On February 3, 2022 Synthekine Inc., an engineered cytokine therapeutics company, reported the dosing of the first patient in a Phase 1a/1b clinical trial of its IL-2 partial agonist, STK-012, for the treatment of solid tumors. STK-012 is designed as an alpha/beta-biased IL-2 partial agonist to selectively stimulate antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid stimulation of toxicity causing immune cells, such as natural killer cells (Press release, Synthekine, FEB 3, 2022, View Source [SID1234607716]).

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"We are proud to begin this year with the important milestone of dosing the first patient in our Phase 1 trial of STK-012," said Debanjan Ray, chief executive officer of Synthekine. "STK-012 is a highly differentiated IL-2 partial agonist tuned to expand the therapeutic index of IL-2 by biasing towards efficacy driving antigen-activated T cells and away from toxicity causing lymphocytes, such as natural killer (NK) cells. STK-012 is the first program from our broad portfolio of biased cytokines to enter the clinic, and its rapid progress into clinical investigation further highlights our team’s tremendous ability to execute efficiently and move our pipeline forward."

Aldesleukin (recombinant IL-2) has shown to be active in certain cancers, but its use is limited due to life threatening toxicities such as capillary leak syndrome (CLS). Synthekine presented preclinical data at AACR (Free AACR Whitepaper) 2021 demonstrating a mouse surrogate of STK-012 achieved superior tumor regression compared to both wild-type mouse IL-2 and a non-alpha-IL-2 agent, representing a different approach to biasing IL-2. In toxicity models, the mouse surrogate of STK-012, unlike these same comparators, was well tolerated and did not induce CLS. In non-human primate studies, STK-012 avoided lymphopenia, NK cell activation and CLS induction, which was observed with both aldesleukin and a non-alpha-IL-2 agent.

The Phase 1a/1b clinical trial is an open-label, multi-center study enrolling patients with advanced solid tumors. The dose escalation portion of the study will evaluate STK-012 both as a monotherapy and in combination with pembrolizumab. Following completion of the dose escalation, Synthekine will initiate expansion cohorts with STK-012. For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT05098132.

On February 3, 2022 Simbec-Orion reported that Lupuzor is an in-development treatment for Lupus, a chronic inflammatory disease thought to affect around 5 million people worldwide (Press release, Simbec-Orion, FEB 3, 2022, View Source [SID1234607666]). Having recently undergone FDA approval, Lupuzor is commencing into phase 3 clinical trials.

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Simbec-Orion are proud to have been selected by ImmuPharma as a partner to conduct the international phase 3 trial of Lupuzor involving pharmacokinetic study. Phase 3 research has been granted ethic committee approval, and volunteer selection and screening is set to be conducted in December 2021.

The Lupuzor phase 3 pharmacokinetic trial aims to deliver data by the end of 2022’s first quarter, with dosing of volunteers getting underway in January 2022. This builds upon the first pivotal phase 3 Lupuzor trial completed in 2018, which assessed the drug through open label extension study.

Progress from phase 1 and 2 Lupuzor trials has been promising. ImmuPharma have taken the opportunity to improve the drug’s product characterisation and analytical method validations. As a result, research has made developments with a new proprietary synthesis of P140, resulting in greater IP protection and lower production costs.

Find out more about our clinical development services.

Lupuzor: Key Findings So Far
ImmuPharma have made significant advancements in developing a new treatment for Lupus. This drug, Lupuzor has shown potential as a treatment for Lupus during clinical research and has undergone significant testing across clinical trial phases.

Throughout clinical research stages, Lupuzor has shown strong efficacy in treating Lupus and has also demonstrated a strong safety profile. This provides promising results in the development of a new Lupus treatment, as the current standard treatment presents several side effects.

Phase 3 LupuzorTrials
As part of phase 3 Lupuzor research, Simbec-Orion partnered with ImmuPharma to complete the initial phase 3 trial. As a CRO with expertise in Lupus research, our team ran the first Lupuzor phase 3 trial, which enrolled 62 patients to complete an open label extension study.

This initial Lupuzor phase 3 trial confirmed a successful safety profile for the drug, reporting no serious side effects or reactions. These insights enabled our trial management team to commence with an optimal phase 3 trial design together with ImmuPharma.

The next stage of phase 3 Lupuzor research will involve a pharmacokinetic study, helping further evaluate the drug’s safety profile and efficacy.

Why Lupus Research is Important
Affecting an estimated 5 million people worldwide, Lupus is a chronic inflammatory, autoimmune disease that can be life threatening. Lupus can impact various parts of the body, including skin, kidneys, the brain, heart and lungs.

