Scholar Rock to Present New Clinical and Biomarker Data from the Phase 1 DRAGON Trial at the SITC 39th Annual Meeting

On October 31, 2024 Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, reported that it will present data from the Phase 1 DRAGON trial of SRK-181, an investigational selective inhibitor of latent TGFβ1 activation, in patients with advanced solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting in Houston on November 6–10 (Press release, Scholar Rock, OCT 31, 2024, View Source [SID1234647624]). In a poster presentation, Scholar Rock will share updated safety, efficacy, and biomarker results for SRK-181 in anti-PD-1 resistant patients with advanced solid tumors from the expansion phase (Part B) of the DRAGON trial.

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"These promising new clinical and biomarker data from the DRAGON trial build upon our robust safety and efficacy data on SRK-181 in multiple solid tumor types," said Jay Backstrom, M.D., MPH, President and Chief Executive Officer of Scholar Rock. "We are excited to share these updates, which support the potential of our highly selective approach to inhibiting TGFβ1 with durable responses observed in heavily pretreated patients. While DRAGON completed enrollment last year, patients have remained on therapy, and we look forward to providing additional updates."

Details of the presentations are as follows:

Title: DRAGON Trial: Durable remission rate with the latent TGFβ1 inhibitor linavonkibart (SRK-181) and pembrolizumab in patients with immune checkpoint inhibitor resistant advanced cancers
Presentation Type: Poster 812
Presenter: Timothy A. Yap, M.D., The University of Texas MD Anderson Cancer Center
Location: Level 1, Exhibit Halls AB, George R. Brown Convention Center, Houston, TX
Date/Time: November 9, 2024, 7:10-8:30 p.m. CST

The abstracts for these presentations are available on SITC (Free SITC Whitepaper)’s website on November 5, 2024: View Source

The presentations 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 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 that TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, as well as suppressing T cell activity, thereby inhibiting anti-tumor immunity.

SRK-181 specifically targets the latent TGFβ1 isoform in a context-independent manner, designed to enable complete inhibition of TGFβ1 in all compartments within the tumor microenvironment. Scholar Rock believes that SRK-181 has the potential to overcome this immunosuppressive tumor microenvironment and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. Enrollment of the DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) was completed in December 2023, and patients who remain on the study continue to be treated. The trial enrolled patients in multiple proof of concept cohorts conducted in parallel, including urothelial carcinoma (UC), cutaneous melanoma (MEL), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), 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.

TME Pharma Awarded €2.4 Million German Federal Grant to Support NOX-A12 Phase 2 Trial in Brain Cancer

On October 31, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a clinical-stage biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that it is awarded a non-refundable grant of €2.4 million from the KMU-innovativ funding program run by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) (Press release, TME Pharma, OCT 31, 2024, View Source [SID1234647623]).

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The non-dilutive non-refundable funding will support TME Pharma’s planned Phase 2 randomized controlled study evaluating its lead asset, the CXCL12 inhibitor NOX-A12, for use in the treatment of aggressive adult brain cancer, glioblastoma. Funds will be disbursed after the relevant costs in the trial have been incurred. This grant complements other non-dilutive support worth approximately €5 million for study aspects that are out of the scope of the BMBF grant.

KMU-innovativ ("Innovative SMEs") is the leading funding program of the BMBF specifically designed to support small and medium-sized enterprises (SMEs) in Germany in the realization of innovative projects. The NOX-A12 Phase 2 study met the objectives of the KMU-innovativ Biomedicine program to strengthen the innovative power of SMEs in medical biotechnology and to promote the development of drugs in Germany that lead to the cure, alleviation or prevention of diseases.

"We are pleased that the scientific review by experts at the BMBF recognized the potential of our lead asset in the difficult-to-treat indication of aggressive adult brain cancer and are very grateful to the BMBF for this significant grant of financial support to TME Pharma’s trial," said Aram Mangasarian, CEO of TME Pharma. "The award of this grant is based on the robust study design of our upcoming Phase 2 trial, underpinned by the substantial clinical results NOX-A12 has already achieved showing extraordinary potential as a therapy for glioblastoma. The fact that this funding is non-dilutive is positive news for our existing shareholders. This complements other non-dilutive support TME has secured for different aspects of the trial that will also be provided once the trial has started."

