On October 28, 2019 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported an update on the ongoing development of its product candidates (Press release, Immutep, OCT 28, 2019, View Source [SID1234549973]).

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Eftilagimod alpha ("efti" or "IMP321") Clinical Update

AIPAC – Phase IIb clinical trial

The Company is fully on track to report progression-free survival data and overall response rate data in Q1 of calendar year 2020. AIPAC is potentially a pivotal clinical trial, meaning it could serve as the basis to pursue appropriate regulatory approval pathways for efti, subject to sufficient and clinically meaningful data from the trial and regulatory interactions. Importantly AIPAC would be the first successful randomised trial in solid tumors for an antigen presenting cell activator and would be a very significant step in validating this new class of products.

TACTI-002 – Phase II clinical trial

Immutep presented initial encouraging data of the first cohort of 17 patients for Part A (patients with first line non-small cell lung cancer) of its TACTI-002 Phase II study, which is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada), in June. Part A has been expanded by the data monitoring committee in September to include 19 additional patients.

Recruitment is ongoing for Part B (second line non-small cell lung cancer) and Part C (second line head and neck squamous cell carcinoma), where 6 and 12 patients have been recruited, respectively. There is also potential to expand Parts B and C, subject to the required number of predefined patient responses being observed in these groups. Hence, in total 35 patients have been recruited across all three groups in TACTI-002.

Immutep will report data updates from the open label TACTI-002 study at SITC (Free SITC Whitepaper) on 8 November, at 7.00am EST, as well as in Q1 2020.

TACTI-mel – Phase I clinical trial

Immutep’s CSO and CMO presented final efficacy data at the World Immunotherapy Congress in Basel on 15 October 2019. The key findings were efti has a favourable safety profile in combination with pembrolizumab with no dose-limiting toxicities and the recommended dosage level for a Phase II trial is 30 mg of efti (this is the dosage level currently being evaluated in the ongoing TACTI-002 Phase II trial).

In addition, final efficacy data has been reported, confirming deep durable responses have been observed, with 12 patients (50%) having a decrease of ³ 75% in the target lesions and 9 patients (38%) being treated for ³ 12 months with pembrolizumab plus efti.

Final safety data is expected to be presented in H1 2020.

INSIGHT-004 – Phase I clinical trial

In June 2019, the first patient was enrolled in Germany and has received the first dose of treatment in INSIGHT-004, the fourth arm of the INSIGHT trial (INSIGHT-004 is also known as Stratum D of INSIGHT) which is being conducted in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. The first cohort (6 mg of efti) is now fully recruited with six patients in total. The second cohort (30 mg of efti) will recruit six patients, bringing the total participants in the study to 12 patients.

Initial safety data from the study is expected to be reported in Q4 2019.

Efti Manufacturing

The company is also working on upscaling the manufacturing process from 200L to 2,000L single-use bioreactors at the WuXi Biologics manufacturing plant (Wuxi, China) in order to be better prepared for potential commercial manufacturing and additional registration trials in multiple indications.

IMP761 Update

IMP761

Immutep is continuing cell line development and the associated manufacturing steps of its IMP761 product candidate following encouraging preclinical results that demonstrated the immunosuppressive activity of IMP761.

Update on Programs Fully Funded by Immutep’s Licensing Partners

GlaxoSmithKline (GSK) – Phase I and II clinical trials

In September, Immutep announced that it will receive a milestone payment from GSK of £4 million (~A$7.39 million) related to the first patient being dosed in GSK’s Phase II clinical trial evaluating GSK2831781 in ulcerative colitis. This milestone payment was received by Immutep from GSK in October.

Novartis – Phase I and II clinical trials

Immutep’s partner Novartis, is conducting five trials of LAG525, derived from IMP701, which is licensed from Immutep. Earlier this year, it commenced the recruitment of 220 patients for its combinatory Phase Ib clinical trial in triple negative breast cancer.

Recruitment is also ongoing for its Phase II study in advanced triple negative breast cancer and its Phase II study in melanoma. A further two trials are active, namely a Phase I/II trial in advanced solid tumors and a Phase II trial in a range of advanced malignancies.

Eddingpharm (EOC Pharma) – Phase I clinical trial

The Phase I clinical study is ongoing with efti for the treatment of metastatic breast cancer.

On October 28, 2019 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the presentation of a development update and validation data for its cutaneous squamous cell carcinoma (SCC) prognostic test, DecisionDx-SCC (Press release, Castle Biosciences, OCT 28, 2019, View Source [SID1234549951]).

