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New Data from Ambry Genetics Showed Concurrent RNA and DNA Testing Identified More Patients with Hereditary Breast Cancer than DNA Testing Alone

On December 10, 2019 Ambry Genetics (Ambry), a leading clinical genetic testing lab, reported that it will announce new data showing that conducting RNA and DNA tests for hereditary cancer risk at the same time identifies more patients with mutations that increase cancer risk than DNA testing alone (Press release, Ambry Genetics, DEC 10, 2019, View Source [SID1234552216]). To be presented at the San Antonio Breast Cancer Symposium (SABCS) this week, the data come from a study of 746 patients with breast cancer that received +RNAinsight, paired RNA and DNA genetic testing for hereditary cancer risk.

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Standard DNA testing for hereditary cancer risk excludes large portions of DNA, thereby missing some mutations. In addition, DNA testing can produce inconclusive results and fail to determine that an error in our DNA increases cancer risk. These limitations impact patients and their families because doctors may not have the information needed to recommend appropriate preventive, early detection, or therapeutic steps. Additionally, relatives may not be referred for genetic testing and obtain the care they would otherwise have gotten if they had learned they had mutations.

Adding RNA to DNA testing overcomes these limitations for a substantial number of patients as it provides considerably more evidence than DNA testing alone about whether our DNA has mutations.

The data showed that adding RNA genetic testing to DNA testing increased the diagnostic yield – the number of people found to have a mutation that increases cancer risk – across 16 hereditary breast and/or ovarian cancer genes. As a result of +RNAinsight, five breast cancer patients were identified to have mutations in clinically-actionable genes that would have otherwise been missed completely or the patient would have received inconclusive results if they had received DNA testing only. These findings included three women with mutations in BRCA1/2, one woman with a mutation in ATM, and one woman with a mutation in PMS2. Additionally, paired RNA and DNA genetic testing decreased the number of inconclusive results, giving patients more definitive answers about whether their breast cancers were hereditary. Additional results will be presented on an expanded breast cancer cohort at the meeting on Saturday, December 14th.

"These data further prove that paired RNA and DNA genetic testing for hereditary cancer should be the industry standard," said Holly LaDuca, MS, CGC, senior manager of Ambry’s clinical affairs research. "Our research has consistently shown that +RNAinsight provides clinicians with more accurate results, better informing patient care."

Researchers from Ambry will also present at SABCS new data from a pre-and post-test clinician survey that assessed how genetic testing for hereditary cancer impacted medical management, such as screening recommendations. The survey found that positive genetic testing results frequently lead to changes in management recommendations in both high risk (e.g. BRCA1) and moderate risk (e.g. ATM) genes. Changes to mammogram, breast MRI, and/or preventive surgery options were reported in 77.3% of positive individuals. Moreover, medical management changes largely adhered to published guidelines, indicating that clinicians are applying recommendations appropriately based on test results.

"With this survey data, clinicians are showing us that they truly do use genetic testing results to implement personalized recommendations, which can be life-saving for a patient," said Carrie Horton, MS, CGC, senior researcher in Ambry’s clinical affairs team. "These data provide further evidence that genetic testing is essential to comprehensive cancer care. Continued study in this area will aid clinicians, laboratories, health plans, and ultimately patients."

Below are summaries of each of the four studies that Ambry will present at SABCS 2019.

Friday, December 13, 5:00- 7:00 PM CST

P5-07-06, Black M, et. al., Performance of Polygenic Risk Score Combined with Clinical Assessment for Breast Cancer Risk

Findings suggest that the 100-SNP polygenic risk score significantly improves estimation of breast cancer risk based on non-genetic models, and can be used to further identify women at increased lifetime risk who would otherwise not be identified by clinical assessment alone.
Saturday, December 14, 7:00 – 9:00 AM CST

P6-08-35, Horton C, et. al., Impact of Multigene Panel Testing on Medical Management: Preliminary Results of a Pre- and Post- Test Clinician Survey

The data from this ongoing study demonstrate that positive genetic test results frequently lead to changes in medical management and in some cases therapeutic recommendations.
P6-08-08, LaDuca H, et. al., Concurrent DNA and RNA Genetic Testing Identifies More Patients with Hereditary Breast Cancer than DNA Testing Alone

Concurrent DNA and RNA genetic testing for hereditary cancer risk through +RNAinsight identified more disease-causing mutations compared to DNA-only testing. In this study, five patients with breast cancer learned of their genetic mutations as a result of +RNAinsight and would have been missed with DNA testing alone.
P6-08-04, Yadav S, et. al., Germline Mutations in Cancer Predisposition Genes in Patients with Invasive Lobular Carcinoma of the Breast

Invasive lobular carcinoma (ILC) is the second-most common type of breast cancer, but the mutations that increase patients’ risk of developing ILC are largely unknown. The findings from this study improve our understanding of the mutations that increase patients’ risks for ILC and suggest that multigene genetic testing should be considered for all ILC patients.

