On April 8, 2024 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in San Diego, CA an update on its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123, an anti-VISTA monoclonal antibody, as monotherapy and in combination with Merck’s anti-PD1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced solid tumors (Press release, Kineta, APR 8, 2024, View Source [SID1234641854]).

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KVA12123 cleared the fifth of six monotherapy dose levels and the second of four cohorts in combination with pembrolizumab. KVA12123 was well tolerated with no dose limiting toxicities (DLT) or cytokine related adverse events at any dose level.

The poster presentation #CT068: "Interim results of the ongoing phase 1/2 clinical trial of KVA12123, an engineered IgG1 targeting VISTA, alone and in combination with pembrolizumab in advanced solid tumors" was presented Monday, April 8, 2024 and reported the following findings (the data cutoff date was February 28, 2024):

Monotherapy Dose Escalation (3 – 300 mg KVA12123 Q2W)

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Of 21 patients enrolled, 12 received at least one baseline and one follow up scan
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Best overall response (BOR) in 9 of 12 patients with at least one follow-up scan is stable disease with a mean duration of 15 weeks
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One patient with non-small cell lung cancer that failed 6 prior lines of therapy, including checkpoint inhibitor (CPI) therapy, has experienced stable disease lasting 28 weeks
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Nine participants remain on-treatment

Combination Therapy Dose Escalation (30-100 mg KVA12123 Q2W, 400 mg pembrolizumab Q6W) Of 9 patients enrolled, 3 received at least one baseline and one follow-up scan
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BOR in 2 of 3 patients with at least one follow up scan is:
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Partial Response in 1 mucoepidermoid carcinoma patient with a 54% reduction in target lesions and a complete response in non-target lesions
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Stable disease in 1 renal cell carcinoma patient that had progressed on prior CPI therapy with a 24% reduction in target lesions
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Eight patients remain on-treatment

Biomarkers

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Dose-dependent induction of on-target pro-inflammatory cytokines and chemokines
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Dose-dependent increases in activated non-classical monocytes, CD4+ and CD8+ T cells, and NK cells

Safety

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No DLTs observed in any patient at any dose level
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No evidence of cytokine release syndrome in any patient at any dose level

"We are pleased to present our progress on the VISTA-101 clinical trial at AACR (Free AACR Whitepaper) this year, with the initial clinical response data and the durability of patient benefit emerging from the study. The safety profile of KVA12123 to date has been remarkable in the monotherapy as well as combotherapy cohorts, supporting advancement to the final monotherapy dosing cohort of KVA12123 and reaching the estimated optimal therapeutic dose," said Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. "Initial read-outs demonstrated that KVA12123 is not only safe but exhibits potential clinical benefit for some patients as either monotherapy or combotherapy and may offer patients a novel approach to address immunosuppression in the tumor microenvironment and better manage solid tumor cancers." In February 2024, the company announced that it is pursuing strategic alternatives to maximize shareholder value due to certain investors indicating they will not fulfill their April 2024 funding obligation in the previously disclosed private placement financing. As a result, the company has suspended new patient enrollment into the Phase 1/2 VISTA-101 trial and will not be recruiting patients into either the sixth cohort in the monotherapy arm or the third cohort in the combination therapy arm. Patients currently enrolled in the trial will be permitted to continue to participate.

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

On April 8, 2024 Starpharma reported it has entered into a strategic partnership with Medicxi, a leading life sciences investment firm dedicated to financing companies developing innovative medicines, to co-found a new UK-based company called Petalion Therapeutics Limited ("Petalion") (Press release, Starpharma, APR 8, 2024, View Source;mc_eid=bf52dd3418 [SID1234641853]).

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Petalion will initially focus on developing novel targeted dendrimer-drug conjugate therapies in oncology, utilising Starpharma’s proprietary DEP dendrimer platform technology.

Medicxi will fund Petalion with an initial investment of up to USD $25 million (~AUD $38 million) to finance the development of a novel oncology drug candidate. Starpharma will license certain intellectual property ("IP") to Petalion as required for the research, development, manufacture and commercialisation of this potential new therapeutic and, in exchange, will receive an equity holding of 22.5% in Petalion.

Collaboration Agreement

Under the terms of the collaboration, Starpharma will license the IP to Petalion on an exclusive basis for a mutually agreed target. In consideration for the IP licence to this specific target, Starpharma will be issued ordinary shares in Petalion. Starpharma will also provide R&D services to Petalion on a fee for service basis.

Medicxi intends to finance Petalion’s development program via a tranched investment plan with defined scientific and technical milestones, culminating in a total investment of up to USD $25 million.