In the Phase 2 study design, approved by the US Food and Drug Administration (FDA) and the German regulator, glioblastoma patients will be treated in five different arms that will address questions of dosing and assess the contribution of the NOX-A12 and bevacizumab components to the overall efficacy of the combination therapy. TME Pharma will be able to optimize late phase development by selecting the best performing treatment arm against standard of care. The Phase 2 results will serve as a basis for discussions with regulatory authorities on the design of the further development strategy, up to market approval, and for discussions with potential partners, such as pharmaceutical companies.

BostonGene to Showcase Innovative Precision Medicine Strategies for Non-Small Cell Lung Cancer at the Advancing Precision Medicine Conference 2024

On October 31, 2024 BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, reported its participation in the Advancing Precision Medicine (APM) Annual Conference 2024, taking place November 1-2, 2024, at the Pennsylvania Convention Center in Philadelphia (Press release, BostonGene, OCT 31, 2024, View Source [SID1234647622]).

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The APM Annual Conference brings together healthcare leaders—including geneticists, oncologists and bioinformaticians—for collaboration and networking in precision medicine. It serves as a vital platform for advancing personalized healthcare and innovative technologies.

Joe Lennerz, MD, PhD, Chief Scientific Officer at BostonGene, will participate in a panel discussion titled "Diagnosis to Treatment – A Case Study in Non-Small Cell Lung Cancer." The session, scheduled for November 1, from 9:00 AM to 10:20 AM, will outline a novel framework for expanding the impact of precision medicine in cancer care. The discussion will emphasize the adoption of NCCN guidelines and strategies to enhance accessibility beyond major cancer centers. It will also focus on leveraging network-based approaches to ensure that world-class diagnostics reach underserved and rural areas, ultimately aiming to reduce disparities in cancer outcomes.

"At APM 2024, we’re excited to explore practical solutions for expanding precision medicine’s reach in cancer care," said Dr. Lennerz. "This session will highlight how network-based approaches can improve diagnostic access in underserved areas, reducing treatment disparities and advancing precision medicine for all patients."

Visit the APM 2024 website for more information.

Vir Biotechnology Reports Third Quarter 2024 Financial Results and Provides Corporate Update

On October 31, 2024 Vir Biotechnology, Inc. (Nasdaq: VIR) reported a corporate update and announced financial results for the third quarter ended September 30, 2024 (Press release, Vir Biotechnology, OCT 31, 2024, View Source [SID1234647621]).

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"This quarter was transformational for Vir. We have bolstered our clinical pipeline with three potential best-in-class dual-masked T-cell engagers in oncology, and have sharpened our focus within infectious diseases to the areas where we believe we can make the most significant impact for patients. We are also thrilled to welcome Jason O’Byrne as our new CFO. Jason brings a wealth of financial leadership experience, further strengthening our ability to bring these potentially transformative therapies to patients as quickly as possible," said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. "Looking ahead, this is an exciting time for the Company. We eagerly anticipate critical data in our hepatitis programs in the fourth quarter and look forward to sharing initial clinical data from our dual-masked T-cell engagers in the first quarter of 2025."

