On November 13, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported positive data from the investigator-initiated INSIGHT-003 Phase I trial evaluating eftilagimod alpha (efti) in combination with KEYTRUDA (pembrolizumab) and chemotherapy for first-line treatment of metastatic non-squamous non-small cell lung cancer (1L NSCLC) patients (Press release, Immutep, NOV 13, 2024, View Source [SID1234648306]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Prof. Dr. Salah-Eddin Al-Batran of the Frankfurt Institute of Clinical Cancer Research (IKF) and project lead stated, "The strength of these mature survival results coupled with a favourable safety profile in first-line treatment of patients with non-squamous NSCLC, the vast majority of whom have negative or low PD-L1 expression, is very encouraging. This promising data in INSIGHT-003 suggests a complementary effect from the addition of efti, a unique MHC Class II agonist, to the standard-of-care combination of pembrolizumab and chemotherapy which has revolutionised the treatment landscape in lung cancer. The IKF will also support and is looking forward to participating in the upcoming TACTI-004 study, which has PFS and OS as dual primary endpoints."

Key Results – Data cutoff – 15 October 2024 The survival data from the triple combination therapy in patients irrespective of PD-L1 expression with a minimum follow-up of 22 months (N=21) at data cut-off shows: INSIGHT-003 Results Median Overall Survival (OS) 32.9 months Median Progression-Free Survival (PFS) 12.7 months 24-month Overall Survival (OS) 81.0% These results compare favourably to the 22.0-month median OS, 9.0-month median PFS, and 24-month OS rate of 45.5% from a registrational trial of anti-PD-1 and doublet chemotherapy in non-squamous 1L NSCLC regardless of PD-L1 expression. 1 Notably, ~19% of the 21 patients in INSIGHT-003 with mature survival data have high PD-L1 expression, who typically respond better to anti-PD-1 therapy, versus ~32% in the registrational trial of anti-PD-1 and doublet chemotherapy

Marc Voigt, CEO of Immutep, stated, "The overall survival and progression-free survival data from this mature cohort of patients in INSIGHT-003 with nearly a 2-year minimum follow-up exceeds our expectations. We are encouraged to see efti build upon the historical clinical outcomes from the most widely used immunotherapy-chemo combination today. Additionally, the early evaluations in the expansion cohort of 19 patients, who all have low or negative PD-L1 expression, are tracking well and we look forward to additional data updates from the INSIGHT-003 trial in 2025 and beyond. Our focus on potentially driving a new standard of care globally in first line treatment of NSCLC is boosted by these results and we are well advanced in our preparations to initiate the TACTI-004 Phase III trial."

Data from all evaluable patients to date (N=40) demonstrates significant improvement of Overall Response Rate (ORR) according to RECIST 1.1 across all levels of PD-L1 expression compared to historical control2 :
• 75.0% ORR versus 62.1% ORR in patients with high PD-L1 expression (TPS >50%)
• 58.8% ORR versus 49.2% ORR in patients with low PD-L1 expression (TPS 1-49%)
• 47.4% ORR versus 32.3% ORR in patients with negative PD-L1 expression (TPS <1%)

In this all-comer PD-L1 trial, the 55.0% ORR and 87.5% Disease Control Rate (DCR) are from the following breakdown of patients by PD-L1 expression: TPS >50% (N=4), TPS 1-49% (N=17), and TPS <1% (N=19). As compared to the general 1L NSCLC patient population of which each of these PD-L1 levels represents roughly one-third, INSIGHT-003 is biased towards low and negative PD-L1 (TPS <50%) patients who are typically less responsive to anti-PD-1 therapy.

In these patients with low and negative PD-L1 expression (36 of 40 patients), the triple combination achieved a 52.8% ORR and 86.1% DCR. Of note, all 19 patients in the expansion cohort have TPS <50% and several with stable disease have potential to become responders.

Safety
Safety continues to be favourable for efti in combination with pembrolizumab and chemotherapy, with no new safety signals.

Next Steps
INSIGHT-003, a multi-centre study led by the Frankfurt Institute of Clinical Cancer Research IKF, is nearing completion of patient enrolment. Additional data updates from this trial are expected in 2025 and beyond.

About INSIGHT-003
INSIGHT-003 is an investigator-initiated, multi-centre study led by the Frankfurt Institute of Clinical Cancer Research (IKF). It is being run as the third arm (Stratum C) of the ongoing Phase I INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. The study is evaluating a triple combination therapy in front line non-small cell lung cancer patients consisting of efti administered subcutaneously in conjunction with an existing approved standard-of-care combination of anti-PD-1 therapy (pembrolizumab) and doublet chemotherapy (carboplatin and pemetrexed) delivered intravenously. The trial will assess the safety, tolerability, and initial efficacy of the combination.

