On June 6, 2022 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vectored immunotherapies, reported first data from the completed Phase 1 trial evaluating NOUS-209 in combination with anti-PD-1 checkpoint inhibitor (pembrolizumab) (Press release, NousCom, JUN 6, 2022, View Source [SID1234615678]). The data, presented yesterday in a poster discussion session at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, demonstrated NOUS-209 to be safe, highly immunogenic and with promising signs of clinical efficacy.

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NOUS-209, Nouscom’s lead product, is an off-the-shelf cancer vaccine targeting 209 shared neoantigens. It has been investigated in a Phase 1 clinical trial, administered in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, for the treatment of deficiency in Mismatch Repair/Microsatellite Instable High (dMMR/MSI-H) unresectable or metastatic gastric, colorectal and gastro-esophageal junction tumors.

The key findings from the study are as follows:

NOUS-209 continues to be safe and well tolerated
NOUS-209 immunogenicity was demonstrated by ex-vivo IFN-ɣ ELISpot assay in 83% of evaluable patients; vaccine induced immune responses were potent and broad
Early signs of clinical efficacy with 10 durable confirmed partial responses (PR), 4 durable stable disease (SD) and 6 progressive disease (PD)
Previously presented interim clinical and translational data of the combination indicated that neoantigen-specific CD8+ T cells expand and diversify only upon treatment with NOUS-209, and successfully infiltrate the tumor microenvironment to exert anti-tumor activity (presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)1 in April 2022).

Professor Marwan G. Fakih, M.D., Medical Oncology Specialist at City of Hope’s Duarte California, and Study investigator said: "With clinical and translational data now available from all patients enrolled in this trial, it is encouraging to see NOUS-209 continuing to be safe, highly immunogenic and have signs of clinical efficacy. Durability of response in all PR and SD patients is particularly encouraging and provides hope for this patient group where there is still a significant unmet need. I look forward to seeing further clinical development of this compound in MSI-H patients."

Dr. Marina Udier, Chief Executive Officer of Nouscom, said: "These new data with all patients enrolled continues to reinforce our compelling and differentiating data for NOUS-209. This is a significant step for the company, validating the potency of our platform in inducing neoantigen specific CD8+ T cells, which are also able to successfully infiltrate tumors of metastatic cancer patients, exerting anti-tumor efficacy. We are actively working on the next stages of NOUS-209’s clinical development plan and look forward to announcing the start of the Phase 2 study in the second half of 2022."

Poster Presentation Details:

Title: First clinical and immunogenicity results including all subjects enrolled in a phase I study of NOUS-209, an off-the-shelf immunotherapy, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability (dMMR)
The abstract is available here

References

AACR Presentation: Characterization of immune correlates of clinical activity for NOUS-209, an Off-the-Shelf immunotherapy, with Pembrolizumab for treatment of tumors characterized by Microsatellite Instability (MSI), Professor Marwan G. Fakih, M.D.
About NOUS-209

NOUS-209 is an off-the-shelf immunotherapy for Microsatellite Instable High (MSI-H) tumors. MSI-H tumors are characterized by a defective DNA mismatch repair system, which generates highly immunogenic frame shift peptides (frameshift mutations, FSPs) that are not found on healthy tissue.

NOUS-209 is designed to comprise 209 shared FSP neoantigens, selected by Nouscom’s proprietary GENESIS (GE(netic)NE(oantigen)S(election)I(n)S(ilico)) algorithm, on the basis that an average of 50 neoantigens on any patient’s tumor will be shared with those in NOUS-209. Nouscom’s heterologous prime/boost platform clones these FSPs into Great Ape Adenoviral (GAd) and Modified Vaccinia Ankara (MVA) vectors, to generate the viral-vectored vaccine, combined with other immunomodulators to harness the full power of the immune response by generating neoantigen specific CD8+ T cells, which successfully infiltrate tumor to exert anti-tumor activity.

NOUS-209 is in Phase 1 clinical trial (NCT04041310), a multicenter, open label, multiple cohorts, first-in-human clinical study of NOUS-209 in combination with pembrolizumab, designed to evaluate safety, tolerability and immunogenicity and to detect preliminary evidence of anti-tumor activity.

On June 6, 2022 The Ottawa Hospital, The Ontario Institute of Cancer Research ("OICR") and Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that data from the INVINCIBLE study, a randomized, phase 2 presurgical Window-Of-Opportunity trial for Intratumoral INT230-6 comprising SHAO (dispersion enhancer), VINblastine (VIN) and Cisplatin (CIS) that is evaluating clinical and Biological Effects in patients with early-stage operable breast cancer (Press release, Intensity Therapeutics, JUN 6, 2022, View Source [SID1234615677]). The study, presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago and virtually from June 3-7, 2022, reported data demonstrating efficacy and tolerability of INT230-6.