Pipeline Programs

Chronic Hepatitis Delta (CHD)

Preliminary data from the Phase 2 chronic hepatitis delta SOLSTICE study was presented at the European Study of the Liver (EASL) Meeting in June 2024. This data demonstrated the potential for transformative treatment for people living with chronic hepatitis delta, with both tobevibart as a monotherapy, and in combination with elebsiran, achieving high rates of virologic response and ALT normalization after 12 and 24 weeks of treatment. No treatment-related serious adverse events were observed.
The combination of tobevibart and elebsiran has been granted Fast Track Designation by the U.S. FDA. Given the robust rates of virologic suppression observed with the combination, the Company is diligently working to advance this regimen into a pivotal development program as quickly as possible to address the urgent needs of these patients.
At the upcoming American Association for the Study of Liver Diseases (AASLD) "The Liver Meeting" in November 2024, the Company will present additional data from the Phase 2 chronic hepatitis delta SOLSTICE trial, including: 24-week clinical data for both study cohorts in approximately 60 patients and further data for those patients who were on study beyond 24 weeks at the time of data cut-off.
One cohort assesses the combination of tobevibart and elebsiran administered every four weeks, while a second cohort evaluates tobevibart monotherapy administered every two weeks.
The SOLSTICE trial is evaluating the safety, tolerability and efficacy of tobevibart and elebsiran for the treatment of chronic hepatitis delta.
Chronic Hepatitis B (CHB)

The Company plans to share end-of-treatment data from the Phase 2 MARCH Part B trial as a Late Breaking presentation at the AASLD meeting in November 2024.
The MARCH-B trial is evaluating the safety, tolerability and antiviral activity of the triplet combination of tobevibart and elebsiran plus peginterferon alfa-2a in approximately 30 participants, and approximately 50 participants treated with the doublet combination of tobevibart and elebsiran.
The Company plans to share further data assessing a potential functional cure in the second quarter of 2025.
Solid Tumors

VIR-5818 is a dual-masked HER2-targeted T-cell engager in clinical development designed to minimize off-tumor toxicity, potentially allowing for higher doses and increased efficacy to address the significant unmet needs of patients with HER2 expressing cancers.
A Phase 1 basket study of VIR-5818 as a monotherapy, and in combination with pembrolizumab, is on-going in multiple tumor types, including metastatic breast cancer and metastatic colorectal cancer.
The Company plans to share initial clinical data for VIR-5818 in the first quarter of 2025.
VIR-5500 is a dual-masked PSMA directed T-cell engager in clinical development designed to minimize off-tumor toxicity and potentially improve efficacy relative to the existing approved PSMA-targeted therapies.
A Phase 1 dose escalation study of VIR-5500 is ongoing to assess its safety profile and optimal dose levels for future development in metastatic-castration resistant prostate cancer.
The Company plans to share initial clinical data for VIR-5500 in the first quarter of 2025.
VIR-5525 is a dual-masked EGFR targeted T-cell engager with a cleared Investigational New Drug Application (IND) from the U.S. FDA.
The Company plans to initiate a Phase 1 basket study of VIR-5525 in the first quarter of 2025 in patients across a number of solid tumor indications of high unmet need, which may include metastatic head and neck squamous cell carcinoma, metastatic adenocarcinoma, squamous non-small cell lung cancer, and metastatic colorectal cancer.
Preclinical Pipeline Candidates

The Company continues to advance pre-clinical assets in respiratory syncytial virus in partnership with GSK and pursue HIV cure in collaboration with the Bill & Melinda Gates Foundation.
Corporate Update

On August 1, 2024 the Company announced an exclusive worldwide license to three clinical-stage masked T-cell engagers (TCEs) with potential applications in a range of cancers, as well as the exclusive use of the proprietary PRO-XTEN masking platform for oncology and infectious disease. The Company announced closing of the agreement with Sanofi on September 9, 2024.
Key employees from Sanofi, possessing extensive scientific and development expertise in TCEs, and in-depth experience with the PRO-XTEN platform, joined the Company following the closing of the agreement.
On August 1, 2024 the Company announced the phase-out of clinical programs in influenza, COVID-19, and its T-cell based viral vector platform. The Company is seeking partners to advance these clinical programs through further development. Additionally, the Company announced a workforce reduction of approximately 25%, or approximately 140 employees, and expects to end 2024 with approximately 435 employees – a decrease of approximately 200 from its peak headcount in the second quarter of 2023.
On September 10, 2024, the Company announced the appointment of Jason O’Byrne as Executive Vice President and Chief Financial Officer, effective October 2, 2024. Mr. O’Byrne is an accomplished executive with more than 20 years of finance and operations experience, and brings leadership in capital allocation and formation, corporate strategy and operational excellence.
The Company will host two virtual investor events instead of the previously scheduled R&D Day in the fourth quarter of 2024. The first event, focusing on our hepatitis programs, will be held in November 2024, following the AASLD conference, and will provide detailed updates on our hepatitis delta and hepatitis B programs. In the first quarter of 2025, the Company will share initial clinical data for our masked T-cell engager programs during a second dedicated investor event.
Third Quarter 2024 Financial Results

