On October 29, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported an update on its activitiesfor the quarter ended 30 September 2024 (Q1 FY25) (Press release, Immutep, OCT 29, 2024, View Source [SID1234647455]).

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!

EFTI DEVELOPMENT PROGRAM FOR CANCER

TACTI-004 (KEYNOTE-PNC91) – 1L NSCLC Phase III Clinical Collaboration with MSD

In July, Immutep received positive feedback from the US Food and Drug Administration (FDA) regarding its planned TACTI-004 Phase III trial of eftilagimod alfa (efti) in combination with KEYTRUDA (pembrolizumab), MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, and histology-based platinum doublet chemotherapy for the treatment of first-line metastatic non-small cell lung cancer (1L NSCLC), regardless of PD-L1 expression.

The FDA feedback builds on previously received guidance from the Paul-Ehrlich-Institut and the Spanish Agency for Medicines and Health Products, successfully concluding the preparatory regulatory interactions for the design of this registrational trial. The study will enrol ~750 patients regardless of PD-L1 expression in order to address the entire 1L NSCLC market eligible for anti-PD-1 therapy

TACTI-003 (KEYNOTE-C34) – Phase IIb clinical trial in 1L HNSCC

TACTI-003 is evaluating efti in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC). The randomized Cohort A portion of the study is evaluating efti in combination with KEYTRUDA as compared to KEYTRUDA monotherapy in patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumours, whereas Cohort B is evaluating efti in combination with KEYTRUDA in patients with PD-L1 negative tumours (CPS <1).

In July, Immutep reported updated positive efficacy and safety results from Cohort B of the TACTI-003 Phase IIb trial at an ESMO (Free ESMO Whitepaper) Virtual Plenary session. In patients with negative PD-L1 expression (CPS <1) in Cohort B, efti in combination with KEYTRUDA achieved a 35.5% objective response rate (ORR). This is among the highest recorded for a treatment approach not containing chemotherapy in patients with CPS <1. The immuno-oncology combination with efti also attained a high complete response rate of 9.7%, which compares favourably to a historical control of 0% from anti-PD-1 monotherapy in 1L HNSCC patients with a CPS <1. Additionally, durability of responses was tracking well.

In September, further data was reported from Cohort A of the TACTI-003 trial in a late-breaking abstract and prestigious Proffered Paper oral presentation at ESMO (Free ESMO Whitepaper) Congress 2024. At ESMO (Free ESMO Whitepaper), late-breaking abstracts are generally reserved for high-quality, new research findings from randomised phase II or phase III trials with implications for clinical practice or understanding of disease processes. Proffered Papers are oral presentations of original data of superior quality, followed by expert discussion and perspectives.

In patients with PD-L1 positive tumours (CPS ≥1), efti in combination with KEYTRUDA outperformance was largest in CPS ≥20 with 31.0% ORR (34.5% ORR including a partial response recorded after data cut-off date) versus 18.5% ORR for KEYTRUDA monotherapy. Efti in combination with KEYTRUDA led to a high durability of response of 17.5 months in patients with CPS ≥1 and the combination continues to have favourable safety profile. Additionally, a statistically significant increase in absolute lymphocyte count, measured as an exploratory biomarker, was seen in the efti with KEYTRUDA arm indicating an effective efti-induced immune response in this randomised setting.

Immutep will continue to follow the maturing data from TACTI-003, with the most relevant endpoint of Overall Survival expected in 2025 and engage with regulatory authorities regarding potential paths forward.

TACTI-002 (KEYNOTE-PN798) – Phase II clinical trial in 1L NSCLC

Immutep continues to follow patients with first-line non-small cell lung cancer (1L NSCLC), in Part A of the TACTI-002 trial, where excellent median Overall Survival (mOS) rates were seen across all levels of PD-L1 expression. Immutep has previously reported final data from the other parts of the TACTI-002 trial.