Diagnosis can be challenging, since Lupus can appear in several different forms and although awareness is steadily increasing, it does not have the greatest level of recognition.

As well as challenges in diagnosis, the current standard treatment for Lupus can often present adverse side effects. As well, the standard treatment has limited efficacy. As a result, there is an unmet need for an effective Lupus treatment with stronger efficacy and fewer side effects.

Partner With Simbec-Orion
Experts in clinical trial management, we’re here to support you with your clinical development. Get in touch with our expert team to find out more.

On February 3, 2022 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that Michael A. Metzger, President and Chief Operating Officer, will transition to the role of Chief Executive Officer, effective today (Press release, Syndax, FEB 3, 2022, View Source [SID1234607684]). Briggs W. Morrison, M.D., Chief Executive Officer, will transition to the role of President, Head of Research and Development (R&D) . Mr. Metzger and Dr. Morrison will remain on the Company’s Board of Directors. Both Mr. Metzger and Dr. Morrison joined Syndax together in 2015 with the goal of building a world-class oncology company.

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"Briggs and I have worked very closely in partnership over the last seven years to expand Syndax’s portfolio of assets through business development transactions while simultaneously building the organization, developing the pipeline, and executing on key capital raising initiatives," said Mr. Metzger. "This transition will better align our roles and priorities with our individual areas of expertise. Going forward, I will be focused on executing on the strategic vision for the Company, including establishing the operational groundwork to expand Syndax into a commercial entity and growing our pipeline through transactions. Briggs will continue to lead the R&D organization, with a key focus on bringing two assets to approval and helping to bring new assets into the organization. I look forward to our continued partnership as we work to deliver innovative therapies to areas of high unmet need in oncology and build long-term value for all of our stakeholders."

"With topline data expected early next year for both of our ongoing SNDX-5613 and axatilimab registration programs, we are keenly focused on preparations for multiple potential New Drug Application filings in 2023," said Dr. Morrison. "I look forward to focusing my efforts, together with the talented team at Syndax, on developing these exciting product candidates into approved therapies and to advancing them into new indications in the clinic, including the first-line and maintenance settings for SNDX-5613 in acute leukemia, and in idiopathic pulmonary fibrosis for axatilimab. We expect this transition of roles to be seamless, and I look forward to continuing to partner with Michael as we work to advance our mission of realizing a future in which people with cancer live longer and better than ever before."

Prior to joining Syndax, Mr. Metzger served as President, Chief Executive Officer and a Director of Regado Biosciences through its merger with Tobira Therapeutics (acquired by Allergan). He has also served in senior leadership and business development roles at Mersana Therapeutics, Forest Laboratories (acquired by Allergan), and in various other industry and investment roles. He received a B.A. from George Washington University and an M.B.A. in finance from the New York University Stern School of Business.

Prior to Syndax, Dr. Morrison served in several senior leadership roles in the industry, including as Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, Head, Medical Affairs, Safety and Regulatory Affairs at Pfizer, and Vice President, Clinical Sciences, Oncology, at Merck & Co. He received a B.S. in biology from Georgetown University and an M.D. from the University of Connecticut.

On February 2, 2022 Medigene AG ( View Source) (Medigene, FSE: MDG1, Prime Standard), a clinical-stage immuno-oncology company focusing on the development of T-cell-based cancer therapies, reported that promising preliminary efficacy and immune monitoring data from the Phase I part of the Phase I/II clinical trial of Medigene’s T cell receptor-modified T cell (TCR-T) therapy MDG1011 in patients with advanced-stage blood cancers (ClinicalTrials.gov Identifier: NCT03503968 ( View Source)) (Press release, MediGene, FEB 3, 2022, View Source [SID1234607703]). Data demonstrating safety and tolerability, with no cases of dose-limiting toxicity (DLT) associated with MDG1011, were published in December 2021.

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MDG1011 is a TCR-T immunotherapy directed against the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma). Patients with relapsed or refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or multiple myeloma (MM) were included in the open-label, dose-escalation Phase I part of the study that was conducted at nine clinical centers in Germany. Following standard pre-conditioning, patients received MDG1011 as a single intravenous infusion at specified dose levels of 0.5, 1 or 5 million TCR-transduced T cells per kg body weight. The primary study objectives were to evaluate safety, tolerability, and feasibility to manufacture autologous MDG1011 TCR-T cells for heavily pretreated patients. In addition, preliminary signs of clinical efficacy and immune monitoring data were investigated.