Dr Mehdi Shahidi, a highly experienced pharmaceutical executive, has been appointed as CEO of Petalion. A clinical oncologist by background, Dr Shahidi has over two decades of experience in pharmaceutical drug development, most recently as Corporate Senior Vice President, Chief Medical Officer, and Global Head of Medicine at Boehringer Ingelheim.

Dr Mehdi Shahidi, CEO of Petalion and Venture Partner at Medicxi, commented:

"I am deeply honoured and thrilled to be leading this ground-breaking endeavour created by Medicxi and Starpharma. Leveraging Starpharma’s world-leading technology and the scientific domain expertise from Medicxi’s asset-centric investment platform, our team at Petalion aims to develop best-in-class dendrimer conjugates with differentiated properties. Our ultimate goal is to cultivate a targeted dendrimer-based drug that can effectively address unmet needs in cancer."

Shyam Masrani, Principal at Medicxi and Board representative of Petalion, commented:

"While the field of targeted conjugates has experienced remarkable growth and led to the approval of several treatment options for patients with cancer, it is also evident that the current approaches have limitations. Medicxi is excited to support Petalion under the leadership of Dr Shahidi from the outset and we look forward to working closely with the Starpharma team to develop a highly differentiated and effective new medicine."

Cheryl Maley, CEO of Starpharma, commented:

"We are excited to announce this strategic partnership, which combines Starpharma’s expertise in developing dendrimer technology with Medicxi’s success in converting development candidates into high-value commercial assets. If successful, the oncology therapies that Petalion will develop have the potential to become an important treatment modality for a potentially wide range of cancer indications.

"Medicxi is a highly innovative organisation with extensive experience in drug development and commercialisation. Their investment in this partnership validates the strong potential of Starpharma’s DEP dendrimer technology as a novel drug delivery platform.

"This is just one of many ongoing efforts to prioritise the commercialisation of Starpharma’s DEP platform and our partnerships to advance the application of the DEP technology in high-value novel therapeutic areas."

On April 8, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported superior recombinant T cell receptor (rTCR) engineered T cell functionality as well as a favorable safety profile when rTCR-T cells are armored and enhanced with the PD1-41BB costimulatory switch protein (CSP) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 taking place April 5-10, 2024, in San Diego, USA (Press release, MediGene, APR 8, 2024, View Source [SID1234641844]).
The poster presentation with the title "TCR-gated control of costimulatory switch protein (CSP) activation in rTCR-T cells expressing PD1-41BB" is available on Medigene’s website at View Source

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Targeting solid tumors with TCR-T therapies still faces significant challenges. Impaired T cell functionality and T cell exhaustion are driven by several factors within the hostile solid tumor microenvironment (TME). Programmed cell death ligand-1 (PD-L1), expressed by tumor cells in the TME engages the programmed cell death protein-1 (PD-1) expressed by activated T cells and induces T cell exhaustion and facilitates tumor immune escape. This is one major factor that allows cancer cells to proliferate and metastasize without being recognized by the host immune system. To counteract this inhibitory mechanism, a PD1-41BB CSP can be co-expressed in rTCR-T cells, turning an inhibitory signal mediated via the PD-1-PD-L1 axis into a costimulatory signal that improves TCR-T cell functionality.

"Medigene’s End-to-End Platform provides differentiated approaches to address the key challenges, including the immunosuppressive TME of solid tumors, in developing effective, safe and durable TCR-T therapies. The PD1-41BB CSP is our proprietary armoring and enhancement technology that improves immune function and persistence of TCR-T cells in the TME, resulting in better efficacy and sustained anti-cancer immune responses," said Dolores Schendel, Chief Scientific Officer of Medigene. "This latest data from our lead program MDG1015, a first-in-class, 3rd generation TCR-T therapy targeting NY-ESO-1/ LAGE-1a, armored and enhanced with our PD1-41BB CSP, shows the gating of the PD1-41BB effects through prior cancer antigen engagement with our 3S TCR. It represents a safe and effective approach to improve clinical outcomes in hard-to-treat solid tumor indications such as gastric cancer, ovarian cancer, myxoid/round cell liposarcoma, and synovial sarcoma. Based on our positive interactions for MDG1015 with regulatory authorities, we look forward to progressing our package for IND / CTA submission and expect to receive IND/CTA approval in the second half of 2024."

