On June 4, 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 that it has entered into a clinical trial collaboration and supply agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA), through a subsidiary, to evaluate eftilagimod alfa (efti) in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) and chemotherapy for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in a pivotal Phase III trial (Press release, Immutep, JUN 4, 2024, View Source [SID1234644091]).

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The potential for efti in combination with KEYTRUDA and chemotherapy is to set a new standard of care, by strengthening clinical outcomes for responders and broadening the number of patients who respond across the entire NSCLC patient population regardless of PD-L1 expression.

TACTI-004 (Two ACTive Immunotherapies-004) Registrational Phase III Trial Design

TACTI-004 will be a 1:1 randomised, double-blind, multinational, controlled clinical study to evaluate Immutep’s efti in combination with KEYTRUDA and standard chemotherapy compared to the standard-of-care combination of KEYTRUDA, chemotherapy and placebo in first-line metastatic NSCLC, regardless of PD-L1 expression. In this pivotal PD-L1 all comer trial, the dual primary endpoints will be progression-free and overall survival with a prespecified futility boundary and a pre-planned interim analysis. The globally conducted study will enrol approximately 750 NSCLC patients (including both squamous and non-squamous subtypes).

Building on Encouraging Data from Prior Trials

"We are eager to build upon the meaningful impact that immunotherapy has brought to patients with NSCLC, one of the largest cancer indications globally, and look for TACTI-004 to confirm the clinical benefits that have been achieved with efti in combination with KEYTRUDA. This collaboration agreement speaks to the strength of the clinical data generated to date from this novel immuno-oncology combination and its future potential. We are thankful for this significant commitment from MSD," stated Marc Voigt, CEO of Immutep.

This collaboration follows two previous collaborations for the TACTI-002 Phase II and TACTI-003 Phase IIb trials, which collectively treated over 350 patients. Under the terms of the agreement, Immutep will conduct the registrational TACTI-004 study and MSD will supply KEYTRUDA. The agreement enables Immutep and MSD to seek marketing authorisation of the combination and to market their respective compounds with a relevant label indication. The parties retain the commercial rights to their respective compounds and are free to conduct other clinical studies, either individually or in combination, in any therapeutic area.

The clinical data generated by the innovative immuno-oncology combination of Immutep’s MHC Class II agonist and MSD’s anti-PD-1 therapy in the TACTI-002 Phase II trial in first-line NSCLC regardless of PD-L1 expression has led to oral presentations at the ASCO (Free ASCO Whitepaper), SITC (Free SITC Whitepaper), and ESMO (Free ESMO Whitepaper) conferences. Efti’s unique activation of dendritic cells (the most potent professional antigen-presenting cells) engages the adaptive and innate immune system to drive a broad anti-cancer immune response, including proliferation of cytotoxic T cells that complements anti-PD-1 therapy in first-line NSCLC across all levels of PD-L1 expression (negative, low, and high).

Notably, over 75% of the patients in both the TACTI-002 and INSIGHT-003 clinical trials had a PD-L1 Tumor Proportion Score (TPS) of <50%, and both studies have shown strong efficacy in these patients with low and negative PD-L1 expression who are typically less responsive to anti-PD-1 therapy. Furthermore, the triple combination of efti, KEYTRUDA and carboplatin/pemetrexed in INSIGHT-003 has been well tolerated.

"KEYTRUDA has revolutionized the treatment landscape in NSCLC and our confidence in efti’s ability to build upon its positive impact on patient outcomes, and potentially expand the number of responding patients, stems from the compelling data in our TACTI-002 and INSIGHT-003 trials. We are excited to confirm the differentiated efficacy and safety that we have seen to date in NSCLC via efti’s first pivotal Phase III study and TACTI-004’s robust randomized, double-blind trial design," added Christian Mueller, Immutep’s SVP, Regulatory and Strategy.