Johnson & Johnson to Host Investor Conference Call on Fourth-Quarter Results

On December 10, 2019 Johnson & Johnson (NYSE: JNJ) reported that it will host a conference call for investors at 8:00 a.m. (Eastern Time) on Wednesday, January 22nd to review fourth-quarter results (Press release, Johnson & Johnson, DEC 10, 2019, View Source;johnson-to-host-investor-conference-call-on-fourth-quarter-results-300972383.html [SID1234552215]). Alex Gorsky, Chairman and Chief Executive Officer; Joseph J. Wolk, Executive Vice President, Chief Financial Officer and Christopher DelOrefice, Vice President, Investor Relations will host the call.

Investors and other interested parties can access the webcast/conference call in the following ways:

The webcast and presentation material are accessible at Johnson & Johnson’s website www.investor.jnj.com. A replay of the webcast will be available approximately three hours after the conference call concludes.

By telephone: for both "listen-only" participants and those financial analysts who wish to take part in the question-and-answer portion of the call, the telephone dial-in number in the U.S. is 877-869-3847. For participants outside the U.S., the dial-in number is 201-689-8261.

A replay of the conference call will be available until approximately 12:00 a.m. on January 30, 2020. The replay dial-in number for U.S. participants is 877-660-6853. For participants outside the U.S., the replay dial-in number is 201-612-7415. The replay conference ID number for all callers is 13697436.

The press release will be available at approximately 6:45 a.m. (Eastern Time) the morning of the conference call.

Please refer to www.investor.jnj.com for a complete list of currently planned 2020 earnings webcast/conference calls, including an updated second-quarter date of Thursday, July 16th, 2020.

Syndivia Raises €1M Investment to Advance Its Tumour Microenvironment Drug Delivery Platform

On December 10, 2019 Syndivia, a biotechnology company focused on the development of new therapeutic modalities for solid cancers based on specific targeting of the tumour microenvironment and anatomical hallmarks, reported a €1 million investment from Cap Innov’Est, an inter-regionally based seed fund (Press release, Syndivia, DEC 10, 2019, View Source [SID1234552214]).

This funding will enable Syndivia to advance its pipeline of proprietary anticancer therapies, including its lead drug candidate (SDV1001), thus completing the preclinical "proof of concept" study of the targeting of the microenvironment of solid tumours.

Sasha Koniev, Syndivia’s CEO, said, "We are very pleased to see Cap Innov’Est joining the company’s founders. This funding will allow us to advance our drug platform for both small-molecule and biologics, which have the unique potential to address a wide range of solid cancer indications by harnessing the specific properties of the tumor microenvironment."

Jean-François Rax, Investment Director at Cap Innov’Est said, "We are truly enthusiastic to be investing in such a promising company. We are convinced that Syndivia’s breakthrough approach in the hands of its experienced management team will be successful in delivering innovative and efficient treatments for cancer patients."

Select Medical Corporation Closes Private Placement of $675 Million of 6.250% Senior Notes due 2026

On December 10, 2019 Select Medical Holdings Corporation ("Holdings") (NYSE: SEM), reported that Select Medical Corporation ("Select") has completed its private placement of $675 million aggregate principal amount of its 6.250% Senior Notes due 2026 as additional notes (the "Additional Notes") under same indenture as Select’s existing $550 million aggregate principal amount of 6.250% senior notes due 2026 that were originally issued on August 1, 2019 and, as such, will form a single series and trade interchangeably with such previously issued notes (Press release, Select Medical, DEC 10, 2019, View Source;300972584.html [SID1234552213]).

Selects intends to use a portion of the net proceeds of this offering, together with a portion of the net proceeds from a $615 million incremental term loan and, if required, available cash, to loan to its joint venture subsidiary, Concentra, Inc. ("Concentra"), pursuant to the terms of an intercompany loan agreement, an amount which will be used by Concentra to repay in full all currently outstanding term loan indebtedness under Concentra’s first lien credit agreement. Any remaining net proceeds from the offering will be used by Select for general corporate purposes.

The notes and related guarantees were sold in a private placement, solely to qualified institutional buyers in reliance on Rule 144A under the Securities Act of 1933, as amended (the "Securities Act"), or outside the United States to persons other than "U.S. persons" in compliance with Regulation S under the Securities Act. The notes and related guarantees have not been registered under the Securities Act or the securities laws of any other jurisdiction and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements.

This notice does not constitute an offer to sell the notes, nor a solicitation for an offer to purchase the notes, in any jurisdiction in which such offer or solicitation would be unlawful. Any offer of the notes will be made only by means of a private offering memorandum. This press release is being issued pursuant to and in accordance with Rule 135c under the Securities Act.

