On April 16, 2024 Mabwell (688062.SH), an innovation-driven biopharmaceutical company with entire industry chain, reported the preclinical research findings of three potential novel drug candidates in poster format at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held from April 5 to 10, 2024 (Press release, Mabwell Biotech, APR 16, 2024, View Source [SID1234642111]).

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Poster Presentation

1. Disrupting IL-11/IL-11R signaling by an efficacious anti-IL-11 antibody 9MW3811 enhances T cell tumor infiltration and synergizes with anti-PD-1 therapies in vivo

Synopsis No.: 2365

The reported 9MW3811 is a high-affinity humanized neutralizing antibody against IL-11 independently developed by Mabwell, and has IND applications approved in China, the United States, and Australia, and its phase I clinical trials are ongoing in Australia and China.

As an important inflammation factor, IL-11 plays a significant role in the development and progression of fibrosis and tumor. Studies have shown that high expression of IL-11 is associated with the prognosis of various tumors such as lung cancer, hepatic cancer, and colorectal cancer. IL-11 not only promotes the growth of tumor cells through the STAT3 pathway but also has a significant impact on immune cells in the tumor microenvironment. 9MW3811 effectively blocks the formation of the IL-11/IL-11Ra/gp130 ternary complex by binding to IL-11, thereby inhibiting the activation of downstream signaling pathways. 9MW3811 has shown good anti-tumor therapeutic effects in multiple preclinical pharmacodynamic models, especially when used in combination with anti-PD-1 antibodies, it significantly promotes lymphocytic infiltration of CD8+ T cells, improves the T cell exhaustion caused by anti-PD-1 antibodies, upregulates the secretion of cytotoxic cytokines, thus exhibiting better combined anti-tumor effects.

2. 2MW4991, a novel ADCC-enhanced integrin αvβ8 blocker, exhibits high anti-tumor potency and was well tolerated in cynomolgus monkeys

Synopsis No.: 6349

The reported 2MW4991 is a high-specificity and high-affinity ADCC-enhanced antibody targeting integrin αvβ8. Integrin αvβ8 is an important activator of TGF-β, and specifically regulates the activity of TGF-β in immune cells. Studies have found that integrin αvβ8 is highly expressed in various tumors, and blocking αvβ8 can completely inhibit the release of TGF-β. 2MW4991 can completely block the release of TGF-β mediated by αvβ8, showing strong anti-tumor activity in various pharmacodynamic models such as CT26 and EMT6, and significantly promotes immune cell infiltration in tumors, greatly increasing the sensitivity of immune-excluded tumors to PD1 inhibitors. 2MW4991 has a significant synergistic effect when used in combination with PD1. The studies conducted in non-primate models have shown that 2MW4991 has good safety and metabolic profiles.

3. 2MW4691, a novel CCR8/CTLA-4 bispecific antibody, displays potent anti-tumor efficacy by specifically depleting tumor-infiltrating Tregs and blocking CTLA-4 signaling on CD8+ T cells

Synopsis No.: 6350

The reported 2MW4691 is an ADCC-enhanced bispecific antibody targeting CCR8/CTLA-4. Targeting CTLA-4 has a strong anti-tumor effect, but its clinical application is limited due to strong side effects. CCR8 is a specific marker of tumor-infiltrating Tregs, and is almost not expressed in other immune cells and peripheral Tregs. Single-cell sequencing analysis of Treg cells infiltrating various tumors found that CCR8 is expressed in a small subset of Treg cells infiltrating tumors, and CTLA-4 is widely expressed in Treg cells and CD8+ T cells. 2MW4691 retains high affinity targeting CCR8 and attenuated CTLA-4-binding and -blocking activity, specifically eliminating Treg cells infiltrating tumors. Due to the lower CTLA-4 expression in the peripheral tissues, 2MW4691 only blocks the immunosuppression mediated by CTLA-4 signaling on peripheral CD8+ T cells. 2MW4691 demonstrates strong anti-tumor activity in preclinical CCR8 single transgenic animal models, CTLA-4 single transgenic animal models, and double transgenic animal models, and has shown good metabolic activity and safety in primate animals.