AIPAC-003 – Integrated Phase II/III trial in MBC

Subsequent to quarter end, Immutep completed patient enrolment in the randomised Phase II portion of the AIPAC-003 trial in October. The Phase II portion enrolled 65 metastatic hormone receptor positive (HR+), HER2-negative/low or triple-negative breast cancer patients who had exhausted endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The patients have been enrolled across 22 clinical sites in Europe and the United States and have been randomised 1:1 to receive either 30mg or 90mg dosing of efti in combination with paclitaxel to determine the optimal biological dose of efti consistent with the FDA’s Project Optimus initiative. Further updates will be provided after data collection, data cleaning and analysis.

INSIGHT-003 – Phase I in non-squamous 1L NSCLC

The investigator-initiated INSIGHT-003 trial continued to enrol patients throughout the quarter and they have been safely dosed across six sites in Germany. Further updates from the trial are anticipated in Q 4 CY2024.

INSIGHT-005 – Phase I trial in Urothelial Carcinoma

The INSIGHT-005 trial is evaluating efti and the anti-PD-L1 therapy BAVENCIO (avelumab) in up to 30 patients with metastatic urothelial cancer. The study is jointly funded with Merck KGaA, Darmstadt, Germany.

EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma

New data from the EFTISARC-NEO Phase II investigator-initiated trial of efti in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS) will be presented on 14 November at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting taking place in San Diego, California.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

In August, Immutep successfully dosed the first participant in the first-in human Phase I trial of IMP761 after receiving regulatory clearance from the ethics and competent authority in the Netherlands to initiate the study. Safety data from this first-in-human study is anticipated by the end of the calendar year 2024, with pharmacokinetics and pharmacodynamics data in first half CY2025.

IMP761 is a first-in-class agonist LAG-3 antibody designed to restore balance to the immune system by enhancing the "brake" function of LAG-3 to silence dysregulated self-antigen-specific memory T cells that cause many autoimmune diseases.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted seven new patents for efti, IMP761 and LAG525 (ieramilimab) in various territories.

Two patents were granted for efti in combination with a PD-1 pathway inhibitor in South Korea and Brazil and one patent was granted in Mexico for a binding assay for determining MHC Class II binding activity. The assay is used in the characterisation of efti in GMP-grade manufacturing.

New patents were also granted for IMP761 in India and Israel. For LAG525, which is exclusively licensed to Novartis by Immutep, two new patents were granted in Australia and Taiwan.

CORPORATE & FINANCIAL SUMMARY

Immutep enters the ASX 300

Following the September quarterly review of the S&P Dow Jones Indices, Immutep was added to the S&P/ASX
300 index. Joining the ASX 300 recognises the Company’s considerable growth over the years, enhances its
market visibility and supports investor confidence.

Cash Flow Summary

During the quarter, Immutep continued to advance its clinical trial programs for efti and preclinical program for IMP761 to create value for shareholders. The Company is well funded with a strong cash and cash equivalent balance as at 30 September 2024 of approximately A$120.3 million. In addition to this cash balance, Immutep has an A$52.0 million bank term deposit, which has been recognised as a short-term investment due to the maturity date of 5-12 months. This aggregate position of A$172.3 million as at 30 September 2024 gives Immutep an expected cash reach to the end of CY2026.

Cash receipts from customers in Q1 FY25 were $20k. During the quarter, Immutep received a €2,194,918 (~A$3,602,362) research and development (R&D) tax incentive payment in cash from the French Government under its Crédit d’Impôt Recherche scheme and $549k from the Australian government R&D tax rebate.

The net cash used in G&A activities in the quarter was $961k, compared to $1.9 million in Q4 FY24. Payments to Related Parties (detailed in item 6.1 of the Appendix 4C) comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of $576k.

The net cash used in R&D activities during the quarter was $9.5 million, compared to $3.8 million to Q4 FY24. The increase is mainly due to the increased level of clinical trial activities. Payment for staff costs was $2.8 million in the quarter compared to $2.0 million in Q4 FY24.

Total net cash outflows used in operating activities in the quarter were $8.6 million compared to $7.4 million in Q4 FY24.

