On April 11, 2022 Priothera Ltd, a late-clinical stage biotechnology company pioneering the development of its S1P receptor modulator mocravimod, reported it has received the two first European country approvals from the Swiss and French national health authorities (Swissmedic and ANSM) to begin its planned pivotal study of mocravimod (Press release, Priothera, APR 11, 2022, View Source [SID1234611928]). The company has also received encouraging feedback from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) on the clinical study design that is closely aligned with earlier feedback from the US Food and Drug Administration (FDA).

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Priothera will initiate a global Phase 2b/3 study (MO-TRANS study) in Europe, US and Japan, assessing the efficacy and safety of mocravimod as an adjunctive and maintenance therapy in adult Acute Myeloid Leukemia (AML) patients undergoing allogenic hematopoietic stem cell transplant (HSCT). The MO-TRANS study is expected to start in the second half of 2022 and preliminary data from this study are expected by the end of 2024.

Florent Gros, Co-Founder and CEO of Priothera, commented "Following on from our recent receipt of orphan drug designations for mocravimod in the US and Europe, we are pleased to have received our first approvals to initiate this key global Phase 2b/3 trial with this highly promising compound. Moreover, the CHMP feedback is encouraging, and is also closely aligned with the feedback we received from the FDA. These first approvals are important regulatory and clinical milestones for Priothera and move us a step closer to bringing mocravimod, an adjunctive and maintenance treatment, to patients with AML and other hematologic malignancies, for whom there remains a significant unmet medical need."

About mocravimod
Mocravimod (also known as KRP203), is a synthetic, sphingosine 1-phosphate receptor (S1PR) modulator. This novel investigational drug has been assessed in Phase 1 and Phase 2 trials for safety and tolerability, as well as for efficacy in several autoimmune indications. Promising data from a Phase 1b/2a clinical study in patients with hematological malignancies led Priothera to further develop mocravimod for the treatment of blood cancers.

Mocravimod will be investigated as an adjunctive and maintenance treatment in a Phase 2b/3 study as a potential treatment for patients with Acute Myeloid Leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (HSCT). Allogenic HSCT is the only potentially curative approach for AML patients, but current treatments have unacceptably high mortality and morbidity rates.

Priothera leverages S1PR modulator’s unique mode of action to maintain anti-leukemia activity – graft-versus leukemia (GVL) while reducing tissue damage resulting from graft-versus-host disease (GVHD), a consequence of allogenic HSCT. This novel treatment approach – mocravimod being the only S1PR modulator treating blood cancers – tackles a high unmet medical need and intends to add quality life to patients.

On April 11, 2022 AIM ImmunoTech Inc. (NYSE: American AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders, and viral diseases, including COVID-19, the disease caused by the SARS-CoV-2 virus, reported the presentation of positive data from a Phase 1 study at Roswell Park Comprehensive Cancer Center in patients with metastatic triple-negative breast cancer using chemokine modulation therapy, including AIM ImmunoTech Inc.’s drug candidate, Ampligen (also known as rintatolimod), interferonα-2b, and pembrolizumab at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held April 8-13, 2022, in New Orleans, Louisiana (Press release, AIM ImmunoTech, APR 11, 2022, View Source [SID1234611926]).

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The presented research was led by Roswell Park medical oncologist Shipra Gandhi, MD, in collaboration with senior investigator Pawel Kalinski, MD, PhD, Chair of Immunology at Roswell Park.

Title: Systemic Rintatolimod and Interferonα-2b selectively reprogram local tumor microenvironment in patients with metastatic triple negative breast cancer for enhanced influx of cytotoxic T-lymphocytes but not regulatory T-cells
Presenter: Shipra Gandhi, MD

"This pilot trial studies the potential of chemokine modulation therapy when given prior to pembrolizumab in participants with triple-negative breast cancer that has spread to other places in the body. Drugs used in chemokine modulation therapy, such as celecoxib, recombinant interferon alfa-2b, and Ampligen appears to work by unleashing or enhancing the body’s immune responses against the cancer by either blocking inhibitory immune elements or by activating stimulatory immune elements. Monoclonal antibodies, such as pembrolizumab, may then be better able to interfere with the ability of tumor cells to grow and spread," commented David R. Strayer, MD, Chief Science Officer.

"The data, while from a small number of subjects, is extremely impressive for four out of six Ampligen plus pembrolizumab patients; three demonstrated disease stabilization and one showed a significant and dramatic rapid destruction of the tumor and metastasis. The potential of this signal is completely consistent with the important survival signal shown by Ampligen and pembrolizumab in the advanced recurrent ovarian cancer study conducted at UPMC", commented Thomas K. Equels, Chief Executive Officer.