Lung cancer is the second most common cancer. Non-small cell lung cancer accounts for approximately 80-85% of all lung cancers, impacting an estimated 1.87 million people annually, and is the highest cause of death among all cancers1-3.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Eftilagimod Alfa (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-ϒ 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 June 4, 2024 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported positive updated results from its Phase 2 clinical trial of HB-200 in combination with pembrolizumab in patients with recurrent/metastatic human papillomavirus 16 positive (HPV16+) head and neck cancer (Press release, Hookipa Biotech, JUN 4, 2024, View Source [SID1234644090]).

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The updated data presented at the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting is as of March 29, 2024 (cutoff date) and includes 46 patients treated with HB-200 plus pembrolizumab in the first line setting. Results showed rapid and durable activation of antigen-specific CD8+ T cells and promising clinical activity.

Among 35 evaluable patients data showed a 37 percent confirmed objective response rate (ORR), 11 percent complete response (CR) rate, and 69% disease control rate (DCR), per RECIST 1.1 criteria. Duration of response was not yet mature with 62 percent of responders still on treatment as of the cutoff date.

In a subset of 17 evaluable patients with CPS of 20 or higher, the updated data showed a 53 percent confirmed ORR, 18 percent CR rate, and 82 percent DCR. These patients are representative of the Company’s planned pivotal Phase 2/3 trial population, which is targeted to begin enrolling patients in the fourth quarter of 2024.

Additionally, preliminary PFS for the CPS 20 or higher subgroup was 16.3 months and is encouraging based on the historical PFS data of 3.4 months reported for pembrolizumab alone1. The preliminary OS rate was 88% at 9 months, and median OS was unreached as of the cutoff date with 16 of 19 patients still alive. Median follow-up for these patients was 8.4 months.

"Based on the evidence from the Phase 2 trial of HB-200 plus pembrolizumab, I am encouraged by the potential this immunotherapy combination may provide as a targeted therapeutic option for HPV16+ head and neck cancer patients," said Dr. Alan Ho, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator. "The data show that this combination has been generally well-tolerated and can likely increase immunogenic tumor cell death, leading to improved response rates and potential durability."

"HPV16+ disease is a unique indication that requires a patient-centric and targeted therapeutic approach. HB-200 plus pembrolizumab has shown to be a potentially powerful combination that has consistently delivered positive outcomes for our patients," said Joern Aldag, Chief Executive Officer of HOOKIPA. "Among published data in HPV+ disease, HOOKIPA has a best-in-class asset with the HB-200 combination. We also have alignment on a clinical development strategy with the U.S. Food and Drug Administration with a path to potential accelerated approval. Importantly, our pivotal seamless Phase 2/3 trial is just the beginning—our platform continues to demonstrate the potential power of arenaviral-based immunotherapies to help provide targeted treatments for patients across disease areas and indications."

Call Details:
HOOKIPA HB-200 ASCO (Free ASCO Whitepaper) Data Update
Tuesday, June 4, 2024, 4:15 p.m. ET
Webcast Registration
Dial-in Registration

Results:
HB-200 in combination with pembrolizumab:
Data were presented as of March 29, 2024, and included 46 first line patients with HPV16+, PD-L1 positive, recurrent or metastatic head and neck squamous cell carcinoma. The updated data continue to demonstrate a favorable safety profile of HB-200 in combination with pembrolizumab and promising clinical activity as a first line treatment.

HB-200 + pembrolizumab was generally well tolerated. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 7 (15%) patients, serious TRAEs in 2 (4%) patients, and TRAEs leading to treatment discontinuation of HB-200 in 2 (4%) patients. No treatment-related deaths were reported.

Among 35 evaluable patients, 4 confirmed complete responses, 9 confirmed partial responses, and 11 confirmed stable disease were observed. Notably, among patients with PD-L1 CPS ≥20 (N=17), ORR was 53% (9/17), complete response rate was 18% (3/17), and DCR was 82% (14/17). All responses were confirmed per RECIST 1.1. Preliminary PFS for the CPS 20 or higher subgroup was 16.3 months. The preliminary OS rate was 88% at 9 months, and median OS was unreached as of the cutoff date with 16 of 19 patients still alive. Median follow-up for these patients was 8.4 months.

