On November 12, 2021 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that data from its open-label Phase 1/2 study of novel lead asset, INT230-6, as a monotherapy or in combination with ipilimumab in adult subjects with metastatic sarcomas, is being presented today, in an oral presentation, at the Connective Tissue Oncology Society Virtual Annual Meeting (CTOS) (Press release, Intensity Therapeutics, NOV 12, 2021, View Source [SID1234595486]).

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"Preliminary data suggests that INT230-6, as a monotherapy, demonstrates direct tumor killing in soft tissue sarcoma subjects (STS) and elicits an anti-cancer immune response within the injected tumor," stated poster presenter and study investigator, Matthew A. Ingham, MD, Assistant Professor of Medicine in the Division of Hematology and Oncology at Columbia University Vagelos College of Physicians and Surgeons and first author of the study. "To date, though in a limited number of patients, INT230-6 treatment related adverse events are mostly low grade and the drug is well-tolerated either as a monotherapy or in combination with checkpoint inhibitor, ipilimumab. Additionally, an exploratory analysis showed an increase in survival with dosing a volume of INT230-6 above forty percent of the total tumor burden, as compared to survival from historical sarcoma studies. These results provide further evidence to continue studying this novel therapeutic drug approach."

Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics, added, "The promising data supports our belief that INT230-6, a locally-delivered anti-cancer product candidate, may potentially lead to clinical benefit with lower levels of off target side effects compared to chemotherapies for patients with advanced soft tissue sarcomas. Given these results, earlier this year we met with and reached alignment with FDA of the design of a randomized Phase 3 trial, subject to review by the Agency of the final protocol, to evaluate INT230-6 versus standard of care in patients with advanced soft tissue sarcomas."

Title: Safety and Efficacy from a Phase 1/2 Study of Intratumoral INT230-6 Alone or In Combination with Ipilimumab [INTENSITY# IT-01; BMS# CA184-592] in Adult Subjects with Metastatic Sarcomas (NCT 03058289)

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

The data presented included results from 19 patients with different metastatic sarcomas treated with INT230-6 either as a monotherapy (n=10), or in combination with a checkpoint inhibitor (n=8) primarily ipilimumab. The enrolled patients’ cancer progressed following a median of three prior lines of therapy (range 0 to 9) including all approved, appropriate therapies for a subject’s particular cancer. Demographics were similar in subjects enrolled in monotherapy and checkpoint inhibitor combination arms. The cumulative dose of INT230-6 IT injections ranged from 20 to 530mL (265mg cisplatin, 53mg vinblastine), with repeated intratumoral injections in multiple tumors. Pharmacokinetic (PK) profile analysis from 18 STS subjects in study IT-01 were analyzed for cisplatin, SHAO and vinblastine and show less than 5% of the drugs enter the blood stream.

A retrospective exploratory analysis of subjects was assessed by comparing INT230-6 dosed at greater than or equal to 40% of their incoming total tumor burden, suggesting promising survival. For sarcoma subjects dosed to >40% of their total tumor burden, approximately 60% of subjects will be alive at 1 year. These results compare favorably to those seen in historical Phase 1/2 studies of sarcoma subjects where approximately 50% of subjects are deceased at 3 to 8 months depending on certain prognostic factors (ECOG, LDH, # of metastatic sites). Abscopal effects were seen in visceral lesions in two subjects, which may be an underestimation, as no tumors under 1 cm and not all larger lesions were followed.

Immunohistochemistry analysis of INT230-6 monotherapy paired (pre- and 28 days post-dose) biopsy of injected lesions from 3 INT230-6 monotherapy STS subjects showed a median of 60% reduction in tumor cell content and a 72% reduction in Ki67 staining (proliferation marker).

Hematoxylin and Eosin assessments demonstrated substantial reductions of cancer cells in biopsies from monotherapy subjects after two injections of INT230-6 when compared to baseline. Local delivery of INT230-6 as monotherapy into tumors induced an immune response with increases of activated CD4+ and CD8+ T-cells in the tumor with a few low grade immune-related adverse events. These clinical results are consistent with immune findings from in vivo models. Most other adverse events were low grade and transient, consisting mostly of pain at the injection site (68.4% of patients), fatigue (42.1%) or decreased appetite (36%). There were no grade 4 or 5 treatment emergent adverse events and no events that were dose limiting.

