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Epizyme Reports Business Progress and Second Quarter 2019 Results

On August 9, 2019 Epizyme, Inc. (Nasdaq: EPZM), a late-stage biopharmaceutical company developing novel epigenetic therapies, reported second quarter 2019 financial results (Press release, Epizyme, AUG 9, 2019, View Source [SID1234538518]).

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"Over the course of the first half of 2019, we made tremendous progress across all aspects of Epizyme’s business, and the second half of the year holds even greater opportunities as we transition to a commercial-stage company and work to achieve our Vision 2020," said Robert Bazemore, president and chief executive officer of Epizyme. "Our vision is to bring tazemetostat to both epithelioid sarcoma and follicular lymphoma patients, while also expanding its development in the future to additional tumor types and combinations, to advance research efforts to bring EZM8266 and other early programs into the clinic, and to further enhance our leadership in the field of epigenetic drug discovery and development. The milestones we have achieved so far this year, along with the anticipated clinical and regulatory catalysts over the next several months, position this to be our most significant year yet. We look forward to continuing our progress in an effort to impact the lives of as many people as we can."

Leadership Team Expansion

Epizyme recently appointed Paolo Tombesi as chief financial officer to further support the company’s transition to a commercial-stage organization. Mr. Tombesi brings over 30 years of extensive financial and accounting expertise to Epizyme, most recently serving as the chief financial officer at Insmed, Inc.

Tazemetostat for Epithelioid Sarcoma (ES)

NDA Submission Accepted for Priority Review: The U.S. Food and Drug Administration (FDA) has accepted for filing Epizyme’s New Drug Application (NDA) for accelerated approval of tazemetostat, its lead investigational agent. The company has proposed an indication for the treatment of patients with metastatic or locally advanced epithelioid sarcoma who are not eligible for curative surgery. The FDA granted Priority Review for the NDA and has set a Prescription Drug User Fee Act (PDUFA) target action date of January 23, 2020. The submission is based primarily upon data from the 62 patient ES cohort in the company’s ongoing Phase 2 trial of tazemetostat, which were recently presented at ASCO (Free ASCO Whitepaper), and the safety and tolerability data generated across the tazemetostat development program.

Confirmatory Program Anticipated to Begin in 2H 2019: Epizyme has aligned on the design of its confirmatory trial to support full approval of tazemetostat for ES. The company plans to conduct a 1:1 randomized, controlled clinical trial in the front-line treatment setting comparing tazemetostat in combination with doxorubicin, a commonly used systemic treatment in this setting, versus placebo plus doxorubicin in approximately 150 patients. The primary efficacy endpoint will be progression-free survival, and secondary efficacy endpoints will include overall survival, disease control rate, overall response rate and duration of response. The safety run-in portion of the study is expected to begin in the second half of 2019.

Tazemetostat for Follicular Lymphoma (FL)

Planned NDA Submission for All-Comer FL on Track for Fourth Quarter: Epizyme is preparing to submit an NDA for accelerated approval of tazemetostat for the treatment of adult patients with relapsed or refractory FL, regardless of their EZH2 mutational status, who have received at least two prior systemic therapies. The company expects to submit the NDA for this indication in the fourth quarter of 2019.

Positive Updated Data from Ongoing Phase 2 Trial: At ICML, Epizyme presented data from the Phase 2 study of tazemetostat, as of a June 7, 2019 data cut off, showing that patients with an EZH2 mutation (n=43) had a 77% overall response rate (ORR) and a median duration of response (DOR) of 8.3 months. Patients with wild-type EZH2 (n=53) had a mature 34% ORR and 13-month DOR. Notably, favorable safety and tolerability were observed, with treatment-related adverse events resulting in only 5% of patients discontinuing treatment due to an adverse event. Enrollment is completed and the study is ongoing.

Confirmatory Program Anticipated to Begin in 2H 2019: To support full approval, Epizyme is planning to conduct a confirmatory program with an adaptive study evaluating the combination of tazemetostat with the chemo-free treatment regimen "R2" (Revlimid plus Rituxan) in the second line or later treatment setting for FL patients, both with and without EZH2 activating mutations. The final design is subject to alignment with FDA, and the company anticipates initiating the safety run-in portion in the second half of 2019.