For the cash flow used in investing activities, the company invested $32.4 million in bank term deposits with maturity between 5 and 6 months which has been recognised as a short-term investment.

Net cash outflow from financing activities for the quarter was approximately $373 k including $254k for the payment of capital raising cost.

A copy of the Appendix 4C -Quarterly Cash Flow Report for the quarter is attached.

On October 28, 2024 Parabilis Medicines (formerly FogPharma), a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer, reported a corporate name change (Press release, Parabilis Medicines, OCT 28, 2024, View Source [SID1234649752]). The company’s new name, Parabilis (pronounced puh-RAH-buh-liss), draws on Greek and Latin etymologies to mean both ‘beyond what’s possible’ and ‘obtainable,’ reflecting the company’s drive to expand what is therapeutically possible for the treatment of serious diseases, and its commitment to ensuring its medicines reach and benefit patients globally.

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!

Parabilis also unveiled its expanded Helicon platform, which seamlessly integrates highly innovative AI and experimental technologies to discover, optimize, and deliver Helicon peptide therapeutics for not-yet-drugged targets, in addition to cutting-edge data science techniques the company is employing to optimize trial design and guide future clinical strategies.

"The name Parabilis captures the tremendous aspirations of a group of passionate innovators who are grounded in pragmatism. We are combining breakthrough science, industry-leading artificial intelligence (AI) capabilities, and a relentless drive to create real medicines that change what is possible in treating disease," said Mathai Mammen, M.D., Ph.D., Chairman and CEO of Parabilis Medicines. "That clarity of ambition is reflected in the way we approach our work, integrating data science and new product planning throughout the drug discovery and development lifecycle to ensure we’re single-mindedly pursuing only those medicines that anticipate and address profound unmet needs. Our new company name embodies this spirit: break boundaries, crush dogma, operate with the highest ambitions, and focus relentlessly on the patient at all times."

Parabilis’s investigational lead candidate, FOG-001, is the only clinical-stage inhibitor of the interaction of β-catenin with TCF, a known driver of colorectal cancer (CRC) with a significant role in multiple additional cancers. This target has been a towering challenge in the pharmaceutical industry, known for decades to be a key node, yet intractable. Now 16 months into its development, FOG-001 continues to enroll mostly CRC patients in its Phase 1 precision guided program. The company is also advancing its discovery portfolio with applications in protein degraders and radioligand therapies for the treatment of cancer, with four late discovery programs and integration of AI and advanced data science into every aspect of the discovery and development process.

In early 2024, the company raised a $145 million Series E financing to support the ongoing clinical development of FOG-001 and accelerate its broader Helicon peptide portfolio and platform.

On October 28, 2024 Ottimo Pharma, a private biotech company, reported the appointment of world class industry veterans David Epstein as Chair & Chief Executive Officer, Mehdi Shahidi as Head of Development & Chief Medical Officer and James Sabry as Vice-Chair of the Board of Directors (Press release, Ottimo Pharma, OCT 28, 2024, View Source [SID1234647466]).

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!

Ottimo Pharma, co-founded by Medicxi and Jonny Finlay in 2020, is developing Jankistomig, a PD1-VEGFR2 bi-functional antibody, designed as a dual-pathway, single agent, IgG therapy targeting immune checkpoint inhibition and angiogenesis in the treatment of cancer.

David Epstein, Chair & Chief Executive Officer of Ottimo Pharma, said: "This new medicine is exquisitely designed and offers large potential benefits to patients across a wide range of solid tumors. It will be exciting to scale the team and deliver on the promise to patients."

James Sabry, Vice-Chair of the Board of Ottimo Pharma, said: "I am excited to join the Board of this highly innovative company with a beautifully designed medicine that has the potential to change the face of cancer immunotherapy."

Jankistomig’s unique mode of action blocks the PD1 and VEGF pathways, leveraging its high affinity for PD1 to enhance tumor immune cell biodistribution while minimizing VEGF-related adverse effects, specifically due to its intentionally designed interaction with VEGFR2.

