On May 15, 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 encouraging efficacy, safety, and pharmacodynamic data from the safety lead-in of the AIPAC-003 Phase II/III trial presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer 2024 Congress (Press release, Immutep, MAY 15, 2024, View Source [SID1234643394]). This lead-in represents the first ever 90mg dosing of eftilagimod alpha ("efti"), a soluble LAG-3 protein and MHC Class II agonist, given in combination with weekly paclitaxel.

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Efficacy

The poster titled "Testing a higher dose (90 mg s.c.) of eftilagimod alpha, a soluble LAG-3 protein, in metastatic breast cancer patients receiving weekly paclitaxel in AIPAC-003" details positive results in six metastatic breast cancer (MBC) patients, who exhausted endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The data shows a confirmed 50% overall response rate, including one complete response and two partial responses, and a 100% disease control rate, with three patients having stable disease as best overall response per RECIST 1.1.

Complete Response Patient Case Study

The patient with a confirmed complete response (CR) was diagnosed with triple-negative breast carcinoma (TNBC) in 2019 and has failed multiple lines of therapy including a CDK 4/6 inhibitor for ER+/PR+ metastasis. During the immuno-oncology (IO)-chemotherapy treatment of efti and paclitaxel, this patient achieved a partial response (PR) that subsequently turned into a CR. This patient’s ongoing CR has been maintained since stopping paclitaxel and being treated with efti monotherapy.

Safety & Pharmacodynamic Effects

The lead-in has also shown that the first-ever 90mg efti dosing in combination with weekly paclitaxel continues to be well tolerated with a favourable safety profile. As of the data cut-off (April 3), no dose-limiting toxicities and no treatment-emergent adverse events of grade 3 or higher severity were recorded.

The 90mg efti dosing leads to a higher maximum concentration of efti in the blood as compared to lower efti doses in past clinical trials, and efti remains detectable at a pharmacologically active level (>1 ng/mL) up to 96 hours after administration. Pharmacodynamic effects also showed an increase of circulating levels of immune cells such as CD8 & CD4 T cells and plasma Th1 biomarker levels. All patients in the AIPAC-003 safety lead-in had a ≥1.4-fold change in interferon-gamma (IFN-g) and ~83% had a ≥1.4-fold change in CXCL10 after a single 90mg efti dose.

Dr. Serafin Morales Murillo, University Hospital Arnau de Vilanova, Lleida, Spain, and AIPAC-003 investigator stated, "It is encouraging to see the high efti dose of 90mg with weekly paclitaxel continue to be safe and well tolerated in these metastatic breast cancer patients. It is also positive at this early stage to see high response and disease control rates, including a complete response, in these patients who have unfortunately all seen their cancers progress after endocrine therapy including CDK 4/6 inhibitors. We are looking forward to further data emerging from this study."

The randomized Phase II portion of the trial, which will include up to 58 evaluable patients, is underway and focused on whether 90mg efti dosing is more efficacious than 30mg dosing. This portion of the trial has enrolled 35 patients to date. Importantly, the determination of the optimal dose in AIPAC-003 is directly tied to the FDA’s Project Optimus initiative and is relevant for the entire efti program.

Further data updates in terms of safety and efficacy from AIPAC-003 are expected in CY2024. The ESMO (Free ESMO Whitepaper) Breast 2024 poster will be available on the Posters & Publications section of Immutep’s website.

About Eftilagimod Alpha (Efti)

Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-g and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).

On May 15, 2024 Oncodesign Precision Medicine (OPM) (ISIN: FR001400CM63; Mnemonic: ALOPM), a biopharmaceutical company specializing in precision medicine for the treatment of resistant and metastatic cancers, and Navigo Proteins GmbH (Halle, Germany), a biopharmaceutical company specializing in the discovery and development of Precision Medicine applications based on the Affilin technology platform, reported the signature of a strategic collaboration agreement for the discovery and development of new systemic radiotheranostic agents (Press release, Navigo Proteins, MAY 15, 2024, View Source [SID1234643378]).

