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Lynparza Phase III PROfound trial in HRR* mutation-selected metastatic castration-resistant prostate cancer met primary endpoint

On August 7, 2019 AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported positive results from the Phase III PROfound trial of Lynparza (olaparib) in men with metastatic castration-resistant prostate cancer (mCRPC) who have a *homologous recombination repair gene mutation (HRRm) and have progressed on prior treatment with new hormonal anticancer treatments (e.g. enzalutamide and abiraterone) (Press release, AstraZeneca, AUG 7, 2019, View Source [SID1234538256]).

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Results from the trial showed a statistically-significant and clinically-meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS) with Lynparza vs. enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or ATM gene mutations, a subpopulation of HRR gene mutations. The safety and tolerability profile of Lynparza was generally consistent with previous trials.

José Baselga, Executive Vice President, Oncology R&D, said: "For men with metastatic castration-resistant prostate cancer the disease remains deadly, especially in those who have failed on a new hormonal anticancer treatment. This trial is the only positive Phase III trial of any PARP inhibitor in metastatic castration-resistant prostate cancer, where the need for new, effective therapies is high. The PROfound trial also demonstrates the potential value of genomic testing in this at-risk patient population. We look forward to discussing these results with global health authorities soon."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Metastatic castration-resistant prostate cancer is a deadly disease and represents an area of critical unmet medical need. The Phase III PROfound trial is another example of MSD and AstraZeneca’s shared commitment to improving long-term outcomes for people living with cancer. These results represent the potential for a new, oral targeted treatment option for this patient population."

AstraZeneca and MSD plan to present the full data from the trial at a forthcoming medical meeting. The companies are also exploring additional trials in prostate cancer, including the ongoing Phase III PROpel trial, testing Lynparza as a 1st-line therapy in mCRPC, in combination with abiraterone.

About PROfound

PROfound is a prospective, multicentre, randomised, open-label, Phase III trial testing the efficacy and safety of Lynparza versus enzalutamide or abiraterone in patients with mCRPC who have progressed on prior treatment with new hormonal anticancer treatments and have a qualifying tumour mutation in one of 15 genes involved in the HRR pathway, including among them BRCA1/2, ATM and CDK12.

About metastatic castration-resistant prostate cancer

Prostate cancer is the second-most common cancer in men, with an estimated 1.3 million new cases diagnosed worldwide in 2018 and is associated with a significant mortality rate.1 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.2 mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.2 Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these will have metastases at the time of CRPC diagnosis.3 Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.3 Despite an increase in the number of available therapies for men with mCRPC, five-year survival remains low.3

About Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in 64 countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is approved in the US, EU, Japan and several other countries as 1st-line maintenance treatment of BRCAm advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 40 countries, including the US and Japan, for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy; in the EU this includes locally advanced breast cancer. Regulatory reviews are underway in other jurisdictions for ovarian, breast and pancreatic cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 25,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

In January 2016, AstraZeneca announced that Lynparza was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) for the monotherapy treatment of BRCA1/2- or ATM gene-mutated mCRPC in patients who have received a prior taxane-based chemotherapy and at least one newer hormonal agent (abiraterone or enzalutamide), based on the positive results of the TOPARP-A Phase II trial.

About the AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as one of AstraZeneca’s four Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

ADC Therapeutics and SOPHiA GENETICS Partner for Biomarker Discovery in Pivotal Phase II Clinical Trial

On August 6, 2019 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of antibody drug conjugates (ADCs), and SOPHiA GENETICS, a leader in Data-Driven Medicine, reported they have entered into a collaboration to identify genomic markers associated with clinical response to ADCT-402 (loncastuximab tesirine) (Press release, ADC Therapeutics, AUG 6, 2019, View Source [SID1234596057]). ADC Therapeutics is currently evaluating ADCT-402 in a pivotal Phase II clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

SOPHiA GENETICS will conduct somatic mutation analysis of more than 4,000 genes in cell-free DNA (cfDNA) samples extracted from blood of DLBCL patients participating in ADC Therapeutics’ Phase II trial. SOPHiA technology will match detected genomic markers with clinical response to ADCT-402. The analytical power of SOPHiA for the detection of cancer mutations is key for this new development phase and illustrates the benefits of adopting Data-Driven Medicine applications for clinical trials.

"Our collaboration with SOPHiA GENETICS has the potential to uncover genomic mutations that correlate with clinical response to ADCT-402," stated Patrick van Berkel, Senior Vice President of Research and Development at ADC Therapeutics. "We have observed significant single-agent clinical activity in our pivotal Phase II trial of ADCT-402 in a broad population of patients with relapsed or refractory diffuse large B-cell lymphoma. The insights from this collaboration will allow us to better identify and understand the characteristics of patients who respond best to treatment. We look forward to the results of this research enabled by SOPHiA’s unique platform."

