and innovation, clinical expertise, and pharmatech knowhow can benefit patients and the development of new technologies. This is not personalised medicine inferred from biomarkers, it is really measured. It is based on function."

Exscientia’s precision medicine platform uses AI techniques to conduct single-cell, high content analysis of individual patient tissue samples to generate clinically-relevant insights into which treatments will deliver the most benefit to an individual patient. The underlying technology was developed by Dr. Gregory Vladimer and Prof. Berend Snijder, now at the ETH Zurich, while working in the laboratory of Giulio Superti-Furga at the CeMM Research Center for Molecular Medicine in Austria.

"Exscientia’s patient-first AI strategy aims to bring patients directly into all aspects of new medicine discovery and development, including target discovery, drug optimization and patient selection for clinical trials," said Andrew Hopkins, Ph.D., Founder and Chief Executive Officer of Exscientia. "These results provide strong validation for our strategy to apply AI to modernize drug development, ultimately aiming to bring better drugs, faster, to patients in need."

On October 11, 2021 Repertoire Immune Medicines reported that the first patient has been dosed in the company’s Phase 1 study of RPTR-168 (PRIME IL-12) in patients with select relapsed or refractory human papillomavirus (HPV)-16-positive tumors (Press release, Repertoire, OCT 11, 2021, View Source [SID1234591080]).

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RPTR-168 is an autologous multi-targeted T cell (MTC) therapeutic candidate derived from rare peripheral blood T cells. The T cells are collected from each patient through apheresis and are primed and expanded by a set of five tumor-associated antigens known to be expressed on HPV-16-positive tumors. RPTR-168 is designed to deliver interleukin-12 (IL-12), a potent immunomodulatory agent that has been shown to improve anti-tumor activity by promoting T cell function inside the tumor microenvironment.

The use of IL-12 has been limited because of dose-related toxicities observed in other settings. To address this, Repertoire utilizes its proprietary technology to tether IL-12 to the surface of RPTR-168 MTCs. This approach is designed to allow direct and localized delivery of IL-12 to the tumor, which may support an anti-tumor immune response.

"We have developed RPTR-168 to target five distinct antigens known to play a role in HPV-16-positive tumor development and armed it with the potent immunomodulatory agent IL-12 using Repertoire’s proprietary tethering technology," said John Cox, chief executive officer, Repertoire Immune Medicines. "RPTR-168 is Repertoire’s second investigational candidate to advance to Phase 1 clinical study. This milestone reflects our team’s commitment to advancing our programs from early research and discovery to the clinical study stage."

The Phase 1 study is being conducted at trial centers in the United States. The first patient was dosed at HonorHealth Research and Innovation Institute in Scottsdale, Arizona.

"The ability to safely deliver IL-12 with a multi-targeted cell therapy would be a significant advancement in the treatment of solid tumors," said Ted Reiss, M.D., MBE, chief medical officer, Repertoire Immune Medicines. "We believe the use of cell-tethered IL-12 has the potential to enhance T cell responses in the microenvironment of solid tumors. We are grateful to the patients, caregivers and healthcare providers who are participating in and supporting this study of RPTR-168."

About the Phase 1 Clinical Study of RPTR-168

The Phase 1 clinical study is an open-label, multi-center trial to characterize the safety and tolerability of RPTR-168 in adult patients with relapsed or refractory metastatic or locally advanced human papillomavirus-16-positive tumors. The primary endpoints are safety and tolerability.

For more information about the clinical study visit: clinicaltrials.gov and use study identifier NCT04762225.

On October 11, 2021 Mission Therapeutics ("Mission"), a drug discovery and development company focused on selectively inhibiting deubiquitylating enzymes (DUBs), reported that its CEO, Anker Lundemose, will attend and present at the 8th Annual Solebury Trout Private Company Showcase, co-hosted with BMO, on 14 October 2021.

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Dr Lundemose will be available for one-to-one meetings and will discuss the Company’s business strategy, technology, discovery platform and development programmes in a 20-minute video presentation at 4.00pm EDT / 9.00pm BST.

As well as these 20-minute video presentations from attending companies, the event’s agenda includes two topical panels and virtual meetings with company executives.

For individuals interested in attending the meeting, please contact the organisers for further information.

On October 11, 2021 CatalYm, reported an update from the dose escalation part of the ongoing first-in-human trial "GDFather" (GDF-15 Antibody-mediated Effector cell Relocation) investigating its lead product candidate, CTL-002, both in monotherapy and in combination with an immune checkpoint inhibitor, nivolumab. CTL-002 is a neutralizing antibody that specifically targets growth and differentiation factor 15 (GDF-15), which is recognized as a negative regulator of antitumoral T cell activity preventing T cell recruitment to the tumor microenvironment as well as potently suppressing an adaptive immune response by additional mechanisms recently identified (Press release, Catalym, OCT 11, 2021, View Source [SID1234591078]). Patients treated with CTL-002 and nivolumab at the first four of five dose levels to be evaluated showed an excellent tolerability profile and no dose limiting toxicities (DLT). Preliminary sequential tumor biopsy analyses for dose level 1-3 showed signs for a tumor-selective influx of T cell under CTL-002 treatment. GDFather is the most advanced clinical trial of a GDF-15-targeting therapeutic in immuno-oncology. The data was presented in an oral presentation at the plenary session ‘New Drugs on the Horizon II’ at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), on October 9, 2021.

