On December 6, 2022 Chimeric reported that it has entered into an exclusive option agreement to license the clinically validated, off the shelf, robust, enhanced natural killer (CORE-NK) cell platform from Case Western Reserve University for the treatment of cancer (Press release, Chimeric Therapeutics, DEC 6, 2021, View Source [SID1234598461]). The CORE-NK platform was designed to overcome the hurdles associated with NK cell development and enables the production of large numbers of highly active universal donor NK cells that are active in the body. The company expects to rapidly move to complete full licensing of the platform.

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Improving NK cells
NK cells are naturally found within the body and are able to recognise and kill cancer cells, but efficacy when used in a therapeutic setting is often limited due to challenges in manufacturing enough of them to halt the growth of many cancers. CORE-NK cells are made by activating and expanding NK cells to make them more active and robust in large numbers.

Enabling an expansion of the pipeline
Besides using CORE-NK cells to target cancer directly, this licensure would allow for the creation of CAR-NK programs to augment the current CLTX CAR T and CDH17 CAR T programmes that are focused on solid tumours. Four new pipeline programmes are expected to be started in 2023 following the anticipated acquisition of the CORE-NK platform. Positive low dose CHM 1101 data from Phase I Data from the low dose cohort of four patients from the Phase I trial of CHM 1101 (CLTX CAR T) was presented in November at the Society for Neuro-Oncology (SNO) annual meeting. Three out of four patients achieved stable disease that was durable for five to eight weeks. In one patient, there was no evidence of progression in the part of the brain in which CHM 1101 was infused intratumourally and progression was only seen in an area of the brain where it was not infused intertumourally. Valuation: A$322m or $0.97 per share We have adjusted our valuation from A$327m or A$0.99 per share to A$322m or A$0.97 per basic share, mainly due to lower net cash. Because the CORE-NK platform is not fully licensed and its associated products are not yet in the clinic, we are not including them in our valuation yet, in accordance with Edison methodology. Once included, they may have a meaningful impact upon the valuation due to the size of the markets targeted by the company.

Chimeric Therapeutics Development update Acquiring an exciting new NK cell technology Price A$0.27 Market cap A$90m A$1.40/US$ Net cash (A$m) at 30 June 2021 17.4 Shares in issue 333.4m Free float 39.2% Code CHM Primary exchange ASX Secondary exchange N/A Share price performance % 1m 3m 12m Abs (13.3) (24.6) N/A Rel (local) (11.4) (21.8) N/A 52-week high/low A$0.39 A$0.24 Business description Chimeric Therapeutics is an oncology-focused Australian-based company that recently went public on the ASX. The lead programme is CHM 1101, currently in Phase I for the treatment of GBM. Beyond GBM, the technology may have applicability for other tumours such as melanoma. The company recently in-licensed a CDH17 CAR T for use in solid tumours and the CORE-NK platform, which may have broad applicability in cancer. Next events Updated CHM 1101 data CY22 CHM 2101 Phase I initiation CY22 Analysts Maxim Jacobs +1 646 653 7027 Jyoti Prakash +91 981 880 393 [email protected] Edison profile page Pharma & biotech Chimeric Therapeutics is a research client of Edison Investment Research Limited Chimeric Therapeutics | 6 December 2021 2 The CORE-NK platform Chimeric has announced that it has entered into an exclusive option agreement to license the CORE-NK platform from Case Western Reserve University. NK cells are found in the body naturally and are able to recognise and kill cancer cells without affecting healthy cells. They are also able to produce cytokines that use the immune system to mount an additional response to kill tumours.

However, efficacy when used in a therapeutic setting is often limited due to challenges in manufacturing enough of them to halt the growth of many cancers. Through the platform, CORENK cells are made by activating and expanding NK cells to make them more active and robust in large numbers. 1 The company expects to rapidly move to complete full licensing of the platform. Financial terms are likely to include development milestones, industry standard royalties (likely single digit in our view) and an upfront payment. The anticipated licensure would enable a significant expansion of the product pipeline past CHM 1101 and CHM 2101, the CLTX and CDH17 CAR T therapies, respectively, currently in development.