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The study titled, "Development and validation of a prognostic gene expression profile (GEP) for stratification of cutaneous squamous cell carcinoma (SCC) patients by 3-year risk of regional or distant metastases," was presented during an Oral Abstract session at the American Society for Dermatologic Surgery (ASDS) Annual Meeting, October 24-27 in Chicago.

Study Background

Approximately 1 million patients are diagnosed with SCC in the U.S. each year, and the incidence continues to grow.
Many patients with SCC will have a favorable prognosis, but an estimated 15,000 people in the U.S. die from SCC each year, surpassing the number of U.S. deaths from cutaneous melanoma estimated to be as high as 9,000.
National guidelines define different treatment pathways and follow-up schedules for low-risk and high-risk SCC patients, but the low positive predictive value (PPV) of available staging systems means that the majority of high-risk patients do not develop metastases. Thus, many high-risk patients may be over-treated with radiation, chemotherapy or other interventions even when they may not be needed.
There is a clear need for more accurate methods to identify high-risk SCC patients to appropriately direct work-up and treatment plans.
To address this need, Castle Biosciences has developed DecisionDx-SCC, a proprietary 40-gene prognostic test. The test was designed to improve upon existing clinicopathologic staging systems and identify SCC patients who are classified as high risk based upon clinicopathologic staging, but who are actually at a low biological risk for metastasis, and thus, can be considered for de-escalation in their treatment plan. Conversely, the test is also designed to identify a biologically high-risk group that has a significantly higher risk of metastasis than would be determined by clinicopathologic staging alone.

Study Findings

Successful development of a 40-gene signature that identifies three groups of patients with significantly different risk for regional/distant metastasis using a training set of 122 patients.
The multicenter validation study included 321 patients, of which 93% had one or more high-risk features and 52 patients experienced metastasis.
Patients with a Class 1 result (n=203; lowest risk group) had a 91.6% 3-year metastasis-free survival (MFS) rate, significantly better than the MFS rate for patients with a high-risk Class 2A (80.6%; n=93) or highest risk Class 2B (44%; n=25) test result (p<0.0001).
The negative predictive value (NPV) for the DecisionDx-SCC Class 1 was 91.1%. Among all patients in the study, 63% had a Class 1 (lowest risk) result. This group could be considered for de-escalation in their treatment plan.
The PPV for DecisionDx-SCC Class 2B was 60% compared to the PPV for Brigham and Women’s Hospital (BWH) staging of 35.3% and American Joint Committee on Cancer (AJCC version 8) staging of 20.9%.
DecisionDx-SCC demonstrated strong independent prognostic value in multivariate analyses compared to the BWH and AJCC v8 staging systems. Specifically, when compared to the BWH staging system, DecisionDx-SCC Class 2B had a hazard ratio (HR) of 8.9 (p<0.001) compared to an HR of 1.9 for BWH high risk (p<0.05). Similarly, when compared to the AJCC v8 staging system, DecisionDx-SCC Class 2B had an HR of 9.8 (p<0.001) compared to an HR of 2.6 for AJCC high risk (p<0.001).
"Clinical validation of this prognostic test for SCC demonstrates significant progress towards improved identification of high-risk patients beyond currently available staging systems," commented Ashley Wysong, M.D., University of Nebraska Medical Center, Omaha NE, study investigator and presenter. "Clinical application of this test may allow us to de-escalate care in patients identified as low risk by tumor biology, as well as provide us objective data to guide implementation of adjuvant radiation, chemotherapy and clinical trial recommendations for those at actual high risk."

Additional DecisionDx-SCC performance studies are currently underway, including a prospective study. The DecisionDx-SCC test is the second skin cancer test discovered, developed and validated by Castle Biosciences.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC), a nonmelanoma skin cancer, is one of the most common cancers. Approximately 1,000,000 patients are diagnosed with SCC each year in the U.S. Most patients have a favorable prognosis, but a subset of patients will develop metastasis and up to 15,000 patients each year die from their disease, exceeding the number of deaths from cutaneous melanoma. As current staging parameters have a low positive predictive value, many more patients are considered high risk than actually develop metastatic disease. Conversely, many patients who develop metastatic disease are misidentified as low risk. This may lead to over and undertreatment of a substantial number of SCC patients. To address this clinical need, Castle Biosciences has developed a gene expression profile test designed to improve upon current staging systems and identify patients with SCC at high risk for metastasis or recurrence, in order to enable more informed clinical decisions regarding adjuvant therapy and other management options.