On April 16, 2024 Volastra Therapeutics, a clinical-stage biotechnology company, reported it has dosed the first patient in its Phase Ib clinical trial evaluating sovilnesib in patients with platinum-resistant or refractory high-grade serous ovarian cancer (HGSOC) (Press release, Volastra Therapeutics, APR 16, 2024, View Source [SID1234642109]). This trial (NCT06084416) is a randomized dose optimization study of once-daily oral sovilnesib at different dose levels to establish the recommended Phase 2 dose.

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Sovilnesib was granted Fast Track designation in this indication by the U.S. Food and Drug Administration (FDA) based on its initial clinical data as well as the high unmet need in this population. Volastra in-licensed sovilnesib (formerly AMG-650) from Amgen in February 2023. The company is also progressing its internally developed KIF18A inhibitor, VLS-1488, in an ongoing Phase 1 clinical trial (NCT05902988).

"Advancing our two chemically differentiated KIF18A inhibitors in parallel Phase 1 clinical trials presents the rare opportunity to efficiently gather comparative clinical data," said Charles Hugh-Jones, M.D., FRCP, Chief Executive Officer at Volastra. "We believe our strategy will allow us to select the first, and potentially best-in-class, medicine for patients to advance to late-stage development for treatment of platinum-resistant or refractory HGSOC."

In the U.S. alone, there are more than 20,000 new cases of ovarian cancer each year, over 75% of which are advanced. The majority of these patients will see disease progression on platinum-based therapy.

"Patients with advanced HGSOC have poor treatment response rates after disease progression on platinum-based chemotherapy, and as a result have a significant need for new treatment options," Dr. Joyce Liu M.D., MPH, Associate Chief and Director of Clinical Research in the Division of Gynecologic Oncology at Dana Farber Cancer Institute and a principal investigator on the trial commented. "We are excited to participate in this trial evaluating a unique treatment approach in hopes of advancing new options for patients."

In addition to clinical development of novel therapeutics, Volastra is deploying multiple unique biomarker approaches to measure chromosomal instability and other predictors of response to KIF18A inhibitors through partnerships with companies including Microsoft, Tailor Bio, and Function Oncology.

On April 16, 2024 Veracyte, Inc. (Nasdaq: VCYT), a leading cancer diagnostics company, reported that nine abstracts focused on its Decipher Prostate and Decipher Bladder Genomic Classifiers will be presented at AUA 2024, the annual meeting of the American Urological Association, taking place May 3-6 in San Antonio (Press release, Veracyte, APR 16, 2024, View Source [SID1234642107]). Studies to be presented include those that evaluate the clinical utility of the company’s Decipher tests in guiding treatment decisions for patients with prostate or bladder cancer. Other presentations will explore new insights into these cancers’ underlying biology, which researchers derived through use of Veracyte’s whole-transcriptome-based Decipher GRID research tool.

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"The data being presented at AUA 2024 expands the extensive clinical evidence supporting our Decipher Prostate and Decipher Bladder tests," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "They also highlight Veracyte’s commitment to collaborating with leading researchers to help understand the biological underpinnings of urologic cancers and advance the science around the disease areas we serve."

The following abstracts will be presented in the Henry B. González Convention Center:

Title:

High Decipher score defines the subgroup most at risk of metastatic progression among patients with lower grade tumors classified as NCCN high-risk based on elevated prostate-specific antigen level alone

Presenter:

David Han, M.D., Columbia University Irving Medical Center

Format:

Poster (MP41-14)

Date/Time:

Saturday, May 4, 2024 / 3:30 p.m. to 5:30 p.m. CT

Room #:

304B

Title:

Decipher Predicts Clinically Significant Upgrading on Final Radical Prostatectomy Pathology

Presenter:

John Sheng, M.D., Rutgers New Jersey Medical School

Format:

Poster (MP49-09)

Date/Time:

Sunday, May 5, 2024 / 7:00 a.m. to 9:00 a.m. CT

Room #:

221B

Title:

Genomic Signatures Associated with Adverse Pathologic Features at Radical Prostatectomy Among Active Surveillance Eligible Men

Presenter:

Eric Li, M.D., Northwestern University

Format:

Poster (MP41-09)

