On December 8, 2022 PDC*line Pharma, a clinical stage biotech company developing a new class of potent and scalable active immunotherapies for cancers, reported the first immunological results of its PDC-LUNG-101 phase I/II clinical trial (NCT03970746) with PDC*lung01, the company’s therapeutic off-the-shelf cancer vaccine candidate for Non-Small Cell Lung Cancer (NSCLC) (Press release, PDC Line Pharma, DEC 8, 2022, View Source [SID1234624974]). The preliminary data was presented today at a poster display session at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2022 (ESMO-IO) in Geneva (Switzerland). Results showed that in a large proportion of subjects PDC*lung01, in monotherapy and combined with pembrolizumab, induces a significant expansion of effector memory CD8+ T-cells specific to the tumor peptides carried by PDC*lung01.

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"We are very pleased to demonstrate that our innovative immunotherapy platform can induce a strong immune response in humans. These first results illustrate the potential targeted mechanism of action of PDC*lung01 to prime naive anti-tumor specific T-Cells and trigger effector memory T-cells in humans."

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The objectives of the phase I/II trial (PDC-LUNG-101) are to assess the safety, tolerability, immunogenicity and preliminary clinical activity of the drug candidate PDC*lung01, associated or not with anti-PD-1 treatment in NSCLC patients. PDC*lung01 will be administered to a total of 64 evaluable HLA-A*02:01 positive NSCLC patients, at two dose levels in two different settings:

As a single agent to patients in the adjuvant setting (A1: Low Dose, A2: High Dose)
Added to standard of care anti-PD-1 monotherapy to patients with first-line stage IV (metastatic) NSCLC disease with a PD-L1 tumor proportion score of ≥50% and no targetable driver mutation (B1: Low Dose, B2: High Dose)
PDC*lung01 is made of irradiated human Plasmacytoid Dendritic Cells (PDC*line), loaded with HLA-A*02:01-restricted peptides, derived from NY-ESO-1, MAGE-A3, MAGE-A4, Multi-MAGE-A, MUC1 and Survivin tumor antigens. It is administered weekly by a subcutaneous and intravenous route, in six consecutive doses. Safety and clinical activity of the product were presented at ESMO (Free ESMO Whitepaper) 2022 in September 2022 in Paris (France). PDC*line is a potent professional antigen-presenting cell line that is able to prime and boost the patient’s antitumor cytotoxic CD8+ T-cells and is synergistic in vitro with anti-Programmed Death-1 (PD-1) treatment. The poster presented the analysis of the immune responses of the first three cohorts of patients.

"We are very pleased that PDC*lung01 is found to be biologically active to trigger an antitumor immune response, detectable without any in vitro restimulation, in a significant number of patients in our NSCLC clinical trial. The first signal of correlation between immune and clinical responses in six metastatic patients from the B1 cohort is encouraging," said Dr. Joël Plumas, co-founder and chief scientific officer of PDC*line Pharma.

"Presenting the first immunological data set from our lead candidate, PDC*lung01, for the treatment of NSCLC at ESMO (Free ESMO Whitepaper)-IO, a major immuno-oncology conference, is an important milestone for the company," added Eric Halioua, CEO of PDC*line Pharma. "We are very pleased to demonstrate that our innovative immunotherapy platform can induce a strong immune response in humans. These first results illustrate the potential targeted mechanism of action of PDC*lung01 to prime naive anti-tumor specific T-Cells and trigger effector memory T-cells in humans."

Key highlights from the poster display

Poster title: The therapeutic cancer vaccine PDC*lung01 induces immune responses with or without anti-PD-1 treatment in patients with non-small cell lung cancer.