On November 13, 2024 Aurealis Therapeutics, a synthetic biology company developing multi-targeting, scalable, low cost of goods cell and gene therapies for high unmet medical needs, reported that it has raised CHF 8 million from existing investors and shareholders (Press release, Aurealis Therapeutics, NOV 13, 2024, View Source [SID1234648194]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The funds will be primarily used to complete Phase 2 clinical studies with Aurealis lead product AUP-16 for Chronic Wounds, such as Diabetic Foot Ulcer (DFU), and accelerate the preclinical and CMC development of the lead candidate AUP-55 for cancers such as ovarian cancer, other peritoneal carcinomatosis and bladder cancer.

Chronic Wounds, deadly cancers, and inflammatory conditions are complex, multi-factorial diseases which represent massive unmet medical needs and require multi-targeting to be cured. Aurealis Therapeutics is committed to developing multi-targeting therapies based on its unique, proprietary platform. Aurealis platform consists of live, biosafety level 1 lactic acid bacteria, genetically modified to synthesize multiple human therapeutic proteins, acting as millions of nanoscale drug bioreactors in the human body, directly at the disease site. The company’s ambition is to create solid clinical and health economic data in Chronic Wounds, deadly cancers and beyond. This, while engaging with strategic partners to enable market entry and ensure this game-changing technology platform will benefit millions of patients throughout the world.

"We are excited to announce this successful funding round and want to express our gratitude for the trust and support that we have received from the investors. We have exciting times ahead as our Phase 2 study in Diabetic Foot Ulcer is close to completion, and our oncology program is moving towards the clinic" said Juha Yrjänheikki, CEO of Aurealis Therapeutics.

"We have successfully developed our platform and key assets AUP-16 for Chronic Wounds and AUP-55 for Cancer. Positive clinical data, existing and new partnerships, and growing investor base and interest at the market makes us highly confident about completing our next CHF 35M equity round and creating substantial value to all stakeholders" continued Laurent Décory, COO of Aurealis Therapeutics.

On November 13, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Biotheus ("Biotheus") reported the signing of a definitive agreement for the acquisition of Biotheus, a clinical-stage biotechnology company dedicated to the discovery and development of novel antibodies to address unmet medical needs of patients with oncological or inflammatory diseases (Press release, BioNTech, NOV 13, 2024, View Source [SID1234648262]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

With the acquisition, BioNTech will obtain full global rights to the late-stage clinical asset BNT327/PM8002, an investigational bispecific antibody targeting PD-L1 and VEGF-A. The transaction is part of BioNTech’s oncology strategy, aimed at enhancing the company’s capabilities to research, develop and commercialize combination therapies using BNT327/PM8002. Clinical trials with BNT327/PM8002 and the PD-(L)1 x VEGF bispecific class of drugs have demonstrated encouraging clinical activity in various tumor types including in patients with PD-L1-low and -negative tumors who have typically been less responsive to current checkpoint inhibitor treatments.

"The acquisition of Biotheus builds on our successful ongoing collaboration on BNT327/PM8002 and other investigational bispecific antibodies," said Prof. Ugur Sahin, M.D., Ph.D., CEO and co-founder of BioNTech. "We believe that BNT327/PM8002 has the potential to set a new standard of care in multiple oncology indications, surpassing traditional checkpoint inhibitors. We are committed to advancing its research and development in combination with our investigational mRNA vaccines, targeted therapies, and immunomodulators with the aim of enhancing outcomes for patients with solid tumors."

"We are thrilled to deepen our bond with BioNTech. We share the goal of advancing the development of BNT327/PM8002 for future combination therapies in the fight against cancer," said Xiaolin Liu, President, CEO, and Co-Founder of Biotheus. "We believe that BNT327/PM8002 holds significant potential across various tumor indications, and we have an exciting pipeline of innovative investigational assets under development including an antibody discovery and development platform. As we move forward, we are committed to leveraging our strengths with the aim of advancing transformative cancer treatments and enhance our ability to develop treatments for patients in need."

BNT327/PM8002 has shown encouraging efficacy and tolerability in patients across various tumor types, with more than 700 patients treated in clinical trials to date. Multiple registrational trials are planned to start in 2024 and 2025, evaluating BNT327/PM8002 plus chemotherapy in various solid tumor indications including in patients with small cell lung cancer, non-small cell lung cancer and triple-negative breast cancer. Additional trials will explore combining BNT327/PM8002 and BioNTech’s proprietary antibody-drug conjugates ("ADCs"). In June 2024, the evaluation of BNT327/PM8002 in combination with BNT325/DB-1305, a Trophoblast Cell-Surface Antigen 2 ("TROP2")-targeted ADC candidate developed by BioNTech in collaboration with Duality Biologics (Suzhou) Co., Ltd. ("DualityBio"), was initiated as part of an ongoing Phase 1/2 clinical trial (NCT05438329).