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 that helps disperse the drugs throughout tumors for diffusion into cancer cells. In addition to local disease control, direct killing of the tumor by INT230-6 creates neoantigens leading to engagement of the immune system and systemic anti-tumor effects in the tumor. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

INT230-6 is currently being evaluated in several Phase 2 cohorts (NCT03058289) in patients with various advanced solid tumors as part of Study IT-01. In 2019, the Company signed a clinical collaboration agreement with Merck Sharpe & Dohme (Merck) to evaluate the combination of INT230-6 and KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, in patients with advanced pancreatic, colon, squamous cell and bile duct malignancies. In 2020, the Company executed a clinical collaboration agreement with Bristol-Myers Squibb Company to evaluate the combination of INT230-6 with Bristol-Myers Squibb’s anti-CTLA-4 antibody, Yervoy (ipilimumab), in patients with advanced liver, breast and sarcoma cancers. In 2021, the Company executed agreements with the Ottawa Hospital Research Institute and the Ontario Institute of Cancer Research to study INT230-6 in a randomized controlled neoadjuvant Phase 2 study in women with early stage breast cancer (the INVINCIBLE study) (NCT04781725).

On November 12, 2021 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that Walter V. Kemp, Founder, President, CEO and Chairman and Dr. John Paul Waymack, Senior Chief Medical Officer will participate in the Virtual Investor Roundtable Event on Thursday, November 18, 2021 at 11:00 AM ET (Press release, Moleculin, NOV 12, 2021, View Source [SID1234595485]).

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Joining the Company’s management team for the roundtable discussion will be Sant P. Chawla, MD, Director, Sarcoma Oncology Center, Director, Cancer Center of Southern California.

As part of the virtual event, the Company will provide a brief presentation, followed by a moderated Roundtable discussion and an interactive Q&A session. In addition to the moderated portion of the event, all investors and interested parties will have the opportunity to submit questions live during the event. Interested parties may also pre-submit questions in advance of the live event, which can be sent via the conference website at virtualinvestorco.com. The Company will answer as many questions as possible during the event.

A live video webcast of the Roundtable Event will be available on the Events page of the Investors section of the Company’s website (moleculin.com). A webcast replay will be available two hours following the live presentation and will be accessible for one year.

On November 12, 2021 Actym Therapeutics reported that ACTM-838 has been selected as a lead clinical development candidate for the treatment of solid tumors (Press release, Actym Therapeutics, NOV 12, 2021, View Source [SID1234595484]). ACTM-838 is based on the company’s immunotherapy platform called STACT (S. Typhimurium-Attenuated Cancer Therapy), which delivers multiplexed immuno-modulatory payloads directly to tumor-resident immune cells . ACTM-838 is a STACT strain that encodes engineered IL-15 (IL-15plex) and STING (eSTING). In preclinical studies, the IL-15plex + eSTING payload combination delivered by STACT resulted in primary human and mouse M2 macrophage production of type I interferon, and repolarization into a novel hybrid M1/M2 phenotype capable of tumor cell phagocytosis and priming of CD8+ T-cells. Complete tumor responses were observed in metastatic, checkpoint refractory tumors (IV dosing), that were entirely dependent on CD8+ T-cells. In primates, the therapy was well tolerated, rapidly cleared, and elicited minimal cytokine responses after IV dosing.

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"The nomination of a lead candidate is a tremendous accomplishment for our company, and we’re excited about the possibility of bringing a desperately needed treatment option to cancer patients," said Christopher Thanos, Ph.D., Cofounder and Chief Executive Officer of Actym Therapeutics.

Actym’s data will be presented on Friday, November 12, 2021, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington D.C. (Presentation #853, Novel Single Agent Immunotherapies).

On November 12, 2021 PathAI, a global provider of AI-powered technology applied to pathology reported that results from a recent exploratory biomarker analysis on digitized slides to apply AI-predicted CD8 topology assessment of patients with advanced melanoma will be presented at the annual Meeting of Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), November 10-14 2021 (Press release, PathAI, NOV 12, 2021, View Source [SID1234595483]).

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The results will be shared in two posters, Lee et al. The utility of AI-powered spatial classification of intratumoral CD8+ immune-cell topology in predicting overall survival in patients with melanoma as part of the CheckMate 067 clinical trial, and Glass et al. Machine Learning Models Can Quantify CD8 Positivity in Melanoma Clinical Trial Samples.

PathAI developed Machine Learning (ML) models to quantify CD8+ T cells in digitized whole slide images (WSI) of melanoma patient samples, and validated their performance against a consensus of pathologists on a held-out data set. These models were deployed on CD8-stained biopsy samples collected from patients with previously untreated advanced melanoma in the CheckMate 067 clinical trial. The AI-based predictions of CD8 positivity were used by ML models created by Bristol Myers Squibb to categorize each WSI by spatial pattern and density of CD8+ T cell infiltration (CD8 topology) as desert (deficient in CD8+ T cells), excluded (CD8+ T cells at the tumor boundaries and surrounding stroma), or inflamed (CD8+ T cells within the tumor parenchyma).