Date/Time:

Saturday, May 4, 2024 / 3:30 p.m. to 5:30 p.m. CT

Room #:

304B

Title:

Variation in Prostate Cancer Genomic Subtypes Across Prostate Magnetic Resonance Imaging PIRADS Scores and Race

Presenter:

Nimrod Barashi Gozal, M.D., Washington University in St. Louis

Format:

Podium Presentation (PD42-01)

Date/Time:

Sunday, May 5, 2024 / 9:30 a.m. to 9:40 a.m. CT

Room #:

303A

Title:

Transcriptomic Features of Clinically Localized Prostate Cancer Arising from Distinct Prostate Zonal Regions

Presenter:

Ross Liao, M.D., Cleveland Clinic

Format:

Poster (MP41-13)

Date/Time:

Saturday, May 4, 2024 / 3:30 p.m. to 5:30 p.m. CT

Room #:

304B

Title:

Glucagon-like peptide-1 Expression in Prostate Cancer

Presenter:

Mohammed Shahait, M.D., Private Practice

Format:

Poster (MP05-10)

Date/Time:

Friday, May 3, 2024 / 7:00 a.m. to 9:00 a.m. CT

Room #:

221C

Title:

Molecular subtyping for predicting non-organ confined disease and survival outcomes after radical cystectomy in clinical high-grade T1 and T2 bladder cancer patients

Presenter:

Yair Lotan, M.D., UT Southwestern Medical Center

Format:

Poster (MP15-07)

Date/Time:

Friday, May 3, 2024 / 1:00 p.m. to 3:00 p.m. CT

Room #:

221C

Title:

The stroma-rich consensus bladder cancer subtype correlates with improved prognosis after neoadjuvant immunotherapy and radical cystectomy

Presenter:

Joep De Jong, Ph.D., Erasmus MC, The Netherlands

Format:

Podium Presentation (PD14-05)

Date/Time:

Friday, May 3, 2024 / 4:10 p.m. to 4:20 p.m. CT

Room #:

301A

Title:

A lncRNA-based classifier identifies high grade T1 bladder cancer patients with excellent outcomes after radical cystectomy

Presenter:

Yair Lotan, M.D., UT Southwestern Medical Center

Format:

Poster (MP15-02)

Date/Time:

Friday, May 3, 2024 / 1:00 p.m. to 3:00 p.m. CT

Room #:

221C

Additional information regarding these presentations and Veracyte’s participation at AUA 2024 can be found at the company’s booth (#607).

About Decipher Prostate

The Decipher Prostate Genomic Classifier is a 22-gene test, developed using RNA whole-transcriptome analysis and machine learning, that helps inform treatment decisions for patients with prostate cancer. The test is performed on biopsy or surgically resected samples and provides an accurate risk of developing metastasis with standard treatment. Armed with this information, the physician can better personalize their patients’ care and may recommend less-intensive options for those at lower risk or earlier, more-intensive treatment for those at higher risk of metastasis. The Decipher Prostate test has been validated in more than 75 studies involving more than 100,000 patients. More information about the Decipher Prostate test can be found here.

About Decipher Bladder

The Decipher Bladder Genomic Classifier is a 219-gene test, developed using RNA whole-transcriptome analysis and machine learning, that is designed for use in patients following bladder cancer diagnosis who face questions regarding treatment intensity. The test classifies bladder tumors into five molecular subtypes, each having distinct tumor biology and potential clinical implications. This information can help physicians and their patients better understand the degree of benefit that would likely be gained from neoadjuvant chemotherapy and/or the likelihood of harboring non-organ-confined disease at time of surgery, respectively. More information about the Decipher Bladder test can be found here.

About Decipher GRID

The Decipher GRID database includes more than 200,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its partners to contribute to continued research and help advance understanding of prostate and other urologic cancers. GRID-derived information is available on a Research Use Only basis. More Information about Decipher GRID can be found here.

On April 16, 2024 VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, reported a business update and announced financial results for the year ended December 31, 2023 (Press release, VBI Vaccines, APR 16, 2024, View Source [SID1234642102]).