Cash, Cash Equivalents and Investments: As of September 30, 2024, the Company had approximately $1.19 billion in cash, cash equivalents and investments, representing a decrease of approximately $245.1 million during the third quarter of 2024. The decrease includes a $103.7 million upfront payment made to Sanofi upon the closing of the agreement and a $75.0 million escrowed milestone payment reclassified to restricted cash. The escrowed milestone is subject to VIR-5525 achieving "first in human dosing" by 2026. Excluding the impact of the Sanofi agreement, the decrease in cash, cash equivalents and investments in the third quarter was approximately $66.4 million.

Revenues: Total revenues for the quarter ended September 30, 2024, were $2.4 million compared to $2.6 million for the same period in 2023.

Cost of Revenue: Cost of revenue was nominal for the third quarter of 2024 and 2023.

Research and Development Expenses (R&D): R&D expenses for the third quarter of 2024 were $195.2 million, which included $8.9 million of non-cash stock-based compensation expense, compared to $145.0 million for the same period in 2023, which included $15.8 million of non-cash stock-based compensation expense. The increase was primarily driven by $102.8 million of the Sanofi upfront payment being recognized as in-process research and development expense, partially offset by lower clinical development costs and manufacturing costs associated with the discontinued flu asset, VIR-2482.

Selling, General and Administrative Expenses (SG&A): SG&A expenses for the third quarter of 2024 were $25.7 million, which included $7.8 million of non-cash stock-based compensation expense, compared to $40.9 million for the same period in 2023, which included $11.1 million of non-cash stock-based compensation expense. The decrease was largely related to cost savings initiatives implemented during the second half of 2023.

Restructuring, long-lived assets impairment and related charges: Restructuring, long-lived assets impairment and related charges for the third quarter of 2024 were $12.7 million compared to $3.4 million for the same period in 2023. The increase was primarily driven by severance charges incurred related to our strategic restructuring announcement in August 2024 and to a lesser extent right-of-use asset impairment charges related to the closing of our Portland, Oregon facility, which was previously announced on December 13, 2023.

Other Income: Other income for the third quarter of 2024 was $17.8 million compared to $20.1 million for the same period in 2023. The decrease was primarily due to lower interest income.

(Provision for) Benefit from Income Taxes: Provision for income taxes for the third quarter of 2024 was $0.2 million compared to a benefit from income taxes of $3.2 million for the same period in 2023.

Net Loss: Net loss attributable to Vir for the third quarter of 2024 was $(213.7) million, or $(1.56) per share, basic and diluted, compared to a net loss of $(163.4) million, or $(1.22) per share, basic and diluted for the same period in 2023.

2024 Financial Guidance

The Company has updated its operating expense guidance for the full-year 2024, which includes the upfront in-process research and development expense associated with the clinical-stage T-cell engagers licensed through its agreement with Sanofi:

(in $ millions)

GAAP operating expense range:

$

660

to

$

680

The following expenses are included in the GAAP operating expense range:

Upfront payment to Sanofi recognized as R&D expense in the third quarter of 2024

$103

Stock-based compensation expense

$

90

to

$

80

Restructuring charges*

$

40

to

$

30

* Restructuring charges include employee severance cash payouts, as well as non-cash expense related to the closing of two R&D sites previously announced on December 13, 2023.