Abstract details: ASCO (Free ASCO Whitepaper) 2024 Annual Meeting
Title: HB-200 arenavirus-based immunotherapy plus pembrolizumab as first-line treatment of patients with recurrent/metastatic HPV16-positive head and neck cancer: Updated results
Presenter: Dr. Alan L. Ho, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator
Abstract Type: Oral abstract
Session Name: Head and Neck Cancer
Session Date and Time: June 4, 2024; 9:45 AM-12:45 PM CDT
Abstract Number: 6005

About HB-200
HB-200 is HOOKIPA’s lead oncology candidate engineered with the company’s proprietary replicating arenaviral vector platform. It comprises two single-vector compounds with arenaviral backbones based on lymphocytic choriomeningitis virus (LCMV) and pichinde virus (PICV). Both express the same transgene encoding an E7E6 fusion protein derived from HPV16. HB-200 is an alternating 2-vector immunotherapy designed to further focus the immune response against the encoded antigen.

HB-200 in combination with pembrolizumab received Fast Track Designation from the U.S. Food and Drug Administration and PRIME designation from the European Medicines Agency for the treatment of first-line HPV16+ recurrent/metastatic oropharyngeal squamous cell carcinoma. These designations are supported by preliminary clinical evidence from the Phase 1/2, open-label, clinical trial (NCT04180215) evaluating safety, T cell response, and efficacy based on objective response rate (ORR) and disease control rate (DCR) as defined by RECIST 1.1.

1 Harrington et al. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Journal of Clinical Oncology. 2023;41(4);790-802.

On June 4, 2024 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported that management will be participating in the following investor and scientific conferences (Press release, Gritstone Bio, JUN 4, 2024, View Source [SID1234644088]):

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Goldman Sachs 45th Annual Global Healthcare Conference (Fireside Chat*)
Date and Time: Tuesday, June 11, 2024 at 1:20pm ET
Location: Miami, FL

JonesHealthcare Seaside Summit 2024 (1x1s)
Dates: Monday, July 15 – Tuesday, July 16
Location: Encinitas, CA

4th Annual mRNA-Based Therapeutics Summit (Panel)
Panel Title: Unpacking 2024’s Successes & Anticipating the Next Challenges to Advance the Future of mRNA-Based Therapeutics & Vaccines
Date and Time: Tuesday, July 30, 2024 at 8:30am ET
Location: Boston, MA

Select events (marked by *) will be webcasted live and webcast details will be available on the ‘Events’ page of Gritstone bio’s website: View Source Archived replays will be accessible for 30 days following each event.

On June 4, 2024 GlycoMimetics, Inc. (Nasdaq: GLYC), a late clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers and inflammatory diseases, reported comprehensive results from the company’s pivotal Phase 3 study of uproleselan in R/R AML (Press release, GlycoMimetics, JUN 4, 2024, View Source [SID1234644087]).

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"There is a wealth of data across large subsets of this pivotal Phase 3 study that help us understand how prespecified stratification factors such as backbone chemotherapy, disease status, and age impacted survival outcomes for patients," said Daniel DeAngelo, M.D., Ph.D., Professor of Medicine, Harvard Medical School, Chief, Division of Leukemia, Dana-Farber Cancer Institute, and Principal Investigator of the pivotal Phase 3 study. "In the primary refractory setting, uproleselan’s improvement of mOS and greater duration of remission were particularly compelling, as there is a significant unmet need for new treatment options in this setting that can extend and improve the lives of patients. These results demonstrate uproleselan has the potential to address this unmet need in primary refractory AML."

"As we have analyzed data from this large, well-balanced, and well-executed study alongside medical, statistical, and regulatory experts, it has become clear that uproleselan may offer clinically meaningful patient benefit in multiple settings, including primary refractory AML," said Harout Semerjian, Chief Executive Officer of GlycoMimetics. "We are committed to addressing unmet needs of AML patients and plan to engage with regulators and NCI to discuss potential paths forward for uproleselan."