The data presented in the poster demonstrated that the CSP-mediated costimulatory signal is TCR-gated, such that costimulation only takes place when a specific peptide-human leukocyte antigen (pHLA) complex is present on a tumor cell and triggers a signal through the rTCR expressed by the TCR-T cells. Enhanced, gated T cell functionality of CSP-armored rTCR-T cells increased secretion of interferon-γ (IFNγ) only when tumor cells simultaneously expressed the pHLA target antigen and PD-L1. In addition, CSP-armored rTCR-T cells showed high sensitivity in recognition of diverse tumor cell lines of different tissue origin, such as melanoma, sarcoma, and gastric cancer which varied in levels of pHLA and PD-L1 in vitro. Rapid and sustained killing of 3D tumor cell-derived spheroids only occurred when PD-L1-positive tumor cells simultaneously expressed the specific pHLA target antigen.

Importantly, no recognition of healthy cells occurred if they lacked the pHLA target antigen, irrespective of PD-L1 expression, underpinning the safety of combining the CSP with a rTCR to generate rTCR-T cells that displayed no signs of toxicity for diverse healthy tissues in vitro.

On April 8, 2024 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported poster presentations featuring its CF33 oncolytic virotherapy VAXINIA and B cell immunotherapy HER-Vaxx at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 5-10 April 2024, in San Diego, CA.

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Daneng Li, M.D., a City of Hope associate professor in the Department of Medical Oncology & Therapeutics Research commented, "The results show that our novel oncolytic virus — both alone or in combination with immunotherapy — has the ability to control various cancer types previously resistant to other treatment options, and these early results provide patients with hope of a new treatment option for cancers refractory to standard treatment."

Imugene Managing Director & CEO Leslie Chong said: "Preliminary data from the MAST trial demonstrates encouraging anti-tumour activity with our oncolytic virus CF33-hNIS (VAXINIA). Notably, one patient with cholangiocarcinoma, or biliary tract cancer, achieved an immunological complete response (CR), meaning the disappearance of all signs of their cancer after treatment with VAXINIA, with no known recurrence after one year. These encouraging results warrant further investigation in patients will biliary tract cancer and other cancers. In addition, further analysis of the T cell repertoire reveals that T cell diversity may serve a predictive biomarker, which can be used to prospectively identify appropriate patients for treatment."

Details on the poster presentations are below:

Presentation Title: Oncolytic virus CF33-hNIS for the treatment of advanced cancer
Abstract Presentation Number: CT182
Session Date and Time: Tuesday April 9, 2024, 9:00 AM – 12:30 PM PT
Session Title: First-in-Human Phase I Clinical Trials 2
Presenter: Daneng Li, MD
Highlights include:

At the data cut-off of 19 December 2023, there were 31 efficacy-evaluable patients in the MAST study. In the intratumoural (IT) cohorts, 7 of 16 (44%) injected lesions had a reduction in tumour burden and 3 lesions were completely eradicated.Three of the IT treated patients had an objective response: 1 complete response by iRECIST in a patient with cholangiocarcinoma and 2 partial responses by RECIST inpatients with melanoma. In the intravenous (IV) cohorts, 9 of 17 (53%) patients achieved stable disease as their best response. Patients who received prior checkpoint blockade therapy derived clinical benefit with and without pembrolizumab. Viral replication, assessed by SPECT, was higher in patients who had a reduction in tumour burden.
Patients with a higher level of T cell diversity in peripheral blood (pre-treatment)respond better to VAXINIA therapy, consistent with the known mechanism of action of oncolytic virotherapies and their ability to promote an anti-tumour T cell response.
Both IT- and IV-treated patients have promising immunological changes in on-treatment tumour biopsies (including increases in cancer fighting CD8 T cells and PD-L1 expression) indicated that VAXINIA can transform the tumour microenvironment.
Several patients have had prior treatment with checkpoint blockade, including astable disease cholangiocarcinoma patient and two melanoma partial response patients. This suggests that VAXINIA +/- checkpoint inhibitor combination could be used in the checkpoint therapy refractory setting, which is seeing a growing and unmet market in oncology, by altering the tumour microenvironment.

