On August 7, 2019 Epigenomics AG (FSE: ECX, OTCQX: EPGNY, the "Company") reported the operational achievements plus financial results for the second quarter and the first half of 2019 (Press release, Epigenomics, AUG 7, 2019, View Source [SID1234538264]).

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Operational highlights

– In January 2019, the Company announced positive results from a microsimulation model for the Epi proColon blood test. The results are awaiting publication.

– In March, the bipartisan "Donald Payne Sr. Colorectal Cancer Detection Act" (HR 1765) was reintroduced into the U.S. House of Representatives. In the meantime, the law has won numerous supporters in both parties and especially in the key committees of Congress. The latter is of great importance so that the law can be voted on – if not individually, then as part of a legislative package.

– On May 3, 2019, the Centers for Medicare & Medicaid Services (CMS) accepted the Company’s application to review Epi proColon as part of a National Coverage Determination (NCD). Once the review process has been opened, there is a statutory timeframe of maximum nine months within which CMS must have reached a decision and Epigenomics therefore has clarity regarding the reimbursement of Epi proColon.

6M 2019 Financial results
– In the first half of 2019, product revenue increased by 84% year-on-year to EUR 660 thousand.

– License revenue decreased to EUR 19 thousand (6M 2018: EUR 413 thousand) due to the termination of the collaboration with the Chinese licensing partner.

– Total revenue in the first six months of 2019 decreased from EUR 771 thousand to EUR 679 thousand compared to the same period in the prior year due to lower license revenue, which were not fully offset by higher product revenue.

– Research and development costs increased from EUR 3,043 thousand in the previous year to EUR 3,867 thousand. This increase resulted from expenses related to the post-approval study for Epi proColon and the HCC (liver cancer test) study in the U.S.

– Selling and administrative expenses rose by from EUR 3,883 thousand to EUR 4,859 thousand in the reporting period, due to an increase in sales and marketing activities related increased product revenue and commercial preparation of reimbursement coverage.

– Overall, operating costs were lower than estimated for the first six months of 2019. Operating expenses increased from EUR 7.1 million to EUR 9.4 million compared to prior year for the abovementioned reasons.

– Adjusted EBITDA (before share-based payment expenses) was EUR -7.2 million in the first six months of 2019 compared to EUR -5.4 million for the same period prior year.

– The net loss for the period was EUR -7.4 million vs. EUR -5.8 million for the prior year; the loss per share decreased to EUR 0.21 (6M 2018: EUR 0.24) due to the higher number of outstanding shares following the capital increase carried out in the second half of 2018.

– Cash consumption from operating activities increased by EUR 3.6 million to EUR 7.8 million in the first half of 2019 due to higher operating costs.

– As of June 30, 2019, liquidity amounted to EUR 9.1 million (including marketable securities) compared to EUR 17.1 million at year-end 2018.

Greg Hamilton, CEO of Epigenomics AG: "We continue to make progress on CMS reimbursement. CMS’s acceptance of our NCD is an important milestone. While the process of opening the NCD is taking longer than we would like we still remain optimistic and will continue to pursue all available paths to achieve coverage for Epi proColon."

Outlook 2019: revenue forecast adjusted
Revenue

– Due to the delays in the reimbursement decision in the U.S. described above, the revenue forecast has been adjusted from between EUR 3.0 million and EUR 6.0 million to between EUR 2.0 million and EUR 4.0 million.

EBITDA / Cash consumption

– Epigenomics AG specifies its guidance for adjusted EBITDA (before share-based payment expenses). For the full year 2019, the Company expects an adjusted EBITDA within the range of EUR -12.5 million to EUR -14.0 million. Cash consumption is expected to be within a range of EUR -13.5 million to EUR -15.0 million, due to payments in the first quarter of 2019 for which the corresponding expenses had already been incurred in 2018.

Further information
The financial report for the first six months of 2019 is available on the Epigenomics website: View Source." target="_blank" title="View Source." rel="nofollow">View Source

Conference call for analysts and investors
Epigenomics AG will host a conference call for analysts and investors today at 4.00 pm (CET) / 10.00 am (EDT). The webcast can be accessed on the Company’s website: View Source
The dial-in numbers for the conference call are:
Dial-in number Germany: +49 30 232 531 411
Dial-in number UK: +44 1635 598 060
Dial-in number USA: +1 516-269-8983
Participants are kindly asked to dial in 10 minutes prior to the start of the call.
An audio replay of the conference call will be provided on the Epigenomics’ website subsequently.

