On April 9, 2021 Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through structure-based drug discovery and development, reported the presentation of data from the company’s HPK1 inhibitor program in a poster at the AACR (Free AACR Whitepaper) Annual Meeting held virtually April 10-15, 2021 (Press release, Nimbus Therapeutics, APR 9, 2021, View Source [SID1234577755]).

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Newly disclosed data show that Nimbus’ small-molecule HPK1 inhibitor, NMBS-2, demonstrates significant tumor growth inhibition as a single agent and in combination with anti-PD1 in multiple mouse syngeneic tumor models. In combination with anti-PD1, NMBS-2 restored cytokine secretion from exhausted human T cells and induced robust tumor growth inhibition in the CT-26 model. Furthermore, animals treated with NMBS-2 and anti-PD1 showed complete rejection of subsequently reintroduced CT-26 tumor cells, suggesting the establishment of a robust and durable immune memory.

"Building on our promising findings to date demonstrating the anti-tumor immune activity of NMBS-2, these latest data provide a compelling picture of its potential clinical utility in a range of tumor types — both as a single agent and as a combination therapy with anti-PD1 treatment," said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. "We’re rapidly progressing IND-enabling studies of NMBS-2 now with plans to initiate first-in-human studies in the second half of 2021."

On April 9, 2021 Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused drug development company, reported to share new data from its ongoing phase II study of paxalisib in glioblastoma, the most common and most aggressive form of primary brain cancer (Press release, Kazia Therapeutics, APR 9, 2021, View Source [SID1234577773]).

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The data is the subject of a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is being held virtually from 10-15 April 2021, and from 17-21 May 2021.

Key Points

Pharmacokinetic (PK) data, which shows how long paxalisib remains in the human body, strongly supports 60mg once daily dosing, confirming planned administration schedule for commercial launch.

Analysis of food effect shows no significant difference between taking paxalisib with food versus on an empty stomach, allowing for a less restrictive administration schedule in commercial use.

Study remains ongoing, with a number of patients still in follow-up. Final data is now expected in 2H CY2021.

Kazia CEO, Dr James Garner, commented, "this is extremely useful and encouraging data, as we begin to compile regulatory documentation for paxalisib and give shape to its potential commercial approval. These results give us great confidence that we are administering the drug at the right dose, at the right frequency, and under the correct conditions. Moreover, the data helps to confirm the approach that we have taken in the GBM AGILE pivotal study."

He added, "a lot of our efforts at present are focused on assembling the complex package of scientific information that is required to secure FDA approval for any new drug. Today’s data provides one more piece in that jigsaw. More broadly, the phase II study is drawing to a conclusion, and we expect to be able to share final data in the second half of this year."

The poster can be viewed on the Company’s website at View Source

Background

The phase II study of paxalisib (NCT03522298) opened to recruitment in May 2018. It was designed to establish the most appropriate dose for use in newly-diagnosed patients, and to seek initial indications of potential clinical efficacy.

The study had previously determined a maximum tolerated dose (MTD) of 60mg, administered once daily. This determination was based primarily on safety findings, which suggested increased toxicity at a higher dose. Today’s PK data corroborates this finding, and shows that increased doses provide limited additional benefit in terms of drug exposure. In effect, these two independent variables both point to a dose of 60mg, giving a high degree of confidence that this is appropriate for future studies and for commercialisation.

Interim analyses of efficacy data from this study have previously shown encouraging signals of clinical efficacy, with a median overall survival (OS) of 17.5 months and a median progression-free survival (PFS) of 8.4 months reported at the most recent data cut. These figures compare very favourably to historical controls for temozolomide, which provide an OS of 12.7 months and a PFS of 5.3 months.

The phase II study remains ongoing, with a number of patients in follow-up, and is expected to deliver final data in 2H CY2021.

In January 2021, paxalisib opened to recruitment in the GBM AGILE pivotal study, which is expected to provide the basis for registration in the US and other territories.

On April 9, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported plans to host a conference call and webcast on Friday, April 16, 2021 at 8:00 a.m. ET to discuss the selection of the NaPi2b biomarker cutoff and the commercial diagnostic development path for the ongoing UPLIFT registration strategy in platinum-resistant ovarian cancer (Press release, Mersana Therapeutics, APR 9, 2021, https://ir.mersana.com/news-releases/news-release-details/mersana-therapeutics-host-conference-call-and-webcast-discuss [SID1234577791]). The presentation will review the Company’s plan to deliver a robust, predictive and reproducible commercial diagnostic assay.

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To access the call, please dial 877-303-9226 (domestic) or 409-981-0870 (international) and provide the Conference ID 4598737. A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com.

On April 9, 2021 CARISMA Therapeutics Inc., a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported study findings accepted for virtual presentation at The American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on Saturday, April 10 – Thursday, April 15 (Press release, Carisma Therapeutics, APR 9, 2021, View Source [SID1234577807]). The accepted data reinforces the potential of CARISMA’s proprietary chimeric antigen receptor macrophage (CAR-M) platform, as well as the importance of evaluating CAR-monocytes (CAR-Mono) as a novel and expedited immunotherapeutic pathway.