Several circulating immune parameters were monitored at different times before and after PDC*lung01 administrations using assays developed by PDC*line Pharma
Leukocyte count and determination of peptide-specific CD8+ T-cells, for which a Limit Of Quantification (LOQ) was defined to better assess the fold changes of the cell expansion. Assays allow evaluation of circulating antitumor specific CD8+ T-cells pre and post treatment, ex vivo with an LOQ of 0.003%, without prior in vitro restimulation

PDC*lung01 is found to be biologically active to trigger an antitumor immune response in a significant number of patients
23 of the 25 patients included received at least four doses and were evaluable. No major changes in circulating lymphocyte frequencies (B cells, NK cells, CD4+, CD8+, or Treg T-cells) were observed during treatment. In contrast, a specific and memory CD8+ T-cell response was induced against the antigens from which are derived the peptides loaded on PDC*lung01 in 33%, 45% and 67% of evaluable patients in, respectively, A1 (six patients), A2 (eleven patients) and B1 (six patients) cohorts

First signal of correlation observed between immune and best overall clinical responses in metastatic patients treated with pembrolizumab

The best overall response in six evaluable patients of the B1 cohort, according to RECIST criteria, included four partial responses, one stable disease and one progressive disease. CD8+ T-cells for at least one of the six lung antigens were observed in the majority of the partial and stable disease patients. In contrast, no immune response was detected in the progressive disease patient.

On December 8, 2022 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, first-in-class immune-based cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported new data from the INVINCIBLE study in a live Spotlight Session Poster Presentation at the San Antonio Breast Cancer Symposium (SABCS) Annual Meeting being held at the Henry B. Gonzalez Convention Center, San Antonio, TX, from December 6-10, 2022 (Press release, Intensity Therapeutics, DEC 8, 2022, View Source [SID1234624973]).

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The INVINCIBLE study (NCT 04781725), a phase 2, randomized study that enrolled 91 women with newly diagnosed, operable early-stage intermediate or high-grade T1-T2 invasive breast cancers 2 to 5 weeks prior to surgery (lumpectomy or mastectomy). Drug dose was set by the diameter of the tumor. Subjects were randomly allocated (2:1) prior to resection to 1 to 3 IT injections of INT230-6 versus no treatment (part 1 n=29) or saline sham injection (part 2 n=58).

INT230-6 demonstrated the ability to cause up to 100% necrosis of presurgical breast cancer tumors in the window period from diagnosis to surgery. Pathway enrichment analysis demonstrated changes in T cell activation, lymphocyte activation and inflammatory response. Analysis is ongoing for part 2 of the clinical trial for changes in Ki67 and other parameters. Adverse events were mostly grade 1 with expected pain at the breast injection site; there were very few systemic adverse effects.

"A diagnosis of breast cancer is a traumatic experience for a patient. There is a waiting period prior to surgery that can last for several weeks, which is a stressful time. For the majority of surgical candidates, there are currently no therapeutic options during the waiting period. Surgeons and patients can feel powerless," said Angel Arnaout, M.D., Scientist and Surgical Oncologist at the Ottawa Hospital, Professor of Surgery at the University of Ottawa and Co-lead of the Ontario Institute for Cancer Research (OICR) Window-of-Opportunity (WOO) Network. "INT230-6 a new drug approach where the drug is directly injected into the tumor. The technology uses a dispersion enhancer that can cause high levels of tumor cell death and necrosis in multiple breast cancer subtypes. The ability to use just one or two doses of this agent to elicit a rapid and marked cytotoxic and immune induction response within the tumor during the surgical waiting period, all without an increase in postoperative complications, is very novel and highly desirable. Patient feedback and acceptance of this new approach has been quite positive. We are excited about how this new approach may fundamentally change the treatment for pre-surgical cancer patients. We look forward to completing our INVINCIBLE study data analysis and new studies to demonstrate that this new agent can make a long-term, positive impact in patients with breast cancer."

"The cell death activates an anti-cancer immune response as we see a relative increase in the abundance of CD4 T naïve, B and NK cells, post treatment when comparing drug treated with control samples within the tumor," said Dr. Melanie Spears, Co-Director, Diagnostic Development for OICR and Co-lead of the WOO Network. "This effect could be systemic and further work is in process to determine whether a global immune activation has occurred."