FL Expansion Plans Established: Multiple additional clinical studies are anticipated to begin in the second half of 2019, and are designed to evaluate tazemetostat in earlier lines of FL treatment and in new combination regimens, including:

a combination study of tazemetostat with rituximab in patients with relapsed and/or refractory FL, and

a combination study of tazemetostat with R-CHOP in front-line patients in collaboration with the Lymphoma Study Association.

Tazemetostat for Additional Solid Tumors

Epizyme is planning several proof-of-concept clinical trials to begin in the second half of 2019 intended to explore the potential of new tazemetostat combinations in multiple solid tumor cancers, including:

a combination study of tazemetostat with the standards of care in patients with castration-resistant prostate cancer, and

a combination study of tazemetostat with a PARP inhibitor in patients with platinum-resistant solid tumors, such as small-cell lung cancer, triple-negative breast cancer and ovarian cancer.

EZM8266 for Sickle Cell Disease

Epizyme anticipates beginning clinical development of EZM8266, a novel, first-in-class G9a inhibitor, with a Phase 1 clinical trial in the second half of 2019.

Second Quarter 2019 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $331.0 million as of June 30, 2019, as compared to $215.6 million as of June 30, 2018.

Revenue: Collaboration revenue for the second quarter of 2019 was $5.9 million, compared to $12.0 million for the second quarter of 2018. The collaboration revenue recognized in the second quarter of 2019 relates to revenue earned as part of the company’s collaboration with Boehringer Ingelheim. In the second quarter of 2018, Epizyme recognized a $12.0 million milestone under its agreement with GlaxoSmithKline.

R&D Expenses: Research and development (R&D) expenses were $40.9 million for the second quarter of 2019, compared to $31.3 million for the second quarter of 2018. The increase is primarily due to a $10.0 million development milestone paid to Eisai in connection with the submission of the NDA in the second quarter of 2019

G&A Expenses: General and administrative (G&A) expenses were $15.7 million for the second quarter of 2019, compared to $10.9 million for the second quarter of 2018. The increase is due primarily to increased pre-commercialization activities and staffing, as well as increased personnel related expenses.

Net Loss Attributed to Common Stockholders: Net loss attributable to common stockholders was $48.5 million, or $0.53 per share, for the second quarter of 2019, compared to $29.1 million, or $0.42 per share, for the second quarter of 2018.

Financial Guidance

Based on its current operating plan, Epizyme continues to expect its cash runway to extend into the first quarter of 2021.

The company will not hold a conference call in conjunction with these results.

Tagrisso significantly improves overall survival in the Phase III FLAURA trial for 1st-line EGFR-mutated non-small cell lung cancer

On August 9, 2019 AstraZeneca reported positive overall survival (OS) results from the Phase III FLAURA trial, a randomised, double-blinded, multi-centre trial of Tagrisso (osimertinib) in previously-untreated patients with locally-advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) mutations (Press release, AstraZeneca, AUG 9, 2019, View Source [SID1234538494]).

Tagrisso showed a statistically-significant and clinically-meaningful improvement in OS, a secondary endpoint in the FLAURA Phase III trial, compared with erlotinib or gefitinib both of which were previous standard-of-care (SoC) treatments in this setting. The FLAURA trial met its primary endpoint in July 2017, showing a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS), increasing the time patients lived without disease progression or death from any cause. The safety and tolerability of Tagrisso was consistent with its established profile.

José Baselga, Executive Vice President, Oncology R&D said: "Today’s positive results show that Tagrisso provides an unprecedented survival outcome versus previous standard-of-care epidermal growth factor receptor tyrosine kinase inhibitors, reaffirming Tagrisso as the 1st-line standard-of-care for EGFR-mutated metastatic non-small cell lung cancer."

AstraZeneca plans to present the OS results from the FLAURA trial at a forthcoming medical meeting.

Tagrisso is currently approved in 74 countries, including the US, Japan and the EU, for 1st-line EGFRm metastatic NSCLC.