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Abstract Title: Intratumoral (IT) INT230-6 can cause tumor necrosis In Vivo: Preliminary results of a phase II randomized presurgical window-of-opportunity study in early breast cancers (the INVINCIBLE study).
First Author: Angel Arnaout, MD, FACS
Session Type/Title: Poster Session/Breast Cancer—Local/Regional/Adjuvant
Session Date and Time: Monday, June 6, 2022, 9:00 AM – 12:00 PM EDT
Location: In-Person & On Demand
Abstract Number: 605
Poster: 376

Copies of the presentation materials will also be available on the Intensity Therapeutics website on the publications and posters page, following completion of the live presentation.

"For a breast cancer patient, the typical waiting period of 2-6 weeks from diagnosis to surgery is a very anxious time. Surgeons and patients feel helpless, as there are currently no therapeutic options for the patient during this time," said Angel Arnaout, M.D., Scientist and Surgical Oncologist at the Ottawa Hospital, and Professor of Surgery at the University of Ottawa. "The active drug agents comprising INT230-6 remain in the tumor following injection and can cause tumor cell death and high levels of necrosis in multiple breast cancer subtypes including triple negative breast cancer, as demonstrated by Part 1 of this study. Interestingly, we also saw immune activation with a relative increase in the abundance of CD4 T naïve, B and NK cells, post treatment, and within the tumor microenvironment, a relative increase in abundance of CD8 memory T, CD4 naïve and B cells, post treatment, when comparing drug treated with control samples. 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 attractive to patients. We are excited about how this may shift the paradigm on how we treat cancer patients awaiting surgery, in general. We look forward to future studies to demonstrate how this intra-tumoral agent can have systemic benefit and long term impact in patients with breast cancer."

"INT230-6 is our novel, proprietary, locally-delivered, tumor dispersive anti-cancer product that has shown favorable clinical results as monotherapy in a basket study of patients with advanced, relapsed and refractory disease," said Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "These first results reported from the INVINCIBLE breast cancer study provide evidence and support for the potential of our drug in treating local disease prior to surgery. The data from Part I of the INVINCIBLE study show that INT230-6 is well tolerated and, as we see in metastatic disease, elicits both rapid direct tumor killing and immune activating effects. We anticipate completing enrollment of Part II this summer and reporting the full patient study results at a future oncology conference."

About the INVINCIBLE Study
The INVINCIBLE study is a phase II, randomized, open label, multi-center study, expected to enroll up to 90 women with newly diagnosed operable early-stage intermediate or high-grade T1-T2 invasive breast cancers who are randomly allocated (2:1) prior to resection to IT injections of INT230-6, no treatment or saline sham injection. The study has two parts. Part I (N=29), now complete, randomized patients 2:1 to either 1-3 doses of INT230-6 injected weekly or no treatment, 2 to 5 weeks prior to surgery (lumpectomy or mastectomy). The purpose of this portion of the trial was to evaluate safety, feasibility, and optimal drug dosing. Part II is a double-blind, randomized arm of up to 60 patients, where patients will be randomized 2:1 to receive one or two IT doses of INT230-6 vs. saline injection. The objective of using saline will be to rule out the potential confounding effect of hydrostatic pressure on tumor necrosis. The results of Part II will further evaluate the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. The INVINCIBLE Study is being conducted under a Health Canada (HC) approved Clinical Trial Application (CTA), under the direction and supervision of Principal Investigator, Dr. Angel Arnaout. OHRI will conduct subject enrollment and treatment, and evaluate clinical responses. OICR will analyze subject immune responses and conduct biomarker analyses.

About Potential INT230-6 Approval Pathways in the Presurgical Setting
The U.S Food and Drug Administration (FDA) instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. Pathological complete response (pCR) is an accepted FDA accelerated approval criterion for approval in high risk breast cancer, such as TNBC subtype. pCR is defined as the absence of residual invasive and in situ cancer after evaluation of the complete resected breast specimen and lymph nodes following completion of neoadjuvant systemic therapy.

Data from the INVINCIBLE study will provide an understanding of the effect of INT230-6 on cancer cell proliferation and tumor necrosis. If INT230-6 causes increased tumor necrosis with good safety, then the addition of INT230-6 to the existing or a modified neoadjuvant (presurgical) systemic standard-of-care treatment regimen may increase pCR rates in TNBC. In November of 2020, Intensity Therapeutics met with FDA and discussed the potential use of INT230-6 in the presurgical neoadjuvant breast cancer setting in an accelerated approval program.

