On December 12, 2019 Zhejiang Medicine, NovoCodex and Ambrx reported positive interim topline data from the ongoing "111" trial (CTR20171162) evaluating ARX788, a novel anti-HER2 ADC, in heavily pretreated patients with metastatic HER2 positive breast cancer (Press release, Zhejiang Medicine, DEC 12, 2019, View Source [SID1234552312]). All patients enrolled had failed prior therapy with trastuzumab and 47% had failed therapy with trastuzumab and lapatinib.

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ARX788 was well tolerated at all dose levels with just two ≥ Grade 3 drug related reversible adverse events observed amongst 51 enrolled patients. ARX788 showed an excellent safety profile with dose escalation continuing. No DLT or MTD was observed as of the November 20, 2019 cut-off date.

Response rates correlated with increased dose levels. As of the cut-off date, the highest dose tested was 1.5mg/kg every three weeks. This cohort, which continues dosing and remains under observation, had already achieved a 63% overall response rate. Prior cohorts at 0.88, 1.1 and 1.3 mg/kg demonstrated overall response rates of 14%, 36% and 56% respectively. Further, the substantial increases in efficacy observed at higher doses was achieved with only mild increases in toxicity.

These data originate from the Fudan University Shanghai Cancer Center in China and are part of a broader global ARX788 development program (NCT03255070 and CTR20171162) that includes clinical sites in China, USA and Australia.

The 42nd Annual San Antonio Breast Cancer Symposium Poster is available at www.ambrx.com

Zhejiang Medicine licensed the commercial rights to ARX788 in China in 2013. The promising clinical data for ARX788 serves as a solid foundation to the second and more recent collaboration. Earlier this year, Ambrx and Zhejiang Medicine (via its subsidiary NovoCodex) entered into their second collaboration to develop and commercialize ARX305 in China. ARX305 is an anti-CD70 Antibody Drug Conjugate for the potential treatment of Renal Cell Carcinoma, Multiple Myeloma, and other solid tumors.

About HER2-Positive Breast Cancer

Almost 300,000 new cases of HER2 positive breast cancer may be diagnosed in 2020 in the US alone (approximately 15-20% of breast cancers are HER2 positive). HER2 positive breast cancer tends to be aggressive and more likely to recur than HER2 negative. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2 positive metastatic breast cancer after progression on T-DM1 (which is not approved in China).

On December 12, 2019 Senhwa Biosciences Inc. (TPEx: 6492), a clinical stage biopharmaceutical company focused on next generation DNA Damage Response (DDR) therapeutics for the treatment of cancer, reported positive results from its Phase 1 trial of CX-5461. CX-5461 is the company’s First-in-Class G-quadruplex stabilizer (Press release, Senhwa Biosciences, DEC 12, 2019, View Source [SID1234552331]). The patients enrolled in the study all presented with advanced solid tumors, with no other available treatment options.

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In 2016, CX-5461 was awarded a Stand Up to Cancer Dream Team Grant. Phase 1 clinical findings were featured within a spotlighted presentation at the annual 2019 San Antonio Breast Cancer Symposium (SABCS) by Senhwa’s clinical partner, Canadian Cancer Trials Group (CCTG).

"CX-5461 has demonstrated clinically meaningful and durable benefits in patients with specific tumor biomarkers that are also resistant to platinum and other chemotherapeutics. The Phase 1 study has validated CX-5461 as a G-quadruplex stabilizer within a novel class of therapy that accelerates dsDNA breaks and has proven human efficacy across certain tumor types," said Dr. Tai-Sen Soong, CEO of Senhwa Biosciences. The clinical results exhibited that CX-5461 has the potential to rescue cancer patients who have developed resistance to platinum and other chemotherapeutics. Additional clinical trials are being planned to further confirm the efficacy seen.