About lung cancer

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths, more than breast, prostate and colorectal cancers combined.1 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% classified as NSCLC.2 Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFR-mutated (EGFRm) NSCLC.3-5 These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKI) which block the cell-signalling pathways that drive the growth of tumour cells. Approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.6 The presence of brain metastases often reduces median survival to less than eight months.7

About Tagrisso

Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against central nervous system metastases. Tagrisso 40mg and 80mg once-daily oral tablets have now received approval in more than 70 countries, including the US, Japan and the EU, for 1st-line EGFRm advanced NSCLC, and in more than 80 countries, including the US, Japan, China and the EU, for 2nd-line use in patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being developed in the adjuvant setting (ADAURA trial), in the locally-advanced unresectable setting (LAURA), in combination with chemotherapy (FLAURA2) and with potential new medicines (SAVANNAH, ORCHARD).

About FLAURA

The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg orally once daily vs. comparator EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was double-blinded and randomised, with 556 patients across 29 countries.

About AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer spanning several stages of disease, lines of therapy and modes of action. We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa (gefitinib) and Tagrisso, and ongoing Phase III trials ADAURA, LAURA, FLAURA and FLAURA2 as well as the Phase II combination trials SAVANNAH and ORCHARD.3-5

Our extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a known genetic mutation which represents up to 50% of all patients with lung cancer. Imfinzi (durvalumab), an anti-PDL1 antibody, is in development as monotherapy (Phase III trials ADJUVANT BR.31, PACIFIC-4, PACIFIC-5, and PEARL) and in combination with tremelimumab and/or chemotherapy (Phase III trials AEGEAN, PACIFIC-2, NEPTUNE, POSEIDON, ADRIATIC and CASPIAN).

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 a key growth driver for AstraZeneca 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.

InnoCure Therapeutics, Accelerating Development of Next-Generation Target Protein Degradation Mechanism New Drug

On August 8, 2019 InnoCure Therapeutics (CEO Hye-dong Yoo) reported the company is accelerating the development of new drugs using next-generation target protein degradation mechanisms (Press release, InnoCure Therapeutics, AUG 8, 2019, View Source;nid=233623 [SID1234651740]). According to the company, they are conducting research to develop treatments for rare diseases including anticancer drugs and degenerative brain diseases by utilizing next-generation new drug development technologies such as ‘PROTAC’ and ‘AUTOTAC’, artificial intelligence (AI) to shorten drug development time and increase drug efficacy, big data analysis, and molecular modeling to induce specific protein degradation mechanisms.

Based on this, InnoCure Therapeutics was recognized for its technological prowess when it was selected for the R&D project of the Ministry of SMEs and Startups’ TIPS program in February 2019, in which Magna Investment participated as the operator.

The company said that it has secured several new substances effective in the field of rare diseases at the research institute that moved to Pangyo, Gyeonggi-do in June, and is currently pursuing IND application for clinical trials in 2021. It is also pursuing joint research with pharmaceutical and bio companies specializing in degenerative brain diseases and rare diseases in the United States.

"InnoCure is actively utilizing PROTAC and AUTOTAC, next-generation technologies that can serve as ‘game changers’ in the new drug development field," said Bae Jun-hak, Vice President of Magna Investment. "The management team, which has experience in global bio companies and a global human network, possesses the know-how in global market entry strategies."

Meanwhile, PROTAC targeted protein degradation technology is known as a drug development technology that can increase efficacy and reduce side effects with small doses. Avinas, founded in 2014 by Professor Craig Crews of Yale University, a pioneer in PROTAC technology, became the first PROTAC technology company to enter clinical trials with a drug using PROTAC technology when its prostate cancer treatment under development received clinical approval from the FDA in March 2019.

InnoCure Therapeutics CEO Yoo Hye-dong is currently conducting clinical research on a drug for degenerative brain diseases that was jointly researched with a U.S. East Coast biotech company specializing in degenerative brain diseases while working at NCE Sciences, a San Francisco-based startup in the U.S. While working at Celgene, she participated in the development of new drugs, including the development of an alternative to the blockbuster nano-oncology drug ‘Abraxane.’

In January 2018, he founded Innocure Therapeutics.

Cytovation and SMS-oncology sign agreement on conduct of phase I/II trial with CyPep-1 in solid tumors

On August 8, 2019 Cytovation AS ("Cytovation") and Specialized Medical Services-oncology BV ("SMS-oncology") reported that SMS-oncology has been selected as the CRO to conduct the phase I/II clinical trial with CyPep-1 in patients with advanced solid cancers (Press release, Cytovation, AUG 8, 2019, View Source [SID1234561561]).

