On November 10, 2022 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative diseases through the inhibition of semaphorin 4D (SEMA4D), and its collaborators at Emory University and the Moffitt Cancer Center reported that two abstracts, including an oral presentation and a poster related to investigator-sponsored trials for pepinemab combinations, are being presented at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting (Press release, Vaccinex, NOV 10, 2022, View Source [SID1234623675]).

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These studies describe novel biomarkers of response and resistance to immunotherapy that inform new potential treatment options in combination with Vaccinex’s pepinemab antibody.

Oral Presentation of pepinemab combinations with immune checkpoint blockade for neoadjuvant treatment of Stage III melanoma:
Dr. Brian Olson of Winship Cancer Institute at Emory University presented results of a collaborative study with Vaccinex investigating biomarkers and benefit of neoadjuvant combination immunotherapy including Vaccinex’s pepinemab antibody in patients with resectable Stage III melanoma who went on to receive adjuvant therapy with nivolumab after surgery (NCT03769155). 100% of patients who received the triple combination of pepinemab, nivolumab and ipilimumab were recurrence free at 24 months. This contrasted with recurrence free survival of less than 40% in patients who received the dual combination of pepinemab and nivolumab or pepinemab and ipilimumab.

Importantly, it was observed that the LAG-3 immune checkpoint is increased on T cells in tumors from the subset of patients who did not respond to the combination of pepinemab plus nivolumab. This provides a strong rationale for a triple combination treatment with pepinemab and inhibitors of both the PD-1 and LAG-3 checkpoint pathways. Further characterization of the tumors resected from these patients demonstrated that combination treatments that include pepinemab give rise to highly organized lymphoid structures consisting of B lymphocytes in close proximity to activated CD8+ and CD4+ T cells. These organized lymphoid structures are believed to provide an environment that supports efficient differentiation of immunoprotective as opposed to immunosuppressive cells.

Poster Presentation of pepinemab combination with adoptive cell therapy for patients with HER2+ metastatic breast cancer:
The important role of CD4+ T cells in directing a productive immune response was also the rationale for an independent adoptive cell therapy trial in breast cancer presented by collaborators, Dr. Hyo S. Han and Dr. Brian Czerniecki of the Moffitt Cancer Center (NCT05378464). In preclinical studies, it was shown that SEMA4D antibody blockade in combination with a dendritic cell vaccine improved trafficking of dendritic cells to tumors and stimulated expansion of tumor-specific B and T cells, resulting in improved regression of both primary and distant tumors. A Phase 1/2 trial involving combination of pepinemab and trastuzumab with a dendritic cell vaccine followed by adoptive transfer of expanded autologous CD4+ T cells is now enrolling patients with HER2+ metastatic breast cancer.

Maurice Zauderer, Ph.D., President and Chief Executive Officer of Vaccinex, remarked, "The investigator-sponsored collaborative studies reported at SITC (Free SITC Whitepaper) 2022 provide safety information and describe novel biomarkers of response and resistance to immunotherapy that inform new potential treatment options in combination with Vaccinex’s pepinemab antibody. We plan to explore such strategies with partners interested in rational combinations to enhance the activity of their drugs through an independent mechanism of action, without notable additional toxicity."

Dr. Zauderer concluded, "Vaccinex is conducting a Phase 1b/2 study in patients with pepinemab in combination with KEYTRUDA for recurrent and metastatic head and neck squamous cell cancer (R/M HNSCC), the KEYNOTE-B84 study. We have previously reported promising initial results from this study, including complete responses in patients with difficult to treat tumors that express low levels of PD-L1. These exciting data build on our understanding of the potent activity of pepinemab in orchestrating and amplifying immune responses in combinations with companion immunotherapies. We continue to observe strikingly improved responses in this patient population and expect to report results of interim analysis from this study in 1Q 2023."

Oral Presentation Details:

"Neoadjuvant SEMA4D blockade with nivolumab alters suppressive myeloid cells while elevating B cell and CD26hi T cell infiltration in the tumors of patients with resectable stage III melanoma".