The Phase 1 dose escalation portion of the CX-5461 trial was designed to determine Recommended Phase 2 Dose (RP2D), as well as evaluate preliminary anti-tumor activity of a single agent (CX-5461), in patients with metastatic and recurrent solid tumors. 41 patients enrolled in the study, due to the fact that all available treatments had failed to treat their malignancies, and 40 of those patients had been treated with different dose levels of CX-5461.

As of the November 25th, 2019 data cutoff, the study findings showed:

32 of 41 patients enrolled were evaluable patients, the median age was 53 (range 25-73).
Of the evaluable patients, 24 had attempted 3 or more prior treatment regimens for their disease.
In this heavily pre-treated Phase 1 population, responses were seen with CX-5461 within the dose range of 100mg/m2 to 650mg/m2.
Patients presented with a range of solid tumors, including metastatic breast cancer (47.5%), Ovary (17.5%), Pancreas (7.5%), Non-small-cell Lung Cancer (5%) and others (22.5%)
Preliminary Safety Analysis:

CX-5461 was well tolerated:
– Treatment-related Adverse Events (AEs ≥20%) were photosensitivity of the skin (58%); eye disorders (including Photosensitivity 20%); nausea (70%); headache (25%); fatigue (73%).
– No Dose Limited Toxicities (DLTs) observed to date. There were 6 treatment-related non-DLT grade 3 photosensitivity events.
– The RP2D was determined to be 475mg/m2 on days 1, 8 and 15 of a 4-week cycle.
UV avoidance and protection measures were successful in mitigating risks associated with photo toxicity.
Preliminary Efficacy Analysis:

As of the data cutoff, 32 patients were evaluable for response. In terms of best response, 4 patients (3 breast cancer, 1 ovary) had a confirmed Partial Response with an additional 4 patients had durable Stable Disease.
Heavily pre-treated (including platinum resistant) patients with specific biomarkers showed significant tumor shrinkage and maintained significant treatment duration in the trial. The maximum duration was 16 cycles, with 28 days per cycle.
G-quadruplex stabilizers are a novel class of therapy that has demonstrated accelerated dsDNA breaks.
About CX-5461

CX-5461 is designed to stabilize DNA G-quadruplexes of cancer cells and leads to disruption of the cell’s replication fork. While acting in concert with HR (Homologous Recombination) pathway deficiency, such as BRCA1/2 mutations, replication forks stall and cause DNA breaks, resulting in cancer cell death. CX-5461 in combination with HRD (Homologous Recombination Deficiency) tumors may be exploited through a synthetic lethality approach, targeting DNA repair defects in HRD tumors.

On December 12, 2019 Toronto Innovation Acceleration Partners ("TIAP") reported the launch of a new project developed under the BRIDGE LAB150, a partnership between Evotec SE and TIAP (Press release, Evotec, DEC 12, 2019, View Source;announcements/press-releases/p/toronto-innovation-acceleration-partners-tiap-adds-novel-kras-oncology-project-to-its-lab150-portfolio-5879 [SID1234552313]). The project will be focusing on breakthroughs in novel cellular drug screening systems in oncology-focused scientific KRAS research by Professor Igor Stagljar at the University of Toronto, a TIAP Member, and aims to develop therapeutics targeting the protein-protein interactions of KRAS and its downstream interacting partners.

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The low survival rates of three of the four most lethal cancers in North America – pancreatic, colorectal and lung – are associated with KRAS mutations, a well-established cancer driver. Although there is an urgent need for KRAS-targeting therapeutics, so far there has been a lack of clinically available drugs as oncogenic KRAS is very difficult to target directly.

LAB150 accelerates academic research towards commercial outcomes by providing funding and access to pharmaceutically validated platforms and expertise. For further information on the new LAB150 projects

On December 12, 2019 Agendia, Inc., a world leader in precision oncology for breast cancer, reported new data comparing genomic profiling results for patients under the age of 50 with early-stage breast cancer (Press release, Agendia, DEC 12, 2019, View Source [SID1234552332]). The data, which are being presented for the first time today at the 2019 San Antonio Breast Cancer Symposium (SABCS), show that the MammaPrint 70-gene assay may more effectively identify premenopausal women who may safely avoid chemotherapy.