Presentation Title: Frontline vaccination with the B-cell peptide compound HER-Vaxx (IMU-131), combined with standard-of-care chemotherapy induces high levels of HER2-specific antibodies mediating ADCC and intracellular phosphorylation inhibition resulting in overall survival benefit in patients with HER2+ metastatic or advanced gastric/GEJ adenocarcinoma – Final results from Phase II/HERIZON study
Poster Number: CT215
Session Date and Time: Tuesday April 9, 2024, 9:00 AM – 12:30 PM PT
Session Title: Phase II Clinical Trials 1
Presenter: Joshua Tobias Ph.D.
Highlights include:

HER-Vaxx treatment produced robust anti-HER2-IgG and IgG1 antibody response (p<0.001).
HER-Vaxx induced HER2-specific antibodies able to mediate antibody-dependent cell cytotoxicity (ADCC) and inhibit intracellular HER2 phosphorylation and correlated with tumour reduction.
The HER-Vaxx induced HER2-specific antibodies demonstrate a similar mechanism of action to HERCEPTIN validating B cell immunotherapy as an alternative anti-cancer agent to monoclonal antibodies.
About the MAST Trial
The multicenter Phase 1 MAST trial commenced by delivering a low dose of VAXINIA to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. The City of Hope-developed oncolytic virus has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models¹. Overall, the study aims to recruit cancer patients across approximately 10 trial sites in the United States and Australia.
The clinical trial is titled "A Phase I, Dose Escalation Safety and Tolerability Study of VAXINIA (CF33- hNIS), Administered Intratumorally or Intravenously as a Monotherapy or in Combination with Pembrolizumab in Adult Patients with Metastatic or Advanced Solid Tumours (MAST)." The trial commenced in May 2022 and is anticipated to run for approximately 24 months while being funded from existing budgets and resources. Full study details can also be found on clinicaltrials.gov under study ID: NCT05346484.

On April 7, 2024 HiFiBiO Therapeutics, a leading clinical stage global biotechnology company committed to advancing patient outcomes through single-cell precision, reported two posters at the AACR (Free AACR Whitepaper) 2024 meeting held on April 5-10, 2024, in San Diego, CA (Press release, HiFiBiO Therapeutics, APR 7, 2024, View Source [SID1234641870]).

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"One of the major challenges cancer immunotherapies face is the difficulties in selecting patients with tumors that will respond. Single-cell technologies can provide valuable insights into disease biology and help discern tumors that are more likely to respond; however, the lack of integrated data across diverse single-cell platforms hinders the potential of these novel technologies to inform clinical decisions." Jack Russella-Pollard, Ph.D., Executive Director, Translational Data Science, commented, "HiFiBiO has built an AI/ML powered curation and data integration process within our Drug Intelligence Science (DIS) translational platform that integrates publicly available datasets with in-house generated datasets to predict tumor response and guide target as well as indication selection."

Jinping Gan, Ph.D., Vice President, Global Head of Research, remarked: "Currently, there is no suitable model to describe complex tumor-immune interactions that can effectively guide clinical decisions. HiFiBiO has successfully constructed semi-mechanistic PKPD models for an anti-TNFR2 agonist and an anti-OX40 agonist that advocate for pulsatile agonism to achieve optimal anti-tumor efficacy. This innovative scientific work serves as a valuable tool for guiding dose and dose regimen optimization for the humanized versions of these T cell co-stimulatory agonists in clinical development."

By harnessing these cutting-edge technologies and tools within its DIS platform, HiFiBiO Therapeutics is steering the development of its drug candidates, including three antibodies currently undergoing Phase 1 evaluation: a first-in-class TNFR2 agonist (HFB200301, NCT05238883), a next-generation OX40 agonist (HFB301001, NCT05229601), and a best-in-class BTLA antagonist (HFB200603, NCT05789069).

These presentations underscore HiFiBiO Therapeutics’ unwavering commitment to innovation and its relentless pursuit of novel therapeutic solutions to address unmet medical needs.

Details on the poster presentations are as follows. E-Posters will be posted on HiFiBiO’s website following the live presentations.

Abstract Number: 6202

Title: Integrating public single-cell transcriptomics and patient profiles to guide clinical development

Presenter: Jack Russella-Pollard, Ph.D., Executive Director, Translational Data Science
Session Category: Bioinformatics / Computational Biology / Systems Biology / Convergent Science

Session Title: Integrative Cancer Science

Session Date and Time: Tuesday Apr 9, 2024, 1:30 PM – 5:00 PM

Location: Poster Section 36

Poster Board Number: 5

View full abstract here.

Abstract Number: 7176

Title: Optimization of T cell co-stimulatory agonists: A semi-mechanistic PKPD model integrating drug properties and tumor-immune interactions

Presenter: Jinping Gan, Ph.D., Vice President, Global Head of Research

Session Category: Experimental and Molecular Therapeutics

Session Title: Pharmacology and Pharmacogenetics

Session Date and Time: Wednesday Apr 10, 2024, 9:00 AM – 12:30 PM

Location: Poster Section 24

Poster Board Number: 17

View full abstract here.