Abstract number: 613
Presentation Date/Time: Friday November 11 at 5:20 PM, EST
Session: 210: Cancer Surgery in the Age of Immunotherapy
Presenter: Dr. Brian Olson of Winship Cancer Institute at Emory University

This Phase 1 open label integrated biomarker study was designed to evaluate immune responses in tumor and blood before and after neoadjuvant treatment with immunotherapy combinations (n=8) compared to standard of care surgery without treatment (n=6). Objectives included biomarker correlates, as well as safety and tolerability in the neoadjuvant setting, and clinical response in terms of pathologic response and recurrence-free survival (RFS). In September 2022, Dr. Michael Lowe from the Emory team presented the clinical safety and efficacy data at the 2022 ESMO (Free ESMO Whitepaper) Congress in Paris, France, reporting that pepinemab enhanced RFS of nivolumab and ipilimumab combinations, yet was well-tolerated and did not enhance toxicities associated with the companion immune checkpoint blockade (ICB) drugs (1). At SITC (Free SITC Whitepaper), Dr. Olson reports the biomarker correlates of this study.

The first of several important findings is that LAG3 expression appears to be an escape mechanism to treatment with the combination of pepinemab plus nivolumab. LAG3 was significantly upregulated on CD8+ and CD4+ T cells in patients who experienced recurrence of cancer within 24 months of treatment, while LAG3 remained low in patients who were recurrence-free. Together with previously reported preclinical data demonstrating dramatic synergy of blocking antibodies to SEMA4D and LAG3, as well as the favorable safety profiles for both pepinemab and LAG-3 antibodies in clinical studies, this provides rationale to evaluate combinations of pepinemab with LAG3 and PD-1/PD-L1 targeted therapies.

Secondly, results demonstrate a striking increase in the formation of tertiary lymphoid structures (TLS) in tumors of patients responding to treatment with combination therapies that include pepinemab, but not single agent nivolumab. These highly organized TLS consist of activated and proliferating B cells surrounded by activated (CD69+) CD8+ and CD4+ T cells. Notably, a significant increase in CD26high CD4+ T cells was induced in all pepinemab combinations, especially in the highly effective triple combination. These cells were previously described by team member, Dr. Chrystal Paulos, to have enhanced multi-functionality, a rich profile of cytokine and chemokine secretion, and, importantly, long-term persistence and memory with improved cytotoxic function and activity in preclinical models of adoptive cell therapy (2, 3). This suggests that addition of pepinemab to adoptive cell and/or CAR-T therapies may more effectively augment or rescue anti-tumor immune responses in patients.

Poster Presentation Details:

"Phase I Study of Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine and Pepinemab/Trastuzumab in Patients with Metastatic HER2-Positive Breast Cancer (NCT05378464)".

Abstract number: 645
Presentation Date/Time: Thursday November 10 at 9:00 AM, EST
Session: Clinical Trials In Progress
Presenter: Dr. Hyo Han of Moffitt Cancer Center

Co-authors from Moffitt Cancer Center and Vaccinex present a newly initiated and actively enrolling trial to evaluate safety and efficacy of a combination therapy involving treatment with pepinemab/trastuzumab/DC-1 dendritic cell vaccine, followed by collection, expansion, and adoptive transfer of CD4+ Th1 cells in patients with trastuzumab-refractory metastatic breast cancer. Primary endpoints include safety and tolerability, with additional assessments of clinical efficacy as well as immune biomarkers in the tumors and blood.

About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody that inhibits SEMA4D, which regulates chronic inflammation in the tumor microenvironment. Preclinical and clinical data show that pepinemab promotes infiltration/activation of dendritic cells/ CD8+ T-cells and reverses immunosuppression within the tumor (4,5).

Results of a Phase 1b/2 study to evaluate the combination of pepinemab with checkpoint inhibitor, BAVENCIO (avelumab, Merck KGaA) were presented at ASCO (Free ASCO Whitepaper) 2020 and were highlighted in the July 2021 publication of Clinical Cancer Research. Vaccinex reported that results of this Phase 1b/2 CLASSICAL-Lung trial showed a 25-33% Overall Response Rate (ORR) for patients with difficult to treat PD-L1 low/negative tumors treated with the combination. The study report also indicated that pepinemab did not increase immune-related toxicities of BAVENCIO but increased penetration of cytotoxic T cells (6). The publication is available electronically at: Clinical Cancer Research.

Vaccinex has global commercial and development rights to pepinemab, and is sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. Additional information about the study is available at: View Source
KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA.

On November 10, 2022 Phio Pharmaceuticals (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology makes immune cells more effective in killing tumor cells, reported the results of several studies of its INTASYL compounds (Press release, Phio Pharmaceuticals, NOV 10, 2022, View Source [SID1234623674]).