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One of the biggest challenges physicians face when treating patients with early stage, curable breast cancer is choosing a treatment path that will mitigate the risk of disease recurrence, while avoiding over- or undertreatment. Genomic profiling has helped address this clinical need, but recent findings suggest age may impact the veracity of results for some assays. A follow up to the TAILORx study published in 2018 led to a change in recurrence score (RS) stratification for patients under 50 and, more importantly, left the ideal treatment plan for those with a RS of 21-25 unclear.

"Understanding how patient age may affect possible benefit from chemotherapy is a critically important question that has needed further exploration and clarification," said William Audeh, MD, MS, chief medical officer, Agendia.

The Agendia Prospective Study of MammaPrint in Breast Cancer Patients with an Intermediate Recurrence Score (PROMIS) trial previously demonstrated that MammaPrint, which provides a binary, High Risk or Low Risk of recurrence, delivers clinically actionable results for patients who receive a RS of 18-30 by the 21-gene assay. The findings presented today at SABCS represent a sub-analysis of the PROMIS data, which Agendia conducted to help determine the potential of the MammaPrint test to clarify adjuvant chemotherapy decisions for premenopausal women.

Results – which are statistically significant – demonstrate that 58 percent of women age 50 and under with RS 18-20 and 46 percent of those with RS 21-25 are categorized as MammaPrint Low, indicating that they may safely forgo chemotherapy. Additionally, 15 percent of women with RS 26-30 were found to be MammaPrint Low Risk and may be potential candidates for de-escalation of adjuvant chemotherapy.

"Treatment recommendations in ER+ patients <50 years: Comparison of the 21-gene assay and 70-gene signature in the PROMIS study" can be found at: View Source

On December 12, 2019 Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage biotechnology company targeting the epigenetic causes of cancer, reported the acceptance of an abstract at the "Epigenetics Symposium: 15 Years of Lysine Demethylases: From Discovery to the Clinic" taking place Monday, December 16, 2019 at the Franklin Institute in Philadelphia, PA (Press release, Flex Pharma, DEC 12, 2019, View Source [SID1234552314]). The trial-in-progress poster presentation will include an overview of the ongoing Phase 1/2 clinical trial for Salarius’ lead drug candidate, Seclidemstat, a potent reversible LSD1 inhibitor being developed as a treatment for Ewing sarcoma, a rare pediatric bone cancer.

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Details of the symposium and poster presentation are as follows:

Abstract Title: Trials in progress: A phase I/II clinical trial of the reversible LSD1 inhibitor, seclidemstat, in patients with relapsed/refractory Ewing sarcoma
Where: The Franklin Institute, 222 North 20th Street, Philadelphia
When: Monday, December 16, 2019 at 8:30 a.m. EST to 7 p.m. EST
Symposium Website: Epigenetics Symposium: 15 Years of Lysine Demethylases: From Discovery to the Clinic

"The Epigenetics Symposium is an ideal event to showcase our progress bringing our lead drug candidate, Seclidemstat, into the clinic and the impact it could have on Ewing sarcoma, a rare and deadly bone cancer that most often strikes children and young adults and for which there are no targeted therapies approved," stated David Arthur, Chief Executive Officer of Salarius Pharmaceuticals. "Lysine demethylase enzymes are a well-known target for epigenetic-based drug development. We have developed Seclidemstat to be a differentiated LSD1 inhibitor, and we are excited that it has reached the clinical trial setting where its safety and therapeutic activity can be assessed. Research shows that LSD1 expression is elevated in 60% of Ewing sarcoma patients and correlates with poor patient prognosis and decreased overall survival. Given the potential of Seclidemstat to address this great unmet need, we look forward to releasing early cohort data next year from our Ewing sarcoma study and a Phase 1 study in advanced solid tumors."