On October 28, 2019 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported that it will release its financial results for the third quarter ended September 30, 2019, after the close of market on Monday, November 11, 2019 (Press release, Castle Biosciences, OCT 28, 2019, https://castlebiosciences.com/press-releases/castle-biosciences-to-release-third-quarter-2019-financial-results-and-host-conference-call-on-monday-november-11-2019/ [SID1234549950]).

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Company management will host a conference call and webcast to discuss its financial results and provide a corporate update at 4:30 p.m. Eastern time on the same day.

Conference Call and Webcast Details

A live webcast of the conference call can be accessed here or via the webcast link on the Investor Relations page of the Company’s website (www.castlebiosciences.com). Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until December 2, 2020.

To access the live conference call via phone, please dial 877-282-2581 from the United States and Canada, or +1 470-495-9479 internationally, at least 10 minutes prior to the start of the call, using the conference ID 4476877.

There will be a brief Question & Answer session following the corporate update.

On October 28, 2019 Applied BioMath (www.appliedbiomath.com), the industry-leader in applying systems pharmacology and mechanistic modeling, simulation, and analysis to de-risk drug research and development, reported their participation at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) occurring November 6th-10th in National Harbor, Maryland (Press release, Applied BioMath, OCT 28, 2019, View Source [SID1234549946]). They will present two posters at the conference Friday, November 8th.

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Katie Williams, PhD, Associate Director, Business Development, Applied BioMath will present the poster titled "A semi-mechanistic platform model to capture individual animal responses to checkpoint inhibitors in a syngeneic mouse model." In this work, we describe the generation of a model platform that captures essential aspects of the pharmacokinetics, cellular and tumor growth effects of murine surrogates of two checkpoint therapeutic antibodies, anti-PD1 and anti-CTLA4, in the CT26 syngeneic tumor model. The model describes individual animal responses regarding drug exposure, key intra-tumoral cell kinetics and tumor volume changes and provides biologically plausible explanations for the observed differences between good and poor responders to treatment with anti-PD1 or anti-CTLA4.

Jennifer Park, PhD, Director, Business Development, Applied BioMath will present the poster titled "Semi-mechanistic PK and target-occupancy modeling to support dose justification for anti-PD-L1 clinical candidate CK-301 (TG-1501) in oncology patients." In this work, a semi-mechanistic pharmacokinetic/target-occupancy (PKTO) model was developed with in vitro, preclinical and clinical data to facilitate dose selection of CK-301 (also known as TG-1501, cosibelimab), an anti-PD-L1 monoclonal antibody (mAb), for ongoing and future clinical trials in oncology patients. The model was used to compare the PK and tumor target occupancy (TO) at steady state under various dosing regimens with cosibelimab to those with three marketed anti-PD-L1 mAbs (i.e. atezolizumab, durvalumab and avelumab).

"We are excited to participate at SITC (Free SITC Whitepaper) for the first time this year!" said John Burke, PhD, Co-founder, President and CEO, Applied BioMath. "We hope to introduce the benefits of systems modeling and simulation to SITC (Free SITC Whitepaper) attendees, and how this analysis can be applied to cancer immunotherapy research and development from very early development through clinical trials."

For more information about all of Applied BioMath’s events, visit View Source

On October 28, 2019 SFA Therapeutics, Inc. reported that FDA has granted an official Orphan Drug Designation (ODD) to SFA001, the company’s novel human-microbiome-based treatment for human hepatocellular carcinoma (HCC) (Press release, SFA Therapeutics, OCT 28, 2019, View Source [SID1234549943]).

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"By granting an Orphan Drug Designation to SFA001, FDA has given a special status to treatment of the most prevalent form of liver cancer. This ODD designation will provide SFA Therapeutics with significant drug development and tax advantages as well as an expanded period of market exclusivity," stated Ira Spector, PhD, SFA Therapeutics’ CEO. "These advantages undoubtedly will speed the drug’s availability for a disease that kills hundreds of thousands of patients annually world-wide."

While hepatocellular carcinoma afflicts 54,000 patients a year in the US (Cancer.net), the World Health Organization estimates the disease causes as many as 880,000 deaths per year globally –especially in China and other parts of Asia. SFA Therapeutics has already been granted two patents recognizing the uniqueness of SFA001 treatment. In validated transgenic HBX animal models, SFA001 blocked the progression of hepatitis B to hepatocellular carcinoma and demonstrated a non-chemotoxic mechanism of action in two different animal models of HCC.