In recent months, Cytovation has progressed through preclinical and toxicology studies with its lead candidate CyPep-1, a first-in-class lytic agent. Through its unique pharmacological properties, CyPep-1 selectively targets and lyses tumor cell membranes based on their altered molecular composition. This mode of action kills cancer cells, releases tumor antigens, and potentially induces a tumor-specific immune response by in-situ immunization.

Cytovation is currently initiating a first-in-human trial with intratumoral injection of CyPep-1 and aims to reach first in patient (FPI) milestone by the end of 2019. An agreement is now concluded with the oncology dedicated CRO SMS-oncology in Schiphol, the Netherlands.

The study is designed as an open-label, dose escalation phase I/II trial to evaluate the safety, efficacy and pharmacokinetics of intratumoral CyPep-1 in patients with advanced solid cancers. The multicenter trial in Europe will enroll approximately 18 patients. SMS-oncology is developing the protocol and giving guidance regarding patient inclusion criteria and investigational sites for a best-fit and seamless transition to clinic. This will be followed by full conduct of the trial, expected to commence in Q4 2019.

Mr. Kjell-Inge, CEO of Cytovation: "We are excited CyPep-1 is now progressing to the next phase of development, which is an important step for our company. We are pleased with selecting SMS-oncology as our partner in this transition to clinic. From the initial discussions, they lived up to their reputation as experts in the field of early phase and immuno-oncology trials. Preparations of the trial are moving forward in a fast pace, and we feel confident our trial will be conducted in an optimal and valuable matter with our goals is mind."

Ms. Philine van den Tol, CEO of SMS-oncology: "We are delighted to support Cytovation and look forward to jointly make the CyPep-1 trial a great success. It is exactly these type of innovative projects SMS-oncology leverages great experience in, and beyond all, is passionate
about. The enthusiasm of Cytovation is catching and our team can’t wait to see results of this promising first-in-class lytic compound."

CyPep-1, in a cream formulation for topical application, is currently being evaluated in a phase I trial in patients with HPV-induced cutaneous tumors (warts).

Autolus Therapeutics Reports Second Quarter 2019 Financial Results and Operational Progress

On August 8, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its financial and operational results for the second quarter ended June 30, 2019 (Press release, Autolus, AUG 8, 2019, View Source [SID1234550688]).

Operational Highlights:

In April, Autolus announced the presentation of initial data from the ongoing Phase 1/2 ALLCAR19 clinical trial of AUTO1 in adult ALL at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, Georgia. As of the data cutoff date of May 18, 2019, 13 patients were leukapheresed, and products for 12 patients were manufactured, including 7 with Autolus’ semi-automated, fully enclosed manufacturing process. Using the Lee criteria, there were no patients with severe cytokine release syndrome (CRS) (≥ Grade 3), and only 2 of 10 patients (20%) with Grade 2 CRS. Tocilizumab was used in 2 of 10 patients (20%). None of the patients were admitted to intensive care due to CRS. One patient developed delayed Grade 3 neurotoxicity following high levels of CAR T expansion, which resolved promptly following administration of steroids. Four patients died while enrolled in the trial, 2 due to progression of the disease and 2 due to sepsis, a common complication in patients with advanced ALL. Nine patients were evaluable for response at 1 month with 8 (88%) achieving a molecular complete response. One patient died of sepsis before the one-month evaluation point. At a median follow-up of 5 months (range 0.62-10.6 months), 6 of 10 patients were alive and continue to be in molecular remission with continued evidence of ongoing B cell aplasia and CAR T persistence.
In April, Autolus completed an underwritten public offering of 4,830,000 American Depositary Shares ("ADSs") representing 4,830,000 ordinary shares, at a public offering price of $24.00 per ADS, which includes an additional 630,000 ADSs issued upon the exercise in full of the underwriters’ option to purchase additional ADSs. Aggregate net proceeds to Autolus, after underwriting discounts but before estimated offering expenses, were $108.8 million.
Pipeline Updates and Anticipated Milestones:

Initiation of a Phase 2 registration trial of AUTO1 in adult ALL in the fourth quarter of 2019 (pending regulatory feedback). Updated Phase 1 data from the ALLCAR19 clinical trial is expected at ASH (Free ASH Whitepaper) 2019.

