On November 11, 2022 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported that its abstract highlighting data from the ongoing Phase 2a study of VBI-1901, the Company’s cancer vaccine immunotherapeutic candidate in recurrent glioblastoma (GBM), was accepted for poster presentation at the 27th Annual Meeting and Education Day of the Society for Neuro-Oncology (SNO), taking place November 16-20, 2022 (Press release, VBI Vaccines, NOV 11, 2022, View Source [SID1234623833]).

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Presentation Details

Poster Number CTIM-14

Title: Comprehensive biomarker analysis of responders and non-responders in a Phase 2a trial of a CMV vaccine immunotherapeutic candidate (VBI-1901)
Session: Poster Session
Date: Friday, November 18, 2022
Poster Session Time: 7:30-9:30PM ET
Poster Presenter: Fabio M. Iwamoto, M.D., Deputy Director, Division of Neuro-Oncology and Assistant Professor of Neurology at the Columbia University Irving Medical Center
About VBI-1901 and GBM

VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI’s enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and has a high mortality.

On November 11, 2022 Scholar Rock (NASDAQ: SRRK), a Phase 3, clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported early data from its Phase 1 DRAGON proof-of-concept trial of SRK-181, a selective inhibitor of latent TGFβ1 activation being developed with the aim of overcoming resistance to checkpoint therapy in patients with advanced cancer (Press release, Scholar Rock, NOV 11, 2022, View Source [SID1234623784]). The data were shared in a poster presentation during the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting & Pre-Conference being held November 8-12 in Boston.

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"Resistance to checkpoint inhibitor therapy remains a significant challenge in the treatment of advanced cancer. The DRAGON trial is investigating our novel TGFβ1 selective monoclonal antibody, SRK-181, which was designed to address this challenge based on the strong, scientific rationale that TGFβ1 is a driving mechanism of resistance to checkpoint inhibitors. Our preclinical work suggests that SRK-181 may overcome this resistance and avoid the cardiotoxicities that have limited other non-selective approaches," said Jay Backstrom, M.D., M.P.H., President and Chief Executive Officer of Scholar Rock. "These early DRAGON findings of safety, target engagement and indications of efficacy support our conviction around Scholar Rock’s differentiated approach and the potential role that SRK-181 may play in addressing the existing treatment hurdles. We are excited to continue advancing DRAGON and look forward to sharing additional data next year."

Data continue to show SRK-181 is generally well tolerated
Safety data from the dose escalation portion of the trial (Part A) continue to show SRK-181 is generally well tolerated when used alone or in combination with anti-PD-(L)1 checkpoint inhibitor therapy. No dose-limiting toxicities were observed in patients receiving SRK-181 as monotherapy (Part A1) when dosed up to 3000 mg once every three weeks (q3w) or 2000 mg once every two weeks (q2w), or in patients receiving SRK-181 in combination with checkpoint inhibitor therapy (Part A2) when dosed up to 2400 mg q3w. All dose levels were generally well tolerated, including the recommended SRK-181 dose of 1500 mg q3w or 1000 mg q2w in combination with anti‑PD-(L)1 for the dose expansion portion of the trial (Part B).

No Grade 4 or 5 treatment-related AEs occurred. Treatment-related Grade 3 adverse events were increased levels of alanine aminotransferase (one patient in Part A1); pruritus (two patients in Part A2), blister, immune-mediated lung disease, rash and rash maculo-papular (one patient each in Part A2). A treatment-related serious adverse event of elevated troponin I (one patient) was observed in Part A1; blister, pruritus, and rash (all in one patient) and immune-mediated lung disease (one patient) were observed in Part A2.

Early indications of efficacy
The response was assessed by principal investigators based on RECIST 1.1. Partial response ("PR") is defined as at least a 30% tumor reduction. As of the data cut-off date (August 29, 2022), 15 patients were enrolled in Part A2 with the following results:

One confirmed PR in a patient with anti-PD-1 resistant clear cell renal cell carcinoma at 800mg in Part A2 of the trial who remained in the study for 30 weeks.
One ongoing patient in the 2400 mg dose group of Part A2 with head and neck cancer experienced a 29.4% tumor reduction.
Nine patients experienced a best response of stable disease. This included six patients whose disease progressed prior to the trial and were stable beyond the 16-week cutoff.
As of the data cut-off date, 14 patients were enrolled in Part B. One ongoing patient with anti-PD-1 resistant clear cell renal cell carcinoma had a confirmed PR.

Biomarker data from Part A consistent with target engagement
The biomarker strategy for DRAGON explores early signs of SRK-181 activity, including target engagement and pathway modulation. It includes measuring effects on both circulating and tumor immune contexture, such as CD8+ T cell infiltration and reductions in myeloid-derived suppressor cell (MDSC) populations, as well as analysis of TGFβ-related pathway signaling.