"The demonstration of 100% tumor necrosis in a tumor on a single dose of INT230-6 is unique," said Lewis H. Bender, President, and Chief Executive Officer of Intensity Therapeutics. "These new results from the INVINCIBLE study, coupled with our previously reported data in metastatic patients, provide further evidence and support for the potential of INT230-6 to treat several different and highly prevalent cancer types from before surgery to late stage disease. We look forward to reporting the full data set from the INVINCIBLE study and further development of our pioneering new medicine."

Spotlight Poster Discussion Presentation
Submission ID: 1310100
Poster ID: PD11-02
Poster Title: A Phase II Randomized Window of Opportunity Trial Evaluating Cytotoxic and Immunomodulatory effects of Intratumoral INT230-6 in Early Stage Breast Cancer: the INVINCIBLE Trial
Session Date: Thursday, December 8, 2022
Time: 7:00 AM – 8:15 AM CST
First Author: Angel Arnaout M.D., FACS

Each Spotlight Poster Discussion Session will consist of two to three sub-topic groups of posters, with an independent clinical oncology expert as a discussant for each group, to speak about the posters, followed by questions addressed to the discussant and the poster presenter, Dr. Arnaout.

The presentation will be accessible on the "Publications, Papers and Posters" page of Intensity’s website at: View Source

About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

On December 8, 2022 Dragonfly Therapeutics, Inc. ("Dragonfly" or the Company), a clinical stage biotechnology company developing novel immunotherapies, reported the first patient dosed in a Phase 1/2 study of the Company’s proprietary EGFR-targeting TriNKET (Press release, Dragonfly Therapeutics, DEC 8, 2022, View Source [SID1234624972]).

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DF9001is the sixth Dragonfly-developed drug to enter into clinical trials. The Company’s first TriNKET, DF1001, entered Phase 2 trials this month after being well-tolerated in Phase 1 with encouraging clinical responses, including showing tumor burden reductions across several tumor types, including in HER2-low and heavily pre-treated patients.

"Given our positive experience over the last two years with Dragonfly’s DF1001 HER2-targeting TriNKET, we are excited to begin offering patients with an even broader set of solid tumor cancers this new EGFR-targeting therapeutic," said Howard P. Safran, MD, Chief of Hematology/Oncology at the Lifespan Cancer Institute and Medical Director for the Brown University Oncology Group. "We see an opportunity for Dragonfly’s next generation of NK cell-engaging immune-oncology therapies to attack solid tumor cancers directly, recruit T cells to cold tumor environments, and offer a broadened therapeutic index – helping patients that presently have very few other therapeutic options."

"Initiating clinical trials with the sixth drug candidate developed by Dragonfly demonstrates how comprehensively we and our Pharma partners are bringing critically-needed new treatment options to patients with cancer," said Jean-Marie Cuillerot, Dragonfly’s Chief Medical Officer.

Dragonfly Therapeutics’ DF9001 Phase 1/2 clinical trial is a first-in-human, multi-part, open-label, non-randomized, multiple-ascending dose study to investigate the safety, tolerability, pharmacokinetics, biological, and clinical activity of DF9001 alone and in combination with a PD-1 checkpoint inhibitor in patients with locally advanced or metastatic solid tumors, followed by expansion in selected indications including Head and Neck Squamous Cell Carcinoma (HNSCC), Colorectal cancer (CRC), and Non-small Cell Lung Cancer (NSCLC).

Additional information about the trial, including eligibility criteria, can be found at: View Source (ClinicalTrials.gov Identifier: NCT05597839).

On December 8, 2022 Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing small molecule immunotherapies in oncology, reported Phase 2a clinical safety and efficacy data on lead therapeutic candidate PT-112 in combination with PD-L1 inhibition, in patients with advanced non-small cell lung cancer (NSCLC) at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2022 (Press release, Promontory Therapeutics, DEC 8, 2022, View Source [SID1234624971]).