The company plans to develop CAR NK versions of both those programmes, develop therapies using the current and next generation CORE-NK platform and an additional CAR NK with an undisclosed target. CAR NK products would be made by inserting CARs into the CORE-NK platform cells. Adding the CARs improves the delivery of the NK cells to specific antigen-expressing tumours. Exhibit 1: Planned Chimeric pipeline post-CORE-NK licensure Programme Construct Type Indication focus Status CHM 1101 CLTX CAR T Autologous Glioblastoma multiforme (GBM), melanoma, colorectal, prostate Phase I ongoing in GBM, second trial in another indication planned for 2022 CHM 2101 CDH17 CAR T Autologous Neuroendocrine, colorectal, pancreatic, gastric Phase I expected 2022 CHM 0201 CORE-NK Platform Allogeneic Both hematologic and solid tumours Phase I complete (9 patients completed all three dose levels with data expected in 2022), further technological enhancements planned for development as combination therapy CHM 0301 Next Generation CORE-NK platform Allogeneic Hematologic tumours Phase I planned 2023 CHM 1301 CLTX CAR-NK Allogeneic Glioblastoma multiforme (GBM), melanoma, colorectal, prostate Phase I planned 2023 CHM 2301 CDH17 CAR-NK Allogeneic Neuroendocrine, colorectal, pancreatic, gastric Phase I planned 2023 CHM 3301 Undisclosed CAR-NK Allogeneic Undisclosed Phase I planned 2023 Source: Chimeric Therapeutics As NK cells are not thought to cause graft-versus-host-disease (GVHD), all these CORE-NK based therapies have the potential to be allogeneic, where cells from a single donor could be used to treat multiple patients.

This is in contrast to autologous therapies where treatments are based on a patient’s own cells. Allogeneic therapies hold the promise of starting with healthier material, lowering manufacturing costs and being rapidly available to patients (the bespoke nature of autologous treatments can delay treatment for weeks). Besides these announced programmes, Chimeric will be seeking additional collaboration and licensing opportunities for the platform. CHM 1101 data from the low-dose cohort At the SNO conference in November, data from the CHM 1101 Phase I was presented. The data focused the four patients who were enrolled at the lowest dose level of 44m CLTX CAR T cells 1 Ojo et al., Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells. Scientific Reports 2019 Oct 17;9(1):14916. Chimeric Therapeutics | 6 December 2021 3 (which were injected intratumourally in a single injection). Stable disease was achieved in three out of the four patients with durability of five to eight weeks. Importantly, in one patient, there was no observed tumour recurrence in the left frontal lobe where the CLTX CAR T cells were administered.

Tumour progression in that patient occurred in the left temporal lobe, which did not receive the infusion. Also, with regards to safety, therapy was generally well tolerated and there were no cytokine release syndrome (CRS) events due to therapy. Dose escalation is planned across four dose levels up to 440m cells through dual intratumoural and intraventricular routes of administration (intraventricular administration only starts at the 88m cell dose level). Valuation We have adjusted our valuation from A$327m or A$0.99 per share to A$322m or A$0.97 per basic share, mainly due to lower net cash. Because the CORE-NK platform is not fully licensed and its associated products are not yet in the clinic, we are not including them in our valuation yet, in accordance with Edison methodology. Once included, they may have a meaningful impact upon the valuation due to the size of the markets targeted by the companyFinancials In the quarterly cash flow report for the first quarter of FY22 (the period ending 30 September 2021), Chimeric reported A$17.4m in cash at Q122.

In FY21 the company had an operating loss of A$15.1m. We have not made any meaningful changes to our financial model following these results and have introduced FY23 estimates, which feature A$14.5m in operating expenses. We may increase our R&D expense estimates once we have more clarity on the clinical programme post the closure of the licensing of the CORE-NK platform. We continue to project a financing need of A$80m through 2026, with A$20m expected to be raised in FY22 and modelled as illustrative debt.

On December 5, 2021 Isofol Medical AB (publ) (Nasdaq Stockholm: ISOFOL), reported on December 3 that the ongoing phase III study AGENT will not reach 300 PFS events with current censoring rules based on FDA decision (Press release, Isofol Medical, DEC 5, 2021, View Source [SID1234596455]). Following this announcement, Isofol invites investors, analysts, and media to an audiocast (in English) with a Q&A-session on December 6, at 08:00 a.m. CET.

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The presentation will be held by Isofol’s CEO Ulf Jungnelius and CMO Roger Tell in English and will conclude with a Q&A session. Questions can be asked on the telephone conference or in written form through the webcast. No preregistration is needed.

Date and time
December 6, 2021, at 08:00 a.m. CET

Webcast link
View Source

Phone number
Call in details will be made available at the following link in good time before the start of the presentation:
View Source

The presentation will also be available on Isofol’s website after the broadcast.

