On December 17, 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 favourable initial safety data from the placebo-controlled, double-blind first-in-human Phase I study evaluating IMP761 (Press release, Immutep, DEC 17, 2024, View Source [SID1234649141]). Through the first three of five single ascending dose cohorts in healthy participants, there have been no treatment related adverse events.

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Dr. Frédéric Triebel, CSO of Immutep, said: "We are very encouraged by the safety data generated to date for IMP761, the world’s first LAG-3 agonist antibody, in this Phase I setting. Derisking this promising asset in this proof-of-concept study in healthy subjects assessing its safety and immunosuppressive efficacy on an antigenspecific T-cell mediated intra-dermal reaction is an important step for this exciting program in autoimmune diseases. Given that IMP761 is potentially addressing the root cause of many different autoimmune diseases, we are eager to see this study generating more data."

The trial in up to 49 participants is being conducted by the Centre for Human Drug Research (CHDR) in Leiden, the Netherlands. In addition to the safety analysis, CHDR is implementing its keyhole limpet haemocyanin (KLH) challenge model to evaluate IMP761’s pharmacological activity. Additional safety data and assessment of pharmacokinetic/pharmacodynamic (PK/PD) relationships to follow in the first half of CY2025.

The LAG-3 (lymphocyte-activation gene-3) immune checkpoint has been identified as a promising target for an agonist antibody to treat rheumatoid arthritis, Type 1 diabetes, and multiple sclerosis, among potentially many other autoimmune diseases.1,2,3 This first-in-class agonist LAG-3 antibody is designed to restore balance to the immune system by enhancing the "brake" function of LAG-3 to silence dysregulated self-antigenspecific memory T cells that cause many autoimmune diseases. In preclinical studies, IMP761 has led to a large decrease in inflammatory cytokines and demonstrated its effectiveness in suppressing antigen-specific T cell–mediated immune responses.4

On December 17, 2024 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported financial results for the fiscal year ended September 30, 2024 and provided a corporate update (Press release, Sonnet BioTherapeutics, DEC 17, 2024, View Source [SID1234649161]).

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"We are very pleased with the progress we have made across all facets of the company’s operations. On the financial front, we have delivered on our stated objective of cutting costs through an approximate 37% reduction in total operating expenses versus last year, which will help to extend our cash runway, combined with being able to leverage non-dilutive funding and capital markets financings. Additionally, we have executed on our partnership plans to advance both our SON-080 program and SON-1210 program to their respective next stages of development and continue to believe in their potential to address indications of significant unmet need," commented Pankaj Mohan, Ph.D., Founder and Chief Executive Officer of Sonnet. "Looking ahead, our focus is on advancing our lead program, SON-1010, and we are pleased to be on track for key data readouts from our ongoing SB101 trial for solid tumors and our SB221 trial for PROC. We look forward to the upcoming data readouts to help further unlock the intrinsic value of our FHAB technology platform."

Recent Highlights

● Announced topline safety data following successful completion of SON-1010 monotherapy dose escalation in the Phase 1 SB101 trial;

● Announced the publication of extensive discovery, development, and preclinical data regarding SON-1010, demonstrating its mechanism of action in a paper entitled, "SON-1010: an albumin-binding IL-12 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy," in Frontiers in Immunology;

● Granted U.S. Patent No. 12,134,635 covering two of its novel drug candidates, SON-1411 (IL-18BPR-FHAB-IL12) and SON-1400 (IL-18BPR-FHAB), each containing a modified version of recombinant human interleukin-18 (BPR = Binding Protein Resistant);

● Entered into a licensing agreement with Alkem Laboratories Limited for the research, development, manufacturing, marketing, and commercialization of the SON-080 molecule for the treatment of DPN in India;

● Received preliminary approval for the sale of tax credits from the New Jersey Technology Business Tax Certificate Transfer Program administered by the New Jersey Economic Development Authority (NJEDA); and

● Entered into a Master Clinical Collaboration Agreement with the Sarcoma Oncology Center to advance the development of SON-1210 in combination with chemotherapy for the treatment of metastatic pancreatic cancer.

Lead Clinical Programs Update

SON-1010: Targeted Immune Activation Cancer Therapy, Turning ‘Cold’ Tumors ‘Hot’, Initially Targeting Solid Tumors and Platinum-Resistant Ovarian Cancer (PROC)

Phase 1 Trial (SB101 Trial): Advanced Solid Tumors (Monotherapy)

This first-in-human study is primarily designed to evaluate the safety, tolerability, PK, and PD of multiple ascending doses of SON-1010 in cancer patients and is being conducted at several sites across the United States. The Company recently completed enrollment and dose escalation in the Phase 1 SB101 clinical trial of SON-1010 (IL12-FHAB) in adult patients with advanced solid tumors. Additionally, the Company reported that results of SON-1010 at the highest dose have been formally evaluated by the Safety Review Committee. The study has enrolled 24 subjects to date. Primary outcome measures for the study were to evaluate the safety and tolerability of SON-1010 and establish the MTD.