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"Over the last 12 months, we’ve seen continued progress across all of our lead programs – with increased use of PreHevbrio and an ever-expanding access and distribution network in place, as well as positive clinical data announcements from all lead pipeline programs, we are helping to make great strides in the fight against GBM, hepatitis B, and coronaviruses," said Jeff Baxter, VBI’s President and CEO. "In the face of a challenging financial market for biotechnology companies, we’ve taken steps to improve our financial stability, including strengthening our balance sheet through equity offerings and business development collaborations, as well as executing on a plan to significantly reduce our debt liability. With a number of near-term milestones expected, we are focused on managing our operational expenses and capital to fuel sustainable growth and value for key stakeholders – patients, healthcare providers, and shareholders."

Recent Key Program Achievements and Projected Upcoming Milestones

PreHevbrio [Hepatitis B Vaccine (Recombinant)]

Product revenue, net of $3.1 million in 2023 compared to $0.9 million in 2022, a 234% year-over-year increase
Preliminary 2024 PreHevbrio U.S. sales demonstrate substantial outpacing of 2023 on a volume basis – through early March 2024, U.S. sales volume totaled approximately 65% of 2023 full year volume
Market segment contracting platforms continue to see growth across Integrated Delivery Networks (IDNs) and large hospital systems, national and regional pharmacy networks, multiple large military and federal facilities, prisons, and independent and public health clinics:
A top-five national health system converted to PreHevbrio in early 2024 with contracting efforts underway to secure additional IDN partners
Retail usage supported by strong ordering from national chains, including Walmart, along with key regional pharmacy networks
PreHevbrio is also available for purchase through the CDC Adult Vaccine Contract
Ex-US – PreHevbri:
Exclusive licensing deal with Brii Biosciences (Brii Bio) announced for the development and commercialization of PreHevbri in the Asia Pacific region (APAC), excluding Japan
An update to the hepatitis B chapter of the Green Book, a resource for healthcare providers with the latest information on vaccines in the UK, was published in April and included detailed information about PreHevbri
PreHevbri became available in Sweden at the end of 2023, and VBI expects that PreHevbri will be made available in certain additional European Union countries in 2024 through its partnership with Valneva
VBI-1901: Cancer Vaccine Immunotherapeutic Candidate – Glioblastoma (GBM)

September 2023: First patients dosed in the randomized, controlled Phase 2b study of VBI-1901, an FDA Fast Track and Orphan Drug Designated cancer vaccine candidate, in recurrent GBM patients
April 2024: Encouraging early tumor response data from Phase 2b study in recurrent GBM presented at World Vaccine Congress 2024:
VBI-1901 Arm: 2 stable disease (SD) observations among patients eligible for evaluation at week 12 (n=2/5), achieving a 40% disease control rate, consistent with 44% disease control rate observed in the Phase 1/2a portion of the study
Control Arm (carmustine or lomustine chemotherapy): No tumor responses have been observed to date (n=0/6; 0% disease control rate) – all evaluable patients experienced a 2-8x increase in tumor size by week 6 and have been taken off study protocol
Mid-Year and Year-End 2024: Additional interim data expected from ongoing randomized Phase 2b study in recurrent GBM patients, subject to speed of enrollment
Novel mRNA-Launched eVLP (MLE) Technology Platform

October 2023:Expansion of proprietary virus-like particle (VLP) platforms announced, supported by preclinical data that demonstrated significant immunologic and manufacturing benefits
MLE technology enables the manufacture of particulate vaccines, capable of driving polyfunctional B-cell and T-cell activation, on accelerated timelines, similar to other mRNA vaccine production timelines
Multiple animal studies have assessed MLE presentation of target antigens compared to mRNA expression alone – studies conducted include target antigens for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and coronaviruses
Breadth and quality of immune response expand the potential for the MLE platform across indications
April 2024: Announced expansion of strategic partnership with Canadian Government to advance the development of the MLE technology platform, supported by the CAD$28 million funding award remaining under the original agreement
Throughout 2024: MLE technology under evaluation by potential partners
VBI-2901: Multivalent Pan-Coronavirus Vaccine Candidate