"We are pleased to partner with ADC Therapeutics, a leader in antibody drug conjugate development, to provide advanced biomarker analysis and turn the results into actionable insights that can improve clinical outcomes for patients and pave the way towards a new era in drug development," said Esteban Czwan, Senior Vice President BioPharma at SOPHiA GENETICS.

Financial terms of the collaboration were not disclosed.

About ADCT-402
ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) comprised of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (NCT03589469), a Phase Ib trial in combination with ibrutinib in patients with R/R DLBCL or mantle cell lymphoma (MCL) (NCT03684694) and a Phase Ib trial in combination with durvalumab in patients with R/R DLBCL, MCL or follicular lymphoma (NCT03685344). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of relapsed or refractory DLBCL and MCL.

Cleave Therapeutics Appoints Amy Burroughs Chief Executive Officer and Completes $12 Million Equity Financing

On August 6, 2019 Cleave Therapeutics, Inc. (formerly Cleave Biosciences), a biopharmaceutical company focused on protein homeostasis and stress pathways in cancer and neurodegeneration, reported that it has appointed industry veterans Amy Burroughs as chief executive officer and Scott Harris as chief operating officer (Press release, Cleave Biosciences, AUG 6, 2019, View Source [SID1234557024]). Cleave also announced the closing of a $12 million financing to advance CB-5339, its second-generation, IND-ready, valosin-containing protein (VCP)/p97 inhibitor through early clinical development. The financing was led by 5AM Ventures, Celgene Corporation, Orbimed, U.S. Venture Partners (USVP), Arcus Ventures, Astellas Venture Management, and Osage University Partners (OUP).

Cleave’s lead drug development candidate, CB-5339, is a potent, oral, selective, secondgeneration inhibitor of VCP/p97, which addresses limitations of earlier compounds, including exposure and selectivity to the target. The company is initiating a Phase 1 clinical study in acute myeloid leukemia (AML), for which there is compelling preclinical data and a significant unmet medical need. In addition, the National Cancer Institute, which has a decades-long interest in VCP/p97 as a target, is planning to sponsor a Phase 1 trial with CB5339 in solid tumors in collaboration with Cleave.

"There is increasing scientific rationale supporting VCP/p97 as a key regulator of cell processes critical for cancer cell survival, particularly in acute myeloid leukemia (AML)," said Peter Thompson, MD, partner, Orbimed and Cleave co-founder. "The Cleave team has made significant progress in overcoming the challenges of earlier molecules, and generated robust preclinical data from strategic collaborators at the National Cancer Institute and academic institutions."

In addition to the management appointments, Laura Shawver, PhD, CEO of Synthorx, was named board chair of Cleave.

"We are thrilled that Cleave will be advancing CB-5339 to clinical development and welcome Ms. Burroughs to lead the company," said Dr. Shawver. "Amy has spent her career helping move novel drug candidates through the drug development process with a focus on understanding market needs, building partnerships and attracting top-notch talent. She will be instrumental as the company prepares for clinical studies in hematologic malignancies and solid tumors and continues to assess the potential in neurodegenerative diseases."

Ms. Burroughs brings more than 25 years of healthcare and life sciences leadership experience, most recently serving as executive-in-residence (EIR) at 5AM Ventures and as a strategic commercial advisor to Crinetics Pharmaceuticals. She began her biopharmaceutical career at Genentech and was previously founder and managing partner of The Ventral Group, a strategic life sciences consulting and investor advisory firm. Ms. Burroughs’ industry experience also includes consulting with Egon Zehnder and serving as the chief commercial officer and head of business development for APT Pharmaceuticals. She received her BA from Dartmouth College and her MBA from Harvard Business School, where she graduated as a Baker Scholar.

Scott Harris brings more than 20 years of broad cross-functional experience advancing novel products through preclinical and clinical development. Mr. Harris most recently held executive positions at two BridgeBio subsidiaries, including serving as executive vice president, corporate development and operations at Navire Pharma. Previously, he was executive vice president of regulatory affairs and technical operations at Adynxx, where he directed development activities from pre-clinical through Phase 2 studies. Mr. Harris also held positions of increasing responsibility at Corthera, BioMarin Pharmaceutical, Attenuon, Angstrom Pharmaceutical and Biosite. He obtained his BS in biochemistry and cell biology from University of California, San Diego, and his MS in regulatory affairs from San Diego State University.