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OPM operates three technological platforms dedicated to precision medicine. OncoSNIPER is a technology using AI to select and validate new therapeutic targets involved in resistant and metastatic cancers, in particular kinases and targets expressed specifically on the tumor cell surface. The aim is to discover and develop new kinase inhibitors based on the Nanocyclix technology platform and new radioligand therapy agents from its 3rd technology platform, Promethe.

The construction of radiotheranostics is based on the identification of a specific target on the cancer cells’ surface (surface antigen), and on small molecule, peptide, antibody or small protein (like Affilin) targeting molecules that are highly specific for the identified target, enabling radioactivity (emitters a, β+- or γ) to be delivered to the tumor cell and thus triggering its detection and destruction. This therapeutic approach has already been clinically proven in the treatment of metastatic prostate cancer (Pluvicto; Novartis) and inoperable or metastatic gastroenteropancreatic neuroendocrine tumors (Lutathera; Novartis).

OPM has chosen Affilins, a proprietary technology from Navigo Proteins GmbH, as biological targeting molecules to support its Promethe platform.

Affilins are small proteins derived from human ubiquitin, a protein naturally present in all cells. A huge number of ubiquitin variants are available in large libraries where each variant is modified in a slightly different way on its surface and has lost its natural biological functions but potentially binds to a given target structure. Phage display selection and screening is applied to identify Affilins that bind selectively and with high affinity to the targeted surface antigen, like antibodies. The molecular weight of Affilins is 1/15th of an antibody improving the pharmacokinetics, particularly the distribution and route of elimination which is predominantly through the kidney. Unlike antibodies, Affilins are resistant to proteases, acids and bases and are highly thermostable facilitating their radiolabeling. Because they are human derived, Affilins have a low immunogenicity risk (unwanted immune reaction after injection). The molecules have no post-translational modification like antibodies which allows their production in simple bacterial systems. Affilins are highly engineerable and can be combined with other functional elements, enabling a modular design of molecules, adapted to clinical needs. For all these reasons, Affilin molecules are ideal for use as radiotheranostic targeting molecules.

Navigo Proteins GmbH, a protein engineering company based in Halle, Germany, is headed by a strong and experienced team committed to leveraging Affilin technology in multiple areas. This collaboration will enable OPM and Navigo to build a first-class entity in the field of radioligand therapy based on the complementary strengths of the two companies. Navigo’s Board is composed of leading professors and scientists in the field of radioligand therapy, such as Oliver Buck (co-founder of ITM and member of the board of directors of Telix Pharmaceuticals).

Under the terms of the agreement, research will initially focus on two different targets in the field of oncology, particularly in resistant and metastatic digestive tract tumors, and molecules will be developed to the stage of drug candidates. Oncodesign Precision Medicine will fund this program over the next 3 years. This agreement is a first step towards a strong strategic alliance between OPM and Navigo Proteins GmbH with the vision to expand the partnership to additional targets.

Philippe GENNE, Co-founder, Chairman and CEO of Oncodesign Precision Medicine, said: " This strategic alliance will provide OPM with the opportunity to rapidly develop its portfolio of radiotheranostics and leverage its extensive knowledge and expertise in the discovery of next generation radioligand therapies. This is a promising therapeutic area that will revolutionize the treatment of inoperable and metastatic tumors. We are proud and delighted to benefit from the technology developed by Navigo, our partner in this collaboration, which in addition to its expertise in terms of Affilin engineering, is also a bio-industrial company with the ability to support innovative bioprocessing of Biologics, often a delicate stage in the development of such molecules. Our objective is to build a world-class player in the field of radioligand therapies in the near future."

Jan HOFLACK, Co-Founder and Chief Medical Officer of Oncodesign Precision Medicine added: " Our Promethe technology represents the 3rd key element in our fight against cancers without therapeutic solution. It is highly complementary to our other technologies, Oncosniper and Nanocyclix. These 3 approaches enable us to position ourselves on metastatic and resistant cancers, using immuno-oncology and radiotheranostics. These methods could be used in synergy in the future. Navigo’s Affilins give us access to a cutting-edge platform in terms of targeting vectors. The strengths and expertise of OPM and Navigo are highly complementary, which is the main reason for our alliance. Despite the logistical challenges associated with these radioligand therapy molecules, their potential to act both as imaging diagnostics at low doses and with an appropriate radioisotope, and as therapeutics at higher doses and with an isotope able to annihilate cancer cells, make them tremendous tools to fight cancers without a solution for the benefit of patients."