For more information about the SB101 clinical trial, visit clinicaltrials.gov and reference identifier NCT05352750.

Phase 1b/2a Trial (SB221 Trial): Advanced Solid Tumors and PROC (Combo with Atezolizumab)

The second trial is a global Phase 1b/2a multicenter, dose-escalation and randomized proof-of-concept study to assess the safety, tolerability, PK, PD, and efficacy of SON-1010 administered subcutaneously (SC) in combination with atezolizumab given intravenously (IV) (in collaboration with Genentech, a member of the Roche Group). This study was recently expanded to include the MTD of SON-1010 from SB101. Enrollment remains ongoing and an update on safety at the MTD in that trial is expected in Q1 2025.

For more information about the SB221 clinical trial, visit clinicaltrials.gov and reference identifier NCT05756907.

SON-1010 Upcoming Milestones

● Phase 1: Solid Tumors (Monotherapy)

○ H1 calendar year 2025: Topline Efficacy Data

● Phase 1b/2a: PROC (Combo with Atezolizumab)

○ Q1 calendar year 2025: Additional Safety Data
○ H2 calendar year 2025: RP2D & Topline Efficacy Data

SON-1210: Proprietary, Bifunctional Version of Human Interleukins 12 (IL-12) and 15 (IL-15), Configured Using Sonnet’s Fully Human Albumin Binding (FHAB) platform, in Combination with Chemotherapy for the Treatment of Advanced Solid Tumors and Metastatic Pancreatic Cancer

As previously announced, the Company successfully completed two IND-enabling toxicology studies of SON-1210 in non-human primates (NHPs), which demonstrated no overt toxicity in the GLP study apart from the expected and mild, on-target changes in hematology and clinical chemistry parameters that resolved completely within 14 to 21 days post-dosing. A significant increase in interferon gamma (IFNγ), which was controlled and prolonged, was noted as early as one day following administration, with no apparent increase in other proinflammatory cytokines. IFNγ is a well-known pharmacodynamic biomarker that is required for anti-tumor efficacy in preclinical models. Other signs of cytokine imbalance, or uncontrolled increase of pro-inflammatory cytokines (including TNF-α, IL-1β, and IL-6) were notably absent from all dose levels tested in the study.

In August 2024, the Company entered into a Master Clinical Collaboration Agreement with the Sarcoma Oncology Center, to conduct an investigator-initiated Phase 1/2a clinical study to evaluate SON-1210 in combination with several chemotherapeutic agents including but not limited to NALIRIFOX (the combination of liposomal irinotecan, 5-fluorouracil/leucovorin, and oxaliplatin) for the specific treatment of metastatic pancreatic cancer. The NALIRIFOX regimen is U.S. FDA-approved for the treatment of metastatic pancreatic cancer in the front-line and refractory settings.

SON-1210 Upcoming Milestones

● Q1 calendar year 2025: IND Submission
● H1 calendar year 2025: 1st Patient Dosed in Investigator-Initiated Phase 1/2a Study

SON-080: Low dose of rhIL-6 for Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Diabetic Peripheral Neuropathy (DPN)

In October 2024, the Company entered into a licensing agreement (the "Licensing Agreement") with Alkem Laboratories Limited ("Alkem") for the research, development, manufacturing, marketing, and commercialization of its SON-080 molecule for the treatment of DPN in India and the manufacturing, marketing, and commercialization of SON-080 for chemotherapy induced neuropathy (CIPN) and autonomic neuropathy in India. Alkem will conduct all clinical trials it believes appropriate to obtain regulatory approval in India of SON-080 for the treatment of DPN.

Summary of Financial Results for the Fiscal Year 2024

As of September 30, 2024, Sonnet had $0.1 million cash on hand. The Company believes that based on cash on hand at September 30, 2024, together with the approximate $7.7 million recently received through the sale of common stock and warrants in November and December 2024, $0.7 million received from the R&D Tax Incentive Program in Australia in November 2024 to satisfy the Company’s incentive tax receivable, and $0.5 million received in October 2024 as an upfront payment related to the License Agreement, which after tax withholdings resulted in a net payment of $0.4 million, it has sufficient funds for projected operations into July 2025.

Research and development expenses were $5.7 million for the year ended September 30, 2024, compared to $11.8 million for the year ended September 30, 2023.

General and administrative expenses were $6.1 million for the year ended September 30, 2024, compared to $7.1 million for the year ended September 30, 2023.