Results of Pivotal Phase 3 Study of Uproleselan in R/R AML

The randomized, double-blind, placebo-controlled Phase 3 clinical study evaluated uproleselan in combination with MEC (mitoxantrone, etoposide and cytarabine) or FAI (fludarabine, cytarabine and idarubicin) in patients with R/R AML. Patients received either uproleselan or placebo for 8 days over 1 cycle of induction and, if applicable, up to 3 cycles of consolidation. The primary endpoint was overall survival (OS), which was not censored for transplant. Secondary endpoints included incidence of severe oral mucositis, complete remission (CR) rate and CR with partial hematologic recovery (CRh). A total of 388 patients in nine countries were randomized 1:1 between treatment and placebo arms. There were 59 sites that enrolled at least one patient. Median follow up was over three years at the time of primary analysis.

Overall Survival

Primary Endpoint: mOS in the intent-to-treat (ITT) population (n=388) was 13.0 months for the uproleselan arm, compared to 12.3 months for the placebo arm (hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.69-1.15); this difference is not statistically significant.
Disease Status
Primary Refractory: mOS for primary refractory patients in the uproleselan arm (n=62) was 31.2 months, compared to 10.1 months (HR 0.58; 95% CI 0.37-0.91) for the placebo arm (n=66). This benefit was irrespective of backbone chemotherapy.
Median duration of response (DoR) for complete remission (CR) was not reached for primary refractory patients in the uproleselan arm compared to a median DoR of 12.7 months for the placebo arm.
Early Relapse: mOS for early relapse patients in the uproleselan arm (n=28) was 3.7 months, compared to 6.4 months (HR 1.50; 95% CI 0.69-3.27) for the placebo arm (n=22).
Late Relapse: mOS for late relapse patients in the uproleselan arm (n=104) was 15.4 months, compared to 18.2 months (HR 1.10; 95% CI 0.77-1.57) for the placebo arm (n=106).
Backbone Chemotherapy:
FAI: mOS for patients treated with uproleselan plus FAI (n=98) was 30.2 months compared to 12.8 months (HR 0.73; 95% CI 0.50-1.06) for patients treated with FAI alone (n=96) in the ITT population.
MEC: mOS for patients treated with uproleselan plus MEC (n=96) was 8.7 months compared to 12.3 months (HR 1.06; 95% CI 0.75-1.51) for patients treated with MEC alone (n=98) in the ITT population.
Transplantation Status:
For patients who received hematopoietic stem cell transplantation (HSCT) after study treatment, mOS was not reached for patients in the uproleselan arm (n=101). In contrast, for HSCT patients in the placebo arm, mOS for patients receiving FAI (n=53) was 26.3 months and for patients receiving MEC (n=46) was 24.4 months.
Secondary Endpoints

7.2% of patients in each arm (n=388) experienced induction emergent severe oral mucositis.
36.1% of patients in the uproleselan arm (n=194) experienced CR at the end of induction (EOI) as determined by an independent endpoint review committee (IERC), compared to 33.5% of patients in the placebo arm (n=194).
46.4% of patients in the uproleselan arm experienced CR/CRh at EOI as determined by IERC, compared to 41.2% of patients in the placebo arm.
Post-treatment HSCT rate was 52.1% in the uproleselan arm and 51.0% in the placebo arm.
Subsequent AML therapy in non-responders was 40.0% in the uproleselan arm (n=80) and 46.2% in the placebo arm (n=78).
Safety

Adverse events were consistent with the known safety profile for backbone chemotherapy regimens.
35.9% of patients in the uproleselan arm experienced serious treatment-emergent adverse events (TEAEs) compared to 34.2% in the placebo arm.
85.9% of patients in the uproleselan arm experienced grade 3 or higher TEAEs compared to 87.6% in the placebo arm.
NCI Phase 2/3 Study of Uproleselan in Frontline AML

In addition to the company’s pivotal Phase 3 trial of uproleselan, the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology are conducting an adaptive Phase 2/3 study of uproleselan in adults with newly diagnosed AML who are 60 years or older and fit for intensive chemotherapy. Their randomized, controlled study is evaluating the addition of uproleselan to a standard cytarabine / daunorubicin regimen (7+3) versus chemotherapy alone. The Phase 2 portion of the study completed enrollment of 267 patients in December 2021. The Company is advancing discussions with the NCI and the Alliance for Clinical Trials in Oncology based on the results of the pivotal Phase 3 study of uproleselan in R/R AML.