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INTASYL compounds are chemically modified siRNA’s that provide efficient, spontaneous cellular uptake and potent, long lasting intracellular activity targeting a broad range of cell types and tissues.

INTASYL drugs precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized formulations or drug delivery systems. INTASYL demonstrated preclinical efficacy in both Direct-to-Tumor and Adoptive Cell Therapy (ACT) applications.

INTASYL is the only self-delivering RNA interference (RNAi) technology focused on immuno-oncology therapeutics. Phio is developing several INTASYL compounds, one of which is in an on-going Phase 1b clinical trial for the treatment of advanced melanoma.

The posters will be presented on November 10th and 11th at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), which is being held in Boston, MA from November 8 – 12, 2022.

About the Posters

Abstract #788 titled: A Phase 1b study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of neoadjuvant use of PH-762 administered intratumorally in subjects with advanced melanoma

About PH-762: PH-762 is an INTASYL compound that reduces the expression of PD-1, a protein that inhibits T cells’ ability to kill cancer cells. By suppressing PD-1, the T cells are re-activated to kill cancer cells. PH-762 is being developed as a standalone drug therapy (Direct-to-Tumor) and also in combination with ACT.

About the poster: This trial in progress poster reports on the clinical trial design and updates on the continuing enrollment in its Phase 1b study of PH-762 for the treatment of patients with advanced melanoma. The study is being conducted at the Gustave Roussy Institute, one of the largest cancer centers in Europe. Topline safety data from the first group of subjects is expected to be announced during the first quarter of 2023. [Review the poster]

Abstract # 1402 titled: PH-894, an INTASYL self-delivering siRNA targeting BRD4, has dual functions to sensitize tumor cell killing and activate CD8 T cells

About PH-894: PH-894 is an INTASYL compound that silences BRD4, a protein that controls gene expression in both T cells and tumor cells, thereby effecting the immune system as well as the tumor. What sets this compound apart is its dual mechanism: INTASYL PH-894 suppression of BRD4 in T cells results in T cell activation; additionally, suppression of BRD4 in tumor cells results in tumors becoming more sensitive to T-cell killing.

About the poster: This poster presentation includes data further exploring the antitumor mechanism of PH-894, a self-delivering RNAi compound that specifically silences the BRD4 gene. In this study, Phio showed that using PH-894 can activate T cells to improve their cancer cell killing ability and to target tumor cells to make them more sensitive to killing. [Review the poster]

Abstract #1431 titled: Intratumoral PH-109 INTASYL; self-delivering RNAi targeting connective tissue growth factor (CTGF) provides efficacy in vivo in a mouse model of metastatic breast cancer

About PH-109: PH-109 is an INTASYL compound that suppresses the Connective Tissue Growth Factor (CTGF) protein, a protein associated with poor prognosis in breast cancer.

About the poster: The poster presentation announces proof-of-concept in vivo data showing efficacy of intratumorally administered PH-109, in an orthotopic 4T1 model of metastatic mammary cancer. These results show that PH-109 reduced tumor growth and reduced metastatic lung lesions compared to the control arms. Mice were also treated with the chemotherapy drug, doxorubicin. In contrast to doxorubicin, PH-109 showed no evidence of toxicity. [Review the poster]

Abstract #537 titled: Local immunotherapy with INTASYL self-delivering RNAi targeting CTLA-4 provides robust tumor control in vivo

About CTLA-4: CTLA-4 is a protein that inhibits the ability of T cells to kill tumor cells. The CTLA-4 targeting INTASYL compound demonstrated dose-associated anti-tumor activity in two tumor models in vivo. Local delivery may avoid/minimize the severe systemic adverse events associated with current CTLA-4 therapeutics.

About the poster: The poster presentation demonstrates proof-of-concept in vivo data showing intratumoral efficacy of a novel INTASYL targeting murine CTLA-4 in two syngeneic mouse tumor models. These study results showed a dose-dependent anti-tumor effect that was comparable to that seen with antibodies. The Company expects treating intratumorally with an INTASYL compound targeting CTLA-4 may have less toxicity than with current antibody treatment, while maintaining similar efficacy. This shows that INTASYL can be used against multiple clinically proven checkpoint inhibitors – CTLA-4 and PD-1. [Review the poster]

Abstract #493 titled: PH-804, an INTASYL self-delivering RNAi compound that targets TIGIT enhances NK cell cytotoxicity to tumor cells

About PH-804: PH-804 is an INTASYL compound that targets TIGIT, a protein that inhibits the activity of Natural Killer (NK) cells.