Decision on Phase 2 initiation for the Alexander study of AUTO3 in DLBCL is expected for mid-2020. Interim Phase 1 data is expected at ASH (Free ASH Whitepaper) 2019.

Development of AUTO1 in pediatric ALL as part of a pediatric investigational program (PIP). Next data update from CARPALL clinical trial is expected at ASH (Free ASH Whitepaper) 2019. Development program includes a next generation version of AUTO1 (AUTO1NG), which incorporates the CD19 CAR of AUTO1 and a novel CD22 CAR. First preclinical data on CD22 CAR expected to be presented at ASH (Free ASH Whitepaper) 2019.

Additional presentations targeted for ASH (Free ASH Whitepaper) 2019 are: data from AMELIA clinical trial of AUTO3 in pediatric ALL and data from clinical trial of AUTO2 in multiple myeloma.

Next generation (NG) programs for AUTO1, AUTO2, AUTO3 and AUTO6 are expected to enter the clinic in 2020.
"This quarter we have focused on expanding operations at our clinical manufacturing site at the Catapult Cell and Gene facility in Stevenage, UK, enabling us to meet our expected clinical trial demand, including a registration trial with AUTO1. In April, we presented encouraging data on our ALLCAR19 clinical trial of AUTO1 in adult ALL. These data show that AUTO1 is well differentiated from the standard of care in ALL and other CAR T products in development, reaching a high level of clinical activity without inducing severe cytokine release syndrome," stated Dr. Christian Itin, chairman and chief executive officer of Autolus. "For the remainder of 2019, our efforts are focused on moving AUTO1 into a Phase 2 registration trial in adult ALL and advancing AUTO3 in DLBCL toward a Phase 2 decision point in Q2 2020."

Financial results for second quarter 2019:

Cash and equivalents at June 30, 2019 totaled $266.2 million, compared with $217.5 million at December 31, 2018.

Net total operating expenses for the three months ended June 30, 2019 were $37.2 million, net of grant income of $0.3 million, as compared to net operating expenses of $16.5 million, net of grant income of $0.4 million, for the same period in 2018. The increase was due, in general, to the increase in development activity; increased headcount primarily in our development and manufacturing functions; and the cost of being a public company.

Research and development expenses increased to $26.2 million for the three months ended June 30, 2019 from $8.9 million for the three months ended June 30, 2018. Cash costs, which exclude depreciation as well as share-based compensation, increased to $20.2 million from $7.1 million. The increase in research and development cash costs of $13.1 million consisted primarily of an increase of compensation-related costs of $5.6 million primarily due to an increase in headcount to support the advancement of our product candidates in clinical development, an increase of $2.3 million in facilities costs supporting the expansion of our research and translational science capability and investment in manufacturing facilities and equipment, an increase of $3.3 million in research and development program expenses related to the activities necessary to prepare, activate, and monitor clinical trial programs, an increase of $0.8 million in professional fees, an increase of $0.5 million in telecom and software costs, and other additional costs in the amount of $0.4 million.

General and administrative expenses increased to $11.4 million for the three months ended June 30, 2019 from $8.1 million for the three months ended June 30, 2018. Cash costs, which exclude depreciation as well as share-based compensation, increased to $7.3 million from $6.9 million. The increase of $0.4 million consisted primarily of an increase in commercial costs of $1.2 million, compensation-related expense of $0.5 million due to an overall increase in headcount, offset by a decrease in legal and professional fees of $1.3 million related to certain corporate reorganization costs that were incurred in the three months ended June 30, 2018.

Net loss attributable to ordinary shareholders was $28.5 million for the three months ended June 30, 2019, compared to $7.7 million for the same period in 2018.

The basic and diluted net loss per ordinary share for the three months ended June 30, 2019 totaled $(0.65) compared to a basic and diluted net loss per ordinary share of $(0.26) for the three months ended June 30, 2018.

Autolus anticipates that cash on hand provides a runway into the second half of 2021.
Conference Call and Presentation Information

Autolus management will host a conference call today, August 8, at 8:30 a.m. EDT/ 1:30pm BST, to discuss the company’s financial results and operational update.

To listen to the webcast and view the accompanying slide presentation, please go to: View Source

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 2763978. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 2763978.