Following treatment with SRK-181 in Part A, circulatory TGFβ1 levels increased in all dose groups. Given the small number of participants in each dosing cohort, dose-dependent increases in circulatory TGFβ1 levels were not apparent. These findings are consistent with preclinical results from a mouse tumor model (MBT-2) that suggest circulatory TGFβ1 may be a potential pharmacodynamic biomarker of SRK-181. Combination treatment with anti-PD-(L)1 therapy also appears to have similar circulatory TGFβ1 levels as monotherapy.

"At this early stage, the biomarker findings are consistent with the circulating TGFβ1 levels observed in our preclinical studies. We also saw target engagement accompanied by robust efficacy measured through MDSC levels as PD biomarker and immune infiltration into tumors and tumor regression in our preclinical studies," said Mo Qatanani, Senior Vice President, Research. "We are excited to generate further biomarker analyses from DRAGON, including MDSC levels to reflect PD activity and present them at future scientific meetings."

The poster will be made available in the Publications & Posters section of Scholar Rock’s website following the conference.

For conference information, visit View Source

About SRK-181
SRK-181 is a selective inhibitor of latent TGFβ1 activation being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies, in advanced cancer. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity. (1) Scholar Rock believes SRK-181, which specifically targets the latent TGFβ1 isoform, has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The trial is currently enrolling and dosing patients in multiple proof of concept cohorts conducted in parallel, including urothelial carcinoma (UC), cutaneous melanoma (MEL), non-small cell lung cancer (NSCLC) and clear cell renal cell carcinoma (ccRCC). SRK-181 is an investigational product candidate and its efficacy and safety have not been established. SRK-181 has not been approved for any use by the FDA or any other regulatory agency.

(1) Martin et al., Sci. Transl. Med. 12: 25 March 2020

On November 11, 2022 IMV Inc. (Nasdaq: IMV; TSX: IMV) ("IMV" or the "Company"), a clinical-stage biopharmaceutical company developing a portfolio of immune-educating therapies based on its novel DPX platform to treat solid and hematologic cancers, reported its financial and operational results and provided an update for the third quarter ended September 30, 2022 (Press release, IMV, NOV 11, 2022, View Source [SID1234623779]).

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"IMV worked diligently to deliver on our clinical goals in the third quarter. We restructured the business to facilitate the achievement of these objectives and remain on track to present meaningful clinical data early next year," said Andrew Hall, Chief Executive Officer of IMV. "We expect 2023 to be a potentially transformative year for IMV, with clinical response read outs of maveropepimut-S from the company-sponsored, Phase 2B trials in both diffuse large B cell lymphoma (DLBCL) and ovarian cancer. Positive results from these trials will provide further validation of the potential clinical efficacy and favorable tolerability profile inherent in our platform technology and may support advancement into registrational trials."

Clinical Programs with Maveropepimut-S (MVP-S)

VITALIZE Phase 2B Study in Relapsed/Refractory DLBCL ("r/r DLBCL")

Site activation and enrollment in the VITALIZE Phase 2B clinical trial increased during the third quarter, advancing our lead compound, maveropepimut-S (MVP-S). VITALIZE is designed to further evaluate the clinical benefit of MVP-S in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with r/r DLBCL.

Details on the VITALIZE Phase 2B study were presented as a trial-in-progress poster at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 (Poster #646TiP).

The Company will present clinical response data in a plenary session at the Immuno-Oncology 360 (IO360) conference to be held in New York City on February 7-10, 2023.

AVALON Phase 2B Trial in Platinum-Resistant Ovarian Cancer

Enrollment of patients continues in the AVALON Phase 2B trial in ovarian cancer (NCT05243524), which is a single arm trial evaluating MVP-S and intermittent low-dose cyclophosphamide (CPA) in patients with recurrent, platinum-resistant ovarian cancer. The goal of the AVALON study is to further validate the encouraging data generated in the Phase 2 DeCidE trial, completed in 2021, wherein response rates doubled that of traditional chemotherapy and nearly half of patients survived 2 years. Enrollment in stage 1 of AVALON (up to 41 patients) is expected to be complete in Q3 2023.

Corporate Update

In September, IMV announced a strategic reorganization in order to focus resources on MVP-S while reducing future cash needs. The restructuring enables IMV to concentrate its investment in the clinical data that will validate MVP-S as an effective therapeutic vaccine candidate for hematologic and solid tumors.

A plan was implemented to reduce the workforce by approximately one third, focusing resources on ongoing MVP-S clinical programs in immuno-oncology (IO): the Phase 2B VITALIZE and AVALON trials.