About the poster: The poster presentation discusses results from a pre-clinical study demonstrating that NK cells, when treated with PH-804, increased activation and enhanced the ability of NK cells to kill cancer cells. [Review the poster]

Abstract #409 titled: Manufacturing of a clinical scale CD8 TIL product, AGX148, with and without gene silencing of PD-1 using self-delivering RNAi INTASYL PH-762

About the poster: This poster presentation by AgonOx, Inc., in collaboration with Phio and the Providence Cancer Institute’s Cell Processing Facility, shows that it has completed three full scale IND-enabling manufacturing runs of its ACT product, AGX148, CD8 tumor infiltrating lymphocytes (TIL) that are highly enriched for tumor-reactivity (DP TIL), with and without Phio’s PH-762, an INTASYL compound that knocks down PD-1 protein expression on cells. These manufacturing runs demonstrate the ability to scale up clinical grade DP TIL and that DP TIL treated with PH-762 demonstrated durable silencing of PD-1 in vivo. PD-1 knockdown also enhanced the activity of DP TIL in in vitro tumor co-culture assays. This step forward in manufacturing is an important part of AgonOx’s movement towards the clinic and will support an IND application with the FDA. AgonOx expects to start a clinical trial evaluating the safety, tolerability, and efficacy of AGX148 combined with PH-762 in subjects with advanced solid malignancies.

On November 10, 2022 IconOVir Bio, Inc. (IconOVir), a preclinical-stage biotechnology company pioneering the next generation of oncolytic virus (OV) therapy to improve the treatment of patients with cancer, reported new preclinical data demonstrating proof-of-concept for its lead program ICVB-1042 (Press release, IconOVir Bio, NOV 10, 2022, View Source [SID1234623673]). ICVB-1042 is an oncolytic adenovirus (Ad), rationally designed with genomic modifications to confer tumor selective replication and enhanced tumor cell killing, as well as allow for either intravenous (IV) or intratumoral (IT) delivery. The data will be presented in three posters at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2022), which is being held in Boston, MA and virtually from November 8-12, 2022.

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"The new data presented at SITC (Free SITC Whitepaper) reaffirm the power of our differentiated approach to OV development, which allows us to create and combine proprietary mutations to optimize OVs, and to translate this engineering into potentially best-in-class product candidates," said Mark McCamish, M.D., Ph.D., President and Chief Executive Officer of IconOVir. "Based on preclinical testing across a range of tumor types and preclinical model systems, we believe ICVB-1042 offers superior tumor selectivity, broader tropism and more effective anti-cancer activity compared to earlier-generation OVs, which could transform the care and treatment of people living with a range of solid tumors. We look forward to advancing ICVB-1042 into Phase 1 studies next year, as we work toward our mission of curing cancer and restoring life to every patient, everywhere."

Preclinical Data Demonstrate ICVB-1042’s Selective Replication, Broad Tumor Tropism, Safety and Anti-Tumor Activity

IconOVir presented two abstracts describing the results of in vitro and in vivo studies. These data demonstrate that ICVB-1042 selectively replicates in tumor cells compared to normal cells, while also benefiting from enhanced tropism, anti-tumor activity and tolerability.

In a poster presentation titled, "Nonclinical characterization of ICVB-1042, a novel E2F-tumor selective oncolytic virus with the potential to treat solid tumors," IconOVir describes key therapeutic properties of IV-administered ICVB-1042, including its high tumor selectivity and ability to replicate effectively in tumor tissue. The data show:

ICVB-1042 is well-tolerated and induces tumor-selective replication and cell killing across a broad range of human tumor cell lines, including breast, prostate, bladder, lung and glioblastoma;
ICVB-1042 is 100-fold more cytotoxic in tumor cells compared to normal cells; and
ICVB-1042 virus particles increase in both tumors and plasma over time, in a manner correlative with efficacy.
In a poster presentation titled, "Evaluation of the anti-tumor activity of ICVB-1042, a novel E2F-tumor selective oncolytic virus, selectively targeting tumor cells in an established human glioblastoma mouse model," IconOVir presents new preclinical data from studies comparing the anti-tumor activity and selectivity of ICVB-1042 with that of ICVB-940, a comparator virus engineered by IconOVir that is based on an adenovirus type-5 (Ad5) clinical-stage OV under evaluation for treatment of glioblastoma. The data show that:

ICVB-1042 demonstrates enhanced tumor cell killing over ICVB-940 in 11 of 13 human glioma tumor cell lines;
ICVB-1042 induces significant decreases in tumor volume and increases in time to progression over ICVB-940; and
ICVB-1042 is well-tolerated, resulting in no deaths or group mean body weight loss in the treatment window.
Preclinical Proof-of-Concept Data for Proprietary Mutations Designed to Improve Tropism

IconOVir presented an abstract demonstrating proof-of-concept for a proprietary mutation made to Ads to enhance tropism to malignant cells. This mutation, the replacement of wild-type fiber with a chimeric Ad5/Ad34 fiber, is incorporated into ICVB-1042.

Viral entry into target cells through interactions with surface receptor proteins is a key determinant of viral tropism. Ads contain a trimeric fiber protein with a central shaft and globular knob that help tether it to the cell surface receptor. Ad5, which was used in first-generation OV therapies, utilizes the coxsackie Ad receptor (CAR) for cell entry, however CAR downregulation during cancer progression limits the therapeutic effect of OVs that rely on this surface protein. Group B Ads instead use CD46, a receptor frequently overexpressed in cancer, for cell entry, creating an opportunity to equip OVs with chimeric fibers to enhance tropism to malignant cells. IconOVir engineered ICVB-1042 to include an Ad5/34 chimeric fiber, which enables viral entry via CD46 instead of CAR proteins, with the goal of addressing limitations of first-generation Ad5-based OVs.

In a poster presentation titled, "The chimeric Ad5/Ad34 fiber of ICVB-1042 oncolytic virus requires the CD46 cell surface receptor for efficient tumor entry," IconOVir describes the cell entry requirements for ICVB-1042 compared to ICVB-421 (wtAd5 + YPET). The data showed:

The Ad5/34 fiber of ICVB-1042 effectively binds CD46 and not CAR;
CD46 expression is required for efficient infection by ICVB-1042;
CD46 deficiency induces resistance to ICVB-1042-induced cytotoxicity; and
The expression of human CD46 on mouse cells allows viral entry, but not replication of ICVB-1042.
Based in part on these results, IconOVir is developing ICVB-1042 for delivery both IV and IT. IconOVir plans to advance into a Phase 1 clinical study evaluating ICVB-1042 delivered IV in patients with advanced solid tumors in the first half of 2023.

On November 10, 2022 Seagen Inc. (Nasdaq: SGEN) reported that data from the company’s diverse pipeline of targeted cancer therapy candidates will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting being held November 8-12 in Boston (Press release, Seagen, NOV 10, 2022, View Source [SID1234623672]). The presentations highlight data from multiple ongoing clinical and preclinical research studies that employ Seagen’s proprietary antibody-drug conjugate (ADC) technology, as well as other novel cancer targeting approaches.

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"Seagen has a deep heritage in pioneering first-in-class antibody-drug conjugates. We are encouraged by initial results from a clinical study of SGN-B6A, a wholly owned investigational antibody-drug conjugate that demonstrated antitumor activity with an acceptable safety profile in previously treated patients with non-small cell lung cancer, head and neck cancer, and esophageal cancer," said Megan O’Meara, M.D., Senior Vice President of Early-Stage Development at Seagen. "We are also sharing new data demonstrating enhanced preclinical activity of enfortumab vetodin in combination with immune checkpoint inhibitors, as well as preclinical data that support the initiation of a first-in-human study of a bispecific molecule called SGN-BB228."

Highlights From SGN-B6A Program Presented at SITC (Free SITC Whitepaper)

Data from an ongoing Phase 1 study of SGN-B6A, an ADC directed to integrin beta-6, which is overexpressed in multiple solid tumors, showed early efficacy signals in at least three cancer types, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and esophageal squamous cell carcinoma (ESCC).

Dose escalation cohorts enrolled 79 participants with metastatic or unresectable solid tumors, whose disease had relapsed or was refractory to standard of care therapies and had not previously received an MMAE-containing agent or agent targeting integrin beta-6. Participants had received a median of 3 lines of therapy for metastatic disease prior to enrollment in the study. SGN-B6A demonstrated a manageable and tolerable safety profile at the explored dose levels and schedules. Intermittent dosing schedules (2Q3W, 2Q4W) are being evaluated further. The initial anti-tumor activity observed in heavily pre-treated patients is encouraging and has triggered expansion cohorts in NSCLC, HNSCC, and ESCC, which are currently ongoing. SGN-B6A is an investigational agent, and its safety and efficacy have not been established.