PD-L1 stained tumor cell positivity scores of either PD-L1 <1% or PD-L1 >1%, collected previously during the CheckMate 067 clinical trial, were combined with the CD8+ spatial phenotype scores to create a composite biomarker. Correlations between overall survival of patients in CheckMate 067 and CD8+ spatial phenotype alone, or the composite biomarker identified a subpopulation of patients with PD-L1 expression < 1%, and a CD8+-excluded tumor spatial pattern that benefited significantly from the drug combination treatment (nivolumab and ipilimumab) compared with PD-L1 negative patients with a CD8+-inflamed tumor spatial pattern (P = 0.002). No difference in survival between excluded and inflamed phenotypes was observed for patients treated with monotherapy (nivolumab alone) (P = 0.41), nor with any patients with PD-L1 >1%.

The data presented here suggest that in addition to PD-L1 positive patients, PD-L1 negative CheckMate 067 patients who were also CD8+ in specific subregions of tumors had overall survival benefit when treated with ipilimumab plus nivolumab combinations compared to those that were treated with ipilimumab monotherapy.

Together, these publications highlight the promise of ML-based CD8+ phenotype scoring to reveal populations of patients that might have the greatest benefit from existing treatments.

On November 12, 2021 Carisma Therapeutics Inc., a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported for the first time preliminary findings from the landmark Phase 1 multi-center clinical trial of CT-0508, a human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M) (Press release, Carisma Therapeutics, NOV 12, 2021, View Source [SID1234595482]).

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The early data were presented by Dr. Kim A. Reiss, MD, Principial Investigator for Carisma’s clinical trial of CT-0508 at the Abramson Cancer Center of the University of Pennsylvania (Penn), at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting. The preliminary findings represent the first clinical data with genetically engineered macrophages in humans and demonstrated that CT-0508 was well tolerated after infusion and there were no dose limiting toxicities. CT-0508 was also successfully manufactured using macrophages obtained from heavily pre-treated, advanced solid tumor patients and showed high CAR expression, viability, and purity. The data also demonstrated that CT-0508 remodeled the solid tumor microenvironment (TME) and mediated expansion/activation of T cells within the tumors. The Food and Drug Administration recently granted Fast Track designation to CT-0508 for the treatment of patients with solid tumors.

"This is the first time that genetically engineered macrophages are being studied in humans and we are encouraged by the safety profile and activity observed thus far," said Debora Barton, MD, Chief Medical Officer at Carisma Therapeutics. "We will continue to enroll patients in the landmark clinical trial of CT-0508 and look forward to making additional observations about how CAR-M therapy can potentially address the unmet needs of patients."

Carisma data also accepted for presentation at the SITC (Free SITC Whitepaper) 36th Anniversary Annual Meeting:

"Chimeric Antigen Receptor Macrophages (CAR-M) Elicit a Systemic Anti-Tumor Immune Response and Synergize with PD1 Blockade in Immunocompetent Mouse Models of HER2+ Solid Tumors," Friday, November 12 at 7:00 am ET
"Development and Characterization of CAR-Mono, a Novel Cell Therapy Platform for Solid Tumor Immunotherapy," Saturday, November 13 at 7:00 am ET
"SIRP⍺ Deficient CAR-Macrophages Exhibit Enhanced Anti-Tumor Function and Bypass the CD47 Immune Checkpoint," Saturday, November 13 at 7:00 am ET
"We are excited by the early Phase I clinical data demonstrating safety, feasibility, and TME remodeling with CT-0508," shared Michael Klichinsky, PharmD, PhD, co-inventor of the CAR-M technology and scientific co-founder and Senior Vice President of Research at Carisma Therapeutics. "Our research team is committed to innovation in the field of genetically modified myeloid cells, and we are excited to also share novel pre-clinical data with CRISPR editing, combination therapy, and manufacturing advances at the upcoming SITC (Free SITC Whitepaper) meeting."

Presentation and posters will be available on the SITC (Free SITC Whitepaper) 36th Anniversary Annual Meeting portal for registered attendees.

Editor’s Note: Dr. Saar Gill and Penn are both co-founders of Carisma and hold equity in the company. Carisma has licensed certain Penn-owned intellectual property from the University, and Penn’s Perelman School of Medicine receives sponsored research funding from the company in support of Dr. Gill’s laboratory and clinical trials at Penn, including the trial led by Dr. Reiss. Penn and Dr. Gill may be entitled to receive future financial benefits from development and commercialization of technologies licensed and optioned to Carisma.