Conference Call Details

To access the call by phone, please go to this registration link and you will be provided with dial in details. Participants are encouraged to connect 15 minutes in advance of the scheduled start time.

A live webcast of the call and the corresponding slides will be available on the "Investors" tab on the GlycoMimetics website. A webcast replay will be available for 30 days following the call.

About AML

AML is the most common acute leukemia in adults. A cancer of the bone marrow, nearly 21,000 people in the United States are diagnosed with AML each year. Despite the availability of multiple treatments, disease prognosis is poor, and new treatment options are needed to improve outcomes. Newly diagnosed AML has the lowest 5-year survival rate of all leukemias at 31.7%. The five-year survival rate for people with relapsed/refractory disease is only 10%.

About Uproleselan

Discovered and developed by GlycoMimetics, uproleselan (yoo’ pro le’se lan) is an investigational, first-in-class E-selectin antagonist. GlycoMimetics has received Breakthrough Therapy and Fast Track designations from the U.S. Food and Drug Administration (FDA) and Breakthrough Therapy designation from the Chinese National Medical Products Administration for uproleselan as a potential treatment for adult AML patients with relapsed or refractory disease. E-selectin is a leukocyte adhesion molecule constitutively expressed on endothelial cells of the vasculature and bone marrow. In AML, there is evidence that E-selectin–ligand interaction between endothelial cells in the protective niche of the Bone Marrow microEnvironment (BME) and leukemic stem cells and blasts promotes leukemic cell survival and hides them from AML therapies. Uproleselan is designed to disrupt E-selectin binding and prevent leukemic myeloid cells using the protective niche of the BME.

On June 4, 2024 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radioconjugates (RCs), reported the successful completion of the acquisition of all of the issued and outstanding shares of Fusion by a wholly-owned subsidiary of AstraZeneca AB by way of a statutory plan of arrangement under section 192 of the Canada Business Corporations Act, referred to as the Arrangement (Press release, Fusion Pharmaceuticals, JUN 4, 2024, View Source [SID1234644085]). The Arrangement marks a major step forward in AstraZeneca delivering on its ambition to transform cancer treatment and outcomes for patients by replacing traditional regimens like chemotherapy and radiotherapy with more targeted treatments.

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The Arrangement complements AstraZeneca’s leading oncology portfolio with the addition of the Fusion pipeline of RCs, including their most advanced program, FPI-2265, a potential new treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), and brings new expertise and pioneering R&D, manufacturing and supply chain capabilities in actinium-based RCs to AstraZeneca. The Arrangement is also expected to strengthen AstraZeneca’s presence in and commitment to Canada.

As a result of the Arrangement, Fusion has become a wholly owned subsidiary of AstraZeneca, with operations continuing in Canada and the US. Fusion shares will be delisted from the Nasdaq Stock Market and deregistered under the U.S. Securities Exchange Act of 1934. Fusion has submitted an application to cease to be a reporting issuer under applicable Canadian securities laws and to otherwise terminate Fusion’s Canadian public reporting requirements.

Financial Considerations

Under the terms of the definitive agreement, AstraZeneca, through a subsidiary, has acquired all of Fusion’s outstanding shares pursuant to the Arrangement for a price of $21.00 per share in cash at closing plus a non-transferable contingent value right of $3.00 per share in cash payable upon the achievement of a specified regulatory milestone prior to August 31, 2029. Combined, the upfront payment and maximum potential contingent value payment, if achieved, represent a transaction value of approximately $2.4 billion. As part of the Arrangement, AstraZeneca acquired the cash, cash equivalents and short-term investments on Fusion’s balance sheet, which totaled $211 million as of March 31, 2024.

The upfront consideration has been provided to Equiniti Trust Company, LLC, as depositary under the Arrangement, and, along with the contingent value rights, will be delivered to former securityholders (as applicable) of Fusion as soon as practicable on or after the date hereof.