Henning Afflerbach, CEO of Navigo Proteins GmbH, concludes: "Our collaboration with Oncodesign Precision Medicine provides us with the ideal opportunity to advance our platform in radiotheranostics towards clinical application. Our proprietary Affilin technology offers unparalleled modularity combined with exceptional biodistribution properties making Affilins invaluable tools in our quest to revolutionize cancer treatment. By leveraging OPM’s expertise in preclinical development, targeted oncology and bio-industrial capabilities, we are keen to tackle together key challenges in targeted therapeutics development. Our alliance with OPM underscores the synergy between our strengths and expertise, aiming to deliver innovative solutions that benefit patients worldwide."

About radiotheranostics

This is a radiotherapy technique used in nuclear medicine in the field of oncology. Unlike external radiotherapy, irradiation is targeted by molecules able to bind to tumors. These are radiolabeled and administered intravenously, in the same way as chemotherapy or other targeted therapy. External radiotherapy is currently used in more than 50% of clinical protocols in oncology, but it is only feasible in the case of a single tumor or a limited number of tumors (oligometastases). Radioligand therapies, on the other hand, are well suited for the treatment of disseminated metastases.

Technologically, radioligand therapies are based on the administration of a targeting molecule containing a radioactive isotope (= radiopharmaceutical) aimed at specifically destroying tumors. Its effectiveness comes from the highly localized energy released in radioactive decay, which results in cell death preferentially of tumor cells, while not damaging adjacent healthy tissue. These particle-emitting radioisotopes are directed at targets over-expressed by tumor cells, using highly specific targeting molecules capable of recognizing and attaching to them. The specificity of the targeting molecule for a tumor marker enables healthy tissue to be spared and guarantees greater efficacy while limiting side effects, a strategy that is particularly well suited to disseminated diseases.

One of the advantages of radioligand therapies is the potential to create a theranostic agent, i.e. a radiopharmaceutical which, depending on the nature of the radiation from the chosen isotope, enables diagnostic imaging (prediction/therapeutic monitoring, β+ or γ emitters) or patient therapy (β-, α, auger emitters).

On May 15, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that four abstracts with Innate’s drug candidates have been accepted for the European Association of Hematology (EHA) (Free EHA Whitepaper) 2024 Congress, taking place June 13-16, 2024 in Madrid, Spain (Press release, Innate Pharma, MAY 15, 2024, View Source [SID1234643377]).

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Two abstracts are related to SAR443579 (IPH6101), an investigational trifunctional anti-CD123 NKp46xCD16 NK cell engager from a joint research collaboration between Innate Pharma and Sanofi and currently being evaluated as a monotherapy in a Sanofi-sponsored Phase 1/2 clinical trial for the treatment of blood cancers with high unmet needs.
Two abstracts are related to IPH6501, Innate’s second generation ANKET for the treatment of relapsed or refractory CD20-expressing B-cell Non-Hodgkin’s Lymphoma, currently in Phase 1/2 clinical trial.
"We’re pleased to see a continued momentum around our ANKET platform assets, SAR443579 and IPH6501," said Dr. Sonia Quaratino, Chief Medical Officer of Innate Pharma. "With their innovative format, we believe that NK Cell Engagers will benefit for patients who are in high unmet medical need, and we look forward to continue the studies with these assets."