Selected Upcoming Milestones

First-half 2023:
Presentation of VITALIZE DLBCL initial response data on February 10, 2023, at the IO360 conference
Summer/Fall 2023:
Provide preliminary clinical response data from the AVALON Phase 2b trial in ovarian cancer
Clinical update from our investigator-initiated trial with MVP-S as neoadjuvant in Breast Cancer
Overview of Third quarter 2022 Financial Results

All dollar amounts noted herein are denominated in United States dollars (unless otherwise noted herein).

On September 30, 2022, the Company had cash and cash equivalents of $21.7 million and working capital of $18.2 million, compared with $38.6 million and $37.1 million, respectively at December 31, 2021.

The net loss and comprehensive loss of $8.9 million ($0.11 per share) for the three months ended September 30, 2022, was $1.5 million lower than the net loss and comprehensive loss of $10.4 million ($0.13 per share) for the three months ended September 30, 2021.

Research and development expenses were $5.9 million for the three months ended September 30, 2022, compared with $5.6 million for the three months ended September 30, 2021. This increase of $0.3 million was mainly due to an increase in costs for our ongoing trials in DLBCL, ovarian cancer and non-muscle invasive bladder cancer as well as personnel costs, including $0.5 million of non-recurring costs associated with the recent reorganization. These increases were partly offset by a decrease in basket trial costs, following completion of enrolment in 2021.

General and administrative expenses were $4.1 million for the three months ended September 30, 2022, compared with $5.3 million for the three months ended September 30, 2021. This decrease of $1.2 million was mainly attributable to non-recurring costs associated with executive leadership changes in the prior year. This decrease was partly offset by an increase in loan interest related to the Horizon venture debt facility.

For the nine-month period ended September 30, 2022, the net loss and comprehensive loss of $29.4 million ($0.36 per share) was $4.4 million higher than the net loss and comprehensive loss of $24.9 million ($0.35 per share) for the nine-month period ended September 30, 2021. The net loss and comprehensive loss for the three and nine months ended September 30, 2022 included $0.7 million in non-recurring restructuring costs associated with the recent reorganization.

As of November 10, 2022, the number of issued and outstanding common shares was 82,369,960 and a total of 17,350,253 stock options, warrants and deferred share units were outstanding.

The Corporation’s unaudited interim condensed consolidated results of operations, financial condition and cash flows for the quarter ended September 30, 2022, and the related management’s discussion and analysis (MD&A) are available on SEDAR at www.sedar.com and on EDGAR at www.sec.gov/edgar as well as the Company’s website at www.imv-inc.com

Conference Call and Webcast Information

Management will host a conference call and webcast on Friday, November 11, 2022, at 8:00 a.m. ET. Financial analysts are invited to join the conference call by registering at this link prior the call to receive their individual dial-in information.

Other interested parties will be able to access the live audio webcast by registering on IMV’s website: View Source The webcast will be recorded and will then be available on the IMV website for 30 days following the call.

On November 10, 2022 –Takara Bio Inc. (Takara Bio), reported that it has decided jointly with Otsuka Pharmaceutical Co., Ltd. (Otsuka), to terminate agreements on co-development and exclusive marketing of NY-ESO-1・siTCRTM gene therapy product (development code: TBI-1301) (Press release, Takara Holdings, NOV 10, 2022, View Source [SID1234635875]).

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　1.　Reasons for the termination

Takara Bio and Otsuka have been jointly developing NY-ESO-1・siTCRTM gene therapy for synovial sarcoma in Japan and preparing for the submission for manufacturing and marketing approval. However after comprehensive discussions between the two companies on policies and strategies related to this product, Takara Bio and Otsuka have agreed to terminate this agreement. This decision is not due to any efficacy or safety issues of the product.

　2.　Details of the termination agreement

Under this termination, Takara Bio regains technical, intellectual property and other rights granted by Takara Bio to Otsuka. In addition, in the future Takara Bio will not receive lump-sum payments upon achievement of milestones under this agreement or receive any sales proceeds for clinical trial product sales.

　3.　Overview of the other party to terminate this agreement

[1] Company name

Otsuka Pharmaceutical Co., Ltd.

[2] Head office

2-9, Kanda-Tsukasamachi, Chiyoda-ku, Tokyo 101-8535, Japan

[3] URL

View Source

　4.　Schedule

Corporate resolution, date of the termination agreement: November 10, 2022

　5.　Future Outlook

The impact of the termination of these agreements on the consolidated financial results of the Company for the fiscal year ending March, 2023 will be minor.

On November 10, 2022 SOTIO Biotech, a clinical stage immuno-oncology company owned by PPF Group, reported preclinical data evaluating the mechanism of action and metabolic function of its BOXR T cell platform in a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, taking place in Boston, Massachusetts from November 8-12, 2022 (Press release, SOTIO, NOV 10, 2022, View Source [SID1234626213]). An additional poster was presented on the trial design of AURELIO-04, an ongoing Phase 2 study evaluating the efficacy and safety of SOT101 in combination with pembrolizumab in patients with advanced solid tumors.