Under the terms of the agreement, BioNTech will pay Biotheus shareholders an upfront consideration of $800 million, predominantly in cash, with a small portion in American depositary shares ("ADS"), to acquire 100 percent of the issued share capital, subject to customary purchase price adjustments, plus additional performance-based contingent payments of up to $150 million if certain milestones are met. The transaction is expected to close in the first quarter of 2025, subject to the satisfaction of customary closing conditions, including regulatory approvals. The acquisition follows an initial exclusive global license and collaboration agreement between BioNTech and Biotheus, which closed in November 2023, granting BioNTech the rights to develop, manufacture and commercialize BNT327/PM8002 globally ex-Greater China.

Upon closing, BioNTech will gain full rights to Biotheus’ pipeline candidates and its in-house bispecific antibody drug conjugate capability. The acquisition will expand BioNTech’s footprint in China, adding a local research and development hub to conduct clinical trials. In addition, BioNTech will gain a state-of-the-art biologics manufacturing facility to contribute to its future global manufacturing and supply, and more than 300 Biotheus employees in R&D, manufacturing and enabling functions are expected to join the BioNTech workforce.

BioNTech’s Innovation Series R&D Day
BioNTech leadership will present additional details on the Biotheus transaction, as well as updates on the corporate strategy, commercial strategy and clinical progress across its pipeline during an edition of the company’s Innovation Series R&D Day on 14 November. The live webcast of the event will be available via this link and will begin at 4:30 pm CET (3:30 pm GMT, 10:30 am EST). A replay of the webcast will be available shortly after the event’s conclusion and archived on BioNTech’s website for one year.

About BNT327/PM8002
BNT327/PM8002 is an investigational bispecific antibody combining PD-L1 checkpoint inhibition with VEGF-A neutralization. The checkpoint inhibition is aimed at restoring T cells’ ability to recognize and destroy tumor cells while targeting VEGF-A is aimed at inhibiting tumor angiogenesis, which cuts off the blood and oxygen supply that feeds tumor cells and thus prevents the tumor from growing and proliferating. The combined blockade of the PD-(L)1 pathway and the VEGF-A driven angiogenesis has been shown to deliver synergistically enhanced anti-tumor immune responses in several solid tumor types.1,2 If successfully developed and approved, BioNTech aims to use this bispecific antibody candidate as a new therapeutic backbone in combination with other treatment modalities targeting different oncogenic pathways.

On November 13, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported financial results for the third quarter of 2024 and provided an update on pipeline progress (Press release, Mural Oncology, NOV 13, 2024, View Source [SID1234648283]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Mural launched as a stand-alone company one year ago with a mission to shepherd in the second wave of immuno-oncology for patients—IO 2.0—and we believe we are well on the path to realize that vision. With our deep expertise of protein engineering and cancer biology, we are working to address key limitations with cytokine therapies and unleash their full potential. We are now focused on clinical execution, with major readouts of our two potentially registrational studies of nemvaleukin in the first half of next year, and commercial readiness. We are also deepening our pipeline with candidate nominations for our IL-18 and IL-12 programs expected by the end of this year," said Caroline Loew, Ph.D., CEO of Mural Oncology.

Clinical Progress & Upcoming Catalysts:

Mural’s late-stage trials of nemvaleukin alfa (nemvaleukin), an engineered fusion protein designed to leverage Interleukin-2’s (IL-2) antitumor effects while mitigating its hallmark toxicities, remain on track. The company shared new information related to study design, statistical assumptions, and study execution at a virtual Investor Day in September 2024, including:

Completion of enrollment in ARTISTRY-7, the company’s potentially registrational phase 3 trial in platinum-resistant ovarian cancer (PROC), with a total of 456 patients enrolled. The study is comparing the combination of nemvaleukin and pembrolizumab versus investigator’s choice single agent chemotherapy. Mural expects to report interim overall survival (OS) results in late Q1 or early Q2 based on an analysis performed at approximately 75% of OS events. If the hazard ratio meets the bar for success (0.727, or a 27.3% reduction in the risk of death assuming exactly 215 OS events), the company plans to file a Biologics License Application (BLA) in 2025 subject to discussions with the U.S. Food and Drug Administration (FDA). The company expects to report final results in the second quarter of 2026.
Completion of enrollment in ARTISTRY-6, Cohort 2, the company’s potentially registrational phase 2 study of single agent nemvaleukin in patients with unresectable or metastatic mucosal melanoma, with 92 patients enrolled. Mural anticipates reporting top-line results from cohort 2 of ARTISTRY-6 in Q2 of 2025. The target response rate is 25%. Mural believes that in this rare and highly aggressive tumor with poor outcomes even in the first line setting, demonstrating durable responses with a response rate of 20-25% would be meaningful for patients, and would support a discussion with the FDA regarding a BLA submission and potential accelerated approval.
For the full updates from Mural’s Investor Day, please visit the webcast on our Events & Presentations page.