Clinical and biological data analysis

MDG1011 contained CD8+ TCR-T cells showing recognition and killing of specific standardized target cells in vitro and was successfully manufactured for 13 patients. The group of patients included ten with AML, two with MM and one with MDS. Four patients succumbed to disease before treatment could be administered, in line with the severity of the underlying condition of study patients. Thus, nine patients received MDG1011 at one of the three specified dose levels.

Patient immune monitoring included detection of PRAME-specific T cells (MDG1011 TCR-T cells) in blood to determine persistence over time and biomarker tracking of PRAME in bone marrow and/or blood (as an indicator for remaining cancer cells) by qPCR.

* One patient with AML treated at the lowest dose experienced complete remission at week 4 after treatment; however, this clinical response was not sustained, and the patient’s disease progressed 8 weeks thereafter. PRAME expression was slightly increased from baseline at week 4 whereas MDG1011 TCR-T cells were below the detection level.
* Two patients with AML, treated at the intermediate and highest dose respectively, experienced transient grade 1 or 2 cytokine release syndrome (CRS) within 3 days of drug administration, providing evidence of biological activity of MDG1011 therapy in vivo. MDG1011 TCR-T cells were still detectable in both patients at week 4.
* One patient with multilineage MDS and myeloproliferative neoplasm (MPN) treated at the highest dose, remained without apparent progression to secondary AML 3 and 6 months after MDG1011 administration and is still monitored. MDG1011 TCR-T cells were found at weeks 4, 8 and 12 and were still present at lower levels at month 6 after treatment. Bone marrow could not be evaluated in this patient. PRAME signals in blood were no longer detected at week 4 but gradually increased thereafter at 2, 3 and 6 months, remaining clearly below the baseline level. In concordance, blast counts both in blood and bone marrow remained well below baseline.
* MDG1011 TCR-T cells were detected in six of eight evaluable patients at one or more time points within four weeks after administration. TCR-T cells were also present in two patients at later time points, albeit at decreased levels.
* The biomarker PRAME was assessed in bone marrow samples from five patients four weeks after MDG1011 administration compared to baseline. PRAME decreases occurred in three AML and one MM patient while a slight increase was noted in another patient with MM. PRAME decreased in blood at week 4 for two patients treated at the highest dose but increased thereafter.

The preliminary clinical observations in two patients and occurrence of CRS in a further two of the nine heavily pretreated cancer patients are both encouraging and consistent with expectations of an adoptive T cell therapy. These observations are corroborated by the immune monitoring data.

Prof. Simone Thomas, from the Department of Internal Medicine III of the University Hospital Regensburg and Leibniz Institute for Immunotherapy, Principal Investigator of the study: "No immune effector cell-associated neurotoxicity syndrome (ICANS) or DLTs were detected, so MDG1011 appears to be safe and well-tolerated at all three doses. The aforementioned clinical observations taken together with the effect on PRAME levels and the persistence of MDG1011 strongly support the hypothesis of biological activity of MDG1011."

Prof. Dolores Schendel, Chief Executive Officer and Chief Scientific Officer at Medigene: "We are very pleased that all MDG1011 TCR-T drug products manufactured from such heavily pre-treated patients with a substantial disease burden showed strong functional activity in vitro, leading to detectable biological and/or clinical activity in four patients.

The effects of PRAME-specific TCR-T immunotherapy on cancer cells should be further investigated based on this safe and well-tolerated treatment. The use of higher cell numbers as well as the treatment of patients with less advanced disease stages could further increase the clinical benefit in the future. Based on our strategic shift to development of TCR-T immunotherapy for solid cancer, Medigene has announced previously that the Phase II part of this study will only be conducted with or by a partner; based on overall results from the Phase I part of the study.

Our current development programs in solid cancer concentrate on TCR discovery for novel tumor-specific antigens and implementation of innovative tools to enhance efficacy and improve safety of T-cell-based immunotherapies."

On February 3, 2022 Sapience Therapeutics, Inc., a biotechnology company focused on the discovery and development of peptide therapeutics to address difficult-to-treat cancers, reported that the company will present at the Guggenheim Healthcare Talks, 2022 Oncology Conference, taking place virtually February 9-February 11, 2022 (Press release, Sapience Therapeutics, FEB 3, 2022, View Source [SID1234607720]).

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Dr. Barry Kappel, CEO and President of Sapience, will present a company overview on Friday February 11th, at 11:30 am ET. Sapience management will also participate in one-on-one meetings with investors during the conference.