Additional Details of Seagen Presentations at SITC (Free SITC Whitepaper) Annual Meeting 2022

All posters will be available at the beginning of the session, both in-person and virtually.

On November 10, 2022 4D pharma plc (AIM: DDDD) (in administration), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, reported that new biomarker data from two ongoing clinical trials of its lead immuno-oncology single strain Live Biotherapeutic, MRx0518, at the at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting (SITC 2022), held from November 8-12, 2022 (Press release, 4d Pharma, NOV 10, 2022, View Source [SID1234623671]). The two e-posters are available via the 4D pharma website at View Source

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"The two posters presented at the prestigious SITC (Free SITC Whitepaper) 2022 event demonstrate 4D pharma’s commitment and leadership in understanding the mechanisms of action of its Live Biotherapeutic Products," said Dr. Alex Stevenson, Chief Scientific Officer at 4D pharma. "Building on previously published clinical and biomarker results, with this new data we show how MRx0518 is able to drive meaningful clinical benefit for patients by acting on both the human immune system to overcome immunosuppression for better outcomes with immune checkpoint inhibitor therapy, and the microbiome"

One poster presentation highlights the suppressed immune state of patients who have acquired resistance to prior anti-PD-1/PD-L1 immune checkpoint inhibitors, at baseline compared to controls. Following treatment with the combination of MRx0518 and KEYTRUDA (pembrolizumab), there is an increased expression of the activation markers HLA-DR and CD86, and a trend in reduction of myeloid cells expressing the immune checkpoint PD-L1, in responders but not non-responders. The results also identify a significant increase in circulating CD8+ T cells after treatment with the combination, in responders but not in non-responders, an immune population well known to correlate with better outcomes for immune checkpoint inhibitor treatment.

A second poster presents the first clinical microbiome and metabolome modulation data for MRx0518, building on previously reported immunomodulatory data from the same study. Following neoadjuvant treatment with MRx0518 monotherapy, there is a significant increase in the presence of MRx0518 in stool samples which then returns to baseline levels. This data supports 4D pharma’s thesis regarding the viability and pharmacokinetics of safe and effective transient colonization of its orally administered Live Biotherapeutics in the human gastrointestinal tract. In addition, the results demonstrate treatment with the single strain LBP MRx0518 is associated with significant shifts in gut microbiome composition and significant increases in short-chain fatty acid metabolites that may contribute to the anti-tumorigenic efficacy demonstrated by MRx0518

Poster presentation details are as follows:

Presentation Title: Combination of MRx0518 and anti-PD-1 overcomes checkpoint inhibitor resistance via myeloid modulation

Presenting Author: Dr. June Li, Research Scientist, Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center

Abstract Number: 838

Presentation Title: Oral administration of MRx0518 in treatment-naïve cancer patients is associated with compositional taxonomic and metabolomic changes indicative of anti-tumorigenic efficacy

Presenting Author: Dr. Mark P. Lythgoe, Academic Clinical Fellow in Medical Oncology and Pharmacist, Imperial College London

Abstract Number: 627

On 24 June 2022, David Pike and James Clark of Interpath Advisory were appointed as administrators of 4D pharma plc. The administrators have had no oversight of or involvement in the preparation of the SITC (Free SITC Whitepaper) 2022 poster presentations nor in any materials which will be circulated in advance of or during SITC (Free SITC Whitepaper) 2022. Therefore, the administrators make no statement or representation in respect of the materials shared or discussed in advance of or during SITC (Free SITC Whitepaper) 2022.

About MRx0518

MRx0518 is single strain Live Biotherapeutic product in development for the treatment of cancer. It is delivered as an oral capsule and stimulates the body’s immune system, directing it to produce cytokines and immune cells that are known to attack tumors. It is currently being evaluated in three clinical trials in cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy study in a variety of solid tumors and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA (pembrolizumab) in patients who have previously progressed on anti PD-1 therapies. The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer. A fourth clinical trial is planned, in collaboration with Merck KGaA and Pfizer Inc., of BAVENCIO (avelumab) in combination with MRx0518 as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.