September 2023: Initial data from Phase 1 study of VBI-2901 reported – the first clinical data from a pan-coronavirus vaccine candidate, demonstrating vaccine benefit represented as boosting and/or greater durability of neutralizing antibody titers
2024: Additional data expected from Phase 1 study
Corporate Updates

February 2024: Announcement of agreement to sell manufacturing capabilities, certain related assets, and enter into new license agreement with Brii Bio – VBI to receive up to $33 million in consideration, subject to achievement of certain activities, which will be used to reduce VBI’s loan obligations due to K2 HealthVentures (K2HV), for:
VBI’s manufacturing capabilities and certain related assets at Rehovot manufacturing facility
Intellectual property for VBI-2601, VBI’s hepatitis B immunotherapeutic candidate
Exclusive Asia Pacific (APAC), excluding Japan, license for development and commercialization of VBI-1901, VBI’s GBM immunotherapeutic candidate
Following completion of all transactions, VBI expects its total debt principal with K2HV to be significantly reduced from $50 million to $17 million
In connection with the transactions, certain covenants in VBI’s loan agreement with K2HV have been amended
To date in 2024, the Company has raised approximately $3.6 million in aggregate gross proceeds from the issuance of its common shares and warrants, and the exercise of previously issued warrants
Financial Results for the Twelve Months Ended December 2023

Cash Position: As of December 31, 2023, VBI had $23.7 million in cash as compared with $62.6 million in cash as of December 31, 2022. Cash position at December 31, 2023, does not include approximately $3.6 million gross proceeds from registered direct offering of common shares and warrants, warrant exercises, and sale of common shares through VBI’s at-the-market facility subsequent to December 31, 2023 and through early April 2024.
Revenues, net: Revenues, net for the full year 2023 were $8.7 million as compared to $1.1 million for the same period in 2022. The revenue increase was a result of an increase in product sales of PreHevbrio in the U.S. and of PreHevbri to VBI’s partner, Valneva, in Europe, in addition to the license revenue and R&D services revenue associated with the agreements with Brii Bio.
Cost of Revenues: Cost of revenues was $12.5 million for the full year 2023 as compared to $11.3 million in 2022. The increase in the cost of revenues was due to increased sales and increased outsourced testing costs during the year ended December 31, 2023.

Research and Development (R&D): R&D expenses for the year ended December 2023 were $9.3 million as compared to $15.5 million in 2022. R&D expenses were offset by $8.3 million for the year ended December 31, 2023, and $8.9 million for the year ended December 31, 2022, due to government grants and funding arrangements. The decrease in R&D expenses is primarily a result of decreased development expenses for VBI’s pan-coronavirus and GBM candidates, VBI-2901 and VBI-1901, due to timing of ongoing clinical studies of each candidate.
Sales, General, and Administrative (SG&A): SG&A expenses for the full year 2023 were $42.1 million as compared to $56.1 million in 2022. The decrease in SG&A expenses was mainly a result of the April 2023 organizational changes that reduced our internal workforce and operating expenses.
Net Cash Used in Operating Activities: Net cash used in operating activities for the full year 2023 was $60.9 million compared to $73.7 million for 2022. The decrease in cash outflows is largely a result of non-cash reconciling items, mainly impairment charges and unrealized foreign exchange loss, and the change in operating working capital, most notably in inventory, other current assets, accounts payable, deferred revenues, and other current liabilities. As a result of the organizational changes announced in April 2023, operating cash outflows in the second half of 2023 were $20 million as compared to $36.3 million in the second half of 2022, representing a 45% reduction.
Net Loss and Net Loss Per Share: Net loss and net loss per share for the full year 2023 were $92.8 million and $6.03, respectively, compared to a net loss and net loss per share of $113.3 million and $13.16 for the full year 2022, respectively.