EHA abstract details:

SAR443579 / IPH6101 (under development by Sanofi)

Abstract: S146
Abstract Title: Completed dose-escalation from the First-in-Human, Phase 1/2 Study of CD123 NK Cell Engager SAR443579 in Relapsed or Refractory Acute Myeloid Leukemia or High Risk-Myelodysplasia
Abstract type: Oral Presentation

Abstract: P475
Abstract Title: Exploring Dose-response Relationship of a Novel CD123 NK Cell Engager SAR443579 in Acute Myeloid Leukemia (AML) Models
Abstract type: Poster Presentation

IPH6501

Abstract: P1251
Abstract Title: Preclinical assessment of IPH6501, a first-in-class IL2V-armed tetraspecific NK Cell Engager directed against CD20 for R/R B-NHL, in comparison with a CD20-targeting T Cell Engager
Abstract type: Poster Presentation
This abstract is embargoed until 23.05.2024 23:00 CEST, until publication by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), Inc. for their 2024 ASCO (Free ASCO Whitepaper) Annual Meeting.

The Abstract PB3041, "A Phase 1/2 trial investigating safety, tolerability, and preliminary antitumor activity of IPH6501, a first-in-class NK Cell Engager, in patients with R/R CD20-expressing NHL" will be available in the EHA (Free EHA Whitepaper) abstracts book.

About ANKET

ANKET (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer. This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.

About IPH6501

IPH6501 is the first Antibody-based NK cell Engager Therapeutic to co-engage activating receptors on NK cells (NKp46 and CD16), IL-2R (but not α subunit) through a variant of human IL-2, and a tumor antigen (CD20) via a single molecule, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells. IPH6501 has shown better anti-tumor efficacy than approved benchmark antibodies in preclinical tumor models (Demaria, EHA (Free EHA Whitepaper) 2023).

About the Innate-Sanofi research collaboration and licensing agreements

The Company has a research collaboration and license agreement with Sanofi to apply Innate’s proprietary technology to the development of innovative multi-specific antibody formats engaging NK cells through the activating receptors NKp46 and CD16 to kill tumor cells.

Under the terms of the 2016 research collaboration and license agreement, Sanofi is responsible for the development, manufacturing and commercialization of products resulting from the research collaboration, which includes SAR443579/IPH6101 (Trifunctional anti-CD123 NKp46xCD16 NK cell engager) and SAR445514/IPH6401 (Trifunctional anti-BCMA NKp46xCD16 NK cell engager). As part of the 2016 agreement, Innate Pharma is eligible to up to €400m in development and commercial milestone payments as well as royalties on net sales.

As part of the license agreement entered in December 2022, Sanofi licensed IPH62 and IPH67 and has the option for one additional target. Under the terms of the 2022 agreement, Innate Pharma is eligible to up to €1.35bn in development and commercial milestone payments as well as royalties on net sales.

On May 15, 2024 Rondo Therapeutics, a biopharmaceutical company pioneering next-generation bispecific antibodies, reported oral presentations at both Protein & Antibody Engineering Summit (PEGS) and Antibody Engineering & Therapeutics (AET) EU (Press release, Rondo Therapeutics, MAY 15, 2024, View Source [SID1234643376]).

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Rondo Therapeutics will describe its immune-cell engaging bispecific antibody platforms and how it is building a clinical pipeline with a focus on treating solid tumors. The company will provide an update on its lead program, RNDO-564, a co-stimulatory T-cell engaging bispecific antibody targeting CD28 and Nectin-4 for the treatment of bladder cancer.

"Presenting our data at PEGS and AET EU represents a significant milestone for our company. This is a golden age for bispecific antibodies and we are delighted to be driving innovation in the field. Targeted signaling through the CD28 pathway is showing a lot of promise as an effective strategy for overcoming the challenges presented by solid tumors. We look forward to sharing our unique approach and commitment to developing novel immunotherapy options for patients with solid tumors," said Shelley Force Aldred, co-founder, and CEO of Rondo Therapeutics.