The GAAP operating expense guidance does not include the effect of GAAP adjustments caused by events that may occur subsequent to the publication of this guidance, including, but not limited to, business development activities, litigation, in-process R&D impairments, and changes in the fair value of contingent considerations.

Conference Call

Vir will host a conference call to discuss the third quarter results at 1:30 p.m. PT / 4:30 p.m. ET today. A live webcast will be available on View Source and will be archived on www.vir.bio for 30 days.

About Tobevibart (VIR-3434)

Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen. It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes, and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart, which incorporates Xencor’s Xtend and other Fc technologies, has been engineered to have an extended half-life and was identified using Vir’s proprietary monoclonal antibody discovery platform. Tobevibart is administered subcutaneously, and it is currently in clinical development for treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta.

About Elebsiran (VIR-2218)

Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. It is the first asset in Vir’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical studies.

About VIR-5818, VIR-5500, VIR-5525

VIR-5818, VIR-5500, VIR-5525 are investigational, clinical candidates currently being evaluated for the treatment of solid tumors. These assets leverage the PRO-XTEN masking technology with three different T-cell engagers (TCEs) targeting HER2, PSMA, and EGFR, respectively.

TCEs are powerful anti-tumor agents that direct the immune system, specifically T-cells, to destroy cancer cells. The PRO-XTEN masking technology is designed to keep the TCEs inactive (or masked) until they reach the tumor microenvironment, where tumor-specific proteases cleave off the mask and activate the TCEs leading to killing of cancer cells. By driving the activity exclusively to the tumor microenvironment, we aim to circumvent the traditionally high toxicity associated with TCEs and increase their efficacy and tolerability. Additionally, the mask also helps drug candidates stay in the bloodstream longer in their inactive form, allowing them to better reach the site of action and potentially allowing more convenient dosing regimens for patients and clinicians.

Kelun-Biotech’s TROP2-ADC SKB264 (sac-TMT) Third NDA Accepted by NMPA, locally advanced or metastatic EGFR-mutant NSCLC

On October 31, 2024 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the new drug application (NDA) (the "Application") based on the positive results from the pivotal phase III OptiTROP-Lung04 study of sacituzumab tirumotecan (sac-TMT, that it formerly SKB264/MK-2870) developed was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China in adult patients with epidermal growth factor receptor (EGFR)-mutant locally advanced or metastatic non-small cell lung cancer (NSCLC) who progressed after treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy (Press release, Kelun, OCT 31, 2024, View Source [SID1234647620]).

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OptiTROP-Lung04 is a multi-center, randomized, registrational phase III clinical study that evaluates the efficacy and safety results of sac-TMT monotherapy versus pemetrexed plus platinum chemotherapy for the treatment of patients with EGFR-mutant locally advanced or metastatic NSCLC who progressed after treatment with EGFR- TKI therapy. At a pre-specified interim analysis, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) as assessed by the blinded independent review committee (BIRC) compared with pemetrexed plus platinum chemotherapy. Sac-TMT also showed a manageable safety profile, with no unexpected safety signals identified.

The Application is the third NDA for sac-TMT that has been accepted by the NMPA. On October 25, 2024, it was announced on the official website of the CDE that the Application was planned to be included in the priority review and approval process of the CDE.

Previously, two NDAs for sac-TMT in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) and for sac-TMT monotherapy in adult patients with locally advanced or metastatic EGFR-mutant NSCLC who experience progression following treatment with an EGFR-TKI and platinum-based chemotherapy, respectively, were accepted by the NMPA.

Sac-TMT, a core product of the Company, is a novel human trophoblast cell-surface antigen 2 (TROP2) antibody-drug conjugate (ADC) in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

Dr. Micheal Ge, CEO of Kelun-Biotech, said, "sac-TMT (sacituzumab govitecan) has received its third NDA. In response to unmet clinical needs, the company has always adhered to the spirit of hard work inherent in Kelun, focusing on original innovation and doing practical work to develop new drugs with differentiated advantages and international potential. We believe that sac-TMT will shine in the field of oncology and contribute Chinese strength to the global health cause."