Ottimo Pharma’s goal is to improve cancer treatment outcomes and reduce healthcare burden through this novel combination of mechanisms of action.

Over the last three years, Ottimo Pharma has been running the full pre-clinical characterization of the molecule and anticipates filing an IND in late 2025.

Francesco De Rubertis, Board Member at Ottimo Pharma & Partner at Medicxi, commented: "As we launch Ottimo Pharma, I am confident that the combined expertise of this stellar leadership team will help accelerate the transformation of the original insight by Jonny Finlay in his Scottish lab into a best-in class asset in cancer therapy."

Jonny Finlay, Scientific Founder & Advisor at Ottimo Pharma, added: "I am extremely excited to see Ottimo Pharma come out of stealth. I can’t wait to see the scientific and clinical breakthroughs made by this superb team and this deeply differentiated molecule."

David Epstein, newly appointed Chair of the Board of Directors & Chief Executive Officer, brings over 30 years of experience in drug development, deal making and commercialization, with a strong track record of success. Most recently, David served as CEO of Seagen, and as a member of its Board, until its acquisition by Pfizer in late 2023. From 2010 to 2016, he served as CEO of

Novartis Pharmaceuticals, a division of Novartis AG, and earlier in his career, he founded and led Novartis’ Oncology and Molecular Diagnostics units.

Mehdi Shahidi, MD, joins Ottimo Pharma as Head of Development & CMO, bringing a wealth of expertise in oncology drug development. With over two decades of experience in pharma, including Global Head of Medicine, Oncology and SVP & Chief Medical Officer at Boehringer Ingelheim, he has overseen the clinical development, regulatory filing and registration of multiple drugs. Mehdi completed his clinical oncology training at the Royal Marsden Hospital in London and had a successful clinical and research career in oncology before transitioning to the pharmaceutical industry.

James Sabry, MD, PhD, joins Ottimo Pharma’s Board as non-executive Vice-Chair, with over 30 years of experience in business development and partnering. He currently serves as EVP, Chief Business Officer of BioMarin Pharmaceutical Inc. Prior to this, James was previously Global Head and EVP of Roche Pharma Partnering where he was instrumental in securing key deals that have significantly advanced the company’s R&D pipeline and led to the launch of numerous new medicines. From 2010, he was Senior Vice President of Genentech Partnering.

On October 28, 2024 Kivu Bioscience, a biotech company developing next-generation antibody-drug conjugates to deliver best-in-class therapeutics, reported the close of a $92 million Series A financing round led by Novo Holdings, with participation from Gimv, Red Tree Venture Capital, HealthCap as well as existing investors BioGeneration Ventures, M Ventures, and Brabantse Ontwikkelings Maatschappij (BOM) (Press release, Kivu Bioscience, OCT 28, 2024, View Source [SID1234647465]). The funding will be used to advance multiple oncology programs into the clinic.

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!

"We’re excited to have the backing of this top-tier syndicate, who share our vision for developing kinder, gentler ADC therapies that are more effective and safer for cancer patients," said Mohit Trikha, Ph.D., President and Chief Operating Officer of Kivu Bioscience. "Our next-generation ADCs address key limitations of current treatments, particularly by engineering stable ADCs we have the potential to reduce off-target side effects which in turn widens the therapeutic window. This funding allows us to accelerate the development of our Topo1i-based ADC pipeline to the clinic, where we plan to quickly differentiate Kivu’s products from past endeavors. We are inspired by patients and driven by data to accelerate transformative medicines."

Kivu is utilizing the proprietary Synaffix site-specific linker-payload technology to deliver next-generation ADC therapeutics. The GlycoConnect technology, which couples the linker specifically to asparagine-297, delivers a clean, highly homogenous product. This technology not only offers a clear manufacturing advantage over other conjugation techniques, but also produces an ADC that is more stable, significantly reducing off-target side effects. This approach widens the therapeutic window, improving the safety profile for patients. Addressing the discontinuation and dose-reduction rates seen with ADCs will establish Kivu’s place in treating solid tumors.