In the study, six evaluable patients (33-75 years) with mTNBC received 6 doses of Ampligen (200 mg i.v.), IFN-2 (INTRON-A; 20MU/m2 i.v.) and COX-2 inhibitor (celecoxib; 2 x 200 mg, p.o.) over 2 weeks, with tumor biopsies obtained before (within 6 days) and after (within 5 days) CKM. All patients received follow-up pembrolizumab (200 mg, i.v, Q3 weeks).

Summary of Key Findings:

The pre-determined primary endpoint of efficacy was met (increase in CD8 in TME).
Uniform increase of immune markers upon treatment was observed: CD8 mRNA (6.1-fold; p-0.034), GZMB mRNA (3.5-fold; p=0.058), ratios of CD8 /FOXP3 and GZMB/FOXP3 (5.7-fold; p=0.036, and 7.6-fold; p=0.024 respectively), thus successfully meeting the pre-determined primary endpoint in the study (increase in CD8 in TME).
In addition, an increase in CTL attractants CXCL10 (2.6-fold; p=0.104) and CCL5 (3.3-fold; p=0.019) was observed. In contrast, Treg marker FOXP3 or Treg attractants CCL22 or CXCL12 were not enhanced.
Three patients had stable disease lasting 2.4, 2.5 and 3.8 months, as of data cut off September 1, 2021.
An additional patient (non-evaluable) had a partial response (breast tumor autoamputation) with massive tumor necrosis in the post-CKM biopsy.
For more information about the study, please visit ClinicalTrials.gov: NCT03599453.

On April 11, 2022 AIM ImmunoTech Inc. (NYSE: American AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders, and viral diseases, including COVID-19, the disease caused by the SARS-CoV-2 virus, reported the presentation of data from the ongoing Phase 2a clinical study at Roswell Park Comprehensive Cancer Center evaluating AIM ImmunoTech Inc. drug candidate, Ampligen (also known as rintatolimod) as a component of treatment for colorectal cancer metastatic to the liver at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held April 8-13, 2022, in New Orleans, Louisiana (Press release, AIM ImmunoTech, APR 11, 2022, View Source [SID1234611925]).

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The presented research was led by Roswell Park medical oncologist Sarbajit Mukherjee, MD, MS, in collaboration with senior investigator Pawel Kalinski, MD, PhD, Chair of Immunology at Roswell Park.

Title: Initial results of a phase II study evaluating a chemokine-modulatory (CKM) regimen in patients with colorectal cancer metastatic to the liver
Presenter: Sarbajit Mukherjee, MD, MS

Based on preclinical data and previous reports showing the prognostic value of intratumoral CD8+ T cell (CTL) in colorectal cancer (CRC) outcomes, it was hypothesized that systemic infusion of the combination of IFNα-2b with Ampligen (selective TLR3 ligand for i.v. use) could reprogram the local balance between the CTL- and regulatory T cell (Treg)-attracting chemokines and the resulting patterns of immune infiltrates in liver tumors.

This early Phase 2a trial studied how well celecoxib, recombinant interferon alfa-2b, and Ampligen work in treating patients with colorectal cancer that has spread to the liver. The study was designed on the basis that 1) celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth; 2) Recombinant interferon alfa-2b is a substance that can improve the body’s natural response and may interfere with the growth of tumor cells; and 3) Ampligen may stimulate the immune system, so that giving celecoxib, recombinant interferon alfa-2b, and Ampligen together may help reprogram the tumor microenvironment and make the tumors more responsive to immune therapy.

For the study, recurrent/metastatic CRC patients with unresectable liver metastases amenable to biopsy were eligible. Patients had prior treatment (Rx) with fluoropyrimidine, irinotecan, oxaliplatin, and an anti-EGFR targeted therapy (if RAS wt), or contra-indication to such. Patients received IFNα-2b IV (20 million units/m2 IV daily) and Ampligen (200 mg IV daily) plus oral celecoxib (200 mg twice daily) on days 1, 2, 3, 8, 9, 10, 15, 16, and 17. Response assessment was done via liver biopsies (pre-Rx and on day 24 ± 4 days) and CT imaging (RECIST v1.1) on Day 46. The primary endpoint was the change in CD8+ T-cells before Rx, with that seen post-Rx (measured by quantitative RT-PCR as a ratio of CD8α to a housekeeping gene, HPRT). With a sample size of N=12 evaluable pts, the study design had a 90% power to detect a 0.77 standard deviation increase (pre- to post Rx) at a significance level of 0.1. Nineteen patients with microsatellite stable (MSS) CRC were enrolled in the study between Apr 2018 and Oct 2020, and 12 were evaluable for the primary endpoint.