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CARISMA will share key findings from recent studies including, "Chimeric antigen receptor macrophages (CAR-M) induce anti-tumor immunity and synergize with T cell checkpoint inhibitors in pre-clinical solid tumor models," presented by Dr. Stefano Pierini, Senior Scientist at CARISMA, which established a fully immunocompetent solid tumor mouse model and evaluated the interaction of CAR-M with the tumor microenvironment and the endogenous adaptive immune system. This study marks the first time CAR-Ms have been assessed in a fully immunocompetent animal model. The findings demonstrate that CAR-M therapy showed significant tumor control, increased overall survival, remodeled the tumor microenvironment, and protected mice from antigen negative tumor recurrence. Additionally, the studies demonstrate that CAR-M synergize with T cell checkpoint inhibitors against PD1 resistant solid tumors. The data build on findings from CARISMA’s foundational CAR-M platform that were published in Nature Biotechnology in March 2020.

Also accepted for AACR (Free AACR Whitepaper) presentation is the clinical trial design and foundational details regarding CARISMA’s lead candidate, CT-0508, a human epidermal growth factor receptor 2 (HER2) targeted CAR-M, "A phase 1, first in human (FIH) study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in subjects with HER2 overexpressing solid tumors," presented by Joshua Bauml, MD, an Assistant Professor of Medicine in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania (Penn). This first-of-its kind Phase 1 clinical trial is actively enrolling patients at two sites, Penn and the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill. Dr. Bauml is the principal investigator for the trial at Penn.

In "Anti-HER2 CAR monocytes demonstrate targeted anti-tumor activity and enable a single day cell manufacturing process," presented by CARISMA Scientist Dr. Linara Gabitova, new data shows the successful development of CAR-Mono with direct anti-tumor activity and capacity to differentiate into M1-polarized CAR-M. In addition, CARISMA established an ultra-rapid, same-day CAR-Mono manufacturing process for this study, which has the potential to significantly reduce the future cost of goods and manufacturing turn-around-time associated with the autologous cell therapy.

"The data presented at the AACR (Free AACR Whitepaper) Annual Meeting build upon the broad engineered monocyte and macrophage platform established by CARISMA Therapeutics," shared Michael Klichinsky, PharmD, PhD, Scientific Co-founder, and Senior Vice President of Research at CARISMA Therapeutics. "These critical pre-clinical data demonstrate that CAR-M not only directly shrink tumors but instill long-term anti-tumor immunity via antigen presentation to T cells, protecting from relapse in the future."

The following presentation and posters will be published on the AACR (Free AACR Whitepaper) Annual Meeting website and available for registered attendees during the dates/times indicated below:

Saturday, April 10 at 8:30 am ET:
A phase 1, first in human (FIH) study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in subjects with HER2 overexpressing solid tumors
Anti-HER2 CAR monocytes demonstrate targeted anti-tumor activity and enable a single day cell manufacturing process
Monday, April 12 at 3:05 pm ET:
Chimeric antigen receptor macrophages (CAR-M) induce anti-tumor immunity and synergize with T cell checkpoint inhibitors in pre-clinical solid tumor models

On April 9, 2021 Palleon Pharmaceuticals, a company pioneering the field of glycan-mediated immune regulation to treat cancer and inflammatory diseases, reported the presentation of data supporting the role of hypersialylation in the immune escape of metastatic melanoma at the AACR (Free AACR Whitepaper) Annual Meeting held virtually April 10-15, 2021 (Press release, Palleon Pharmaceuticals, APR 9, 2021, View Source [SID1234577756]).

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The research, conducted in collaboration with Massachusetts General Hospital, used Palleon’s HYDRA technology to quantify immunosuppressive sialoglycans of melanoma tumor samples. The tumor tissue had been surgically removed from patients with stage IV melanoma (n=54) who had had zero to four prior rounds of immunotherapy treatment, prior to their initiation of treatment with a PD1 inhibitor. Hypersialylation of tumor cell-surface glycans is known to correlate with poor cancer prognosis, potentially by enabling tumors to evade immune detection. In this study, researchers aimed to evaluate how hypersialylation might contribute to a cancer’s resistance to immune checkpoint therapies.

Results of this analysis showed that patients who had high HYDRA signatures experienced poor outcomes on PD1 inhibitor therapy both in terms of progression-free survival and overall survival. Additionally, these signatures did not correlate with other common melanoma biomarkers such as BRAF-mutation, liver metastases, or TILs, suggesting that hypersialylation may impact response to PD1 inhibitors independently of these pathways.

"This analysis represents an important validation of HYDRA for detecting hypersialylation signature as a potential prognostic biomarker for patients undergoing cancer treatment. Melanoma patients resistant to PD1 inhibitors with high HYDRA signatures may be candidates for the enzymatic sialoglycan degrader that Palleon is now advancing toward clinical studies," said Li Peng, Ph.D., Chief Scientific Officer of Palleon and the poster’s principal author. "We are continuing to hone the HYDRA technology, including via ongoing longitudinal study of this patient cohort. We believe HYDRA could offer a powerful tool to support Palleon’s clinical trial patient enrichment strategies and to guide optimal dosing of Palleon’s therapeutic candidates."

The poster, titled "Melanoma patients with multi-Siglec ligands as profiled by HYDRA technology are refractory to PD1 blockade," can be accessed at the conference (#491) or via Palleon’s website on Saturday morning, April 10th at 8:30am ET.