"ADCs are an established modality for treating cancer, but tolerability issues limit the pace of advancement in the space. The early data from Kivu suggested superior stability of the constructs, clearly pointing toward targets that have been pursued by earlier generations of ADCs, but which failed due to high rates of drug discontinuation. That data in the hands of this outstanding management team tells an incredibly compelling story – one we are excited to support. We see tremendous opportunity for the Kivu pipeline to produce a new generation of targeted therapies as best-in-class novel ADCs across a broad range of cancers," said Daniel O’Connell, M.D., Ph.D., Partner, Novo Holdings.

Kivu’s assets are in late-stage preclinical studies and target areas of high unmet medical need. The company’s platform is differentiated by its superior ability to avoid the issues seen with currently marketed ADCs and addresses key limitations related to stability and therapeutic precision and delivery. The company is set to begin Phase 1 trials for its lead candidate in 2025.

On October 28, 2024 BPGbio, Inc., a leading biology-first, AI-powered, clinical stage biopharma focused on mitochondrial biology and protein homeostasis, reported its participation in the inaugural Google Cancer AI Symposium, in Boston. BPGbio President and CEO Niven R. Narain, Ph.D., will deliver a presentation on "Making AI for Discovery Real – Prioritizing Biology before Tech," on October 30 at 2:45 pm (Press release, BPGbio, OCT 28, 2024, View Source [SID1234647464]).

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!

Dr. Narain’s session will delve into the evolving landscape of AI-driven drug discovery, highlighting both the opportunities and challenges. Drawing from BPGbio’s pioneering history in the intersection of AI and Biology and his lens of experience, Narain will share best practices that have fueled the company’s robust clinical pipeline, which includes its BPM31510, currently in a phase 2b for glioblastoma multiforme (GBM) and a phase 2a for pancreatic cancer, as well as a potential pivotal trial targeting multiple primary CoQ10 deficiency mutations.

"It is a privilege to be invited to speak at Google’s inaugural Cancer AI Summit, especially on a topic BPGbio has pioneered for the past decade," said Dr. Narain. "I look forward to sharing our journey, use cases, and wins with industry leaders and esteemed researchers. By combining the strengths of biology and AI technology, we can address the immense challenges of cancer research and accelerate the development of more effective therapeutics. I also plan to highlight the community of global partners who helped galvanize our road to success."

During the presentation, Dr. Narain will also provide updates on BPGbio’s robust portfolio of therapeutic candidates, many of which are in late-stage clinical trials. These candidates have been identified/guided using the company’s proprietary AI-powered NAi Interrogative Biology Platform, which facilitates target discovery, biomarker identification, and drug development through all stages—from preclinical to late-stage development. The NAi Platform is currently advancing key partnerships with pharmaceutical companies, academic institutions, and government organizations on various disease indications.

BPGbio’s therapeutic pipeline includes candidates for glioblastoma (orphan drug), pancreatic cancer (orphan drug), primary CoQ10 deficiency (rare pediatric disease designation), epidermolysis bullosa (orphan drug), squamous cell carcinoma (orphan drug), sarcopenia, solid and liquid tumors, Huntington’s disease, and Parkinson’s disease.

For more information on BPGbio’s participation in the Google Cancer AI Symposium, visit www.bpgbio.com.

About the NAi Interrogative Biology Platform

The NAi Interrogative Biology Platform combines BPGbio’s industry-leading, clinically annotated proprietary biobank, purpose-built Bayesian artificial intelligence, and the compute power of the world’s fastest supercomputer, Frontier, housed at Oak Ridge National Laboratory.

Collectively, these tools enable the company to bring artificial intelligence to biology, inspiring AI-driven target nomination, discovery, molecule design, and more. The platform has been used to identify more than 100 drug targets and diagnostic biomarkers and supported research collaborations with a range of government, industry and academic partners including the U.S. Department of Defense (DoD), Sanofi, and Harvard Medical School.