Presentation Details

Protein & Antibody Engineering Society (Boston, MA)
Date: Wednesday, May 15
Title: Bispecific Antibody Combination Strategies for Treating Solid Tumors
Presenter: Nathan D. Trinklein, PhD, Co-Founder and President, Rondo Therapeutics
Conference Link: https://www.pegsummit.com/

Antibody Engineering & Therapeutics EU (London, UK)
Date: Tuesday, June 5
Title: Co-stimulatory Bispecific Antibody Strategies for Treating Solid Tumors
Presenter: Starlynn Clarke, PhD, Director of Preclinical Biology, Rondo Therapeutics
Conference Link: https://informaconnect.com/antibody-engineering-europe/

On May 15, 2024 TriSalus Life Sciences Inc., (Nasdaq: TLSI), reported its financial results for the first quarter ended March 31, 2024, and provided a business update (Press release, TriSalus Life Sciences, MAY 15, 2024, View Source [SID1234643375]).

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"I’m proud to highlight our strong start in the first quarter of 2024 with 116% growth in revenues compared to the first quarter of 2023 and significantly improving our financial position with our debt financing facility with OrbiMed," said Mary Szela, Chief Executive Officer of TriSalus. "With our recent positive developments in reimbursement, clinical data, and the dedication of our seasoned executive team, we’re confident in our ability to execute our company-building strategy. Our objectives of achieving over 50% top-line revenue growth, advancing our pipeline, and strengthening our operational foundations remain firmly on track."

First Quarter 2024 and Subsequent Highlights

Secured up to $50 million of debt financing with OrbiMed to support TriNav Infusion System growth initiatives

In April, TriSalus announced the closing of a debt financing facility with OrbiMed, a healthcare investment firm. Under the terms of the Credit Agreement with OrbiMed, the Company borrowed $25 million at closing. In addition, an aggregate of up to an additional $25 million is available in two tranches at the Company’s option, subject to the Company’s achievement of certain revenue thresholds.

The $25 million draw, along with cash and cash equivalents on hand of $4 million at March 31, 2024, are expected to provide sufficient cash runway to fund the Company’s operations through the end of 2024. Including our SEPA agreement and other existing sources of liquidity and assuming we achieve the revenue targets and borrow the remaining $25 million of the debt financing, the Company expects to have sufficient cash runway to fund operations through the end of 2025.

Liselotte Hyveled appointed to the Board of Directors

In May, TriSalus announced the appointment of Liselotte Hyveled to its Board of Directors. Ms. Hyveled currently serves as the Chief Patient Officer at Novo Nordisk, where she is responsible for ensuring the integration of patient needs and perspectives into the company’s decision-making processes and operations. She brings over two decades of experience stimulating scientific innovation and advancing pharmaceutical pipelines through research and development excellence.

Financial Results for Q1 2024

Revenue, all of which is from the sale of the TriNav Infusion System, was $6.5 million in the first quarter ended March 31, 2024. This amount represents growth of 116% compared to the first quarter of 2023, primarily due to increased selling resources and continued market share increases.

Gross margins were 85% in the first quarter ended March 31, 2024, versus 78% in the first quarter of 2023. The improvement is due to increased factory volumes and improved operations efficiency.

Operating losses were $11.7 million in the first quarter ended March 31, 2024, versus $10.1 million in the first quarter of 2023. Increased investment in sales and marketing, research and development, as well as general and administrative costs associated with becoming a public company more than offset increased gross profit in 2024.

Net losses available to common stockholders were $13.2 million in the first quarter ended March 31, 2024, versus $8.3 million in the first quarter of 2023. Net losses in 2024 include the impact of non-cash related gains/(losses) on change in fair value of SEPA and warrant liabilities of $2.5 million and change in fair value of contingent earnout liabilities of ($4.0) million. Net losses in 2023 include the impact of non-cash related gains/(losses) on equity issuance of ($1.5) million, extinguishment of tranche liabilities of $0.9 million, and change in fair value of SEPA and warrant liabilities of $2.4 million.

Basic and diluted loss per share for the first quarter ended March 31, 2024, was $0.60 versus $0.57 per share in the first quarter of 2023.

Conference Call

The event will be webcast live on the investor relations section of TriSalus’ website at View Source on May 15, 2024, at 9:00 a.m. EDT. Following the conclusion of the event, a webcast replay will be available on the website for approximately 90 days. Interested parties participating by phone will need to register using this online form. After registering for the webcast, dial-in details will be provided in an auto-generated e-mail containing a link to the conference phone number along with a personal pin.