On August 7, 2019 ArQule, Inc. (Nasdaq: ARQL) reported its financial results for the second quarter of 2019 (Press release, ArQule, AUG 7, 2019, View Source [SID1234538263]).

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For the quarter ended June 30, 2019, the Company reported a net loss of $9.1 million, or $0.08 per basic share, compared with net income of $5.2 million, or $0.05 per diluted share, for the quarter ended June 30, 2018.

As of June 30, 2019, the Company had a total of approximately $182.8 million in cash, cash equivalents, and marketable securities.

Key Highlights from Q2, 2019

In June 2019, the Company raised approximately $104 million of gross proceeds in a public offering of common stock. Net proceeds will be used to fund clinical programs and for general corporate purposes
ARQ 531, our potent and reversible dual inhibitor of both wild-type and C481S-mutant BTK.
Presented first-of-its kind clinical proof-of-concept data at the 2019 European Hematology Association (EHA) (Free EHA Whitepaper) Annual meeting from the ongoing phase 1 trial, including 4 Partial Responses (PRs) out of 6 evaluable CLL patients in the 65 mg QD dose cohort, a PR in a Richter’s transformation patient at the same dose and a PR in a follicular lymphoma patient on therapy for approximately two years. Subsequent to the EHA (Free EHA Whitepaper) presentation an additional PR was observed in a DLBCL patient and was disclosed in the context of the recent public offering
Selected 65 mg QD as the recommended starting phase 2 dose (RP2D) after assessing incremental clinical activity and tolerability data from cohorts 7 (65 mg QD) and 8 (75 mg QD); no additional dose limiting toxicities have been observed and a maximum tolerated dose has not been reached
Commenced preparations for the next phase of development, including planned regulatory interactions and design of expansion cohorts at the RP2D in multiple B-Cell malignancies, including C481S mutant CLL
Miransertib, our potent and selective first-generation AKT inhibitor.
Presented updated Proteus syndrome and PIK3CA-related Overgrowth Spectrum (PROS) data at the 2019 European Society of Human Genetics conference in Gothenburg, Sweden
Finalized the registrational protocol, received initial IRB approvals, nearing dosing of first patient
ARQ 751, our highly potent and selective next-generation AKT inhibitor.
Continued the signal generation work in genetically-defined solid tumors
Derazantinib, our FGFR inhibitor, partnered with Basilea and Sinovant, in a registrational trial for intrahepatic cholangiocarcinoma.
Clinical activities ongoing with our partners, Basilea and Sinovant
Paolo Pucci, Chief Executive Officer of ArQule, commented, "Our second quarter was punctuated by the proof-of-concept data presented at EHA (Free EHA Whitepaper) for ARQ 531, and we are gratified that our recent public offering will allow us to pursue the next phase of clinical development with ARQ 531."

"Having observed substantial clinical activity with ARQ 531 at a well-tolerated dose in the target populations, we have been able to select a phase 2 dose and are aggressively taking the drug into the expansion phase," commented Dr. Brian Schwartz, Chief Medical Officer of ArQule. "We are also excited to have opened additional sites in our registrational MOSAIC study in Proteus syndrome and PROS."

Revenues and Expenses

Revenues for the second quarter, 2019, were $0.3 million compared with revenues of $13.7 million for the second quarter, 2018.

Research and development expenses in the second quarter, 2019 were $6.3 million compared with $6.8 million for the second quarter, 2018.

General and administrative expenses in the second quarter, 2019 were $3.2 million compared with $2.2 million for the second quarter, 2018.

2019 Financial Guidance

For 2019, ArQule expects revenue to range between $3 and $5 million. Net loss is expected to range between $40 and $43 million, and net loss per share to range between $(0.35) and $(0.37) for the year. As a result of our common stock offering in June, we are updating our cash guidance. ArQule now expects to end 2019 with approximately $160 million in cash and marketable securities which will support the current business plan into 2022.

Conference Call and Webcast

ArQule will hold its second quarter financial results call today, August 7, 2019 at 9:00 a.m. ET. The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations." You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. A replay will be available two hours after the completion of the call and can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations."

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.

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).

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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.

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).

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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.