On December 5, 2021 Jacobio Pharma (1167.HK) reported that it has received the Investigational New Drug (the "IND") approval of the combination therapy of KRAS G12C inhibitor JAB-21822 and Cetuximab injection from the Center for Drug Evaluation of China (the "CDE") on Dec 3, 2021 (Press release, Jacobio Pharmaceuticals, DEC 5, 2021, View Source [SID1234596458]).

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After received the approval, Jacobio will start a phase I/II, open-label, multi-center, dose-escalation and expansion clinical trial in China. The clinical trial is aiming to explore the safety, tolerability and preliminary efficacy of the combination therapy of JAB-21822 and Cetuximab in KRAS G12C mutant patients with advanced colorectal cancer.

Jacobio’s preclinical study shows that the combination therapy of JAB-21822 and Cetuximab can enhance the anti-tumor activity of JAB-21822 inhibitors in colorectal cancer tumor models, make tumor regression, and delay tumor re-growth after the cessation of using the drug.

JAB-21822 has been approved for five clinical trials in China and the United States, including mono therapies and combination therapies with either PD-1 antibody or Cetuximab to treat KRAS G12C mutant patients with advanced solid tumors including non-small cell lung cancer and colorectal cancer.

About JAB-21822

JAB-21822 is the Jacobio’s in-house innovative small molecule anti-cancer drug, which is designed to target KRAS G12C mutation. JAB-21822 has best-in-class potential among KRAS G12C inhibitors and has been approved for clinical trials in China and the United States. Internal pre-clinical head-to-head studies have shown that JAB-21822 has a superior pharmacokinetic (PK) profile and favorable tolerability as well as potential for a superior dosing profile compared with its competitors.

About Cetuximab

Cetuximab is an IgG1 monoclonal antibody against the EGF receptor. The cetuximab injection used in the clinical trial of the combination therapy is an approved treatment for RAS wild type patients with metastatic colorectal cancer, head and neck cancers and other diseases.

On December 5, 2021 KDx Diagnostics, Inc. (KDx), and Lister Hospital (East and North Hertfordshire NHS Trust), Stevenage, UK, reported the launch in the United Kingdom (UK) of KDx’s URO17 test for detection of bladder cancer (Press release, KDx Diagnostics, DEC 5, 2021, View Source [SID1234596460]). This non-invasive urine test for bladder cancer is highly sensitive for identifying bladder cancer in patients with hematuria and recurrent bladder cancer during post-treatment monitoring.

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There are over 197,000 newly diagnosed cases of bladder cancer in Europe, and 430,000 globally, with 81,000 cases in the US alone. Accurate detection of new bladder cancer is difficult and expensive, requiring invasive camera-based testing methodology. Excitingly, KDx’s URO17 test has demonstrated 100% sensitivity and over 90% specificity in detecting bladder cancer in multiple peer-reviewed studies.

"We are excited to have the non-invasive URO17 test available in the UK to determine with high confidence whether a patient has bladder cancer. Testing has shown the URO17 urine test can detect the presence or absence of bladder cancer with high sensitivity. We are confident that the application of URO17 in clinical practices can significantly improve patient care in the UK," said Nam W. Kim, Ph.D., KDx’s CEO, and CTO.

"Bladder cancer is expensive cancer to treat due to a high rate of recurrence, and it often requires invasive procedures to diagnose. KDx’s URO17 urine test is revolutionizing how bladder cancer is detected, managed, and treated. We are excited that Lister Hospital in Stevenage is now a Core Lab offering URO17 test and that patients from all over the UK will have access to this test," said Sholeh Jahanfard, President and COO of KDx Diagnostics Inc.

Mr. Nikhil Vasdev – Consultant Urological Surgeon at Lister Hospital and Associate Medical Director for cancer services at East and North Hertfordshire NHS Trust, which runs the hospital – was the chief investigator and the lead author of a paper describing a recent study on URO17. "We are pleased to be the first NHS trust in the UK and Europe to make URO17 test available for patients," said Mr. Vasdev, who is also a Senior Clinical Lecturer at the University of Hertfordshire. "Our ability to detect bladder cancer simply, accurately, and non-invasively using URO17 will greatly improve detection at an early stage when it can be treated most effectively while minimizing the number of unnecessary and invasive procedures in patients who are suspected of having bladder cancer," he added.

Dr. Michael Chilvers – Medical Director at East and North Herts NHS Trust, said: "I am really pleased that the partnership between KDx and this Trust has led to this major step forward in the non-invasive detection of bladder cancer, and undoubtedly to improved outcomes for our patients."