On December 17, 2024 Plus Therapeutics, Inc. (Nasdaq: PSTV) ("Plus" or the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system cancers, reported data updating the progress of its ReSPECT-LM Phase 1 clinical trial of Rhenium (186Re) Obisbemeda (Rhenium Nanoliposome, 186RNL) in leptomeningeal disease (LM) with a specific focus on breast cancer patients (Press release, Plus Therapeutics, DEC 17, 2024, View Source [SID1234649162]). The data were presented at the 2024 San Antonio Breast Cancer Symposium on December 10-13.

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The data were presented in a session titled "Rhenium (186Re) Obisbemeda (Rhenium Nanoliposome, 186RNL) for the Treatment of Leptomeningeal Metastases (LM): Update on Phase 1 Dose Escalation Study," by Andrew Brenner, M.D., Ph.D., Professor and Kolitz/Zachry Endowed Chair Neuro-Oncology Research; Co-Leader, Experimental and Developmental Therapeutics Program, University of Texas Health, San Antonio.

Key Highlights from the Presentation:

Nine of 20 patients with LM primary breast cancer were treated and evaluable through five dose escalation cohorts, with the maximum tolerated dose yet to be reached
Primary breast cancer biomarker status across the 9 patients were:
ER positive/HER2 negative: n=3
HER2 positive: n=2
Triple negative: n=4
Patients received a single intrathecal dose of Rhenium (186Re) Obisbemeda, ranging from 6.6 to 66.14 mCi of radiation
Only one dose-limiting toxicity (thrombocytopenia) was reported (Cohort 5)
A linear increase in absorbed dose was observed from Cohorts 1 through 5, with an average absorbed dose of 253 Gy to the cranial subarachnoid space in Cohort 5
Circulating tumor cell (CTC) and radiographic (MRI) response data were available for 8 of the 9 breast cancer patients with LM, and clinical response data were available for 7 of the 9 patients
Best response rates (response only) were:
CTC: 88% (7/8)
MRI imaging: 25% (2/8)
Clinical: 29% (2/7)
Clinical benefit rates (response and stable disease) were:
CTC: 100% (8/8)
MRI imaging: 75% (6/8)
Clinical: 71 % (5/7)
Median overall survival for 9 breast cancer patients was 9 months, with 2 patients surviving beyond 600 days post-treatment
Next steps:

Initiate ReSPECT-LM Phase 1b single-dose breast expansion cohort in Q1 2025 to further evaluate single-dose safety and efficacy of Rhenium (186Re) Obisbemeda
"Breast cancer is the most common primary cancer associated with leptomeningeal metastases," said Marc H. Hedrick, M.D., Plus Therapeutics’ President and Chief Executive Officer. "Based on the promising data observed thus far, we intend to move forward rapidly into a breast cancer focused expansion cohort along with our planned multiple dose expansion trial."

About Leptomeningeal Metastases (LM)
LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells; yet, there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

About Rhenium (186Re) obisbemeda
Rhenium (186Re) obisbemeda is a novel injectable radiotherapy specifically formulated to deliver direct targeted high dose radiation in CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. Rhenium (186Re) obisbemeda has the potential to reduce off target risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue, and gamma energy for real-time imaging. Rhenium (186Re) obisbemeda is being evaluated for the treatment of recurrent glioblastoma and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).

On December 17, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) and Terray Therapeutics, Inc. reported that the companies have entered into a strategic collaboration to discover and develop novel, small molecule therapies across multiple targets (Press release, Gilead Sciences, DEC 17, 2024, View Source [SID1234649163]).

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Terray’s tNova platform combines high-throughput chemical experimentation and computational analysis with a generative AI-driven drug discovery engine. The company’s iterative approach applies AI-empowered methods to an extensive library of quantitative, purpose-built, structure activity data to find the right molecules to solve complex problems in drug discovery.

"Next-generation, AI-driven platforms using custom-generated large, relevant data sets will serve as important tools in our efforts to shape the future of drug discovery in our ongoing pursuit of innovative treatments across our therapeutic areas of focus," said Flavius Martin, M.D., Executive Vice President, Research, Gilead Sciences. "We are excited to collaborate with Terray and explore how their integrated discovery platform will complement our own internal research capabilities and expertise."

"We’re proud to strategically partner with Gilead," said Jacob Berlin, Ph.D., Chief Executive Officer, Terray Therapeutics. "We’re very excited to put tNova’s unique blend of experimentation and computation to work alongside the deep expertise of our collaborators at Gilead to find transformational small molecule therapeutics that bring relief to patients in need."