Net Loss and Net Loss Per Share, Excluding Impairment Charges and Foreign Exchange Loss: Net loss and net loss per share, excluding impairment charges and foreign exchange loss, for the full year 2023 were $61.7 million and $3.96, respectively, compared to $85.8 million and $9.97 for the year ended 2022, respectively. See "Use of Non-GAAP Financial Measures" below for additional information regarding this non-GAAP financial measure, and "GAAP to Non-GAAP Reconciliation" for a reconciliation of this non-GAAP financial measure to net loss and net loss per share.
Impairment charges andforeign exchange loss for the full year 2023 were $24.6 million and $6.5 million, respectively, as compared to none and $27.5 million in 2022. Certain intercompany loans between the Company and its subsidiaries are denominated in a currency other than the functional currency of each entity. The primary driver of the increase in foreign exchange loss was the impact of the relative strengthening of the U.S. and Canadian Dollars against the New Israeli Shekel upon translation of these intercompany loans.

On April 16, 2024 TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer, reported an update on its solid tumor and heme malignancies clinical programs (Press release, TScan Therapeutics, APR 16, 2024, View Source [SID1234642101]).

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"We continue to make meaningful progress across both our solid tumor and heme malignancies Phase 1 clinical programs. As we rapidly approach dosing the first patients in the solid tumor program, I am pleased to share that over 40 patients have completed all biomarker testing in the screening protocol, with the majority qualifying for at least one TCR-T in our ImmunoBank and many qualifying for multiplex therapy. This should allow for rapid enrollment into the treatment protocol over the course of the year," said Gavin MacBeath, Ph.D., Chief Executive Officer. "With respect to the heme program, we are encouraged to see continued positive data with all treatment-arm patients remaining relapse-free with no detectable cancer to date, now with a median follow-up of over 10 months."

Solid Tumor Program: TScan continues to expand the ImmunoBank, a collection of therapeutic TCR-Ts that target different cancer-associated antigens presented on diverse HLA types. TScan’s strategy is to treat patients with multiple TCR-Ts to overcome tumor heterogeneity and prevent resistance that may arise from either target or HLA loss (screening protocol: NCT05812027; treatment protocol: NCT05973487).

•
Phase 1 solid tumor clinical study has been initiated; first three patients expected to be dosed in early May 2024.

•
More than 40 patients have completed all biomarker testing in the screening protocol across a broad array of tumor types. 60% of patients qualify for at least one TCR-T in the ImmunoBank and approximately 30% are eligible for multiplex therapy (T-Plex), potentially enabling rapid enrollment into the treatment protocol upon disease progression.

•
Patients have been identified across all six TCR-T cohorts with dosing expected to commence early May.

•
Initial data on patients from both singleplex and multiplex cohorts expected in the second half of 2024.

•
Additional IND filings planned to continue to expand the ImmunoBank.

•
Long-term duration of response data for multiplex therapy anticipated in 2025.

Heme Malignancies Program: TScan’s two lead TCR-T cell therapy candidates, TSC-100 and TSC-101, are designed to treat residual disease and prevent relapse in patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT) (NCT05473910).

•
All eight patients treated with TSC-100 or TSC-101 remain MRD negative, relapse-free with no detectable cancer to date in either bone marrow biopsies or peripheral blood (median follow-up of >10 months) and no dose limiting toxicities observed to date.

•
To date, all but one patient has exhibited complete donor chimerism in all subsets of blood cells at all time-points, indicating that only donor-derived cells are present in these patients following treatment with either TSC-100 or TSC-101. One patient with T-ALL who was treated with TSC-100 at the lowest dose level exhibited minimally detectable (<0.3%) mixed donor chimerism at 10.5 months and 12 months post-transplant.

•
No detectable mixed chimerism was observed in the malignant cell lineage (CD3+ T-cells) for this patient; mixed chimerism was only observed in healthy nonmalignant blood cells (CD33+ myeloid cells)

•
In contrast, for the control arm (transplant alone), eight patients have now been enrolled and only one has achieved and maintained complete donor chimerism to date. Two patients relapsed approximate six months post-transplant and one of these patients died approximately three months later. A third patient required clinical intervention on day 133 because of concerns of impending relapse, and a fourth died 21 days post-transplant.

•
Opening of expansion cohorts at the recommended Phase 2 dose level to further characterize safety and evaluate translational and efficacy endpoints is planned for the third quarter of 2024.

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Completion of Phase 1 enrollment and reporting of one-year clinical and translational data on initial patients is anticipated in the second half of 2024.

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Expects to initiate registration trial pending feedback from regulatory authorities and report two-year relapse data in 2025.