"The primary endpoint of this study, a significant increase in CD8a expression post-treatment, along with increases in CTL-attracting chemokines coupled with a decrease in a key Treg/MDSC attractant indicate a positive immune effect on the tumor microenvironment and suggest this CKM approach has the potential to increase tumor responses to checkpoint inhibitors", commented David R. Strayer, MD.

Summary of Key Findings:

The study’s primary endpoint was met, evidenced by increased CD8a expression post-treatment (p=0.046).
Saw increase in the CD8a/CD4 (p=0.03), CD8a/FOXP3 (p<0.01) and GZMB/FOXP3 (p<0.01) ratios.
The expression of CTL-attracting chemokines CCL5 (p=0.08), CXCL9 (p=0.05), and CXCL10 (p=0.06) were increased, while expression of the Treg/MDSC attractant CXCL12 (p=0.07) was decreased post-treatment.
Median OS was 10.5 (90% CI 2.2-15.2) months, and the median PFS was 1.5 (90% CI 1.4, 1.8) months.
No tumor responses were seen. The treatment was well tolerated. Of all enrolled patients (N=19), adverse events were noted in 74% of patients, with the most common being fatigue (58%). Grade 3 or higher adverse events were rare (5%).
For more information about the study, please visit ClinicalTrials.gov: NCT03403634.

On April 11, 2022 Vivesto AB, an oncology-focused specialty pharmaceutical company, reported the appointment of Dr. Daniel Tesfa as Chief Medical Officer (CMO), who will be responsible for leading the clinical development of all Vivesto’s oncology programmes in concert with our CSO, Dr. Reinhard Koenig, responsible for all pre-clinical activities (Press release, Vivesto, APR 11, 2022, View Source [SID1234611901]). Dr. Tesfa, who will join Vivesto no later than 1 July, will report to CEO Francois Martelet and will also join Vivesto’s Management team.

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Dr. Tesfa brings extensive experience in clinical development and precision oncology over 20 years. Most recently, from 2020, he served as Medical Director, Clinical and Translation Science Hematology at listed Swedish biopharmaceutical company SOBI (Swedish Orphan Biovitrum AB), where he led clinical development.

Prior to his time at SOBI, from 2018 until 2020, Dr. Tesfa worked as Head of Oncology and Hematology at Bayer, Scandinavia, where he was a Medical Advisor and manager for the medical team.

Other prior roles include Country Medical Manager Oncology and Hematology, at Roche, Sweden, where he acted as a Medical Advisor and had a leading role in launching the hemophilia and lymphoma products, and also worked on treatments for colorectal, breast and lung cancers. Dr. Tesfa also brings first-hand experience as a specialist doctor as he was Head of Polyclinical Section at the former Hematology Center Karolinska Huddinge.

Dr. Tesfa holds a PhD in Medicine from Karolinska Institutet and an M.D. from the University of Lund, Sweden. He is also a fellow of Swedish Society of Medicine, and a member of the Swedish Hematology and Oncology Association.

François Martelet, M.D., CEO, commented: "We are delighted to welcome Daniel to the Vivesto team. His extensive and first-hand experience working in clinical development and oncology makes him a perfect fit for Vivesto going forward, as we extend our internal capabilities for the development of solutions for hard-to-treat and late-stage cancers."

Dr. Daniel Tesfa, CMO, said: "I am looking forward to joining Vivesto and helping to deliver the mission to improve survival and quality of life for patients with cancer, as the company progresses its pipeline of exciting clinical stage development programmes."

On April 11, 2022 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that data from its ongoing first-in-human Phase 1/2 trial evaluating the safety and preliminary efficacy of the Company’s novel CAR-T cell therapy candidate, BNT211, in patients with advanced solid tumors (Press release, BioNTech, APR 11, 2022, View Source [SID1234611899]). The preliminary results demonstrated an encouraging safety profile and anti-tumor activity in testicular cancer patients at the first evaluated dose levels of BNT211. The data were presented in the Clinical Trials Plenary Session at the AACR (Free AACR Whitepaper) Annual Meeting 2022 by Prof. John Haanen, M.D., Ph.D., Netherlands Cancer Institute (NKI), Amsterdam, Netherlands.