Terms of the Agreement

Under the terms of the agreement, Terray will utilize the Terray tNova platform to discover and develop small molecule compounds against a set of targets selected by Gilead. If Gilead exercises its option to exclusively license the compounds directed to a target, Gilead will be responsible for further development and commercialization activities for products resulting from the collaboration. Terray will receive an upfront payment and is eligible to receive milestone payments associated with the achievement of preclinical, clinical, and sales milestones as well as tiered royalties on net sales of products commercialized by Gilead in connection with the collaboration.

Gilead does not exclude acquired IPR&D expenses from its non-GAAP financial measures. This transaction with Terray is expected to reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $0.01.

On December 17, 2024 Akamis Bio, a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene (T-SIGn) therapy platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, reported $60 million in funding linked to the close of a Series A Prime financing round and entry into a strategic partnership for the development of its lead clinical candidate, NG-350A (Press release, Akamis Bio, DEC 17, 2024, View Source [SID1234649185]).

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The new funding will support the company’s work to advance NG-350A through a Phase 1b clinical proof-of-concept (PoC) study in patients with locally advanced rectal cancer (LARC). NG-350A is an intravenously delivered, transgene-armed tumor gene therapy designed to drive intratumoral expression of a CD40 agonist monoclonal antibody in both primary and metastatic epithelial-derived solid tumors. The Phase 1b PoC study, known as FORTRESS (NCT06459869), will evaluate clinical complete response (cCR) rates to NG-350A in combination with chemoradiotherapy (CRT) in adult patients with LARC and at least one risk factor for local or distant recurrence.

The Series A Prime financing was led by Sedgwick Yard, a global biotech venture capital firm with Greater China roots. In a separate transaction, Akamis Bio entered into a licensing agreement granting Xuanzhu Biopharma the Greater China Region Rights to NG-350A. Under the terms of the licensing agreement, Akamis Bio is eligible to receive undisclosed upfront payments plus regulatory and sales milestones, as well as tiered royalties in the high single- to low double-digit range on Greater China Region NG-350A sales.

"We are grateful for this strong vote of confidence in NG-350A, the T-SIGn platform and the Akamis Bio team. The Sedgwick Yard-led Series A Prime financing and Xuanzhu Biopharma licensing deal demonstrates our shared commitment with these partners to rapidly advancing NG-350A while also demonstrating the broader potential of T-SIGn," said Howard Davis, PhD, CEO of Akamis Bio. "Compelling clinical data from our prior studies have shown the consistent safety profile of T-SIGn, as well as the potential of intravenously-delivered NG-350A to drive sustained transgene expression capable of altering the tumor microenvironment. Our aim over the next 12-18 months is to deliver clinical proof-of-concept data for NG-350A via the FORTRESS study."

"We believe T-SIGn offers a true platform approach and that NG-350A is just the beginning of what we anticipate will become a robust pipeline of IV-delivered, tumor-targeted immunotherapies. We are very confident in the scientific and drug development acumen of the Akamis Bio management team, as well as in their ability to deliver on this opportunity to advance the standard of care for patients with difficult to treat solid tumors," said Richard Shen, Managing Director, Sedgwick Yard.

A recently published paper in the Journal for ImmunoTherapy of Cancer (JITC), described data from the FORTITUDE first-in-human dose escalation study in patients with metastatic/advanced epithelial tumors that provided initial proof-of-mechanism for NG-350A and highlighted the advantages of its intravenous route of administration. These data demonstrated the consistent safety profile of NG-350A, as well as providing strong evidence of tumor-selective delivery, replication and transgene expression. Additionally, this study demonstrated that intravenous delivery of NG-350A results in a superior overall pharmacokinetic and pharmacodynamic profile, with no apparent disadvantages versus intratumoral injection.

"We are thrilled to partner with Akamis Bio to develop and commercialize NG-350A in the Greater China Region. The T-SIGn platform has the potential to revolutionize the treatment of advanced metastatic solid tumors, and we look forward to working closely with the Akamis Bio team to bring this novel tumor gene therapy to patients," said Jiakui Li, PhD, CEO of Xuanzhu Biopharma.

Linked to the close of the Series A Prime financing, Akamis Bio added two new members to its Board of Directors: Richard Shen, Managing Director, Sedgwick Yard, and Adrian Chan, Managing Director, Sedgwick Yard.

About T-SIGn

Akamis Bio’s T-SIGn therapeutics are based on a replication competent, chimeric group B adenovirus backbone which has been adapted via directed evolution to home specifically to both primary and metastatic epithelial-derived solid tumor tissue following intravenous delivery. Once at the tumor site, T-SIGn therapeutics can drive the intratumoral expression of multiple transgene payloads, turning solid tumor cells into "drug factories" while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. T-SIGn therapeutics have the potential to be used in the monotherapy setting, as well as in combination with other immuno-oncology agents to target the key mechanisms that tumors use to evade the immune system.