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"Preclinical results from the study of our BOXR T cell therapy platform indicate a strong clinical path for our first transgene-expressing CAR-T cell, BOXR1030, as a potential clinical treatment for the 90% of adult cancer patients with solid tumors," said Radek Spisek, M.D., Ph.D., chief executive officer of SOTIO. "The GOT2 infused CAR-T cell therapy improved metabolic fitness, increased cell survival and proliferative capacity of CAR-T cells when exposed to suppressive tumor microenvironments, indicating potentially improved access to solid tumors; a long-standing challenge for CAR-T and other cancer therapies to date. We look forward to initiating first-in-human safety studies of BOXR1030 in the coming months."

Pratirodh Koirala, Ph.D., presenting author from SOTIO Biotech Inc. (U.S.) commented: "CAR-T cell therapy has made significant strides in the treatment of hematological malignancies, yet solid tumors remain resistant to current CAR-T strategies due to suppression by the tumor microenvironment. The preclinical data presented at this year’s SITC (Free SITC Whitepaper) annual meeting demonstrate a promising mechanism of action for SOTIO’s BOXR1030 and underscore the potential that GOT2-expressing CAR-T cells have for enhanced metabolic fitness or more durable early memory phenotypes – benefits which could improve clinical outcomes against solid tumors despite a suppressive tumor microenvironment."

An analysis of the BOXR1030 T cell data show that the BOXR CAR-T cells co-expressing the metabolic gene GOT2 have a higher frequency of less differentiated stem cell memory T cell (TSCM) populations and more CD27+ cells in all memory T cell subsets, suggesting fewer terminally differentiated cells compared to control CAR-T cells lacking the GOT2 transgene. When BOXR1030 T cells were exposed to stressful conditions characteristic of difficult-to-penetrate tumor microenvironments such as low glucose and chronic stimulation, the cells exhibited improved metabolic fitness, increased cell survival and proliferative capacity, multiple characteristics of less differentiated or early memory T cell populations, and retention of effector functions relative to control CAR-T cells.

Dr. Spisek added: "Additionally, progressing our lead clinical asset, SOT101 into the Phase 2 AURELIO-04 study has been a significant clinical milestone for SOTIO. The trial size of 320 patients, all of whom are facing a variety of metastatic cancers that present high unmet needs, will enable us to significantly increase our data pool as SOT101 continues to advance through the clinic."

The design of the Phase 2 AURELIO-04 study, launched by SOTIO in July of 2022, was presented by Aurélien Marabelle, M.D., Ph.D., immuno-oncologist from the Drug Development Department at Gustave Roussy Cancer Center.

The AURELIO-04 study (NCT05256381) is a Phase 2, open-label, single-arm, multicentered study of SOT101 in combination with pembrolizumab to evaluate the efficacy and safety in patients with multiple advanced solid tumor indications. The solid tumor selection was based on previous pembrolizumab studies and/or data from other checkpoint inhibitors (CPI) and includes both CPI-relapsed and/or CPI-naïve tumors. The study will enroll up to a total of approximately 320 patients with a maximum of 50 to 57 per indication in Europe and the United States. SOTIO entered into a clinical trial collaboration and supply agreement with MSD (a tradename of Merck & Co., Inc., Rahway, NJ, USA). MSD supplies KEYTRUDA for the study. In a Phase 1 study, SOT101 in combination with pembrolizumab has reported clinical benefit in 15 out of 19 patients with at least one post-baseline tumor assessment.

Poster presentations from SITC (Free SITC Whitepaper) are available below.

About the BOXR Technology:
SOTIO’s BOXR cell therapy platform is designed to improve the functionality of immune cells such as CAR-T cells by identifying novel "bolt-on" transgenes that can be co-expressed with tumor-targeting receptors to overcome resistance and improve the function of respective immune cells in the solid tumor microenvironment. BOXR-discovered transgenes are selected to address T cell metabolism and overcome multiple mechanisms of immunosuppression, including competition for metabolites, exhaustion due to chronic stimulation, and resistance to immunosuppressive cells.

About SOT101:
SOT101 is a subcutaneously administered IL-15Rβγ superagonist based on IL-15 fused to the sushi+ domain of the IL-15 receptor α chain. SOT101 has demonstrated strong preclinical in vivo efficacy in various tumor models showing increased long-term survival and tumor regression, as well as a favorable toxicology profile. SOT101 has been shown in pre-clinical models to synergize with checkpoint inhibitors and antibody therapies exerting ADCC.