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 potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile and the induction of an anti-cancer systemic immune response resulting in shrinkage of uninjected tumors.

On June 6, 2022 NeoImmuneTech, Inc. (NIT or "NeoImmuneTech"), a clinical-stage T cell-focused biopharmaceutical company, reported that new data from two on-going clinical studies at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, 3-7 June 2022 (Press release, NeoImmuneTech, JUN 6, 2022, View Source [SID1234615676]). The data, presented in poster discussion and poster display sessions, combine its lead asset NT-I7 (efineptakin alfa), a long-acting human IL-7, with check-point inhibitors (CPI) pembrolizumab and atezolizumab, and showed that anti-cancer and safety results associated with NT-I7 were consistent with previously communicated results.

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In the phase 2a study NIT-11o, NT-I7 combined with pembrolizumab showed preliminary anticancer activity and a manageable toxicity profile in heavily pretreated patients with immunologically cold microsatellite stable tumors (MSS), colorectal cancers (CRC), and pancreatic ductal adenocarcinoma cancers (PDAC) not previously treated with CPIs, as well as in CPI-treated patients with triple negative breast cancers (TNBC), non-small cell lung cancers (NSCLC), and small-cell lung cancers (SCLC). CPIs are usually ineffective in patients with immunologically cold tumors, such as MSS-CRC or PDAC, and in patients progressing despite prior PD-1/PD-L1 inhibition. ORR for the MSS-CRC cohort was 11.1% with 40.7% DCR; and the PDAC cohort had an ORR of 7.7% with 34.6% DCR (per iRECIST). Two patients out of 26 in the PDAC cohort showed significant target lesion reduction (- 100% and -72% respectively). In all cohorts, including CPI-treated and CPI-naïve subjects, NT-I7 plus pembrolizumab led to an increase in change of mean absolute lymphocyte count from baseline.

In the phase 1b/2a study NIT-106, the combination of NT-I7 with atezolizumab showed favorable safety and anticancer activity in CPI-relapsed/refractory high-risk skin cancer patients. The recommended phase 2 dose (RP2D) was determined so that phase 2a dose expansion is now enrolling. The combination increased by 30-fold the stem-cell memory T cells (Tscm), which may be associated to better anti-tumor activity.

Dr. Se Hwan Yang, Ph.D., President and Chief Executive Officer of NeoImmuneTech said: "We are pleased to gather additional evidence of the efficacy and safety of NT-I7 in combination with check-point inhibitors. Encouraging preliminary results from study NIT-110 led us to expand patient recruitment in the MSS-CRC and PDAC cohorts in order to enhance statistical significance. While study NIT-110 is still on-going, we look forward to more mature data by Q4 2022 that could confirm the benefit of combining our T cell amplifier NT-I7 with a checkpoint inhibitor (CPI) in patients with immune-cold microsatellite stable colorectal cancer or pancreatic cancer and in those who progressed on previous CPI treatment."

As part of the ASCO (Free ASCO Whitepaper) 2022 poster program, a Trial-in-Progress poster was also presented on the design of Phase 1b study NIT-112, indicating progress of NT-I7 plus CAR-T development.

The links to the posters are as follows:

Primary Author

Poster Title

Poster link

Naing, A

Efficacy and Safety of NT-I7, Long-Acting Interleukin-7, plus
Pembrolizumab in patients with advanced solid tumors: results
from the Phase 2a study

Poster #170

Gastman, B

A phase 1b/2a study of safety and efficacy of NT-I7 in
combination with anti-PD-L1 (atezolizumab) in patients with
anti-PD-1/PD-L1 naïve or relapsed/refractory (R/R) high-risk
skin cancers: The phase 1b report.

Poster #154

Ghobadi, A

Trial in Progress: A phase 1b study evaluating the safety,
tolerability and preliminary anti-tumor activity of NT-I7
(efineptakin alfa), a long-acting human IL-7, post-
tisagenlecleucel in subjects with relapsed/refractory large B-cell
lymphoma

Poster #239b

About NT-I7 (efineptakin alfa) (rhIL-7-hyFc)

NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety profiles, making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

On June 6, 2022 OriCell Therapeutics Co., Ltd (OriCell), a leading innovative biopharmaceutical company pioneering novel oncology cell therapies for the unmet medical needs in in hematology and oncology, reported the positive results from Phase I POLARIS study, an investigator-sponsored study evaluating Ori-CAR017, an autologous GPRC5D-directed CAR-T cell, in patients with relapsed/refractory multiple myeloma at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, OriCell Therapeutics, JUN 6, 2022, View Source [SID1234615675]).