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Prof. Dr. Eugen Leo, Chief Medical Officer at CatalYm commented, "GDF-15 has been recently identified by us and others as a tumor-derived key negative regulator of the immune response against cancer. We are delighted to see the excellent tolerability of CTL-002 in combination with nivolumab and initial evidence for targeted activity from dose level 1 onwards, which is reflected by induction of a tumor-selective influx of T cells. Additional biomarker analyses and relevant data for all cohorts will be available before year-end and we are very keen to take this drug forward into the next stage of clinical development to serve the anti-PD1/PD-L1 refractory patient population, which represents a significant number of patients in many solid tumors."

Dr. Phil L’Huillier, Chief Executive Officer at CatalYm added, "The opportunity to provide this data update at the "New Drugs on the Horizon" plenary session of the ACR-NCI-EORTC conference reflects the scientific innovation and clinical relevance presented by our approach. Although the data is still preliminary at this stage, it corroborates our preclinical data and confirms the proposed mode of action of CTL-002. Our ultimate goal is to provide meaningful clinical benefit to a patient population with very poor prognosis, refractory to checkpoint inhibitors and all other standard of care treatments. We look forward to further evaluating CTL-002 in this heavily pretreated patient population."

The ongoing first-in-human GDFather trial (GDF-15 antibody-mediated effector cell relocation) consists of two parts. In the dose escalation phase (Part A), up to 24 patients will receive escalating doses of CTL-002 in a "3+3" manner with the lead candidate given as a monotherapy and followed by combination with an anti-PD-1 checkpoint inhibitor. In the second dose expansion phase (Part B, phase 2a), several cohorts with tumors identified to be GDF-15-dependent will be treated to further evaluate safety and preliminary efficacy of CTL-002 treatment. Additional biomarker data, safety information and first efficacy readouts from all dose levels tested in dose escalation of CTL-002 both for monotherapy and in combination with nivolumab may be available by year-end.

About CTL-002

CTL-002 is a humanized, monoclonal antibody designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15). GDF-15 secretion by the tumor has been shown to prevent T cell migration into the tumor and suppresses T cell function and the adaptive immune response in the tumor microenvironment. This enables the tumor to evade the immune system and become resistant to standard of care and current immunotherapy approaches such as checkpoint inhibitors. CTL-002 counteracts these immuno-suppressive mechanisms by neutralizing GDF-15, enhancing the infiltration of immune cells into the tumor, improving both priming of T cells by dendritic cells and tumor killing by T cells and NK cells.

On October 11, 2021 ChemoCentryx, Inc., (Nasdaq: CCXI), reported the appointment of Rita I. Jain, M.D., as Executive Vice President, Chief Medical Officer (Press release, ChemoCentryx, OCT 11, 2021, View Source [SID1234591077]). In this role, she will oversee development activities including clinical development, development operations, regulatory affairs, and drug safety and pharmacovigilance. Dr. Jain will continue to serve on the ChemoCentryx board of directors (where she has served since March of 2019) as an executive employee director. Dr. Jain, a board-certified rheumatologist, brings more than 20 years of drug development experience leading multiple global programs across early and late stages of development.

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"Today we bolster our strength as an organization – and across a range of extremely important therapeutic areas – by bringing Rita Jain to the ChemoCentryx leadership team," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "We welcome her; we cite her impressive track record in drug development with years of experience in leading highly innovative programs. All of these qualities, combined with her dedication to making a fundamental difference in patients’ lives, are a perfect complement to our ChemoCentryx mission."

"Through my role on ChemoCentryx’s Board of Directors I’ve seen firsthand the value of the science and promise of the company’s pipeline. I’m excited to now join the leadership team and play a larger role in driving these assets forward, particularly at such a transformational time," said Dr. Jain. "I am impressed with the company’s successful execution to date and look forward to supporting its future achievements."

Dr Jain previously served as Chief Medical officer of Immunovant, Inc. and prior to that Senior Vice President and Chief Medical Officer of Akebia Therapeutics, Inc. Before joining Akebia, Dr. Jain was Vice President of Men’s and Women’s Health and Metabolic Development at AbbVie, Inc., and prior to that served in various leadership roles including Divisional Vice President at Abbott Laboratories. Dr. Jain led the design and execution of multiple late-stage programs, including for Orilissa and Oriahnn. She has also led programs across a diverse set of therapeutic areas including inflammation, pain, immunology and nephrology, among others.

Before Abbott, she held management positions in the Arthritis, Inflammation and Pain Group at G.D. Searle (acquired by Pharmacia and subsequently Pfizer). Earlier in her career, Dr. Jain was a faculty member at North Shore University Hospital in New York, with an academic appointment as Assistant Professor of Medicine, New York University School of Medicine.

Dr. Jain received her B.S. in biology from LIU/C.W. Post and her M.D. from the State University of New York at Stony Brook School of Medicine. Dr. Jain completed her medical training in internal medicine at Staten Island University Hospital followed by a Fellowship in Rheumatology at North Shore University Hospital and a Clinical Research Fellowship at the University of Texas Southwestern Medical Center, Dallas.