Ascentage Pharma Releases Updated Data of its Novel BCR-ABL Inhibitor, HQP1351, in an Oral Presentation Nominated for "Best of ASH"

On December 10, 2019 Ascentage Pharma (6855.HK), a globally-focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the updated results from the Phase I study of the company’s novel investigational drug HQP1351 were reported in an oral presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, Ascentage Pharma, DEC 10, 2019, View Source [SID1234552212]). The presentation titled "Updated Safety and Efficacy Results of Phase I Study of HQP1351, a Novel 3rd Generation BCR-ABL Inhibitor in Patients with Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia" was delivered by the principal investigator of the study, Qian Jiang, M.D., from Peking University People’s Hospital. In addition, the presentation data was nominated for the "Best of ASH (Free ASH Whitepaper)", a recognition that only a handful of innovative clinical programs from China have achieved.

HQP1351 is a novel, orally active potent 3rd generation BCR-ABL Tyrosine Kinase Inhibitor (TKI) under development for the treatment of patients with chronic myeloid leukemia (CML) resistant to current TKI-therapies including those with T315I mutation.

Key results from the trial:

The study is a Phase 1 trial of HQP1351 in Chinese patients with TKI-resistant CML in the chronic phase (CP) or accelerated phase (AP). Patients received treatment in one of the eleven dose cohorts ranging from 1mg to 60mg. 60mg QOD was identified as the dose-limiting toxicity (DLT) dose, 50mg QOD was considered as the maximum-tolerated dose (MTD), and 40mg was identified as RP2D;
As of May 27, 2019, 101 CML patients including 87 CP patients and 14 AP patients were enrolled in the study. The median duration of follow-up was 12.8 months (range, 1.2-31.5). The 18-month progression free survival (PFS) rate was 94% in CP and 61% in AP;
HQP1351 was well-tolerated in all dose cohorts with the exception of the 60mg cohort. Of all the treatment-related adverse events (TRAEs), most of the non-hematologic TRAEs were reported as Grade 1 or Grade 2; the most common hematologic TRAE of Grade 3/4 was thrombocytopenia (50%). The incidence of TRAEs declined with longer duration of treatment. No treatment-related deaths or Grade 5 AEs occurred;
HQP1351 showed potent anti-leukemic activities and a high response rate in TKI-resistant CML patients. The response rate and the depth of responses were further improved with longer duration of treatment. In the evaluable patients, the complete hematologic response (CHR) rate was 95% in CP and 85% in AP;
In the 95 evaluable patients with non-complete cytogenetic response (non-CCyR) at baseline, 69% of the CP patients achieved a major cytogenetic response (MCyR), of which 61% achieved a complete cytogenetic response (CCyR); 43% of the AP patients achieved MCyR, of which 36% achieved CCyR;
In the evaluable patients, the major molecular response (MMR) rate was 37% in CP and 36% in AP;
HQP1351 showed strong response in TKI-resistant CML patients with the T315I mutation. Among the T315I-mutant CP patients, the MCyR rate was 82%, and the CCyR rate was 78%.
"Drug-resistance to TKIs is an urgent unmet need and a major challenge in the treatment of CML. No third-generation TKI is currently approved in China, and no imported third-generation TKIs are expected to enter China in the foreseeable future," said presenting author Dr. Qian Jiang. "The updated results from this Phase I trial of HQP1351 have further validated its tolerability and anti-leukemic potential in refractory chronic myeloid leukemia. We look forward to collecting additional data from the pivotal Phase II trials and hope our work will soon benefit drug-resistant CML patients."

"The Phase I results on this third-generation BCR-ABL inhibitor have further demonstrated its clinical promise. HQP1351 returned to ASH (Free ASH Whitepaper) this year with an oral presentation and a nomination for ‘Best of ASH (Free ASH Whitepaper)’, all of which reaffirms the recognition of HQP1351’s potential clinical efficacy and safety by the international hematology community," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "There are three ongoing pivotal Phase II trials of HQP1351 in China, two of them have reached planned enrollment targets. The data readouts as well as an NDA submission in China are expected in 2020. In addition, the clinical development program of HQP1351 in the U.S. is ready to begin its patient enrollment. We hope HQP1351 will soon get the regulatory approval and reach the market to benefit drug-resistant CML patients in China and around the world."

About HQP1351

HQP1351 is a novel kinase inhibitor developed by Ascentage Pharma. It is an oral third-generation BCR-ABL inhibitor targeting a broad spectrum of BCR-ABL mutants, including those with the T315I mutation, to treat drug-resistant CML patients. A Phase I clinical trial for patients with TKI-resistant CML has been completed and the pivotal Phase II clinical trials are ongoing in China. In addition, a Phase Ib trial in patients with GIST and a Phase Ib trial are also ongoing in China and in the U.S., respectively.