Mural is also evaluating a less-frequent intravenous (LFIV) dose of nemvaleukin in patients with cutaneous melanoma in ARTISTRY-6, Cohort 3 (monotherapy) and Cohort 4 (combination with pembrolizumab). The company continues to expect preliminary data readouts in the monotherapy cohort in the first half of 2025, and in the combination cohort in the second half of 2025.

Preclinical Program Updates:

Mural plans to nominate development candidates for its IL-18 and IL-12 programs by the end of 2024. The company expects to submit an Investigational New Drug (IND) Application for its IL-18 program to the FDA in Q4 2025.

Other Recent Corporate Highlights:

In September, Mural announced the appointment of Sachiyo Minegishi to its board of directors and chair of the Audit Committee. Ms. Minegishi brings over two decades of biopharma experience, with a focus on corporate strategy, finance, development, and commercialization. She is currently the Chief Operating Officer at Rectify Pharmaceuticals, driving corporate and financing strategy to advance its lead program from discovery to clinical stage. Prior to Rectify, she was Chief Financial Officer at Akouos, Inc., where she led corporate finance and business development strategy and played a key role in the acquisition of the company by Eli Lilly.

In October, Mural continued to prepare for potential launch readiness by creating a new commercial division in the company. Brandon Kotaniemi, SVP of Commercial, will drive Mural’s commercial strategy as the company prepares for the potential BLA submission and launch of nemvaleukin. He will also partner closely with Mural’s development team as the company looks to move its IL-18 program into the clinic.

In November, Mural presented clinical and preclinical data at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). The three poster presentations included tumor microenvironment pharmacodynamic data from the phase 1/2 ARTISTRY-3 study of nemvaleukin as well as data from Mural’s two preclinical research programs in IL-18 and IL-12.

Financial Results for the Quarter Ended September 30, 2024:

Cash Position: As of September 30, 2024, cash, cash equivalents, and marketable securities were $175.5 million.

R&D Expenses: Research and development expenses were $27.6 million for the third quarter of 2024 compared to $40.4 million for the third quarter of 2023. This decrease in R&D expenses was primarily due to different team composition compared to the personnel previously allocated to us by Alkermes plc (Alkermes), our former parent prior to the separation, as well as decreased spend on the ARTISTRY-1 and ARTISTRY-2 trials as activities related to these trials wound down in 2023, and decreased spend on the ARTISTRY-7 trial due to the timing of patient enrollment.

G&A Expenses: General and administrative expenses were $6.5 million for the third quarter of 2024 compared to $6.0 million for the third quarter of 2023. This increase in G&A expenses was primarily due to costs associated with operating as a standalone company after the separation. This includes professional fees as well as differences in costs of insurance and taxes compared to amounts previously allocated to us by Alkermes prior to the separation.

Net Loss: Net loss was $31.8 million for the third quarter of 2024 compared to $51.3 million for the third quarter of 2023.

Financial Guidance:
The company reaffirms guidance that its cash, cash equivalents, and marketable securities as of September 30, 2024 are expected to fund its operations into the fourth quarter of 2025.

As noted previously, management forecasts lower operating expenses in 2025 versus 2024 due to the timing of clinical trial expenses.

On November 13, 2024 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported that company management will participate in the following investor conferences (Press release, Tyra Biosciences, NOV 13, 2024, View Source [SID1234648307]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jefferies London Healthcare Conference, November 19-21st, 2024:

Todd Harris, CEO of TYRA, will participate in a fireside chat on Tuesday, November 19th, at 2:00 pm GMT.
TYRA management will also participate in one-on-one investor meetings and B2B meetings.
36th Annual Piper Healthcare Conference, December 3-5th, 2024, New York:

Mr. Harris will participate in a fireside chat on Wednesday, December 4th, at 10:30 am ET.
TYRA management will also participate in one-on-one meetings with investors.
A live and archived webcast of the fireside chats will be available via the For Investors page on the TYRA website.