About VCP/p97
VCP/p97 is a critical enzyme in the AAA (ATPases Associated with diverse cellular Activities) family of ATPases and is a key regulator of various aspects of protein homeostasis and cellular stress pathways that are critical for cancer cell growth and survival. Inhibition of VCP/p97 has been shown to impact multiple stress response pathways — including proteotoxic stress and DNA damage repair where cancer cells are differentially sensitive— and drive cancer cells past the tipping point towards apoptosis. In neurodegenerative diseases, VCP/p97 has been shown to be important for the health and function of mitochondria, and Cleave’s research has demonstrated the potential for therapeutic benefit for patients with these debilitating diseases.

Applied DNA Schedules Fiscal 2019 Third Quarter Financial Results Conference Call for Tuesday, August 13, 2019 at 4:30 PM ET

On August 6, 2019 Applied DNA Sciences, Inc. (NASDAQ: APDN), reported it plans to release financial results for its fiscal 2019 third quarter ended June 30, 2019 after market close on Tuesday, August 13, 2019 (Press release, Applied DNA Sciences, AUG 6, 2019, View Source [SID1234538639]). In conjunction with the release, the Company has scheduled a conference call at 4:30 p.m. Eastern Time that will also be broadcast live over the Internet.

What: Applied DNA’s Fiscal 2019 Third Quarter Financial Results Conference Call

When: Tuesday, August 13, 2019, at 4:30 p.m. Eastern Time

Where: Via phone by dialing +1 844-887-9402 or +1 412-317-6798 and ask to join the Applied DNA call;
via webcast.

A telephonic replay of the conference call will be available for one day and may be accessed by calling +1 877-344-7529 or +1 412-317-0088 with the passcode 10133063. The webcast will be archived within the ‘Events and Presentations’ portion of the ‘Investors’ page to the company’s website.

Aurinia Reports Second Quarter 2019 Financial Results and Operational Highlights

On August 6, 2019 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH / TSX:AUP) ("Aurinia" or the "Company"), a late- stage clinical biopharmaceutical company focused on advancing voclosporin in multiple indications, reported financial results for the three and six months ended June 30, 2019 and recent operational highlights (Press release, Aurinia Pharmaceuticals, AUG 6, 2019, View Source [SID1234538319]). Amounts, unless specified otherwise, are expressed in U.S. dollars.

"During the past quarter, the Aurinia team has taken multiple steps forward preparing the organization for the next phase of its evolution into a commercial-stage entity. In anticipation of the AURORA Phase 3 results in lupus nephritis, we are appropriately scaling the organization ahead of data, which if confirmatory, sets the stage for a NDA filing during the first half of next year. If approved, we project a commercial launch of voclosporin in early 2021 as a potentially first-line treatment, in combination with mycophenolate mofetil and low-dose steroids for lupus nephritis," commented Peter Greenleaf, President and Chief Executive Officer of Aurinia.

Michael Martin, Chief Operating Officer stated, "In parallel, we are taking all of the steps necessary to initiate a Phase 2/3 clinical trial with VOS for the potential treatment of DES. This Phase 2/3 trial follows a well-established development path for ophthalmic drugs in this therapeutic area."

Mr. Greenleaf further said, "With respect to our ongoing proof-of-concept study for FSGS, we have added additional clinical trial sites and have modified the study protocol to broaden the inclusion of patients who have received limited corticosteroids exposure prior to enrollment. We expect that these actions will lead to enhanced enrollment."

VOS Phase 2/3 AUDREY ("Aurinia Dry Eye Study") Clinical Study in DES

Based upon the VOS exploratory Phase 2a results, Aurinia has initiated plans for a Phase 2/3 study which is expected to enroll its first patient in the fourth quarter of 2019. This study will include certain critical regulatory requirements that the FDA has traditionally required for DES product approval, which include both dose-optimization along with a comparison to vehicle.

The Phase 2/3 clinical study otherwise known as, "THE AUDREY STUDY" is designed as a randomized, double-masked, vehicle-controlled, dose ranging study to be conducted in the U.S., AUDREY will evaluate the efficacy and safety of VOS in subjects with DES. Approximately 480 subjects are to be enrolled. The study will consist of four arms and in a 1:1:1:1 randomization schedule to either 0.2% VOS, 0.1% VOS, 0.05% VOS or vehicle, dosed twice daily for 12 weeks. The primary outcome measure for the study is the proportion of subjects with 10mm improvement in Schirmer Tear Test ("STT") at 4 weeks.

Secondary outcome measures, which will be assessed at multiple time points include, STT, Fluorescein Corneal Staining ("FCS"), change in eye dryness, burning/stinging, itching, photophobia, eye pain and foreign body sensation, change in Symptom Assessment in Dry Eye ("SANDE") score and additional safety endpoints.