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BNT211 is a potential first-in-class therapeutic approach which comprises two drug products, an autologous CAR-T cell therapy targeting the oncofetal antigen Claudin-6 (CLDN6) and a CLDN6-encoding CAR-T cell amplifying RNA vaccine (CARVac), which is based on BioNTech’s mRNA-lipoplex technology to improve persistence and functionality of the adoptively transferred cells.

The presentation included data from 16 patients who received CLDN6 CAR-T cells at dose levels 1 (1×107 CAR-T cells) and 2 (1×108 CAR-T cells) alone or combined with CARVac. Tumor indications included testicular cancer (n=8) ovarian cancer (n=4), endometrial cancer, fallopian tube cancer, sarcoma, and gastric cancer (1 patient each). Treatment with CLDN6 CAR-T alone or in combination with CARVac up to dose level 2 was well tolerated and showed encouraging signs of clinical activity. All 16 patients showed robust CAR-T cell expansion 10-17 days after infusion with cell frequencies close to 109 total counts in dose level 2. Adverse events and dose limiting toxicities were manageable; cytokine release syndromes of grade 1 and 2 and one transient occurrence of neurotoxicity grade 1 were observed.

At the first efficacy assessment 6 weeks post infusion, 6 of 14 evaluable patients showed a partial response, and 5 patients had stable disease with shrinkage of target lesions. One patient showed no change from baseline and two patients were progressing. Responses were seen in testicular (n=4) and ovarian cancer (n=2) patients. At 12 weeks, 4 of the 6 patients with a partial response showed deepening and durability of responses with one patient reaching a complete response 18 weeks after infusion. All 4 testicular cancer patients in the higher dose level had disease control and 3 of these patients showed objective responses. In addition, 1 testicular cancer patient showed partial response after infusion of the lowest CAR-T dose level in combination with CARVac. Antitumor activity tended to be higher at the higher CAR-T dose and when combined with the vaccine, with 4 of 5 patients in the CARVac combination group showing a partial response.

"Seeing first anti-tumor effects even at the lowest CAR-T cell dose in this heavily pre-treated patient population is truly remarkable and points to the potential of our CAR design and our CARVac approach," said Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "The results support our assumption that Claudin-6 is a well-suited new tumor target. Bringing these innovations together in one regimen may benefit patients with hard-to-treat solid tumors with an otherwise poor prognosis, such as advanced testicular cancer. Our preliminary data indicate that the successes of CAR-T in hematological cancers may indeed be transferred to solid tumors."

"Claudin-6 was never targeted with cellular therapy before, but in this study, the approach is already showing an efficacy that may be better than the data from other CAR-T trials in solid tumors," said John Haanen, M.D., Ph.D. a medical oncologist at the Netherlands Cancer Institute (NKI), Amsterdam, Netherlands, and principal investigator of the study. "While the data are very early, it is remarkable that all patients with testicular cancer showed clinical benefits at dose level 2, and the responses we have observed can be deep, including one ongoing complete remission. I look forward to further evaluating this exciting new modality for solid tumor patients."

The ongoing Phase 1/2 study (NCT04503278; 2019-004323-20) aims to evaluate the safety and preliminary efficacy of the CLDN6 CAR-T therapy alone and in combination with CARVac in heavily pretreated patients with CLDN6-positive relapsed or refractory advanced solid tumors and is conducted at multiple sites across Germany and the Netherlands. The next data update is expected later this year.

About BNT211
To harness the power of cell therapies for solid cancers and overcoming hurdles to date, BioNTech has combined their CAR-T and FixVac platform technologies to develop a highly tumor-specific CAR-T cell therapy product which is consecutively enhanced by a CAR-T Cell Amplifying RNA Vaccine (CARVac) that is based on BioNTech`s mRNA-lipoplex technology and encodes for the respective CAR-T target antigen. The vaccine has the potential to boost CAR-T activity, thus enabling and maintaining a therapeutic effect even at low CAR-T doses. BNT211 is a CAR-T cell therapy directed against the novel oncofetal antigen Claudin-6 (CLDN6), a target expressed on multiple solid tumors such as ovarian cancer, sarcoma, testicular cancer, endometrial cancer and gastric cancer. The program is currently being evaluated in a first-in-human Phase 1/2 trial as a monotherapy and in combination with a CLDN6-encoding CARVac, aiming to boost persistence and functionality of the CLDN6-CAR-T cells, in patients with CLDN6-positiv relapsed or refractory advanced solid tumors.