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The poster titled, "A phase 2a study of the novel immunogenic cell death (ICD) inducer PT-112 plus avelumab in advanced non-small cell lung cancer patients," demonstrated that the PT-112 and avelumab combination is well-tolerated with manageable safety profile, and showed meaningful clinical benefits in patients without known predictive markers for immunotherapy response. Based on the clinical activity observed, the study’s results support further evaluation of PT-112 combinations with immuno-oncology agents and assessment of PT-112’s immunological effects in patients.

"These data give us proof of principle for the use of immunogenic cell death inducer PT-112 in combination with immune checkpoint inhibition in NSCLC patients, and are supportive of future opportunities to bring our intended immunotherapy combinations to cancer patients," said Matthew Price, Promontory Therapeutics co-founder and Chief Operating Officer. "Along with immune correlative findings, the results are encouraging. As the field of immunogenic small molecules continues to evolve, we are pleased to continue to demonstrate the ICD effects of PT-112 in human patients. Our published clinical and non-clinical studies to date have shown the potential of this approach."

The 18 patients enrolled in the study were treated with 360 mg/m2 of PT-112 on days one, eight, and 15, and 800 mg of avelumab on days one and 15, of a 28-day cycle. Eligible patients received no more than 4 prior lines of therapy and were required to have progressive disease and to have received prior anti-PD-1/PD-L1 and platinum treatment. Findings from the study include:

Common treatment-related adverse events (TRAEs) were anemia (50%), fatigue (50%), thrombocytopenia (44%), nausea (44%) and anorexia (44%).
There were no PT-112 grade 4-5 TRAEs reported.
Of the 15 patients evaluable for efficacy, six patients (40%) had stable disease or better by iRECIST criteria.
Two cases of radiographic and clinical improvement were noted:
One patient achieved unconfirmed partial response at the first imaging follow-up, with documentation of a 70% decrease in target lesions, followed by a complete response in target and non-target lesions along with relief of pulmonary symptoms. Post-progression, PET images showed that the patient’s disease remained well-controlled for an additional ~7 months with no subsequent treatments, suggestive of extended immune-related clinical benefit.
One patient achieved a metabolic FDG-PET response, showed increased T-cell fraction on treatment, and remained stable with a progression-free survival of 7.3 months.
Based on preclinical models, PT-112 is an immunogenic small molecule that induces ICD, recruits immune effector cells in the tumor microenvironment, and synergizes with immune checkpoint inhibitors.

For more information about PT-112 and Promontory Therapeutics’ clinical pipeline visit www.PromontoryTx.com.

About PT-112
PT-112 is the first small-molecule conjugate of pyrophosphate in oncology, and possesses a unique pleiotropic mechanism of action that promotes immunogenic cell death (ICD), through the release of damage associated molecular patterns (DAMPs) that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 represents a highly potent inducer of this immunological form of cancer cell death. Further, PT-112 harbors a property known as osteotropism, or the propensity of the drug to reach its highest concentrations in certain areas of the bone, making it a candidate for treatment of patients with cancers that originate in, or metastasize to, the bone. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and won "Best Poster" within the Developmental Therapeutics category at the ESMO (Free ESMO Whitepaper) 2018 Annual Congress. The combination Phase 1b dose escalation study of PT-112 with PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO (Free ESMO Whitepaper) 2020 Virtual Congress and the Phase 2a dose confirmation cohort in non-small cell lung cancer (NSCLC) patients reported at ESMO (Free ESMO Whitepaper) IO 2022. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH (Free ASH Whitepaper) is the third completed Phase 1 study of PT-112. Monotherapy Phase 2 development is ongoing in mCRPC, and now includes the Phase 2 proof of concept study in thymic epithelial tumors under the company’s formal collaboration with the NCI.

On December 8, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported preliminary results from its ongoing potentially pivotal trial evaluating Berubicin for the treatment of recurrent glioblastoma multiforme (GBM) (Press release, CNS Pharmaceuticals, DEC 8, 2022, View Source [SID1234624970]).