Voclosporin for Focal Segmental Glomerulosclerosis ("FSGS")

Aurinia initiated a Phase 2 proof-of-concept, open-label study for FSGS in June 2018. The study was designed to evaluate the role of voclosporin for treatment-naïve patients diagnosed with primary FSGS. In response to slower than anticipated enrollment, Aurinia has recently opened additional clinical trial sites outside of the United States and has amended the study to allow enrollment of FSGS patients who have previously received limited corticosteroid exposure. Up to approximately 20 patients are expected to be enrolled with interim results anticipated in 2020.

Financial Liquidity at June 30, 2019

As at June 30, 2019, Aurinia had cash and cash equivalents of $131.5 million compared to $144.3 million of cash, cash equivalents and short-term investments at March 31, 2019 and $125.9 million at December 31, 2018. Net cash used in operating activities was $13.3 million for the second quarter ended June 30, 2019 compared to $12.3 million for the second quarter ended June 30, 2018.

The Company believes, that based on its current plans that it has sufficient financial resources to fund the existing LN program, including the AURORA trial and the AURORA 2 extension trial, complete the NDA submission to the FDA, conduct the ongoing Phase 2 study for FSGS, initiate the AUDREY Phase 2/3 study, and fund operations into the second half of 2020.

Second Quarter 2019 Financial Results

For the three months ended June 30, 2019 Aurinia reported a consolidated net loss of $15.9 million or $0.17 per common share compared to a consolidated net loss of $15.7 million or $0.19 per common share for the same period in 2018.

Research and development expenses (R&D) increased slightly to $11.2 million for the three months ended June 30, 2019, compared to $10.5 million for the three months ended June 30, 2018. The increase in these expenses reflected higher costs incurred for the AURORA 2 extension trial, the drug-drug interaction ("DDI") study preparation costs associated with the planned NDA submission for LN and preparation costs for the Phase 2/3 DES clinical study.

Corporate, administration and business development expenses increased to $4.9 million for the three months ended June 30, 2019, compared to $3.5 million for the same period in 2018. The increase was primarily due to an increase in consulting fees related to recruitment fees and pre-commercial activities, such as market and payor research, and higher personnel and sponsorship costs.

Non-cash stock compensation expense was $2.0 million for the second quarter ended June 30, 2019 as compared with $2.0 million for the same period in 2018 and is included in both research and development and corporate, general and business development expenses.

Aurinia incurred other expenses of $720,000 during the three months ended June 30, 2019 associated with the successful defense of a proxy contest in connection with its June 26, 2019 annual general meeting. There was no similar expense in the comparable period.

Aurinia also recorded a non-cash reduction of $625,000 in the estimated fair value of derivative warrant liabilities which reduced the loss for the second quarter ended June 30, 2019 compared to an increase of $1.9 million in the estimated fair value of derivative warrant liabilities which increased the loss for the second quarter ended June 30, 2018. The derivative warrant liabilities will ultimately be eliminated on the exercise or forfeiture of the warrants and will not result in any cash outlay by the Company.

Financial Results for Six Months Ended June 30, 2019

For the six months ended June 30, 2019, Aurinia reported a consolidated net loss of $28.3 million or $0.31 per common share compared to a consolidated net loss of $31.2 million or $0.37 per common share for the comparable period in 2018.

R&D expenses were $21.8 million for the six months ended June 30, 2019 compared to $19.4 million for the same period in 2018. The increase in these expenses reflected higher costs incurred for the AURORA 2 extension trial, the DDI study and preparation costs associated with the planned LN NDA submission partially offset by lower AURORA trial costs as this trial nears completion.

Corporate, administration and business development expenses were $8.8 million for the six months ended June 30, 2019 compared to $7.3 million for the same period in 2018. The increase reflects the same items as noted in the second quarter corporate, administration and business development expenses.

Non-cash stock compensation expense totaled $3.6 million for the six months ended June 30, 2019 as compared with $4.1 million for the same period in 2018 and is included in both research and development and corporate, general and business development expenses.

For the six months ended June 30, 2019 Aurinia recorded a decrease of $2.4 million in the estimated fair value of derivative warrant liabilities compared to an increase of $4.6 million for the comparable period in 2018.

This press release should be read in conjunction with our unaudited interim condensed consolidated financial statements and the Management’s Discussion and Analysis for the second quarter ended June 30, 2019 which are accessible on Aurinia’s website at www.auriniapharma.com, on SEDAR at www.sedar.com or on EDGAR at www.sec.gov/edgar.

Aurinia will host a conference call and webcast to discuss the second quarter ended June 30, 2019 financial results today, Tuesday, August 6, 2019 at 4:30 p.m. ET. This event can be accessed on the investor section of the Aurinia website at www.auriniapharma.com.