On December 4, 2021 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that positive final data from a phase II clinical study of paxalisib as first line therapy in patients with glioblastoma (NCT03522298) (Press release, Kazia Therapeutics, DEC 4, 2021, View Source [SID1234596461]). The results confirm the previously reported safety and efficacy profile with paxalisib in this high unmet need disease.

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Key Points

The study recruited 30 patients with newly diagnosed glioblastoma and unmethylated MGMT promotor status, a genetic profile which confers primary resistance to temozolomide, the only existing FDA-approved drug treatment for first line treatment.
60mg once daily was identified as the maximum tolerated dose (MTD) and selected for future studies.
Median overall survival (OS) in the intent-to-treat (ITT) population (n=30) was 15.7 months (11.1 – 19.1), which compares very favourably to 12.7 months historically reported with temozolomide in this patient group.1
Median progression-free survival (PFS) in the ITT population was 8.4 months (6.6 – 10.2), representing a substantial increment over the comparable figure of 5.3 months associated with temozolomide.
In the modified ITT (mITT) population (n=27), which includes only those patients evaluable for efficacy, OS increased to 15.9 months (12.8 – 19.1).
The safety profile of paxalisib was highly consistent with previous clinical studies: hyperglycaemia, oral mucositis, and skin rash were among the most common drug-related toxicities.
Kazia expects to receive a final clinical study report in 1Q CY2022 and intends to seek publication of these data in a peer-reviewed scientific journal thereafter.
Kazia CEO, Dr James Garner, commented, "We are delighted to report positive final data from the completed phase II study of paxalisib. The data continue to demonstrate a clear efficacy signal and favourable safety profile, suggesting a meaningful advantage over temozolomide, the existing standard of care, and validating our decision last year to join the GBM AGILE pivotal study. We have gleaned invaluable insights from this trial, and we are tremendously grateful to the investigators and to the patients who participated. Our task now, as we move rapidly toward a potential marketing authorization, is to confirm and quantify the benefit associated with paxalisib in glioblastoma patients. This indeed is the focus of our participation in GBM AGILE, which commenced recruiting to the paxalisib arm in January 2021. We are increasingly also exploring additional patient populations for which a brain penetrant PI3K/mTOR inhibitor may provide significant advantages over the standard of care."

Professor Patrick Wen, Principal Investigator at Dana Farber Cancer Institute, commented "We are pleased to see the phase II study of paxalisib successfully completed. This data supports the inclusion of paxalisib in the GBM AGILE study, which has recently expanded to Canada. Glioblastoma remains a disease in urgent need of new therapeutic options, and we look forward to seeing further data for paxalisib from GBM AGILE in due course."

Clinical Trial Design

The phase II study of paxalisib was an adaptive trial, conducted in two stages. The first stage sought to determine the most appropriate dose in newly diagnosed patients. The second stage was intended to provide additional information on dosing and to seek a preliminary efficacy signal in order to de-risk transition to a larger, pivotal study.

Consistent with these objectives, the primary objective of the study was to evaluate the safety and tolerability of paxalisib in patients with newly diagnosed glioblastoma. The secondary objectives included typical pharmacokinetic parameters, and efficacy endpoints including overall survival (OS) and progression-free survival (PFS).

The phase II study was conducted in 30 patients at six centres in the United States. It was a single arm study in which all patients received paxalisib as a monotherapy. As such, all data must be interpreted in the context of historical comparators. Specifically, Kazia has referred to the pivotal study of temozolomide, the only existing FDA-approved drug for this patient population. Such comparisons are always inexact, and this study was not designed either to precisely quantify the benefit associated with paxalisib or to demonstrate statistical significance. Rather, these are among the objectives of the ongoing GBM AGILE pivotal trial.

Next Steps

On the basis of earlier interim analyses of this study, Kazia made the decision in 4Q CY2020 to commence participation in the GBM AGILE pivotal study. This global trial recruited its first patient to the paxalisib arm in January 2021 and recruitment is ongoing. Kazia provisionally expects indicative data in CY2023.

Seven other studies of paxalisib are ongoing in other forms of primary brain cancer and in various forms of cancer that has metastasized to the brain. The company is working with investigators to crystalise the timing of initial data read-outs from these studies. Kazia had expected at least two further read-outs by the end of CY2021. Clinicians have now indicated that data early in CY2022 is most likely. The company will continue to keep shareholders closely informed as it receives further feedback from investigators.

Having successfully concluded the phase II study in glioblastoma, the investigators are composing a manuscript for submission and publication to a peer-reviewed academic journal in 2022. Once the data has been more thoroughly analysed, Kazia expects to share further detail with investors as it becomes available.