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Single Infusion of OriCAR-017 Demonstrates an Early, Deep and Durable Responses at All Dose Levels in Heavily Pretreated RRMM Patients, including Patients Who Relapsed from BCMA CAR-T Therapy.
Overall Response Rate(ORR) was 100% with Complete Response (CR)/ stringent Complete Response (sCR) rate of 60%，including Five patients with prior BCMA CART therapy achieved 2 sCR, 2 VGPR and 1PR. Patient medium follow up time 175 days (range 35-281). All patients were progression free without additional therapy at data cutoff. Results Highlights a Major Advance for OriCAR-017 Future Potential in RRMM Setting, regardless prior BCMA Targeted Therapy.
No Dose Limiting Toxicities (DLTs) or Serious Adverse Events (SAE) was observed. No Immune effector Cell Associated Neurotoxicity Syndrome(ICANS). Only Grade 1/2 Cytokine Release Syndrome(CRS). Most common Grade 3/4 AE was cytopenia, mainly due to lymphodepleting chemotherapy.
"We are delighted to share the FIH data from our Phase I POLARIS study, we strongly believe these data has demonstrated our advantages from the proprietary platforms for CAR-T optimization structure. Next step, we will be focusing on filling an IND with the NMPA and FDA for Ori-CAR017." said Dr. Helen Yang, Chairman and CEO of OriCell. "We look forward to continue developing novel cell therapies, to provide patient with better treatment option in the future."

Prof. He Huang, M.D., Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University said: "Multiple Myeloma (MM) remains incurable with extremely low overall survival for relapsed/refractory patients. Therapies using newer targets are urgently needed. The data presented at ASCO (Free ASCO Whitepaper) 2022 demonstrated that OriCAR-017 is a safe and effective treatment for patients with RRMM who received multiple lines of therapy, especially those who relapsed after BCMA-targeted therapy. I look forward to advancing the research of Ori-CAR017, a first-in-class autologous GPRC5D-directed CAR-T cell, with OriCell, so that patients can benefit from clinical results as soon as possible."

On June 6, 2022 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that it will host a key opinion leader (KOL) webinar on RVU120, a first-in-class CDK8/19 inhibitor, the Company’s lead asset currently in Phase I studies for hematological malignancies and solid tumors on Monday, June 13, 2022, at 2:30 pm Eastern Time (Press release, Ryvu Therapeutics, JUN 6, 2022, View Source [SID1234615674]).

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The webinar will feature a presentation by KOL Dr. Michael Savona, MD, from Vanderbilt University School of Medicine, who will discuss the current treatment landscape and unmet medical need in treating patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS).

The Ryvu Therapeutics leadership team will discuss the underlying mechanism of action of RVU120, which targets hematological malignancies and solid tumors characterized by deregulated transcription. Additionally, an update on the Phase I data for RVU120 will be provided.

A live question and answer session will follow the formal presentations. To register for the event, please click here.

Michael Savona, MD is the Head of Hematology, Cellular Therapy, and Stem Cell Transplant, the Beverly and George Rawlings Director of Hematologic Malignancies Research, and Professor of Internal Medicine and Cancer Biology at Vanderbilt University.

Dr. Savona led the development and approval of several novel therapies for myeloid malignancies. He has been involved in medical research for over 20 years and has published over 100 manuscripts in major academic journals.

Dr. Savona is board certified in medical oncology and hematology, an elected fellow of the American College of Physicians, and a Leukemia and Lymphoma Society Clinical Scholar. Dr. Savona obtained his bachelor’s degree in philosophy from Davidson College and medical degree at Wake Forest University School of Medicine in Winston-Salem, North Carolina. He did post-graduate clinical and research training at the University of California Davis, and the University of Michigan. He also served as a physician in the United States Air Force and is a veteran of Operation Enduring Freedom/Operation Iraqi Freedom.

About RVU120 (SEL120)

RVU120 (SEL120) is a clinical-stage, highly specific, and orally bioavailable dual inhibitor of CDK8/CDK19 kinases, which has demonstrated efficacy in a number of solid tumor in vitro and in vivo models as well as in hematologic malignancies.

At present, Ryvu is conducting two clinical studies with RVU120: (i) Phase Ib in patients with AML/HR-MDS (NCT04021368) and (ii) Phase I/II in relapsed/refractory metastatic or advanced solid tumors (NCT05052255). Additionally, multiple translational research activities are underway.

On March 25, 2020, the U.S. Food and Drug Administration (FDA) granted an orphan drug designation (ODD) to RVU120, for the treatment of patients with AML.

RVU120 has been internally discovered by Ryvu and has received support from the Leukemia & Lymphoma Society Therapy Acceleration Program (TAP).