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"Although data are still early, we are pleased with these results in terms of recruiting a balanced patient population to compare Berubicin to Lomustine in the treatment of GBM, which may highlight Berubicin’s potential to provide a better therapeutic option for patients after first-line therapy for their disease. We remain steadfast in our efforts to drive patient enrollment across the U.S. and Europe and are making significant progress toward our planned interim analysis, which we expect to occur in mid-2023. Our team remains dedicated to moving this important program forward and to providing patients, families and physicians with a much needed treatment opportunity for this devastating disease," commented John Climaco, CEO of CNS Pharmaceuticals.

"Berubicin continues to demonstrate its ability to be an innovative treatment in GBM as a safe and potentially effective therapy. These preliminary findings bolster our conviction in Berubicin as we continue to advance this study forward. Based on the results we’ve seen preclinically and in the clinic thus far, we remain confident in Berubicin’s potential to provide a consequential and much needed clinical benefit for GBM patients. We are making excellent progress with patient recruitment worldwide and, because we have currently described a balanced randomized population, we look forward to providing a meaningful comparison between Berubicin and what has been considered a standard of care for second line therapy (Lomustine)," added Sandra Silberman, MD, PhD, Chief Medical Officer of CNS Pharmaceuticals.

The preliminary results showed that the enrolled patients have comparable demographics, including age, gender, race, BSA and KPS and, in addition, the unmethylated MGMT population, which was approximately 40% in both arms. The percentage of patients that are currently continuing on study or having withdrawn is also comparable between arms. All grades of adverse events occurring in more than 5% of patients, as well as Grade 3-5 events, were also similar in the Berubicin and Lomustine arms.

As of the data cutoff of October 17, 2022, 49 patients were enrolled in this potentially pivotal trial with 35 subjects on Berubicin and 14 subjects on Lomustine, reflective of the Company’s 2:1 randomization schema. This study is evaluating the efficacy of this novel drug in terms of overall survival (OS), with the goal of providing the first approved therapeutic option for patients after first-line therapy. A pre-planned, non-binding futility analysis of OS will be performed after approximately 30 to 50% of all planned patients are enrolled in the study. These patients will be evaluated at 6 months after enrollment in the study, which we expect mid-year 2023. This review will include additional evaluation of safety as well as secondary efficacy endpoints related to the efficacy of Berubicin. Enrollment will not be paused during this interim analysis.

The data were recently presented by Dr. Silberman at the Society of Neuro-Oncology’s 27th Annual Meeting in a poster titled, "A Randomized, Controlled Trial of Berubicin, a Doxorubicin Analog That Effectively Crosses the Blood-Brain Barrier (BBB), After First-Line Therapy for Glioblastoma Multiforme (GBM): Preliminary Results1."

The Company can now report that subsequent to Dr. Silberman’s presentation at the Society of Neuro-Oncology’s 27th Annual Meeting, enrollment has increased to 67 patients in this potentially pivotal study. "It is a remarkable testament to both the design of our study and the magnitude of the unmet clinical need in this terrible disease that our study is enrolling at this rapid pace. We are extremely grateful to our patients, our investigators and to our investors who are all facilitating this potentially game-changing clinical program," said John Climaco, Chairman and CEO of CNS Pharmaceuticals, Inc.

For more information about the ongoing potentially pivotal Berubicin trial, visit clinicaltrials.gov and reference identifier NCT04762069.

About Berubicin

Berubicin is an anthracycline, a class of anticancer agents that are among the most powerful chemotherapy drugs and effective against more types of cancer than any other class of chemotherapeutic agents. Anthracyclines are designed to utilize natural processes to induce deoxyribonucleic acid (DNA) damage in targeted cancer cells by interfering with the action of topoisomerase II, a critical enzyme enabling cell proliferation. Berubicin treatment of brain cancer patients appeared to demonstrate positive responses that include one durable complete response in a Phase 1 human clinical trial conducted by Reata Pharmaceuticals, Inc. Berubicin, was developed by Dr. Waldemar Priebe, Professor of Medicinal Chemistry at The University of Texas MD Anderson Cancer Center. The FDA has granted CNS Pharmaceuticals Fast Track Designation and Orphan Drug Designation for Berubicin.